cssi/SciSciGPT-SciSciNet huggingface dataset:
Electrically stretched capacitive membranes for stiffness sensing and analyte concentration measurement

A novel method for stiffness sensing is developed using an electret capacitive sensor. The electret membrane is coated with a recognition layer that responds with a change in its stiffness/elasticity in the presence of a target analyte. Since the electret membrane is stretched by electrostatic pulling towards a metallic base plate, a change in stiffness of the composite membrane results in deflection of the membrane. This deflection is measured as a change in capacitance of the sensor. The sensitivity of the sensor to stiffness changes depends on the strength of the preset electric field. The developed sensor operates in a quasi-static mode and eliminates the need for resonant monitoring. The sealed capacitive sensor is ideal for monitoring analytes in both gas and liquid environments. The final sensor package with the capacitance measurement circuitry has a low power consumption (<30 mW). A proof-of-concept carbon dioxide gas concentration sensor is developed by coating the electret sensor with a single-walled nanotube film whose stiffness changes in the presence of carbon dioxide. Experimental results prove the viability of the sensing technique.
Comprehensive model for allosteric regulation of mammalian ribonucleotide reductase: refinements and consequences.

Reduction of NDPs by murine ribonucleotide reductase (mRR) requires catalytic (mR1) and free radical-containing (mR2) subunits and is regulated by nucleoside triphosphate allosteric effectors. Here we present the results of several studies that refine the recently presented comprehensive model for the allosteric control of mRR enzymatic activity [Kashlan, O. B., et al. (2002) Biochemistry 41, 462−474], in which nucleotide binding to the specificity site (s-site) drives formation of an active R12R22 dimer, ATP or dATP binding to the adenine site (a-site) drives formation of a tetramer, mR14a, which isomerizes to an inactive form, mR14b, and ATP binding to the hexamerization site (h-site) drives formation of an active R16R26 hexamer. Analysis of the a-site D57N variant of mR1, which differs from wild-type mR1 (wt-mR1) in that its RR activity is activated by both ATP and dATP, demonstrates that dATP activation of the D57N variant RR arises from a blockage in the formation of mR14b from mR14a, and provides st...
To Map or Not to Map: Assessing the Impact of Crime Maps on Police Officer Perceptions of Crime

An increasingly popular strategy within community oriented and problem oriented policing is to provide patrol officers with crime analysis information in the form of crime maps. The strategy is designed to encourage officers to use maps to determine problem areas within their beats and to modify their patrol strategies accordingly. Despite the promise of crime maps and GIS in general, no research has evaluated the use of crime maps by patrol officers. This paper assesses the effects of crime maps on officers' perceptions of crime patterns and their subsequent patrol activities. Results indicate that simply providing officers with maps of crime distributions will not alone improve their understanding of crime patterns within their jurisdiction. Moreover, in order to have any real impact on officer perception and subsequent police activities, agencies need to invest in training and infrastructure to allow the full capabilities of crime mapping to be realised. In addition to a discussion of the relevant find...
A new class of UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) inhibitors for the treatment of Gram-negative infections: PCT application WO 2008027466.

Background: Human infections due to Gram-negative bacteria cause significant morbidity and mortality. Identification of new strategies, molecular targets, and agents for the treatment of Gram-negative bacterial infections are needed urgently. Lipid A is a necessary component of the lipopolysaccharide-containing outer membrane of Gram-negative bacteria. The zinc-dependent hydrolase UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) involved in the first committed step in the biosynthetic pathway of lipid A has no sequence homology to any known mammalian enzymes and has emerged as an attractive Gram-negative antibacterial molecular target. Most previously described LpxC inhibitors contain a hydroxamic acid, which can lead to low specificity vs. other metal-dependent enzymes and can consequently result in unwanted side effects. Objective: This review examines a new reported class of nonhydroxamic LpxC inhibitors for the treatment of Gram-negative infections. Methods: The new class of inhibi...
Effects of Various Degrees of Undernutrition of Mice on Pregnancy and Conceptus

Maternal intake of drastically (1/2 of control) and substantially (1/3 of control) reduced feeding was studied in pregnant mice during gestation and embryonic development. Resorptions, fetal mortality rate and fetal weight were significantly affected by maternal undernutrition during the treatment period. The number of fetuses with intrauterine weight retardation was also significant.
Optimal output feedback for non-zero set point regulation: the discrete-time case

Optimal discrete-time static output feedback is considered for a non-zero set point problem with non-zero mean disturbances. The optimal control law consists of a closed-loop component for feeding back the measurements and a constant open-loop component which accounts for the non-zero set point and non-zero disturbance mean. An additional feature is the presence of state-, control- and measurement-dependent white noise. It is shown that in the absence of multiplicative disturbances, the closed-loop controller can be designed independently of the open-loop control.
Fuel-optimal maneuvers of a spacecraft relative to a point in circular orbit

