cssi/SciSciGPT-SciSciNet huggingface dataset:
Ion permeation through a narrow channel: using gramicidin to ascertain all-atom molecular dynamics potential of mean force methodology and biomolecular force fields.

We investigate methods for extracting the potential of mean force (PMF) governing ion permeation from molecular dynamics simulations (MD) using gramicidin A as a prototypical narrow ion channel. It is possible to obtain well-converged meaningful PMFs using all-atom MD, which predict experimental observables within order-of-magnitude agreement with experimental results. This was possible by careful attention to issues of statistical convergence of the PMF, finite size effects, and lipid hydrocarbon chain polarizability. When comparing the modern all-atom force fields of CHARMM27 and AMBER94, we found that a fairly consistent picture emerges, and that both AMBER94 and CHARMM27 predict observables that are in semiquantitative agreement with both the experimental conductance and dissociation coefficient. Even small changes in the force field, however, result in significant changes in permeation energetics. Furthermore, the full two-dimensional free-energy surface describing permeation reveals the location and magnitude of the central barrier and the location of two binding sites for K+ ion permeation near the channel entrance—i.e., an inner site on-axis and an outer site off-axis. We conclude that the MD-PMF approach is a powerful tool for understanding and predicting the function of narrow ion channels in a manner that is consistent with the atomic and thermally fluctuating nature of proteins.
Points of view: effective partnerships between K-12 and higher education.

Erin Dolan and Kimberly Tanner . . . 35Note from the EditorsCBE is pleased to present ‘‘Points of View,’’ a series designed toaddress issues faced by many people within the life scienceseducational realm. We present several differing points of view back-to-back on a given topic to promote discussion of the topic. Readersare encouraged to participate in the online discussion forum hostedby Cell Biology Education at www.cellbioed.org/discussion/public/main.cfm. We hope op-ed pieces on Points of View willstimulate thought and dialogue on significant educational issues.In this issue, we address the question ‘‘How do we constructeffective partnerships between K-12 education and higher educa-tion?’’ K-12 educators and college/university faculty share manyinterests, and need to work together to ensure effective teachereducation and that curricula are articulated. Yet, we work indifferent settings; some would say different cultures. In PointsView, we examine the needs and the responsibilities of ourinstitutions of higher education to support K-12 science education,and examine how we can build interactions that recognize thestrengths and help remedy the weaknesses of each partner.The points of view we present in this issue provide a number ofresponses to those questions. We invite you to share your ideas,experiences and insights on the discussion board.
Nonmethane hydrocarbons at Pico Mountain, Azores: 2. Event-specific analyses of the impacts of mixing and photochemistry on hydrocarbon ratios

[1] Nonmethane hydrocarbon (NMHC) measurements at Pico Mountain observatory are analyzed in combination with FLEXPART transport simulations. The results are used to assess the utility of NMHC as indicators for the occurrence of atmospheric transport events and photochemical processing on an event-specific basis. Continuous in situ observations were made in lower free tropospheric air that had experienced a wide range of photochemical aging and traveled 3–10 days since last encountering significant emissions. They therefore provide a data set suitable for investigating the interaction of emissions, transport, and mixing in aged air parcels. Measurements of ethane, propane, and n-butane during April 2005 are analyzed in detail to assess the degree to which the magnitude and variability of hydrocarbon ratios can be quantitatively understood as resulting from the mixing of emissions that have experienced varying degrees of photochemical oxidation. The age distribution of emissions was estimated with FLEXPART; resulting hydrocarbon ratios were simulated by applying first-order decay to these emissions using the method of Parrish et al. (2007). These simulations capture the magnitude and large variations of observed hydrocarbon ratios. The relationship between the distribution of the timing of upwind emissions and measures of photochemical age calculated using these hydrocarbon ratios is discussed using the FLEXPART age distributions. The results demonstrate that continuous NMHC observations can be used to derive measures of photochemical age that can be quantitatively interpreted without the need for assumptions regarding mixing. Such analyses are valuable for studying OH levels and the distribution of upwind emission timing during pollution transport events.
Adhesion of Human Umbilical Vein Endothelial Cells to the Immediate-Early Gene Product Cyr61 Is Mediated through Integrin αvβ3

