cssi/SciSciGPT-SciSciNet huggingface dataset:
High-performance computing for drug design

High performance computing has become a major focus of attention by government, industry, medical centers and academic institutions. The U.S. government has made this a ldquotop national priorityrdquo, linking the development of a ldquodata superhighway systemrdquo to national competitiveness and national research interest. High performance supercomputing approaches have been used for sequence analysis, gene finding, protein structural prediction, all-atom simulation such as molecular dynamics and quantum calculations, modeling biological networks such as systems biology and more recently drug design and drug discovery. All these approaches are highly computationally demanding, in terms of compute load, communication speed, and memory load. Supercomputing based drug design and drug discovery use high-performance super-computers and bioinformatics approaches to discover, enhance, and study drugs and related biologically active molecules as well as the sites of protein interactions. Methods include molecular modeling using biophysical approaches such as molecular dynamics, semi-empirical quantum mechanics methods, ab initio quantum chemistry methods, density functional theory, receptor-ligand interactions and protein docking and so on. The success of the high-throughput drug design and drug discovery now directly relies on the high-performance computing capabilities. Many research and computational products that were used to be considered impossible now proved to be feasible and effective with the help of todaypsilas supercomputing techniques. In particular, the identification of diseases relating to protein structural changes challenges biomedicine as the result of the sophisticated protein interaction networks that demand effective drug design using supercomputing based on mathematical, computational and biophysical models and algorithms for solving the model equations, and the bioinformatics techniques to analyze and validate the results. Those will need our deeper studies of biophysical phenomena and interesting biophysical and algorithmic problems using supercomputing. In this keynote lecture, we follow the scenario of Koshlandpsilas ldquoinduced-fitrdquo to demonstrate that the identification of intrinsically disordered/unstructured proteins will became increasingly important to the drug design and discovery, because many proteins are folding upon interaction with drugs. The high-performance computing approaches help to reduce the number of targets for a good drug that has to be eventually tested by expensive and time-consuming synthesis and laboratory and toxicology experiments. High-performance computing study of intrinsically unstructured protein related pathways focuses on the discovery and development of novel drugs for the treatment of metabolic and mis-folding related diseases by targeting the metabolic and biological pathways in the protein interaction network. The advances of supercomputing will foster the synergistic relation between biophysical and computational sciences towards translational bioinformatics in the future.
Measuring T-cell responses against LCV and CMV in cynomolgus macaques using ELISPOT: Potential application to non-clinical testing of immunomodulatory therapeutics

AbstractA number of immunomodulatory therapeutics increase the risk of disease associated with latent herpesviruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV), a member of the lymphocryptovirus (LCV) family that infects humans. The diseases associated with loss of immunity to these viruses can have major impacts on patients as well as on the commercial viability of the immunomodulatory therapeutics. In an effort to develop non-clinical methods for measuring effects on anti-viral immunity, we have developed an interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISPOT) assay to quantify the number of CMV or LCV-reactive T-cells in peripheral blood of cynomolgus macaques. After optimization of various parameters, the IFN-γ ELISPOT assay was characterized for specificity, intra-assay, monkey-to-monkey, and longitudinal variability and sensitivity to immunosuppression. The results show that nearly all animals have detectable responses against both CMV and LCV and responses were derived from ...
Use of Interrupted Time Series Analysis in Evaluating Health Care Quality Improvements

Interrupted time series (ITS) analysis is arguably the strongest quasi-experimental research design. ITS is particularly useful when a randomized trial is infeasible or unethical. The approach usually involves constructing a time series of population-level rates for a particular quality improvement focus (eg, rates of attention-deficit/hyperactivity disorder [ADHD] medication initiation) and testing statistically for a change in the outcome rate in the time periods before and time periods after implementation of a policy/program designed to change the outcome. In parallel, investigators often analyze rates of negative outcomes that might be (unintentionally) affected by the policy/program. We discuss why ITS is a useful tool for quality improvement. Strengths of ITS include the ability to control for secular trends in the data (unlike a 2-period before-and-after t test), ability to evaluate outcomes using population-level data, clear graphical presentation of results, ease of conducting stratified analyses, and ability to evaluate both intended and unintended consequences of interventions. Limitations of ITS include the need for a minimum of 8 time periods before and 8 after an intervention to evaluate changes statistically, difficulty in analyzing the independent impact of separate components of a program that are implemented close together in time, and existence of a suitable control population. Investigators must also be careful not to make individual-level inferences when population-level rates are used to evaluate interventions (though ITS can be used with individual-level data). A brief description of ITS is provided, including a fully implemented (but hypothetical) study of the impact of a program to reduce ADHD medication initiation in children younger than 5 years old and insured by Medicaid in Washington State. An example of the database needed to conduct an ITS is provided, as well as SAS code to implement a difference-in-differences model using preschool-age children in California as a comparison group.
Optic nerve sectioning in rats.

