cssi/SciSciGPT-SciSciNet huggingface dataset:
CD40 Ligand Levels in Pediatric Cohorts Correlate with Baseline Platelet Count and Transplant-Associated Mortality but Not with Endothelial Injury

Introduction CD40 ligand (CD40L), primarily expressed on activated CD4+ T lymphocytes, is also secreted in soluble form by T cells and platelets. CD40L modulates the immune response, largely via binding to CD40 on B lymphocytes. CD40L is also expressed on endothelial cells and with CD40 regulates endothelial cell integrity and vascular inflammation. Recently, it has been reported that single nucleotide polymorphisms (SNPs) in the CD40LG gene are associated with increased risk of endothelial complications following allogeneic stem cell transplantation (Rachakonda et al JCO 36(8)789-800). We hypothesized that incidence of thrombotic microangiopathy (TMA), a severe endothelial complication, would be associated with protein levels of CD40L early after transplant. Methods We analyzed serum collected prospectively from two cohorts of pediatric HSCT patients at their pre-transplant baseline. Serum was analyzed at day + 14 after transplant for cohort 1. CD40L levels were measured via R&D Quantikine ELISA. Genotyping of the previously reported SNPs (rs3092920 rs3092952 and rs3092936) was performed for cohort 1 using Applied Biosystems TaqMan technology. Results Initial analysis of cohort 1 revealed that patients with bone marrow failure syndromes had dramatically decreased CD40L levels as compared to other diagnoses, likely due to underlying cytopenias (Figure 1). These patients were excluded from further analysis due and a total of 125 patients were then analyzed across two cohorts. Associations between baseline CD40L levels and outcome are shown in Table 1. There is no significant correlation between CD40 level and TMA or GVHD. Cohort 1 also showed no correlation between CD40L level and GVHD or TMA at day +14. Interestingly, in both cohorts there is a significant association between post-transplant mortality and low baseline CD40L levels. This finding is independent of the indication for transplantation. CD40L is produced by platelets and platelet counts correlated with CD40L level at baseline. Mortality was increased in those with lower pre-transplant platelet counts. There was no association between genotype at the assessed SNPs and baseline CD40L levels or mortality (Table 2). No association was seen with genotype and day +14 CD40L levels. Conclusion CD40L levels prior to HSCT and at day +14 (when endothelial injury occurs) do not correlate with the risk of developing TMA. Levels of CD40L do not correlate with genotype at three SNPs either, including rs3092936 where the CC/CT genotype has been reported to increase risk of TMA and death. However, lower baseline levels of CD40L are associated with risk for post-transplant mortality, independent of diagnosis. Additionally, they correlate with baseline platelet count. We hypothesize that CD40L levels serve as a surrogate for platelet count and that baseline platelet count itself may predict risk for transplant related mortality.
Informed Consent for Bedside Procedures in Pediatric and Neonatal ICUs: A Nationwide Survey.

Objectives Primary objectives were to discover current practices of informed consent for bedside procedures in the PICU and neonatal ICU and how trainees learn to obtain consent. We also attempted to gauge if program directors felt that one method of consent was subjectively superior to another in the way it fulfilled established ethical criteria for informed consent. Design An online anonymous survey. Participants were asked about how and by whom informed consent is currently obtained, training practices for fellows, and attitudes about how different consent methods fulfill ethical criteria. Setting All U.S. fellowship programs for neonatology (n = 98) and pediatric critical care (n = 66) in the fall of 2017. Subjects Neonatal and pediatric critical care fellowship program directors. Interventions None. Measurements and main results The overall response rate was 50% (82 of 164). The most common method for obtaining consent in both ICU types was via a written, separate (procedure-specific) consent (63% neonatal ICUs, 83% PICUs); least common was verbal consent (8% neonatal ICUs and 6% PICUs). Fellows were reported as obtaining consent most often (91%), followed by mid-level practitioners (71%) and residents (66%). Residents were one-fifth as likely to obtain consent in the PICU as compared with the neonatal ICU. Sixty-three percent of fellowship directors rated their programs as "strong" or "very strong" in preparing trainees to obtain informed consent. Twenty-eight percent of fellowship directors reported no formal training on how to obtain informed consent. Conclusions Most respondents' ICUs use separate procedure-specific written consents for common bedside procedures, although considerable variability exists. Trainees reportedly most often obtain informed consent for procedures. Although most fellowship directors report their program as strong in preparing trainees to obtain consent, this study reveals areas warranting improvement.
Brief in-Home Assessments of Low-Income Mothers and Children using a New Affection Subscale of the HOME Inventory

Family services providers and researchers have a great need for efficient and valid assessment instruments. This secondary analysis explored whether the validity of a brief observational screener o...
Physical activity and sleep quality and duration among Hispanic postpartum women at risk for type 2 diabetes: Estudio PARTO.

