cssi/SciSciGPT-SciSciNet huggingface dataset:
Determinants of Maximal Oxygen Transport and Utilization

Maximal V& (V-ax) has mostly been the province of exercise physiologists wishing to provide a measure of athletic potential or to characterize subjects in exercise-related research. It is also used clinically to determine a patient's exercise capacity. More recently, it has been recognized that the study of V&max can provide fundamental insight into 02 transport at all points between inspired air and muscle mitochondria. This review focuses on understandqg how Vamax is set and concludes that the more athletic one is, the more V&max is sensitive to 02 transport conductances in the lungs, circulation, and skeletal muscle. These transpofl conductances form an integrated system, all components interacting to define Vamax. A particularly important component is diffusive conductance in muscle. This appears to be abnormal in chronic conditions such as obstructive pulmonary disease and heart and renal failure and may well explain why comction of central cardiovascular defects in 02 transport in such patients fails to restore exercise capacity.
Runtime prevention of concurrency related type-state violations in multithreaded applications

We propose a new method for runtime prevention of type state violations in multithreaded applications due to erroneous thread interleavings. The new method employs a combination of static and dynamic program analysis techniques to control the execution order of the method calls to suppress illegal call sequences. The legal behavior of a shared object is specified by a type-state automaton, which serves as the guidance for our method to delay certain method calls at run time. Our main contribution is a new theoretical framework for ensuring that the runtime prevention strategy is always safe, i.e., they do not introduce new erroneous interleavings. Furthermore, whenever the static program analysis is precise enough, our method guarantees to steer the program to a failurefree interleaving as long as such interleaving exists. We have implemented the new method in a tool based on the LLVM compiler framework. Our experiments on a set of multithreaded C/C++ applications show that the method is both efficient and effective in suppressing concurrency related type-state violations.
Symptomatic paroxysmal pacemaker-induced ventricular tachycardia.

Abstract A case is presented documenting the clinical picture and the electrocardiographic changes in a patient with symptomatic pacemaker-induced ventricular tachycardia resulting from malfunction of a self-contained, long term, implantable, electronic pacemaker after 16 months of uneventful performance. The steps in management and the associated clinical and electrocardiographic phenomena are also described.
Thyrocervical to vertebral artery transposition and ipsilateral carotid endarterectomy.

BACKGROUND We report a new method for treating patients with symptomatic high-grade stenosis of the proximal vertebral artery associated with high-grade stenosis of the ipsilateral carotid artery. METHODS Our patient had high-grade stenosis of the proximal right vertebral artery as well as high-grade stenosis of the ipsilateral carotid artery and suffered continued posterior circulation ischemic neurological deficits despite anticoagulation. RESULTS The patient was successfully treated with a carotid endarterectomy and thyrocervical-to-vertebral artery transposition in a single operation. CONCLUSION This procedure has the advantage in this setting of avoiding additional cross clamping on the diseased carotid artery that would normally be required for the vertebral-to-carotid artery transposition with carotid endarterectomy. Also, thrombosis at one anastamosis site would not endanger the other site as well.
Strategic planning: determining the impact of environmental characteristics and uncertainty.

This paper continues a line of research into the effect of environmental characteristics and uncertainty on strategic planning. Results suggest that measures of uncertainty and the environment need...
Maintenance of gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone release despite desensitization of GnRH-stimulated cytosolic calcium responses.

Involvement of ionized cytosolic calcium ([Ca2+]i) and protein kinase-C (PKC) in GnRH-stimulated LH release was assessed by correlating measurable changes in [Ca2+]i and LH release in PKC-depleted and nondepleted gonadotropes. Primary cultures of anterior pituitary cells were loaded with the calcium-sensitive fluorescent dye fura-2 and placed in a perifusion chamber. GnRH pulses were delivered to the cells, and changes in fura-2 fluorescence and LH release were determined. The level of [Ca2+]i (assessed by fura-2) increased rapidly to a maximum within 20-40 sec, followed by a slower decline over the next minute (spike phase) to a sustained intermediate value (plateau phase). GnRH-stimulated LH release was unaffected by loading cells with fura-2. Both LH release and changes in [Ca2+]i were directly dependent on GnRH concentration. Pretreatment with the GnRH antagonist Antide (50 nM; [NAcD2Nal1-DpClPhe2-D3Pal3-Ser4-NicLys5-++ +DNicLys6-Leu7-ILys8-Pro9-DAla10]NH2 ) had no effect on basal [Ca2+]i or basal LH ...
Transforming growth factor‐β1 accelerates bone bonding to a blended calcium phosphate ceramic coating: A dose‐response study

In vivo strain measurements can facilitate the study of the bone remodeling response to loading and load changes. Calcium phosphate ceramic (CPC) coatings have been used to attach strain gauges to bone for extended periods of time, but require up to 12 weeks for adequate CPC-to-bone bonding. Transforming growth factor beta 1 (TGF-β1), an osteoinductive growth factor, was used as a surface enhancement to accelerate bone growth and bonding to CPC particles. The aim of this study was to find an optimal dosage of TGF-β1 to accelerate the attachment process. CPC-coated strain gauges were enhanced with doses of 0.5, 1.0, or 2.0 μg of TGF-β1 per gauge. Gauges were placed on the femora of dogs, which were exercised daily and fed ad libitum. After 3, 6, and 12 weeks, gauge attachment was quantitatively assessed using mechanical testing and histomorphometry. Gauge attachment was also qualitatively assessed using back scatter electron microscopy. Agreement of the mechanical test results with both the back scatter electron microscopy images and histomorphometry results showed that the 1.0 μg per gauge dose of TGF-β1 is an optimal dose to accelerate bone formation and attachment to CPC-coated strain gauges. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 537–543, 2004
Modelling Principal Components with Structure