Abstract A simple certain method was described for blinding rats with a minimum of trauma by sectioning of the optic nerves.
The Dystrophinopathies: An Alternative to the Structural Hypothesis

Abstract Abnormal expression of the cytoskeletal protein dystrophin has deleterious consequences for skeletal muscle, cardiac muscle, and the central nervous system. A complete failure to express the protein produces Duchenne muscular dystrophy (DMD), in which there is extensive and progressive skeletal muscle necrosis, the development of a life-threatening dilated cardiomyopathy, and mild mental retardation. Dystrophin binds the F-actin cytoskeleton and is normally expressed in a complex of transmembrane proteins (the “dystrophin protein complex”) that interact with external components of the basal lamina. One pathogenic model for DMD (the “structural hypothesis”) suggests that this complex forms a structural bridge between the external basal lamina and the internal cytoskeleton and that the absence of dystrophin produces a defect in membrane structural support that renders skeletal muscle susceptible to plasmalemmal ruptures (or “tears”) during the course of contractile activity. This review attempts to critically evaluate the structural hypothesis for DMD and presents an opposing model (the “channel aggregation model”) that highlights the role of dystrophin in organizing the membrane cytoskeleton and the role of the cytoskeleton in aggregating ion channels and neurotransmitter receptors. Since ion channel aggregation is a process that is common across organ systems, the idea that channel function can be altered when aggregated ion channels interact with a dystrophic cytoskeleton has immediate implications for the expression of the dystrophinopathies in skeletal muscle, cardiac muscle, and the central nervous system.
Entry strategies into the process improvement initiative

One of the more important steps in starting a process improvement initiative is to determine the appropriate tasking and the scope of the process improvement program. There is great temptation for an organization to attempt to take on too much too fast, especially if it feels that it must catch up with its competition. For example, an organization will assess its capability against all of the key process areas (KPAs) of the Capability Maturity Model (CMM) and try to set up working groups and action plans in a broadly based approach to implement multiple levels of KPAs at the same time. While it is natural to want to initiate a program quickly, it is important for an organization trying to get a process improvement initiative started to be as realistic as possible in these beginning stages. It might not be appropriate for an organization to conduct an assessment right away, yet another organization might want to focus on only a few areas to get its process improvement initiative started, show positive results and then expand. This paper will identify critical factors to consider and discuss process improvement entry strategies that the authors have helped their clients to achieve over the past five years. Copyright © 1998 John Wiley & Sons, Ltd.
Teaching Wikipedia as a mirrored technology

Digital spaces on the World Wide Web can be consumed as windowed technologies, providing apparently transparent access to information, or as mirrors, multi–layered and complex, requiring critical reflexivity for productive participation. Approaching Wikipedia as a mirrored technology exploits its potential as a pedagogical tool with which students can improve their research practices and writing proficiency in digital environments. Students can learn to grapple with Wikipedia as a complex, living discourse community, whose rhetorical practices and technical conventions they must learn in order to make contributions to it that are accepted by fellow editors of the site and withstand its unique editorial processes. By writing for Wikipedia , students become critical users of this digital resource, develop rhetorical and technological proficiency, and generate texts that prompt real–world response and provide potentially useful information for fellow users of this massive digital resource.
Lessons in reducing volcano risk

Since 1980, volcanologists have confronted more volcanic crises than any time since the Mont Pelee catastrophe in 1902. Good science alone will not do the job of reducing volcano risk.
Challenges in defining and identifying patients with non-small cell lung cancer and poor performance status

Performance status (PS), a subjective measure of the functional status of a patient with cancer and his or her ability to perform normal activities, is influenced both by tumor-related and by comorbidity-related factors. It is a reliable independent prognostic indicator for survival in patients with advanced non-small cell lung cancer. Patients with a poor PS (PS2) constitute up to 30% to 40% of the population of patients with advanced non-small cell lung cancer, yet they are underrepresented in clinical trials. These patients are heterogeneous, which makes it challenging to use their PS scores alone to guide their therapy. A greater understanding of PS scores and the factors that affect them can be gained through PS2-specific clinical trials, which can lead to the development of better PS instruments to aid in making therapeutic decisions.
Efficient input queuing and cell scheduling scheme for scalable ultrabroadband optoelectronic ATM switching

Input queuing has advantages for building ultra-broadband ATM switches with the throughput beyond 100Gb/s because it imposes minimal memory bandwidth requirements. Using a novel multi-tag-queue input module and a novel matrix-unit-cell-scheduling module, our input queue-based ATM switch avoids head-of-line blocking and provides almost 100% utilization. In a 32-port configuration, the switch can deliver an aggregate throughput of 128Gb/s.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Ileocolonic anastomotic ulcers: a case series and review of the literature