Fuel optimal maneuvers of spacecraft relative to a body in circular orbit are investigated using a point mass model in which the magnitude of the thrust vector is bounded. All nonsingular optimal maneuvers consist of intervals of full thrust and coast and are found to contain at most seven such intervals in one period. Only four boundary conditions where singular solutions occur are possible. Computer simulation of optimal flight path shapes and switching functions are found for various boundary conditions. Emphasis is placed on the problem of soft rendezvous with a body in circular orbit.
Every Woman's Share: Female Sexuality in Fannie Hurst's Imitation of Life

Concurrent with medical literature in the 1930s that argued that a healthy and fulfilling lifestyle required female sexual satisfaction, Fannie Hurst's novel Imitation of Life (1933) argues that female sexual power is not centered within a woman's conspicuous sexual desirability to attract a man but rather within a conscious and adaptable sexual autonomy she now has a right to exercise. A reevaluation of the novel's feminist message not only to reestablishes Hurst as a significant feminist critic of her time but also reclaims the cultural significance of Imitation of Life as a prescient examination of modern sexual identity.
Blocking with serial and simultaneous compounds in a trace conditioning procedure

Blocking of conditioned suppression in rats was studied in three experiments using serial and simultaneous compounds in Pavlovian trace conditioning procedures. Experimental groups were first given trace conditioning trials with a 2-sec stimulus (A) presented at least 60 sec before an electric grid shock US. Next, both experimental and control groups received reinforced trials with a compound stimulus (AB). Both A and B were 2 sec in duration and were presented at least 60 sec before the US. For some groups during AB training, the A stimulus preceded the B stimulus; for others, B preceded A; for still others, A and B occurred simultaneously. Conditioning was subsequently assessed separately to both A and B. The results were as follows: First, varying the interval between the onset of A and the US during A training appeared to produce significantly different levels of conditioning to A but did not detectably affect A’s ability to block conditioning to B. Second, blocking was observed in both simultaneous and serial procedures. Third, in the serial procedure, A blocked conditioning to B whether it preceded B or followed B in the AB compound. Fourth, in tests given after AB conditioning, the experimental and control groups suppressed similarly to A. The relevance of these results to the conditioning model of Rescorla and Wagner (1972) and to Mackintosh’s (1975b) theory of attention are discussed.
Teachers' perceptions related to smoking education between 1973 and 1982.

The perceptions of public school teachers from the same school system about student smoking and smoking education were studied in 1973 and again in 1982. The data were analyzed according to three categories: changes that had occurred over time, areas that did not change, and changes in the data that were specifically related to teacher smoking status. The two major findings were: 1) there has been relatively little change in teachers' perception related to smoking education over the nine years, and 2) teachers that smoke are more resistant to participating in education programs to reduce student smoking behavior than teachers who do not smoke were nine years ago. The study lists three proposals to participate in smoking education. These include: 1) the development of in-service education programs; 2) the establishment of curriculum units on smoking education in teacher education institutions; and 3) workshops focussed on soliciting the cooperation of teachers who smoke.
Absolute temperatures as a consequence of Carnot's general axiom

1. Program In our book, Concepts and Logic of Classical Thermodynamics,1 Mr. BHARATHA and I developed classical thermodynamics on the basis of Part I of Carnot's General Axiom, namely, the motive power of a Carnot cycle is positive and is determined by its operating temperatures and by the amount of heat it absorbs. For a given body, then, there is a function G such that for any Carnot cycle # L(%) = G(0+,0 ,C + (^j)>0. (1) The domain of G is the set of operating temperatures and heats absorbed that may appertain to Carnot cycles for the body in question. It is part of the definition of a Carnot cycle that 6+>6~ and that C+(^)>0. This definition and 1 C. Truesdell & S. Bharatha, Concepts and Logic of Classical Thermodynamics as a Theory of Heat Engines, Rigorously Constructed upon the Foundation Laid by S. Carnot and F. Reech, N.Y. etc., Springer-Verlag, 1977.
Soft computing applications in transportation infrastructure asset management

In the past three decades, infrastructure management has evolved from individual systems that manage one type of infrastructure asset to integrated asset management systems. This paper makes the case that systematic asset management is today's best approach for balancing growing demands, aging infrastructure, and constrained resources. Furthermore, it emphasizes that the existing process may be improved by taking advantage of novel soft computing technologies. Given the amount of uncertainty and imprecision encountered in the infrastructure inventory and condition data, the incorporation of soft computing technologies into the decision-making process of maintaining our transportation infrastructure systems may enhance tractability and robustness of the proposed solutions, and may allow a better rapport
Understanding (and explaining) imaging performance metrics.

