bluuebunny/crossref_metadata_2025 huggingface dataset:
Twelve‐year Incidence of Exfoliation Syndrome in the Reykjavik Eye Study
Authors: Arnarsson Arsaell , Sasaki Hiroshi , Jonasson Fridbert
Published: January 2012

Purpose: To examine the 12‐year incidence of exfoliation syndrome (XFS) in persons aged 50–79 years at baseline and also to monitor changes in related ophthalmologic variables, to identify possible risk factors for incidence and to estimate the reliability of our diagnostic criteria.

Methods: Baseline examination was performed in 1996 on a random sample of 1045 participants from the population of Reykjavik, 50 years and older. Five years later, in 2001, 88.2% of survivors returned for a follow‐up. In 2008, 12 years after the baseline examination, a total of 573 participants returned for the third examination (71.5% of survivors). On all three occasions, the participants underwent a thorough eye examination including slitlamp examination specifically looking for XFS and answered a comprehensive questionnaire.

Results: A total of 8.0% of participants developed XFS during the follow‐up period in at least one eye, with women being more commonly affected than men, 9.2% versus 6.6%. The overall 12‐year incidence for either eye increased with increasing age, from 6.5% in those participants aged 50–59 years at baseline to 10.6% in those that were 70–79 years at baseline; 71% of clinically unilateral cases had converted to bilateral over 12 years.

Conclusions: Twelve‐year incidence of XFS is higher in women than in men and higher in older age groups than in younger ones. Most persons deemed on the slitlamp to be unilaterally affected have converted to bilateral over 12 years. Eyes with XFS at baseline were 3–4 times more likely to have cataract surgery during the 12 years. Our definition of definite XFS generally holds, while our definition of probable XFS is of no prognostic value over 12 years.
Subfoveal choroidal blood flow and central retinal function in early glaucoma
Authors: Marangoni Dario , Falsini Benedetto , Colotto Alberto , Salgarello Tommaso , Anselmi Gianmario , Fadda Antonello , Di Renzo Antonio , Campos Emilio C. , Riva Charles E.
Published: January 2012

Purpose:  To assess subfoveal choroidal blood flow (ChBF) in patients with early manifest glaucoma (EMG) and to compare blood flow with functional measures of central retinal integrity, standard automated perimetry (SAP) and pattern electroretinogram (PERG).

Methods:  Subfoveal ChBF was determined by confocal, real‐time laser Doppler flowmetry in 24 patients with EMG [>−6 dB mean deviation (MD), age range: 29–77 years, visual acuity: 20/25–20/20] and 23 age‐matched control subjects. All patients had a therapeutically (topical beta‐blockers with or without prostaglandin analogues) controlled intraocular pressure (IOP < 20 mmHg). Subfoveal choroidal blood volume (ChBVol), velocity (ChBVel) and ChBF were determined as the average of three 60 second recordings. In all patients and controls, the PERG and SAP (Humphrey 30‐2), following standardized protocols, were also recorded.

Results:  In patients with EMG, reductions in average ChBVel and ChBF were roughly equal, respectively, by 30% and 33.4% (p < 0.01), when compared to control subjects, so that there was no significant difference in ChBVol between the two groups. Pattern electroretinogram amplitudes were reduced by 46% (p < 0.01) in patients compared to controls. No correlation was found between any of the ChBF parameters and PERG amplitude, or Humphrey 30‐2 MD and pattern standard deviation.

Conclusion:  The results suggest a significant alteration of both ChBVel and ChBF in EMG, which does not appear to be associated with the severity of central retinal dysfunction. These findings may contribute to a better understanding of the pathophysiology of early glaucomatous damage in EMG and have implications for the treatment of this pathologic condition.
Time to consider a new treatment protocol for aggressive posterior retinopathy of prematurity?
Authors: Spandau Ulrich , Tomic Zoran , Ewald Uwe , Larsson Eva , Åkerblom Hanna , Holmström Gerd
Published: January 2012

Purpose:  To discuss treatment modalities for aggressive posterior retinopathy of prematurity (AP‐ROP).

Methods:  The medical charts of all infants with AP‐ROP at Uppsala University Hospital, Sweden, during a 2‐year period (2009 and 2010) were reviewed. Eight infants (16 eyes) with a mean gestational age of 23.8 weeks and a mean birth weight of 592 g were treated with laser and/or intravitreal injections of bevacizumab (0.4 and 0.625 mg). RetCam photography was used to document the retinal appearance before and after treatment.

Results:  All infants (16 eyes) had AP‐ROP in zone I. Mean time at initial treatment was 34 weeks postmenstrual age. Two eyes (one infant) were only treated with laser, and six eyes (three infants) were treated with laser therapy or cryopexy and, because of lack of regression, with bevacizumab as salvage therapy. Eight eyes (four infants) were treated with a first‐line bevacizumab injection and four of these eyes (two infants) with additional laser ablation for continued disease progression in zone II. Macular dragging occurred in one eye of one infant primarily treated with laser.