Abstract Objectives Poor sleep among postpartum women is associated with adverse maternal outcomes. Physical activity (PA) is associated with better sleep. However, few studies have been conducted among postpartum Hispanic women. The objective of this study was to examine the association between PA and sleep quality and duration among postpartum Hispanic women. Design A cross-sectional analysis using baseline data from Estudio PARTO, an ongoing randomized controlled trial aimed at reducing type 2 diabetes risk among Hispanic women. Setting Baystate Medical Center, in Western Massachusetts, which serves an ethnically and socioeconomically diverse population. Participants Hispanic women, at elevated risk for type 2 diabetes, at a mean of 11 weeks (SD = 4.5) postpartum. Measurements PA was measured with the Pregnancy Physical Activity Questionnaire (PPAQ), and sleep was measured with the Pittsburgh Sleep Quality Index (PSQI). Results Mean sleep duration was 5.9 hour/night (SD = 1.7) and PSQI score was 6.5 (SD = 3.9). In multivariable logistic models, sports/exercise was associated with lower odds of very poor sleep quality (PSQI >10) (OR = 0.18, 95% CI = 0.05 to 0.69). Sports/exercise (OR = 0.05, 95% CI = 0.01 to 0.26) and vigorous intensity PA (OR = 0.13, 95% CI = 0.04 to 0.42) were associated with lower odds of short (vs normal) sleep duration. There were no statistically significant relationships between PA in any other domain or intensity and sleep quality or duration Conclusions Findings can inform interventions designed to improve postpartum sleep via increasing opportunities for exercise among postpartum women.
Help-seeking from indigenous healers among persons of African ancestry in the United States: Ethnic and racial disparities in mental and physical health

Abstract Objective Racial disparities in mental and physical health status are a persistent problem for people of African ancestry in the United States (U.S.). The current study seeks to determine whether indigenous help-seeking is related to ethnic and racial differences in health problems in persons of African ancestry. Methods/design Complex sampling produced a nationally representative sample of 3570 African Americans, 1623 Caribbean Blacks, and 1006 non-Hispanic Whites. All 3750 African Americans, 1438 (88.6%) African Caribbeans, and 891(88.6%) European Americans had relevant data for the current study. Respondents to the National Survey of American Life (NSAL) were studied with structural equation modeling (SEM) to evaluate a model of help seeking from “faith healers,” “herbalists or rootworkers,” or “astrologists or psychics.” Mental and physical health were predicted by this indigenous help-seeking. Results Consistent with the hypothesis, SEM analyses indicated better model fit for African Americans with greater similarly to African Caribbean respondents (r = .901, p = .001) than European Americans counterparts (r = -.332, p = .382) in measurement models. These analyses also showed African Americans’ indigenous help-seeking was negatively correlated with lifetime diagnoses of any DSM psychiatric disorders but positively correlated with burden of chronic diseases. The association between indigenous help-seeking and professional diagnoses of chronic diseases was negative for Caribbean Blacks. Conclusion Culturally competent psychological or medical services by Western practitioners to people in the U.S Black population require attention to indigenous healing systems.
Incidence of and Risk Factors for Hepatic Encephalopathy in a Population-Based Cohort of Americans With Cirrhosis.

Hepatic encephalopathy (HE) is a devastating complication of cirrhosis. Data are limited regarding the incidence of and risk factors for HE among contemporary patients in the context of the shifting epidemiology of cirrhosis. We examined a 20% random sample of U.S. Medicare enrollees with cirrhosis and Part D prescription coverage from 2008 to 2014. We modelled incident HE using demographic, clinical, and pharmacologic data. Risk factors for HE were evaluated, including demographics/socioeconomics, cirrhosis etiology, severity of liver disease, and pharmacotherapy, along with gastroenterology consultation, as time-varying covariates. Among 166,192 Medicare enrollees with cirrhosis followed for 5.25 (interquartile range [IQR], 2.00-7.00) years, the overall incidence of HE was 11.6 per 100 patient-years. The cohort's median age was 65 years (IQR, 57-72), 31% had alcohol-related cirrhosis, and 49% had likely nonalcoholic fatty liver disease cirrhosis. The two strongest associations with HE were alcohol-related cirrhosis (adjusted hazard ratio [AHR], 1.44; 95% confidence interval [CI], 1.40, 1.47, relative to nonalcoholic nonviral cirrhosis) and the presence of portal hypertension (AHR, 3.42; 95% CI, 3.34, 3.50). Adjusting for confounders, benzodiazepines (AHR, 1.24; 95% CI, 1.21, 1.27), gamma aminobutyric acid (GABA)ergics (AHR, 1.17; 95% CI, 1.14, 1.21), opioids (AHR, 1.24; 95% CI, 1.21, 1.27), and proton pump inhibitors (PPIs) (AHR, 1.41; 95% CI, 1.38, 1.45) were all associated with incident HE. Only benzodiazepines, however, were associated with the risk of hospitalization with HE (incidence-rate ratio, 1.23; 95% CI, 1.20, 1.26). Conclusion: Novel data regarding the risk of HE for contemporary patients with cirrhosis are provided. The incidence of HE in an older population of Americans with cirrhosis is high, particularly among those with alcohol-related cirrhosis and portal hypertension. Several medication classes, namely PPIs, opiates, GABAergics, and benzodiazepines, represent potentially modifiable risk factors for HE.
Characterization of stimulus response curves obtained with transcranial magnetic stimulation from bilateral tibialis anterior muscles post stroke.

