gebhart/patrepeval huggingface dataset:
TRPM6 Forms the Mg2+ Influx Channel Involved in Intestinal and Renal Mg2+ Absorption (2003)

Mg2+ is an essential ion involved in a multitude of physiological and biochemical processes and a major constituent of bone tissue. Mg2+ homeostasis in mammals depends on the equilibrium between intestinal Mg2+ absorption and renal Mg2+ excretion, but little is known about the molecular nature of the proteins involved in the transepithelial transport of Mg2+ in these organs. Recently, it was shown that patients with mutations in TRPM6, a member of the transient receptor potential family of cation channels, suffer from hypomagnesemia with secondary hypocalcemia (HSH) as a result of impaired renal and/or intestinal Mg2+ handling. Here, we show that TRPM6 is specifically localized along the apical membrane of the renal distal convoluted tubule and the brush-border membrane of the small intestine, epithelia particularly associated with active Mg2+ (re)absorption. In kidney, parvalbumin and calbindin-D28K, two divalent-binding proteins, are co-expressed with TRPM6 and might function as intracellular Mg2+ buffers in the distal convoluted tubule. Heterologous expression of wild-type TRPM6 but not TRPM6 mutants identified in HSH patients induces a Mg2+- and Ca2+-permeable cation channel tightly regulated by intracellular Mg2+ levels. The TRPM6-induced channel displays strong outward rectification, has a 5-fold higher affinity for Mg2+ than for Ca2+, and is blocked in a voltage-dependent manner by ruthenium red. Our data indicate that TRPM6 comprises all or part of the apical Mg2+ channel of Mg2+-absorbing epithelia.
Separate neural subsystems within `Wernicke's area' (2001)

Over time, both the functional and anatomical boundaries of 'Wernicke's area' have become so broad as to be meaningless. We have re-analysed four functional neuroimaging (PET) studies, three previously published and one unpublished, to identify anatomically separable, functional subsystems in the left superior temporal cortex posterior to primary auditory cortex. From the results we identified a posterior stream of auditory processing. One part, directed along the supratemporal cortical plane, responded to both non-speech and speech sounds, including the sound of the speaker's own voice. Activity in its most posterior and medial part, at the junction with the inferior parietal lobe, was linked to speech production rather than perception. The second, more lateral and ventral part lay in the posterior left superior temporal sulcus, a region that responded to an external source of speech. In addition, this region was activated by the recall of lists of words during verbal fluency tasks. The results are compatible with an hypothesis that the posterior superior temporal cortex is specialized for processes involved in the mimicry of sounds, including repetition, the specific role of the posterior left superior temporal sulcus being to transiently represent phonetic sequences, whether heard or internally generated and rehearsed. These processes are central to the acquisition of long- term lexical memories of novel words.
Thymidine Kinase-Deleted Vaccinia Virus Expressing Purine Nucleoside Phosphorylase as a Vector for Tumor-Directed Gene Therapy (1999)

Tumor-directed gene therapy faces many obstacles. Lack of tissue targeting and low in vivo transduction efficiency represent some of the limitations for a successful therapeutic outcome. A thymidine kinase-deleted mutant vaccinia virus has been shown in marker studies to replicate selectively in tumor tissue in animal models. Purine nucleoside phosphorylase (PNP), from E. coli, converts the nontoxic prodrug 6-methylpurine deoxyriboside (6-MPDR) to the toxic purine 6-methylpurine. In this study, we investigated the cytotoxic properties of PNP, expressed by an optimized synthetic early/late promoter in a vaccinia virus (vMPPNP). In vitro cytotoxicity of psoralen-inactivated vMPPNP (1 microg of psoralen, 4 min of LWUV [365 nm]) at the maximum tolerated dose (MTD) of 6-MPDR (80 microM) reduced cell viability by day 3 to 1.7%. At an MOI of 0.002, replication-competent vMPPNP and 6-MPDR (80 microM) caused reduction of cell viability to 19.8% within 4 days. Furthermore, there was complete abrogation of viral replication after intracellular conversion of prodrug into the active toxin. The potency of such a system was similar among all histologies tested. Finally, the cytotoxic efficacy has been shown to be more rapid and complete than that of cytosine deaminase (CD), a more established enzyme/prodrug system. When virus was delivered intraperitoneally into athymic mice with hepatic metastases, followed by administration of prodrug, there was a significant prolongation of survival and a 30% cure rate. In summary, owing to its tumor-targeting capabilities, high transduction efficiency, and high gene expression, a vaccinia virus expressing PNP could prove to be a potent and valuable vector for tumor-targeted gene therapy.
DNA aptamers detecting generic amyloid epitopes (2012)