Conclusions:  Given the high complication rate of the extensive laser treatment for zone I ROP, it is worth considering anti‐vascular endothelial growth factor treatment as an alternative therapy. Further knowledge concerning side effects and long‐term ocular and systemic outcome is warranted before this drug becomes general clinical practice.
KENT V. UNITED STATES SUPREME COURT JUVENILE CASE
Authors: Lefstein Norman
Published: January 2012

As we went to press the decision was issued. Because of its significance the Journal will treat the case in two phases. The article that follows concerns itself with the facts and issues presented; the next issue will interpret the decision. This is the first time the U.S. Supreme Court has passed on the legality of juvenile court procedures.
THE MANPOWER CRISIS IN THE JUVENILE COURT
Authors: THURSTON PHILLIP B.
Published: January 2012

The Joint Commission on Correctional Manpower and Training, strongly supported by state governors and with wide bipartisan backing in Congress, is the first attempt at a unified national approach to the increasingly serious problem of correctional rehabilitation. It has undertaken a far‐ranging threeyear study which will lead to a series of action programs and legislative recommendations on federal, state and local levels. Our National Council is a member. The author is our representative on the Commission.
Renal Disease in Cats Infected with Feline Immunodeficiency Virus
Authors: Baxter K.J. , Levy J.K. , Edinboro C.H. , Vaden S.L. , Tompkins M.B.
Published: January 2012

Background

Feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) infection cause similar clinical syndromes of immune dysregulation, opportunistic infections, inflammatory diseases, and neoplasia. Renal disease is the 4th most common cause of death associated with HIV infection.

Objective

To investigate the association between FIV infection and renal disease in cats.

Animals

Client‐owned cats (153 FIV‐infected, 306 FIV‐noninfected) and specific‐pathogen‐free (SPF) research colony cats (95 FIV‐infected, 98 FIV‐noninfected).

Methods

A mixed retrospective/prospective cross‐sectional study. Blood urea nitrogen (BUN), serum creatinine, urine specific gravity (USG), and urine protein:creatinine ratio (UPC) data were compared between FIV‐infected and FIV‐noninfected cats. In FIV‐infected cats, total CD4+ and CD8+ T lymphocytes were measured using flow cytometry, and CD4+:CD8+ T lymphocyte ratio was calculated. Renal azotemia was defined as a serum creatinine ≥ 1.9 mg/dL with USG ≤ 1.035. Proteinuria was defined as a UPC > 0.4 with an inactive urine sediment.

Results

Among the client‐owned cats, no association was detected between FIV infection and renal azotemia (P = .24); however, a greater proportion of FIV‐infected cats were proteinuric (25.0%, 16 of 64 cats) compared to FIV‐noninfected cats (10.3%, 20 of 195 cats) (P < .01). Neither neuter status nor health status were risk factors for proteinuria in FIV‐infected cats, but UPC was positively correlated with the CD4+:CD8+ T lymphocyte ratio (Spearman's rho = 0.37, P = .01). Among the SPF research colony cats, no association was detected between FIV infection and renal azotemia (P = .21) or proteinuria (P = .25).

Conclusions and Clinical Importance

Proteinuria but not azotemia was associated with natural FIV infection.
Does the Numerical Underrepresentation of the Working Class in Congress Matter?
Authors: CARNES NICHOLAS
Published: January 2012

Working‐class citizens have been numerically underrepresented in policymaking institutions throughout most of America's history. Little is known, however, about the political consequences of this enduring feature of our democratic system. This essay examines the relationship between legislators' class backgrounds and their votes on economic policy in the House of Representatives during the twentieth century. Like ordinary Americans, representatives from working‐class occupations exhibit more liberal economic preferences than other legislators, especially those from profit‐oriented professions. These findings provide the first evidence of a link between the descriptive and substantive representation of social classes in the United States.
A Gender Gap in Policy Representation in the U.S. Congress?
Authors: GRIFFIN JOHN D. , NEWMAN BRIAN , WOLBRECHT CHRISTINA
Published: January 2012

In the first article to evaluate the equality of dyadic policy representation experienced by women, we assess the congruence between U.S. House members' roll‐call votes and the policy preferences of their female and male constituents. Employing two measures of policy representation, we do not find a gender gap in dyadic policy representation. However, we uncover a sizeable gender gap favoring men in districts represented by Republicans, and a similarly sizeable gap favoring women in districts represented by Democrats. A Democratic majority further improves women's dyadic representation relative to men, but having a female representative (descriptive representation) does not.
The Strategic Use of Legislative Voting Procedures
Authors: CRISP BRIAN F. , DRISCOLL AMANDA
Published: January 2012

Legislative votes can be taken by roll call—noting the position of each individual member—or by some form of indication (sitting or standing, shouting yea or nay, etc.)—noting only an aggregate outcome. Cameral rules define one method of voting as the standard operating procedure and how to invoke any alternative voting methods. We develop a series of hypotheses related to position taking to explain why, when procedures would typically lead to a vote taken by indication, legislators choose to vote by roll call—a means that makes it much easier for actors outside the chamber to observe the positions taken by individual legislators and partisan blocs. With data from Argentina and Mexico, we test these hypotheses regarding the strategic choice of vote procedures and their relationship to observed party unity.
Public Approval ofU.S. State Legislatures
Authors: RICHARDSON, JR. LILLIARD E. , KONISKY DAVID M. , MILYO JEFFREY
Published: January 2012