W1 radiologists should be able to inform a patient of the probability that a “positive mammogram actually is a cancer” and that a “negative mammogram means disease is absent.” Table 1 shows the number of true-positive findings (n = 3), true-negative findings (n = 946), false-positive findings (n = 50), and false-negative findings (n = 1) pertaining to our hypothetical sample of 1000 asymptomatic patients. Patients and caregivers clearly want to be able to interpret positive and negative test results, which is possible by generating the data shown in Table 1. The positive predictive value (5.7%) is the likelihood that a positive result will actually turn out to be breast cancer, and the negative predictive value (99.9%) is the likelihood that a negative result means the patient is disease free. The data presented in Table 1, however, can also help explain why this traditional approach is so confusing to most medical imaging practitioners. Our confusion occurs because the “reference class” for the three key parameters (i.e., incidence, sensitivity, specificity) is never the same [2]. Disease prevalence refers to all patients, sensitivity refers to those patients with cancer, and specificity refers to those patients without the disease.
On high-pressure melting of tantalum

Abstract The issues related to high-pressure melting of Ta are discussed within the context of diamond-anvil cell (DAC) and shock wave experiments, theoretical calculations and common melting models. The discrepancies between the extrapolations of the DAC melting curve and the melting point inferred from shock wave experiments, cannot be reconciled either by superheating or solid–solid phase transition. The failure to reproduce low-pressure DAC melting curve by melting models such as dislocation-mediated melting and the Lindemann law, and molecular dynamics and quantum mechanics-based calculations, undermines their predictions at moderate and high pressures. Despite claims to the contrary, the melting curve of Ta (as well as Mo and W) remains inconclusive at high pressures.
Lower bounds for eigenvalues of self-adjoint problems.

Abstract The equation y″ + [λ - q(x)]y = 0 on (0, ∞) or (-∞, ∞), in which q(x) → ∞ as x → ∞ or x → ± ∞, has a complete set of eigenfunctions with discrete eigenvalues {λn}n=0∞. We derive an inequality that contains λn, by using a quick and elementary method that does not employ a comparison theorem or assume anything special. Explicit lower bounds for λn can often be easily obtained, and three examples are given. The method also gives respectable lower bounds for λn in the classical Sturm—Liouville case.
The structure and formation of the cuticulin layer in the epicuticle of an insect, Calpodes ethlius (Lepidoptera, Hesperiidae).

The cuticulin layer is defined as the dense lamina (120–175 A thick in Calpodes larvae, depending upon the stage) forming the outer part of the epicuticle in insects. It completely invests an insect except for the gut and the openings of some sense organs. It is the first layer to be secreted during the formation of new cuticle. The formation of the cuticulin membrane may be a useful model for studying the origin of membranes in general. It arises as a triple layer de novo and is not a modified plasma membrane. Growth is by accretion at the edges of patches of cuticulin which increase in area until they cover the new surface. The triple layer (i.e. three dense laminae) may develop striations about 30 A apart transverse to the membrane, which perhaps form a sieve allowing small molecules to pass while protecting the cell from enzymes in the molting fluid. A similar porous structure persists in the tracheoles. After the resorption of molting fluid the triple layered structure again becomes obvious and the outermost layer separates from the other two to become what may be the surface lipid monolayer. The surface patterns in cuticle of various sorts probably arise by buckling of the cuticulin layer as it increases in surface area.
Molecular isotope effects in the thermal-energy charge exchange between He+ and N2

Abstract The N+ and N+2 products of the thermal-energy reaction of He+ with 14N2 and 15N2 have been examined by mass spectrometry and the emission from the product C2Σ+u state of 14N+2 has been investigated by optical spectrometry. A strong isotope effect is observed in both the N+/N+2 ratio and the optical emission. Lower limits are placed on the production of excited N+2 states other than the C2Σ+u state.
Large-Scale MD Simulations Reveal Structural Elements of the Activated State in the 5-HT2a Receptor and their Relation to Cholesterol Dynamics

The 5-HT2A Serotonin receptor (5-HT2AR) is a G-protein coupled receptor (GPCR) targeted by therapeutic drugs as well as hallucinogens such as LSD. We have previously shown that different modes of receptor activation and distinct cellular signaling are produced by hallucinogens and nonhallucinogenic congeners acting on the 5-HT2AR (Weinstein, 2006). We characterize the ligand-dependent states of 5-HT2AR from MD simulations of an experimentally-validated homology model based on rhodopsin and β2AR structures complemented by cognate information about other GPCRs. At different stages of 0.3 μs simulations of 5-HT-bound 5-HT2AR we observe sequential conformational changes that produce structural characteristics of receptor activation: (1) the extracellular part of TM6 moves inwards; (2) the toggle switch W6.48 flips to become parallel to the membrane; (3) the intracellular part of TM6 moves outwards and (4) the ionic lock in the DRY motif breaks. In the parallel simulations of 5-HT2AR with LSD (currently at 0.12 μs), only some of the same active-like components are observed (e.g., TM7 moving away from TM2, and the breaking of the ionic lock). Comparing the dynamics of 5-HT2AR complexed with LSD and 5-HT, we found that H8 of the LSD-bound receptor undergoes less rearrangement during the same time period, and that the interaction of extracellular loop 2 with LSD is stronger than with 5-HT, but that local distortions in TMs (e.g., proline kinks) are similar in the two systems. Interestingly, correlation analysis indicates that some of the local changes in 5-HT2AR relate to the dynamics of cholesterol in the membrane, at a series of preferred sites of interaction with the receptor, in a manner similar to those reported previously from μs rhodopsin simulations (Grossfield et al., 2006; Khelashvili et al., 2009).
High speed optical interconnection using thin film PDs embedded in polymer waveguides on electrical boards