Abstract OBJECTIVE: Although gastric anastomotic ulcers have been well described, there are only a few reports in the literature, mostly in the pediatric population, of ulcers occurring at colonic anastomotic sites. Our aim was to determine the clinical profile of postoperative colonic anastomotic ulcers in adult patients undergoing colonoscopy at our institution. METHODS: We performed a retrospective review of colonoscopies done at our institution between 1993 and 1997. RESULTS: Six patients with colonic anastomotic ulcers were identified; all had ileocolonic anastomoses. All patients presented with iron deficiency anemia with evidence of gastrointestinal (GI) blood loss and this was the indication for colonoscopy. The age at the time of ileocolonic anastomoses ranged from birth to 74 yr and age at the time of colonoscopy ranged from 24 to 76 yr. The interval between surgery and detection of anastomotic ulcer ranged from 15 months to 28 yr. Only two patients had a possible etiology: one with previous small bowel Crohn’s disease, and the other with significant nonsteroidal antiinflammatory drugs (NSAID) use and evidence of small-bowel ulcers in the adjacent ileum as well. Three of the patients had previously undergone surgical resection and revision of the anastomosis without benefit; the ulcers recurred at the new anastomosis and continued to bleed. CONCLUSIONS: Ulcers can develop at sites of ileocolonic anastomoses. The commonest presentation is with iron deficiency anemia due to occult blood loss. The etiology of the ulcer, in most patients, remains speculative. The therapeutic approach to these ulcers is to discontinue all NSAIDs, treat underlying inflammatory bowel disease, if present, and supplement with oral iron. Surgery should be reserved for life-threatening bleeds or for anemia refractory to oral iron therapy.
Progress toward measuring the unitarity angle γ

Measuring the angle γ of the unitarity triangle is an important part of overconstraining the standard model’s explanation of CP violation and testing for new physics contributions to CP violation. Although there are many ways to measure γ, all of them have significant experimental or theoretical challenges. This talk presents progress at the BABAR experiment toward measuring γ usingB meson decays.
Effects of bladder resorption on pharmacokinetic data analysis.

In modern pharmacokinetic analysis, the urinary bladder is usually viewed as a nonreturning compartment or storage site for renally excreted compounds. Our previous studies have indicated appreciable bladder resorption of drugs. The present study used computer simulations to evaluate the quantitative importance of several potential determinants of bladder resorption, namely the bladder resorption rate constant (ka), interval between bladder voiding (Δtvoid),ratio of renal elimination rate constant to overall elimination rate constant (kex:kel ratio), andkel ort1/2. The data identifiedka, Δtvoid, andkex:kel ratio as the three most important determinants of the rate and extent of bladder resorption. We further examined the errors introduced in the derived pharmacokinetic parameters due to omission of bladder resorption. Plasma concentration-time profiles and urinary excretion-time profiles were generated by simulations using different values ofka, Δtvoid, andkex:kel ratio. These profiles were used to derive the pharmacokinetic parameters, including the renal clearance (CLrenal), total body clearance (CLtotal), nonrenal clearance (CLnonrenal),t1/2, mean residence time (MRT), amount and fraction of dose excreted in urine (Aex andfe), and volume of distribution at steady state (Vdss). Data show that resorption of drug from the bladder into the systemic circulation increased the area under the plama concentration-time profile,MRT andt1/2, but decreasedCLrenal,CLtotal,Aex, andfe.Vdss was relatively unchanged. Overestimation of MRT andt1/2 was dependent onka,kex:kel ratio,and Δtvoid. Underestimation inCLrenal,Aex, andfe was not dependent on thekex:kel ratio, but was affected by changes inka and Δtvoid.CLrenal andfe were the most sensitive pharmacokinetic parameters, with a≥50% underestimation at aka value that we reported previously, for the bladder absorption of antipyrine in rats with intact urothelium. In summary, these data indicate (i) alteration in the plasma concentration-time profiles and urinary excretion-time profiles due to bladder resorption, and (ii) substantial over-or underestimation in the derived pharmacokinetic parameters due to erroneous omission of bladder resorption.
Glucocorticoid sensitivity and receptors in BALB/c T cell lymphoma lines expressing restricted patterns of Ly differentiation antigens.

Abstract Three BALB/c T cell lymphoma cell lines which express restricted patterns of Ly differentiation antigens were examined for their sensitivity to glucocorticoids and their receptor content. BALENTL 4 (Ly 1− 2+), BALENTL 9 (Ly 1+2+) and BALENTL 13 (Ly 1+2−) were all found to be growth inhibited and ultimately lysed by the action of dexamethasone. These three cell lines contained high affinity, saturable, specific glucocorticoid receptors as quantitated by cytoplasmic and whole cell binding assays. The latter technique consistently resulted in a higher number of specific binding sites/cell. Incubation at 37°C but not at 0°C resulted in the nuclear translocation of cytoplasmic [3H]-dexamethasone-receptor complexes. Phosphatase inhibitors (NaF or NaMoO4) included in the homogenization buffer had no effect on the subsequent cytoplasmic binding of [3H]-dexamethasone, which suggests that receptors were not being rapidly inactivated by dephosphorylation. Although the inhibitor of proteolysis, PMSF, had no effect on the cytoplasmic binding of [3H]-dexamethasone, TPCK significantly reduced specific binding by presumably oxidizing free sulfhydryl groups. BALENTL 4 was shown to have suppressor activity when used as a third party in the mixed lymphocyte response and this suppressor activity could be blocked by pretreating the cells with dexamethasone. These data demonstrate that glucocorticoid sensitivity may be retained by transformed cells which express restricted patterns of Ly differentiation antigens and some associated immunological functions.
Natural convection in an air layer enclosed between two vertical plates with different temperatures