The determinants of public approval for state legislatures have not received much attention, but one important finding is that more professionalized legislatures experience lower levels of public support. We argue that this result is an artifact of limited data and problematic model specifications. Analyzing a large national survey sample, we demonstrate that the negative relationship holds primarily for conservatives and to a lesser extent for moderates but not liberals. Additionally, we find that legislative approval in states with term limits and ballot initiatives is no different than in states without these institutions.
The Strategic Use of Prisons in Partisan Gerrymandering
Authors: KELLY JASON P.
Published: January 2012

The census data used to redraw legislative districts counts the country's nearly 2 million prisoners in the location of their incarceration, rather than their previous place of residence. By drawing these phantom populations into districts that lean heavily toward the majority party, legislators can free up eligible voters from those districts to be distributed among neighboring marginal ones, thereby increasing that party's likelihood of winning additional seats in the state legislature. An analysis of state senate district finds that prison populations shift systematically from districts controlled by one party to districts controlled by the other following a switch in partisan control.
Assessing individual heterogeneity using model selection criteria: how many mixture components in capture–recapture models?
Authors: Cubaynes Sarah , Lavergne Christian , Marboutin Eric , Gimenez Olivier
Published: January 2012

1. Capture–recapture mixture models are important tools in evolution and ecology to estimate demographic parameters and abundance while accounting for individual heterogeneity. A key step is to select the correct number of mixture components i) to provide unbiased estimates that can be used as reliable proxies of fitness or ingredients in management strategies and ii) classify individuals into biologically meaningful classes. However, there is no consensus method in the statistical literature for selecting the number of components.

2. In ecology, most studies rely on the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC) that has recently gained attention in ecology. The Integrated Completed Likelihood criterion (ICL; IEEE Transactions on Pattern Analysis and Machine Intelligence, 2000, 22, 719) was specifically developed to favour well‐separated components, but its use has never been investigated in ecology.

3. We compared the performance of AIC, BIC and ICL for selecting the number of components with regard to a) bias and accuracy of survival and detection estimates and b) success in selecting the true number of components using extensive simulations and data on wolf (Canis lupus) that were used for management through survival and abundance estimation.

4. Bias in survival and detection estimates was <0.02 for both AIC and BIC, and more than 0.09 for ICL, while mean square error was <0.05 for all criteria. As expected, bias increased as heterogeneity increased. Success rates of AIC and BIC in selecting the ‘true’ number of components were better than ICL (68% for AIC, 58% for BIC, and 16% for ICL). As the degree of heterogeneity increased, AIC (and BIC in a lesser extent) overestimated the number of components, while ICL often underestimated this number. For the wolf study, the 2‐class model was selected by BIC and ICL, while AIC could not decide between the 2‐ and 3‐class models.

5. We recommend using AIC or BIC when the aim is to estimate parameters. Regarding classification, we suggest taking the classification quality into account by using ICL in conjunction with BIC, pending further work to adapt its penalty term for capture–recapture data.
Barcoding's next top model: an evaluation of nucleotide substitution models for specimen identification
Authors: Collins Rupert A. , Boykin Laura M. , Cruickshank Robert H. , Armstrong Karen F.
Published: January 2012

1. DNA barcoding studies use Kimura's two‐parameter substitution model (K2P) as thede factostandard for constructing genetic distance matrices. Distances generated under this model then provide the basis for most downstream analyses, but uncertainty in model choice is rarely explored and could potentially affect how reliably DNA barcodes discriminate species.

2. Using information‐theoretic approaches for a data set comprising 14 472 DNA barcodes from 14 published studies, we tested whether the K2P model was a good fit at the species level and whether applying a better fitting model biased error rates or changed overall identification success.

3. We report that the K2P was a poorly fitting model at the species level; it was never selected as the best model and very rarely selected as a credible alternative model. Despite the lack of support for the K2P model, differences in distance between best model and K2P model estimates were usually minimal, and importantly, identification success rates were largely unaffected by model choice even when interspecific threshold values were reassessed.

4. Although these conclusions may justify using the K2P model for specimen identification purposes, we found simpler metrics such aspdistance performed equally well, perhaps obviating the requirement for model correction in DNA barcoding. Conversely, when incorporating genetic distance data into taxonomic studies, we advocate a more thorough examination of model uncertainty.
Heat and Mass Transfer in Solid State Hydrogen Storage: A Review
Authors: Srinivasa Murthy S.
Published: January 2012

Metal hydrides are formed when certain metals or alloys are exposed to hydrogen at favorable temperatures and pressures. In order to sustain the sorption of hydrogen during this exothermic process, the generated heat has to be removed effectively. Release of hydrogen is an endothermic process needing supply of heat to the metal hydride matrix. Depending on the application, the heat transfer medium can be either a liquid or a gas. Reduction of the total weight of hydrogen storage devices is essential toward utilization of hydrogen for mobile and portable applications. While a variety of new storage materials with desirable sorption characteristics are being suggested, optimal thermal design of the storage device remains a major challenge. Lack of thermodynamic, transport, and thermophysical property data of the material particles and of the bed is another drawback which needs to be addressed.
Heat Transfer to Foods: Ensuring Safety and Creating Microstructure
Authors: Fryer Peter J. , Bakalis S.
Published: January 2012

