gebhart/patrepeval huggingface dataset:
Survival, bacterial clearance and thrombocytopenia are improved in polymicrobial sepsis by targeting nuclear transport shuttles (2017)

The rising tide of sepsis, a leading cause of death in the US and globally, is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments. Severe microvascular injury and multiple organ failure in sepsis are attributed to a "genomic storm" resulting from changes in microbial and host genomes encoding virulence factors and endogenous inflammatory mediators, respectively. This storm is mediated by stress-responsive transcription factors that are ferried to the nucleus by nuclear transport shuttles importins/karyopherins. We studied the impact of simultaneously targeting two of these shuttles, importin alpha 5 (Imp α5) and importin beta 1 (Imp β1), with a cell-penetrating Nuclear Transport Modifier (NTM) in a mouse model of polymicrobial sepsis. NTM reduced nuclear import of stress-responsive transcription factors nuclear factor kappa B, signal transducer and activator of transcription 1 alpha, and activator protein 1 in liver, which was also protected from sepsis-associated metabolic changes. Strikingly, NTM without antimicrobial therapy improved bacterial clearance in blood, spleen, and lungs, wherein a 700-fold reduction in bacterial burden was achieved while production of proinflammatory cytokines and chemokines in blood plasma was suppressed. Furthermore, NTM significantly improved thrombocytopenia, a prominent sign of microvascular injury in sepsis, inhibited neutrophil infiltration in the liver, decreased L-selectin, and normalized plasma levels of E-selectin and P-selectin, indicating reduced microvascular injury. Importantly, NTM combined with antimicrobial therapy extended the median time to death from 42 to 83 hours and increased survival from 30% to 55% (p = 0.022) as compared to antimicrobial therapy alone. This study documents the fundamental role of nuclear signaling mediated by Imp α5 and Imp β1 in the mechanism of polymicrobial sepsis and highlights the potential for targeting nuclear transport as an adjunctive therapy in sepsis management.
Design and implementation of a gateway for Web-based interaction and management of embedded devices (2009)

Embedding and integrating wireless sensor networks into the Web is ongoing research with many problems to be resolved. Although the Web by design provides scalability, extensibility and evolvability, we cannot directly apply these features to legacy sensor networks. Sensors and embedded devices have constrained resources in terms of CPU, memory and computational power, possibly interact in mobile environments, and most of the times they are not Web-enabled. Many solutions have been proposed and existing middlewares come up with promising ideas and concepts. Despite that fact, we think that no current solution properly integrates with the design principles of the Web. We therefore present the smart gateway A framework that simplifies the integration of sensors and wireless sensor networks into the Web. The smart gateway helps rapid development and deployment of Web-mash-ups from existing sensor resources. The smart gateway represents physical devices with existing Web technology, giving access and control to low-level devices to anyone through the Web browser. By implementing a device abstraction that allows to integrate any kind of device, we enrich the Web with first class citizens capable to sense and interact with the real world. The smart gateway therefore provides the first building blocks to empower users to create the next generation of the World Wide Web, namely the vision of the Web of Things.
Effect of Distance between Homologous Sequences and 3′ Homology on the Frequency of Retroviral Reverse Transcriptase Template Switching (1999)

Deletion of direct repeats in retroviral genomes provides an in vivo system for analysis of reverse transcriptase (RT) template switching. The effect of distance between direct repeats on the rate of deletion was determined for 16 murine leukemia virus (MLV)-based vectors containing a 701-bp direct repeat of overlapping fragments of the herpes simplex virus thymidine kinase gene (HTK). The direct repeats were separated by spacer fragments of various lengths (0.1 to 3.5 kb). Southern analysis of infected cells after one replication cycle indicated that all vectors in which the distance between homologous sequences was >1,500 bp deleted at very high rates (>90%). In contrast, vectors containing <1,500 bp between homologous sequences exhibited lower frequencies of deletion (37 to 82%). To analyze the pattern of locations at which RT switched templates, restriction site markers were introduced to divide the downstream direct repeat into five regions. RT switched templates within all five regions of the 701-bp direct repeat and the frequency of template switching was greater within the 5' regions in comparison to the 3' regions. The probability of RT switching templates within the 5' regions doubled when the MLV packaging sequence (Psi) was placed between the 701-bp direct repeats. However, Psi did not increase the rate of template switching for shorter direct repeats. These results indicate that linear distance between homologous sequences increases the rate of template switching and suggest that duplex formation between nascent DNA and homologous template sequences 3' of RT promote template switching.
Simultaneous Determination of Hydrochlorothiazide and Valsartan in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry (2008)

