Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple-dose pharmacokinetics and toleration of intravenously administered cefoperazone and sulbactam when given as single agents or in combination

The multiple-dose pharmacokinetics and toleration of cefoperazone (3 g every 12 h) and sulbactam (1.5 g every 12 h) were studied when these antimicrobial agents were administered continuously over 7 days as a 15-min infusion of individual agents and as a 3/1.5-g cefoperazone-sulbactam combination. Fourteen male volunteers participated in an open, three-way crossover study of Latin Square design with a 1-week washout period between phases. On days 1 and 7 of each phase, serial serum samples and urine were collected for drug assay over a 12-h period. Hematological and clinical chemistry determinations were made within 10 days before the first antibiotic dose and for each treatment phase just before the first dose, on day 4 of treatment, and within 24 h of the last dose. For cefoperazone as a single agent on days 1 and 7, the average maximal concentration in serum (Cmax) was approximately 430 micrograms/ml, the terminal elimination half-life (t1/2) was 1.8 h, and the average percentage of dose excreted unchanged in the urine (%Ur) was 30%. For sulbactam as a single agent, the Cmax was approximately 90 micrograms/ml, the t1/2 was 1 h, and the %Ur was 89% on days 1 and 7. When comparing individual versus simultaneous drug administration, the only pharmacokinetic alteration observed was a statistically significant but minor (about 10%) decrease in sulbactam renal clearance, on both days 1 and 7, resulting in a similar decrease in total body clearance (CL). The area under the curve, apparent volume of distribution by the area method (V), t1/2, and Cmax were not significantly altered. Although cefoperazone pharmacokinetic parameters were not significantly altered when comparing single-agent to combination drug administration, the area under the curve was slightly lower and CL, nonrenal clearance, and V were modestly higher from day 1 to day 7. Because Cmax and t1/2 were unaffected, these minor day effects would not be of clinical significance. Intravenous administration of cefoperazone and sulbactam given as individual agents compared with the combination did not show pharmacokinetic differences that are likely to produce clinically relevant effects. The combination of cefoperazone and sulbactam was well tolerated, and the safety profile of the combination was similar to that either drug given alone under the conditions of this study.
Tracheal extubation

Respiratory complications after tracheal extubation are three times more common than complications occurring during tracheal intubation and induction of anaesthesia (4.6% vs 12.6%). A closed claims analysis of the American Society of Anesthesiologists database revealed that death or brain damage with induction of anaesthesia decreased from 62% of perioperative claims in 1985–1992 to 35% in 1993– 1999. This may reflect widespread adoption of difficult airway guidelines which predominantly address induction of anaesthesia. In contrast, the claims for death or brain damage associated with maintenance, extubation, and recovery remained almost the same. Development of specific airway management plans addressing these periods of risk should improve patient safety. This article reviews the controversies and problems related to emergence and extubation after anaesthesia.
Cyclin D1 Is Expressed in Neoplastic Cells of Langerhans Cell Histiocytosis but Not Reactive Langerhans Cell Proliferations

Langerhans cell histiocytosis (LCH) is characterized by frequent activating mutations involving the mitogen-activated protein kinase (MAPK) pathway. Therefore, downstream markers of MAPK pathway activation such as cyclin D1 may be useful as novel diagnostic markers of neoplasia in LCH. The goal of this study was to investigate cyclin D1 expression in LCH and reactive Langerhans cell accumulations using immunohistochemistry on archival tissue. All LCH cases tested (39/39) showed cyclin D1 expression in CD1a/Langerin+ cells. Most cases (22/39; 56%) showed strong cyclin D1 expression in the majority (≥50%) of lesional cells. Only a few cases (6/39; 15%) showed cyclin D1 expression in a small subset (<20%). Nearly all LCH cases (26/27; 96%) showed p-ERK expression by immunohistochemistry, parallel to cyclin D1 expression. CD1a+ Langerhans cells in all cases of florid dermatopathic lymphadenopathy and normal skin were negative for cyclin D1, as demonstrated by CD1a/cyclin D1 double staining. The majority of skin specimens (14/18; 78%) with dermatitis-related changes did not show cyclin D1 expression in the CD1a+ epidermal Langerhans cell aggregates. A minority (4/18; 22%) showed weak cyclin D1 staining in a small subset (5% to 10%) of CD1a+ Langerhans cells. We conclude that cyclin D1 is ubiquitously expressed in LCH, in keeping with the known near universal MAPK activation in this disease. Further, it is not significantly expressed in reactive Langerhans cell proliferations in lymph node or skin. Therefore, cyclin D1 immunohistochemistry may be useful in excluding non-neoplastic mimics of LCH.
CloudNetSim++: A toolkit for data center simulations in OMNET++