Heat transfer in foods is commonplace in the home and restaurant, but is also the basis for a very large industry. Foods are complex non-Newtonian soft solids or structured liquids whose thermal behavior is difficult to model; engineering understanding is needed to develop processes that are safe and products that are attractive to the consumer. The increasing incidence of obesity in the developed world, and of food shortage elsewhere, demands that the industry adopts processes that give nutritious products in environmentally acceptable ways. Heat transfer is often limited by the low thermal conductivity of foods and increasing heating and cooling rates is critical in maximizing product quality. This paper briefly reviews the heat transfer problems found in food processing, with particular reference to the modeling of heating to ensure safety, problems found in the fouling and cleaning and process plant, and how heating and cooling are used to generate food microstructure. Research challenges for the future are outlined.
Numerical Prediction of Heat Transfer Patterns in a Subject-Specific Human Upper Airway
Authors: Saksono Prihambodo H. , Nithiarasu Perumal , Sazonov Igor
Published: January 2012

In this paper, the flow and heat transfer patterns in a subject-specific geometry of the human upper airway is numerically studied. The study was conducted for steady, inspiratory flow associated with quiet normal breathing with a tidal volume of VT = 0.5 L/min and flow rate of Q = 250 cm3/s. The numerical results confirmed in vivo measurement that the majority of heat transfer process takes place inside the nasal cavity. It is apparent that even for extreme cases (T∞ = −30 °C and Twall = 37 °C), the inspired air approached the body temperature by the time it passes the distal nasopharyngeal region. The air temperature reached the body temperature by the time it is in the vicinity of the larynx.
Perfusion Characteristics of the Human Hepatic Microcirculation Based on Three-Dimensional Reconstructions and Computational Fluid Dynamic Analysis
Authors: Debbaut Charlotte , Vierendeels Jan , Casteleyn Christophe , Cornillie Pieter , Van Loo Denis , Simoens Paul , Van Hoorebeke Luc , Monbaliu Diethard , Segers Patrick
Published: January 2012

The perfusion of the liver microcirculation is often analyzed in terms of idealized functional units (hexagonal liver lobules) based on a porous medium approach. More elaborate research is essential to assess the validity of this approach and to provide a more adequate and quantitative characterization of the liver microcirculation. To this end, we modeled the perfusion of the liver microcirculation using an image-based three-dimensional (3D) reconstruction of human liver sinusoids and computational fluid dynamics techniques. After vascular corrosion casting, a microvascular sample (±0.134 mm3) representing three liver lobules, was dissected from a human liver vascular replica and scanned using a high resolution (2.6 μm) micro-CT scanner. Following image processing, a cube (0.15 × 0.15 × 0.15 mm3) representing a sample of intertwined and interconnected sinusoids, was isolated from the 3D reconstructed dataset to define the fluid domain. Three models were studied to simulate flow along three orthogonal directions (i.e., parallel to the central vein and in the radial and circumferential directions of the lobule). Inflow and outflow guidances were added to facilitate solution convergence, and good quality volume meshes were obtained using approximately 9 × 106 tetrahedral cells. Subsequently, three computational fluid dynamics models were generated and solved assuming Newtonian liquid properties (viscosity 3.5 mPa s). Post-processing allowed to visualize and quantify the microvascular flow characteristics, to calculate the permeability tensor and corresponding principal permeability axes, as well as the 3D porosity. The computational fluid dynamics simulations provided data on pressure differences, preferential flow pathways and wall shear stresses. Notably, the pressure difference resulting from the flow simulation parallel to the central vein (0–100 Pa) was clearly smaller than the difference from the radial (0–170 Pa) and circumferential (0–180 Pa) flow directions. This resulted in a higher permeability along the central vein direction (kd,33 = 3.64 × 10−14 m2) in comparison with the radial (kd,11 = 1.56 × 10−14 m2) and circumferential (kd,22 = 1.75 × 10−14 m2) permeabilities which were approximately equal. The mean 3D porosity was 14.3. Our data indicate that the human hepatic microcirculation is characterized by a higher permeability along the central vein direction, and an about two times lower permeability along the radial and circumferential directions of a lobule. Since the permeability coefficients depend on the flow direction, (porous medium) liver microcirculation models should take into account sinusoidal anisotropy.
Multi-phase model for reflection anisotropy spectra of copper phthalocyanine films on anisotropic silicon substrates
Authors: Seidel Falko , Ding Li , Gordan Ovidiu D. , Zahn Dietrich R. T.
Published: January 2012

