Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic-pharmacodynamic modeling of the anticonvulsant and electroencephalogram effects of phenytoin in rats.

In this study a pharmacokinetic-pharmacodynamic model is proposed for drugs with nonlinear elimination kinetics. We applied such an integrated approach to characterize the pharmacokinetic-pharmacodynamic relationship of phenytoin. In parallel, the anticonvulsant effect and the electroencephalogram (EEG) effect were used to determine the pharmacodynamics. Male Wistar-derived rats received a single intravenous dose of 40 mg . kg-1 phenytoin. The increase in the threshold for generalized seizure activity (TGS) was used as the anticonvulsant effect and the increase in the total number of waves in the 11.5 to 30 Hz frequency band was taken as the EEG effect measure. Phenytoin pharmacokinetics was described by a saturation kinetics model with Michaelis-Menten elimination. Vmax and Km values were, respectively, 386 +/- 31 microg . min-1 and 15.4 +/- 2.2 microg . ml-1 for the anticonvulsant effect in the cortical stimulation model and 272 +/- 31 microg . min-1 and 5.9 +/- 0.7 microg . ml-1 for the EEG effect. In both groups, a delay to the onset of the effect was observed relative to plasma concentrations. The relationship between phenytoin plasma concentrations and effect site was estimated by an equilibration kinetics routine, yielding mean ke0 values of 0.108 and 0.077 min-1 for the anticonvulsant and EEG effects, respectively. The EEG changes in the total number of waves could be fitted by the sigmoid Emax model, but Emax values could not be estimated for the nonlinear relationship between concentration and the increase in TGS. An exponential equation (E = E0 + Bn . Cn) derived from the sigmoid Emax model was applied to describe the concentration-anticonvulsant effect relationship, under the assumption that Emax values cannot be reached within acceptable electric stimulation levels. This approach yielded a coefficient (B) of 2.0 +/- 0.4 microA . ml . microg-1 and an exponent (n) of 2.7 +/- 0.9. The derived EC50 value of 12.5 +/- 1. 3 microg . ml-1 for the EEG effect coincides with the "therapeutic range" in humans.
Molecular Systems Biology Peer Review Process File Inflating Bacterial Cells by Increased Protein Synthesis Transaction Report

(Note: With the exception of the correction of typographical or spelling errors that could be a source of ambiguity, letters and reports are not edited. The original formatting of letters and referee reports may not be reflected in this compilation.) Thank you again for submitting your work to Molecular Systems Biology. We have now heard back from the three referees who agreed to evaluate your manuscript. Overall, the referees acknowledge that the presented findings seem potentially interesting. However, they raise a series of concerns, which should be carefully addressed in a revision of the manuscript. As you will see from the reports below, reviewers #1 and #2 are cautiously positive and mostly raise relatively minor issues (i.e. related to text modification and providing clarifications throughout the manuscript). However, reviewer #3 is more critical and refers to the need to apply the presented observations for deriving new conclusions (i.e. in the context of the "threshold initiation model of bacterial cell-size control"), in order to enhance the overall impact of the study. In line with the comments of the reviewers, we think that the text should be carefully rewritten in order to make the main findings/conclusions more easily accessible to the reader. Moreover, some of the key experimental data should be moved from the Supplement into the main figures. If you feel you can satisfactorily deal with these points and those listed by the referees, you may wish to submit a revised version of your manuscript. Please attach a covering letter giving details of the way in which you have handled each of the points raised by the referees. A revised manuscript will be once again subject to review and you probably understand that we can give you no guarantee at this stage that the eventual outcome will be favorable.
Subcellular localization and some properties of lipoxygenase activity in human blood platelets.

