SALT LAKE CITY (AP) — A Utah man who is no longer facing charges for eating a live baby rat says the act was grotesque, but shouldn't be considered as animal cruelty.
Prosecutors charged Andy Ray Harris with animal cruelty in April, after authorities viewed a posted Facebook video of him eating what appeared to be the baby rat. The …
OSI Pharmaceuticals rejected a $3.5-billion takeover bid from Astellas Pharma Inc., telling shareholders Monday the offer was too low.
Astellas has attempted to acquire OSI for more than a year and, after repeated rejections, the Japanese company filed suit to prevent the OSI's board from interfering and made a hostile bid earlier this month.
On Monday, OSI Chairman Robert Ingram said the offer "does not fully reflect OSI's fundamental, intrinsic value."
The board voted unanimously to reject Astellas again. The offer expires March 31.
Astellas said in a statement responding to the rejection that it "continues to firmly …
In a perfect world, overnight guests should be able to drop in ata moment's notice without disrupting, in the least, the rhythm andflow of your very collected household. That's because in a perfectworld, we would all have little guest cottages, perfectly appointedand standing by to welcome old college roommates, grown nieces,various in-laws and the couple you met on a cruise who threatened todrop in one day and then actually did.
Alas, we don't live in a perfect world, and impromptu guests canoften throw even an organized household into chaos. This isunfortunate, because lots of times we are actually very pleased,flattered even, to see and receive whoever turns up at our …
NAGPUR, India (AP) — India has beaten New Zealand by an innings and 198 runs in the final test at the Vidarbha Cricket …
Henrik Stenson knows better than most how quickly fortunes can change in golf.
His performance in The Players Championship, where he putted for birdie on all but two holes in the final round and turned a five-shot deficit into a four-shot victory, beefed up his credentials as the No. 5 player in the world.
Stenson also knows the lean times. The 33-year-old Swede smiled behind those intimidating sunglasses as he spoke earlier in the week about the time he played St. Andrews without having any idea where the ball was going.
"I'm standing on the 17th hole, and as I get ready to hit my tee shot, I can see my caddie out of the corner of my eye …
Summit Group reports improved results
Summit Financial Group Inc., the corporate parent of SummitCommunity Bank, reported improved results for the second quarter andfirst half of 2011.
The company reported second-quarter 2011 net income of $831,000.In comparison, Summit posted a $2.95 million loss in the samequarter a year ago.
For the first half of 2011, Summit reported net income of$509,000. In comparison, the company posted a $2.91 million loss inthe first half of 2011.
Charles Maddy, Summit's president and chief executive officer,said, "While we are pleased to have returned to profitability thisquarter, our job one remains to reduce our …
ORLANDO, Fla. - Rich history wasn't enough to lure Billy Donovan away from Florida. In the end, it was just riches. Donovan will have plenty of them after he was hired to coach the Orlando Magic on Thursday. The team confirmed the hiring Thursday night and scheduled a news conference for Friday morning.
Donovan agreed to a five-year deal paying $5.5 million annually, an official in the NBA told The Associated Press.
"Billy Donovan is a winner," general manager Otis Smith said. "We feel he is the right person to develop and maximize the talents of our players. We look forward to Billy leading us to the next level."
Donovan has been the subject of speculation since …
A suicide truck bomber plowed through a sandbag barrier to strike a police station in the northern city of Mosul on Tuesday, killing at least seven people and wounding 17, police said.
It was the latest challenge to efforts by Iraqi forces to take over their own security as the United States prepares to withdraw all its forces by the end of 2011.
The bomber broke through the first checkpoint on the station's perimeter, which was made of sandbags, then detonated his explosives when he reached the concrete wall a few yards (meters) away from the building, according to local police.
The attack occurred about 6:30 a.m. at the Mahta police station in …
Q. I am divorced and live with my three children in a housewhich still has my ex-husband's name on it with me. He is a violentman who drinks a lot. He threatens to "get even" someday by settingfire to the house and cause me to lose everything.
If he ever makes good on his threat, will my homeowner insurancewhich is still in both of our names have to pay for the belongings Ilost? He says homeowner insurance doesn't have to pay if thepolicyholder set the fire.
He's got me half crazy with fear. How can I be protected?
A. I'm not making light of your problem, but deadly seriousabout advising you to install good fire alarms all around the house.You have a …
WASHINGTON (AP) — President Barack Obama and Australian Prime Minister Julia Gillard couldn't say enough about the close friendship between their two countries during Gillard's first White House visit Monday. But on one issue there was no common ground: Vegemite.
Obama winced at the mere mention of the Australian food paste when a student asked about it during a classroom visit the two leaders conducted. "It's horrible!" the president declared.
Gillard displayed some diplomacy befitting a world leader on her first Washington tour, calling the issue "a little bit of a division between the president and I. I love Vegemite."
Obama and Gillard began with a more traditional …
Strong overseas sales and cost-cutting kept a decline in Tiffany & Co.'s third-quarter profit to a bare minimum, causing the luxury jeweler to raise its full-year profit outlook heading into the crucial holiday season.
The luxury sector has seen sales drop sharply during the recession, but Tiffany's results signal that the high end is on the mend, said Edward Jones analyst Matt Arnold.
"The main thing that sticks out to me is that trends continue to improve, and this should persist for a while," Arnold said.
Tiffany lifted its full-year forecast on efforts to tighten inventory and cut costs, sending shares up $1.65, or 4 percent, to …
ABSTRACT
Linear dichroism (LD) can be used to study the alignment of absorbing chromophores within long molecules. In particular, Couette flow LD has been used to good effect in probing ligand binding to DNA and to fibrous proteins. This technique has been previously limited by large sample requirements. Here we report the design and application of a new micro-volume Couette flow cell that significantly enhances the potential applications of flow LD spectroscopy by reducing the sample requirements for flow linear dichroism to 25 �L (with concentrations such that the absorbance maximum of the sample in a 1-cm pathlength cuvette is ~1). The micro-volume Couette cell has also enabled the measurement of fluorescence-detected Couette flow linear dichroism. This new technique enables the orientation of fluorescent ligands to be probed even when their electronic transitions overlap with those of the macromolecule and conversely. The potential of flow-oriented fluorescence dichroism and application of the micro-volume Couette LD cell are illustrated by the collection of data for DNA with minor groove and intercalating ligands: DAPI, Hoechst, and ethidium bromide. As with conventional fluorescence, improved sensitivity compared with absorbance LD is to be expected after instrumentation optimization.
INTRODUCTION
Linear dichroism (LD) is a phenomenon caused by the differential absorption of light polarized parallel and perpendicular to an orientation axis. It has a long history and a wide range of applications, all requiring a means of orienting the sample. For biological molecules, where the sample has to be hydrated, the most versatile sample orientation method has proved to be solution phase Couette flow orientation (Bloemendal and Vangrondelle, 1993; Hofricheter and Eaton, 1976; Nord�n et al., 1992; Rodger, 1993). The main applications of such flow LD to date have been to DNA and DNA drug systems (Nord�n et al., 1992; Wada, 1964; Wada and Kozawa, 1964). Recent applications of LD for structural characterization of biomacromolecular systems include both membrane-bound and fibrous proteins, which can be difficult to study using other methods (Dafforn et al., 2004; Johansson and Davidsson, 1985; Rodger, 1993; Rodger et al., 2002). However, despite recent sample reduction (Rodger el al., 2002), the sample requirements of flow LD experiments to date (200 �L of a sample whose absorbance is ~1 in a 1-cm cuvette) has precluded its use in systems where limited material is available.
Couette cells are derived from the work of Couette (1890) and were first developed into an instrument for flow dichroism by Wada and Kozawa (1964). Sample orientation is effected by viscous drag generated by a flow gradient imposed on solution flowing in a narrow gap between the walls of a rotating cylindrical cell (Fig. 1). Previous studies have used either a rotating inner and fixed outer cylinder (Wada and Kozawa, 1964), or a rotating outer and fixed inner cylinder (Lee and Davidson, 1968; Oriel and Schellman, 1966). The former design offers more flow stability and has been the most popular. The light path through the cell is made of ultraviolet (UV) transparent materials, usually quartz, that allow optimal transmission of light. If the center rotates then it needs to be made of optically transparent material and the stationary outer cylinder requires at least two transparent windows, and vice versa. The incident light beam can be either perpendicular (Wada and Kozawa, 1964) or parallel (Lee and Davidson, 1968) to the axis of rotation. We adopt the perpendicular orientation in all of our applications.
The micro-volume Couette LD cell developed here is based on a quartz capillary (~5-mm outer diameter and ~3-mm inner diameter) and centrally mounted rod (2-2.5-mm outer diameter) inserted into the capillary (Fig. 2). Flow orientation is generated by rotating the outer capillary. The capillary and rod are demountable for easy cleaning and are in principle disposable. In our previous low-volume Couette (Dafforn et al., 2004; Rodger et al., 2002) the annular gap between an outer stationary cylinder and an inner rotating one was reduced to 50 �m (the standard gap is typically 500 �m). The volume required for the 50-�m cell is ~200 �L, compared to 1800 �L or more (with a 1-mm pathlength) in earlier cells. In this article the new micro-volume Couette LD cell reduces the sample volume by a further order of magnitude (with a pathlength of ~0.5 mm) at the same time opening the way to disposable LD sample holders and also flow-oriented fluorescence dichroism. It is this micro-volume 250-�m annular gap Couette LD cell that has been used for all the work reported in this article.
As well as the application of standard LD to new systems (such as liposomes and fibers) a potential area of advance has been the coupling of LD with other techniques. This was first mentioned by Wada (1972), who proposed combination of LD with infrared absorbance fluorescence, and light scattering. Until now, however, fluorescence-detected flow linear dichroism (FDFLD) has not been possible using Couette shear flow due to lack of suitable instrumentation. The micro-volume Couette LD cell offers this possibility because of its small diameter, therefore allowing the collection of photons emitted perpendicular to the incident light direction (Fig. 3). The 90� configuration cell allows the study of fluorophores that exhibit spectral overlap with other species in the solution, so cannot be studied using the standard 180� configuration LD cell. This enhances the capacity of LD for the study of ligand orientation on linear molecules.