Reflection anisotropy spectroscopy (RAS) and spectroscopic ellipsometry (SE) have extensively been applied to inorganic and organic structures and, because of the similarity of these two techniques, the evaluation procedure of RA spectra can be performed in a similar way as for SE. Especially for thin films, RA spectra are often strongly enhanced in the spectral region where optical interference occurs and the superposition of interference features can lead to an incorrect interpretation of RA spectra. By simulation of the origin of each RAS feature it is possible to distinguish interference from true film anisotropy. Also, the effect of surface roughness on the RA spectra is discussed.
Comment on “The Gibbs paradox and the distinguishability of identical particles,” by M. A. M. Versteegh and D. Dieks [Am. J. Phys. 79, 741–746 (2011)]
Authors: Corti David S.
Published: January 2012

We revisit recent discussions concerning the Gibbs paradox—the apparent discrepancy between the entropy change upon mixing identical gases as evaluated from the statistical mechanics of classical distinguishable particles and macroscopic thermodynamics. Contrary to what is often stated, we show that thermodynamics does not require this entropy of mixing to be zero. A zero value follows from the implicit assumption that the identical gas particles are indistinguishable. If the identical particles are explicitly assumed to be distinguishable, thermodynamics yields the same entropy of mixing as classical statistical mechanics.
Chaotic motors
Authors: Laroche C. , Labbé R. , Pétrélis F. , Fauve S.
Published: January 2012

We show that electric motors and dynamos can be used to illustrate most elementary instabilities or bifurcations discussed in courses on nonlinear oscillators and dynamical systems. These examples are easier to understand and display a richer behavior than the ones commonly used from mechanics, electronics, hydrodynamics, lasers, chemical reactions, and population dynamics. In particular, an electric motor driven by a dynamo can display stationary, Hopf, and codimension-two bifurcations by tuning the driving speed of the dynamo and the electric current in the stator of the electric motor. When the dynamo is driven at constant torque instead of constant rotation rate, chaotic reversals of the generated current and of the angular rotation of the motor are observed. Simple deterministic models are presented which capture the observed dynamical regimes.
A Better 2-D Mechanical Energy Conservation Experiment
Authors: Paesler Michael
Published: January 2012

A variety of simple classical mechanics energy conservation experiments are used in teaching laboratories. Typical one-dimensional (1-D) setups may involve falling balls or oscillating springs. Many of these can be quite satisfying in that students can confirm—within a few percent—that mechanical energy is conserved. Students generally have little trouble identifying discrepancies such as the loss of a few percent of the gravitational potential energy due to air friction encountered by a falling ball. Two-dimensional (2-D) systems can require more sophisticated analysis for higher level laboratories, but such systems often incorporate complicating components that can make the exercise academically incomplete and experimentally less accurate. The following describes a simple 2-D energy conservation experiment based on the popular “Newton's Cradle” toy that allows students to account for nearly all of the mechanical energy in the system in an academically complete analysis.
Inertial Navigation: A Bridge Between Kinematics and Calculus
Authors: Sadler Philip M. , Garfield Eliza N. , Tremblay Alex , Sadler Daniel J.
Published: January 2012

Those who come to Cambridge soon learn that the fastest route between Harvard and MIT is by the subway. For many students, this short ride is a quick and easy way to link physics and calculus. A simple, homemade accelerometer provides all the instrumentation necessary to produce accurate graphs of acceleration, velocity, and displacement position on this subterranean route. Each graph, in turn, reveals a story of the train's trip: speeding up and braking, varying track conditions, top speed, and the distance between subway stops deep beneath Massachusetts Avenue.
Binder clip optics bench for Young's double-slit experiment
Authors: Van Domelen Dave
Published: January 2012

Young's double slit is one of the standard experiments in wave optics, but getting the equipment to run it can be pretty expensive, and unless you expect to run a large number of different optics labs, it may not be a worthwhile capital outlay. But with some ingenuity and office supplies, a lot of the “real” equipment can be replicated well enough to let introductory students perform the experiment.
Diffraction experiments with infrared remote controls
Authors: Kuhn Jochen , Vogt Patrik
Published: January 2012

In this paper we describe an experiment in which radiation emitted by an infrared remote control is passed through a diffraction grating. An image of the diffraction pattern is captured using a cell phone camera and then used to determine the wavelength of the radiation.1
Speaking the same language in physics and math
Authors: Harvey Marci
Published: January 2012

“Hey, is that the same thing as a derivative from calculus?” “Isn't that a quadratic equation?” These are some of the math-related questions my physics students ask every year. Some students realize that determining velocity from a position-time graph is the same thing as taking the first derivative in calculus or they recognize a quadratic equation has a t2 term. Why can all students not make the connection between the two? I wonder if we, as teachers of two different subjects, are making this learning more difficult because we have different terminology for identical concepts. We have an opportunity to create a learning environment that offers multiple opportunities to improve student comprehension. Teachers can connect the concepts from various classes into a cohesive set of information that can be used for higher-level thinking and processing skills.
Roles of
fkbN
in Positive Regulation and
tcs7
in Negative Regulation of FK506 Biosynthesis in Streptomyces sp. Strain KCTC 11604BP
Authors: Mo SangJoon , Yoo Young Ji , Ban Yeon Hee , Lee Sung-Kwon , Kim Eunji , Suh Joo-Won , Yoon Yeo Joon
Published: January 2012

