Miracle-dz/UniFAR-FTUs huggingface dataset:
AMPA Antagonist ZK200775 in Patients With Acute Ischemic Stroke: Possible Glial Cell Toxicity Detected by Monitoring of S-100B Serum Levels

Background and Purpose— S-100B and neuron-specific enolase (NSE) serum concentrations can be used as peripheral markers of glial cell and neuronal damage, respectively. We investigated these markers in a clinical trial with the &agr;-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) antagonist ZK200775 in acute ischemic stroke patients. Methods— In a multicenter, double-blind, randomized, placebo-controlled phase 2 trial, 61 ischemic stroke patients were treated with either placebo or active drug in a dose-finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 hours (dose group 1), and 13 patients received a total dose of 525 mg in 48 hours (dose group 2). Eleven patients received a total dose of 105 mg over a period of 6 hours (dose group 3; reduction of total dose and infusion time because of adverse events in group 2). Serum concentrations of S-100B and NSE were analyzed with the use of a monoclonal sandwich immunoluminometric assay. Neurological outcome was assessed with the National Institutes of Health Stroke Scale (NIHSS). Results— In group 2 there was a significant transient worsening in the mean NIHSS score 48 hours after the start of treatment. The mean increase was 11 points. This was due to reduction of consciousness (stupor and coma) in 8 of 13 patients. Neurological deterioration in group 2 was associated with a higher increase of S-100B concentrations, but not of NSE concentrations, than in the placebo group. The trial was stopped prematurely for safety reasons. Conclusions— The AMPA antagonist ZK200775 transiently worsened the neurological condition in patients with acute ischemic stroke. Our results suggest that in addition to neuronal dysfunction, glial cell toxicity may have occurred. It may be useful to introduce monitoring of serum markers of brain damage in phase 2 trials with glutamate receptor antagonists.
Built upon sand: Theoretical ideas inspired by granular flows

Granulated materials, like sand and sugar and salt, are composed of many pieces that can move independently. The study of collisions and flow in these materials requires new theoretical ideas beyond those in the standard statistical mechanics or hydrodynamics or traditional solid mechanics. Granular materials differ from standard molecular materials in that frictional forces among grains can dissipate energy and drive the system toward frozen or glassy configurations. In experimental studies of these materials, one sees complex flow patterns similar to those of ordinary liquids, but also freezing, plasticity, and hysteresis. To explain these results, theorists have looked at models based upon inelastic collisions among particles. With the aid of computer simulations of these models they have tried to build a ‘‘statistical dynamics’’ of inelastic collisions. One effect seen, called inelastic collapse, is a freezing of some of the degrees of freedom induced by an infinity of inelastic collisions. More often some degrees of freedom are partially frozen, so that there can be a rather cold clump of material in correlated motion. Conversely, thin layers of material may be mobile, while all the material around them is frozen. In these and other ways, granular motion looks different from movement in other kinds of materials. Simulations in simple geometries may also be used to ask questions like When does the usual Boltzmann-Gibbs-Maxwell statistical mechanics arise? , What are the nature of the probability distributions for forces between the grains? , and Might the system possibly be described by uniform partial differential equations? One might even say that the study of granular materials gives one a chance to reinvent statistical mechanics in a new context. [S0034-6861(99)00701-1]
Predicting breast cancer outcome: Traditional prognosticators still on center stage

Commentary to: Traditional and new prognosticators in breast cancer: Nottingham index, Mib-1 and estrogen receptor signaling remain the best predictors of relapse and survival in a series of 289 cases Tiziana Megha, Alessandro Neri, Valeria Malagnino, Stefano Caruso, Monica Onorati, Franco Roviello and Piero Tosi
The CAPM Debate