Abstract Cyr61 is a member of a family of growth factor-inducible immediate-early gene products thought to act cooperatively with the activities of growth factors. Upon synthesis, Cyr61 is secreted and is predominantly incorporated into the extracellular matrix. Recently, we demonstrated that Cyr61 promotes cell adhesion and migration and augments growth factor-induced DNA synthesis (Kireeva, M. L., Mo, F.-E., Yang, G. P., and Lau, L. F. (1996) Mol. Cell. Biol. 16, 1326–1334). In the present study, we investigated possible candidate receptor(s) on human umbilical vein endothelial cells (HUVECs) mediating adhesion to Cyr61. Under both serum-containing and serum-free conditions, adhesion of HUVECs to Cyr61 was dose-dependent, saturable, and abolished by affinity-purified anti-Cyr61 antibodies. Cell adhesion to Cyr61 was divalent cation-dependent and specifically inhibited by the peptide RGDS and LM609, a monoclonal antibody against integrin αvβ3. Furthermore, purified αvβ3 bound directly to an affinity matrix of Cyr61-coupled Sepharose 4B, and this interaction was specifically blocked by anti-Cyr61 antibodies. Additionally, in a solid phase binding assay, soluble Cyr61 bound to immobilized αvβ3 in a dose-dependent manner, and half-saturation binding occurred at approximately 5 nm Cyr61. As expected, the interaction of Cyr61 with immobilized αvβ3 was blocked by RGDS and LM609. In sum, these results identified Cyr61 as a novel ligand for αvβ3 and indicate that the adhesion of HUVECs to Cyr61 is mediated through interaction with this integrin. The possibility that integrin αvβ3 functions as a signaling receptor for Cyr61 accounts for most if not all activities that can be ascribed to Cyr61 to date and suggests a mechanism of action discussed herein.
Prolyl Isomerase Pin1 Promotes Amyloid Precursor Protein (APP) Turnover by Inhibiting Glycogen Synthase Kinase-3β (GSK3β) Activity NOVEL MECHANISM FOR Pin1 TO PROTECT AGAINST ALZHEIMER DISEASE

Alzheimer disease (AD) is characterized by the presence of senile plaques of amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP) and neurofibrillary tangles made of hyperphosphorylated Tau. Increasing APP gene dosage or expression has been shown to cause familial early-onset AD. However, whether and how protein stability of APP is regulated is unclear. The prolyl isomerase Pin1 and glycogen synthase kinase-3β (GSK3β) have been shown to have the opposite effects on APP processing and Tau hyperphosphorylation, relevant to the pathogenesis of AD. However, nothing is known about their relationship. In this study, we found that Pin1 binds to the pT330-P motif in GSK3β to inhibit its kinase activity. Furthermore, Pin1 promotes protein turnover of APP by inhibiting GSK3β activity. A point mutation either at Thr-330, the Pin1-binding site in GSK3β, or at Thr-668, the GSK3β phosphorylation site in APP, abolished the regulation of GSK3β activity, Thr-668 phosphorylation, and APP stability by Pin1, resulting in reduced non-amyloidogenic APP processing and increased APP levels. These results uncover a novel role of Pin1 in inhibiting GSK3β kinase activity to reduce APP protein levels, providing a previously unrecognized mechanism by which Pin1 protects against Alzheimer disease.
A novel technique for increasing charge injection capacity of neural electrodes for efficacious and safe neural stimulation

Neural prostheses require chronically implanted small area penetrating electrode arrays that can stimulate and record neural activity. The fundamental requirement of neural electrodes is to have low interface impedance and large charge injection capacity (CIC). To achieve this fundamental requirement, we developed a novel technique to modify the surface of the Utah Electrode Array (UEA) to increase the real surface area without changing the geometrical surface area. Pt was coated on modified and unmodified (control) UEAs and electrochemical characterization such as impedance and CIC was measured and compared. The surface modified electrode impedance and CIC was ∼188 Ohm and ∼24 mC/cm2 respectively. Increasing the real surface area of electrodes decreases the impedance by 1000 times and increases the CIC by 80 times compared to the control samples. The CIC of modified UEA was significantly higher than of any material reported in the literature, higher than sputtered iridium oxide (4 mC/cm2) or PEDOT (15 mC/cm2).
Caspase remodeling of the spectrin membrane skeleton during lens development and aging.

Abstract Terminal differentiation of lens fiber cells resembles the apoptotic process in that organelles are lost, DNA is fragmented, and changes in membrane morphology occur. However, unlike classically apoptotic cells, which are disintegrated by membrane blebbing and vesiculation, aging lens fiber cells are compressed into the center of the lens, where they undergo cell-cell fusion and the formation of specialized membrane interdigitations. In classically apoptotic cells, caspase cleavage of the cytoskeletal protein α-spectrin to ∼150-kDa fragments is believed to be important for membrane blebbing. We report that caspase(s) cleave α-spectrin to ∼150-kDa fragments and β-spectrin to ∼120- and ∼80-kDa fragments during late embryonic chick lens development. These fragments continue to accumulate with age so that in the oldest fiber cells of the adult lens, most, if not all, of the spectrin is cleaved to discrete fragments. Thus, unlike classical apoptosis, where caspase-cleaved spectrin is short lived, lens fiber cells contain spectrin fragments that appear to be stable for the lifetime of the organism. Moreover, fragmentation of spectrin results in reduced membrane association and thus may lead to permanent remodeling of the membrane skeleton. Partial and specific proteolysis of membrane skeleton components by caspases may be important for age-related membrane changes in the lens.
Particle dynamics near the surface of a horizontal tube in a gas-fluidized bed