Abstract Background Stimulus response curves (SR curves), measured using transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEP), yield important information regarding corticomotor connectivity. Limited understanding of SR curve analyses techniques for leg muscles after stroke may limit the utility of TMS data for walking recovery. Objective To compare linear and non-linear curve fitting for MEP responses from the non-paretic and paretic tibialis anterior (TA) muscles. Methods Accuracy of fit was measured using coefficient of determination (R2). Similarities of the fit were compared using slopes and area under the curve (AUC). Results The non-linear function demonstrated higher R2 and slopes. The AUC was not significantly different between the two analyses approaches. The non-linear non-paretic SR slopes and paretic AUC had significant associations with walking speed. Conclusion Our results highlight the differences between non-linear and linear approaches to best fit the SR curves from bilateral TA muscles in stroke survivors. Although the linear function can appropriately fit the SR curve of the paretic and non-paretic TA, the non-linear function estimated a higher slope. We found the AUC to be a more robust measure that was not affected by the type of curve-fitting approach and only the AUC of the paretic TA showed significant association with walking speeds. A better understanding of SR curve fitting approaches for the TA muscles in individuals with chronic stroke allows for their optimal use in interpretation of TMS data and literature.
The impact of COVID-19 on neurosurgeons and the strategy for triaging non-emergent operations: a global neurosurgery study.

The COVID-19 pandemic has disrupted all aspects of society globally. As healthcare resources had to be preserved for infected patients, and the risk of in-hospital procedures escalated for uninfected patients and staff, neurosurgeons around the world have had to postpone non-emergent procedures. Under these unprecedented conditions, the decision to defer cases became increasingly difficult as COVID-19 cases skyrocketed. Data was collected by self-reporting surveys during two discrete periods: the principal survey accrued responses during 2 weeks at the peak of the global pandemic, and the supplemental survey accrued responses after that to detect changes in opinions and circumstances. Nine hypothetical surgical scenarios were used to query neurosurgeons’ opinion on the risk of postponement and the urgency to re-schedule the procedures. An acuity index was generated for each scenario, and this was used to rank the nine cases. There were 494 respondents to the principal survey from 60 countries. 258 (52.5%) reported that all elective cases and clinics have been shut down by their main hospital. A total of 226 respondents (46.1%) reported that their operative volume had dropped more than 50%. For the countries most affected by COVID-19, this proportion was 54.7%. There was a high degree of agreement among our respondents that fast-evolving neuro-oncological cases are non-emergent cases that nonetheless have the highest risk in postponement, and selected vascular cases may have high acuity as well. We report on the impact of COVID-19 on neurosurgeons around the world. From their ranking of the nine case scenarios, we deduced a strategic scheme that can serve as a guideline to triage non-emergent neurosurgical procedures during the pandemic. With it, hopefully, neurosurgeons can continue to serve their patients without endangering them either neurologically or risking their exposure to the deadly virus.
Investigation of the performance of Machine Learning Classifiers for Pneumonia Detection in Chest X-ray Images

Pneumonia is one of the serious and life-threatening diseases that is caused by a bacterial or viral infection of the lungs and have the potential to result in severe consequences within a short period. Therefore, early diagnosis is a significant factor in terms of the successful treatment process. Thus, there is a need for an intelligent and automatic system that has the capability of diagnosing chest X-rays, and to simplify the Pneumonia detection process for experts and novices. This study aims to develop a model that will help with the classification of chest X-ray medical images into normal(healthy) vs. abnormal(sick). To achieve this, seven existing state-of-the-art Machine Learning techniques and well-known Convolutional Neural Network models have been used to increase efficiency and accuracy. In this study, we propose our Deep Learning for the classification task, which is trained with changed images, through multiple steps of pre-processing. Experimentally, it showed that the Deep Learning technique for the classification task performs the best, compared to the other seven Machine Learning techniques. In this study, we successfully classified chest infection in Chest X-ray Images using Deep Learning based on CNN with an overall accuracy of 98.46%. It achieved a more successful result in detecting Pneumonia cases.
Energy-Efficient Deep Neural Networks with Mixed-Signal Neurons and Dense-Local and Sparse-Global Connectivity : (Invited Paper)