This article describes the academic debate about the usefulness of the capital asset pricing model (the CAPM) developed by Sharpe and Lintner. First the article describes the data the model is meant to explain? the historical average returns for various types of assets over long time periods. Then the article develops a version of the CAPM and describes how it measures the risk of investing in particular assets. Finally the article describes the results of competing studies of the model's validity. Included are studies that support the CAPM (Black; Black, Jensen, and Scholes; Fama and MacBeth), studies that challenge it (Banz; Fama and French), and studies that challenge those challenges (Amihud, Christensen, and Mendelson; Black; Breen and Korajczyk; Jagannathan and Wang; Kothari, Shanken, and Sloan). The article concludes by suggesting that, while academic debate continues, the CAPM may still be useful for those interested in the long run.
Wavelets and radial basis functions: a unifying perspective

Wavelets and radial basis functions (RBF) are two rather distinct ways of representing signals in terms of shifted basis functions. An essential aspect of RBF, which makes the method applicable to non-uniform grids, is that the basis functions, unlike wavelets, are non-local-in addition, they do not involve any scaling at all. Despite these fundamental differences, we show that the two types of representation are closely connected. We use the linear splines as motivating example. These can be constructed by using translates of the one-side ramp function, or, more conventionally, by using the shifts of a linear B-spline. This latter function, which is the prototypical example of a scaling function, can be obtained by localizing the one-side ramp function using finite differences. We then generalize the concept and identify the whole class of self-similar radial basis functions that can be localized to yield conventional multiresolution wavelet bases. Conversely, we prove that, for any compactly supported scaling function, there exist a one-sided central basis function that spans the same multiresolution subspaces. The central property is that the multiresolution bases are generated by simple translation without any dilation.
Assessing the Impact of Product Use Variation on Environmental Sustainability

The goal of this research is to characterize the effects of use patterns on the environmental sustainability of consumer products, and to enable decision making throughout design processes that encourages product sustainability. Life Cycle Assessments (LCA) are currently used to evaluate the environmental impact of a product, but there can be considerable uncertainty in these analyses, especially relating to the use phase of the product. To better understand this uncertainty, we conducted environmental impact assessments of 20 household products, and employed two uncertainty quantification approaches to accommodate variation in the use phase of these products. The results from each product were then compared to products with similar attributes to find generalizations. This knowledge was integrated into decision trees so designers can better understand the degree to which use-phase uncertainty can affect quantitative measures of environmental impact before performing LCAs. This work enables designers to make more informed decisions about the intended use and use lifetimes of consumer products, potentially leading to a reduced environmental impact of this life cycle phase.
Capillary haemangiomatosis of the lungs

A case of capillary haemangiomatosis affecting both lungs. The angiomatous growth involved particularly the intralobular fibrous septa and appeared locally aggressive as it had destroyed and obstructed the pulmonary veins and venules. Some pulmonary arteries and bronchi were affected to a lesser extent. Pulmonary venous obstruction, sometimes simulating pulmonary veno‐occlusive disease, caused severe haemosiderosis and interstitial fibrosis. The clinical features and the lung biopsy erroneously suggested a diagnosis of primary pulmonary haemosiderosis. No comparable case has been found in the literature.
Evaluating the Linearized Almost Ideal Demand System

Linearizing the Almost Ideal Demand System (LAIDS) by recourse to the Stone share weighted price index is common practice. Two issues are addressed here. First, scrutiny of the errors-in-variables implications of the linearization reveals that, not only is the SUR estimator inconsistent, but a consistent IV estimator cannot be constructed. Second, some alternatives to the Green-Alston elasticities specifically designed for the LAIDS model are developed, but neither these nor the Green-Alston elasticities are found to have any advantages over the conventional elasticity formulae. Some errors in the Green-Alston (1990) paper are corrected. The inconsistency and elasticity issues are documented by a Monte Carlo investigation.
Ganglioside GM1 Binding Peptides: A Potential Adjuvant for Transcutaneous Immunization