The knowledge of particle concentration, their velocities and residence times at an immersed surface in a gas-fluidized bed is essential for proper reactor design. The voidage distribution is needed to validate any mechanistic theory for heat transfer. Recently renewed interest has arisen in understanding the particle dynamics near the tube surface due to its implication in explaining and understanding the phenomenon of boiler tube erosion in fluidized-bed combustors. This led to the development of an image carrying fiber optic probe technique to investigate the variation of /epsilon//sub s/ around the periphery of a horizontal tube as a function of superficial fluidizing velocity, U. However, this study was confined to only values of U smaller than 1.10 U /sub mf/. Here U/sub mf/ is the value of the superficial minimum fluidization velocity. This restriction was due to the use of low speed (30 frames per second) TV camera and video cassette recording system. In the work reported here a high speed Kodak Ekta Pro 1000 motion analysis equipment is used and particle dynamics investigated over a wide velocity range.
Evolution of the Earth's mantle: perspective from the Re-Os isotopic system

The Re-Os isotopic system (Allegre and Luck, 1980; Faure, 1986; Shirey, 1991) has seen increasing use as a unique tracer, complementry to other radioisotope systems because of its chaleophile/siderophile behavior. Increased use has followed improvements in measurement sensitivity (Creaser et al., 1991; Vlkening et aL, 1991), analytical accuracy (Walczyk et al., 1991; Yin et al., 1993) and chemical separation and spike sample equilibration (Morgan and Walker, 1989; Morgan et aL, 1991) at picogram levels (walker, 1988; Shirey and Walker, 1994).
RosettaBackrub—a web server for flexible backbone protein structure modeling and design

The RosettaBackrub server (http://kortemmelab.ucsf.edu/backrub) implements the Backrub method, derived from observations of alternative conformations in high-resolution protein crystal structures, for flexible backbone protein modeling. Backrub modeling is applied to three related applications using the Rosetta program for structure prediction and design: (I) modeling of structures of point mutations, (II) generating protein conformational ensembles and designing sequences consistent with these conformations and (III) predicting tolerated sequences at protein-protein interfaces. The three protocols have been validated on experimental data. Starting from a user-provided single input protein structure in PDB format, the server generates near-native conformational ensembles. The predicted conformations and sequences can be used for different applications, such as to guide mutagenesis experiments, for ensemble-docking approaches or to generate sequence libraries for protein design.
Recent progress in continuously processed IBAD MgO template meters for HTS applications

Abstract We discuss our recent progress using IBAD MgO as a template for subsequent deposition of YBa 2 Cu 3 O 7− δ (YBCO) high-temperature superconductors on metallic substrate tapes. We have refined the process by improving substrate preparation and by using reflected high-energy electron diffraction to monitor and improve IBAD MgO films. High quality, continuously processed IBAD MgO (c-IBAD) has been deposited on moving meter-length metal tape. By incorporating these optimized processing parameters, we have been able to deposit biaxially textured MgO on metallic substrates continuously with the best in-plane mosaic spreads near 9°. The subsequent pulsed laser deposition of 1–2 μm thick YBCO films on c-IBAD has resulted in superconducting transport critical current densities>1 MA/cm 2 (75 K, SF) on small area samples. Longer 4.5 cm samples of c-IBAD tape have also been coated with a 1 cm wide sample carrying 93 A (75 K, SF) for a 1.5 μm thick YBCO.
A Call to Serve

Once Barack Obama becomes the 44th president of the United States in January 2009, he will, sooner or later, appoint individuals to science and technology policy positions within the executive branch of government. It seems as though every science- and engineering-related think tank either has published, or shortly will, a report calling on the new administration to appoint these people quickly and give them the authority and tools to do their job.
BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients.

BK virus nephritis: Risk factors, timing, and outcome in renal transplant recipients. Background BK virus nephritis (BKVN) has emerged as an important cause of renal transplant failure. Quantified analysis of its timing and clinical course is generally lacking. We have thus quantified the timing, risk factors, evolution of renal function, and transplant graft outcome in renal transplant recipients with BKVN from our center. Methods A total of 41 cases of BKVN were diagnosed in 1001 renal and renal/pancreas transplant recipients. There were 2 groups: group I (N = 16), with diagnosis based on renal biopsy alone from January 1996 to August 2001, and group II (N = 25), with diagnosis based on quantitative blood BKV-PCR and biopsy from September 2001 to December 2003. The demographics, the clinical course, immunosuppressive therapy, renal function, and graft outcome were quantified. Donor, recipient, and transplant risk variables were studied using a univariate analysis. Actuarial graft survival was calculated. An immunosuppressive scale created to evaluate the degree of immunosuppression in these patients and its reduction after the diagnosis of BKVN. Results The median time from transplant to BKVN diagnosis was 318 days (range 48-1356). The actuarial graft survival in patients with BKVN at 6 months, 1, 3, and 5 years was 97%, 90%, 58%, and 47%. The corresponding values for those without BKVN were 94%, 92%, 83%, and 76%, respectively, P Conclusion BKVN is a relatively late complication of renal transplantation. Despite reduction in immunosuppression, graft loss occurred in 46% of patients. There was a steep decline in renal function in months preceding the diagnosis of BKVN, and reduction in calcineurin inhibitor dose, but not overall immunosuppression, correlated with stabilization of renal function.
Effect of CCK antibodies on food intake and weight gain in zucker rats