Abstract A rapid and specific liquid chromatography/tandem mass spectrometry method was described for the simultaneous determination of hydrochlorothiazide and valsartan in human plasma. After extracted from plasma using methanol, hydrochlorothiazide, valsartan and hydroflumethiazide, irbesartan, used as the internal standard, respectively, were chromatographically analyzed on a Phenomenex Kromasil C8 column with water and methanol (27:73, v/v) as the mobile phase. Selected reaction monitoring was specific for mass detection employing negative electrospray ionization. The calibration standards were linear over the concentration range (3.13–800 ng/ml for hydrochlorothiazide and 11.72–3000 ng/ml for valsartan). The method was found to be suitable for application to a pharmacokinetic study after oral administration of dispersible tablet containing 12.5 mg hydrochlorothiazide and 80 mg valsartan to 20 healthy volunteers.
A Theoretical Model for Designing Modified Atmosphere Packaging with a Perforation (1996)

A theoretical model based on the kinetic molecular theory of gases for predicting gas exchange through a polymeric film with a perforation was developed, and its feasibility for design of modified atmosphere packaging (MAP) systems was discussed. Simulated gas flux through perforations was closely approximated to experimental data at three levels of temperature and under two types of initial gas conditions. Changes in the gas compositions in polymeric pouches with a perforation was fairly predicted using the proposed model. Atmospheric changes in MAP systems with perforations for two kinds of fresh produce were also predicted very well by the proposed equations. The model proposed in the present study was valid for the design of MAP systems.
Antimicrobial activity of silver‐containing dressings on wound microorganisms using an <i>in vitro </i>biofilm model (2007)

Antimicrobial dressings such as those containing silver are now being used widely to control wound bioburden, and tests to demonstrate their efficacy predominantly involve in vitro models using free-living or planktonic bacteria. In this present study a wide range of antibiotic-sensitive and resistant bacteria were tested in their quasi-sessile state using a standard agar assay and a second method used a poloxamer gel (true biofilm state - poloxamer encourages microorganisms to exhibit a more clinically relevant biofilm phenotype) technique. The antimicrobial activity of two silver dressings, a silver-containing Hydrofiber (SCH) dressing and a nanocrystalline silver-containing dressing (NCS), were evaluated on a variety of microorganisms, using a zone-of-inhibition (ZOI) test. When grown on agar (presenting a quasi-sessile state of each organism), the antibiotic-susceptible microorganisms were generally more susceptible to the SCH dressing compared with the NCS. ZOIs associated with SCH dressing ranged between 5.7 and 17.5 mm; those for the NCS against the same group of organisms ranged between 1.9 and 8.6 mm. When grown on poloxamer gel, (presenting the biofilm state of each organism) the same group of microorganisms were less susceptible to both dressings. The SCH dressing was most effective against strains of Pseudomonas aeruginosa, Candida albicans and Staphylococcus aureus (ZOI range: 2.6-6 mm); the NCS was most effective against strains of Klebsiella pneumoniae, Enterococcus faecalis and Escherichia coli (i.e. ZOI range: 1-2.8 mm). Similarly to the antibiotic-susceptible microorganisms, nine of ten antibiotic-resistant bacterial strains when grown on agar were more susceptible to the SCH dressing compared with the NCS. Although the microorganisms tested were universally less susceptible to the silver dressings when in their biofilm state, in the majority of cases, the SCH dressing demonstrated greater biofilm-inhibiting activity than the NCS.
Increasing the Reactivity of an Artificial Dithiol−Disulfide Pair through Modification of the Electrostatic Milieu (2005)