Abstract The temperature field in an air layer enclosed between two isothermal vertical plates with different temperatures has been investigated with the help of a Zehnder-Mach interferometer. Local heat transfer coefficients were derived from the temperature gradients in the air normal to the plate surfaces. Below a certain Grashof number and above a certain value of the height to thickness ratio. heat is transferred from the hot to the cold boundary by conduction in the central part of the layer. Convection contributes only in the corner regions. For large Grashof numbers and below a certain limit of the height to thickness ratio, boundary layers exist along the surfaces of the enclosure, whereas in the central core the temperature is uniform in horizontal planes. The temperature increases, however, in vertical direction. Fluctuations in the flow and wave motions were observed in some of the experiments. Relations for local and average heat transfer are presented.
Transfusion-Associated Hepatitis B: Past and Present

Thus, it can be concluded that: (1) Hepatitis B, even before the introduction of donor screening for HBsAg, probably never accounted for more than one-quarter of all cases of transfusion-associated hepatitis. (2) As of 1988, the frequency of this viral infection in blood recipients, now that sensitive donor screening for HBsAg is routine, is less than 10%. The exception are multiply transfused populations, such as hemophiliacs, the majority of whom have evidence of current or past exposure to hepatitis B. However, new inactivation procedures are likely to reduce the attack rate in virgin populations of hemophiliacs. (3) Interdiction of paid blood has proved far more effective than donor screening for HBsAg in reducing the overall frequency of transfusion-associated hepatitis. (4) The current requirement that all donors be screened for anti-HBc and ALT as surrogate markers of non-A, non-B hepatitis infection, and for anti-HIV, is likely to reduce the hepatitis B attack rate even more, perhaps to near zero. (5) The long-term outcome of transfusion-associated hepatitis B has not been determined, a task that will remain difficult to accomplish because of the paucity of current cases. Information in this regard will need to be derived from the recall and reevaluation of pedigreed patients who participated in prospective studies that were conducted in the distant past.
Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity

A number of strategies have been investigated to enhance the mechanical stability of engineered tissues. In this study, we utilized lysyl oxidase (LO) to enzymatically crosslink extracellular matrix (ECM) proteins, particularly collagen and elastin, to enhance the mechanical integrity of the ECM and thereby impart mechanical strength to the engineered tissue. Vascular smooth muscle cells (VSMCs) were liposomally transfected with the LO gene. Both Northern and Western analyses confirmed increased LO expression. Increased LO activity was demonstrated using a fluorescent enzyme substrate assay and by observation of the presence of increased levels of desmosine, a product of LO crosslinking, in the ECM. The mechanical effects of altered crosslink densities within tissue-engineered constructs were demonstrated in a VSMC-populated collagen gel model. When smooth muscle cells transfected with lysyl oxidase were seeded in collagen gels, the tensile strength and elastic modulus in these constructs increased by approximately two-fold compared to constructs seeded with mock-transfected VSMCs. Also, desmosine levels in the LO-populated collagen gels were higher than they were in mock-seeded gels, as demonstrated via immunohistochemical staining. Compositional analysis of the ECM deposited by the transformed cells showed similar collagen and elastin levels, and cell proliferation rates were similar as well, thus attributing increased mechanical properties to ECM crosslinking.
Bandwidth- and power-efficient routing in linear wireless networks

The goal of this paper is to establish which practical routing schemes for wireless networks are most suitable for power-limited and bandwidth-limited communication regimes. We regard channel state information (CSI) at the receiver and point-to-point capacity-achieving codes for the additive white Gaussian noise (AWGN) channel as practical features, interference cancellation (IC) as possible, but less practical, and synchronous cooperation (CSI at the transmitters) as impractical. We consider a communication network with a single source node, a single destination node, and N-1 intermediate nodes placed equidistantly on a line between them. We analyze the minimum total transmit power needed to achieve a desired end-to-end rate for several schemes and demonstrate that multihop communication with spatial reuse performs very well in the power-limited regime, even without IC. However, within a class of schemes not performing IC, single-hop transmission (directly from source to destination) is more suitable for the bandwidth-limited regime, especially when higher spectral efficiencies are required. At such higher spectral efficiencies, the gap between single-hop and multihop can be closed by employing IC, and we present a scheme based upon backward decoding that can remove all interference from the multihop system with an arbitrarily small rate loss. This new scheme is also used to demonstrate that rates of O(log N) are achievable over linear wireless networks even without synchronous cooperation.
Encapsulation and release of Amphotericin B from an ABC triblock fluorous copolymer.