While exogenous administration of cholecystokinin (CCK) decreases food intake in many species, it has not been demonstrated conclusively that CCK is necessary for satiety to occur. In these experiments the role of CCK in eliciting satiety was further investigated by using endogenously produced and exogenously administered antibodies to CCK which were hypothesized to sequester circulating CCK. In the first experiment Zucker obese (n = 12, 192 +/- 16 g) and lean (n = 12, 152 +/- 11 g) male rats were administered CCK-8 conjugated to bovine serum albumin or bovine serum albumin by subcutaneous administration in Freund's adjuvant. Average percent binding of 125I-gastrin-17 by serum taken 4, 8 and 12 weeks after treatment initiation was increased (19.9 vs. 2.1, p less than 0.001) in rats treated with CCK conjugate than controls, and the increase was greater in lean (27.5 vs. 1.9) than in obese (12.2 vs. 2.2, p less than 0.001) rats. In lean, but not obese rats, average daily food intake and weight gain were increased (9 and 17% p less than 0.04 and p less than 0.02 respectively) in rats with CCK-AB compared with rats with no CCK-AB during the three months. Development of CCK-AB did not affect food intake response to exogenously administered CCK-8 or pancreas weight relative to body weight. In Experiment 2 increased food intakes of obese and lean rats 30 min after intraperitoneal injection of rabbit serum with CCK-AB were greater than those after intraperitoneal injection of rabbit serum without CCK-AB (1.92 vs. 1.41, g, p less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)
“TrustDroid™”: Preventing the use of SmartPhones for information leaking in corporate networks through the used of static analysis taint tracking

Over the last 12 years three important dates have marked the beginning of a major paradigm shift in computing and the security models applied to protect an emerging computing environment - March 1999, January 9th, 2007, and July 2007. These dates roughly correspond to the birth of SalesForce.com, the most successful Software as a Service (SaS) provider to date, Steve Jobs introduction of the Iphone,, and the discovery of the Zeus Botnet. These innovations have been instrumental in enabling a paradigm shift in computing, away from a corporate network centric model with Windows end-point devices to what we called in this manuscript the Circa 2020 Computing Model. In the circa 2020 Computing model applications and data reside in the Cloud, the concept of an extended Trust Domain (network) disappears - there is no corporate network, and finally the end-point device is a SmartPhone owned and operated by employees - Bring Your Own Device (BYOD). In such an environment, the end-point device is not “Trusted”, and there is a high likelihood that the BYOD can be used as a channel to leak sensitive data. In this manuscript, we present a new mechanism to prevent such a situation. We called this mechanism “TrustDroid™”. TrustDroid™ is a static analyzer based on taint tracking that can be used to prevent leakage of sensitive information by an un-trusted Android SmartPhone.
Parameter estimation for the cusp catastrophe model

Before catastrophe models can achieve scientific legitimacy, they must be subjected to empirical tests with real data. This research report provides the details of a recently developed statistical procedure for the estimation of the parameters of the canonical cusp catastrophe model. The procedure is computationally no more complicated than multiple regression, and is based on the method of moments. As an example of the use of this estimation technique, it is shown that extroversion can be used as a splitting factor in the prediction of driving speed after the ingestion of alcohol. This is an example in which catastrophe theory supplies a nontrivial and successful description of the effect of a higher-level system characteristic (extroversion-introversion) on a lower-level measure of system performance (driving speed). Of course, catastrophe models can be used in and between all system levels.
Catheter-Associated Sepsis Caused by Ochrobactrum anthropi: Report of a Case and Review of Related Nonfermentative Bacteria

Ochrobactrum anthropi, formerly known as CDC group Vd, is an oxidase-producing, gram-negative, non-lactose-fermenting bacillus that oxidizes glucose and grows readily on MacConkey agar. Only occasionally isolated from human clinical specimens, this organism has rarely been found to be pathogenic. We describe the first reported case of infection due to O. anthropi in a child, that of bacteremia in a 3-year-old girl undergoing chemotherapy for retinoblastoma. In addition, we review the literature concerning cases of infection due to this and closely related bacterial species, namely Alcaligenes xylosoxidans subspecies xylosoxidans, Agrobacterium radiobacter, and "Achromobacter" group B. Finally, we attempt to clarify the confusing history and taxonomy of these organisms as well as make recommendations regarding antimicrobial therapy for infections caused by them.
A Minimum Path Algorithm Among 3D-Polyhedral Objects

