Miracle-dz/UniFAR-FTUs huggingface dataset:
The Development of Drotrecogin Alfa (Activated) for the Treatment of Severe Sepsis

Activation of the innate immune system is the first phase of the human response to invading microorganisms (1, 2). In the majority of instances, activation of innate immunity results in a localized inflammatory and procoagulant response that is beneficial in limiting spread of the infection, in clearing pathogens, and in aiding tissue healing (3, 4). However, in a significant number of patients, activation of the immune system is poorly regulated resulting in a systemic inflammatory and procoagulant response that, if left unchecked, is frequently fatal (5, 6). Multiple consensus conferences have attempted to apply acceptable nomenclature to describe serious infection and its sequelae (7, 8). Although some debate still exists, general definitions have emerged for localized infection or infection associated with systemic signs and symptoms (ie, sepsis). Severe sepsis (sepsis associated with acute organ dysfunction) and septic shock (sepsis associated with hypotension) represent the more severe complications of an uncontrolled immune response to infection. Implicit in the definition of severe sepsis is that the associated organ dysfunctions result from the host’s response to infection and are distant from the primary site of infection. Severe sepsis and septic shock are associated with an estimated mortality rate ranging between 30 to 50% and are the most common causes of death in non-coronary intensive care units (9). Activated protein C, an endogenous vitamin K-dependent serine protease, is an important modulator of the host systemic response to severe infection (10). Activated protein C exhibits antithrombotic properties via inhibition of activated Factors V and VIII (11, 12) and pro-fibrinolytic properties via inhibition of plasminogen activator-inhibitor 1 (13, 14). Inhibition of thrombin production results in indirect antiinflammatory properties (15). Additionally, activated protein C may exhibit direct anti-inflammatory and anti-apoptotic (16) properties via interaction with its receptor on the endothelium (17), neutrophil (18), monocyte (19), eosinophil (20), and airway epithelial cells (21). In severe sepsis, circulating levels of protein C (the inactive precursor to activated protein C) are abnormally low (22, 23) and conversion of protein C to activated protein C may be impaired (24). Consequently, disruption of the protein C pathway plays an important role in the pathophysiology of sepsis-associated multiple organ dysfunction. Drotrecogin alfa (activated), a recombinant form of human activated protein C, has been shown to significantly improve survival of adult patients with severe sepsis when added to the best standard of care (23). The following review will summarize the pre-clinical and clinical development of drotrecogin alfa (activated) that led to its approval by regulatory agencies for the treatment of severe sepsis. Information acquired since approval is incorporated to provide insights into potential mechanisms of action of drotrecogin alfa (activated) and insights into the syndrome of severe sepsis.
A new technique to efficiently entrap leuprolide acetate into microcapsules of polylactic acid or copoly(lactic/glycolic) acid.

The aim of this work was to develop injectable microcapsules containing leuprolide acetate, that would deliver that drug at a zero-order rate over a period of about one month. A large amount of leuprolide acetate, a hydrophilic drug, was entrapped into polylactic aicd (PLA) and copoly-(lactic/glycolic) acid (PLGA) microcapsules prepared by an in-water dring method using a (w/o)/w emulsion. The basic techniques were designed to increase the viwcosities of the inner water phase and w/o emulsion. Under the conditions used, it was possible for the drug to be completely entrapped by the microcapsules in the range of 10 to 20% on the basis of the polymer. However, the release profiles of the drug in vitro were inadequate for controlled release for one month.
A Versatile Analytical Expression for the Inverse Abel Transform Applied to Experimental Data with Noise

A method for reconstruction of radially distributed plasma emission coefficients from projections with noise is proposed. The method represents the projections based on overlapping piecewise polynomial least squares fitting to take the inversion. Parameters that affect the inversion accuracy are analyzed and discussed in detail. Results for profiles with various shapes are presented and compared with those obtained with other methods. It is shown that for data with different numbers of points and different levels of noise, our method is more accurate and yields markedly better results for very sparse data. In addition, excellent results have been obtained from experimental intensities of an arc plasma without filtering of noise.
Expression of the Escherichia coli dam methylase in Saccharomyces cerevisiae: effect of in vivo adenine methylation on genetic recombination and mutation

