gebhart/patrepeval huggingface dataset:
JAK/STAT Signaling Is Associated With Cardiac Dysfunction During Ischemia and Reperfusion (2001)

These findings suggest that activation of the JAK/STAT signaling pathway is a significant contributing factor to the pathogenesis of myocardial ischemia and that interference in activation of the pathway potentiates recovery in cardiac function.
Oligosaccharides As Modulators of Rheology in Complex Mucous Systems (2011)

Mucus rheology is integral to physiological function with the exact secretion rheology resulting from the macromolecular components, both mucin and nonmucin, and the interactions between these macromolecules. Here we present data demonstrating that low-molecular-weight guluronic acid oligomers extracted from alginate are able to disrupt intermolecular interactions in both purified and native mucous systems, resulting in rheological changes that are compatible with a lower cross-link density and thus reduced resistance to deformation. Additionally, these changes are associated with altered physiological function, raising the possibility of the use of such oligomers in biomedical applications.
Kelp Fly Virus: a Novel Group of Insect Picorna-Like Viruses as Defined by Genome Sequence Analysis and a Distinctive Virion Structure (2005)

The complete genomic sequence of kelp fly virus (KFV), originally isolated from the kelp fly, Chaetocoelopa sydneyensis, has been determined. Analyses of its genomic and structural organization and phylogeny show that it belongs to a hitherto undescribed group within the picorna-like virus superfamily. The single-stranded genomic RNA of KFV is 11,035 nucleotides in length and contains a single large open reading frame encoding a polypeptide of 3,436 amino acids with 5' and 3' untranslated regions of 384 and 343 nucleotides, respectively. The predicted amino acid sequence of the polypeptide shows that it has three regions. The N-terminal region contains sequences homologous to the baculoviral inhibitor of apoptosis repeat domain, an inhibitor of apoptosis commonly found in animals and in viruses with double-stranded DNA genomes. The second region contains at least two capsid proteins. The third region has three sequence motifs characteristic of replicase proteins of many plant and animal viruses, including a helicase, a 3C chymotrypsin-like protease, and an RNA-dependent RNA polymerase. Phylogenetic analysis of the replicase motifs shows that KFV forms a distinct and distant taxon within the picorna-like virus superfamily. Cryoelectron microscopy and image reconstruction of KFV to a resolution of 15 A reveals an icosahedral structure, with each of its 12 fivefold vertices forming a turret from the otherwise smooth surface of the 20-A-thick capsid. The architecture of the KFV capsid is unique among the members of the picornavirus superfamily for which structures have previously been determined.
Ribosome Dysfunction Is an Early Event in Alzheimer's Disease (2005)

Alzheimer's disease (AD) is a progressive and devastating disorder that is often preceded by mild cognitive impairment (MCI). In the present study, we report that in multiple cortical areas of MCI and AD subjects, there is a significant impairment in ribosome function that is not observed in the cerebellum of the same subjects. The impairment in ribosome function is associated with a decreased rate and capacity for protein synthesis, decreased ribosomal RNA and tRNA levels, and increased RNA oxidation. No alteration in the level of initiation factors was observed in the brain regions exhibiting impairments in protein synthesis. Together, these data indicate for the first time that impairments in protein synthesis may be one of the earliest neurochemical alterations in AD and directly demonstrate that the polyribosome complex is adversely affected early in the development of AD. These data have important implications for AD studies involving proteomics and studies analyzing proteolysis in AD, indicate that oxidative damage may contribute to decreased protein synthesis, and suggest a role for alterations in protein synthesis as a novel contributor to the onset and development of AD.
Human Embryonic and Fetal Mesenchymal Stem Cells Differentiate toward Three Different Cardiac Lineages in Contrast to Their Adult Counterparts (2011)

Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.
Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens (2010)

The envelope spike of HIV is one of the most highly N-glycosylated structures found in nature. However, despite extensive research revealing essential functional roles in infection and immune evasion, the chemical structures of the glycans on the native viral envelope glycoprotein gp120--as opposed to recombinantly generated gp120--have not been described. Here, we report on the identity of the N-linked glycans from primary isolates of HIV-1 (clades A, B, and C) and from the simian immunodeficiency virus. MS analysis reveals a remarkably simple and highly conserved virus-specific glycan profile almost entirely devoid of medial Golgi-mediated processing. In stark contrast to recombinant gp120, which shows extensive exposure to cellular glycosylation enzymes (>70% complex type glycans), the native envelope shows barely detectable processing beyond the biosynthetic intermediate Man5GlcNAc2 (<2% complex type glycans). This oligomannose (Man5-9GlcNAc2) profile is conserved across primary isolates and geographically divergent clades but is not reflected in the current generation of gp120 antigens used for vaccine trials. In the context of vaccine design, we also note that Manalpha1-->2Man-terminating glycans (Man6-9GlcNAc2) of the type recognized by the broadly neutralizing anti-HIV antibody 2G12 are 3-fold more abundant on the native envelope than on the recombinant monomer and are also found on isolates not neutralized by 2G12. The Manalpha1-->2Man residues of gp120 therefore provide a vaccine target that is physically larger and antigenically more conserved than the 2G12 epitope itself. This study revises and extends our understanding of the glycan shield of HIV with implications for AIDS vaccine design.
Bacterial Acyltransferases as an Alternative for Lipase‐Catalyzed Acylation for the Production of Oleochemicals and Fuels (2008)