In this work we introduce a minimum path theorem for 3D case. We also develop an algorithm based on the theorem we prove. The algorithm will be implemented on the software package we develop using C language. The theorem we introduce states that; "Given the initial point I, final point F and S be the set of finite number of static obstacles then an optimal path P from I to F, such that PA S = 0 is composed of straight line segments which are perpendicular to the edge segments of the objects." We prove the theorem as well as we develop the following algorithm depending on the theorem to find the minimum path among 3D-polyhedral objects. The algorithm generates the point Qi on edge ei such that at Qi one can find the line which is perpendicular to the edge and the IF line. The algorithm iteratively provides a new set of initial points from Qi and exploits all possible paths. Then the algorithm chooses the minimum path among the possible ones. The flowchart of the program as well as the examination of its numerical properties are included.
Curve and Surface Duals and the Recognition of Curved 3D Objects from their Silhouettes

This article addresses the problem of recognizing a solid bounded by a smooth surface in a single image. The proposed approach is based on a new representation for two- and three-dimensional shapes, called their signature, that exploits the close relationship between the dual of a surface and the dual of its silhouette in weak-perspective images. Objects are modeled by rotating them in front of a camera without any knowledge of or constraints on their motion. The signatures of their silhouettes are concatenated into a single object signature. To recognize an object from novel viewpoint other than those used during modeling, the signature of the contours extracted from a test photograph is matched to the signatures of all modeled objects signatures. This approach has been implemented, and recognition examples are presented.
The influence of antenna pattern on Faraday rotation in remote sensing at L-band

The influence of the antenna pattern on measured Faraday rotation is examined in the context of passive remote sensing at L-band. It is shown that while I = Tv + Th is independent of Faraday rotation to first order, I has rotation dependence when realistic antenna patterns are included in the analysis. Also, it is shown that the angle retrieved from the 3rd Stokes parameter can be biased relative to Faraday rotation at boresight.
Seven Decades of Calcium Depletion in Organic Horizons of Adirondack Forest Soils

We used repeated sampling of the forest floor to determine if there was a net loss of Ca from organic horizons of Adirondack forest soils between 1930 and 2004. In 1984, we established 48 permanent plots in spruce-fir, northern hardwood, and pine stands located in areas sampled by Carl C. Heimburger in the early 1930s. Following Heimburger's protocols and analytical methods, we measured pH and dilute-HCl-extractable Ca in Oe and Oa horizons, and determined that there was a statistically significant decrease in Ca concentration during the 1932 to 1984 interval. In the 36 plots that we could locate in 2004, we again sampled organic horizons. During the >70-yr interval, HCl-extractable Ca concentrations in the Oe and Oa horizons decreased in each forest type (P < 0.05). We also measured NH 4 Cl-extractable Ca and Al in the 1984 and 2004 samples and found a significant decrease in Ca concentration in the pooled Oe horizons. High-elevation spruce-fir plots showed a Ca loss rate between 1984 and 2004 of 7.6 to 9.8 kg ha -1 yr -1 . This compares well with a 4-yr Ca cycling study conducted in an equivalent spruce-fir forest at Whiteface Mt. in the Adirondacks, which showed an annual forest floor Ca loss of 8.4 kg ha -1 yr -1 . Based on uptake and anion flux data from the Whiteface Mt. study, we estimated that about 25 to 30% of the 1984 to 2004 forest floor Ca loss in the spruce-fir plots is attributable to leaching driven by atmospheric SO 4 2- deposition.
Romans 13:1-7 Apartheid's Last Biblical Refuge:

That the interpretation of Romans 13:1-7 has been integral to much theological discussion in South Africa for over a decade is no accident. Having abandoned its previous biblical bases for support of apartheid ideology, the white Dutch Reformed church, in common with the state, and certain fundamentalist missionary groups, often connected with the American religious right, have pointed to this passage and its parallels as the ultimate sanction for enforced submission to present power relations. Liberationist and black theologians who signed The Kairos Document of 1985-86 castigate such use of the passage as an aspect of idolatrous "state theology." Their approach is to relativize its applicability by reference to situational and total biblical context. In contributing to the debate, Walter Wink argues that the passage forbids only violent, not non-violent opposition to the state. This view is criticized, and yet another approach proposed, based on the hypothesis that Romans 13:1-7 is part of an overall re...
A reduced-order modeling approach to represent subgrid-scale hydrological dynamics for land-surface simulations: application in a polygonal tundra landscape

Abstract. Existing land surface models (LSMs) describe physical and biological processes that occur over a wide range of spatial and temporal scales. For example, biogeochemical and hydrological processes responsible for carbon (CO2, CH4) exchanges with the atmosphere range from the molecular scale (pore-scale O2 consumption) to tens of kilometers (vegetation distribution, river networks). Additionally, many processes within LSMs are nonlinearly coupled (e.g., methane production and soil moisture dynamics), and therefore simple linear upscaling techniques can result in large prediction error. In this paper we applied a reduced-order modeling (ROM) technique known as "proper orthogonal decomposition mapping method" that reconstructs temporally resolved fine-resolution solutions based on coarse-resolution solutions. We developed four different methods and applied them to four study sites in a polygonal tundra landscape near Barrow, Alaska. Coupled surface–subsurface isothermal simulations were performed for summer months (June–September) at fine (0.25 m) and coarse (8 m) horizontal resolutions. We used simulation results from three summer seasons (1998–2000) to build ROMs of the 4-D soil moisture field for the study sites individually (single-site) and aggregated (multi-site). The results indicate that the ROM produced a significant computational speedup (> 103) with very small relative approximation error (
Insertion of anthrax protective antigen into liposomal membranes: Effects of a receptor