The thiol-disulfide exchange reaction plays a central role in the formation of disulfide bonds in newly synthesized proteins and is involved in many aspects of cellular metabolism. Because the thiolate form of the cysteine residue is the key reactive species, its electrostatic milieu is thought to play a key role in determining the rates of thiol disulfide exchange reactions. While modest reactivity effects have previously been seen in peptide model studies, here, we show that introduction of positive charges can have dramatic effects on disulfide bond formation on a structurally restricted surface. We have studied properties of vicinal cysteine residues in proteins using a model system based on redox-sensitive yellow fluorescent protein (rxYFP). In this system, the formation of a disulfide bond between two cysteines Cys149 and Cys202 is accompanied by a 2.2-fold decrease in fluorescence. Introduction of positively charged amino acids in the proximity of the two cysteines resulted in an up to 13-fold increase in reactivity toward glutathione disulfide. Determination of the individual pK(a) values of the cysteines showed that the observed increase in reactivity was caused by a decrease in the pK(a) value of Cys149, as well as favorable electrostatic interactions with the negatively charged reagents. The results presented here show that the electrostatic milieu of cysteine thiols in proteins can have substantial effects on the rates of the thiol-disulfide exchange reactions.
Correlation between neural release of VIP and adrenomedullary catecholamine secretion in vivo (1995)

The aim of the present study was to determine whether vasoactive intestinal peptide (VIP) can be released along with catecholamines from the adrenal gland in response to direct splanchnic nerve stimulation in anesthetized dogs. An attempt was made to verify whether VIP was released mainly from chromaffin cells or from the splanchnic nerve terminals. The first group received a supramaximal stimulation (12 V) given on the left splanchnic nerve at three successive frequencies of 0.2, 2, and 20 Hz. The second group received increasing doses of 1,1-dimethyl-4-phenylpiperazinium (DMPP) locally infused into the denervated left adrenal gland. In response to nerve stimulation, adrenal venous catecholamine concentration significantly increased in a frequency-dependent manner, whereas VIP-like immunoreactive substance (VIP-ir) reached a significant level only at the highest frequency. The multiple linear regression analyses revealed that the net increases in adrenal venous catecholamine concentrations were strongly correlated with combined variables of VIP-ir concentration and frequencies, indicating r = 0.915 and 0.949 (n = 42, P < 0.0001) for epinephrine and norepinephrine concentrations, respectively. In response to local DMPP infusion, adrenal venous catecholamines increased in a dose-dependent manner, whereas VIP-ir remained unchanged. The results indicate that VIP-ir is released along with catecholamines from the dog adrenal gland in response to direct splanchnic nerve stimulation in vivo. The study also suggests that VIP is mainly released from splanchnic nerve endings.
Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. (1990)

The aim of this study was to evaluate the clinicopathological spectrum of eosinophilic gastroenteritis and identify possible difficulties in establishing the diagnosis. All patients with a diagnosis of eosinophilic gastroenteritis, defined by the presence of gastrointestinal symptoms and eosinophilic infiltration of the gut (38), or a radiological diagnosis with peripheral eosinophilia (two), were identified from the Mayo Clinic records; in none was there evidence of extraintestinal disease. Patients were divided into three groups according to the Klein classification: predominant mucosal (23), muscular (12), or subserosal disease (five). A fourth group of patients (10) for comparison had abdominal symptoms and unexplained peripheral eosinophilia but no proven eosinophilic infiltration of the gut. It was found that a history of allergy was reported by 20 of 40 patients with eosinophilic gastroenteritis. Peripheral eosinophilia was absent in nine of 40. The patients with subserosal disease were distinct from the other groups in presentation (abdominal bloating, ascites), higher eosinophil counts and in their dramatic responses to steroid therapy. Otherwise the patients were similar regarding demographic factors, presenting symptoms (abdominal pain, nausea, weight loss, diarrhoea), and laboratory parameters. The ESR was moderately raised in 10 of 40 patients. The disease may affect any area of the gastrointestinal tract; eosinophilic infiltration was documented in the oesophagus in one patient and in the colon in two cases. Endoscopic biopsies missed the diagnosis in five of 40 presumably because of patchy disease. Eosinophilic gastroenteritis should be considered in the differential diagnosis of unexplained gastrointestinal symptoms even in the absence of peripheral eosinophilia.
Hypervisor-based background encryption (2012)