Bacterial acyltransferases are a new class of enzymes, and the first member was identified as WS/DGAT in Acinetobacter baylyi ADP1. Their unspecificity have been used in several biotechnological applications for lipid modification, a field that has been dominated by the use of lipases. Examples are the biosynthesis of jojoba-like wax esters and fatty-acid ethyl esters. In addition, these enzymes are also capable of synthesizing acylthioesters. Acyloxoesters and acylthioesters can thus be produced in vivo by whole-cell fermentations rather than in vitro in an enzyme reactor. In this Minireview, we focus on the biotechnological utilization of acyltransferases for the production of modified lipids from renewable resources.
Detection of an Extrasolar Planet Atmosphere (2002)

We report high-precision spectrophotometric observations of four planetary transits of HD 209458, in the region of the sodium resonance doublet at 589.3 nm. We find that the photometric dimming during transit in a bandpass centered on the sodium feature is deeper by (2.32 +/- 0.57) x 10(-4) relative to simultaneous observations of the transit in adjacent bands. We interpret this additional dimming as absorption from sodium in the planetary atmosphere, as recently predicted from several theoretical modeling efforts. Our model for a cloudless planetary atmosphere with a solar abundance of sodium in atomic form predicts more sodium absorption than we observe. There are several possibilities that may account for this reduced amplitude, including reaction of atomic sodium into molecular gases and/or condensates, photoionization of sodium by the stellar flux, a low primordial abundance of sodium, and the presence of clouds high in the atmosphere.
Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial (2008)

While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with clopidogrel in patients with ACS.
STAT3 is required for IL-21–induced secretion of IgE from human naive B cells (2008)

The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced by the fact that it comprises less than 0.0001% of serum Ig, and aberrant production causes atopic conditions, including allergy, rhinitis, and anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human and murine B cells, whereas interferon-gamma can antagonize this effect. IL-21 has also been recognized for its ability to suppress IL-4-induced IgE production by murine B cells. Here, we identified IL-21 as an inducer of IgE production by CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B cells, such that the levels detected under these conditions exceeded those induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations revealed that the ability of IL-21 to induce IgE secretion, and augment that driven by IL-4, was STAT3-dependent. These findings highlight a fundamental difference between the regulation of IgE production by human and murine B cells and have implications for the dysregulated production of IgE in conditions characterized by extremely high levels of serum IgE.
Coherent dynamics of a Josephson charge qubit (2004)

We have fabricated a Josephson charge qubit by capacitively coupling a single-Cooper-pair box (SCB) to an electrometer based upon a single-electron transistor (SET) configured for radio-frequency readout (rf-SET). Charge quantization of $2e$ is observed and microwave spectroscopy is used to extract the Josephson and charging energies of the box. We perform coherent manipulation of the SCB by using very fast dc pulses and observe quantum oscillations in time of the charge that persist to $\ensuremath{\simeq}10\mathrm{ns}.$ The observed contrast of the oscillations is high and agrees with that expected from the finite ${E}_{J}{/E}_{C}$ ratio and finite rise time of the dc pulses. In addition, we are able to demonstrate nearly $100%$ initial charge state polarization. We also present a method to determine the relaxation time ${T}_{1}$ when it is shorter than the measurement time ${T}_{\mathrm{meas}}.$
Principles of Video Annotation Markup Language (VAML). (2003)

The creation of hypertext and World Wide Web provided a powerful mechanism for organizing and distributing the warehouse of information. However, video-based hypermedia may represent the future of the Internet since it provides a much better viewing experience. Our ongoing project - the Video Annotation Markup Language (VAML) aims to enhance the hypervideo framework. In this paper, we give a detailed description of VAML and its principles.
Hepatitis B virus replication (2007)

Hepadnaviruses, including human hepatitis B virus (HBV), replicate through reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription: it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA, epsilon, as template, and depends on cellular chaperones; moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids. This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV (DHBV), now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cell-free systems. At this time, they can, unfortunately, not be complemented by three-dimensional structural information on the involved components. However, at least for the epsilon RNA element such information is emerging, raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.
Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection (2000)