Applications of principal component analysis often involve data with some predetermine structure. For instal1ce, Jackson (1991, chapter 5) gives an example with eight variables, four being the hearing loss at four different frequencies in the left ear, and the other four the corresponding measurements on the right ear. Another example is the Frets (1921) anthropometric data on head length and breadth of the first and second adult sons of 25 families; see, e.g., Anderson (1984), Izenman (1980). Modelling covariances with constraints imposed according to the structure in the variables has been treated by Szatrowski (1985), Andersson (1975), and others, but the connection to principal component analysis is usually not made.
Optical Characterization of Quantum Well Structures

A survey of the most common and useful interband optical techniques for characterizing semiconductor quantum well structures is presented. These are divided into three sections; ground state spectroscopy which deals with the transition between the lowest energy state of the conduction band well and the highest energy state of the valence band well; density-of-states spectroscopy which probes higher energy transitions between excited states in the conduction and valence band wells; and other spectroscopies which entails more sophisticated experiments which don’t fit conveniently into the first two categories. Examples are given of each in order to demonstrate the power of optical spectroscopy to elucidate the properties of semiconductor quantum wells.
Processing of Transcranial Doppler for assessment of blood volume loss

Among all fields of critical patient care, hemorrhagic shock, which is encountered in most traumatic injuries, is a significant factor associated with the chance of survival. Then, it is highly desirable to assess the severity of blood loss and predict the occurrence of hemorrhagic shock (HS) from biomedical signals. In this study, transcranial Doppler (TCD) signal is used to predict and classify the degree of severity of blood loss either as mild, moderate, and severe or as severe and non-severe. The data for this study were generated using the human simulated model of hemorrhage which is called lower body negative pressure (LBNP). The analysis is done by applying discrete wavelet transformation (DWT). The wavelet-based features are defined using the detail and approximate coefficients and machine learning algorithms. The objective of this study is to assess our methods of processing TCD signal for predicting the hemorrhagic. The results of this study show the prediction accuracy of 84.2% achieved by support vector machine for predicting severe/non-severe states.
Immune responses to plasmid DNA encoding the hepatitis C virus core protein.

Hepatitis C virus (HCV) is a major causative agent of parenterally transmitted non-A, non-B hepatitis. The genomic region encoding the virion-associated core protein is relatively conserved among HCV strains. To generate a DNA vaccine capable of expressing the HCV core protein, the genomic region encoding amino acid residues 1 to 191 of the HCV-1 strain was amplified and cloned into an eukaryotic expression vector. IntramuscularinoculationofrecombinantplasmidDNAintoBALB/cmice(H-2 d )generatedHCVcore-specific antibody responses, lymphoproliferative responses, and cytotoxic T-lymphocyte activity. Our results suggest that the HCV core polynucleotide warrants further investigation as a potential vaccine against HCV infection. Hepatitis C virus (HCV) has been identified as the major causative agent of parenterally transmitted non-A, non-B hepatitis (3). It accounts for a large portion of community-acquired acute and chronic non-A, non-B viral hepatitis and is associatedwithlivercirrhosisandhepatocellularcarcinoma(1, 3). Approximately 1% of the world’s population (greater than 50 million people) is chronically infected. Chronic hepatitis is the ninth leading cause of death in the United States, and recent estimates suggest that HCV contributes to over 40% of these deaths (11). HCVisclassifiedasamemberofthefamilyFlaviviridae.The HCV genome is a linear positive-strand RNA molecule of ;9,500 bp and encodes a polyprotein precursor of ;3,000 amino acids (3). The genomic region encoding the HCV core protein (;21 kDa) is located at the N terminus of the polyprotein precursor and is believed to be cleaved by a signal peptidase located in the lumen of the endoplasmic reticulum (9). In contrast to the putative envelope glycoproteins, the virionassociated core protein shows greater sequence conservation among HCV strains (10). Cytotoxic activity against the HCV coreproteinhasbeenobservedintheliver-infiltratinglymphocytes of patients with HCV-associated chronic hepatitis (14). ImmunizationofBALB/cmicewithrecombinantvacciniavirus expressing HCV structural proteins has been shown to generate cytotoxic activity in spleen cells (21). A highly conserved antigenic site (amino acid residues 129 to 144) of the HCV coreproteinrecognizedbybothmurineandhumancytotoxicT lymphocytes (CTL) was identified by those investigators. The murine epitope was further mapped to a decapeptide (amino acid residues 133 to 142) presented by class I major histocompatibility molecules (H-2D d ) to conventional CD4 2 CD8 1
Anthropologizing Sri Lanka: A Eurocentric Misadventure.