Cholera toxin (CT) binds ganglioside GM1 and has been used as an adjuvant in transcutaneous immunization. To determine if the adjuvant property of CT was merely due to binding to ganglioside GM1, mice were immunized by the transcutaneous route using hen egg lysozyme (HEL) as the antigen, and either CT or synthetic peptides that bind to ganglioside GM1 as the adjuvant, and the immune responses were evaluated. Both CT and GM1 binding peptides (GM1- bp) induced HEL-specific antibodies and T-cell proliferation. However, the immune responses when GM1-bp was used as the adjuvant, was much lower when compared to CT as the adjuvant. GM1-bp maintained or enhanced the co-stimulatory molecules on antigen presenting cells, in particular on JAWS II dendritic cells. Overall, the data suggests that the binding of GM1-bp to ganglioside GM1 alone can induce immune responses to the co-administered antigen.
Structural abnormalities in gyri of the prefrontal cortex in individuals with schizophrenia and their unaffected siblings

Background The relatives of individuals with schizophrenia exhibit deficits of overall frontal lobe volume, consistent with a genetic contribution to these deficits. Aims To quantify the structure of gyral-defined subregions of prefrontal cortex in individuals with schizophrenia and their siblings. Method Grey matter volume, cortical thickness, and surface area of the superior, middle and inferior frontal gyri were measured in participants with schizophrenia and their unaffected (non-psychotic) siblings (n = 26 pairs), and controls and their siblings (n = 40 pairs). Results Grey matter volume was reduced in the middle and inferior frontal gyri of individuals with schizophrenia, relative to controls. However, only inferior frontal gyrus volume was also reduced in the unaffected siblings of those with schizophrenia, yielding a volume intermediate between their affected siblings and controls. Conclusions The structure of subregions of the prefrontal cortex may be differentially influenced by genetic factors in schizophrenia, with inferior frontal gyrus volume being most related to familial risk.
Secretion of Glucose-Dependent Insulinotropic Polypeptide in Patients With Type 2 Diabetes

OBJECTIVE To investigate glucose-dependent insulinotropic polypeptide (GIP) secretion in patients with type 2 diabetes and nondiabetic control subjects during oral glucose or meal tests. RESEARCH DESIGN AND METHODS Eligible trials were identified by The Cochrane Library, MEDLINE, Embase, and Web of Science. Data were retrieved and random-effects models for the primary meta-analysis, random-effects meta-regression, and subgroup and regression analyses were applied. RESULTS Random-effects meta-analysis of GIP responses in 23 trials during 28 different stimulation tests showed that patients with type 2 diabetes (n = 363) exhibited no significant differences (P = not significant) in peak plasma GIP, total area under the curve (tAUC), time-corrected tAUC (tAUC × min−1), and time-corrected incremental area under the curve (iAUC × min−1) in comparison with nondiabetic control subjects (n = 325) but had lower GIP responses as evaluated from iAUC (weighted mean difference, −648 pmol/L × min; 95% CI, −1,276 to −21). Fixed-effects models meta-analyses confirmed most of the results of the primary meta-analysis but showed iAUC × min−1 to be reduced and showed tAUC and tAUC × min−1 to be higher in diabetic patients. Random-effects meta-regression of the primary meta-analysis showed that age (peak GIP, tAUC, iAUC, and iAUC × min−1), BMI (tAUC, iAUC, and iAUC × min−1), and HbA1c (iAUC and iAUC × min−1) predicted some of the GIP outcomes. Post hoc subgroup analysis showed a negative influence of age and of HbA1c on GIP responses and showed a positive influence of BMI on GIP responses. CONCLUSIONS Our results suggest that patients with type 2 diabetes are characterized by preserved GIP secretion in response to oral glucose and meal tests. They also suggest that high BMI is associated with increased GIP responses but increasing age and HbA1c are associated with reduced GIP secretion.
The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks

Genetically related Mycobacterium tuberculosis strains with alterations at codon 516 in the rpoB gene were observed amongst a substantial number of patients with drug resistant tuberculosis in the Eastern Cape Province (ECP) of South Africa. Mutations at codon 516 are usually associated with lower level rifampicin (RIF) resistance, while susceptibility to rifabutin (RFB) remains intact. This study was conducted to assess the rationale for using RFB as a substitution for RIF in the treatment of MDR and XDR tuberculosis outbreaks. Minimum inhibitory concentrations (MICs) of 34 drug resistant clinical isolates of M tuberculosis were determined by MGIT 960 and correlated with rpoB mutations. RFB MICs ranged from 0.125 to 0.25 µg/ml in the 34 test isolates thereby confirming phenotypic susceptibility as per critical concentration (CC) of 0.5 µg/ml. The corresponding RIF MICs ranged between 5 and 15 µg/ml, which is well above the CC of 1.0 µg/ml. Molecular-based drug susceptibility testing provides important pharmacogenetic insight by demonstrating a direct correlation between defined rpoB mutation and the level of RFB susceptibility. We suggest that isolates with marginally reduced susceptibility as compared to the epidemiological cut-off for wild-type strains (0.064 µg/ml), but lower than the current CC (≤0.5 µg/ml), are categorised as intermediate. Two breakpoints (0.064 µg/ml and 0.5 µg/ml) are recommended to distinguish between susceptible, intermediate and RFB resistant strains. This concept may assist clinicians and policy makers to make objective therapeutic decisions, especially in situations where therapeutic options are limited. The use of RFB in the ECP may improve therapeutic success and consequently minimise the risk of ongoing transmission of drug resistant M. tuberculosis strains.
Archaeology, Conservation, and Public Engagement at Omrit: A Case Study

abstract:This article tells the story of Omrit in its evolution from a new archaeological site to a place of on-site conservation, the establishment of off-site exhibitions centered around a locus of regional cultural heritage, and future plans for a national park and nature reserve. We believe Omrit may serve as a case study of the stages other archaeological sites may ultimately experience. We discuss the initial stage of excavations, the development of in-situ conservation and stabilization, the decisions to embark on ex-site exhibits, the introduction of digitization of objects and finds, and conclude with a discussion of plans and proposals for the site done in concert with in-country authorities.
Isolation and characterization of a gene (CBF2) specifying a protein component of the budding yeast kinetochore

We have cloned and determined the nucleotide sequence of the gene (CBF2) specifying the large (110 kD) subunit of the 240-kD multisubunit yeast centromere binding factor CBF3, which binds selectively in vitro to yeast centromere DNA and contains a minus end-directed microtubule motor activity. The deduced amino acid sequence of CBF2p shows no sequence homologies with known molecular motors, although a consensus nucleotide binding site is present. The CBF2 gene is essential for viability of yeast and is identical to NDC10, in which a conditional mutation leads to a defect in chromosome segregation (Goh, P.-Y., and J. V. Kilmartin, in this issue of The Journal of Cell Biology). The combined in vitro and in vivo evidence indicate that CBF2p is a key component of the budding yeast kinetochore.
Likelihood-based non-uniform allocation of Gaussian kernels in scalar dimension for HMM compression

A new, likelihood-based non-uniform allocation of Gaussian kernels in scalar (feature) dimension is proposed to compress complex, Gaussian mixture-based, continuous density HMMs into computationally efficient, small footprint models. Different from the objective of the previously proposed Kullback-Leibler divergence-based (KLD-based) allocation (Li et al., 2005), which is to make a better representation of the original model, the objective of the likelihood-based approach is to make the current compressed model be a better representation of the training data. It is implemented based on the unequal likelihood contributions of different features with uniform representation resolutions. Our experiments on the resource management database show that likelihood-based allocation outperforms uniform allocation and KLD-based non-uniform allocation due to its better representation of the training data.
Gaussian process optimization through sampling from the maximum distribution

This paper first presents a novel algorithm approximating the distribution of the maximum (both its position and its value) of a Gaussian process. This algorithm uses particles in a similar way as Sequential Monte Carlo samplers. It is subsequently applied to the problem of Gaussian Process Optimization (GPO). The resulting GPO algorithm does not use an acquisition function, which makes it different from other GPO algorithms. Through various example problems, including a wind turbine load mitigation example, we find that the resulting algorithm on average outperforms existing GPO algorithms. In addition, because no acquisition function has to be optimized, the algorithm can easily and efficiently be applied to problems with high-dimensional input spaces.
Acute pulmonary embolism: part II: treatment and prophylaxis.