Lipoxygenase activity was measured in human platelet subcellular fractions. From a sonicated platelet preparation, a granule fraction, mixed membranes (surface and intracellular) and cytosol fractions were separated by differential centrifugation. With respect to activities in the sonicated preparation, the lipoxygenase was slightly enriched in both the cytosol and mixed-membrane fractions and consistently de-enriched in the granule fractions. Approx. 65% and 20% of the total cell enzyme activity were found in the cytosol and mixed membranes respectively, with only 8% present in the granule fraction. Additionally we measured the lipoxygenase activity in purified surface- and intracellular-membrane subfractions prepared from the mixed membranes by free-flow electrophoresis. There was a slight enrichment in activity in the intracellular membrane fraction compared with that in the mixed membranes, and a depletion of activity in the surface membranes. Characterization of the enzyme activity, i.e. time course, pH-dependence, Ca2+-dependence, Vmax. and Km for arachidonic acid, and the carbon-position specificity for this acid, failed to reveal any significant differences between the membrane-bound and soluble forms of the lipoxygenase. These findings suggest that in human platelets the same lipoxygenase is associated with the membranes as in the cytosol and that the membrane-bound activity predominates in intracellular membrane elements.
Optimization of thin n-in-p planar pixel modules for the ATLAS upgrade at HL-LHC

The ATLAS experiment will undergo around the year 2025 a replacement of the tracker system in view of the high luminosity phase of the LHC (HL-LHC) with a new 5-layer pixel system. Thin planar pixel sensors are promising candidates to instrument the innermost region of the new pixel system, thanks to the reduced contribution to the material budget and their high charge collection efficiency after irradiation. The sensors of 50-150 μm thickness, interconnected to FE-I4 read-out chips, have been characterized with radioactive sources and beam tests. In particular active edge sensors have been investigated. The performance of two different versions of edge designs are compared: the first with a bias ring, and the second one where only a floating guard ring has been implemented. The hit efficiency at the edge has also been studied after irradiation at a fluence of 1015 neq/cm2. Highly segmented sensors will represent a challenge for the tracking in the forward region of the pixel system at HL-LHC. In order to reproduce the performance of 50x50 μm2 pixels at high pseudo-rapidity values, FE-I4 compatible planar pixel sensors have been studied before and after irradiation in beam tests at high incidence angles with respect to the short pixel direction. Results on the hit efficiency in this configuration are discussed for different sensor thicknesses.
Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews.

G197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on disease expression. Index cases from Israel (n=46), South Africa (n=24), Russia (n=7), The Netherlands (n=1), and the United States (n=1) were enlisted. All trace their ancestry to Lithuania. A highly conserved haplotype (D19S221:104-D19S865:208-D19S413:74) was identified in G197del chromosomes, suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the deletion was found to be 20 +/- 7 generations (the 95% confidence interval is 15-26 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 14th century. This corresponds with the founding of the Jewish community of Lithuania (1338 a.d.), as well as with the great demographic expansion of AJ individuals in eastern Europe, which followed this settlement. The penetrance of mutation-linked severe hypercholesterolemia is high (94% of heterozygotes have a baseline concentration of LDL cholesterol (LDL-C) that is >160 mg/dl), and no significant differences in the mean baseline lipid level of G197del carriers from different countries were found. Polymorphisms of apolipoprotein E and of scavenger-receptor class B type I were observed to have minor effects on the plasma lipid profile. With respect to determinative genetic influences on the biochemical phenotype, there is no evidence that could support the possibility of a selective evolutionary metabolic advantage. Therefore, the founder effect in a rapidly expanding population from a limited number of families remains a simple, parsimonious hypothesis explaining the spread of G197del-LDLR-linked FH in AJ individuals.
Determination of baseline Widal titre among apparently healthy population in Dehradun City