FK506 is an important 23-member polyketide macrolide with immunosuppressant activity. Its entire biosynthetic gene cluster was previously cloned from
Streptomyces
sp. strain KCTC 11604BP, and sequence analysis identified three putative regulatory genes,
tcs2
,
tcs7
, and
fkbN
, which encode proteins with high similarity to the AsnC family transcriptional regulators, LysR-type transcriptional regulators, and LAL family transcriptional regulators, respectively. Overexpression and in-frame deletion of
tcs2
did not affect the production of FK506 or co-occurring FK520 compared to results for the wild-type strain, suggesting that
tcs2
is not involved in their biosynthesis.
fkbN
overexpression improved the levels of FK506 and FK520 production by approximately 2.0-fold, and a deletion of
fkbN
caused the complete loss of FK506 and FK520 production. Although the overexpression of
tcs7
decreased the levels of FK506 and FK520 production slightly, a deletion of
tcs7
caused 1.9-fold and 1.5-fold increases in FK506 and FK520 production, respectively. Finally,
fkbN
overexpression in the
tcs7
deletion strain resulted in a 4.0-fold (21 mg liter
−1
) increase in FK506 production compared to that by the wild-type strain. This suggests that
fkbN
encodes a positive regulatory protein essential for FK506/FK520 biosynthesis and that the gene product of
tcs7
negatively regulates their biosynthesis, demonstrating the potential of exploiting this information for strain improvement. Semiquantitative reverse transcription-PCR (RT-PCR) analyses of the transcription levels of the FK506 biosynthetic genes in the wild-type and mutant strains proved that most of the FK506 biosynthetic genes are regulated by
fkbN
in a positive manner and negatively by
tcs7
.
Microbial Community Succession during Lactate Amendment and Electron Acceptor Limitation Reveals a Predominance of Metal-Reducing Pelosinus spp
Authors: Mosher Jennifer J. , Phelps Tommy J. , Podar Mircea , Hurt Richard A. , Campbell James H. , Drake Meghan M. , Moberly James G. , Schadt Christopher W. , Brown Steven D. , Hazen Terry C. , Arkin Adam P. , Palumbo Anthony V. , Faybishenko Boris A. , Elias Dwayne A.
Published: January 2012

The determination of the success of
in situ
bioremediation strategies is complex. By using controlled laboratory conditions, the influence of individual variables, such as U(VI), Cr(VI), and electron donors and acceptors on community structure, dynamics, and the metal-reducing potential can be studied. Triplicate anaerobic, continuous-flow reactors were inoculated with Cr(VI)-contaminated groundwater from the Hanford, WA, 100-H area, amended with lactate, and incubated for 95 days to obtain stable, enriched communities. The reactors were kept anaerobic with N
2
gas (9 ml/min) flushing the headspace and were fed a defined medium amended with 30 mM lactate and 0.05 mM sulfate with a 48-h generation time. The resultant diversity decreased from 63 genera within 12 phyla to 11 bacterial genera (from 3 phyla) and 2 archaeal genera (from 1 phylum). Final communities were dominated by
Pelosinus
spp. and to a lesser degree,
Acetobacterium
spp., with low levels of other organisms, including methanogens. Four new strains of
Pelosinus
were isolated, with 3 strains being capable of Cr(VI) reduction while one also reduced U(VI). Under limited sulfate, it appeared that the sulfate reducers, including
Desulfovibrio
spp., were outcompeted. These results suggest that during times of electron acceptor limitation
in situ
, organisms such as
Pelosinus
spp. may outcompete the more-well-studied organisms while maintaining overall metal reduction rates and extents. Finally, lab-scale simulations can test new strategies on a smaller scale while facilitating community member isolation, so that a deeper understanding of community metabolism can be revealed.
Correlation between Composition of the Bacterial Community and Concentration of Volatile Fatty Acids in the Rumen during the Transition Period and Ketosis in Dairy Cows
Authors: Wang Xiaoxu , Li Xiaobing , Zhao Chenxu , Hu Pan , Chen Hui , Liu Zhaoxi , Liu Guowen , Wang Zhe
Published: January 2012

The transition period is a severe challenge to dairy cows. Glucose supply cannot meet demand and body fat is mobilized, potentially leading to negative energy balance (NEB), ketosis, or fatty liver. Propionate produces glucose by gluconeogenesis, which depends heavily on the number and species of microbes. In the present study, we analyzed the rumen microbiome composition of cows in the transition period, cows with ketosis, and nonperinatal cows by terminal restriction fragment length polymorphism (TRFLP) analysis of 16S rRNA genes and quantitative PCR. TRFLP analysis indicated that the quantity of
Veillonellaceae
organisms was reduced and that of
Streptococcaceae
organisms was increased in rumen samples from the transition period and ketosis groups, with the number of
Lactobacillaceae
organisms increased after calving. Quantitative PCR data suggested that the numbers of the main propionate-producing microbes,
Megasphaera elsdenii
and
Selenomonas ruminantium
, were decreased, while numbers of the main lactate-producing bacterium,
Streptococcus bovis
, were increased in the rumen of cows from the transition period and ketosis groups, with the number of
Lactobacillus
sp. organisms increased after calving. Volatile fatty acid (VFA) and glucose concentrations were decreased, but the lactic acid concentration was increased, in rumen samples from the transition period and ketosis groups. Our results indicate that the VFA concentration is significantly related to the numbers of
Selenomonas ruminantium
and
Megasphaera elsdenii
organisms in the rumen.
Heterogeneity in Mitochondrial Morphology and Membrane Potential Is Independent of the Nuclear Division Cycle in Multinucleate Fungal Cells
Authors: Gerstenberger John P. , Occhipinti Patricia , Gladfelter Amy S.
Published: January 2012