As an alternative approach to current electrical interconnection technology, optical interconnections at high speeds offer several potential advantages including small footprint, simple system design (in comparison to transmission lines), and immunity to electromagnetic interference. There are a number of approaches to integrating optical signal paths in electrical interconnection substrates such as backplanes, boards, and modules. One approach utilizes the heterogeneous integration of thin film optoelectronic (OE) devices embedded in waveguides. Optical signals can be coupled in from external fibers or from thin film lasers integrated onto the substrate, propagated, distributed, and processed in a planar waveguide format, and then coupled from the waveguide to an embedded thin film photodetector by evanescent field or direct coupling. This approach achieves alignment through assembly and successive masking layers and thus minimizes alignment issues. In addition, the integrated optical signal distribution system can be integrated onto the electrical interconnection substrate after the substrate has been fabricated using post processing, thus, the board facility is not impacted through the integration of the optical links. In this paper, a discussion of the fabrication processes as well as coupling efficiency and speed measurement results for thin film InGaAs PDs embedded in polymer waveguides integrated onto Si substrates is included. These results are compared to theoretical estimates of the coupling efficiency, which was estimated using the finite difference beam propagation method.
Duck red cell 2, 3 diphosphoglycerate: its presence in the embryo and its disappearance in the adult.

Summary Erythrocytes drawn from embryos of the white Peking duck ( Anas domesticus ) contain appreciable amounts of 2,3 diphosphoglycerate and negligible amounts of inositol hexaphosphate. In the adult, inositol hexaphosphate becomes the major phosphorylated intermediate while 2,3 diphosphoglycerate is no longer detectable by ion-exchange column chromatographic separation and colorimetric assay procedures. This indicates that the metabolic pathways for the biosynthesis of 2,3 diphosphoglycerate and inositol hexaphosphate are influenced differentially during avian development. To our knowledge, this is the first report on the presence of 2,3 diphosphoglycerate in avian erythrocytes.
Using lacustrine turbidites to illuminate past earthquakes

To fully understand earthquake occurrence patterns, especially at underwater subduction zones, scientists often look to the past. Geological structures such as turbidites—the deposits from sediment-infused, dense, watery landslides caused by undersea earthquakes—can be good proxies by which scientists study past earthquakes.
Negative salience in impressions of character: Effects of extremeness of stimulus information

Ss were given incompatible positive and negative information from which to evaluate the character of a stranger. Narrative descriptions of low, medium, or high valence difference were administered in positive-negative or negative-positive order. Ratings were made after each block of information and again a week later. Final ratings indicated a disproportionate influence of negative information at all valence intensities. Originally negative impressions that had been revised upward by positive information reverted to the negative within a week; originally positive impressions that had been revised downward were not subsequently restored.
The prehistory and biogeography of terrestrial vertebrates on Guam, Mariana Islands

Aim By establishing a prehistoric fossil record for the vertebrate fauna of Guam, we can document the composition of the island’s fauna prior to Western contact. It will also complement the extensive prehistoric fossil data already known from the nearby islands of Rota, Tinian and Aguiguan, and improve our understanding of natural distributional patterns through a chronologically deeper view of the biogeography of the Mariana Islands. Location Northern Guam, Mariana Islands, Micronesia. Methods Fossil-bearing sediment was removed from karst features with vertically and horizontally controlled excavation methods. Age determinations of the fossils were estimated by radiocarbon dating associated wood charcoal samples. Results The 3314 bones (fossils) of terrestrial vertebrates date to the past two millennia and represent 34 species. Among 12 species of squamate reptiles, one is extinct (a gekkonid lizard) and another, the monitor lizard, Varanus indicus, was introduced to Guam no later than about 1600 years ago. The 17 species of birds feature five that are extinct. Two others not recorded previously on Guam are extirpated. Eight others were lost on Guam in historic times. We also recovered bones of two species of indigenous bats, (Pteropus sp., extirpated; Emballonura semicaudata, probably extirpated), and non-native rodents, (Rattus spp.). Main conclusions Guam’s contemporary faunal losses have been well documented since invasion of the Brown Treesnake (Boiga irregularis) during or shortly after WWII. Other exotics, as well as habitat deterioration, have abetted this snake’s deleterious presence. Our data further show that human impact led to declines or losses of vertebrate populations by late prehistoric times. Numerous anthropogenic extirpations would not be evident without studying fossils. Our chrono-stratigraphic evidence argues for the arrival of non-native rats (Rattus sp.) only about 1000 years ago, which helps to explain why a flightless rail survived on Guam into modern times, unlike on most other islands in Oceania.
Xylazine hydrochloride for immobilizing captive white‐tailed deer (Odocoileus virginianus)