Present study was conducted to determine the baseline widal titer of healthy population of Dehradun city. A total of 300 serum samples were collected from healthy individual with no history of fever and who had not received any vaccination for enteric fever. Tube agglutination test was done with commercially available antigens which contained the Salmonella enterica serovar typhi O and H antigens, the Salmonella enterica serovar paratyphi AH antigen and paratyphi BH antigen. In the present study an agglutination titer for TO - 1:20 is 28%, for 1:40 is 24%, followed by 1:80 and 1: 160 which is 10%, 4% respectively. The highest sample with an anti-H titre found with 1:20 (22%) followed by 1:40(17%). Based upon the results of the study it has been recommended that a single Widal can be significant in an endemic region when higher titre (1:160) is obtained. I. INTRODUCTION Enteric fever is endemic in developing country like India and it continues to be one of the major health problem here (1). Typhoid fever is a systemic infection which is caused by the bacterium, Salmonella enterica serotype typhi. This highly adapted human specific pathogen has evolved remarkable mechanism for its persistence in its host that helps the organism to ensure its survival and transmission(2). Enteric fever afflicts the local community and the travelers to the endemic areas. The incidence tends to be rise during the rainy season due to water logging and contamination of the water with sewage. The social factors that add to the enigma are the pollution of the drinking water supplies due to open air defecation, urination, contaminated food, personal hygiene, habits and poor health practices. The definite diagnosis of enteric fever in the patients with a compatible clinical picture is made on the basis of isolation of the Salmonella from blood, bone marrow, stool or urine and demonstration of the 4 fold rise in the antibody titer to both O and the H antigen of the organism between the acute and the convalescent phase (3). In developing countries, facilities for isolation and culture are often not available especially in smaller hospitals, and diagnosis relies upon the clinical features of the disease and detection of agglutinating antibodies to S. typhi and S. paratyphi by Widal test. Classically four-fold rise of antibody in paired sera is considered diagnostic of typhoid fever (4). But paired sera are often difficult to obtain and specific chemotherapy has to be instituted on the basis of a single Widal test (5). The aim of the present study was to determine the baseline titer of healthy population of Dehradun city.
Indoor and outdoor parametrized gait execution with modular snake robots

This video shows the mechanical structure, module length possibilities, skin options and some of the locomotion capabilities, including indoor and outdoor demonstrations of parametrized gaits for a modular snake robot, used to research at Pontificia Universidad Javeriana by the Systems, Intelligence, Robotics and Perception Research group (SIRP).
Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin

ABSTRACT Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. IMPORTANCE Dengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Moreover, we observed a direct correlation with the concentration of MBL in human serum and neutralization of DENV infection. Our studies suggest that common genetic polymorphisms that result in disparate levels and function of MBL in humans may impact DENV infection, pathogenesis, and disease severity. Dengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation, neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Moreover, we observed a direct correlation with the concentration of MBL in human serum and neutralization of DENV infection. Our studies suggest that common genetic polymorphisms that result in disparate levels and function of MBL in humans may impact DENV infection, pathogenesis, and disease severity.
Singular Isothermal Disks. II. Nonaxisymmetric Bifurcations and Equilibria

We review the difficulties of the classical fission and fragmentation hypotheses for the formation of binary and multiple stars. A crucial missing ingredient in previous theoretical studies is the inclusion of dynamically important levels of magnetic fields. As a minimal model for a candidate precursor to the formation of binary and multiple stars, we therefore formulate and solve the problem of the equilibria of isopedically magnetized, singular isothermal disks, without the assumption of axial symmetry. Considerable analytical progress can be made if we restrict our attention to models that are scale-free, i.e., that have surface densities that vary inversely with distance ϖ from the rotation axis of the system. In agreement with earlier analysis by Syer & Tremaine, we find that lopsided (M = 1) configurations exist at any dimensionless rotation rate, including zero. Multiple-lobed (M = 2, 3, 4,…) configurations bifurcate from an underlying axisymmetric sequence at progressively higher dimensionless rates of rotation, but such nonaxisymmetric sequences always terminate in shock waves before they have a chance to fission into M = 2, 3, 4,… separate bodies. On the basis of our experience in this paper and the preceding Paper I, we advance the hypothesis that binary and multiple star formation from smooth (i.e., not highly turbulent) starting states that are supercritical but in unstable mechanical balance requires the rapid (i.e., dynamical) loss of magnetic flux at some stage of the ensuing gravitational collapse.
Collaborative memory in a serial combination procedure

This article describes a new approach for studying collaborative memory that examines people's editing processes for naturally occurring memory errors. In this approach, memories of individuals are combined via a chaining method in which each participant indirectly receives information from the previous participant. Participants were asked to individually study word lists and recall as many words as possible in an online setting. Once a participant completed the recall task, his/her answers were provided for the next participant as suggested answers for their own recall. However, that participant was allowed to add or subtract words from the provided list of suggested answers. The final answer of the group was an aggregate of recalled words based on the answer given by the last participant in the chain. Results showed that participants displayed a very high accuracy of recall throughout the chain, although they were not able to replicate the entire study list or eliminate all errors by the end of the chain. This procedure has the advantage that it allows examination of the memory-editing processes individuals utilise when they communicate information indirectly, independent from social factors that arise in face-to-face group memory settings.
New evidence for Kuroshio inflow and deepwater circulation in the Okinawa Trough, East China Sea: Sedimentary mercury variations over the last 20 kyr