Neuromorphic Computing has become tremendously popular due to its ability to solve certain classes of learning tasks better than traditional von-Neumann computers. Data-intensive classification and pattern recognition problems have been of special interest to Neuromorphic Engineers, as these problems present complex use-cases for Deep Neural Networks (DNNs) which are motivated from the architecture of the human brain, and employ densely connected neurons and synapses organized in a hierarchical manner. However, as these systems become larger in order to handle an increasing amount of data and higher dimensionality of features, the designs often become connectivity constrained. To solve this, the computation is divided into multiple cores/islands, called processing engines (PEs). Today, the communication among these PEs are carried out through a power-hungry network-on-chip (NoC), and hence the optimal distribution of these islands along with energy-efficient compute and communication strategies become extremely important in reducing the overall energy of the neuromorphic computer, which is currently orders of magnitude higher than the biological human brain. In this paper, we extensively analyze the choice of the size of the islands based on mixed-signal neurons/synapses for 3-8 bit-resolution within allowable ranges for system-level classification error, determined by the analog non-idealities (noise and mismatch) in the neurons, and propose strategies involving local and global communication for reduction of the system-level energy consumption. AC-coupled mixed-signal neurons are shown to have 10X lower non-idealities than DC-coupled ones, while the choice of number of islands are shown to be a function of the network, constrained by the analog to digital conversion (or vice-versa) power at the interface of the islands. The maximum number of layers in an island is analyzed and a global bus-based sparse connectivity is proposed, which consumes orders of magnitude lower power than the competing powerline communication techniques.
A Duplex Fluorescent Microsphere Immunoassay for Detection of Bluetongue and Epizootic Hemorrhagic Disease Virus Antibodies in Cattle Sera

Bluetongue virus (BTV) causes internationally reportable hemorrhagic disease in cattle, sheep, and white-tailed deer. The closely related, and often co-circulating, epizootic hemorrhagic disease virus causes a clinically similar devastating disease in white-tailed deer, with increasing levels of disease in cattle in the past 10 years. Transmitted by Culicoides biting midges, together, they constitute constant disease threats to the livelihood of livestock owners. In cattle, serious economic impacts result from decreased animal production, but most significantly from trade regulations. For effective disease surveillance and accurate trade regulation implementation, rapid, sensitive assays that can detect exposure of cattle to BTV and/or EHDV are needed. We describe the development and validation of a duplex fluorescent microsphere immunoassay (FMIA) to simultaneously detect and differentiate antibodies to BTV and EHDV in a single bovine serum sample. Performance of the duplex FMIA for detection and differentiation of BTV and EHDV serogroup antibodies was comparable, with higher sensitivity than commercially available single-plex competitive enzyme-linked immunosorbent assays (cELISA) for detection of each virus antibody separately. The FMIA adds to the currently available diagnostic tools for hemorrhagic orbiviral diseases in cattle as a sensitive, specific assay, with the benefits of serogroup differentiation in a single serum sample, and multiplexing flexibility in a high-throughput platform.
Weakly Supervised Deep Learning Approach to Breast MRI Assessment.

Rationale and Objectives To evaluate a weakly supervised deep learning approach to breast Magnetic Resonance Imaging (MRI) assessment without pixel level segmentation in order to improve the specificity of breast MRI lesion classification. Materials and Methods In this IRB approved study, the dataset consisted of 278,685 image slices from 438 patients. The weakly supervised network was based on the Resnet-101 architecture. Training was implemented using the Adam optimizer and a final SoftMax score threshold of 0.5 was used for two class classification (malignant or benign). 278,685 image slices were combined into 92,895 3-channel images. 79,871 (85%) images were used for training and validation while 13,024 (15%) images were separated for testing. Of the testing dataset, 11,498 (88%) were benign and 1531 (12%) were malignant. Model performance was assessed. Results The weakly supervised network achieved an AUC of 0.92 (SD ± 0.03) in distinguishing malignant from benign images. The model had an accuracy of 94.2% (SD ± 3.4) with a sensitivity and specificity of 74.4% (SD ± 8.5) and 95.3% (SD ± 3.3) respectively. Conclusion It is feasible to use a weakly supervised deep learning approach to assess breast MRI images without the need for pixel-by-pixel segmentation yielding a high degree of specificity in lesion classification.
Does it matter whether we or I talk about us? Distinguishing we-talk in couples’ conflict discussions and partners’ private thoughts before and after conflict:

According to extensive evidence, we-talk—couples’ use of first-person, plural pronouns—predicts better relationship quality and well-being. However, prior work has not distinguished we-talk by its ...
Relaxed Substrate Requirements of Sterol 14α-Demethylase from Naegleria fowleri Are Accompanied by Resistance to Inhibition.

Naegleria fowleri is the protozoan pathogen that causes primary amoebic meningoencephalitis (PAM), with the death rate exceeding 97%. The amoeba makes sterols and can be targeted by sterol biosynthesis inhibitors. Here, we characterized N. fowleri sterol 14-demethylase, including catalytic properties and inhibition by clinical antifungal drugs and experimental substituted azoles with favorable pharmacokinetics and low toxicity. None of them inhibited the enzyme stoichiometrically. The highest potencies were displayed by posaconazole (IC50 = 0.69 μM) and two of our compounds (IC50 = 1.3 and 0.35 μM). Because both these compounds penetrate the brain with concentrations reaching minimal inhibitory concentration (MIC) values in an N. fowleri cellular assay, we report them as potential drug candidates for PAM. The 2.1 A crystal structure, in complex with the strongest inhibitor, provides an explanation connecting the enzyme weaker substrate specificity with lower sensitivity to inhibition. It also provides insight into the enzyme/ligand molecular recognition process and suggests directions for the design of more potent inhibitors.
Three dimensional modeling of the lower extremity for the study of static standing postures in Functional Electrical Stimulation (FES)