Anthropologizing Sri Lanka:. Eurocentric Misadventure. Susantha Goonatilake. Bloomington: Indiana University Press, 2001. 306 pp.
A Review of: “Colin Mooers, ed., The New Imperialists: Ideologies of Empire.”

The pieces in this edited volume draw on marginal but powerful themes in U.S. foreign policy analysis, foremost among which is the idea that American strategic planning is determined primarily by t...
Quantitative evaluation of porcine endothelial cell antigens recognized by human natural antibodies: An analysis by Western blotting

: Xenoreactive natural antibodies recognize a series of glycoproteins in porcine endothelial cell membranes, the epitopes being Galα1–3Gal substitutions on those proteins. We recently identified the glycoprotein antigens as members of the integrin family, von Willebrand factor, and DM-GRASP. The antibodies that react with these structures are adsorbed during perfusion of a porcine organ, indicating that these antigens may be the biologically relevant targets. To evaluate the relative importance of the glycoproteins as targets of xenoreactive natural antibodies, immunoreactive electrophoretic bands containing these glycoproteins were analyzed by photodensitometry. The relevance of these antigens in the recognition of endothelial cell antigens by xenoreactive natural antibodies was assessed by an analysis of the differences between antigens recognized by normal human serum and those recognized by human serum that had been depleted of xenoreactive natural antibodies. Depletion of xenoreactive natural antibodies was performed by adsorption of serum on cultured porcine aortic endothelial cell monolayers and by perfusion through a porcine kidney. The analysis revealed that greater than 91% of the antibodies binding to porcine cell surfaces are specific for antigens identified in porcine endothelial cell membrane extracts. Quantitative analysis of antigens recognized by affinity purified antibodies confirmed that integrins are indeed the primary xenogeneic targets recognized on Western blots of porcine aortic endothelial cell membranes.
Bridge System Performance Assessment from Structural Health Monitoring: A Case Study

Based on the long-term monitored strain data induced by heavy vehicle traffic on an existing bridge, this paper presents an efficient approach to assessing the bridge system performance through a series-parallel system model consisting of bridge component reliabilities. The correlations among the bridge component safety margins are obtained by using actual traffic and strain data from structural health monitoring SHM. The prediction of bridge system reliability in the future is dependent on the performance functions of components. Sensitivity studies with respect to system modeling, correlations, extreme value probability distributions, measurement errors, and number of observations are carried out. A case study of the proposed approach is provided on an existing highway bridge in Wisconsin, which was monitored in 2004 by the Advanced Technology for Large Structural Systems Center, a National Engineering Research Center at Lehigh University, Bethlehem, Pa, USA. This study provides a solid basis for integrating SHM data into practical assessment of bridge system performance. DOI: 10.1061/ASCEST.1943-541X.0000014 CE Database subject headings: Bridges; Structural reliability; Structural safety; Monitoring; Assessments.
Kaposi's Sarcoma-Associated Herpesvirus ORF45 Mediates Transcriptional Activation of the HIV-1 Long Terminal Repeat via RSK2

Robust activation of human immunodeficiency virus type 1 (HIV-1) gene expression occurs upon superinfection with Kaposi’s sarcoma-associated herpesvirus (KSHV), a common AIDS-associated pathogen. Though the mechanisms underlying this phenotype remain unknown, several KSHV-encoded factors have been reported to stimulate HIV-1 long terminal repeat (LTR) activity. Here, we systematically evaluated the ability of KSHV tegument proteins to modulate the activation of an integrated HIV-1 LTR and revealed that the most potent individual activator is ORF45. ORF45 directs an increase in RNA polymerase II recruitment to the HIV-1 LTR, leading to enhanced transcriptional output. ORF45 is a robust activator of the p90 ribosomal S6 kinases (RSK), and we found that this activity is necessary but not sufficient to increase transcription from the LTR. Of the three widely expressed RSK isoforms, RSK2 appears to be selectively involved in LTR stimulation by both KSHV ORF45 and HIV-1 Tat. However, constitutively active RSK2 is unable to stimulate the LTR, suggesting that ORF45 may preferentially direct this kinase to a specific set of targets. Collectively, ourfindings reveal a novel transcriptional activation function for KSHV ORF45 and highlight the importance of RSK2 in shaping the transcriptional environment during infection. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) is a prominent AIDS-associated pathogen. Previous studies have shown that infection of cells containing human immunodeficiency virus type 1 (HIV-1) with KSHV leads to potent stimulation of HIV-1 gene expression by activating the HIV-1 promoter, termed the long terminal repeat (LTR). Here, we compared the abilities of various KSHV proteins to activate gene expression from the HIV-1 LTR and found that KSHV ORF45 is the most potent activator. ORF45 is known to induce cell signaling through ribosomal S6 kinase (RSK) and enhance protein translation. However, we revealed that the activation of a specific isoform of RSK by ORF45 also leads to increased mRNA synthesis from the LTR by the host RNA polymerase. Collectively, ourfindings provide new insight into the interviral interactions between KSHV and HIV that may ultimately impact disease.
The Relationship between Clinical Tooth Status and Receipt of Sealants among Child Medicaid Recipients