With the availability of low cost, on demand, and pay-as-you-go model based utility computing services offered by clouds, multiple businesses consider moving their services to the cloud. Typically, the clouds comprise of geographically distributed data centers connected through a high speed network. Most of the research and development is focused on cloud services, applications, and security issues; however, very limited effort has been devoted to address energy efficiency, scalability, and high-speed inter and intra-data center communication. We present CloudNetSim++, a modeling and simulation toolkit to facilitate simulation of distributed data center architectures, energy models, and high speed data centers' communication network. The CloudNetSim++ is designed to allow researchers to incorporate their custom protocols and, applications, to analyze under realistic data center architectures with network traffic patterns. CloudNetSim++ is the first cloud computing simulator that uses real network physical characteristics to model distributed data centers. CloudNetSim++ provides a generic framework that allows users to define SLA policy, scheduling algorithms, and modules for different components of data centers without worrying about low level details with ease and minimum effort.
Bargaining and Network Structure: An Experiment

We consider bargaining in a bipartite network of buyers and sellers, who can only trade with the limited number of people with whom they are connected. Such networks could arise due to proximity issues or restricted communication flows, as with information transmission of job openings, business opportunities, and transactions not easily regulated by external authorities. We perform an experimental test of a graph-theoretic model that allows us to decompose any two-sided network into simple networks of three types, with unique predictions about equilibrium prices for the networks in our sessions. We begin with two separate simple networks, which are then joined by an additional link. Participants appear to quickly grasp important characteristics of the networks. The results diverge sharply depending on how this connection is made, typically conforming to the theoretical directional predictions. Payoffs can be systematically affected even for agents who are not connected by the new link. We find strong evidence that shares (publicly) allocated in the past to others in one’s current position substantially and significantly affect what one is willing to accept.
Cellular Automaton Models of Tumor Development: a Critical Review

Cancer development can be viewed as an example of spatio-temporal pattern formation. Several attempts have been made to model and predict malignant tumor behavior and also to account for immune system response and the impact of possible clinical treatments. Modeling started from a macroscopic perspective and developed towards cell-based approaches, from which cellular automaton (CA) models are an example.In this article, we first introduce the general concept of CA systems. Then, we review CA models of tumor development, focusing on avascular and vascular growth, tumor invasion and angiogenesis. Finally, a comparative analysis of the models as well as criteria for designing new CA models are provided and future perspectives are outlined.
Plasma membrane channels formed by connexins: their regulation and functions.

Members of the connexin gene family are integral membrane proteins that form hexamers called connexons. Most cells express two or more connexins. Open connexons found at the nonjunctional plasma membrane connect the cell interior with the extracellular milieu. They have been implicated in physiological functions including paracrine intercellular signaling and in induction of cell death under pathological conditions. Gap junction channels are formed by docking of two connexons and are found at cell-cell appositions. Gap junction channels are responsible for direct intercellular transfer of ions and small molecules including propagation of inositol trisphosphate-dependent calcium waves. They are involved in coordinating the electrical and metabolic responses of heterogeneous cells. New approaches have expanded our knowledge of channel structure and connexin biochemistry (e.g., protein trafficking/assembly, phosphorylation, and interactions with other connexins or other proteins). The physiological role of gap junctions in several tissues has been elucidated by the discovery of mutant connexins associated with genetic diseases and by the generation of mice with targeted ablation of specific connexin genes. The observed phenotypes range from specific tissue dysfunction to embryonic lethality.
Differences in Gene Expression between the Classical and El Tor Biotypes of Vibrio cholerae O1

ABSTRACT Differences in whole-genome expression patterns between the classical and El Tor biotypes of Vibrio cholerae O1 were determined under conditions that induce virulence gene expression in the classical biotype. A total of 524 genes (13.5% of the genome) were found to be differentially expressed in the two biotypes. The expression of genes encoding proteins required for biofilm formation, chemotaxis, and transport of amino acids, peptides, and iron was higher in the El Tor biotype. These gene expression differences may contribute to the enhanced survival capacity of the El Tor biotype in environmental reservoirs. The expression of genes encoding virulence factors was higher in the classical than in the El Tor biotype. In addition, the vieSAB genes, which were originally identified as regulators of ctxA transcription, were expressed at a fivefold higher level in the classical biotype. We determined the VieA regulon in both biotypes by transcriptome comparison of wild-type and vieA deletion mutant strains. VieA predominantly regulates gene expression in the classical biotype; 401 genes (10.3% of the genome), including those encoding proteins required for virulence, exopolysaccharide biosynthesis, and flagellum production as well as those regulated by σE, are differentially expressed in the classical vieA deletion mutant. In contrast, only five genes were regulated by VieA in the El Tor biotype. A large fraction (20.8%) of the genes that are differentially expressed in the classical versus the El Tor biotype are controlled by VieA in the classical biotype. Thus, VieA is a major regulator of genes in the classical biotype under virulence gene-inducing conditions.
S-Scrum: a Secure Methodology for Agile Development of Web Service