Amyloids are fibrillar protein aggregates resulting from non-covalent autocatalytic polymerization of various structurally and functionally unrelated proteins. Previously we have selected DNA aptamers, which bind specifically to the in vitro assembled amyloid fibrils of the yeast prionogenic protein Sup35. Here we show that such DNA aptamers can be used to detect SDS-insoluble amyloid aggregates of the Sup35 protein, and of some other amyloidogenic proteins, including mouse PrP, formed in yeast cells. The obtained data suggest that these aggregates and the Sup35 amyloid fibrils assembled in vitro possess common conformational epitopes recognizable by aptamers. The described DNA aptamers may be used for detection of various amyloid aggregates in yeast and, presumably, other organisms.
Perceptual video compression with combined scene analysis and eye-gaze tracking (2004)

No abstract available.
Main and interaction effects of acetic acid, furfural, andp-hydroxybenzoic acid on growth and ethanol productivity of yeasts (1999)

The influence of the factors acetic acid, furfural, and p-hydroxybenzoic acid on the ethanol yield (YEtOH) of Saccharomyces cerevisiae, bakers' yeast, S. cerevisiae ATCC 96581, and Candida shehatae NJ 23 was investigated using a 2(3)-full factorial design with 3 centrepoints. The results indicated that acetic acid inhibited the fermentation by C. shehatae NJ 23 markedly more than by bakers' yeast, whereas no significant difference in tolerance towards the compounds was detected between the S. cerevisiae strains. Furfural (2 g L-1) and the lignin derived compound p-hydroxybenzoic acid (2 g L-1) did not affect any of the yeasts at the cell mass concentration used. The results indicated that the linear model was not adequate to describe the experimental data (the p-values of curvatures were 0.048 for NJ 23 and 0.091 for bakers' yeast). Based on the results from the 2(3)-full factorial experiment, an extended experiment was designed based on a central composite design to investigate the influence of the factors on the specific growth rate (mu), biomass yield (Yx), volumetric ethanol productivity (QEtOH), and YEtOH. Bakers' yeast was chosen in the extended experiment due to its better tolerance towards acetic acid, which makes it a more interesting organism for use in industrial fermentations of lignocellulosic hydrolysates. The inoculum size was reduced in the extended experiment to reduce any increase in inhibitor tolerance that might be due to a large cell inoculum. By dividing the experiment in blocks containing fermentations performed with the same inoculum preparation on the same day, much of the anticipated systematic variation between the experiments was separated from the experimental error. The results of the fitted model can be summarised as follows: mu was decreased by furfural (0-3 g L-1). Furfural and acetic acid (0-10 g L-1) also interacted negatively on mu. Furfural concentrations up to 2 g L-1 stimulated Yx in the absence of acetic acid whereas higher concentrations decreased Yx. The two compounds interacted negatively on Yx and YEtOH. Acetic acid concentrations up to 9 g L-1 stimulated QEtOH, whereas furfural (0-3 g L-1) decreased QEtOH. Acetic acid in concentrations up to 10 g L-1 stimulated YEtOH in the absence of furfural, and furfural (0-2 g L-1) slightly increased YEtOH in the absence of acetic acid whereas higher concentrations caused inhibition. Acetic acid and furfural interacted negatively on YEtOH.
Cytokine signaling-regulation of the immune response in normal and critically ill states (2000)