This study investigated the association between caries status and sealant need at a prior survey and subsequent sealant use in a Medicaid program. Clinical data from a 1986-87 statewide epidemiological survey (N = 8026) representative of North Carolina (NC) schoolchildren (grades K-12) were linked with all NC Medicaid dental claims submitted during 1987-92, yielding 570 children in the survey who had at least one dental visit during 1987-1992. From the 570, 390 children were included: 71 who received sealants (S) and 319 who received non-sealant care (NS). Children were excluded based on age, having pre-existing sealants, or having no sealant-eligible molars or premolars. S and NS were compared on baseline dfs, DMFS, and sealant need, controlling for the patient's age, number of visits, and the provider's propensity to seal. At all ages, NS was twice as likely to have had prior dfs or DMFS (OR = 2.04, 95% CI = 1.15, 3.70). The association between sealant receipt and prior sealant need varied by age. At 6 ...
Endothelin receptors and pain.

Abstract The endogenous endothelin (ET) peptides participate in a remarkable variety of pain-relatedprocesses. Pain that is elevated by inflammation, by skin incision, by cancer, during a Sickle Cell Disease crisis and by treatments that mimic neuropathic and inflammatory pain and are all reduced by local administration of antagonists of endothelin receptors. Many effects of endogenously released endothelin are simulated by acute, local subcutaneous administration of endothelin, which at very high concentrations causes pain and at lower concentrations sensitizes the nocifensive reactions to mechanical, thermal and chemical stimuli. Perspective In this paper we review the biochemistry, second messenger pathways and hetero-receptor coupling that are activated by ET receptors, the cellular physiological responses to ET receptor activation, and the contribution to pain of such mechanisms occurring in the periphery and the CNS. Our goal is to frame the subject of endothelin and pain for a broad readership, and to present the generally accepted as well as the disputed concepts, including important unanswered questions.
Use of the Quadratic Growth Response to Dietary Protein and Energy Concentrations in Least-Cost Feed Formulation

Abstract Quadratic growth responses to cumulative protein and energy intakes were observed in birds fed corn-soybean meal-wheat middlings and poultry oil-based diets. The linear and quadratic parts of a fitted equation identified diminishing marginal productivity of protein and energy; the interaction term identified the effect of the marginal physical product of one being a function of the other (R2>.99). The ingredient and nutrient coefficient matrices of one of the United States’ leading broiler producing firms were combined with the response equation by appropriate transformations. Ingredient prices were also added, and the resulting model was analyzed to indicate an exact point of economic efficiency (least cost per kilogram of broiler produced). As the price of corn increased, the concentrations of protein and energy in the diet that maximized weight gain for a given bird cost were affected only slightly. As the price of soybean meal increased, protein concentrations giving maximum gains decreased, and energy concentrations giving maximum gains increased. Quadratic programming (QP) constraints (maximum gain per input) produced a 1.84-kg broiler for 1.54¢ less than linear programming constraints (those suggested by the National Research Council, 1977). This was due to higher protein and lower energy concentrations by QP that resulted in a technical feed conversion that was of least cost with respect to the protein and energy values inherent at available feed ingredient prices.
Statistical simulation of multithreaded architectures

Detailed, cycle-accurate processor simulation is an integral component of the design and study of computer architectures. However, as the detail of simulation and processor design size increase, simulation times grow exponentially, and it becomes increasingly necessary to find fast, efficient simulation techniques that still ensure accurate results. At the same time, multithreaded multi-core designs are increasingly common, and require increased experimental design evaluation for a number of reasons including higher system complexity, interaction of multiple co-scheduled application threads, and workload selection. Although several effective simulation techniques exist for single-threaded architectures, techniques have not been effectively applied to the simulation of multithreaded and multi-core architecture models. Moreover, multithreaded processor simulation introduces unique challenges in all simulation stages. This work introduces systematic extensions of commonly-used statistical simulation techniques to multithreaded systems. The contributions of this work include: tailoring simulation fast-forwarding for individual threads, the effects of cache warming on application threads, and an analysis of the primary issues of efficient multithreaded simulation.
The Quiet Solar Transition Region

The results of recent studies (in the UV) of the structure and dynamics of the quiet solar transition region and its role in the mass and energy balance of the outer layers of the solar atmosphere are summarized. The region is one in which temperature increases from 25,000 K to about 1 million K and the matter density, fed by the outward flowing wind and the inward streaming plasma, increases by a factor of 40. The morphology of the region is described, along with the theoretical models being applied to the observed nonthermal line broadening, Doppler wavelength shifts, temporal fluctuations, and fine structure. Deficiencies in existing simple models of the region are discussed.
Allies, Targets, and the Effectiveness of Coalition Protest: A Comparative Analysis of Labor Unrest In the U. S. South

*† Social movement scholars suggest that coalitions comprise a significant and growing portion of all protest mobilizations. Such organizational collaboration is of great practical importance to the labor movement in particular, as unions struggle to succeed on their own in a difficult economic and political environment. Yet surprisingly little is known about the factors underlying the development and success of coalitions. In this article we advance literature on labor and social movement coalitions, bringing a comparative historical approach to bear on the problem and examining two influential and far-reaching labor campaigns that occurred in the U.S. South. Our argument and findings demonstrate the importance of the relative fit among coalition members, the vulnerabilities of collective action targets, and their interplay for coalition outcomes. We conclude by discussing the implications of the findings for labor and social movement challenges more generally.
High Selectivity of Porous Graphene Electrodes Solely Due to Transport and Pore Depletion Effects