Protective antigen (PA), the receptor-binding component of anthrax toxin, heptamerizes and inserts into the endosomal membrane at acidic pH, forming a pore that mediates translocation of the enzymic components of the toxin to the cytosol. When the heptameric pre-insertion form of PA (the prepore) is acidified in solution, it rapidly loses the ability to insert into membranes. To maximize insertion into model membranes, we examined two ways to bind the protein to large unilamellar vesicles (LUV). One involved attaching a His tag to the von Willebrand factor A domain of one of the PA receptors, ANTXR2, and using this protein as a bridge to bind PA to LUV containing a nickel-chelating lipid. The other involved using a His tag fused to the C terminus of PA to bind the protein directly to LUV containing the same lipid. Both ways enhanced pore formation at pH 5.0 strongly and about equally, as measured by the release of K+. Controls showed that pore formation in this system faithfully reproduced that in vivo. We also showed that binding unmodified ANTXR2 von Willebrand factor A to the prepore in solution enhanced its pore forming activity by slowing its inactivation at acidic pH. These findings indicate that an important role of PA receptors is to promote partitioning of PA into the bilayer by maintaining the prepore close to the target membrane and presumably in the optimal orientation as it undergoes the acidic pH-dependent conformational transition to the pore.
Optical absorption and neutron scattering by lattice vibrations of incommensurate lattices

The lattice dynamics of discrete incommensurate lattices are studied numerically by linearizing the equations of motion for the Frenkel-Kontorova model (which consists of a chain of masses connected by springs sitting in a sinusoidal potential) about the equilibrium positions of the atoms, which are determined numerically. The optical-absorption and neutron scattering cross sections are studied. It is found that despite the fact that the incommensurate system lacks translational invariance (because there does not exist a unit cell), the optical-absorption and neutron scattering spectra always appear to consist of a few sharp lines, no matter how strong the coupling of the two periodic systems. The calculations should be applicable to incommensurate charge-density waves, ionic order in potassium hollandite, a one-dimensional ionic conductor, and other systems exhibiting two incommensurate periodicities.
Delayed hypersensitivity in several strains of mice studied with six different tests.

Abstract Delayed hypersensitivity (tuberculin allergy) was induced in seven different strains of mice and detected by means of six different kinds of tests in order to compare both the tests and mouse strains under standardized conditions. The mice were sensitized by two weekly subcutaneous injections of living H37Ra tubercle bacilli suspended in water-in-oil emulsions, and they were tested three weeks after the first vaccination. C57BL, C57BR, C57L, DBA, and CF#1 mouse strains were not essentially different, either in frequency or in intensity of hypersensitization. C3H mice appeared to be less frequently sensitized than mice of other strains but, when sensitive, reacted as strongly. Swiss Webster mice were sensitized as frequently but reacted somewhat more intensely. The six tests employed were divided into primary and secondary categories by reliability, sensitivity, versatility, and simplicity. Footpad, intracutaneous, and intramuscular tests made up the first category; lung density, body temperature, and systemic tests comprised the second. Some basic data concerning delayed hypersensitivity in the mouse as well as its detectability by the traditional skin test have been presented and discussed.
Long-lasting transient conditions in simulations with heavy-tailed workloads

Recent evidence suggests that some characteristics of computer and telecommunications systems may be well described using heavy tailed distributions — distributions whose tail declines like a power law, which means that the probability of extremely large observations is nonnegligible. For example, such distributions have been found to describe the lengths of bursts in network traffic and the sizes of files in some systems. As a result, system designers are increasingly interested in employing heavy-tailed distributions in simulation workloads. Unfortunately, these distributions have properties considerably different from the kinds of distributions more commonly used in simulations; these properties make simulation stability hard to achieve. In this paper we explore the difficulty of achieving stability in such simulations, using tools from the theory of stable distributions. We show that such simulations exhibit two characteristics related to stability: slow convergence to steady state, and high variability at steady state. As a result, we argue that such simulations must be treated as effectively always in a transient condition. One way to address this problem is to introduce the notion of time scale as a parameter of the simulation, and we discuss methods for simulating such systems while explicitly incorporating time scale as a parameter.
Role for RpoS but Not RelA of Legionella pneumophila in Modulation of Phagosome Biogenesis and Adaptation to the Phagosomal Microenvironment

The induction of virulence traits by Legionella pneumophila at the post-exponential phase has been proposed to be triggered by the stringent response mediated by RelA, which triggers RpoS. We show that L. pneumophila rpoS but not relA is required for early intracellular survival and replication within human monocyte-derived macrophages and Acanthamoeba polyphaga. In addition, L. pneumophila rpoS but not relA is required for expression of the pore-forming activity. We provide evidence that RpoS plays a role in the modulation of phagosome biogenesis and in adaptation to the phagosomal microenvironment. Thus, there is no functional link between the stringent response and RpoS in the pathogenesis of L. pneumophila.
Biomechanical effects of hardware configuration after union of proximal femoral and shaft fractures