White-tailed deer (Odocoileus virginianus) were immobilized with intramuscular doses of xylazine hydrochloride to facilitate blood sampling. Injection was either remotely by modified dart syringe or manually by hand syringe. In 86 attempts to immobilize female deer (aged 2, 5–6 yr) 73.3% were effectively immobilized for 90 min while 108 attempts to immobilize male deer (aged 2–3 yr) for at least 30 min resulted in 94.4% effective immobilization. Induction times averaged approximately 10 min for both sexes. Treated deer exhibited sedation, hypothermia, reduced respiration rates, anorexia, salivation, tongue paralysis and diarrhea. Deer also showed a loss or partial loss of pedal, palpebral, corneal, and swallowing reflexes during immobilization. Side effects of xylazine and length of immobilization appeared to be dose dependent. Mortality as a result of xylazine immobilization was four male deer out of a total of 194 immobilizing attempts on both sexes. Recommendations are given concerning care of deer during immobilization and recovery.
Short-pulse scattering from a dielectric BOR buried in a lossy layered medium

A method of moments (MoM) analysis has been developed for ultra-wideband (UWB) electromagnetic scattering from a dielectric body of revolution (BOR) embedded in a layered medium. The layered-medium can be lossy and dispersive, of interest for simulating soil (and/or a covering snow layer). To make such an analysis tractable, we use the discrete complex image technique to evaluate Sommerfeld integrals, characteristic of the Green's functions for a layered medium. Example results are presented for a model plastic mine, including a comparison to the results obtained for a perfectly electric conducting (PEC) mine with the same geometry.
Flagellar arrest behavior predicted by the geometric clutch model is confirmed experimentally by micromanipulation experiments on reactivated bull sperm

The central tenet of the Geometric Clutch hypothesis of flagellar beating is that the internal force transverse to the outer doublets (t-force) mediates the initiation and termination of episodes of dynein engagement. Therefore, if the development of an adequate t-force is prevented, then the dynein-switching necessary to complete a cycle of beating should fail. The dominant component of the t-force is the product of the longitudinal force on each outer doublet multiplied by the local curvature of the flagellum. In the present study, two separate strategies, blocking and clipping, were employed to limit the development of the t-force in Triton X-100 extracted bull sperm models. The blocking strategy used a bent glass microprobe to restrict the flagellum during a beat, preventing the development of curvature in the basal portion of the flagellum. The clipping strategy was designed to shorten the flagellum by clipping off distal segments of the flagellum with a glass microprobe. This limits the number of dyneins that can contribute to bending and consequently reduces the longitudinal force on the doublets. The blocking and clipping strategies both produced an arrest of the beat cycle consistent with predictions based on the Geometric Clutch hypothesis. Direct comparison of experimentally produced arrest behavior to the behavior of the Geometric Clutch computer model of a bull sperm yielded similar arrest patterns. The computer model duplicated the observed behavior using reasonable values for dynein force and flagellar stiffness. The experimental data derived from both blocking and clipping experiments are fully compatible with the Geometric Clutch hypothesis.
NT-proBNP measurement fails to reliably identify subclinical hypertrophic cardiomyopathy in Maine Coon cats

The purpose of this study was to evaluate the value of measuring plasma NT-proBNP concentration as a screening tool in cats with varying severity of subclinical hypertrophic cardiomyopathy (HCM). Plasma NT-proBNP concentration was measured in 35 cats that had previously been classified as normal, equivocal, moderate HCM or severe HCM via echocardiography. No cat had ever been in congestive heart failure. Cats with severe HCM had a significantly higher NT-proBNP concentration compared to the other groups (P<0.0003), however, the sensitivity of NT-proBNP for diagnosing cats with severe disease was only 44% (cutoff≤100pmol/l) to 55% (cutoff≤40pmol/l). There was no significant difference in NT-proBNP concentration between normal, equivocal and moderate categories (sensitivity for detecting moderate HCM was 0%). Based on the results of this study, NT-proBNP concentration is not considered adequate as a screening test for detecting mild to moderate HCM in Maine Coon cats and it appears that it may miss many cats with severe HCM.
Role of Phosphatidylinositol 3′ Kinase and a Downstream Pleckstrin Homology Domain–Containing Protein in Controlling Chemotaxis inDictyostelium

We show that cells lacking two Dictyostelium class I phosphatidylinositol (PI) 3′ kinases (PI3K and pi3k1/2 -null cells) or wild-type cells treated with the PI3K inhibitor LY294002 are unable to properly polarize, are very defective in the temporal, spatial, and quantitative regulation of chemoattractant-mediated filamentous (F)-actin polymerization, and chemotax very slowly. PI3K is thought to produce membrane lipid-binding sites for localization of PH domain–containing proteins. We demonstrate that in response to chemoattractants three PH domain–containing proteins do not localize to the leading edge in pi3k1/2 -null cells, and the translocation is blocked in wild-type cells by LY294002. Cells lacking one of these proteins, phdA -null cells, exhibit defects in the level and kinetics of actin polymerization at the leading edge and have chemotaxis phenotypes that are distinct from those described previously for protein kinase B (PKB) ( pkbA )-null cells. Phenotypes of PhdA-dominant interfering mutations suggest that PhdA is an adaptor protein that regulates F-actin localization in response to chemoattractants and links PI3K to the control of F-actin polymerization at the leading edge during pseudopod formation. We suggest that PKB and PhdA lie downstream from PI3K and control different downstream effector pathways that are essential for proper chemotaxis.
PIRSpred: a web server for reliable HIV-1 protein-inhibitor resistance/susceptibility prediction