A highly desirable enhancement to Functional Electrical Stimulation (FES) aided standing would be the ability to stand without using the upper extremities for support or balance (hands free standing). To achieve this, a deeper insight into the stability of the system is required to design robust but simple controllers for maintaining the posture. We are examining this problem using simulations with a full three-dimensional modeling of the lower extremities and pelvis. This paper describes a major step in this effort: solving the inverse dynamics for the closed chain model of a typical stance. We have critically examined the main reasons why the closed chain model is problematic and have developed an equivalent approach that avoids using a closed chain model by accurately estimating the ground reaction forces. This approach has been applied to the inverse dynamics problem related to human static standing.
Clonal analysis of vertebrate myogenesis: II. Environmental influences upon human muscle differentiation

Abstract In vitro procedures for obtaining the differentiation of human fetal muscle colonies were developed, and the sensitivity of clonal differentiation to environmental influences was examined. Human muscle colonies are capable of differentiating in the absence of an exogenous collagen substrate. The dependence of clonal diffeentiation upon the addition of chick embryo extract to the culture medium is determined by the serum type used in the medium and by the substrate upon which the colonies are grown. Clonal differentiation also depends upon conditioning of the medium by the colonies. The rate of medium conditioning is affected by clonal density and initial medium composition. The required medium modification is not species specific since medium conditioned by chick muscle cells also permits the early differentiation of human muscle clones. By manipulating the various environmental parameters described above it has been possible to define a number of in vitro conditions which permit a normal rate of cell proliferation but do not permit cell fusion. Results from these experiments are discussed in terms of their developmental implications.
Electronic Technology and Rehabilitation

Summary Advantages to the use of the personal computer for simulation gaming are presented in this article. One therapeutic simulation game in particular, BUSTED, is discussed in detail. BUSTED was designed to reduce antisocial behavior in youthful offenders. Making choices and receiving the consequences of these decisions form the primary educational method for achieving this goal. This article details how BUSTED is played. Conclusions about the impact of BUSTED have not been reached. However, an extensive evaluation program has been planned to provide information regarding its effectiveness. A preliminary evaluation done in two high school classrooms yielded positive results.
Effect of acute nitrate supplementation on neurovascular coupling and cognitive performance in hypoxia

The matching of oxygen supply to neural demand (i.e., neurovascular coupling (NVC)) is an important determinant of cognitive performance. The impact of hypoxia on NVC remains poorly characterized. NVC is partially modulated by nitric oxide (NO), which may initially decrease in hypoxia. This study investigated the effect of acute NO-donor (nitrate) supplementation on NVC and cognitive function in hypoxia. Twenty healthy men participated in this randomized, double-blind, crossover design study. Following normoxic cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 min of hypoxia (11.6% ± 0.1% O2) and all cognitive/NVC testing was repeated. NVC was assessed as change in middle cerebral artery (MCA) blood flow during a cognitive task (incongruent Stroop) using transcranial Doppler. Additional computerized cognitive testing was conducted separately to assess memory, executive function, attention, sensorimotor, and social cognition d...
Critical Factors Governing the Residual Response of Reinforced Concrete Beams Exposed to Fire

This paper presents results from a set of numerical studies on critical factors influencing residual response of fire exposed reinforced concrete (RC) beams. The numerical model, developed using finite element computer program ABAQUS, accounts for distinct material properties of reinforcing steel and concrete during fire exposure (both heating and cooling phases) and residual (after cool down) phase. In addition, residual plastic deformations that develop in the beam during fire exposure are also taken into consideration in evaluating post-fire response of RC beams. The validity of the model is established by comparing predictions from the numerical analysis with response parameters measured during fire and residual capacity tests. The validated model is employed to conduct a parametric study for varying fire intensity, level of loading (load ratio), restraint conditions, and cross-sectional sizes of the beam. Results from the parametric study indicate that load level has significant influence on both post-fire residual capacity, as well as residual deformations in the beam. The cross-sectional size of the beam also influences residual capacity and increasing the depth of section leads to improved residual capacity in the RC beam. Presence of axial restraint however, has only moderate influence on the residual response of RC beams exposed to fire. Moreover, under most parametric fire scenarios, RC beams can retain up to 70% of their room temperature capacity provided tensile rebar temperature does not exceed 450°C.
Enhanced work zone safety through cooperative autonomous vehicle systems

Despite improvements in work zone safety, injuries and fatalities remain a significant problem for work zone personnel. Crew and vehicles are often protected with the use of a vehicle located at the rear of the work zone, which is fitted with a mechanism to attenuate the impact energy of a vehicle. This vehicle, called an impact attenuation, or crash cushion, vehicle, is designed and placed to be struck by any errant vehicles; however, this vehicle is an active part of the work crew and is often manned by a member of the work crew, and this person can still be injured or killed when the vehicle is struck. This paper will present recent work by SwRI in conjunction with the Texas Department of Transportation (TxDOT) to replace this manned vehicle with a fully-autonomous vehicle, capable of communicating with other vehicles in the work crew, traffic management systems, and, using visual recognition techniques, follow other vehicles in the crew or even respond to arm gestures by a member of the work crew.
New techniques in antibiotic discovery and resistance: Raman spectroscopy