LD experiments are usually undertaken using adapted circular dichroism (CD) spectropolarimeters as LD has the same issues as CD with regard to the equivalence of the intensity of the two polarized light beams. In our case we increase the voltage across the photoelastic modulator (PEM) so that it becomes an oscillating half-wave plate with alternating horizontal and vertical polarizations. The key component of the micro-volume Couette LD cell to enable its use in standard CD spectropolarimeters, where light beams are large, is the use of a focusing lens before the capillary housing to ensure the light is only incident on the central part of the unit. The diverging lens effect of the capillary/rod requires another focusing lens after the sample. FDFLD is detected by addition of an exit hole at 90� to the incident light and the use of a lens to focus any emitted light onto the photomultiplier tube (PMT), which for the purposes of these experiments was relocated to a position on the back of the CD spectropolarimeter sample compartment at 90� to the incident light (Fig. 3 b). This design is not optimized for FDFLD, in particular all scattered photons are detected, resulting in comparatively poor signal/noise ratios. However, as discussed below, we have confirmed that there are no intrinsic problems with the capillary design leading to spectroscopic artifacts.
MATERIALS AND METHODS
Design of micro-volume Couette flow LD cell
A cross section of the micro-volume Couette flow LD cell is shown in Fig. 4. This was designed and built by Crystal Precision Optics, Rugby, UK. The major innovation in our design is the use of quartz capillaries and rods to hold and orient the sample (Glass Precision Engineering, Leighton Buzzard, UK and Enterprise-Q, Manchester, UK). The capillary units are demountable for removal during cleaning and sample loading. This also provides the possibility for use as a disposable sample holder, an attractive idea in the case of some samples. In this work, the capillaries are sealed at the base with Araldite Rapid (Bostik Findley, Stafford, UK) and held in position in the metal base unit by an "O"-ring. A quartz rod is held suspended rigidly from the lid and is inserted into the capillary before operation (Fig. 2).
The motor used to drive the capillary is mounted directly below the cell. It is controlled electronically by an EP-603 (0-30 V) power supply, adapted to allow more precise measurements (two decimal places) of applied voltage by the addition of a 10-turn potentiometer. Potential vibration was excluded by using a flexible coupling between the driver spindle and motor. Rotation speeds from 0 to 7000 revolutions per minute (rpm) can be achieved, without inducing turbulent flow. Rotation speeds were ascertained in a calibration experiment by marking the outside of the capillary and measuring the frequency with which the light beam was interrupted using a fast kinetic program on the spectropolarimeter (Fig. 5).
Before collecting the data reported in this article, extensive work was undertaken to demonstrate that different batches of quartz capillaries had no depolarizing effects on the incident light beam. In addition we have shown that the intrinsic LD signal from the capillary is independent of the face of the capillary that is in the light beam. This means that the baseline spectrum for an LD experiment can be collected simply by stopping the rotating capillary and hence the alignment. This is an extremely attractive option and contrasts with our previous practice of emptying and refilling the cell with water. In the case of light-scattering samples, measuring the baseline on the same sample usually produces better baselines. However, the rods are not as uniform as the capillaries and it is essential that they are always inserted into the capillary in the same orientation.
Due to the size of the surface area of the capillary and the need to have light incident only on the middle front and back of the solution (otherwise an averaging over samples oriented perpendicular and parallel to the propagation direction would occur) a 2.54-cm diameter � 10-cm focal length lens (Edmund Optics, York, UK) was placed 10 cm in front of the center of the rod. The beam diverges after the capillary unit (in part due to the first lens and in part due to the capillary/rod), so a second lens (2.54-cm diameter � 6-cm focal length) was placed after the sample to focus the light onto the PMT, thereby improving the signal/ noise ratio by maximizing the number of photons reaching the PMT. The focal length of this lens can be varied somewhat without compromising the quality of the data.
The micro-volume 180� Couette flow LD cell was adapted to detect light emitted at 90� by drilling an extra exit hole in the capillary housing at 90� from the path of the incident beam and putting a long focal length lens (2.54-cm diameter � 15-cm focal length) close to this hole to capture and focus maximum light onto the PMT (which is located further from the cell in this configuration).
The minimum volume of sample required depends on the amount of Araldite Rapid used to seal the bottom end of the capillaries because the height of the light beam and the O-ring are fixed. In our standard system a depth of ~4 mm Araldite Rapid was used to seal the capillaries, the rod was lowered to ~1 mm above this when fully assembled, and the total pathlength of the system was ~500 �m. Volumes of at least 25 �L gave the same LD signal, however, higher volumes (e.g., 40 �L) are easier to load without introducing bubbles.
Construction of micro-volume Couette flow LD cell
A major consideration when constructing the micro-volume Couette LD cell was to ensure the rotating quartz capillary and the stationary quartz rod remained parallel. The main body of the micro-volume Couette LD cell is manufactured from laboratory and food industry specification stainless steel (Fig. 4). The bearings and drive spindle were also stainless steel and designed to be dust and water resistant. The drive spindle has a precision-located rubber insert to maintain parallelism and friction drive. The baseplate has been designed specifically for a Jasco CD spectropolarimeter (Tokyo, Japan) with a large sample compartment, but can readily be modified for other CD spectropolarimeters. The base incorporates positioning dowels. These are sufficient to ensure that the cell body is automatically located to line up with the center of the light beam.
The stationary suspended quartz rod is held firmly in position by a cell cap. This has been designed to enable different diameter rods to be installed, allowing the option of changing the annular gap between the inside of the capillary and the outside of the rod without losing the axial parallelism between the capillary and the rod. The base unit of the LD cell has three slots to hold the lenses machined to an accuracy of 10 �m in the linear path and 0.001� in the 90� plane to ensure concentricity in all paths relative to the center line of the rotating capillary. The lens holders were fabricated to ensure that the center of the lens was concentric with the center of the capillary and vertically with the light beam. The optical pathlength of the beam could be adjusted by the linear movement of the lenses along the precision-machined slide ways.
DNA and ligand preparation
Calf thymus DNA, highly lypholized, and the well-characterized DNA groove binders 4',6-diamidino-2-phenylindole (DAPI) and bisbenzimide H33258 (Hoechst), and ethidium bromide were all supplied by Sigma (Poole, UK). Stock solutions were prepared in water (18.2 Mohm). DNA solutions were prepared by hydration of ct-DNA overnight in deionized water. Concentrations of ct-DNA were determined spectrophotometrically using the molar absorption coefficient per base of [epsilon]^sub 259^ = 6600 M^sup -1^ cm^sup -1^ (Wells et al., 1970). High-purity groove binders/intercalators were used and their concentrations determined by mass using a Sartorius supermicro seven-figure balance (Goettingen, Germany).
Control and validation experiments
The effect of using capillaries as a sample holder for LD and FDFLD was investigated by comparing to reference data collected for LD, CD, and fluorescence. For LD, comparisons against a large-volume Couette flow LD cell (1800 �L) with an inner quartz cylinder that rotates within a steel housing unit with two quartz windows (pathlength 1 mm) was undertaken using ct-DNA solutions at a range of concentrations from 0 to 1000 �M in sodium cacodylate buffer (10 mM, pH 7, Sigma) and NaCl (10 mM, Sigma) (Rodger, 1993). Buffer baseline subtracted LD data were collected from 400 to 190 nm at a data pitch of 0.5 nm, scanning speed of 500 nm min^sup -1^, a response of 0.25 s, bandwidth of 2 nm, and averaging over four scans. CD analysis using ammonium camphor sulphonate (0.02% w/v, Jasco) was carried out with the capillary stationary within the baseplate setup and the spectra compared with a 5-mm pathlength quartz cuvette in the normal position for CD analysis. Water baseline corrected CD data were collected between 350 and 185 nm every 0.5 nm, scanning at 200 nm min ^sup -1^, a response of 0.5 s, bandwidth of 2 nm, and averaging eight scans. Both of these measurements were collected using the Jasco J-715 spectropolarimer in appropriate modes. Fluorescence data were collected using a Perkin Elmer LS50B fluorimeter (Buckinghamshire, UK) not adapted for the use of capillaries, comparing a masked (mimicking the location of the rod) capillary and a 5-mm pathlength quartz cuvette with four polished sides. Aqueous solutions of ct-DNA (317 �M, Sigma), ethidium bromide (30 �M, Sigma) in sodium cacodylate buffer (10 mM, pH 7, Sigma), and NaCl (10 mM, Sigma) were used. Buffer baseline corrected data were collected in excitation mode with the emission wavelength set at 0 nm. Fluorescence data were collected from 600 to 200 nm at a scanning speed of 200 nm min^sup -1^, excitation slit widths of 5 nm, and emission slit widths of 2.5 nm. Data were averaged over four scans.
The design of the micro-volume Couette LD cell at present is such that all samples need to be preprepared and loaded into a clean capillary, as it is not possible to remove and replace the rod unit and accurately titrate into the capillary. Validation of the micro-volume Couette LD cell was carried out using ct-DNA (200 �M) comparing repeat analyses in the same capillary and different capillaries. Data were collected using the parameters detailed above under LD control experiments. Analysis of the negative signal at 259 nm yielded information about the errors associated with sample reloading and cell reassembly.
DNA-ethidium bromide binding validation experiments
An application of the micro-volume Couette LD cell is in the analysis of DNA-ligand binding. An example of the binding of ethidium bromide, a classical intercalator, and DNA is shown in this article. The concentration of ct-DNA was held constant at 200 �M and the concentration of ethidium bromide was varied from 5 to 50 �M in 5-�M increments. All solutions were buffered at pH 7.0 using sodium cacodylate buffer ( 10 mM, Sigma) and contained NaCl (10 mM, Sigma).
LD and fluorescence linear dichroism experiments of DNA-ligand complexes
Applications involving LD and FDFLD of ligands binding to DNA are also reported here. The fluorescent ligands chosen include ethidium bromide, a DNA intercalator with [alpha] ~ 90�, and two DNA minor groove binders, Hoechst and 4',6-diamidino-2-phenylindole (DAPI) with [alpha] ~ 45� for long-axis polarized transitions and [alpha] ~ 90� for short-axis polarized transition. These ligands were expected to provide both positive and negative LD and/or FDFLD signals at a range of different wavelengths. LD and FDFLD experiments of DNA-ligand complexes were performed using calf thymus DNA and groove binder/intercalator solutions of concentration 1000 �M and 50 �M, respectively, thus giving a mixing ratio of 20:1. The solutions were buffered at pH 7 using sodium cacodylate (10 mM, Sigma).
LD and FDFLD data were collected using a Jasco J-715 circular dichroism spectropolarimeter with a large sample compartment that was adapted for LD measurements by turning the PEM into an oscillating half-wave plate. CD artifacts are less likely with this configuration than when a quarter-wave plate is added to an unadapted CD machine. There is no evidence in any spectra of such artifacts. All spectra were taken at room temperature (23�C) using the same quartz capillary and rod with the following parameters: 600-200 nm, data pitch 0.5 nm, scan speed 500 nm min^sup -1^, response 0.25 s, bandwidth 2 nm, and averaged over four separate scans. The corrected spectra were calculated by subtracting a baseline from the stationary capillary, when no LD signal would be present.