The Escherichia coli DNA adenine methylase (dam) gene has been introduced into Saccharomyces cerevisiae on a yeast-E. coli shuttle vector. Sau3AI, MboI, and DpnI restriction enzyme digests and Southern hybridization analysis indicated that the dam gene is expressed in yeast cells and methylates GATC sequences. Analysis of digests of total genomic DNA indicated that some GATC sites are not sensitive to methylation. The failure to methylate may reflect an inaccessibility to the methylase due to chromosome structure. The effects of this in vivo methylation on the processes of recombination and mutation in mitotic cells were determined. A small but definite general increase was found in the frequency of mitotic recombination. A similar increase was observed for reversion of some auxotrophic markers; other markers demonstrated a small decrease in mutation frequency. The effects on mutation appear to be locus (or allele) specific. Recombination in meiotic cells was measured and was not detectably altered by the presence of 6-methyladenine in GATC sequences.
Effect of Maternal Administration of Betamethasone on Peripheral Arterial Development in Fetal Rabbit Lungs

Objectives: Glucocorticoids promote lung maturation and reduce the incidence of respiratory distress syndrome in premature newborns. We hypothesized that betamethasone (BM), which is known to induce thinning of the alveolar walls, would also thin the arterial media and adventitia of intra-parenchymatic vessels in developing rabbit lungs. Study Design: 112 fetuses from 21 time-mated, pregnant, giant white rabbits received maternal injections of BM at either 0.05 or 0.1 mg/kg/day on days 25–26 of gestational age. Controls received either saline (10 does, 56 fetuses) or no injection (10 does, 59 fetuses). Fetuses were harvested from day 27 onwards until term (day 31). 44 additional fetuses (8 does) were harvested between days 23 and 26. Endpoints were wet lung-to-body weight ratio, vascular morphometric indices and immunohistochemistry staining for α-smooth muscle actin, Flk-1, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). ANOVA (Tukey’s test) and independent t test (p < 0.05) were used for comparison between BM and saline groups. Results: Maternal BM injected on days 25–26 to pregnant rabbits induced a significant decrease in fetal body and lung weight and the lung-to-body weight ratio in the preterm pups shortly after injection. BM led to a dose-dependent thinning of the arterial media and adventitia (pulmonary arteries with an external diameter (ED) of <100 µm), to an increase in the percentage of non-muscularized peripheral vessels (ED <60 µm), in eNOS and VEGF immunoreactivity of the endothelial and smooth muscle cells in the pulmonary vessels and to an increase in Flk-1-positive pulmonary epithelial cell density. Conclusions: Maternal administration of BM caused thinning of the arterial wall of pulmonary vessels (ED <100 µm) and a decrease in muscularization in peripheral vessels (ED <60 µm). This coincided with increased expression of Flk-1 in the endothelium and smooth muscle cells of the pulmonary arteries. All the effects studied were dose-dependent.
Analysis and design of a double tuned Clapp oscillator for multi-band multi-standard radio

This paper reports a wideband Clapp oscillator design using a combination of capacitor banks and a switchable inductor for frequency timing in a 0.5 /spl mu/m SiGe BiCMOS technology. It is found that the performance of this wideband oscillator is adequate for HiperLAN2 and Bluetooth applications.
Ca2+ Homeostasis during Mitochondrial Fragmentation and Perinuclear Clustering Induced by hFis1*[boxs]