Purpose PEG-phospholipid-based micelles have been successfully used for the solubilization of several hydrophobic drugs but generally lack sustained stability in blood. Our novel PEG-Fluorocarbon-DSPE polymers were designed to increase stability and improve time-release properties of drug-loaded micelles.
A noninvasive method for the measurement of flow-induced surface displacement of a compliant surface

A noninvasive optical method is described which allows the measurement of the vertical component of the instantaneous displacement of a surface at one or more points. The method has been used to study the motion of a passive compliant layer responding to the random forcing of a fully developed turbulent boundary layer. However, in principle, the measurement technique described here can be used equally well with any surface capable of scattering light and to which optical access can be gained. The technique relies on the use of electro-optic position-sensitive detectors; this type of transducer produces changes in current which are linearly proportional to the displacement of a spot of light imaged onto the active area of the detector. The system can resolve displacements as small as 2 μm for a point 1.8 mm in diameter; the final output signal of the system is found to be linear for displacements up to 200 μm, and the overall frequency response is from DC to greater than 1 kHz. As an example of the use of the system, results detailing measurements obtained at both one and two points simultaneously are presented.
Dehydroepiandrosterone and a β-agonist, energy transducers, alter antioxidant enzyme systems: Influence of chronic training and acute exercise in rats☆

We examined the influence of dehydroepiandrosterone (DHEA), a beta-agonist, and exercise training on enzymes that detoxify toxic oxygen species. Feeding 0.4% DHEA decreased hepatic cytosolic (c) selenium-dependent glutathione peroxidase (GPX), (-26%, P less than 0.0001) and increased hepatic mitochondrial (m) Mn superoxide dismutase (SOD), (+38%, P less than 0.001). DHEA decreased myocardial c-GPX (-21%, P less than 0.05) when compared to a beta-agonist (beta A; L644969 Merck and Co.) fed at 5 ppm but neither differed from the Control (C). In contrast, the beta A increased hepatic m-GPX (+25%, P less than 0.05). In skeletal muscle, DHEA and beta A decreased muscle c-GPX by 20 and 12%, respectively (P less than 0.0009). DHEA increased both muscle (+20%, P less than 0.01) and myocardial (+20%, P less than 0.05) c-glutathione S-transferase (GST) over beta A (+20%, P less than 0.01) but neither was significantly different from C. Similar to DHEA, chronic training (Tr) (1 h/day, 5 days/week at 27 m/min, 15% grade on treadmill) decreased hepatic c-GPX (-16%, P less than 0.003). Tr elevates muscle c-GPX (+36%, P less than 0.05) in C. Tr increased myocardial c-GPX by 28% in the beta A-treated rats, whereas Tr decreased myocardial c-GPX by 22% in the C (P less than 0.05, interaction). One hour of acute exercise (Ex) (70% VO2 max relative work load) decreased hepatic homogenate catalase (-12%, P less than 0.02) and increased hepatic m-Mn SOD (+28%, P less than 0.03). Ex decreased myocardial c-GST (P less than 0.05) only in the DHEA-treated rats. DHEA and Tr may improve efficiency of oxygen utilization at the tissue level with lower antioxidant enzyme activity in liver and locally protective up-regulation in muscle. beta A stresses oxygen utilization systems and liver responds by up-regulation of antioxidant enzymes. The increase in myocardial c-GPX activity in the beta A-treated group may be a protective effect against indirect catecholamine-induced myocardial necrosis which results from free radical generation.
Clinical features of mitral valve prolapse associated with low body weight

Abstract An association between mitral valve prolapse (MVP) and low body weight has been well documented in family, 1 general population, 2 and clinical 3 studies. The low body weight of patients with MVP may exert a clinically beneficial effect by permitting lower levels of blood pressure in MVP patients than in comparable control subjects. 1,4 The observation of a low prevalence of mitral clicks or murmurs in MVP patients, however, in 2 studies in which UVP was strongly associated with low body. weight 2,5 has led some investigators to suggest that MVP in lean patients might represent a variant of normal devoid of the auscultatory features encountered in patients with clinically recqgnized MVP. To test this hypothesis, we related body habitus to auscultatory and other demographic and clinical features of MVP in consecutive adult family members documented to have MVP in a family study that has been previously reported in part. 1,6–7
Acute Dissection of the Descending Aorta: A Case Report and Review of the Literature