UV-visible absorbance spectra and fluorescence spectra were recorded using a Jasco V-550 UV-visible spectrophotometer and a Perkin Elmer LS50B fluorimeter, respectively. A 1-mm pathlength quartz cuvette was used to collect UV spectra of ct-DNA and ligands, and a 1-cm pathlength cuvette used for the concentration determination of ct-DNA. Fluorescence excitation spectra were collected in a 5-mm pathlength cuvette with the emission wavelength set to 0 nm, which means all wavelengths emitted and scattered light are collected. This was done to reflect fluorescence data collected in the micro-volume Couette LD system, because the J-715 spectropolarimeter does not have a second monochromator. For fluorescence measurements of the groove binders (DAPI and Hoechst) an excitation slit width of 4 nm and emission slit width of 2.5 nm were used, whereas for ethidium bromide an excitation slit width of 10 nm and emission slit width of 5 nm was used. Data were averaged over four scans at 200 nm min^sup -1^ scanning speed.
Fluorescence LD control experiments were also carried out using both ct-DNA (1000 �M) and each respective drug (50 �M) at pH 7.0 to ensure that the signal being detected is not due to background scatter or intrinsic properties of the components of the DNA-ligand mixtures.
RESULTS
Verification that capillaries as sample holders do not distort spectra
Control linear dichroism (capillary system versus large-volume Couette flow LD cell with a pathlength of 1 mm), circular dichroism (3-mm inner diameter (i.d.) capillary versus 5-mm pathlength rectangular cuvette) and fluorescence (3-mm i.d. capillary versus 5-mm square fluorescence cuvette) experiments using the capillaries were carried out to show that there are no intrinsic problems with undertaking spectroscopic experiments in the extruded quartz capillaries.
LD spectra of ct-DNA in the range 0-1000 �M measured with the micro-volume Couette LD cell were able to be rescaled so that there was good agreement with data collected in the standard Couette cell across the whole wavelength range down to 200 nm (data not shown). All spectra were consistent with those in the literature (Hofricheter and Eaton, 1976; Houssier et al., 1974; Lee and Davidson, 1968; Nord�n et al., 1992; Nord�n and Kurucsev, 1994; Simonson and Kubista, 1993; Wada, 1964; Wilson and Schellman, 1978).
CD measurements were undertaken using ammonium camphor sulfonate (0.02% w/v), a standard routinely used for the calibration of CD spectropolarimeters. It yields two signals, a negative signal at 192.5 nm and the other a positive signal at 290.5 nm, with the ratio of the two being 2 (Lowry, 1935; Miles et al., 2003; Takakuwa et al., 1985). The i.d. of the capillaries used is three-fifths that of the reference quartz cuvette. The 3-mm i.d. capillary when rescaled by the appropriate pathlength gave a very good agreement with the reference cuvette data down to 190 nm (data not shown). This shows that the capillary is giving accurate data down to these wavelengths.
Both the LD and CD validation experiments were done with the capillary in the Jasco J-715 CD spectropolarimeters with holders that have been designed for that instrument's baseplate and light beam. With regard to the fluorescence experiments, the controls were undertaken in an LS50B fluorimeter for which we were not able to design a holder that focused the light beam appropriately, therefore the data were of much poorer quality. However, when using ct-DNA (317 �M) and ethidium bromide (30 �M) a masked capillary yielded fluorescence spectra that overlaid with the controls from the same instrument, albeit with less intensity and more noise (data not shown).
Validation of micro-volume Couette flow LD cell
Measurement of a number of individual capillaries established that their pathlength differs by <1% when capillaries are cut from the same local region of the extruded quartz source material. Multiple LD analyses of the same sample were undertaken, by comparing the signal intensity at 259 nm of a sample of ct-DNA (200 �M) over 15 separate loadings of the capillary. The relative standard deviation (RSD) was 1.1%. An analogous experiment on the same sample without reloading gave an RSD of 0.8%. Thus the errors from realignment and small pathlength variations from sample reloading and cell reassembling contribute an acceptably small amount to overall variation.
Fig. 5 shows the relationship between voltage and rpm using a ct-DNA (200 �M) sample. It can be seen that a minimum voltage of 3 V is required to ensure sufficient rotation of this cell. This value will depend on the motor being used. As the voltage and rpm increases, the intensity of the LD signal also increases. A linear relationship was observed at voltages above 3 V (which fortuitously corresponds to 3000 rpm).
The LD of DNA in the micro-volume Couette LD cell (Fig. 6 a) shows a typical DNA LD spectrum: a negative maximum at 259 nm due to [pi]-[pi]* transitions of the DNA bases. Fig. 6 b shows a plot of LD^sub 259^ versus DNA concentration at constant rotation speed. These follow the Beer-Lambert law and show the orientation of DNA is not dependent on concentration over this range. The extent of DNA orientation was found to be 10-15% by substituting values for the LD and absorbance and using an average DNA base orientation of 86� (Chou and Johnson, 1993).
Ethidium bromide-DNA systems
Fig. 7 shows a plot of a titration series of ethidium bromide, a classical DNA intercalator, and DNA. The negative peak at 520 nm is due to [pi]-[pi]* transitions of ethidium bromide; the negative LD signal arises because ethidium bromide intercalates between DNA basepairs in accord with literature (Norden and Tjerneld, 1976). As the concentration of ethidium bromide is increased, the intensity of this signal increases. Ethidium bromide transitions are also observed below 350 nm in accord with literature expectations.
Fluorescence LD studies on ligands bound to ct-DNA
It should be noted that the final line of this equation is based on the assumptions that: i), the sample can be represented as some fully aligned and some unaligned molecules, ii), [gamma] is small, and iii), the DNA does not rotate significantly between excitation and emission. LD90 is thus expected to be negative for 0 < [alpha] < 60� and positive for 60� < [alpha] < 90�. By way of contrast, the change-over point is 54.7� for LD^sub 180^.
DNA is not expected to have an LD^sub 90^ signal because it is not fluorescent, as is in fact the case. However, upon adding DAPI, Hoechst, and ethidium bromide, the spectra of Figs. 8-10 were observed. Absorbance, LD^sub 180^ and standard excitation fluorescence spectra (with wide open emission slit as described above) are also shown.
DNA-DAPI interactions
The absorption spectra of free and ct-DNA-bound DAPI (Fig. 8 a) shows, in accord with literature reports, a red shift of the absorbance maximum by ~15 nm upon binding of DAPI to ct-DNA. There is also a hypochromism of ~20%. The fluorescence excitation spectrum of ct-DNA-bound DAPI with all emitted photons collected is shown in Fig. 8 b; this shows a maximum at ~369 nm and a shoulder at ~335 nm. The LD spectra of ct-DNA and ct-DNA in the presence of DAPI are given in Fig. 8 c. The ct-DNA shows a characteristic negative peak with maximum at 259 nm. When DAPI is present there is a contribution in this region of the spectrum as seen by a wavelength shift of the peak maximum from 259 nm to 257 nm. There is also a small increase in the ct-DNA LD signal intensity. A broad positive peak centered at ~345 nm is due to the long-axis polarized transition of the groove bound DAPI (where it is expected to bind for AT-rich DNA (Eriksson et al., 1993; Kubista et al., 1987)). There is also a slight negative region at 400 nm due probably to a small population of major groove bound, probably partially intercalated, DAPI at GC-rich regions (Eriksson, 1992; Kim et al., 1993).
The FDFLD spectrum of DAPI bound to ct-DNA is given in Fig. 8 d. There is a large negative peak at ~350 nm corresponding to the positive LD^sub 180^ band in Fig. 8 c. There is also a smaller negative peak at ~265 nm. This feature corresponds to the 262-nm peak in the DAPI absorbance spectrum that is approximately half the intensity of the one at 347 nm. Thus LD^sub 90^ is able to probe ligand transitions usually masked by the DNA absorbance. It should be noted that the FDFLD intensity will be dependent on the quantum yields of different binding modes and/or different sequences. In addition there is also the possibility of enhanced intensity due to energy transfer from the DNA bases. Given the magnitude of this peak such an effect is not obvious in this spectrum.
DNA-Hoechst interactions
The absoiption spectra of free and ct-DNA-bound Hoechst is shown in Fig. 9 a. It can be seen that there is red shift of absorbance maximum of ~20 nm upon the binding of Hoechst to ct-DNA. There is also a hypochromism of ~60%. Fig. 9 b shows the fluorescence excitation of Hoechst bound to ct-DNA with all emitted photons collected. A peak maximum is seen at ~367 nm with a shoulder at ~338nm. The LD spectra of ct-DNA and ct-DNA in the presence of Hoechst are given in Fig. 9 c. The ct-DNA shows a characteristic negative peak at 259 nm. When Hoechst is present there is a decrease in LD signal intensity compared to ct-DNA alone that could be a Hoechst contribution or a reduction in DNA alignment. It has previously been concluded from studies by Moon et al. (1996) that Hoechst binds in the minor groove of AT-rich regions (though the consensus of opinion is that Hoechst binds in the major groove of GC-rich DNA probably in some kind of partially intercalated binding mode; Colson et al., 1995; Moon et al., 1996), and the positive peak ~360 nm is due to the Hoechst bound to ct-DNA along the minor groove.
Fig. 9 d shows the FDFLD spectrum of Hoechst bound to ct-DNA. There is a broad negative peak in the 290-440 nm region. This corresponds well with the fluorescence excitation data collected and with the broad positive peak at ~360 nm in the LD spectrum. The positive FDFLD peak at 273 nm is the red-shifted signal of the 260-nm free Hoechst absorbance, consistent with this being a long-axis polarization transition whose LD signal is usually buried under that of the DNA. The superficial similarity of the DAPI and Hoechst FDFLD in the DNA region is misleading as one should note that the baselines slope so the 260-nm region is an FDFLD maximum for DAPI, whereas for Hoechst the same region is an absorbance minimum so not a signal. Similarly the ~270-nm positive peak is in fact zero for DAPI and an FDFLD signal for Hoechst.