We introduce a publicly available webserver, PIRSpred (http://protinfo.compbio.washington.edu/pirspred/), for accurate human immunodeficiency virus type 1 (HIV-1) genotypic resistance/susceptibility prediction. The server accepts mutant HIV-1 protease or reverse transcriptase (RT) enzyme sequences as input and predicts resistance/susceptibility to several FDA-approved inhibitors using three approaches: linear regression, docking with dynamics, and their consensus. The predictions made by the server outperform other publicly available HIV-1 genotypic interpretation algorithms, and can be used efficiently and economically in a clinical setting to guide treatment against HIV-1 infection.
Diversion, transition programs target nursing homes' status quo.

As millions of Americans age and exercise their preference for long-term care in the least restrictive environment, policymakers search for ways to increase community-based services. A new federal program—Money Follows the Person—is off to a slow but promising start. The program’s “downstream” approach moves residents out of nursing homes and into community care settings. For example, states with mature nursing home transition programs have managed to relocate 25–35 percent of their nursing home residents to assisted living. Other programs successfully using “upstream” strategies to keep people out of nursing homes have not been widely copied. The challenge for policymakers is to maintain funding and flexibility so that nursing homes are no longer the default option for older adults and people with disabilities.
Analysis of 16,192 Anterior Cruciate Ligament Reconstructions From a Community-Based Registry

Background:Orthopaedic registries have shown value in tracking and surveillance of patients, implants, and outcomes associated with procedures. No current anterior cruciate ligament reconstruction registry (ACLRR) exists in the United States.Purpose:To describe the current cohort captured by an institutional ACLRR and describe the outcomes observed in the registered patients and how findings from the ACLRR are disseminated.Study Design:Cohort study; Level of evidence, 2.Methods:The anterior cruciate ligament reconstructions (ACLRs) registered between February 2005 and September 2011 by 244 surgeons in 48 medical centers were evaluated. The ACLRR collected data intra- and postoperatively using paper forms and electronic medical records. The ACLRR cohort was longitudinally followed and outcomes were prospectively ascertained. Outcomes (ie, revisions, subsequent operations, venous thromboembolism, and surgical site infections) were adjudicated via chart review. Descriptive statistics are used to describe the...
A Model for Migratory B Cell Oscillations from Receptor Down-Regulation Induced by External Chemokine Fields

A long-standing paradigm in B cell immunology is that effective somatic hypermutation and affinity maturation require cycling between the dark zone and light zone of the germinal center. The cyclic re-entry hypothesis was first proposed based on considerations of the efficiency of affinity maturation using an ordinary differential equations model for B cell population dynamics. More recently, two-photon microscopy studies of B cell motility within lymph nodes in situ have revealed the complex migration patterns of B lymphocytes both in the preactivation follicle and post-activation germinal center. There is strong evidence that chemokines secreted by stromal cells and the regulation of cognate G-protein coupled receptors by these chemokines are necessary for the observed spatial cell distributions. For example, the distribution of B cells within the light and dark zones of the germinal center appears to be determined by the reciprocal interaction between the level of the CXCR4 and CXCR5 receptors and the spatial distribution of their respective chemokines CXCL12 and CXCL13. Computer simulations of individual-based models have been used to study the complex biophysical and mechanistic processes at the individual cell level, but such simulations can be challenging to parameterize and analyze. In contrast, ordinary differential equations are more tractable, but traditional compartment model formalizations ignore the spatial chemokine distribution that drives B cell redistribution. Motivated by the desire to understand the motility patterns observed in an individual-based simulation of B cell migration in the lymph node, we propose and analyze the dynamics of an ordinary differential equation model incorporating explicit chemokine spatial distributions. While there is experimental evidence that B cell migration patterns in the germinal center are driven by extrinsically regulated differentiation programs, the model shows, perhaps surprisingly, that feedback from receptor down-regulation induced by external chemokine fields can give rise to spontaneous interzonal and intrazonal oscillations in the absence of any extrinsic regulation. While the extent to which such simple feedback mechanisms contributes to B cell migration patterns in the germinal center is unknown, the model provides an alternative hypothesis for how complex B cell migration patterns might arise from very simple mechanisms.
In vitro stability of therapeutically relevant, internally truncated dystrophins