Raman spectroscopy can play a role in both antibiotic discovery and understanding the molecular basis of resistance. A major challenge in drug development is to measure the population of the drug molecules inside a cell line and to follow the chemistry of their reactions with intracellular targets. Recently, a protocol based on Raman microscopy has been developed that achieves these goals. Drug candidates are soaked into live bacterial cells and subsequently the cells are frozen and freeze-dried. The samples yield exemplary (nonresonance) Raman data that provide a measure of the number of drug molecules within each cell, as well as details of drug-target interactions. Results are discussed for two classes of compounds inhibiting either β-lactamase or dihydrofolate reductase enzymes in a number of Gram-positive or Gram-negative cell lines. The advantages of the present protocol are that it does not use labels and it can measure the kinetics of cell-compound uptake on the time scale of minutes. Spectroscopic interpretation is supported by in vitro Raman experiments. Studying drug-target interactions in aqueous solution and in single crystals can provide molecular level insights into drug-target interactions, which, in turn, provide the underpinnings of our understanding of data from bacterial cells. Thus, the applicability of X-ray crystallographic-derived data to in-cell chemistry can be tested.
Strategy for yield improvement with sub-10 nm photochemical filtration

Process and equipment engineers are always seeking ways to improve yield quickly and efficiently, especially on newly developing processes. These engineers have many tools at their disposal – equipment enhancements, software upgrades, and materials improvements. Many of these tools come from OEMs (other equipment suppliers) and materials suppliers who all benefit from close collaboration with IDMs to improve yield. This paper will discuss the strategies utilized to improve yield on 32 nm BEOL (back end of line) lithography processes with sub-10 nm photochemical filtration. This collaboration generated electrical yield data that validated the performance of several sub-10 nm photochemical filters on various resist and ancillary chemicals used in a tri-layer stack. Examples of yield enhancement include the use of 5 nm UPE (ultra high molecular weight polyethylene) in OPL (optical planarizing layers) which showed a 69% improvement in overall median yield for an OPL material used in the first metallization layer, and a 26% improvement for a second OPL material used in subsequent metallization processes . In addition, this paper will present data studying pre-wetting of a 5 nm point-of-use filter before track installation. Building on the success of this collaboration, an example filtration roadmap is also explored to show the benefits of using advanced filtration in 32 nm technologies and beyond.
Organische Phosphorverbindungen XIII. Über einige Reaktionen des Methylthiophosphonsäure‐dibromids CH3P(S)Br2 und verwandter Verbindungen [1]

Several insecticides containing a P-C bond have been prepared. The physical properties and the insecticidal activity of these compounds are reported. The structure of phosphinothionic anhydrides has been elucidated.
Using benthic indicators to assess status at HUC levels: A robust hierarchical modeling approach

Abstract Decisions often need to be made about the ecological status of regions based on limited or variable quantities of data. The United States Forest Service, for example, has developed a subwatershed condition classification approach to classify status of National Forest subwatersheds (level 6 hydrological units) based on a variety of indicators including biological indicators. For forests in Western Virginia, benthic macroinvertebrate data are commonly collected and used to estimate biological status. Available data varies in sample size from 1 to 20 samples per HUC. One approach to improve estimation of the biological status of a region using the biological indicator is to use a model based estimate. A hierarchical model is proposed to aid in estimating the status of regions based on a HUC level 6 classification. The hierarchical model involves components associated with regressors at both the subwatershed and sampling level, a model for the error that allows for extreme values and for a spatial component. The model based estimates have lower mean square error than the estimates using the mean and the model may be used to estimate the status as well as the associated uncertainty or variability. The distribution of the multimetric is used to predict the risk category associated with each subwatershed.
Truncation of Human Squalene Synthase Yields Active, Crystallizable Protein☆

Abstract Squalene synthase catalyzes the first committed step in cholesterol biosynthesis and thus is important as a potential target for therapeutic intervention. In order to determine the important functional domains of the protein, the amino and carboxyl terminal regions thought to be involved in membrane association of the enzyme were removed genetically. The 30 N-terminal amino acids were deleted with no apparent effect on activity. Additional deletion of 81 or 97 amino acids from the C-terminus completely ablated activity. However, a protein with a C-terminal deletion of 47 amino acids retained full activity. The latter enzyme was readily overexpressed inEscherichia coliand purified to homogeneity. The pure, doubly truncated enzyme exhibited a specific activity similar to that reported for the protease-solubilized rat liver enzyme, had aKMfor farnesyl diphosphate similar to that observed for native enzyme, and was inhibited by anionic compounds to the same degree as native enzyme. Using the vapor diffusion method, the protein was crystallized as an enzyme–inhibitor complex, yielding orthorhombic crystals which diffracted to 2.2 A.
Dissolution of alkaline earth sulfates in the presence of montmorillonite