To prevent data breaches, many organizations deploy full disk encryption to their computers. While OS-based encryption is widely accepted in practical situations, hypervisor-based encryption offers significant advantages such as OS independence and providing more secure environments. Unfortunately, the initial deployment cost of hypervisor-based encryption systems is rarely discussed. In this paper, we present a hypervisor-based encryption scheme that allows instant deployment of full disk encryption into existing systems without disturbing user's activities. To avoid waiting for encryption to be completed, hypervisors perform background encryption that does not incur significant performance penalty on guest OSs by carefully watching guest OS activities and moderating the degree of encryption speed. Our scheme does not require conversion of disk images or modification of OS configurations to install hypervisors by exploiting BitVisor, a thin hypervisor for enforcing security, that can be easily injected to existing systems. Our experimental results on Windows 7 show that application benchmark scores are not significantly affected by the background encryption and the overhead on sequential disk access throughput is at most 24%. The throughput of our background encryption is comparable to that of existing OS-based background encryption systems.
Gaussian Kernel Fuzzy C-Means Algorithm for Service Resource Allocation (2020)

With respect to the cluster problem of the evaluation information of mass customers in service management, a cluster algorithm of new Gaussian kernel FCM (fuzzy C-means) is proposed based on the idea of FCM. First, the paper defines a Euclidean distance formula between two data points and makes them cluster adaptively based on the distance classification approach and nearest neighbors in deleting relative data. Second, the defects of the FCM algorithm are analyzed, and a solution algorithm is designed based on the dual goals of obtaining a short distance between whole classes and long distances between different classes. Finally, an example is given to illustrate the results compared with the existing FCM algorithm.
Performance Analysis of Junctionless Transistors Based on Monte Carlo Simulation (2012)

A junctionless (JL) transistor has no pn junctions and has a number of advantages to fabricate ultrashort-channel metal-oxide-semiconductor field-effect transistors. In this paper, we study the electron transport in JL transistors based on a Monte Carlo simulation. We demonstrate that high channel doping will not degrade the drive current seriously, because ionized impurities scatter electrons mostly forward, and thus there is less chance for scattered electrons to return back to the source. We also find that smaller parasitic resistance in the source of a JL transistor also contributes to achieve high drive current.
Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017)

Impaired clearance of amyloid-β peptide (Aβ) leads to abnormal extracellular accumulation of this neurotoxic protein that drives neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD patients. However, the role of CTGF in AD pathogenesis remains unclear. Here we characterized the neuroprotective activity of CTGF. We found that CTGF facilitated Aβ uptake and subsequent degradation within primary glia and neuroblastoma cells. CTGF enhanced extracellular Aβ degradation via membrane-bound matrix metalloproteinase-14 (MMP14) in glia and extracellular MMP13 in neurons. In the brain of a Drosophila AD model, glial-expression of CTGF reduced Aβ deposits, improved locomotor function, and rescued memory deficits. Neuroprotective potential of CTGF against Aβ42-induced photoreceptor degeneration was disrupted through silencing MMPs. Therefore, CTGF may represent a node for potential AD therapeutics as it intervenes in glia-neuron communication via specific MMPs to alleviate Aβ neurotoxicity in the central nervous system.
Geometry of Crumpled Paper (2005)