DNA-ethidium bromide interactions
Fig. 10 a shows the absorption spectra of free and ct-DNA-bound ethidium bromide. The absorption maximum at 525 nm shows a red shift of ~40 nm upon the binding to ct-DNA. There is also a hypochromism of ~25%. The fluorescence excitation spectrum of ethidium bromide bound to ct-DNA with all emitted photons collected is shown in Fig. 10 b. A peak maximum at ~300 nm with a shoulder at ~330 nm is observed. A more intense peak is also present at ~530 nm. The LD spectra of ct-DNA and ct-DNA in the presence of ethidium bromide are given in Fig. 10 c. The ct-DNA shows a characteristic negative peak at 259 nm. When ethidium bromide is present there is an increase in LD signal intensity compared to ct-DNA alone. Ethidium bromide is a well-known and well-characterized intercalator. This means that the aromatic rings of ethidium bromide are able to insert between basepairs on the DNA making the DNA more rigid therefore increasing alignment (Norden and Tjerneld, 1976). There are two negative signals due to the ethidium bromide, one at ~520 nm and one showing as a shoulder and wavelength shift on the DNA signal at ~300 nm.
Fig. 10 d shows the FDFLD spectrum of ethidium bromide bound to ct-DNA. There is a broad positive peak with a maximum at 525 nm, corresponding to the negative LD band at that wavelength. There is also a broad positive peak from 250 to 350 nm corresponding to the absorbance peaks in this region. These signals are consistent with an intercalated ethidium bromide and show that it is possible to use absorbance signals that are usually complicated by being masked by DNA spectroscopy. Enhanced signals due to energy transfer from the DNA bases are more likely for an intercalator than for a groove binder. Once again although this possibility cannot be ruled out at this stage, the ethidium FDFLD does not resemble the DNA absorbance shape, so we conclude at least that this is not a dominant effect.
CONCLUSIONS
A micro-volume Couette flow cell has been designed and developed for linear dichroism spectroscopy for applications where sample availability is restricted. This is particularly a relevant issue for biological samples. Flow orientation is achieved by the alignment of linear molecules between a fixed quartz rod and rotating quartz capillary. The capillaries used are optically uniform and have advantages of being cheap and removable, which means that they have the potential of being disposable as well as being significantly easier to clean than other LD cells. Focusing lenses are used to focus the light beam onto the capillary, therefore, maximizing the photon count interacting with the sample. The capillaries do not distort LD, CD, or fluorescence spectra as shown by comparison with data collected using standard sample cells. Method validation using calf thymus DNA and groove binding and intercalating DNA binding ligands has shown sample volumes of ~25 �L are sufficient to obtain reproducible stable LD spectra, although slightly larger volumes reduce the risk of introducing air bubbles into the capillary upon loading. The ct-DNA has been oriented with an orientation parameter of S = 10-15% assuming an angle of 86� between the macroscopic orientation axis and the DNA base transition moment.
The capillary design of the micro-volume Couette flow LD cell has also enabled a new technique of fluorescence-detected flow linear dichroism to be undertaken. Exit holes from the cell at both 90� and 180� to the incident light enable measurement of fluorescence LD and normal LD, respectively. In both cases lenses have been placed close to the exit hole to capture the maximum amount of the emitted light and focus this toward the PMT. For measurements of fluorescence LD it was also necessary to move the PMT to be at right angles to the incident light beam.
The FDFLD showed the intrinsic contribution to the LD of the bound ligands whose bands lie under the DNA bands thus showing the potential of FDFLD for probing fluorophores in LD independently from other chromophores. The data are of sufficient quality that it has been possible to probe clearly transitions that are usually hidden by overlapping DNA absorbances. The quality of the fluorescence LD data are less good than the standard LD signal, however, due to the configuration of the spectrometer rather than the cell design. The use of filters or a second monochromator would improve the signal/noise in these experiments. Work is in progress to design a new spectrometer with smaller light beams and both fluorescence and linear dichroism capabilities to significantly improve the quality of the FDFLD data. It will be advantageous for this experiment to record actual differences in intensities of emitted light rather than logarithms of ratios.
[Reference]
The authors gratefully acknowledge the help of the referees as well as discussions with Y. Dupont and S. Windsor in leading to an understanding of the underlying basis of what had been measured. The technical skill and enthusiasm of Rhoderick Mortimore of Crystal Precision Optics in constructing the LD cells is gratefully acknowledged.
Financial support from the Engineering and Physical Sciences Research Council, UK (GR/M91105) and Syngebta, UK was also essential to the progress of this work.
REFERENCES
Bloemendal, M., and R. Vangrondelle. 1993. Linear-dichroism spectroscopy for the study of structural properties of proteins. Mol. Biol. Rep. 18:49-69.
Canet, D., K. Doering, C. M. Dobson, and Y. Dupont. 2001. High-sensitivity fluorescence anisotropy detection of protein-folding events: application to [alpha]-lactalbumin. Biophys. J. 80:1996-2003.
Chou, P., and W. C. Johnson. 1993. Base inclinations in natural and synthetic dyes. J. Am. Chem. Soc. 115:1205-1214.
Colson, P., C. Houssier, and C. Bailly. 1995. Use of electric linear dichroism and competition experiments with intercalating drugs to investigate the mode of binding of Hoechst-33258, Berenil and Dapi to Gc sequences. J. Biomol. Struct. Dyn. 13:351-366.
Couette, M. 1890. Etudes sur le frottement des liquides. Ann. Chim. Phys. 6:433-510.
Dafforn, T. R., J. Rajendra, D. J. Halsall, L. C. Serpell, and A. Rodger. 2004. Protein fibre linear dichroism for structure determination and kinetics in a low-volume, low-wavelength Couette llow cell. Biophys. J. 86:404-410.
Eriksson, S. 1992. DNA-Ligand Interactions Studied by Optical Spectroscopy. Chalmers University of Technology and University of Goteburg, Goteborg, Sweden.
Eriksson, S., S. K. Kim, M. Kubista, and B. Nord�n. 1993. Binding of 4',6-diamidino-2-phenylindole (DAPI) to AT regions of DNA: evidence for an allosteric conformational change. Biochemistry. 32:2987-2998.
Hofricheter, J., and W. Eaton. 1976. Linear dichroism of biological chromophores. Annual Review of Biophysical Bioengineering. 5:511-560.
Houssier, C., B. Hardy, and E. Fredercq. 1974. Interaction of ethidium bromide with DNA. Optical and electrooptical study. Biopolymers. 13: 1141-1160.
Johansson, L. B. A., and A. Davidsson. 1985. Analysis and application of linear dichroism on membranes - description of a linear-dichroism spectrometer. Journal of the Chemical Society-Faraday Transactions 1. 81:1375-1388.
Kim, S. K., S. Eriksson, M. Kubista, and B. Nord�n. 1993. Interaction of 4',6-diamidino-2-phenylindole (DAPI) with poly[d(G-C)^sub 2^] and poly[d(G-m^sup 5^C)^sub 2^]: evidence for major groove binding of a DNA probe. J. Am. Chem. Soc. 115:3441-3447.
Kubista, M., B. Akerman, and B. Nord^sup e^n. 1987. Characterization of interaction between DNA and 4',6-diamidino-2-phenylindole by optical spectroscopy. Biochemistry. 26:4545-4553.
Lee, C., and N. Davidson. 1968. Flow dichroism of deoxyribonucleic acid solutions. Biopolymers. 6:531-550.
Lowry, T. M. 1935. Optical Rotatory Power. F. G. Donnan, editor. Longmans, Green and Co., London, UK. 405-408.
Miles, A. J., F. Wien, J. G. Lees, A. Rodger, R. W. Janes, and B. A. Wallace. 2003. Calibration and standardisation of synchrotron radiation circular dichroism and conventional circular dichroism spectrophotometers. Spectroscopy. 17:653-661.
Moon, J. H., S. K. Kim, U. Sehlstedt, A. Rodger, and B. Nord�n. 1996. DNA structural features responsible for sequence-dependent binding geometries of Hoechst 33258. Biopolymers. 38:593-606.
Nord�n, B., M. Kubista, and T. Kurucsev. 1992. Linear dichroism spectroscopy of nucleic-acids. Q. Rev. Biophys. 25:51-170.
Nord�n, B., and T. Kurucsev. 1994. Analysing DNA complexes by circular and linear dichroism. J. Mol. Recognit. 7:141-156.
Nord�n, B., and F. Tjerneld. 1976. High-sensitivity linear dichroism as a tool for equilibrium analysis in biochemistry. Stability constant of DNA-ethidium bromide complex. Biophys. Chem. 4:191-198.
Oriel, P., and J. Schellman. 1966. Studies of the birefringence and birefringence dispersion of polypeplides and proteins. Biopolymers. 4:469-494.
Rodger, A. 1993. Linear dichroism. Methods Enzymol. 226:232-258.
Rodger, A., J. Rajendra, R. Marrington, M. Ardhammar, B. Nord�n, J. D. Hirst, A. T. B. Gilbert, T. R. Dafforn, D. J. Halsall, C. A. Woolhead, et al. 2002. Flow oriented linear dichroism to probe protein orientation in membrane environments. Physical Chemistry Chemical Physics. 4:4051-4057.
Simonson, T., and M. Kubista. 1993. DNA orientation in shear How. Biopolymers. 33:1225-1235.
Takakuwa, T., T. Konno, and H. Meguro. 1985. A new standard for calibration of circular dichroism: ammonium d-10-camphorsulfonate. Analytical Sciences. 1:215-218.
Wada, A. 1964. Chain regularity and flow dichroism of deoxyribonucleic acids in solution. Biopolymers. 2:361-380.
Wada, A. 1972. Dichroic spectra of biopolymers oriented by flow. Applied Spectroscopy Reviews. 6:1-30.
Wada, A., and S. Kozawa. 1964. Instrument for the studies of differential flow dichroism of polymer solutions. Journal of Polymer Science Part A. 2:853-864.
Wells, R. D., J. E. Larson, R. C. Grant, B. E. Shortle, and C. R. Cantor. 1970. Physicochemical studies on polydeoxyribonucleotides containing defined repeating nucleotide sequences. J. Mol. Biol. 54:465-497.
Wilson, R., and J. Schellman. 1978. The flow linear dichroism of DNA: comparison with the bead-spring theory. Biopolymers. 17: 1235-1248.
[Author Affiliation]
Rachel Marrington,* Timothy R. Dafforn,[dagger] David J. Halsall,[double dagger] and Alison Rodger*
* Department of Chemistry, University of Warwick, Coventry, CV4 7AL, United Kingdom; [dagger] Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom; and [double dagger] Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, CB2 2QQ, United Kingdom
[Author Affiliation]
Submitted September 19, 2003, and accepted for publication June 14, 2004.
Address reprint requests to Alison Rodger, E-mail: a.rodger@warwick.ac.uk.
WASHINGTON The Supreme Court permitted the Bush administrationSaturday to continue intercepting Haitians at sea and forciblyreturning them to their homeland without determining whether they arepolitical refugees.