In a study of the effect of montmorillonite on the dissolution of BaSO4 (barite), SrSO4 (celestite), and226Ra from U mill tailings, it was found that: (1) More of these substances dissolve in an aqueous system that contains montmorillonite than dissolve in a similar system without clay, due to the ion exchange properties of the clay; (2) Na-montmorillonite is more effective in aiding dissolution than is Ca-montmorillonite; (3) the amount of Ra that moves from mill tailings to an exchanger increases as solution sulfate activity decreases. Leaching experiments suggest that226Ra from H2SO4-Circuit U mill tailings from Edgemont, South Dakota, is not present as pure Ra sulfate or as an impurity in anhydrite or gypsum; it is less soluble, and probably occurs as a trace constituent in barite.
Thermal-Hydro-Mechanical Analysis of Frost Heave and Thaw Settlement

AbstractFrost heave and thaw settlement are the cause of substantial damage to infrastructure in regions of seasonal freezing as well as seasonal thawing (permafrost). While frost heaving of soils has been researched for decades, less attention has been paid to quantitative estimates of settlement and loss of strength of soils due to thawing. A constitutive model is developed, capable of simulating freezing and thawing of soils, and associated changes in the soil strength. While the porosity growth parameters describing frost heaving have been calibrated and validated for a specific soil, the description of the thawing phase has not been validated due to a lack of experimental data. The yielding of the frozen soil is described using the critical state concept, with the pore ice content being an important parameter affecting the yield function. The model was calibrated using available laboratory test data and used in the simulation of a freezing–thawing cycle in the soil with embedded footing.
Implementing Language Support in High-Level Languages

One of the requirements for building an operating system in a high-level operating system language, such as Ada, Concurrent Pascal, or Modula, is the construction of a language support system, or kernel. This paper presents a model that generalizes the concept of a kernel, and defines a kernel and the processes it supports to be at different levels of abstraction. A high-level language mechanism, the Execute statement, is then proposed as the basis of the interface between a kernel and the processes it supports. Software capabilities control access between levels and the Execute statement controls processor context switching between levels. The mechanisms rely on data typing for reliability and protection. They encourage systems that are well protected and exhibit an explicit hierarchical structure. Software capabilities and the Execute statement are illustrated with a pilot implementation on the Prime 650. An experimental operating system that encompasses their use is discussed. Extensions are presented which manage interrupts, timeslicing and preemption, and hardware protection mechanisms.
PERCEPTUAL INTERPRETATION OF THE SOCIAL DIAD: I. JUDGMENTS OF ACCEPTANCE.

(1964). Perceptual Interpretation of the Social Diad: I. Judgments of Acceptance. The Journal of Social Psychology: Vol. 63, No. 1, pp. 169-177.
Developmental Exposure and Changing Vocational Preferences in the Out Island Bahamas

As economic development may be viewed as a type of environmental change, an ecological or systems approach was selected for analyzing certain data from two Out Island Bahamian communties that have been differentially exposed to economic changes. More specifically, it was asserted that differential exposure to economic development (an environmental variable) would lead the two populations to change their vocational preferences (a system variable) in predictable ways. It was further asserted that different locations in time (e.g., age) and space (i.e., place of residence) would lead individuals and groups to differing perceptions, evaluations, and behavioral decisions.
Surface-Enhanced Two-Photon Excitation Fluorescence of Various Fluorophores Evaluated Using a Multiphoton Microscope

We present a rapid, low-power testbed for the detection and imaging of fluorescent probes utilizing two-photon excitation fluorescence (2PEF). The 2PEF signal from fluorophores commonly used in biological imaging have been enhanced using plasmonic substrates that have been designed to have a high plasmonic resonance over a narrow band that matches the source. The samples were illuminated and imaged using a low-power, in-house multiphoton microscope. A green fluorescent protein (bfloGFPa1), chlorophyll, or rhodamine 6G were deposited onto the plasmonic substrates and their 2PEF signals were measured relative to planar samples. The fluorescence intensities from the green fluorescent protein, chlorophyll, and rhodamine were enhanced by factors of 50, 8, and 4, respectively, with the structured substrates (relative to the planar substrates).
Contributions of Starch‐Granule Bound α‐Amylase to Q‐Enzyme from Cotton Leaves

Starch granules with tightly bound α-amylase and a branching enzyme (Q-enzyme) were isolated from cotton leaves. The activity of α-amylase was regulated by various concentrations of EDTA and exogenous α-amylase. Starch granules were incubated for a simultaneous interaction between α-amylase with its products and a branching enzyme. The increase in bound α-amylase activity caused an increase in amounts of maltodextrin products, the molecular weights of which ranged from 1,500 to 20,000 daltons. The amounts of branched glucans synthesized by Q-enzyme also changed in direct proportion to the amounts of maltodextrins and the levels of bound endogenous α-amylase activity. The absorption spectrum of natural cotton leaf amylopectin was similar to those of the synthesized glucans. Their molecular weights, however, were smaller than those of the natural products in the absence of chain lengthening donor substrate.
On a property of the reducibility exponent of linear differential systems