We contrast the performance of monolayer electrodes and thin porous film electrodes of highly reduced functionalized graphene to demonstrate that the introduction of electrode porosity gives rise to strong apparent electrocatalytic effects resulting in vastly improved electrode selectivity. This is despite graphene showing no intrinsic advantage over glassy carbon electrodes when used as a monolayer. The simultaneous electro-oxidation of ascorbic acid, dopamine, and uric acid is used as an experimental model electrolyte system. Our results suggest that a large number of reports claiming the superior surface chemistry of carbon nanomaterials as the reason for outstanding electrochemical characteristics should be revisited considering electrode morphology as a significant contributor to the observed behavior. Our experimental results are supported by numerical simulations explaining the porosity-induced electrode selectivity by the dominance of pore depletion over diffusion-limited currents.
Branched grafts for thoracoabdominal aneurysms: off-label use of FDA-approved devices.

PurposeTo report off-label use of approved off-the-shelf endografts with no modification to the devices for the management of thoracoabdominal aneurysms (TAAA).TechniqueThe parallel endograft octop...
Metabolic Fate of S35 Administered to Rabbits as Sulfate.

SummaryThe metabolic fate of S35-labeled sulfate in young rabbits was studied. Absorption of S35 after labeled sulfate was administered by stomach tube was very rapid, with the peak appearing in blood around 6 hours after dosing. Some synthesis of labeled cystine and methionine took place, with S35-labeled cystine and methionine appearing in the liver. When the habitual practice of coprophagy was interfered with by fitting the rabbit with a collar which prevented fecal refection, the amount of labeled cystine and methionine was greatly reduced.
Uncertainty Analysis and Robust Design of Drill Under Framework of Multidisciplinary Design Optimization

Multidisciplinary design optimization,uncertainty analysis and robust design are introduced.Some problems of uncertainty analysis and robust design under the framework of multidisciplinary design optimization are researched,and design outlines of drill are discussed in detail.
Nutritional guidelines and labeling.

In implementing recommendations of the White House Conference on Food, Nutrition and Health, the Food and Drug Administration has adopted entirely new philosophies with respect to both content and labeling of processed foods. Development of the FDA’s programs for nutritional guidelines and nutrient labeling are discussed here.
Receptors for insulin-like growth factors I and II

The somatomedins (SMs) comprise a family of growth hormone (GH)-dependent, insulin-like peptides with metabolic and mitogenic actions in a wide variety of cell lines (Phillips and Vassilopoulou-Sellin 1980). While their precise role in the regulation of cellular replication remains uncertain, a growing body of data supports the hypothesis that these peptides mediate many of the anabolic actions of GH (Phillips and Vassilopoulou-Sellin 1980; Schoenle et al. 1982). Two human SMs, insulin-like growth factors (IGF) I and II, have been purified, sequenced, and found to have 62% identity in amino acid positions (Rinderknecht and Humbel 1978a, b). Furthermore, these peptides have a striking structural homology to proinsulin. The sequences of cDNAs encoding for human pre-proIGF-I and -II have been elucidated and their respective 130 and 180 amino acid precursors predicted (Jansen et al. 1983; Bell et al. 1984; Dull et al. 1984). IGF-II has been mapped to the short arm of chromosome 11, tightly linked to both the insulin gene and the c-Ha-ras 1 proto-oncogene (Brissenden et al. 1984; Tricoli et al. 1984). IGF-I maps to chromosome 12, which is evolutionarily related to chromosome 11 and carries the gene for the c-Ki-ras2 proto-oncogene. These striking homologies suggest evolutionary conservation of a common critical peptide skeleton and raise important questions concerning the precise role of each peptide and how cells mediate each peptide’s biological activities. As their structural homology would suggest, IGF-I and -II have weak insulin-like metabolic effects, while insulin shares the mitogenic and growth-promoting actions of the IGFs (Rosenfeld and Hintz 1986).
A Bayesian inference method for the analysis of transcriptional regulatory networks in metagenomic data