To care for security in early stages of software development has always been a major engineering trend. However, due to the existence of unpreventable and accidental security faults within the system, it is not always possible to entirely identify and mitigate the security threats. This may eventually lead to security failure of the target system. To avoid security failure, it is required to incorporate fault tolerance (i.e. intrusion tolerant) into the security requirements of the system. In this paper, we propose a new technique toward description of security requirements of Intrusion Tolerant Systems (ITS) using fuzzy logic. We care for intrusion tolerance in security requirements of the system through considering partial satisfaction of security goals. This partiality is accepted and formally described through establishment of a Goal-Based Fuzzy Grammar (GFG) and its respective Goal-Based Fuzzy Language (GFL) for describing Security Requirement Model (SRM) of the target ITS.
The Microbe-Free Plant: Fact or Artifact?

Plant–microbe interactions are ubiquitous. Plants are threatened by pathogens, but they are even more commonly engaged in neutral or mutualistic interactions with microbes: belowground microbial plant associates are mycorrhizal fungi, Rhizobia, and plant-growth promoting rhizosphere bacteria, aboveground plant parts are colonized by internally living bacteria and fungi (endophytes) and by microbes in the phyllosphere (epiphytes). We emphasize here that a completely microbe-free plant is an exotic exception rather than the biologically relevant rule. The complex interplay of such microbial communities with the host–plant affects multiple vital parameters such as plant nutrition, growth rate, resistance to biotic and abiotic stressors, and plant survival and distribution. The mechanisms involved reach from direct ones such as nutrient acquisition, the production of plant hormones, or direct antibiosis, to indirect ones that are mediated by effects on host resistance genes or via interactions at higher trophic levels. Plant-associated microbes are heterotrophic and cause costs to their host plant, whereas the benefits depend on the current environment. Thus, the outcome of the interaction for the plant host is highly context dependent. We argue that considering the microbe-free plant as the “normal” or control stage significantly impairs research into important phenomena such as (1) phenotypic and epigenetic plasticity, (2) the “normal” ecological outcome of a given interaction, and (3) the evolution of plants. For the future, we suggest cultivation-independent screening methods using direct PCR from plant tissue of more than one fungal and bacterial gene to collect data on the true microbial diversity in wild plants. The patterns found could be correlated to host species and environmental conditions, in order to formulate testable hypotheses on the biological roles of plant endophytes in nature. Experimental approaches should compare different host–endophyte combinations under various relevant environmental conditions and study at the genetic, epigenetic, transcriptional, and physiological level the parameters that cause the interaction to shift along the mutualism–parasitism continuum.
Sensorless control of a doubly fed induction machine based on an Extended Kalman Filter

This paper presents a sensorless control strategy for a doubly fed induction machine, usually used as a generator for wind power. The proposed scheme consists of an Extended Kalman Filter fed by the voltages and currents of the stator and rotor in order to provide an estimation of the speed and position of the rotor. The simulation results prove the scheme's feasibility over a wide range of speed and load.
Dynamic Power Control of a PV-Fuel Cell Hybrid Energy System Used in DC Motors Applications

A control structure for a hybrid renewable energy source tied to a direct current (DC) motor is proposed. The energy system is composed by a Photovoltaic (PV) array as the primary power source and a Fuel-Cell (FC) as an auxiliary or secondary power source. The control system has been developed to guarantee motor speed regulation and maximum power generation of the energy sources under any environmental and load condition, for instance low irradiance levels or a high demand in the load torque. A simulation of the system using real environmental data is presented in this document.
Toward a Tool-Based Development Methodology for Pervasive Computing Applications

Despite much progress, developing a pervasive computing application remains a challenge because of a lack of conceptual frameworks and supporting tools. This challenge involves coping with heterogeneous devices, overcoming the intricacies of distributed systems technologies, working out an architecture for the application, encoding it in a program, writing specific code to test the application, and finally deploying it. This paper presents a design language and a tool suite covering the development life-cycle of a pervasive computing application. The design language allows us to define a taxonomy of area-specific building-blocks, abstracting over their heterogeneity. This language also includes a layer to define the architecture of an application, following an architectural pattern commonly used in the pervasive computing domain. Our underlying methodology assigns roles to the stakeholders, providing separation of concerns. Our tool suite includes a compiler that takes design artifacts written in our language as input and generates a programming framework that supports the subsequent development stages, namely, implementation, testing, and deployment. Our methodology has been applied on a wide spectrum of areas. Based on these experiments, we assess our approach through three criteria: expressiveness, usability, and productivity.
Amyloid-precursor Like Proteins APLP1 and APLP2 Are Dispensable for Normal Development of the Neonatal Respiratory Network