In the multinucleate filamentous fungus
Ashbya gossypii
, nuclei divide asynchronously in a common cytoplasm. We hypothesize that the division cycle machinery has a limited zone of influence in the cytoplasm to promote nuclear autonomy. Mitochondria in cultured mammalian cells undergo cell cycle-specific changes in morphology and membrane potential and therefore can serve as a reporter of the cell cycle state of the cytoplasm. To evaluate if the cell cycle state of nuclei in
A. gossypii
can influence the adjacent cytoplasm, we tested whether local mitochondrial morphology and membrane potential in
A. gossypii
are associated with the division state of a nearby nucleus. We found that mitochondria exhibit substantial heterogeneity in both morphology and membrane potential within a single multinucleated cell. Notably, differences in mitochondrial morphology or potential are not associated with a specific nuclear division state. Heterokaryon mutants with a mixture of nuclei with deletions of and wild type for the mitochondrial fusion/fission genes
DNM1
and
FZO1
exhibit altered mitochondrial morphology and severe growth and sporulation defects. This dominant effect suggests that the gene products may be required locally near their expression site rather than diffusing widely in the cell. Our results demonstrate that mitochondrial dynamics are essential in these large syncytial cells, yet morphology and membrane potential are independent of nuclear cycle state.
Resistance Phenotypes Mediated by Aminoacyl-Phosphatidylglycerol Synthases
Authors: Arendt Wiebke , Hebecker Stefanie , Jäger Sonja , Nimtz Manfred , Moser Jürgen
Published: January 2012

The specific aminoacylation of the phospholipid phosphatidylglycerol (PG) with alanine or with lysine catalyzed by aminoacyl-phosphatidylglycerol synthases (aaPGS) was shown to render various organisms less susceptible to antibacterial agents. This study makes use ofPseudomonas aeruginosachimeric mutant strains producing lysyl-phosphatidylglycerol (L-PG) instead of the naturally occurring alanyl-phosphatidylglycerol (A-PG) to study the resulting impact on bacterial resistance. Consequences of such artificial phospholipid composition were studied in the presence of an overall of seven antimicrobials (β-lactams, a lipopeptide antibiotic, cationic antimicrobial peptides [CAMPs]) to quantitatively assess the effect of A-PG substitution (with L-PG, L-PG and A-PG, increased A-PG levels). For the employed Gram-negativeP. aeruginosamodel system, an exclusive charge repulsion mechanism does not explain the attenuated antimicrobial susceptibility due to PG modification. Additionally, the specificity of nine orthologous aaPGS enzymes was experimentally determined. The newly characterized protein sequences allowed for the establishment of a significant group of A-PG synthase sequences which were bioinformatically compared to the related group of L-PG synthesizing enzymes. The analysis revealed a diverse origin for the evolution of A-PG and L-PG synthases, as the specificity of an individual enzyme is not reflected in terms of a characteristic sequence motif. This finding is relevant for future development of potential aaPGS inhibitors.
Application of electrochemical impedance spectroscopy to the study of surface processes
Authors: Rueda Rueda Manuela , Prieto Dapena Francisco
Published: January 2012

The application of Electrochemical Impedance Spectroscopy to the study of surface electrode processes is reviewed. The impedance expressions and the physical meaning of the parameters included in them are shown for three surface processes: adsorption kinetics, diffusion towards partially blocked electrodes and surface confined redox reactions. The models are applied to selected examples, showing the capability of Electrochemical Impedance Spectroscopy to obtain fundamental kinetic information of these processes. A review with 83 references.
Cough and upper airway disorders in elite athletes: a critical review
Authors: Boulet Louis-Philippe
Published: January 2012

Respiratory diseases such as asthma, chronic cough, recurrent respiratory infections and various upper airways conditions are common in elite athletes, but these conditions are often underdiagnosed and undertreated. Recurrent cough, often observed after exercise, is the most commonly reported symptom in athletes, particularly winter athletes, but it does not predict airway function; its intensity correlates with the dryness of inspired air but may not be associated with airway hyper-responsiveness. Rhinitis, either allergic or not, is highly prevalent in athletes, particularly non-allergic rhinitis in swimmers. Finally, dysfunctional breathing, including vocal cord dysfunction, may mimic or accompany asthma in a significant number of athletes. These conditions should be recognised and treated properly according to current guidelines, although how these last apply in the athlete is uncertain. Furthermore, regulatory agencies' restrictions on the type of drugs allowed for therapeutic use of these conditions in competitive athletes should be checked.
Effect of air pollution on athlete health and performance
Authors: Rundell Kenneth William
Published: January 2012