Objectives The use of two implants to manage concomitant ipsilateral femoral shaft and proximal femoral fractures has been indicated, but no studies address the relationship of dynamic hip screw (DHS) side plate screws and the intramedullary nail where failure might occur after union. This study compares different implant configurations in order to investigate bridging the gap between the distal DHS and tip of the intramedullary nail. Methods A total of 29 left synthetic femora were tested in three groups: 1) gapped short nail (GSN); 2) unicortical short nail (USN), differing from GSN by the use of two unicortical bridging screws; and 3) bicortical long nail (BLN), with two angled bicortical and one unicortical bridging screws. With these findings, five matched-pairs of cadaveric femora were tested in two groups: 1) unicortical long nail (ULN), with a longer nail than USN and three bridging unicortical screws; and 2) BLN. Specimens were axially loaded to 22.7 kg (50 lb), and internally rotated 90°/sec until failure. Results For synthetic femora, a difference was detected between GSN and BLN in energy to failure (p = 0.04) and torque at failure (p = 0.02), but not between USN and other groups for energy to failure ( vs GSN, p = 0.71; vs BLN, p = 0.19) and torque at failure ( vs GSN, p = 0.55; vs BLN, p = 0.15). For cadaveric femora, ULN and BLN performed similarly because of the improvement provided by the bridging screws. Conclusions Our study shows that bicortical angled screws in the DHS side plate are superior to no screws at all in this model and loading scenario, and suggests that adding unicortical screws to a gapped construct is probably beneficial.
Understanding the basis of a class of paradoxical mutations in AraC through simulations

Most mutations at position 15 in the N-terminal arm of the regulatory protein AraC leave the protein incapable of responding to arabinose and inducing the proteins required for arabinose catabolism. Mutations at other positions of the arm do not have this behavior. Simple energetic analysis of the interactions between the arm and bound arabinose do not explain the uninducibility of AraC with mutations at position 15. Extensive molecular dynamics (MD) simulations, carried out largely on the Open Science Grid, were done of the wild-type protein with and without bound arabinose and of all possible mutations at position 15, many of which were constructed and measured for this work. Good correlation was found for deviation of arm position during the simulations and inducibility as measured in vivo of the same mutant proteins. Analysis of the MD trajectories revealed that preservation of the shape of the arm is critical to inducibility. To maintain the correct shape of the arm, the strengths of three interactions observed to be strong in simulations of the wild-type AraC protein need to be preserved. These interactions are between arabinose and residue 15, arabinose and residues 8-9, and residue 13 and residue 15. The latter interaction is notable because residues L9, Y13, F15, W95, and Y97 form a hydrophobic cluster which needs to be preserved for retention of the correct shape.
Managing your online professional identity

Editor's Summary Confusion around names and identity features can undermine professional standing, but it can be avoided by carefully managing one's online personal and professional identity. It is advisable to routinely check hits on one's name online to be sure desired information is not clouded by mistakes or misinformation or overshadowed by another with the same name. Professionals should create personal e-portfolios and tie them to LinkedIn and other appropriate social networking sites. Active participation on those sites helps boost search returns tied with one's professional identity. Promotional websites such as Vizilibity.com can be made more effective by adding keywords to highlight interests and achievements, while MyWebCareer.com evaluates one's networking profile. By customizing privacy settings, one can limit access to personal information. Managing personal information takes time but is critical to be sure online information accurately represents your identity.
Making team science better: Applying improvement‐oriented evaluation principles to evaluation of cooperative research centers

The rise of the research center has changed the landscape of U.S. research enter-prise. It has also created a number of evaluation challenges, particularly when considering strategically focused, multifaceted cooperative research centers (CRCs). The author argues that although recent CRC evaluation efforts have gone a long way toward meeting the needs of groups interested in accountabil-ity, they do little to meet the needs of inexperienced scientist managers who try to lead and manage these organizationally complex initiatives. An exception to this trend is described: the improvement-oriented evaluation strategy pio-neered by the National Science Foundation IUCRC program. © Wiley Period-icals, Inc.
The effect of load on muscle output.

Analytic consideration of muscle output resulted in an expression that relates the power output of a muscle to the imposed load. The simplest theory predicted that maximum power output would occur when the load impedance was equal to the impedance of the muscle system involved. Modification of this theory to accommodate the inverse type of relationship between the force generated and the speed of contraction, in agreement with physiological considerations, predicted the maximum power output at a load impedance (moment of inertia) five to ten times the impedance of the muscle system involved. Experimental observations over a wide range of loads on a specially constructed inertial dynamometer confirmed the predictions and gave a power curve similar to the predicted one.
André Beauneveu and Mehun-sur-Yèvre