Cytokines are produced during the activation of innate and acquired immunity, and are the principal means for intercellular communication of a microbial invasion. Cytokines serve to initiate the inflammatory response and to define the magnitude and the nature of the acquired immune response. The response of critically ill patients to their injury and/or invading pathogens is dependent, in large part, on the pattern of cytokines which are produced. The immunologic response of critically ill patients can vary from a strongly proinflammatory response, characterized by increased production of tumor necrosis factor-alpha, interleukin (IL)-1, interferon (IFN)-gamma, and IL-12 to one predominantly of anergy, characterized by increased production of T(H)2 cytokines, like IL-10 and to IL-4. Therapeutic efforts to modify the host immune response in critical illness will require a more thorough understanding of the cytokine milieu and the factors that determine their production.
Hindered transport of large molecules in liquid‐filled pores (1987)

Abstract Transport in liquid‐filled pores of molecular dimensions plays an important role in membrane separations, in various forms of chromatography, and in catalysis, to name a few examples. A frequent observation is that if the pore dimensions are of the same order as those of a solute molecule, the apparent diffusion coefficient of that solute is much lower than in bulk solution. Likewise, rates of convective transport of such solutes are generally lower than the product of bulk concentration and volume flow rate. Thus, solute transport is typically “hindered” or restricted. A key objective of research on hindered transport is to be able to predict the applicable transport coefficients from such fundamental information as the size, shape, and electrical charge of the solutes and pores. The present status of this research is reviewed.
Stratified false discovery control for large‐scale hypothesis testing with application to genome‐wide association studies (2006)

The multiplicity problem has become increasingly important in genetic studies as the capacity for high-throughput genotyping has increased. The control of False Discovery Rate (FDR) (Benjamini and Hochberg. [1995] J. R. Stat. Soc. Ser. B 57:289-300) has been adopted to address the problems of false positive control and low power inherent in high-volume genome-wide linkage and association studies. In many genetic studies, there is often a natural stratification of the m hypotheses to be tested. Given the FDR framework and the presence of such stratification, we investigate the performance of a stratified false discovery control approach (i.e. control or estimate FDR separately for each stratum) and compare it to the aggregated method (i.e. consider all hypotheses in a single stratum). Under the fixed rejection region framework (i.e. reject all hypotheses with unadjusted p-values less than a pre-specified level and then estimate FDR), we demonstrate that the aggregated FDR is a weighted average of the stratum-specific FDRs. Under the fixed FDR framework (i.e. reject as many hypotheses as possible and meanwhile control FDR at a pre-specified level), we specify a condition necessary for the expected total number of true positives under the stratified FDR method to be equal to or greater than that obtained from the aggregated FDR method. Application to a recent Genome-Wide Association (GWA) study by Maraganore et al. ([2005] Am. J. Hum. Genet. 77:685-693) illustrates the potential advantages of control or estimation of FDR by stratum. Our analyses also show that controlling FDR at a low rate, e.g. 5% or 10%, may not be feasible for some GWA studies.
Epidemiology of antiretroviral drug resistance in drug-naïve persons (2006)

Purpose of review An update is given on the epidemiology of transmitted antiretroviral drug resistance among HIV-1-infected adults. Recent findings Reported prevalence surveys show inter-region and intra-region variability, in part as a result of methodological differences. Temporal trends are difficult to define as rates appear stable or declining in some cohorts but increasing in others. While the highest prevalence continues to be observed in North America, Western Europe and areas of South America, transmitted antiretroviral drug resistance is emerging in countries where access to therapy is being scaled up, including regions of sub-Saharan Africa. Resistance patterns in drug-experienced and drug-naïve persons, transmission efficiency of resistant variants and their ability to persist as dominant species in the absence of drug pressure determine the prevalence of resistance mutations in persons with transmitted antiretroviral drug resistance. The most frequently detected mutations are in reverse transcriptase, especially thymidine analogue mutations, whereas protease mutations other than natural polymorphisms are generally less prevalent. Summary A consensus is required internationally on how transmitted antiretroviral drug resistance should be investigated and reported. Although routine testing methods provide only minimal estimates of the prevalence of transmitted antiretroviral drug resistance, successful treatment outcomes are observed in patients with resistance receiving first-line therapy guided by baseline resistance testing.
Joint optimization of signal constellation and bit labeling for bit-interleaved coded modulation with iterative decoding (2005)