Case presentation : A 66-year-old man with a history of deep venous thrombosis (DVT) presented with acute dyspnea. He was normotensive, with a resting tachycardia of 110 beats per minute and an oxygen saturation of 76% on room air. The only electrocardiographic abnormality was sinus tachycardia. His brain-type natriuretic peptide (BNP) and cardiac troponin levels were elevated. Chest computed tomography (CT) with contrast demonstrated a large saddle pulmonary embolus and increased diameter of the right ventricle (RV) compared with the left ventricle (LV). The patient received intravenous bolus followed by continuous infusion unfractionated heparin. Within several hours, the patient became progressively more hypotensive and hypoxemic. Bedside transthoracic echocardiography (TTE) showed RV dilatation and hypokinesis. He then received intravenous fibrinolysis, with rapid improvement in hemodynamics and oxygenation. What were the clues that he was likely to suffer from progressive hypotension and hypoxemia? Pulmonary embolism (PE) represents a spectrum of syndromes ranging from small peripheral emboli causing pleuritic pain to massive PE resulting in cardiogenic shock or cardiac arrest. Most patients with PE present with normal blood pressure. However, some may rapidly deteriorate and manifest systemic hypotension, cardiogenic shock, and sudden death despite therapeutic levels of anticoagulation. Risk stratification to identify such patients has emerged as a critical component of care. The history and physical examination provide the starting point for risk stratification. The International Cooperative Pulmonary Embolism Registry (ICOPER) identified age >70 years, cancer, congestive heart failure, chronic obstructive pulmonary disease, and systolic blood pressure less than 90 mm Hg as significant predictors of increased mortality.1 Elevated cardiac biomarkers correlate with the presence of RV dysfunction, a powerful independent predictor of early mortality.2 Whereas cardiac troponins are released as a result of microinfarction due to RV pressure overload, BNP is secreted from cardiac myocytes in response to RV shear …
A directory comparison and manipulation tool

Nowadays file browsers represent a common means to organize hierarchically structured data provided by a file system. However, when it comes to comparing and merging different directory structures, file browsers often do not explicitly support users to accomplish such a task. In this paper, we present a special-purpose approach focusing on the manipulation of directory structures in the context of comparison. To this end, two directory structures including subdirectories and files are displayed side by side while links between them indicate similar files. Drag-and-drop operations allow the users for interactively manipulating or merging both directory structures.
Somatic mutations in salivary duct carcinoma and potential therapeutic targets

Background Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. Results 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p.H1047R: Everolimus), ERBB2 (p.V842I: Lapatinib), HRAS (p.Q61R: Selumetinib) and KIT (p.T670I: Sorafenib). Furthermore, alterations in PTEN, PIK3CA and HRAS that alter response to androgen deprivation therapy and HER2 inhibition were also seen. Materials and Methods Somatic mutation analysis was performed on DNA extracted from 15 archival cases of SDCa using the targeted Illumina TruSeq Amplicon Cancer Panel. Potential targetable genetic alterations were identified using extensive literature and international somatic mutation database (COSMIC, KEGG) search. Immunohistochemistry for androgen receptor and immunohistochemistry and fluorescent in situ hybridization for HER2 were also performed. Conclusions SDCa show multiple somatic mutations, some that are amenable to pharmacologic manipulation and others that confer resistance to treatments currently under investigation. These findings emphasize the need to develop testing and treatment strategies for SDCa.