Cardiovascular disease is the leading cause of death worldwide. Acute aortic syndromes, which include aortic dissection, intramural hematoma, and penetrating aortic ulcer, represent the most morbid presentations of aortic disease and can be difficult to diagnose. Recent advances in imaging have allowed for more rapid and accurate diagnosis of acute aortic syndromes and the options for management are expanding. This case report and review presents the case of a 43-year-old man with acute type B aortic dissection who underwent two endovascular procedures for malperfusion syndrome. The review focuses on the presentation, diagnosis, medical management, and procedural options for acute dissection of the descending aorta.
HISTONE H1 RIBOSOMAL RNA SYNTHESIS AND CELL DIFFERENTIATION

Abstract It is proposed that histone H1° prevents binding of the rRNA transcription factor UBF to regulatory sequences of the rRNA gene. This has a role in reducing rRNA synthesis and inhibiting cell proliferation. This affords the opportunity for other mechanisms to promote cell differentiation.
Quantitative analysis of locomotor defects in neonatal mice lacking proprioceptive feedback.

Abstract Proprioceptive feedback derived from specialized receptors in skeletal muscle is critical in forming an accurate map of limb position in space, and is used by the central nervous system to plan future movements and to determine accuracy of executed movements. Knockout mouse strains for genes expressed by proprioceptive sensory neurons have been generated that result in generalized motor deficits, but these deficits have not been quantitatively characterized. Here we characterize a conditional knockout mouse model wherein proprioceptive sensory neuron synaptic transmission has been blocked by selective ablation of munc18-1, a synaptic vesicle associated protein required for fusion of synaptic vesicles with the plasma membrane. Proprioceptive munc18-1 conditional mutants are impaired in surface righting – a dynamic postural adjustment task – and display several specific deficits in pivoting, an early locomotor behavior. Before the emergence of forward locomotion during postnatal development, animals explore their surroundings through pivoting, or rotating the upper torso around the relatively immobile base of the hind limbs. 3-D kinematic analysis was used to quantitatively describe this pivoting behavior at postnatal days 5 and 8 in control and munc18-1 conditional mutants. Mutant animals also pivot, but demonstrate alterations in movement strategy and in postural placement of the forelimbs during pivoting when compared to controls. In addition, brief forelimb stepping movements associated with pivoting are altered in mutant animals. Step duration and step height are increased in mutant animals. These results underscore the importance of proprioceptive feedback even at early stages in postnatal development.
CT-based assessment of regional pulmonary blood flow parameters: an update

We have previously reported a deconvolution-based technique to recover regional microvascular transport characteristics from dynamic CT images. We have refined our deconvolution algorithm and used Monte Carlo simulations to estimate the error and confidence interval of the resulting regional microvascular mean transit time (MIT) measures. Random errors, assumed to be due to white noise in the imaging process, were superimposed upon known input (PA) and regional parenchymal time-intensity (blood flow) data. The resulting simulated data were then fit to gamma variate functions and processed via our deconvolution algorithm to provide microvascular MTT measures for the simulated curves. The magnitude of the noise used in the simulations was obtained by subtracting two consecutively acquired images (approximately 1.5 sec delay between the two images) from a dynamic imaging sequence of a supine dog imaged at FRC. A total of 35 simulations were performed for each of five sample locations spanning the dependent to nondependent extent of the lungs. Microvascular MTT ranged from 3.39 sec to 9.67 sec as sample locations were moved from dependent to nondependent areas of the lungs. The standard error associated with these measures ranged from plus or minus 0.03 sec in the dependent portion of the lungs to plus or minus 0.27 sec in the non-dependent area of the lungs.
Access to occupations through social ties

Abstract Previous studies which examine the theory linking social resources to instrumental action have focused on a particular activated set of social ties in order to assess the effects of social resources on a specific action (finding a job or finding a stranger). However, the theory also implies that an individual's access to such social resources is contingent upon his/her social position as well as the nature of the social ties used. Assuming positions in the occupational structure represent resources, this paper reports a study designed to examine access to occupations through social ties. Data tend to support two major propositions in the theory. The strength of positions (as indicated by father's occupation) as well as the strength of ties (as indicated by the nature of the tie being a relative, friend or acquaintance) affect one's access to high-prestige occupations and affect the range of occupations accessed. Higher original positions and weaker ties (friends and acquaintances rather than relatives) provide better access to white-collar or more prestigious occupations, and, as a consequence, provide access to a wider range of occupations. Weaker ties provide better access to social resources than stronger ties, especially for those whose original positions are relatively low. There is also some evidence that friends, as opposed to relatives and acquaintances, may provide the widest access to different positions in the occupational structure. However, this finding is tentative since access through acquaintances may have been underestimated due to the particular measure used and to the possibility of a recall problem.
RESOLUTION OF GRANULES FROM RABBIT HETEROPHIL LEUKOCYTES INTO DISTINCT POPULATIONS BY ZONAL SEDIMENTATION