Metagenomics enables the analysis of bacterial population composition and the study of emergent population features, such as shared metabolic pathways. Recently, we have shown that metagenomics datasets can be leveraged to characterize population-wide transcriptional regulatory networks, or meta-regulons, providing insights into how bacterial populations respond collectively to specific triggers. Here we formalize a Bayesian inference framework to analyze the composition of transcriptional regulatory networks in metagenomes by determining the probability of regulation of orthologous gene sequences. We assess the performance of this approach on synthetic datasets and we validate it by analyzing the copper-homeostasis network of Firmicutes species in the human gut microbiome. Assessment on synthetic datasets shows that our method provides a robust and interpretable metric for assessing putative regulation by a transcription factor on sets of promoter sequences mapping to an orthologous gene cluster. The inference framework integrates the regulatory contribution of secondary sites and can discern false positives arising from multiple instances of a clonal sequence. Posterior probabilities for orthologous gene clusters decline sharply when less than 20 % of mapped promoters have binding sites, but we introduce a sensitivity adjustment procedure to speed up computation that enhances regulation assessment in heterogeneous ortholog clusters. Analysis of the copper-homeostasis regulon governed by CsoR in the human gut microbiome Firmicutes reveals that CsoR controls itself and copper-translocating P-type ATPases, but not CopZ-type copper chaperones. Our analysis also indicates that CsoR frequently targets promoters with dual CsoR-binding sites, suggesting that it exploits higher-order binding conformations to fine-tune its activity. We introduce and validate a method for the analysis of transcriptional regulatory networks from metagenomic data that enables inference of meta-regulons in a systematic and interpretable way. Validation of this method on the CsoR meta-regulon of gut microbiome Firmicutes illustrates the usefulness of the approach, revealing novel properties of the copper-homeostasis network in poorly characterized bacterial species and putting forward evidence of new mechanisms of DNA binding for this transcriptional regulator. Our approach will enable the comparative analysis of regulatory networks across metagenomes, yielding novel insights into the evolution of transcriptional regulatory networks.
Optimization of power AlGaN/GaN vertical HEMT devices with low on-state resistance and high breakdown voltage

Recently [1,2] we have developed a numerical technique for the optimization of parameters in semiconductor devices. This technique allows the computation (“redesign”) of the doping profiles of most semiconductor devices such as MOSFETs and SOI transistors, in order to decrease (or increase) the values of given parameters of the device. In this presentation we show how to adjust this optimization technique to the minimization of the on-state resistance (R on ) in AlGaN/GaN vertical HEMT devices with high breakdown voltage (BV). The technique is based on the computation of doping sensitivity functions of R on and BV and the minimization of R on , in which the optimization variables are the values of the doping concentrations at each location inside the device. Constraints are taken into consideration by using the method of Lagrange multipliers.
Cortical Lesions in Multiple Sclerosis

The presence and frequency of cortical lesions (CLs) in 24 pediatric patients with relapsing-remitting multiple sclerosis (RRMS) were compared to 15 adult patients with RRMS and 10 pediatric healthy controls, in a study at University Ospedale San Raffaele, Milan and other centers in Italy.
The Intimacies of Four Continents, by Lisa Lowe: Duke University Press, 2015. Print

It comes as dogma that our twenty-first century is flat and interconnected, built upon principles of liberalism that catalyzed the world into the modern age. The question of why and how we arrived ...
Nationwide incidence, treatment, and outcomes of patients 80 years and older with rectal adenocarcinomas: Analysis of 5,076 patients.

723Background: Elderly patients have been underrepresented in randomized clinical trials of rectal cancer, and the value and tolerance of treatment options in this population remain unclear. We used the National Cancer Data Base (NCDB) to assess the incidence, treatment patterns, and overall survival (OS) outcomes of patients 80 years or older with newly diagnosed non-metastatic rectal adenocarcinomas. Methods: 5076 patients 80 years and older diagnosed with non-metastatic rectal adenocarcinomas from 2004 to 2013 were identified. Univariable and multivariable (MVA) analysis were performed to identify patient, tumor, and treatment characteristics associated with receipt of standard of care therapy (SOCT) and factors predictive of OS. SOCT was defined as surgical resection for Stage I patients and receipt of neoadjuvant therapy followed by surgical resection for Stage II/III patients. Kaplan-Meier curves were generated to assess the effect of stage and treatment received on overall survival. Results: At pre...
State-of-Charge and Deformation-Rate Dependent Mechanical Behavior of Electrochemical Cells

The state-of-charge and deformation-rate dependent mechanical behavior of cylindrical lithium-ion battery cells was investigated. The research revealed that both state of charge and deformation rates affected the stiffness of the battery cells. Battery mechanical failure load was only weakly dependent on the state of charge. For the deformation-rate dependency on the mechanical integrity of battery cells, the battery mechanical failure load was either decreased significantly at high state of charge or decreased slightly at low state of charge as deformation rate increased. For the correlation between mechanical integrity and electrical failure, the displacement at the battery mechanical failure load coincided with a voltage drop. However, at high state of charge, premature and incomplete voltage drops were observed before the definite final voltage drop. No such premature voltage drop was observed in low state-of-charge specimens. The results of this research may be used as a reference for the design of impact and damage tolerant electric vehicle battery systems.
The wall and the wash: Security, infrastructure and rescue on the US-Mexico border

Based on ethnographic research with firefighters trained as EMTs (emergency medical technicians) or paramedics in northern Sonora and southern Arizona, this article takes the vantage point of emergency responders on both sides of the US-Mexico border to trace the harmful effects of the security assemblage on those who inhabit and trespass this militarized landscape. Interested in the materiality of security – how its discursive and affective qualities are anchored in urban and desert terrain by means of infrastructure and technology – this article focuses on two such ‘anchors’, the wall and the wash, in order to address the legal and ethical issues that result from the deployment of tactical infrastructure on the border.
Role of monoaminergic systems and ambient temperature in bath salts constituent 3,4-methylenedioxypyrovalerone (MDPV)-elicited hyperthermia and locomotor stimulation in mice.