The X-linked recessive disease Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding the protein dystrophin. Despite its large size, dystrophin is a highly stable protein, demonstrating cooperative unfolding during thermal denaturation as monitored by circular dichroism spectroscopy. In contrast, internal sequence deletions have been associated with a loss of the cooperative unfolding and cause in vitro protein aggregation. Several emerging therapy options for DMD utilize internally deleted micro-dystrophins and multi-exon-skipped dystrophins that produce partially functional proteins, but the stability of such internally truncated proteins has not been investigated. In this study, we analyzed the in vitro stability of human dystrophin constructs skipped around exon 45 or exon 51, several dystrophin gene therapy constructs, as well as human full-length and micro-utrophin. Constructs were expressed in insect cells using the baculovirus system, purified by affinity chromatography, and analyzed by high-speed sedimentation, circular dichroism spectroscopy, and differential scanning fluorimetry. Our results reveal that not all gene therapy constructs display stabilities consistent with full-length human dystrophin. However, all dystrophins skipped in-frame around exon 45 or exon 51 show stability profiles congruent with intact human dystrophin. Similar to previous studies of mouse proteins, full-length human utrophin also displays stability similar to human dystrophin and does not appear to be affected by a large internal deletion. Our results suggest that the in vitro stability of human dystrophin is less sensitive to smaller deletions at natural exon boundaries than larger, more complex deletions present in some gene therapy constructs.
Using Supermatrices for Phylogenetic Inquiry: An Example Using the Sedges

In this article, we use supermatrix data-mining methods to reconstruct a large, highly inclusive phylogeny of Cyperaceae from nucleotide data available on GenBank. We explore the properties of these trees and their utility for phylogenetic inference, and show that even the highly incomplete alignments characteristic of supermatrix approaches may yield very good estimates of phylogeny. We present a novel pipeline for filtering sparse alignments to improve their phylogenetic utility by maximizing the partial decisiveness of the matrices themselves through a technique we call "phylogenetic scaffolding," and we present a new method of scoring tip instability (i.e. "rogue taxa") based on the I statistic implemented in the software Mesquite. The modified statistic, which we call I S , is somewhat more straightforward to interpret than similar statistics, and our implementation of it may be applied to large sets of large trees. The largest sedge trees presented here contain more than 1500 tips (about one quarter of all sedge species) and are based on multigene alignments with more than 20 000 sites and more than 90% missing data. These trees match well with previously supported phylogenetic hypotheses, but have lower overall support values and less resolution than more heavily filtered trees. Our best-resolved trees are characterized by stronger support values than any previously published sedge phylogenies, and show some relationships that are incongruous with previous studies. Overall, we show that supermatrix methods offer powerful means of pursuing phylogenetic study and these tools have high potential value for many systematic biologists. (Cyperaceae; decisiveness; megaphylogeny; PHLAWD; supermatrix.)
Transforming Growth Factor-β Mediates Astrocyte-Specific Regulation of Brain Endothelial Anticoagulant Factors

Background and Purpose —Astrocytes are potent regulators of brain capillary endothelial cell function. Recently, astrocytes were shown to regulate brain capillary endothelial expression of the fibrinolytic enzyme tissue plasminogen activator (tPA) and the anticoagulant thrombomodulin (TM). To study the mechanism of this process, we examined the hypothesis that astrocyte regulation of endothelial tPA and TM is mediated by transforming growth factor-β (TGF-β). Methods —Brain capillary endothelial cells were grown in blood-brain barrier models. We examined astrocyte-endothelial cocultures, endothelial monocultures, and astrocyte-conditioned media (ACM) for the expression of TGF-β. We also incubated endothelial cells with ACM to determine the role of TGF-β. Following 24 hours of incubation, we assayed for tPA and TM mRNA, as well as tPA and TM activity. Results —Astrocyte-endothelial cocultures and ACM exhibited significantly higher levels of active TGF-β than brain endothelial monocultures and endothelial cells grown in nonconditioned media, respectively. Brain endothelial cells incubated with ACM exhibited reduced tPA and TM mRNA and activity. Treatment with exogenous TGF-β produced dose-dependent reductions in tPA and TM. The effects of ACM on both tPA and TM were blocked by TGF-β neutralizing antibody. Conclusions —These data indicate that TGF-β mediates astrocyte regulation of brain capillary endothelial expression of tPA and TM.
A Comparison of the Performance of Open-End and Ring Spun Yarns in Terry Toweling:

The relative moisture uptake characteristics of ring and open-end yarns are investigated by a variety of methods. Wicking height and volume of moisture elevated differ as the yarn structure is altered. Open-end yarn wicks better and more evenly but only elevates about the same volume of water for a given yarn count as ring yarn. Water can enter a fabric from the edge (by wicking) or by contact with the surface, and this affects the performance marginally. The yarn and fabric structures both play a part in determining performance. It is concluded that there is little difference in the ultimate capacity of ring and open-end yarns of a similar twist and count when made up into a similar fabric. The rate of dye exhaustion is initially, more rapid for open-end yarns and this is of benefit in dyeing.
Robust Source-Seeking Hybrid Controllers for Autonomous Vehicles

We consider the problem of steering an autonomous vehicle to locate a radiation source utilizing measurements of the radiation intensity only. We propose a control algorithm that locates the source through a sequence of line minimizations of the radiation intensity. We implement in a hybrid controller, with sample-and-hold and logic variables, a discretized version of the algorithm suitable for steering a point-mass vehicle. The algorithm confers global convergence and practical stability properties to the closed-loop hybrid system. We discuss these properties and characterize the region of convergence for the vehicle. Convergence and stability results are supplemented with simulations.
Safety analysis of all-inside arthroscopic repair of peripheral triangular fibrocartilage complex.