Postnuclear supernates from homogenates of essentially pure rabbit heterophil leukocytes were fractionated by means of zonal differential centrifugation through a discontinuous sucrose gradient at various speeds. Three distinct groups of granules were characterized biochemically and morphologically. They were, in order of decreasing sedimentation coefficient: (a) Large, relatively dense granules, identified morphologically as the azurophil or primary granules, and containing essentially all of the myeloperoxidase activity of the preparations, about one-third of their lysozyme activity, and between 50 and 80% of their content in five acid hydrolases typically associated with lysosomes in other cells; (b) smaller, less dense granules, with the morphological appearance of the specific or secondary granules, and carrying most of the alkaline phosphatase and the remainder of the lysozyme activity of the preparations; (c) a second group of lysosome-like particles, associated with a morphologically heterogeneous fraction, and containing the remainder of the acid hydrolases, but little or no myeloperoxidase. When p-nitrophenyl phosphate was used instead of beta-glycerophosphate for the assay of acid phosphatase, only small proportions of the total activity accompanied the two main lysosomal bands, and considerable activity was found in a zone slightly retarded with respect to the slowly moving band of acid hydrolases.
Hydrodynamics of a ship/whale collision

article i nfo All endangered large whale species are vulnerable to collisions with large ships; and "ship strikes" are the greatest known threat to one of the world's rarest whales, the North Atlantic right whale (Eubalaena glacialis). The magnitude of this threat is likely to increase as maritime commerce expands. Factors influencing the incidence and severity of ship strikes are not well understood, although vessel speed appears to be a strong contributor. The purpose of this study was to characterize the hydrodynamic effects near a moving hull that may cause a whale to be drawn to or repelled from the hull, and to assess the accelerations exerted on a whale at the time of impact. Using scale models of a container ship and a right whale in experimental flow tanks, we assessed hydrodynamic effects and measured accelerations experienced by the whale model in the presence of a moving vessel. Accelerations at impact were measured while the whale was at the surface, for various vessel speeds, orientations of the whale relative to the vessel path, and distances off the direct path of the vessel. Accelerations experienced by the whale model in a collision: increased in magnitude with increasing ship speed; were not dependent on whale orientation to the vessel path; and decreased exponentially with increasing separation distances from the ship track. Subsequent experiments with the whale model submerged at one to two times the ship's draft indicated a pronounced propeller suction effect, a drawing of the whale toward the hull, and increased probability of propeller strikes resulting from this class of encounter. Measured accelerations are a proxy for impact severity, but do not constitute a detailed study of injury mechanism in a living animal, though they may help inform future work. We present a heuristic map of the hydrodynamic field around a transiting hull likely involved in close whale/ vessel encounters. These results may have bearing on policy decisions, particularly those involving vessel speed, aimed at protecting large whales from ship strikes worldwide. Published by Elsevier B.V.
Optimization of information storage systems

In this paper the writers have developed a model and an optimization technique for the design of hierarchical structures of memory so as to minimize the average access time to blocks of information stored in the hierarchy for a given cost constraint. The assumption is made that the “activity profile” giving the relative frequencies with which blocks are accessed (for a given set of problems) is available. The designs are tailored to fit the given activity profiles. The first part of the paper introduces the basic problem solved and some terminology used in the development of the theory. The second part consists of: (a) A method of evaluating memory types, i.e., a method of selecting an optimum subset of memory types which will compose the hierarchy from the set of all available memory types, and (b) The determination of the optimum sizes of each memory type in the subset so as to minimize the average access time to addresses in the hierarchy for a given cost constraint and a given activity profile. (c) The third part develops the optimization technique when the number of members in the memory hierarchy is limited. The last part is a discussion on the possible application of the technique to the evaluation of multi-precision arithmetic and to language translation. The second part also considers the problem of deriving the cost-average-access-time characteristic for a given profile. This characteristic will be useful in memory allocation problems as well as a valuable tool to computer designers for determination of memory sizes.
Spine X-ray image retrieval using partial vertebral boundaries

The anterior osteophyte (AO) is a bony spur on the vertebra and is symptomatic of osteo-arthritis of the spine. We present advances in our research into matching vertebral boundaries based on pathological (severity) and visual similarity. Proposed image retrieval methods are based on partial shape matching (PSM) that use landmarks along sagittal vertebral outlines that are consistent with those used by medical experts. Besides the two PSM methods that are improved algorithms of our previously developed methods, a new PSM method that is based on a simple but effective localized shape feature is proposed. The methods are evaluated and tested on a dataset of 856 segmented vertebrae and their performance is compared using precision-recall and average precision graphs. The best approaches are combined and integrated into our Web-based Spine Pathology & Image Retrieval System (SPIRS).
The Study on Vibration of Marine Riser under Deep Water