Recent studies using animal models indicated that the members of the amyloid precursor protein (APP) gene family are important for the formation, maintenance, and plasticity of synapses. Despite this, the specific role of the APP homologs APLP1 and APLP2 within the CNS and PNS is still poorly understood. In contrast to the subtle phenotypes of single mutants, double knockout mice (DKO) lacking APP/APLP2 or APLP1/APLP2 die within the first day after birth. Whereas APP/APLP2-DKO mice show severe deficits of neuromuscular morphology and transmission, the underlying cause of lethality of APLP1/APLP2-DKO mice remains unclear. Since expression of both proteins was confirmed by in situ hybridization, we aimed to test the role of APLP1/APLP2 in the formation and maintenance of synapses in the brainstem, and assessed a potential dysfunction of the most vital central neuronal network in APLP1/APLP2-DKO mice by analyzing the respiratory network of the medulla. We performed in vivo unrestrained whole body plethysmography in newborn APLP1/APLP2-DKO mice at postnatal day zero. Additionally, we directly tested the activity of the respiratory network in an acute slice preparation that includes the pre-Bötzinger complex. In both sets of experiments, no significant differences were detected regarding respiratory rate and cycle variability, strongly arguing against central respiratory problems as the primary cause of death of APLP1/APLP2-DKO mice. Thus, we conclude that APLP1 and APLP2 are dispensable for the development of the network and the generation of a normal breathing rhythm.
Nerve growth factor promotes survival of septal cholinergic neurons after fimbrial transections

Several findings obtained in recent years suggest that NGF, aside from its well-established function as a neurotrophic factor for peripheral sympathetic and sensory neurons, also has trophic influence on the cholinergic neurons of the basal forebrain. The present study assessed whether NGF was able to affect survival of central cholinergic neurons after axonal transections in adult rats. The septo-hippocampal pathway was transected unilaterally by cutting the fimbria, and animals were implanted with a cannula through which NGF or control solutions were injected intraventricularly over 4 weeks. The lesions reduced the number of large cell bodies, as visualized by Nissl staining in the medial septal nucleus and in the vertical limb of the diagonal band of Broca. Furthermore, in the same nuclei, they reduced the number of cell bodies positively stained for AChE after pretreatment with diisopropylfluorophosphate (a method known to result in reliable identification of cholinergic neurons in the septal area). On lesioned sides, the number of cholinergic cells in medial septal nucleus and the vertical limb of the diagonal band was reduced by 50 +/- 4%, as compared to the number on contralateral sides. On lesioned sides of animals chronically treated with NGF, the number of AChE-positive cells in these areas was reduced only by 12 +/- 6%, as compared to control levels. These findings suggest that fimbrial transections resulted in retrograde degeneration of cholinergic septo-hippocampal neurons and that NGF treatment strongly attenuated this lesion-induced degeneration. (ABSTRACT TRUNCATED AT 250 WORDS)
Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion.
GeneMerge - Post-genomic Analysis, Data Mining, and Hypothesis Testing

SUMMARY GeneMerge is a web-based and standalone program written in PERL that returns a range of functional and genomic data for a given set of study genes and provides statistical rank scores for over-representation of particular functions or categories in the data set. Functional or categorical data of all kinds can be analyzed with GeneMerge, facilitating regulatory and metabolic pathway analysis, tests of population genetic hypotheses, cross-experiment comparisons, and tests of chromosomal clustering, among others. GeneMerge can perform analyses on a wide variety of genomic data quickly and easily and facilitates both data mining and hypothesis testing. AVAILABILITY GeneMerge is available free of charge for academic use over the web and for download from: http://www.oeb. harvard.edu/hartl/lab/publications/GeneMerge.html.
Half hemispherical DRA array for very large bandwidth high gain and monopole-like radiation pattern

A novel coaxial-fed dielectric resonator antenna is proposed as a wideband uniform radiator having its radiation pattern very similar to an electric monopole. However, compared to electric monopole, the newly proposed antenna shows much larger bandwidth and gain over the entire spectrum. Nearly 40% bandwidth (10 dB return loss) with 4 to 5 dBi gain has been obtained. The design data are generated using Ansoft HFSS code.