The action, sought by the Justice Department, temporarily blocksa federal appeals court ruling Wednesday that voided President Bush'stwo-month-old executive order that Haitians fleeing by boat beescorted back to Haiti.
In a 7-2 vote, the Supreme Court gave the government until Aug.24 to ask the high court to consider the merits of the case.
Justices Harry Blackmun and John Paul Stevens dissented, sayingthat the fleeing Haitians face "the real and immediate prospect ofpersecution, terror and possibly even death at the hands of those towhom they are being forcibly returned."
Lawyers for the Haitians say they are entitled to immigrationhearings to determine whether they should be classified as refugeeseligible to come to this country.
The Bush administration has said concern for the safety of theHaitians was a major consideration for its actions. Deputy presssecretary Judy Smith said the White House was pleased that the stay"will continue to discourage Haitians from taking unseaworthy vesselsto the United States."
Lucas Guttentag, attorney for the Haitians, said he is confidentthat when the case is heard, "the court will find that thepresident's order violates the most fundamental principles of U.S andinternational obligations."
The lawyers representing the Haitians will ask the courttomorrow to hear the case on an accelerated basis, Guttentag said.
"My only hope is that either Congress does something orelections sweep out President Bush," said another lawyer for theHaitians, Michael Ratner.
Thousands of Haitians have been intercepted at sea and returnedto their country since the president's order of last spring, Ratnersaid.
And thousands of Haitians have sought asylum at the U.S. Embassyin Port-au-Prince in the last few months.
A Justice Department statement issued a few days ago encouragedthe asylum requests. To date, less than 100 have been grantedadmission to the United States.
About 30,000 Haitians fled their country after a military coupdeposed President Jean-Bertrand Aristide last fall.
Bush signed his executive order in May, permitting the return ofthe refugees.
The boat traffic declined immediately after the United Statesdecided to return those picked up at sea directly to Haiti.
The Bush administration says most of those fleeing Haiti areseeking a better economic life and do not qualify for politicalasylum.
In the dissent, Blackmun said the government has offered only "avague invocation of harm to foreign policy, immigration policy andthe federal treasury."
Observations of a severe thunderstorm that spawned a large F3 tornado near Almena, Kansas, on 3 June 1999 showed remarkably few cloud-to-ground lightning (CG) flashes. During a 4.5-h lifetime, in which the storm went from low-precipitation supercell to classic supercell and back, there were just 17 CG flashes. The low CG flash rate highlights the fact that accurate assessments of storm intensity cannot reliably be made using CG lightning flash data alone.
The CG rates for the Almena storm occurred despite the large tornado and baseball-sized hail at the surface. The rates were considerably less than the smallest documented in prior research on CG lightning in violent tornadic storms. In contrast, the data from a portable detector showed that total lightning rates were large enough to suggest the storm was very severe. Total lightning rates during the large tornado were very large-approximately 100/min.
One reason for the lack of CG lightning in the Almena storm may have been its complete isolation from other storm anvils and cirrus clouds. Such clouds, common in severe events, can seed cumulonimbus clouds, alter their microphysical properties, and possibly enhance their precipitation and CG lightning rates.
This study suggests the desirability of obtaining new total flash rate observations from geostationary satellites.-E. W. MCCAUL JR. (UNIVERSITIES SPACE RESEARCH ASSOCIATION), D. E. BUECHLER, S. HODANISH, AND S. J. GOODMAN. "The Almena, Kansas, Tornadic Storm of 3 June 1999: A Long-lived Supercell with Very Little Cloud-to-Ground Lightning," appearing in the February Monthly Weather Review.
CHICAGO - A girl and her grandparents have sued the Chicago Board of Education, alleging that a substitute teacher showed the R-rated film "Brokeback Mountain" in class.
The lawsuit claims that Jessica Turner, 12, suffered psychological distress after viewing the movie in her eighth-grade class at Ashburn Community Elementary School last year.
The film, which won three Oscars, depicts two cowboys who conceal their homosexual affair.
Turner and her grandparents, Kenneth and LaVerne Richardson, are seeking around $500,000 in damages.
"It is very important to me that my children not be exposed to this," said Kenneth Richardson, Turner's guardian. "The teacher knew she was not supposed to do this."
According to the lawsuit filed Friday in Cook County Circuit Court, the video was shown without permission from the students' parents and guardians. Richardson had previously complained to school officials about reading material he said contained curse words.
"This was the last straw," he said. "I feel the lawsuit was necessary because of the warning I had already given them on the literature they were giving out to children to read."
Messages left over the weekend with school district officials were not immediately returned.
MEXICO CITY Millions of smog-sick residents of Mexico City maybe breathing a little easier, at least for a couple of months.
In an unusually aggressive attempt to clean up the world's mostpolluted air, authorities have told car owners in the sprawlingmetropolitan area of 18 million people that they must leave theirvehicles at home one day a week.
Violators of the government's new "Day Without a Car" program,scheduled to last through February, face a $100 fine and their carswill be impounded for a day.
In a related move, the state oil company Petroleos Mexicanos, orPemex, is making available a blend of low-lead gasoline that is farcleaner than the leaded fuel common here. Pemex has agreed to pickup the estimated $16 million cost for the next three months.
"These programs may come just in time to avoid a catastrophe inMexico City," says environmental scientist Luis Manuel Guerra. "Butto make a difference, they must be permanent. A three-month-a-yearanti-pollution program isn't enough in a city where the air isdeadly."
Motorists have been issued color-coded stickers that tell themon which weekday they cannot drive. Frequent radio announcements andbright signs around the capital publicize the program.
To encourage compliance, officials have beefed up bus fleets toimprove mass transit, and Mayor Manuel Camacho has promised to resumethe subway expansion halted amid financial constraints two years ago.
The new measures come after milder, mostly voluntary stepsfailed to have much impact on the thick, gray haze that blankets thecity, often leaving Mexicans wheezing, red-eyed and unable to seemore than five blocks on the city's busiest streets.
During the past two years, pollution in the city has been sosevere that birds have dropped dead from the sky, and children havebeen given extra school holidays to get them away from the worstzones.
But local newspapers have warned that corrupt police are alreadyundermining the "Day Without a Car" program, accepting $25 bribes tolet motorists off the hook. A radio station reported brisk sales of$30 bogus decals.
"When I see the politicians taking the subway to work, I'llbelieve they're serious about fighting pollution," said Ruben Solina,a local businessman, as he waited for a bus.
Yet some ecologists are encouraged.
"The government has always been very timid when it comes tofighting pollution," Guerra says. "We're hoping this marks the end ofsymbolic ecology and the start of action."
Patterns of European Industrialization: The Nineteenth Century. Edited by Richard Sylla and Gianni Toniolo London: Routledge, 1991. xii + 276 pp. Figures, tables, contributors, and index. $22.50. ISBN 0-415-08156-4.
Richard Sylla and Gianni Toniolo have collected twelve insightful essays on Alexander Gerschenkron's contributions to our understanding of European economic development. Gerschenkron's research interests covered several aspects of European industrialization, synthesizing many interpretations of industrialization into a `relative backwardness' concept in contrast with the prevailing 'stage' theories of industrialization of the 1960s. In their introduction the editors state that "[a]ccording to Gerschenkron, relative backwardness-however measured-is a powerful explanatory variable of such characteristics of industrial development as timing, growth rates and structural change.... The variables to be considered, however, should be those most relevant for the emergence of preconditions for subsequent economic development. Among such variables he therefore included savings ratios, literacy, some technology-related indicators (e.g. patents), per capita social overhead capital, and even less measurable ones such as ideology" (p. 6). The essays in this volume use these variables, and others, to test some of Gerschenkron's hypotheses.
In their introduction, Sylla and Toniolo couch their interest in European industrialization within the context of trying to understand the rapid economic, social and political changes currently taking place in Eastern Europe. In some former Soviet countries economic growth has been impressive; in others, disappointing. Given uncertainty about the future paths of development in Eastern Europe, can historical analysis, through the lens of Gerschenkron's hypotheses, give us any focal ideas on which to concentrate? As the editors note, nineteenth-century industrialization may provide some general insights into the transition to a market economy, but we should proceed with caution in applying historical lessons, because the current initial conditions for this transition differ so greatly from those a century or more ago.
The eleven remaining essays divide into two sections: institutions, ideologies and interpretations, as well as country studies. Knick Harley's essay on institutional endogeneity starts the first section forcefully. Harley examines Gerschenkron's ideas on substitutions for lacking prerequisites, citing such modern work as Oliver Williamson's (1975, 1984) research on the substitution of hierarchies for markets, particularly in less developed economies. Richard Sylla analyzes the role of banks in European industrialization, discussing Gerschenkron's fascination with banking along the way. Paul Gregory uses Russia as a case study of the role of the state in promoting economic development, arguing that one of the important missing preconditions in Russia in the nineteenth century was a strong middle class. William Parker examines the connection between industrialization and political ideology with a comparative study of American and European patterns of growth. Donald McCloskey contributes an analysis of Gerschenkron's industrialization rhetoric, focusing on his use of words and metaphors.
N. F. R. Crafts, S. J. Leybourne and T. C. Mills open the country studies section of the volume by looking at British industrialization. This essay summarizes many of Crafts' earlier contributions and uses sophisticated time-series analysis to conclude that Britain's industrialization was indeed unique relative to the nations of continental Europe, with a longer, slower growth-rate trend, leading into the mid-nineteenth century. Maurice LevyLeboyer and Michel Lescure discuss French growth, although they seem to skirt an issue essential to Gerschenkron's contribution. They argue that France was more advanced in the nineteenth century than previously thought, based on evidence such as railroad investment; however, France's available capital for railroad construction came predominantly from the government. Gerschenkron argued that the government substituted for imperfect capital markets in backward countries, implying that France was relatively backward. Richard's Tilly's analysis of German industrialization suggests some difficulties with Gerschenkron's model, particularly the absence of "an explanation of state behavior and changes in it.... Explaining the role of the state means developing an appropriate model of political change" (p. 192). Giovanni Frederico and Gianni Toniolo apply Gerschenkron's model to Italy; they find that German banks may not have played much of a role in Italian industrialization, and that "around 1900, the Italian economy was probably richer and more diversified than Gerschenkron supposed, so that several causes were at work in producing the 'spurt' " (p. 213). David Good's essay on Austria-Hungary echoes some of Tilly's observations on Germany, indicating that while Austria-Hungary did not "confirm" (p. 218) Gerschenkron's relative backwardness thesis, the economics of Austro-Hungarian history is intertwined with the interplay of society and state prevalent throughout Habsburg history (p. 239). In the final essay, Olga Crisp analyzes Russian industrialization. Crisp argues that more recent historical work has brought to light information highly inconsistent with Gerschenkron's hypotheses about Russian industrialization; she emphasizes particularly the role of railroads and the persistence of stable agricultural growth rates. As with the Levy-Leboyer/Lescure chapter on France, though, Crisp fails to address the question of how advanced Russia really was if the government was providing the capital for railroad investment.