Mitochondria modulate Ca2+ signals by taking up, buffering, and releasing Ca2+ at key locations near Ca2+ release or influx channels. The role of such local interactions between channels and organelles is difficult to establish in living cells because mitochondria form an interconnected network constantly remodeled by coordinated fusion and fission reactions. To study the effect of a controlled disruption of the mitochondrial network on Ca2+ homeostasis, we took advantage of hFis1, a protein that promotes mitochondrial fission by recruiting the dynamin-related protein, Drp1. hFis1 expression in HeLa cells induced a rapid and complete fragmentation of mitochondria, which redistributed away from the plasma membrane and clustered around the nucleus. Despite the dramatic morphological alteration, hFis1-fragmented mitochondria maintained a normal transmembrane potential and pH and took up normally the Ca2+ released from intracellular stores upon agonist stimulation, as measured with a targeted ratiometric pericam probe. In contrast, hFis1-fragmented mitochondria took up more slowly the Ca2+ entering across plasma membrane channels, because the Ca2+ ions reaching mitochondria propagated faster and in a more coordinated manner in interconnected than in fragmented mitochondria. In parallel cytosolic fura-2 measurements, the capacitative Ca2+ entry (CCE) elicited by store depletion was only marginally reduced by hFis1 expression. Regardless of mitochondria shape and location, disruption of mitochondrial potential with uncouplers or oligomycin/rotenone reduced CCE by ∼35%. These observations indicate that close contact to Ca2+ influx channels is not required for CCE modulation and that the formation of a mitochondrial network facilitates Ca2+ propagation within interconnected mitochondria.
Characterization of the expression pattern of the PRC2 core subunit Suz12 during embryonic development of Xenopus laevis

The Polycomb repressive complex 2 is a multimeric aggregate that mediates silencing of a broad range of genes, and is associated with important biological contexts such as stem cell maintenance and cancer progression. PRC2 mainly trimethylates lysine 27 of histone H3 and is composed of three essential core subunits: EZH2, EED, and SUZ12. The Xenopus orthologs of PRC2 subunits Ezh2 and Eed have been described but Suz12 remained unidentified. Here, we report the cloning of the Xenopus Suz12, and determine its spatiotemporal expression during development. Xsuz12 transcript is provided maternally and continues to be expressed throughout development, particularly in the anterior part of the developing central nervous system. Importantly, comparative analysis of the expression of the PRC2 subunits Xez, Xeed, and Xrbbp4 indicates that their expression largely coincides with Xsuz12 in the nervous system, suggesting that PRC2 may have unexplored functions in the development of the frog central nervous system. Developmental Dynamics 238:3185–3192, 2009. © 2009 Wiley‐Liss, Inc.
Health monitoring of non-human primate colonies

Recommendations of the Federation of European Laboratory Animal Science Associations (FELASA) Working Group on Non-Human Primate Health accepted by the FELASA Board of Management, 21 November 1998 FELASA Working Group on Non-Human Primate Health: H. Weber (Convenor), E. Berge, J. Finch, P. Heidt, F. -J. Kaup, G. Perretta, B. Verschuere & S. Wolfensohn
Association of Novel and Highly Diverse Acid-Tolerant Denitrifiers with N2O Fluxes of an Acidic Fen

ABSTRACT Wetlands are sources of denitrification-derived nitrous oxide (N2O). Thus, the denitrifier community of an N2O-emitting fen (pH 4.7 to 5.2) was investigated. N2O was produced and consumed to subatmospheric concentrations in unsupplemented anoxic soil microcosms. Total cell counts and most probable numbers of denitrifiers approximated 1011 cells·gDW−1 (where DW is dry weight) and 108 cells·gDW−1, respectively, in both 0- to 10-cm and 30- to 40-cm depths. Despite this uniformity, depth-related maximum reaction rate (vmax) values for denitrification in anoxic microcosms ranged from 1 to 24 and −19 to −105 nmol N2O h−1· gDW−1, with maximal values occurring in the upper soil layers. Denitrification was enhanced by substrates that might be formed via fermentation in anoxic microzones of soil. N2O approximated 40% of total nitrogenous gases produced at in situ pH, which was likewise the optimal pH for denitrification. Gene libraries of narG and nosZ (encoding nitrate reductase and nitrous oxide reductase, respectively) from fen soil DNA yielded 15 and 18 species-level operational taxonomic units, respectively, many of which displayed phylogenetic novelty and were not closely related to cultured organisms. Although statistical analyses of narG and nosZ sequences indicated that the upper 20 cm of soil contained the highest denitrifier diversity and species richness, terminal restriction fragment length polymorphism analyses of narG and nosZ revealed only minor differences in denitrifier community composition from a soil depth of 0 to 40 cm. The collective data indicate that the regional fen harbors novel, highly diverse, acid-tolerant denitrifier communities capable of complete denitrification and consumption of atmospheric N2O at in situ pH.
Deconjugation of bile acids by lactobacilli in the mouse small bowel