We establish that the reducibility exponent (Differentsial’nye Uravneniya, 2007, vol. 43, no. 2, pp. 191–202) of each linear system $$ \dot x = A(t)x, x \in \mathbb{R}^n , t \geqslant 0 $$ , with piecewise continuous bounded coefficient matrix A does not belong to the set of values of σ for which the perturbed system (1A+Q) with an arbitrary piecewise continuous perturbation Q satisfying the condition \( \overline {\lim } _{t \to + \infty } t^{ - 1} \ln \left\| {Q(t)} \right\| \leqslant - \sigma \) is reducible to the original system (1A) by some Lyapunov transformation.
Minimal length uncertainty relation and the hydrogen spectrum

Modifications of Heisenberg's uncertainty relation have been proposed in the literature which imply a minimum position uncertainty. We study the low energy effects of the new physics responsible for this by examining the consequent change in the quantum mechanical commutation relations involving position and momenta. In particular, the modifications to the spectrum of the hydrogen atom can be naturally interpreted as a varying (with energy) fine structure constant. From the data on the energy levels we attempt to constrain the scale of the new physics and find that it must be close to or larger than the weak scale. Experiments in the near future are expected to change this bound by at least an additional order of magnitude.
An angioscopic method for intraluminal aortic evaluation and stent placement

Purpose: The purpose of this study was to develop an angioscopic technique to visualize the endoluminal surface of the aorta and to guide vascular stent placement. Methods: A fiberoptic angioscope, fitted with a balloon at its tip, was passed via a carotid arteriotomy into the abdominal aorta of seven anesthetized pigs. Saline solution inflation of the balloon allowed for blood displacement and clear visualization of the endoluminal anatomy. After the left renal artery orifice had been identified with angioscopy, a catheter was inserted via a left femoral sheath to cannulate the orifice under direct visualization. The position of the catheter was verified angiographically. A vascular stent was loaded onto an angioplasty balloon, inserted through a right femoral arteriotomy, positioned by use of angioscopic visualization, and deployed immediately below the left renal artery orifice. Results: The aortic trifurcation and the lumbar and renal artery orifices were clearly visualized in every animal. Vascular stents were placed in seven animals within an average of 3.14±1.14 mm (mean±SEM, range 0 to 8 mm) below the inferior rim of the left renal artery orifice. No stents were positioned above a renal artery orifice or obstructed blood flow. Conclusions: This angioscopic technique permitted detailed evaluation of aortic endoluminal anatomy and precise implantation of vascular stents. Direct endovascular visualization may facilitate other endovascular procedures, including endovascular grafting.
Yeast centromere binding protein CBF1, of the helix-loop-helix protein family, is required for chromosome stability and methionine prototrophy

The centromere and its binding proteins constitute the kinetochore structure of metaphase chromosomes, which is crucial for the high accuracy of the chromosome segregation process. Isolation and analysis of the gene encoding a centromere binding protein from the yeast S. cerevisiae, CBF1, are described in this paper. DNA sequence analysis of the CBF1 gene reveals homology with the transforming protein myc and a family of regulatory proteins known as the helix-loop-helix (HLH) proteins. Disruption of the CBF1 gene caused a decrease in the growth rate, an increase in the rate of chromosome loss/nondisjunction, and hypersensitivity to the antimitotic drug thiabendazole. Unexpectedly, the cbf1 null mutation concomitantly resulted in a methionine auxotrophic phenotype, which suggests that CBF1, like other HLH proteins in higher eukaryotic cells, participates in the regulation of gene expression.
Alarm Bells from the Past: The Troubling History of American Military Commissions

Among the most controversial of President George W. Bush's responses to the deadly September 11, 2001 al-Qaeda attacks on the World Trade Center and the Pentagon was his issuance two months later of an order authorizing the trial before military commissions of aliens suspected of membership in that murderous organization or of involvement in terrorist activities.1 Two years after Bush's promulgation of that November 13, 2001 military order, no terrorist has yet stood trial before such a tribunal. That is not a bad thing. The history of American military commissions suggests that this is a legal device vulnerable to abuse that should be used only with the utmost caution.
Stratal slicing, Part I: Realistic 3-D seismic model

Two-dimensional, fenced 2-D, and 3-D isosurface displays of some realistic 3-D seismic models built in the lower Miocene Powderhorn Field, Calhoun County, Texas, demonstrate that a seismic event does not necessarily follow an impedance boundary defined by a geological time surface. Instead, the position of a filtered impedance boundary relative to the geological time surface may vary with seismic frequency because of inadequate resolution of seismic data and to the en echelon or ramp arrangement of impedance anomalies of sandstone. Except for some relatively time-parallel seismic events, the correlation error of event picking is large enough to distort or even miss the majority of the target zone on stratal slices. In some cases, reflections from sandstone bodies in different depositional units interfere to form a single event and, in one instance, an event tying as many as six depositional units (interbedded sandy and shaly layers) over 50 m was observed. Frequency independence is a necessary condition for selecting time-parallel reference events. Instead of event picking, phantom mapping between such reference events is a better technique for picking stratal slices, making it possible to map detailed depositional facies within reservoir sequences routinely and reliably from 3-D seismic data.