We optimize signal constellation and bit labeling for bit-interleaved coded modulation with iterative decoding (BICM-ID). Target is to minimize bit error rate floor and signal to noise ratio for the turbo cliff. Various optimal non-orthogonal 16-QAM mappings are presented. An improvement of 0.2 dB is shown compared to state of the art orthogonal QAM-constellation with approx. the same error floor. To obtain these results, we derive the probability density function of extrinsic L-values of the demapper for perfect a priori knowledge in closed form. This allows fast computation of mutual information in the EXIT chart.
Innovation Diffusion and New Product Growth Models in Marketing (1979)

This paper assesses the state-of-the-art of the diffusion models of new product acceptance. A number of issues related to the further development and validation of these models are discussed.
Recognition of the Intrinsically Flexible Addiction Antidote MazE by a Dromedary Single Domain Antibody Fragment (2003)

The Escherichia coli mazEF operon defines a chromosomal addiction module that programs cell death under various stress conditions. It encodes the toxic and long-lived MazF and the labile antidote MazE. The denaturation of MazE is a two-state reversible dimer-monomer transition. At lower concentrations the denatured state is significantly populated. This leads to a new aspect of the regulation of MazE concentration, which may decide about the life and death of the cell. Interactions of MazE with a dromedary antibody domain, cAbMaz1 (previously used as a crystallization aid), as well as with promoter DNA were studied using microcalorimetric and spectroscopic techniques. Unique features of cAbMaz1 enable a specific enthalpy-driven recognition of MazE and, thus, a significant stabilization of its dimeric native conformation. The MazE dimer and the MazE dimer-cAbMaz1 complex show very similar binding characteristics with promoter DNA, i.e. three binding sites with apparent affinities in micromolar range and highly exothermic binding accompanied by large negative entropy contributions. A working model for the MazE-DNA assembly is proposed on the basis of the structural and binding data. Both binding and stability studies lead to a picture of MazE solution structure that is significantly more unfolded than the structure observed in a crystal of the MazE-cAbMaz1 complex.
High-Resolution STM Imaging of Novel Poly(G)−Poly(C) DNA Molecules (2006)

High-resolution scanning tunneling microscopy (STM) imaging of single double-stranded poly(G)-poly(C) DNA molecules, made by a novel synthesis method, shows the molecules morphology. The STM images reveal a periodic structure of approximately 4 nm, seen as repeating "bulbs" along the molecules. These "bulbs" are associated with the molecule helix (the major grooves). "Nicks", two per 100 nm on the average, are observed along the DNA as well. The STM measurements were supported by a morphological statistics of the DNA molecule groove length and apparent height relative to the surface.
Beyond neutrophil recovery: manipulation of the tumor microenvironment by GM-CSF to control cancer. (2002)

The detailed map of the human genome can potentially transform future cancer therapy by merging genomics with pharmacology, thereby identifying which patients will benefit from specific therapeutic agents. Single-nucleotide polymorphisms (SNPs) provide a valuable tool for this pharmacogenetic approach to cancer therapy. The discovery of SNPs as disease markers may facilitate identification of populations at increased risk for certain cancers. In addition, SNP genetic screening may facilitate administration of appropriate treatment modalities or reveal specific genetic profiles that have importance in drug efficacy and toxicity. In addition to SNP analysis, DNA and tissue microarray analyses have the potential to transform the future of cancer therapy. For example, DNA microarrays may improve tumor classification systems as well as provide a molecular level dissection of global gene expression changes that occur in carcinogenesis. Tissue microarrays would allow one to verify candidate genes, identified from DNA microarrays, against archival tumor specimens with known clinical outcome. In addition, both microarray technologies may be combined to rapidly validate gene targets. We will review and discuss these state-of-the-art technologies including data suggesting that the combined use of these high throughput technologies will facilitate our understanding of the genetic complexities inherent in cancer and will revolutionize cancer therapy.
Rapid death of injected myoblasts in myoblast transfer therapy (1996)