Conjugated and unconjugated bile acid concentrations in the small bowel contents and portal serum samples collected from mice with and without lactobacilli (RLFL and RLF, respectively) as gastrointestinal inhabitants were measured. The major portion of bile acids in the small bowel contents of RLFL mice was unconjugated (67.9%) in contrast to that of RFL animals in which a smaller portion of bile acids was unconjugated (23.5%). This study demonstrated that bile salt hydrolase produced by lactobacilli is active under the conditions prevailing in the proximal small bowels of mice.
Connectivity of the anterior insula differentiates participants with first-episode schizophrenia spectrum disorders from controls: a machine-learning study

Background Early diagnosis of schizophrenia could improve the outcomes and limit the negative effects of untreated illness. Although participants with schizophrenia show aberrant functional connectivity in brain networks, these between-group differences have a limited diagnostic utility. Novel methods of magnetic resonance imaging (MRI) analyses, such as machine learning (ML), may help bring neuroimaging from the bench to the bedside. Here, we used ML to differentiate participants with a first episode of schizophrenia-spectrum disorder (FES) from healthy controls based on resting-state functional connectivity (rsFC). Method We acquired resting-state functional MRI data from 63 patients with FES who were individually matched by age and sex to 63 healthy controls. We applied linear kernel support vector machines (SVM) to rsFC within the default mode network, the salience network and the central executive network. Results The SVM applied to the rsFC within the salience network distinguished the FES from the control participants with an accuracy of 73.0% (p = 0.001), specificity of 71.4% and sensitivity of 74.6%. The classification accuracy was not significantly affected by medication dose, or by the presence of psychotic symptoms. The functional connectivity within the default mode or the central executive networks did not yield classification accuracies above chance level. Conclusions Seed-based functional connectivity maps can be utilized for diagnostic classification, even early in the course of schizophrenia. The classification was probably based on trait rather than state markers, as symptoms or medications were not significantly associated with classification accuracy. Our results support the role of the anterior insula/salience network in the pathophysiology of FES.
Acute Coronary Syndrome and Cardiogenic Shock: Management in the Cardiac Catheterization Laboratory

Cardiogenic shock remains a serious syndrome associated with high rates of mortality. A variety of conditions can lead to cardiogenic shock and early recognition with prompt initiation of support is prudent. Initial therapy of cardiogenic shock often begins in the cardiac catheterization laboratory, but frequently, additional care is required in the operating room (OR) by surgeons and anesthesiologists. Cardiogenic shock is defined as inadequate cardiac output (CO) to meet tissue perfusion, despite the presence of adequate intravascular volume. The hemodynamic criteria for cardiogenic shock include: sustained hypotension (systolic blood pressure <90 mm Hg for at least 30 min), a reduced cardiac index (< 2.2 L/min/m), and an elevated pulmonary capillary wedge pressure (PCWP) (> 15 mm Hg). Key factors in the management of acute heart failure syndromes and cardiogenic shock in the catheterization laboratory include identification of etiology and assessment of hemodynamic stability. Common causes of
A perturbation of multimodal GABA functions underlying the formation of focal cortical malformations: Assessments by using animal models