With the development of deep water drilling engineering, marine riser has become the important equipment. With the increase in water depth, the failure of marine riser is very serious, the vibration is the main reason. According to the actual situation, the model of marine is set up, the rule of lateral vibration is obtained. The result is helpful to avoid the phenomena of resonance of marine riser under wave loads.
Effects of Progressive Muscle Relaxation Training on Anxiety and Depression in Patients Enrolled in an Outpatient Pulmonary Rehabilitation Program

Background: This prospective, randomized controlled trial examined the effect of progressive muscle relaxation (PMR) training on anxiety and depression in patients with chronic brea
Anxiety disorders in women

Women have higher overall prevalence rates for anxiety disorders than men. Women are also much more likely than men to meet lifetime criteria for each of the specific anxiety disorders: generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), simple phobia, panic disorder, and agoraphobia. Considerable evidence suggests that anxiety disorders remain underrecognized and undertreated despite their association with increased morbidity and severe functional impairment. Increasing evidence suggests that the onset, presentation, clinical course, and treatment response of anxiety disorders in women are often distinct from that associated with men. In addition, female reproductive hormone cycle events appear to have a significant influence on anxiety disorder onset, course, and risk of comorbid conditions throughout a woman's life. Further investigations concerning the unique features present in women with anxiety disorders are needed and may represent the best strategy to increase identification and optimize treatment interventions for women afflicted with these long-neglected psychiatric disorders.
Comment on “Further evidence for lightning at Venus”

In contradiction to the findings of Singh and Russell (1986), the Pioneer Venus Orbiter (PVO) electric-field data are not found to provide evidence for either lightning or volcanism at Venus. It is suggested that the noise considered by Singh and Russell to be clustered at low altitudes actually appears frequently at high altitudes. The frequent appearance of the broadband noise in the upper ionosphere indicates that this noise, like that attributed to lightning by Scarf et al. (1980), is actually generated within the ionosphere near the PVO by the solar wind interaction with the ionosphere.
Into the Wild: Low-Cost Ubicomp Prototype Testing

We have developed ActivityStudio (http:// activitystudio.sourceforge.net), an open source suite of tools for prototyping and in situ testing of low-cost ubicomp application prototypes. The tool suite's design environment, ActivityDesigner, lets designers create rich ubicomp prototypes in a few hours, using high-level abstractions and techniques such as activity models, storyboards, and programming by demonstration.
The Debate on the Trial of the Templars (1307–1314)

Jochen Burgtorf, Paul F. Crawford, and Helen J. Nicholson (eds) The Debate on the Trial of the Templars (1307–1314). Farnham, UK, and Burlington, VT: Ashgate, 2010. Pp. xxvi. 399. The trial of the ...
The site of the aldosterone induced stimulation of sodium transport.

Abstract The content and concentration of major ions within the scraped mucosal epithelial cells of the urinary bladder of the toad Bufo marinus were determined using [ 14 C]- and [ 3 H]-inulin to correct for adherent extracellular fluid. In aldosterone treated hemi-bladders the radioactive sodium content and concentration increased significantly as compared with paired control hemi-bladders when both tissues were exposed to [ 24 Na] in the mucosal bathing medium. Changes in total non-inulin space sodium were not detected but the stimulation of transepithelial sodium transport by aldosterone in this set of observations was small, averaging only some 30% above control. The results are compatible with our hypothesis that the major action of aldosterone is to facilitate the entry of sodium from the mucosal medium across the apical permeability barrier of the transporting mucosal cells.
Convergence of Trust Region Augmented Lagrangian Methods Using Variable Fidelity Approximation Data

To date the primary focus of most constrained approximate optimization strategies is that application of the method should lead to improved designs. Few researchers have focused on the development of constrained approximate optimization strategies that are assured of converging to a Karush-Kuhn-Tucker (KKT) point for the problem. Recent work by the authors based on a trust region model management strategy has shown promise in managing the convergence of constrained approximate optimization in application to a suite of single level optimization test problems. Using a trust-region model management strategy, coupled with an augmented Lagrangian approach for constrained approximate optimization, the authors have shown in application studies that the approximate optimization process converges to a KKT point for the problem. The approximate optimization strategy sequentially builds a cumulative response surface approximation of the augmented Lagrangian which is then optimized subject to a trust region constraint. In this research the authors develop a formal proof of convergence for the response surface approximation based optimization algorithm. Previous application studies were conducted on single level optimization problems for which response surface approximations were developed using conventional statistical response sampling techniques such as central composite design to query a high fidelity model over the design space. In this research the authors extend the scope of application studies to include the class of multidisciplinary design optimization (MDO) test problems. More importantly the authors show that response surface approximations constructed from variable fidelity data generated during concurrent subspace optimizations (CSSOs) can be effectively managed by the trust region model management strategy. Results for two multidisciplinary test problems are presented in which convergence to a KKT point is observed. The formal proof of convergence and the successfull MDO application of the algorithm using variable fidelity data generated by CSSO are original contributions to the growing body of research in MDO.