Abstract 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit bath salts products, and in vitro studies implicate monoamine transporters as mediators of its pharmacological effects. Locomotor and thermoregulatory effects of MDPV depend on ambient temperature, so the current studies aimed to gauge the involvement of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in MDPV-induced locomotor stimulation and hyperthermia in the mouse at different ambient temperatures. Mice were pretreated with the selective 5-HT-reuptake inhibitor fluoxetine (3 mg/kg), the NE-reuptake inhibitor desipramine (3 mg/kg), the DA-reuptake inhibitor bupropion (10 mg/kg), or saline, followed by 10 mg/kg MDPV while thermoregulation and locomotor activity were monitored via radiotelemetry. In other studies, mice were pretreated for three days with saline, 100 mg/kg of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (p-CPA), or 100 mg/kg of the tyrosine hydroxylase inhibitor α-methyl-para-tyrosine (α-MPT) before receiving 10 mg/kg MDPV on the fourth day. All manipulations were conducted at both 20 °C and 28 °C ambient temperatures. MDPV increased locomotor activity under both ambient conditions and modestly increased core body temperature at 20 °C; however, neither pretreatment with monoamine reuptake inhibitors nor monoamine synthesis inhibitors significantly altered these effects. At 28 °C, MDPV induced a more pronounced hyperthermic effect which was attenuated by bupropion, desipramine, or fluoxetine pretreatment, but not by the monoamine synthesis inhibitors. These results suggest that MDPV may have a more complex pharmacological profile than suggested by in vitro studies, perhaps extending beyond interactions with monoamine transporters. A more thorough binding profile of MDPV at various brain recognition sites should be developed. This article is part of the Special Issue entitled ‘Designer Drugs and Legal Highs.’
Pantoprazole, an Inhibitor of the Organic Cation Transporter 2, Does Not Ameliorate Cisplatin-Related Ototoxicity or Nephrotoxicity in Children and Adolescents with Newly Diagnosed Osteosarcoma Treated with Methotrexate, Doxorubicin, and Cisplatin.

Lessons learned Using a randomized crossover design and continuous variables such as change in hearing threshold and biomarkers of acute renal injury as short-term endpoints, it was determined that pantoprazole, an organic cation transporter 2 inhibitor, did not ameliorate cisplatin-associated nephrotoxicity or ototoxicity.Cystatin C is a robust method to estimate glomerular filtration rate in patients with cancer. Using a patient-reported outcome survey, all patients identified tinnitus and subjective hearing loss occurring "at least rarely" after cycle 1, prior to objective high-frequency hearing loss measured by audiograms.New therapies that improve outcome with less acute and long-term toxicity are needed. Background Organic cation transporter 2 (OCT2), which is a cisplatin uptake transporter expressed on renal tubules and cochlear hair cells but not on osteosarcoma cells, mediates cisplatin uptake. Pantoprazole inhibits OCT2 and could ameliorate cisplatin ototoxicity and nephrotoxicity. Using a randomized crossover design, we evaluated audiograms, urinary acute kidney injury (AKI) biomarkers, and glomerular filtration rate (GFR) estimated from cystatin C (GFRcysC) in patients receiving cisplatin with and without pantoprazole. Materials and methods Cisplatin (60 mg/m2 × 2 days per cycle) was administered concurrently with pantoprazole (intravenous [IV], 1.6 mg/kg over 4 hours) on cycles 1 and 2 or cycles 3 and 4 in 12 patients with osteosarcoma (OS) with a median (range) age of 12.8 (5.6-19) years. Audiograms, urinary AKI biomarkers, and serum cystatin C were monitored during each cycle. Results Pantoprazole had no impact on decrements in hearing threshold at 4-8 kHz, post-treatment elevation of urinary AKI biomarkers, or GFRcysC (Fig. 1, Table 1). Histological response (percent necrosis) after two cycles was similar with or without pantoprazole. All eight patients with localized OS at diagnosis are alive and in remission; three of four patients with metastases at diagnosis have died. Conclusion Pantoprazole did not ameliorate cisplatin ototoxicity or nephrotoxicity. The decrease in GFRcysC and increase in N-acetyl-s-glucosaminidase (NAG) and creatinine demonstrate that these biomarkers can quantify cisplatin glomerular and proximal tubular toxicity. OCT2 inhibition by pantoprazole did not appear to alter antitumor response or survival.
Identification of new PDE9A isoforms and how their expression and subcellular compartmentalization in the brain change across the life span.