One mark of Gerschenkron's influence on economic history is the flurry of research activity over the past three decades stemming from trying to explore his relative backwardness concept even further, and to test its resultant hypotheses. This collection of interesting essays is a testament to the continued importance of Gerschenkron's work.
[Author Affiliation]
Lynne Kiesling is assistant professor of economics at the College of William and Mary.
PHILADELPHIA (AP) — Roy Oswalt threw seven dominant innings, Raul Ibanez hit a grand slam and the Philadelphia Phillies clinched their fifth straight NL East title with a 9-2 victory over the St. Louis Cardinals on Saturday night.
In a season where nothing less than a World Series championship would be considered a success, there wasn't much of a party on the field. The Phillies had a been-there, done-that attitude toward winning the division last year, and this time was no different.
Players ran onto the diamond a bit faster than usual, but they simply exchanged handshakes, hugs and high-fives as if this was an ordinary game in April. They did at least put on shirts and hats proclaiming themselves division champs.
The fans didn't even scream all that loud, even when the Phillie Phanatic ran on the field with a big flag that said 2011.
Once they reached the clubhouse, however, the Phillies popped open the bubbly and celebrated their achievement.
With the Four Aces leading the way, the Phillies are seeking their third NL pennant in four years and second World Series title.
They've taken care of the first step. Now they'll use the 12 remaining games to get ready for the postseason. It's still uncertain who the Phillies will face in the best-of-five first round when the NL playoffs begin Oct. 1.
The major league-leading Phillies (98-52) are four wins away from setting a single-season club record.
Oswalt (8-9) allowed no runs and five hits, striking out seven. Brad Lidge got one out in the eighth after Michael Stutes ran into trouble, and Ryan Madson finished with a seven-run cushion.
St. Louis fell 4½ games behind Atlanta in the wild-card race. They had won eight of nine to narrow the gap from 8½ back on Sept. 6.
Cardinals starter Jake Westbrook (12-9) allowed one earned run and five hits in 3 1-3 innings. He's given up two earned runs or less in 11 of his 16 road starts this season, but fell to 8-4 away from home.
Oswalt, Philadelphia's best pitcher down the stretch last year after coming over from Houston in a trade on July 29, left spring training as the No. 3 starter behind Roy Halladay and Cliff Lee. But he struggled after starting 3-0, and a back injury forced him to the disabled twice.
The three-time All-Star was vintage Oswalt against the Cardinals. His fastball reached 94 mph a few times, and he had a nasty curveball.
Oswalt struck out Skip Schumaker on a 76 mph curve to leave two runners on in the seventh. All of his Ks came on swings.
Stutes nearly blew a 3-0 lead in the eighth after getting the first two outs. Four straight singles by John Jay, Albert Pujols, Lance Berkman and David Freese got the Cardinals within 3-2.
But Lidge came in and retired Allen Craig on a grounder to second on his first pitch to end the inning.
The Phillies then blew it open with six unearned runs in the eighth. Carlos Ruiz reached second when his grounder skipped past third baseman Daniel Descalso for an error. Ruiz went to third on Jimmy Rollins' one-out single and scored on Shane Victorino's single up the middle.
After Chase Utley was hit by a pitch, Ryan Howard struck out.
Octavio Dotel entered and Hunter Pence hustled out an infield single to shortstop Rafael Furcal to drive in another run. Ibanez then hit his slam to right to put it away.
Pence gave the Phillies a 1-0 lead on an RBI double in the first. An error by Furcal helped the Phillies add a run in the fourth. Placido Polanco led off with a walk. Oswalt sacrificed with one out and Furcal dropped the throw to second. Rollins followed with a single to load the bases. Victorino walked to force in Polanco to make it 2-0.
That ended Westbrook's night.
Arthur Rhodes came in and retired Utley on a shallow fly and Howard on a grounder.
Victorino hit a solo homer off Kyle McClellan in the sixth. He's been slumping lately, batting just .163 (14 for 86) in his previous 21 games.
Oswalt likely will be the fourth starter in the postseason after Halladay, Lee and Cole Hamels. Rookie Vance Worley would go to the bullpen, despite an 11-2 record.
NOTES: A crowd of 45,470 was the 211th straight sellout at Citizens Bank Park, including playoffs. ... This was the fastest the Phillies ever clinched a division title. The previous was Game No. 156 in 1976. ... The Phillies had all their regulars in the starting lineup for the first time since Aug. 6. ... Rollins was 4 for 5. He was 3 for 20 coming in. ... The Phillies have scored just 22 runs in the last nine games and no more than three in any of them. ... The Cardinals are 6-28 when scoring fewer than three runs. ... St. Louis used seven pitchers. ... Hamels (14-8) faces Chris Carpenter (9-9) when the teams meet Sunday night.
Britain's domestic spy agency MI5 is tracking a number of terrorism plots against the U.K., despite successes in curbing the threat from extremists since deadly attacks on London's transit network five years ago, an official said Wednesday.
Prime Minister David Cameron marked the fifth anniversary of the July 7, 2005, suicide bombings on three subway cars and a bus, sending a wreath and handwritten note to be laid at a memorial to the 52 commuters killed in the attack.
"It was a dreadful day, but it is also a day that will remain, I believe, a symbol of the enduring bravery of the British people," Cameron told the House of Commons.
As the bereaved and injured marked the anniversary, security officers said they continue to monitor hundreds of suspected extremists and plots, but believe work at home and overseas has hampered the ability of terrorists to mount major attacks.
Britain raised its threat level to "severe" in January, the second highest level on a five-point scale, in the wake of the failed attempt to bring down a Detroit-bound airliner on Christmas Day.
Security officials said a range of threats at various stages of development are currently being monitored in Britain _ but did not offer a specific figure on how many are under surveillance.
"The threat level is at severe, which means an attack is highly likely," said a government security official, who demanded anonymity to discuss such issues. "There are a range of operations being conducted at any one time."
In January, MI5 director Jonathan Evans told lawmakers his officers are monitoring "a couple of hundred cases of one sort or another," and previously confirmed about 2,000 people in Britain are suspected of involvement in terrorism. He has acknowledged that a series of hefty jail terms handed to convicted terrorists in recent years and the killing of senior al-Qaida operatives in Pakistan and elsewhere have led to a fall in the number of major plots in Britain.
Evans was quoted in an agency history published last year as saying recent convictions have had "a chilling effect on the enthusiasm of the plotters."
Abdulla Ahmed Ali, the British ringleader of a plot to bring down trans-Atlantic airliner bound for North America with liquid explosives, was jailed last year for a minimum of 40 years. Briton Dhiren Barot was jailed for life in 2006 over plans to bomb U.S. financial landmarks and luxury London hotels.
Officials also say they now have a better understanding of the links between suspected terrorists, and are better able to comb through the contacts of those arrested to uncover other plotters.
Lawmakers reported last year that police and security officials likely missed possible chances to identify the London bombers as a potential threat ahead of the 2005 attacks.
One of the London bombers was tracked by intelligence officers as early as 2001, and he and an eventual accomplice were monitored in 2004, but dismissed as petty con artists while officials focused on more pressing threats.
In April, MI5 and police claimed to have disrupted an al-Qaida bomb plot against Britain after making a series of arrests across northern England. All 12 suspects detained were later released without charge, though then-Prime Minister Gordon Brown insisted a "major terrorist plot" had been averted.
Cameron told lawmakers Tuesday that "every day, intelligence officers track terrorist threats and disrupt plots."
Tony Blair, prime minister at the time of the London bombings, said in a statement Wednesday that while the four suicide bombers had succeeded in striking London, "in truth, the terrorists failed."
"Britain resolved, even more surely, to defeat the extremism and intolerance which drove the attackers and stand up for the values of freedom, democracy and the rule of law which as a nation we cherish," Blair said.
Families of some of the victims of the 2005 attacks said Wednesday they were saddened by a decision not to hold an official remembrance ceremony.
Graham Foulkes, whose 22-year-old son David was killed in the Edgware Road bombing, said the fifth anniversary was significant and the absence of the prime minister or London Mayor Boris Johnson at the ceremony was disappointing.
Britain's government said other relatives had asked the government to step back this year to allow a more private ceremony to take place.
SCIENCE + INSANITY = HUMOR
Regular readers of this column will recognize some of these whacked-out scientific research papers mentioned in past columns, but since they were so thoughtfully compiled in an article called "The 10 Most Bizarre Scientific Papers," it gives me a chance to revisit these bits of classic weird science. Check out Oddee.com for the stories behind these bizarre titles: "The Effect of Country Music on Suicide;" "Love and Sex with Robots;" "Chickens Prefer Beautiful Humans;" "Safe and Painless Manipulation of Penile Zipper Entrapment;" "Pressures Produced When Penguins Poo-Calculations on Avian Defecation;" "Ultrasonic Velocity in Cheddar Cheese as Affected by Temperature;" "Impact of Wet Underwear on Thermoregulatory Responses" and "Thermal Comfort in the Cold."
GARBAGE, GARBAGE EVERYWHERE
Oceanographers are claiming that there is a heap of garbage twice the size of Texas floating in the Pacific Ocean between San Francisco and Hawaii. Dubbed the Great Pacific Garbage Patch, the heap of debris is said to weigh around 3.5 million tons and consists of about 80 percent plastic garbage. Supposedly most of the non-biodegradable trash that ends up in the oceans is sucked into this area by a combination of wind and waves, making the trash heap grow with each passing year. Even worse, there is nothing we can do to remove the trash as no single country will take responsibility for it and the cleanup would take an international effort which would cost billions of dollars. So stop throwing your plastic crap in the ocean, OK? (SF Gate)
GLOBAL WETTING
Even though sea levels have only risen 19.5 centimeters since 1870 (that's about 1.44 millimeters per year), climate researchers have created a list of mega-cities that might be highly vulnerable to flooding thanks to global warming by the year 2015. So if you live in any of the following cities, you might want to consider moving uphill a few centimeters within the next eight years: Dhaka, Buenos Aires, Rio de Janeiro, Shanghai, Tianjin, Alexandria, Mumbai, Kolkata, Jakarta, Tokyo, Osaka-Kobe, Lagos, Karachi, Bangkok, Thailand, New York and Los Angeles. (Associated Press)
NOT COOL
You can now order the world's first global warming coffee mug. A map of the world adorns the outside of this mug, which is cool, but when you fill it up with a hot drink, the low-lying land masses on the map begin to disappear as the ice caps melt and the ocean spreads across the coast lines. Get yours from Firebox.com.