Myoblast transplantation has been proposed as a potential therapy for Duchenne muscular dystrophy (DMD). A Y-chromosome-specific probe was used to track the fate of donor male myoblasts injected into dystrophic muscles of female mdx mice (which are an animal model for DMD). In situ analysis with the Y-probe showed extremely poor survival of isolated normal male (C57B1/10Sn) donor myoblasts after injection into injured or uninjured muscles of dystrophic (mdx) and normal (C57B1/10Sn) female host mice. A decrease in the numbers of donor (male) myoblasts was seen from 2 days and was marked by 7 days after injection: few or no donor myoblasts were detected in host muscles examined at 3-12 months. There was limited movement of the injected donor myoblasts and fusion into host myofibers was rare. The results of this study strongly suggest that the failure of clinical trials of myoblast transplantation in boys with DMD may have been due to rapid and massive death of the donor myoblasts soon after myoblast injection.
Irreversible electroporation of the pancreas: Definitive local therapy without systemic effects (2011)

This animal model demonstrates that IRE of the pancreas performed at an optimal voltage is well tolerated, with rapid resolution of pancreatic inflammation and preservation of vascular structures.
Rule-Based Anomaly Detection on IP Flows (2009)

Rule-based packet classification is a powerful method for identifying traffic anomalies, with network security as a key application area. While popular systems like Snort are used in many network locations, comprehensive deployment across Tier-1 service provider networks is costly due to the need for high-speed monitors at many network ingress points. Since ISPs already collect flow statistics ubiquitously, can we use it for detecting the same anomalies as the packet based rules in spite of aggregation and absence of payload information? We exploit correlations between packet and flow level information via a machine learning (ML) approach to associate packet level alarms with a feature vector derived from flow records on the same traffic. We describe a system architecture for network-wide flow- alarming and describe the steps required to establish a proof- of-concept. We evaluate prediction accuracy of candidate ML algorithms on actual packet traces. The duration of prediction effectiveness is an issue for ML approaches and more so in resource intensive network applications. Initial results show little impairment of performance over periods of one or two weeks.
Inter-α-Trypsin Inhibitor Attenuates Complement Activation and Complement-Induced Lung Injury (2007)

Complement activation is a central component of inflammation and sepsis and can lead to significant tissue injury. Complement factors are serum proteins that work through a cascade of proteolytic reactions to amplify proinflammatory signals. Inter-alpha-trypsin inhibitor (IaI) is an abundant serum protease inhibitor that contains potential complement-binding domains, and has been shown to improve survival in animal sepsis models. We hypothesized that IaI can bind complement and inhibit complement activation, thus ameliorating complement-dependent inflammation. We evaluated this hypothesis with in vitro complement activation assays and in vivo in a murine model of complement-dependent lung injury. We found that IaI inhibited complement activation through the classical and alternative pathways, inhibited complement-dependent phagocytosis in vitro, and reduced complement-dependent lung injury in vivo. This novel function of IaI provides a mechanistic explanation for its observed salutary effects in sepsis and opens new possibilities for its use as a treatment agent in inflammatory diseases.
Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice (2004)

Production of thromboxane (TX) A2 and PG I2/prostacyclin (PGI2) is increased in patients with atherosclerosis. However, their roles in atherogenesis have not been critically defined. To examine this issue, we cross-bred atherosclerosis-prone apoE-deficient mice with mice deficient in either the TXA receptor (TP) or the PGI receptor (IP). Although they showed levels of serum cholesterol and triglyceride similar to those of apoE-deficient mice, apoE-/-TP-/- mice exhibited a significant delay in atherogenesis, and apoE-/-IP-/- mice exhibited a significant acceleration in atherogenesis compared with mice deficient in apoE alone. The plaques in apoE-/-IP-/- mice showed partial endothelial disruption and exhibited enhanced expression of ICAM-1 and decreased expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) in the overlying endothelial cells compared with those of apoE-/-TP-/- mice. Platelet activation with thrombin ex vivo revealed higher and lower sensitivity for surface P-selectin expression in platelets of apoE-/-IP-/- and apoE-/-TP-/- mice, respectively, than in those of apoE-/- mice. Intravital microscopy of the common carotid artery revealed a significantly greater number of leukocytes rolling on the vessel walls in apoE-/-IP-/- mice than in either apoE-/-TP-/- or apoE-/- mice. We conclude that TXA2 promotes and PGI2 prevents the initiation and progression of atherogenesis through control of platelet activation and leukocyte-endothelial cell interaction.