Abstract 3′,5′-Cyclic nucleotide phosphodiesterases (PDEs) degrade 3′,5′ cyclic adenonosine monophosphate (cAMP) and 3′,5′ cyclic guanosine monophosphate (cGMP), with PDE9A having the highest affinity for cGMP. We show PDE9A6 and 3 novel PDE9 isoforms (PDE9X-100, PDE9X-120, and PDE9X-175) are reliably detected in the brain and lung of mice, whereas PDE9A2 and other isoforms are found elsewhere. PDE9A localizes to the membrane in all organs except the bladder, where it is cytosolic. Brain additionally shows PDE9 in the nuclear fraction. PDE9A mRNA expression/localization dramatically changes across neurodevelopment in a manner that is strikingly consistent between mice and humans (i.e., decreased expression in the hippocampus and cortex and inverted-U in the cerebellum). Study of the 4 PDE9 isoforms in the mouse brain from postnatal day 7 through 24 months similarly identifies dramatic effects of age on expression and subcellular compartmentalization that are isoform specific and brain region specific. Finally, PDE9A mRNA is elevated in the aged human hippocampus with dementia when there is a history of traumatic brain injury. Thus, brain PDE9 is localized to preferentially regulate nuclear- and membrane-proximal pools of cGMP, and its function likely changes across the life span.
Intercalated graphene oxide for flexible and practically large thermoelectric voltage generation and simultaneous energy storage

Abstract We report a new planar-type “thermally” chargeable supercapacitor (pTCSC) that can be charged by converting thermal energy into electricity without an external electrical power supply. The pTCSC was fabricated using a facile and scalable laser irradiation on graphene oxide films intercalated by sulfate ions (SGO) to control the mobility and concentration of dissociated protons without any liquid-phase electrolytes typically used in conventional supercapacitors. We utilized the Soret effect as a dominant transport mechanism for producing a very high thermally induced voltage up to 9 mV/K, compared with typically much lower thermoelectric voltages mainly from the Seebeck effect in traditional inorganic and organic thermoelectric materials. The key parameters to obtain the strikingly high thermopower with decent electrical conductivity were identified to be the improved mobility and concentration of proton. At the same time, the harvested electrical energy was stored on the reduced SGO electrodes. With a temperature gradient of 10.5 K, our “single” pTCSC device generated a large thermally charged voltage of 58 mV without electrical power supply. We also demonstrated that an array of pTCSC can be batch-fabricated and connected together to linearly raise the output voltage as large as 2.1 V, suggesting excellent suitability for roll-to-roll mass manufacturing of practical pTCSC. We demonstrated that it is feasible to operate an electrochromic device that darkens with power supply like a smart window using the batch-fabricated pTCSC when a temperature gradient is applied. Our results suggest that the pTCSC could eliminate needs for battery replacement and wired connections to power lines for various distributed electronic systems whenever and wherever a temperature gradient is present.
Mechanisms of Ultrafast Charge Separation in a PTB7/Monolayer MoS2 van der Waals Heterojunction

Mixed-dimensional van der Waals heterojunctions comprising polymer and two-dimensional (2D) semiconductors have many characteristics of an ideal charge separation interface for optoelectronic and photonic applications. However, the photoelectron dynamics at polymer–2D semiconductor heterojunction interfaces are currently not sufficiently understood to guide the optimization of devices for these applications. This Letter reports a systematic exploration of the time-dependent photophysical processes that occur upon photoexcitation of a type-II heterojunction between the polymer PTB7 and monolayer MoS2. In particular, photoinduced electron transfer from PTB7 to electronically hot states of MoS2 occurs in less than 250 fs. This process is followed by a 1–5 ps exciton diffusion-limited electron transfer from PTB7 to MoS2 and a sub-3 ps photoinduced hole transfer from MoS2 to PTB7. The equilibrium between excitons and polaron pairs in PTB7 determines the charge separation yield, whereas the 3–4 ns lifetime of p...
Rapidly Progressive Glomerulonephritis

Rapidly progressive glomerulonephritis is rare in children and adolescents and is seen predominantly in the context of immune complex-mediated diseases. Children often present with non-specific signs and symptoms and may deteriorate rapidly, with the development of alveolar hemorrhage. Since early diagnosis and treatment are critical in improving outcomes, the care of these children should be performed by multidisciplinary teams that have the requisite experience. Serologic testing and renal biopsy are critical to guide therapy; however, therapy should not wait for diagnostic confirmation due to risk of disease progression. While the mortality associated with rapidly progressive glomerulonephritis has declined, outcomes remain suboptimal.
Immune Checkpoint Inhibitors in Pediatric Solid Tumors: Status in 2018

Background: Checkpoint inhibitors have transformed the treatment of cancer in adults. This class of drugs has demonstrated encouraging results in various malignancies such as metastatic melanoma, bladder cancer, renal cancer, and non–small cell lung carcinoma. However, researchers have only begun investigating the effectiveness and tolerability of checkpoint inhibitors in pediatric patients. Methods: We conducted a review of PubMed indexed literature and clinicaltrials.gov using combinations of the keywords checkpoint, inhibitor, pediatric, CTLA-4 (cytotoxic T lymphocyte antigen-4), PD-1 (programmed cell death-1), and PD-L1 (programmed cell death receptor-1 ligand) to find every recently completed and ongoing trial evaluating checkpoint inhibitors in patients younger than 21 years old. Pertinent articles and clinical trials discussing the role of immune checkpoint inhibitors in the pediatric population were selected for final analysis and manuscript citation. Results: This review presents an overview of the cellular mechanisms involved in checkpoint inhibition and of studies evaluating checkpoint inhibitors in humans. The review also details results and side effects from studies conducted with pediatric patients, current pediatric clinical trials, and future implications. Conclusion: Immune checkpoint inhibitors have the potential to further therapeutic advances in pediatric oncology; however, we need more clinical trials and combination drug strategies targeted toward pediatric cancers.