CURIOUS HEADLINE OF THE WEEK
As seen in Scotland's Daily Record last week: "Nun Murdered by Ninja Warrior."
MORE CRAP FOR SALE
According to a group called Consumers International, the single worst consumer product in the world is Rozerem, a sleeping pill marketed for children. The drug's manufacturer, Takeda Pharmaceuticals, was awarded the honor after airing television commercials in the United States featuring groggy children returning to school with the suggestion that Rozerem could help your child with his or her sleeplessness. The group also wagged its finger at CocaCola for using regular tap water for its Dasani brand of bottled water, and Mattel for selling over 19 million products that had to be recalled in the past year. (AFP)
BREAK OUT THE RUM AND EGGNOG A LITTLE EARLIER THIS YEAR
OK, before you start hanging up those Christmas decorations, don't forget to celebrate these special days: according to unreliable sources Nov. 15 is Clean Out Your Refrigerator Day; Nov. 19 is Have A Bad Day Day; Nov. 22 is Start Your Own Country Day and Nov. 30 is Stay At Home Because You're Well Day.
NO CURE FOR PARANOID DELUSIONS
If you're being harassed by God, Satan, aliens, zombies, Bigfoot, or death, a mere five bucks will get a restraining order against any of the above-mentioned evils at ParanormalRestrainingOrders.com.
INTERNET FACT OF THE WEEK
All the numbers on a roulette wheel add up to 666.
More bizarro news at CuriousTimes.com.
Jim Lindeman's fifth-inning home run backed a combinedsix-hitter by John Tudor and Todd Worrell as the St. Louis Cardinalsdefeated the host Cincinnati Reds 2-1 Friday night to end a five-gamelosing streak. The Cardinals boosted their National League East leadto 3 1/2 games over the Mets and four over the Expos.
Tudor (4-2) pitched 6 2/3 innings for the victory, giving upfive hits. Worrell hurled the final 2 1/3 innings for his 26th save.Guy Hoffman (8-9) took the loss.
Lindeman's seventh homer of the season was almost caught by Redscenter fielder Eric Davis. Davis, who has made four over-the-wallcatches this season, got a glove on the ball, but lost both the balland his glove over the left-center field wall.
The Cardinals scored the eventual winning run in the sixth onTerry Pendleton's double and a run-scoring single by Willie McGee.Cincinnati closed to 2-1 in the seventh on consecutive doubles byDave Concepcion and Dave Collins.
Giants 6, Expos 3: Jeffrey Leonard hit a three-run homer, his17th of the season, and pitcher Dave Dravecky had two hits and scoredtwice as visiting San Francisco defeated Montreal and took a one-gamelead over Cincinnati in the NL West. Dravecky (7-9) went 5 2/3innings, allowing 10 hits. Don Robinson finished for his 15th save.Dennis Martinez (7-2) was tagged for 10 hits in his 6 2/3 innings andtook Montreal's third straight loss.
Padres 6, Mets 2: John Kruk hit a two-run homer and Jimmy Jones(6-4) won his fourth straight decision to lift visiting San Diegoover New York.
Kruk's 16th home run, a two-run shot in the third inning, cameoff Ron Darling (10-8), who had a personal six-game winning streakstopped.
Indians sweep Tigers: John Farrell pitched a six-hitter in hisfirst major league start and host Cleveland beat Detroit 8-3 tocomplete a sweep of their doubleheader. Cleveland stopped theTigers' five-game winning streak with a 12-4 victory in the opener.The losses left first-place Detroit .002 ahead of Toronto in the ALEast.
Angels 3, Blue Jays 1: Devon White and Tony Armas delivered solohome runs off Phil Niekro in the sixth inning to carry hostCalifornia over Toronto. Niekro (7-13) had never allowed a home runto a California batter in 81 2/3 innings since coming to the AmericanLeague from Atlanta in 1982.
A pair of National League castoffs, Jerry Reuss (4-1) and GregMinton, combined on an eight-hitter to halt the Angels' three-gamelosing streak.
Athletics 6, Yankees 4: Alfredo Griffin's two-run homer and MarkMcGwire's two-run double highlighted a five-run third inning and hostOakland beat New York to pull within three games of first-placeMinnesota in the AL West.
Steve Ontiveros (7-6) gave up eight hits in 8 2/3 innings. Hestruck out a career-high seven and walked one. Jay Howell got thefinal out for his 16th save, his first since July 6. The loser wasRon Guidry (3-8). Guidry, who has lost three straight, gave up sevenhits in his second complete game.
Red Sox 11, Twins 3: Roger Clemens scattered six hits and struckout nine before being bailed out of a seventh-inning jam by WesGardner as host Boston handed Minnesota its fourth straight loss.Clemens (13-7) won for the ninth time in his last 10 decisions.Frank Viola (14-8) lost for the second time in 10 decisions. RookieMike Greenwell drove in three runs with a triple and two singles.
Phillies sweep Dodgers: Milt Thompson knocked in the winning runin both games as host Philadelphia swept a doubleheader from LosAngeles 2-1 in 11 innings and 7-3. Thompson's sixth-inning, two-rundouble in the nightcap helped Shane Rawley to his NationalLeague-leading 16th victory against five losses. Tim Leary (3-9)took the loss.
Thompson, who went 7-for-11 with four hits in the first game andthree in the second, has knocked in the winning run in each of hislast four games, tying a NL record set by Johnny Ray.
Braves 5, Pirates 4: Dale Murphy hit his 300th career home runand Gerald Perry singled in the winning run in the seventh inning asAtlanta edged visiting Pittsburgh. Murphy's 34th homer of the yearcame off starter Brian Fisher.
Mariners 3, Orioles 2: John Moses and Phil Bradley homered andMike Moore (6-15) hurled a club record fifth straight complete gameto lead host Seattle over Baltimore.
THERE'S NO SENSE BEMOANING THE PROLIFERATION OF MOBILE DEVICES IN THE ENTERPRISE. THAT 'GENIE' ESCAPED YEARS AGO. NOW IT'S UP TO IT EXECUTIVES TO MANAGE THE MYRIAD MOBILE DEVICES USED BY EMPLOYEES, DEVELOP COHERENT USAGE POLICIES AND DEPLOY SECURITY TO PROTECT CORPORATE ASSETS.
ASK ANY EXECUTIVE FOR A LIST OF GAME-CHANGING technologies, and mobility is likely to appear near the top. Smartphones, PDAs, laptops, netbooks, Wi-Fi, cellular broadband and a variety of other tools make it possible to exchange e-mail, sales leads and other data from almost any point on Planet Earth. The widespread availability of real-time communication has ushered in a new era of opportunity and efficiency.
Forrester Research reports that 73 percent of global enterprise work forces will be mobile by 2012. Managing a plethora of devices, developing coherent policies and instituting adequate security are no small tasks.
"CIOs and other IT executives face enormous challenges," says Sean Ryan, research analyst for Mobile Enterprise at IDC. "With so many devices and so much fragmentation in the marketplace, it's difficult to develop sound policies, procedures and practices that address all the issues."
Unfortunately, the situation isn't getting any easier. While executives may clamor for BlackBerrys, a sales force may demand iPhones. While some workers connect their laptops via secure cellular connections, others tap into the network via unsecure Wi-Fi.
Then there's the issue of business versus personal use. With so many options and possibilities, IT can find itself reeling. Who provides the devices and who pays for them? Should an organization standardize on one or two platforms, or create an open environment? And what security policies are required to keep corporate assets safe?
There is no one-size-fits-all approach. "It's important for an organization to thoroughly understand its business processes and workflows-as well as who is using the devices and how they are using them," says Bill Clark, research vice president at Gartner. In addition, it's vital to build a framework that's flexible and cost-efficient. "A cradle-to-grave viewpoint is essential," he adds. "Without strong oversight, it's difficult to manage mobility effectively."
A SOUND APPROACH
Mobile technology has emerged as a mainstream tool that reaches every level of an enterprise-and beyond. However, getting a handle on mobile assets and developing a strategy for managing them can prove daunting. Although software applications can handle the mechanics of keeping track of devices, they do nothing to help an organization develop a coherent strategy for purchasing, issuing, and overseeing the technology and the way it is used.
A 2009 mobility study conducted by Motorola found that the biggest challenges facing a mobile enterprise are cost of hardware; security concerns and risks; cost of software, integration, service and support; difficulties in employee training and support; and difficulties integrating mobile applications into the existing infrastructure. Although the survey focused on the hospitality industry, it's clear that these issues are something that all organizations must cope with.
A starting point, Clark says, is to identify what tasks take precedence, and then map devices and tools to specific roles across the organization. While BlackBerrys may be ideal for executives who message heavily, an iPhone loaded with the right CRM application or database tool may unleash the full potential of a sales force or field support agent. "It's important to eliminate steps, simplify data entry and access, and make people more strategic," he says.
Of course, no two businesses are created equal. Safelite AutoGlass repairs and replaces automobile windshields at facilities and mobile service vans scattered across every U.S. state. The company, headquartered in Columbus, Ohio, found that by consolidating on a single platform-in this case, BlackBerrys equipped with a Bluetooth pen and a printer-it could streamline an array of processes and manage scheduling and field transactions far more efficiently. It adopted the mobile platform four years ago. Today, it has more than 3,300 smartphones in the field, says Chris Delong, director of open systems and infrastructure.
Standardizing on a single platform was all about dollars and sense. Since field technicians require the devices for messaging and handling transactions, the company installed a BlackBerry Enterprise Server and created a blacklist and whitelist of Web sites. There are no limits on voice calls. Instead, the company uses trip wires that indicate only whether an employee is placing international calls or venturing beyond an established threshold for calls or text messages.
Safelite allows some executives to use iPhones or Windows Mobile devices because they have more complex requirements. "There is a smattering of other devices but, from an operational perspective, the BlackBerry is the device of choice because it simplifies IT management and provides tight controls," Delong notes.
In fact, the company oversees the entire mobile device environment with a four-person IT staff. "Standardization, along with a mature, robust BlackBerry platform, has allowed us to maximize ROI," he adds.
STANDARDIZATION IS DIFFICULT
Safelite's situation is not typical, and many firms find it difficult to standardize on a single mobile device or platform. Different departments and employees have diverse needs, so locking in on a single system can undermine productivity. As Gartner's Clark puts it: "An organization that lacks flexibility and the right tools can find itself at a strategic disadvantage."