MEHUN-SUR-YEVRE must have been the climax of magnificence among the splendid ch6teaux of the Duke of Berry.' It was the cherished gem of 'le plus grand batisseur de la maison de Valois'2 and a most sumptuous accent in the secular art of the fourteenth century. A miniature of the Temptation of Christ, in the Duke's celebrated Tres riches Heures, shows this chAteau as the dominating feature, occupying most of the foreground (fig. 1) .3 Representations of other castles belonging to the Duke are to be seen in various other miniatures of the same manuscript. Those in the calendar, provide incidental background setting for the subject appropriate to the particular month, thus suggesting personal, associative, seasonal or temporal meaning.4 The scene showing Mehun, however, is charged with pointed iconographic significance. None, better than the precious castle and this beautiful island panorama, could epitomize 'all the kingdoms of the world'5 with which Satan hoped to tempt Christ. Upon Mehun were lavished the creative energies of a remarkable constellation of artists whom the Duke had gathered into his service. Construction was directed by the bold and original architect, Guy de Dammartin.6 Andre Beauneveu, renowned in France and the Netherlands, was in charge of painting and sculpture.7 Among his younger associates was Jean de Cambrai, a gifted sculptor, destined to become head of the atelier in his turn.8 To view the works which these men created, there were invited artists of distinction matched only by the masters themselves. One such
Growth and 2-methylisoborneol production by the cyanobacterium Phormidium LM689

Growth and production of 2-methylisoborneol (MIB) was characterized in the cyanobacterium Phormidium sp. LM689 isolated from Lake Mathews, California, USA. The effects of: 1) uptake of several organic amendments related to pigment biosynthesis, 2) Fe availability, and 3) copper algicides were examined. Growth was estimated by total chlorophyll and soluble protein accumulation. Pyruvate additions up to 1250 mM did not effectively alter biomass accumulation. Mevalonic lactone increasingly stimulated (protein) growth but not MIB output at the same range of concentrations. Geraniol did not inhibit overall cyanobacterial growth when added to 300 μM, but did slightly decrease chlorophyll accumulation. Farnesol exhibited an antibiotic effect at all concentrations from 10 to 100 μM. Phormidium was tolerant to 1 ppm Cu+2 added as copper sulfate or as chelated copper. Siderophore production and growth in Fe and chelator-free medium was also demonstrated.
Recognition of another member of the malignant catarrhal fever virus group: an endemic gammaherpesvirus in domestic goats

A novel gammaherpesvirus in goats that is herein tentatively designated as caprine herpesvirus-2 was identified based on the sequence of a fragment from the herpesvirus DNA polymerase gene. Sequence alignment analysis revealed that the virus sequence isolated from goats was 67% identical to the homologous sequence from alcelaphine herpesvirus-1, 71% identical to ovine herpesvirus-2 and 73% identical to a recently recognized herpesvirus causing malignant catarrhal fever in white-tailed deer. Combined serological and PCR-survey data demonstrated that this virus is endemic in goats and its transmission pattern may be similar to that of ovine herpesvirus-2 in sheep.
GRAPH THEORY AS A PROXY FOR SPATIALLY EXPLICIT POPULATION MODELS IN CONSERVATION PLANNING

Spatially explicit population models (SEPMs) are often considered the best way to predict and manage species distributions in spatially heterogeneous landscapes. However, they are computationally intensive and require extensive knowledge of species' biology and behavior, limiting their application in many cases. An alternative to SEPMs is graph theory, which has minimal data requirements and efficient algorithms. Although only recently introduced to landscape ecology, graph theory is well suited to ecological applications concerned with connectivity or movement. This paper compares the performance of graph theory to a SEPM in selecting important habitat patches for Wood Thrush (Hylocichla mustelina) conservation. We use both models to identify habitat patches that act as population sources and persistent patches and also use graph theory to identify patches that act as stepping stones for dispersal. Correlations of patch rankings were very high between the two models. In addition, graph theory offers the ability to identify patches that are very important to habitat connectivity and thus long-term population persistence across the landscape. We show that graph theory makes very similar predictions in most cases and in other cases offers insight not available from the SEPM, and we conclude that graph theory is a suitable and possibly preferable alternative to SEPMs for species conservation in heterogeneous landscapes.
High temperature performance of high-power GaAs Schottky and silicon p-i-n rectifiers in hard- and soft-switching power converters

The dynamic switching characteristics of 200 V high-power GaAs Schottky and Si p-i-n rectifiers are studied at various temperatures under both hard and soft switching conditions. Devices were first characterized to measure forward and reverse I-V, C-V, reverse breakdown voltage and reverse recovery performances. The same devices were characterized for turn-on and turn-off in switching circuits designed to study the dynamic switching performances under hard and soft switching conditions at different temperatures. Advanced finite element based mixed device and circuit simulations were used to study the internal plasma dynamics under boundary conditions imposed by circuit operation. It is shown that, for hard switching applications, GaAs Schottky power rectifiers exhibit significantly reduced switching power losses compared to Si p-i-n rectifiers. For soft switching applications, there is no significant difference in the switching power losses for these two devices. Diode performance at elevated temperatures is studied and the temperature dependencies of switching and conduction power losses are analyzed.