Unfavourable effects on the respiratory and the cardiovascular systems from short-term and long-term inhalation of air pollution are well documented. Exposure to freshly generated mixed combustion emissions such as those observed in proximity to roadways with high volumes of traffic and those from ice-resurfacing equipment are of particular concern. This is because there is a greater toxicity from freshly generated whole exhaust than from its component parts. The particles released from emissions are considered to cause oxidative damage and inflammation in the airways and the vascular system, and may be related to decreased exercise performance. However, few studies have examined this aspect. Several papers describe deleterious effects on health from chronic and acute air pollution exposure. However, there has been no research into the effects of long-term exposure to air pollution on athletic performance and a paucity of studies that describe the effects of acute exposure on exercise performance. The current knowledge of exercising in the high-pollution environment and the consequences that it may have on athlete performance are reviewed.
Efficacy and safety of 4 weeks' treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial
Authors: Lötvall J , Bakke P S , Bjermer L , Steinshamn S , Scott-Wilson C , Crim C , Sanford L , Haumann B
Published: January 2012

Background

Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting β2agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma.

Trial design

A multicentre, randomised, double-blind, parallel-group, placebo-controlled study.

Methods

Participants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 μg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 μg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0–4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV1) (23–24 h postdose; day 29) and wm FEV1(0–4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 μg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment.

Results

60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV1per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0–4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI −3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV1(mean difference 183 ml) and 0–4 h postdose wm FEV1(mean difference 236 ml).

Conclusion

FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD.

Trial registration number

clinical trials.gov—NCT00731822.
Design and rationale of the tobacco, exercise and diet messages (TEXT ME) trial of a text message-based intervention for ongoing prevention of cardiovascular disease in people with coronary disease: a randomised controlled trial protocol: Figure 1
Authors: Chow C K , Redfern J , Thiagalingam A , Jan S , Whittaker R , Hackett M , Graves N , Mooney J , Hillis G S
Published: January 2012

Background

Although supporting lifestyle change is an effective way of preventing further events in people with cardiovascular disease, providing access to such interventions is a major challenge. This study aims to investigate whether simple reminders about behaviour change sent via mobile phone text message decrease cardiovascular risk.

Methods and analysis

Randomised controlled trial with 6 months of follow-up to evaluate the feasibility, acceptability and effect on cardiovascular risk of repeated lifestyle reminders sent via mobile phone text messages compared to usual care. A total of 720 patients with coronary artery disease will be randomised to either standard care or the TEXT ME intervention. The intervention group will receive multiple weekly text messages that provide information, motivation, support to quit smoking (if relevant) and recommendations for healthy diets and exercise. The primary end point is a change in plasma low-density lipoprotein cholesterol at 6 months. Secondary end points include a change in systolic blood pressure, smoking status, quality of life, medication adherence, waist circumference, physical activity levels, nutritional status and mood at 6 months. Process outcomes related to acceptability and feasibility of TEXT ME will also be collected.

Ethics and dissemination

Primary ethics approval was received from Western Sydney Local Health Network Human Research Ethics Committee—Westmead. Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences.

Clinical trials registration number

ACTRN12611000161921.
Transparency and disclosure, neutrality and balance: shared values or just shared words?
Authors: Greenland Sander
Published: January 2012

Values influence choice of methodology and thus influence every risk assessment and inference. To deal with this inescapable reality, we need to replace vague and unattainable calls for objectivity with more precise operational qualities. Among qualities that seem widely valued are transparency (openness) and neutrality (balance, fairness). Conformity of researchers to these qualities may be evaluated by considering whether their reports disclose key information desired by readers and whether their methodology encourages initial neutrality among hypotheses of concern. A case study is given in which two authors appearing to share these values and writing on ostensibly the same issues (disclosure and methodology) nonetheless appear to have very different concepts of what the values entail in practice. Thus, more precision is needed in explicating and implementing such values.
A clinical approach to paediatric acid–base disorders
Authors: Carmody J Bryan , Norwood Victoria F
Published: January 2012

Acid–base disorders are common in pediatric patients. We present a simple methodology for assessing both simple and complex acid–base disorders that is applicable to patients of all ages, and focus specifically on the usefulness of this approach in the pediatric patient. The application of four simple rules in sequence will define even the most complicated acid–base disturbance. However, because acid–base disorders are manifestations of systemic disorders, the primary value of characterizing them is that each generates a unique differential diagnosis. For each of the cardinal acid base disorders, the common and clinically-relevant causes in pediatric patients are explored. Additional diagnostic tools (including the serum anion gap, the delta–delta, the alveolar-arterial gradient, urine anion gap, and urine chloride), certain easily-recalled mnemonics, and empiric rules of thumb are also useful in specific situations. The treatment of acid–base disturbances is also considered, though treatment is generally best directed at the underlying disorder.