We measure the geometry of a crumpled sheet of paper with laser-aided topography and discuss its statistical properties. The curvature of an elastoplastic fold scales linearly with applied force. The curvature distribution follows an exponential form with regions of high curvature localized along ridges. The measured ridge length distribution is consistent with a hierarchical model for ridge breaking during crumpling. A large fraction of the ridges are observed to terminate without bifurcating, and the ridge network connectedness is not as complete as anticipated. The self-affinity of the surface is characterized by a Hurst exponent of 0.71+/-0.01 in contrast with previous results.
Prognostic role of plasmaviscosity in breast cancer. (2002)

Tumor growth leads to tissue hypoxia and tissue hypoxia, in turn, is a strong stimulus for expression of genes encoding factors that promote tumor growth. Likewise, hypoxia is a key condition within the vicious cycle of autogenous neoplastic dissemination. A marker of the presence of tissue hypoxia may be the presence of high blood viscosity, which is found in a number of neoplastic diseases including gynecological cancer. At the time of diagnosis of breast cancer, patients dying of this disease had had significantly higher initial pv (1.40+/-0.18 mPa s; p<0.0001) when compared to patients not dying of cancer (1.30+/-0.10 mPa s). In multivariate proportional hazard regression analysis, next to tumor size (p=0.03) and nodal status (p=0.004), pv was found an independent prognostic marker for overall survival of breast cancer patients (RR=130.2; 95% CI: 11.6-1,460.6; p<0.0001). An optimized preoperative cut-off value above 1.40 mPa s was significantly associated with poor outcome (log-rank-test) in the Kaplan-Meier survival-estimates, even in node-negative breast cancer (n=153; 54.6%). The most likely explanation for these findings is that increased fibrinogen/fibrin turnover and breakdown products characteristically associated with tumor-cell dissemination contribute to the increased plasma viscosity while the hematocrit, leukocyte count, and platelet count contributed little to the increased blood viscosity in patients with breast cancer. These findings may constitute an approach for new strategies in cancer therapy since it might be possible that reduction of plasma viscosity by treatment improves responsiveness to radio/chemotherapy and thus survival of patients.
Small hepatocytes in culture develop polarized transporter expression and differentiation (2004)

Rat small hepatocytes have been shown to proliferate in culture and to form organoids with differentiated hepatocytes in vitro. To evaluate the degree of polarized transporter differentiation of rat small hepatocytes during 9 weeks of culturing, we studied the time-dependent expression and subcellular localization of the major bile salt and organic anion transport systems of hepatocytes [i.e. the basolateral sodium-taurocholate co-transporting protein (Ntcp), organic-anion-transporting polypeptide 1b2 (Oatp1b2), the canalicular bile-salt export pump (Bsep) and multidrug-resistance-associated protein 2 (Mrp2)]. Small hepatocytes proliferated and differentiated in culture and formed sharply demarcated colonies as assessed by morphology, alpha-fetoprotein, albumin and Mrp1 expression. Polarized surface transporter expression was evident after 5 weeks of culturing for Ntcp, Oatp1b2 and Mrp2, and after 7 weeks for Bsep. After 9 weeks in culture, the vast majority of matured hepatocytes expressed Ntcp/Oatp1b2 at the basolateral and Bsep/Mrp2 at the canalicular plasma-membrane domains. This polarized transporter expression was accompanied by canalicular secretion of fluorescein-diacetate and cholylglycyl-fluorescein. Furthermore, an anastomizing three-dimensional network of bile canaliculi developed within piling-up colonies. These data demonstrate that cultured rat small hepatocytes acquire a fully differentiated transporter expression phenotype during their development into hepatic 'organoid-like' clusters of mature hepatocytes. Thereby, the time-dependent sequence of transporter expression mirrored the ontogenesis of transporter expression in developing rat liver, supporting the concept that small hepatocytes correspond to the hepatocyte lineage derived from embryonic hepatoblasts and/or from a different pool of 'committed hepatocyte progenitor cells'.