In order to study how the formation of focal cortical malformations is attributed to perturbation of developmentally multimodal γ‐aminobutyric acid (GABA) functions, we made a focal cortical freeze‐lesion on a rodent cerebral cortex at P0 (postnatal day 0). The microgyrus was formed at P7. GABA neurons were accumulated in the region surrounding necrosis at P4. Cortical plate cells born at E17.5 gathered, surrounding the GABA neurons, forming the cell dense portions in layer 2 of the microgyrus. Ambient GABA level was increased in the area corresponding to populated GABA neurons at P4. A KCC2 expression was downregulated, whereas an NKCC1 expression was upregulated in both the gathering GABA and cortical plate neurons, suggesting these cells had high intracellular Cl− concentration rendering GABA action depolarizing. GABAA receptor activation was involved in Ca2+ oscillation in these gathering cells. In vivo blockade of GABAA receptor prevented the above characteristic pattern of cell accumulation and hence microgyrus formation. Thus, neonatal freeze‐lesion causes characteristic accumulation of differential populations of neurons preceded by characteristic release of GABA at an early stage, which induces GABAA receptor‐mediated depolarization and Ca2+ oscillation. This paracrine/autocrine GABA may underlie the formation of neocortical malformations such as polymicrogyria.
Plasma amyloid-β levels are significantly associated with a transition toward Alzheimer's disease as measured by cognitive decline and change in neocortical amyloid burden.

BACKGROUND We evaluated the utility of longitudinal measures of plasma amyloid-β (Aβ) as a means to identify pre-symptomatic cognitive decline in Alzheimer's disease (AD) when coupled to neuroimaging and neuropsychological parameters. METHODS Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were grouped based upon cognitive change and changes in measurable levels of neocortical amyloid over 36 months. Participants were classified as those who transitioned for cognitive decline and change in neocortical amyloid, those healthy controls that did not transition, and stable AD participants over 36 months. RESULTS Comparisons of plasma Aβ levels between the transition and non-transitional groups showed Aβ1-42 and the Aβ1-42/Aβ1-40 ratio were significantly decreased at baseline (p = 0.008 and p = 0.002, respectively) and at 18 months (p = 0.003 and p = 0.004, respectively). Both measures of neocortical amyloid and two previously published composite scores validated the creation of the novel transitional grouping (p < 0.0001). In addition Aβn-42 performed well as a longitudinal prognostic indicator of transition toward cognitive decline, with a significant decrease in the transition group at the 18 month time point (p = 0.01). CONCLUSION We demonstrated that baseline plasma Aβ1-42 and the Aβ1-42/Aβ1-40 ratio were putative biomarkers indicative of cognitive decline and validated this result using 18 month data. We created a novel transitional grouping and validated this measure using published measures of neocortical amyloid and composite memory scores. These findings suggest that longitudinal plasma Aβ could contribute to a pre-symptomatic biomarker panel for AD.
Exploiting symbolic techniques within genetic algorithms for power optimization

Proposes an optimization algorithm for reducing the power dissipation in a sequential circuit. The encoding of the different states in a finite-state machine is modified to obtain a functionally equivalent circuit that exhibits a reduced power dissipation. The algorithm is based on a newly-proposed power estimation function that is able to quickly give an accurate estimate of the dissipated power without actually synthesizing the circuit. Given this estimate, a genetic algorithm provides a state re-encoding for the circuit. The estimation function is computed in a very efficient way by exploiting some symbolic computations with binary decision diagrams. The algorithm is experimentally shown to provide good results from the power optimization point of view, at a limited cost in terms of area increase, when compared with similar approaches.
Personality Inventory for DSM-5–Short Form (PID-5-SF): Reliability, Factorial Structure, and Relationship With Functional Impairment in Dual Diagnosis Patients

Section III of the Diagnostic and Statistical Manual of Mental Disorders–Fifth edition (DSM-5) has generated a personality paradigm consisting of 25 personality facets identified in five domains. The developed assessment instrument Personality Inventory for DSM-5 (PID-5) has showed good psychometric properties, but the potential for certain improvements still remain. In this article, a sample of 282 dual diagnosis patients is used to provide evidence of the psychometric properties of the PID-5–Short Form. The mean value of Cronbach’s alpha coefficients reached . 73 on the facets and . 84 for domains and test–retest values ranged between . 57 to . 83 for facets and . 70 to . 87 for the domains. Confirmatory factor analyses conducted showed good fit on both models tested: the five correlated factor structure and hierarchical structure of personality traits. The WHODAS 2.0 domains of understanding and communicating, and participating in society, appear to show the strongest relationship with personality facets. In general, the PID-5–Short Form shows adequate psychometric properties for use in dual diagnosis patients.