Platforms and preferences are key issues facing the Nationwide Mutual Insurance Co. The Columbus, Ohio, firm, with $1.7 billion in 2008 sales, has traditionally relied on BlackBerrys for messaging and voice communication. It has also used cellular broadband-equipped laptops for certain situations. "The goal has been to make data widely available within a secure, managed environment," says Robert Burkhart, director of new technology.
In the past, Nationwide owned smartphones and various employee-used devices, but it may soon shift to an employee ownership model. The proliferation of iPhones and other devices-along with more advanced management and security capabilities-is forcing decision-makers to rethink things.
"There's no reason for people to carry two or more devices," Burkhart says. "And pricing plans have come down to the point where limits for personal calls and minutes aren't necessary." But the firm will likely continue to impose caps on data usage.
To embrace a more open and flexible environment, Nationwide turned to Sybase Afaria, which supports Open Mobile Alliance Device Management standards. Burkhart says the environment also helps reduce costs by offering troubleshooting and help-desk capabilities, while passing the bulk of the responsibility onto manufacturers and carriers.
Gartner's Clark says it's essential to understand organizational roles and usage patterns so the enterprise doesn't overspend on devices or on calling and data plans. "Not everyone needs an iPhone," he says. "Not everyone needs a data plan loaded with minutes. An organization must look at the efficient use of resources and basic costcontainment issues."
DIALING INTO A STRATEGY
It's critical to create a strategy for managing a mobile environment. Applications such as Sybase Afaria, Trellia, Microsoft Systems Center Device Manager and Odyssey Software Athena provide increasingly sophisticated mobile management features. These include the ability to configure devices remotely, enforce different sets of policies for different users and devices, and view applications running on all of them.
Many of these packages also provide diagnostics features and support troubleshooting and help desk activities. The latter is important because mobile devices travel off premises and away from hands-on IT support.
IDC's Ryan urges enterprises to examine device management applications carefully. And there's no single template even within the same industry. "Some organizations support only a single platform, and others support multiple platforms," he says. "You have to understand what you want to achieve and where you're headed so you don't wind up getting boxed in."
Flexibility is only part of the story, however. Mobile device management also involves thinking through a spate of practical issues, such as who pays the phone bill, who owns the phone number, how to deliver tech support, and which applications the enterprise allows on smartphones and laptops. Further complicating matters, various groups of employees usually have entirely different needs and usage patterns.
These are all issues that Soberman LLP, a Toronto-based public accounting firm, faced when it moved to a mobile platform. The 150-person company has specialists who spend about 90 percent of their time in the field providing accounting and auditing services. In some cases, they are at a client site for a week to 10 days. As a result, mobile tools are essential, and staying connected to enterprise systems is unavoidable. What's more, security, privacy and confidentiality are vital, notes Susan Hodkinson, chief operating officer.
Soberman has turned to a mix of devices and systems. Accountants mostly carry BlackBerrys, but employees also rely on laptops equipped with dial-up, 3G data cards, Wi-Fi and WiMax. And a few executives carry netbooks.
Within this environment, it's crucial to achieve a high level of IT compliance and security. So Soberman opted for a Trellia mobile management system that provides provisioning, simplifies compliance and standardizes various processes. The solution also helps the company track billing and cost issues, including which devices make sense for various user groups.
No less important, the application allows the firm to designate which Wi-Fi networks employees are allowed to connect with and the order in which they can connect. "Creating a whitelist and a blacklist is enormously important," says Robin Persaud, senior network engineer at Soberman. "We're able to secure the devices and the network far more effectively."
These systems can assist in other ways. Many organizations, including Safelite and Soberman, are moving away from a reimbursement model for mobility devices and are adopting an employer-paid model. This approach makes it easier to control the device and phone number, while also amping up security. It also sheds paperwork by eliminating expense reports for mobile devices.
"For many companies, it makes a lot more sense to set limits and look for exceptions, rather than tracking everyone and everything," says IDC's Ryan.
MAKING SECURITY COUNT
Although mobility offers compelling advantages, it also presents an array of security concerns. For example, it's estimated that 70 percent or more of enterprise data now resides in some form on mobile devices. Remarkably, approximately three out of four organizations lack comprehensive formalized policies for dealing with mobile devices and data.
As workers try to connect their personal devices to a corporate network and access Microsoft Exchange Servers and other applications, the potential headaches mushroom. Typical corporate asset management and security issues are also magnified by the fact that mobile and wireless devices travel beyond the physical boundaries of the enterprise. Moreover, content streams past the corporate firewall, and smartphones and computers are easily lost or stolen. There's also the issue of ensuring that devices can no longer be used to access corporate data after an employee leaves the company.
When IDC asked business leaders whether their organizations have deployed mobile device management tools to track handheld devices used by employees, only 53 percent answered yes. Although this figure is a major improvement over 2008, when only a third of companies had management and security systems in place, it still translates into a huge risk. As Ryan puts it, "Mobile management and security are closely linked."
In fact, Vodaphone UK found that 25 percent of all businesses have experienced security breaches as a result of employees using their laptops and mobile devices outside of work-and essentially ignoring company policies. Moreover, half of all workers weren't aware that different policies exist for using devices and systems for work versus outside of work. No less unsettling: Onethird of the respondents either didn't know their organization had an IT policy or they had never read it.
Administration and security issues are inextricably linked at Addison Avenue Federal Credit Union, which serves 140,000 members at companies scattered across 10 states and Puerto Rico. It also reaches members around the world through its online channels. Three years ago, the company, based in Palo Alto and Rocklin, Calif., developed a policy framework for meshing business requirements with a mobile strategy.
"We spent a lot of time talking to users, and we put a control group in place to better understand how they use devices," says Ken Smith, director of customer support and information security. From this, the firm created a policy document for its employees, including the sales force. This led to specific administration and security strategies.
Addison Avenue divides mobile accounts into two tiers: company-liable and employee-liable. The organization owns the devices and phone numbers for the first group. "We pay the bills," Smith says. The second group, however, required a bit more analysis. "These individuals select and provision their own device," he says. "They get the bill, and we reimburse them for certain uses. We know that they do need to use the device for business purposes from time to time."
That meant defining a set of standards and security policies-and ensuring that the employees understood and acknowledged them. Whereas a BlackBerry Enterprise Server provides much of the protection needed for the company-owned BlackBerry devices, Addison Avenue is testing security for other devices, including iPhones and Windows Mobile smartphones. In addition, the company uses device locks for time-outs and has remote management and wipe capabilities on company-issued devices.
IDC's Ryan says the ability to track and lock devices, encrypt data and use a remote-wipe feature is essential. "Smartphones, netbooks, notebooks and other devices constantly go missing," he points out. "With the amount of data stored on these devices-and the ability to access enterprise applications and databases-there's no margin for error."
Moreover, the right software slides the dial on device management from policy to practice. There's no possibility of employees forgetting or sidestepping a rule. Finally, organizations can implement blocking features or lock down specific components, such as camera phones, that may pose a security risk.
CONNECTING TO SUCCESS
Mobile device management isn't likely to get simpler any time soon. Ryan sees the consumerization of mobile devices continuing and various platforms- including BlackBerry, iPhone, Windows Mobile, Palm, Android and Symbian- remaining viable over the next few years. What's more, complex business requirements, greater regulatory concerns and rapidly changing technology make mobile device management a challenging IT proposition. "It creates issues that don't exist for traditional IT," he says.
The good news, says Christopher Isaac, a partner at PricewaterhouseCoopers Advisory Practice, is that the Internet and the maturation of mobile and wireless technologies are ushering in greater simplicity and an ability to connect various platforms and systems. Also, growing competition among providers translates into opportunities for astute companies.
"Convergence means that hardware suppliers are competing with software providers, who are competing with service providers," he says. "In such circumstances, opportunities abound to negotiate favorable service agreements."
Nevertheless, organizations must take a proactive stance. Those that plot out a business case and develop policies and procedures for handling mobile devices are likely to reduce costs, improve efficiency and trim risk. There's no single route to success, but a focus on managing the environment holistically pays dividends.
"The genie is out of the bottle," cautions IDC's Ryan. "Employees expect leading-edge mobility tools, and the enterprise requires them to compete effectively. So it's up to IT to manage the environment effectively."
[Sidebar]
According to Plan
It's not unusual for an enterprise to rely on more than one cellular service provider. In many cases, different devices and services demand a multipartner approach. Of course, it's crucial to negotiate contracts with different providers.
As Chris Delong, director of open systems and infrastructure at Safelite AutoGlass, explains, "Negotiating with vendors is somewhat of an art. You try to get the best deal you can based on your bargaining position."
Volume counts, to be sure. But there's also the issue of ensuring that employees are on the right plans, that they're not blasting past data limits and paying higher rates, and that they're using the best available network. In some cases, such as with laptops and netbooks, Bill Clark, research vice president at Gartner, says that it's easy for employees to rack up daily Wi-Fi charges through providers like T-Mobile and Boingo, when a cellular modem could cut costs. Too often, he says, organizations set up systems and then neglect to re-examine them or make needed changes.
Online sites such as OnlineBillReview.com and Validas analyze bills and find inconsistencies and waste. They charge modest fees or take a cut of the savings, but many organizations find it worthwhile.
In addition, experts advise organizations to make sure that employees don't have phones they don't need and features they don't use. For example, not every worker requires an unlimited dialing plan or a multimedia messaging service (MMS).
Finally, try to consolidate accounts to a single carrier, if possible. Volume typically translates into lower costs, and it's increasingly possible to pool minutes.-S.G.
[Sidebar]
Aligning Your Mobile Management Strategy
Effective mobile device management means tackling a number of challenges. According to Christopher Isaac, a partner at PricewaterhouseCoopers Advisory Practice, an organization should focus on several key areas:
STRATEGY
* A mobility strategy that's in line with overall company or IT objectives
* Executive support to avoid unrealized benefits, cost overruns and poor decision making
MANAGEMENT
* A consistent framework for evaluating, monitoring and measuring performance of mobility solutions
POLICY AND GOVERNANCE
* Avoiding security, privacy or regulatory violations due to the lack of a defined mobility policy and governance structure
* Steering clear of excess expenditures due to a focus on individual segmented solutions
TECHNOLOGY
* Adoption of sound management practices to boost the odds of a successful rollout and spur the adoption of new mobile solutions
* A focus on core business processes rather than the available technology
BUSINESS PROCESS
* The creation of new business models, operational effectiveness and an enhanced user experience
* A sound project management approach that reduces-if not eliminates-deployment delays and cost overruns and improves return on benefits.-S.G.
[Sidebar]
'It's up to IT to manage the environment effectively.'
-Sean Ryan, IDC
[Sidebar]
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