Purpose The purpose of this study was to determine whether an all-inside peripheral triangular fibrocartilage complex (TFCC) repair using the FasT-Fix device (Smith & Nephew Endoscopy, Andover, MA) is safe by measuring the proximity of the anchors to ulnar-sided anatomic structures. Methods Eleven fresh-frozen cadaveric wrists were thawed and placed in traction. Under direct arthroscopic visualization, an all-inside arthroscopic peripheral TFCC repair was completed by placing a single FasT-Fix device in a vertical mattress fashion. The wrists were then dissected to visualize the 2 anchors. The distance between these anchors and the flexor carpi ulnaris (FCU), extensor carpi ulnaris (ECU), and dorsal branch of the ulnar sensory nerve (DBUN) were measured with digital calipers and recorded. Results The peripheral anchor averaged 4.2 mm (range, 0 to 14 mm) from the ECU tendon, 3.8 mm (range, 0 to 9 mm) from the DBUN, and 8.3 mm (range, 1 to 15 mm) from the FCU tendon. The central anchor averaged 9.6 mm (range, 2 to 15 mm) from the ECU tendon, 6.8 mm (range, 1 to 13 mm) from the DBUN, and 7.6 mm (range, 1 to 13 mm) from the FCU tendon. Conclusions This study exposes some safety concerns with the all-inside peripheral TFCC repair using the FasT-Fix device, which was found to reside in close proximity to the ECU, FCU, and DBUN. In multiple wrists the anchors were noted to underlie the anatomic structure that we measured, making it possible to pierce these structures with the needle before deployment of the anchor. Clinical Relevance Though technically feasible, all-inside arthroscopic repair of the peripheral TFCC risks injury to the ulnar-sided anatomy.
Estimation of Left Ventricular Residual Volume in the Dog by a Thermodilution Method

Thermodilution was used to estimate left ventricular volumes by the indicator-dilution principle. The results of multiple determinations in the same animal were in close agreement. Average values determined in 16 dogs anesthetized with a chloralose-urethane mixture were SV 18 ml., ESV 37 ml., EDV 56 ml., and CO 2.54 L./min. The ratio ESV/EDV averaged 66 per cent, which was significantly less than the ESV to EDV ratio of 79 per cent observed in 14 other dogs anesthetized with sodium pentobarbital and studied in a comparable fashion. This difference was attributed primarily to the myocardial depressant effects of the barbiturate anesthetic. The ability to perform multiple determinations without "indicator" accumulation, to record the time-temperature curve directly at the base of the aorta without sampling through a catheter system, to avoid introducing substances into the circulation which may produce significant circulatory effects, and to perform calibration quickly and easily suggests that the thermodilution technique offers a simple, rapid, and reproducible method for estimating ventricular volumes.
David Noy and Hanswulf Bloedhorn. Inscriptiones Judaicae Orientis. III Syria and Cyprus. Texts and Studies in Ancient Judaism 102. Tübingen: Mohr Siebeck, 2004. 284 pp.

David Noy has labored in the past decade to update J. B. Frey's Corpus inscriptionum iudaicarum (vol. 1 [Rome 1936; revised by B. Lifshitz, New York, 1975]; vol. 2 [Rome, 1952]). He has already produced two volumes on the North Mediterranean (the Balkans and southern Italy, 1993, and Rome, 1995) and another for Greco-Roman Egypt (with William Horbury, 1992).
Low Temperature Fabrication and Surface Modification Methods for Fused Silica Micro- and Nanochannels

Electrokinetic based micro- and nanofluidic technologies provide revolutionary opportunities to separate, identify and analyze biomolecular species. Key to fully harnessing the power of such systems is the development of a robust method for integrated electrodes as well as a thorough understanding of the influence of the electrokinetic surface properties with and without different surface modifications. In this work, we demonstrate a surface micromachined fabrication approach for integrated addressable metal electrodes within centimeter-long nanofluidic channels using a low-temperature, xenon diflouride dry-release method for novel biosensing applications, as well as recent results from a joint theoretical and experimental study of electrokinetic surface properties in nano- and microfluidic channels fabricated with fused silica. The main contribution of this fabrication process involves the addition of addressable electrodes to a novel dry-release channel fabrication method, produced at <300°C, to be used in nanofluidic electronic sensing of biomolecules. Finally, we also show a novel method with which to coat our channels with silane based chemistries. Certain modifications are observed to show improved resistance to non-specific adhesion of both small molecules and proteins, indicating their further use as compatible surfaces in micro- and nanofluidic applications.