The evolution of the Kuroshio Current (KC) in the Okinawa Trough (OT) has long been of paleoceanographic interest and has been the focus of many investigations because of its large impacts on both the ocean environment and the climate in East Asia. Here, we present a new high-resolution mercury (Hg) record from the OT sediments that provides robust evidence for the glacial-interglacial variabilities of KC inflow. The Hg levels are anomalously high in the Holocene deposits, which feature a large and abrupt Hg increase at ~9.6 ka and a significant drop at 4.5–3.2 ka. Our observations show that most Hg was derived from seafloor hydrothermal plumes via active lateral transportation. Thus, the generally high Hg levels since ~9.6 ka are associated with enhanced basin-wide deep-water circulation triggered by the KC inflow. This driving mechanism for the deposition and widespread of Hg is also evidenced by an abrupt drop in Hg levels during the late Holocene neoglacial cold period (~5–3 ka) when the KC inflow was temporarily interrupted and deep-water circulation was consequently weak or even absent in the OT. The changes in sedimentary Hg appear to be synchronous with those in other geochemical proxies that suggest that bottom water conditions switched from anoxic to oxic due to increased upwelling from the bottom in tandem with the strengthening KC and reduced freshwater effect since ~9.6 ka. This study shows that the hydrothermal Hg is a sensitive and independent tool for the reconstruction of palaeo-dynamics of KC in the OT.
Complexity in geometric SINR

In this paper we study the problem of scheduling wireless links in the geometric SINR model, which explicitly uses the fact that nodes are distributed in the Euclidean plane. We present the first NP-completeness proofs in such a model. In particular, we prove two problems to be NP-complete: Scheduling and One-Shot Scheduling. The first problem consists in finding a minimum-length schedule for a given set of links. The second problem receives a weighted set of links as input and consists in finding a maximum-weight subset of links to be scheduled simultaneously in one shot. In addition to the complexity proofs, we devise an approximation algorithm for each problem.
Sensory recovery of the reverse homodigital island flap in fingertip reconstruction: a review of 66 cases.

OBJECTIVES The location of the fingertip entitles it to have significant cosmetic and functional values, but also places it at high risk for injury. During repair, finger length and function should be maintained, and stiffness and neuroma should be avoided. Various flaps have been described for reconstruction of distal finger defects with bone, tendon, or joint exposures, including reverse flow homodigital island flap. In this study, we present our experience of reverse flow homodigital island flap in terms of sensory recovery. METHODS Sixty-six patients (70 fingers) with fingertip amputations were included in the study. Patients were treated with homodigital island flaps. All patients underwent sensitivity assessment by 2-point discrimination and Semmes-Weinstein monofilament tests at 6, 12, and 18 months during follow-up, and complications were recorded. RESULTS Monofilament testing results were normal in 64 fingers (91.4%), and diminished light touch was found in six fingers. Two-point discrimination results were normal (<6 mm) in 40 fingers and fair (6-10 mm) in 30 fingers (mean 5.7 mm, range 4-9 mm). Complications included one partial flap necrosis, three flexion contractures, and two neuromas. CONCLUSION In repair of injuries to areas in which sensory feedback is critical, such as the index finger, the homodigital flap may be the treatment of choice.
The projectron: a bounded kernel-based Perceptron

We present a discriminative online algorithm with a bounded memory growth, which is based on the kernel-based Perceptron. Generally, the required memory of the kernel-based Perceptron for storing the online hypothesis is not bounded. Previous work has been focused on discarding part of the instances in order to keep the memory bounded. In the proposed algorithm the instances are not discarded, but projected onto the space spanned by the previous online hypothesis. We derive a relative mistake bound and compare our algorithm both analytically and empirically to the state-of-the-art Forgetron algorithm (Dekel et al, 2007). The first variant of our algorithm, called Projectron, outperforms the Forgetron. The second variant, called Projectron++, outperforms even the Perceptron.