Treatment with fumagillin at 60 mg/day for 14 days has promise as an effective oral treatment for E. bieneusi infections.
RHex: A Simple and Highly Mobile Hexapod Robot (2001)

In this paper, the authors describe the design and control of RHex, a power autonomous, untethered, compliant-legged hexapod robot. RHex has only six actuators—one motor located at each hip— achieving mechanical simplicity that promotes reliable and robust operation in real-world tasks. Empirically stable and highly maneuverable locomotion arises from a very simple clock-driven, open-loop tripod gait. The legs rotate full circle, thereby preventing the common problem of toe stubbing in the protraction (swing) phase. An extensive suite of experimental results documents the robot’s significant “intrinsic mobility”—the traversal of rugged, broken, and obstacle-ridden ground without any terrain sensing or actively controlled adaptation. RHex achieves fast and robust forward locomotion traveling at speeds up to one body length per second and traversing height variations well exceeding its body clearance.
Fabrication of porous polymeric matrix drug delivery devices using the selective laser sintering technique (2001)

New techniques in solid freeform fabrication (SFF) have prompted research into methods of manufacturing and controlling porosity. The strategy of this research is to integrate computer aided design (CAD) and the SFF technique of selective laser sintering (SLS) to fabricate porous polymeric matrix drug delivery devices (DDDs). This study focuses on the control of the porosity of a matrix by manipulating the SLS process parameters of laser beam power and scan speed. Methylene blue dye is used as a drug model to infiltrate the matrices via a degassing method; visual inspection of dye penetration into the matrices is carried out. Most notably, the laser power matrices show a two-stage penetration process. The matrices are sectioned along the XZ planes and viewed under scanning electron microscope (SEM). The morphologies of the samples reveal a general increase in channel widths as laser power decreases and scan speed increases. The fractional release profiles of the matrices are determined by allowing the dye to diffuse out in vitro within a controlled environment. The results show that laser power and scan speed matrices deliver the dye for 8-9 days and have an evenly distributed profile. Mercury porosimetry is used to analyse the porosity of the matrices. Laser power matrices show a linear relationship between porosity and variation in parameter values. However, the same relationship for scan speed matrices turns out to be rather inconsistent. Relationships between the SLS parameters and the experimental results are developed using the fractional release rate equation for the infinite slab porous matrix DDD as a basis for correlation.
Confidence intervals for the 50 per cent response dose (2003)

Confidence intervals for the 50 per cent response dose are usually computed using either the Delta method or Fieller's procedure. Recently, confidence intervals computed by inverting the asymptotic likelihood ratio test have also been recommended. There is some controversy as to which of these methods should be used. By means of an extensive simulation study we examine these methods as well as confidence intervals obtained by the approximate bootstrap confidence (ABC) procedure and an adjusted form of the likelihood ratio based confidence intervals.
An Orally Active Selective Androgen Receptor Modulator Is Efficacious on Bone, Muscle, and Sex Function with Reduced Impact on Prostate (2006)

A number of conditions, including osteoporosis, frailty, and sexual dysfunction in both men and women have been improved using androgens. However, androgens are not widely used for these indications because of the side effects associated with these drugs. We describe an androgen receptor (AR) ligand that maintains expected anabolic activities with substantially diminished activity in the prostate. LGD2226 is a nonsteroidal, nonaromatizable, highly selective ligand for the AR, exhibiting virtually no affinity for the other intracellular receptors. We determined that AR bound to LGD2226 exhibits a unique pattern of protein-protein interactions compared with testosterone, fluoxymesterone (an orally available steroidal androgen), and other steroids, suggesting that LGD2226 alters the conformation of the ligand-binding domain. We demonstrated that LGD2226 is fully active in cell-based models of bone and muscle. LGD2226 exhibited anabolic activity on muscle and bone with reduced impact on prostate growth in rodent models. Biomechanical testing of bones from animals treated with LGD2226 showed strong enhancement of bone strength above sham levels. LGD2226 was also efficacious in a sex-behavior model in male rats measuring mounts, intromissions, ejaculations, and copulation efficiency. These results with an orally available, nonaromatizable androgen demonstrate the important role of the AR and androgens in mediating a number of beneficial effects in bone, muscle, and sexual function independent from the conversion of androgens into estrogenic ligands. Taken together, these results suggest that orally active, nonsteroidal selective androgen receptor modulators may be useful therapeutics for enhancing muscle, bone, and sexual function.
Soluble Receptors for Cytokines and Growth Factors (1996)

Soluble cytokine and growth factor receptors are currently believed to play an important role in the regulation of biological activities of their ligands. In this review, the current ideas on the mechanisms and regulation of generation of soluble receptors and their possible physiological functions are presented. Furthermore, implications of soluble cytokine and growth factor receptors as disease markers and therapeutical agents are summarized and discussed.
Model-Based Vulnerability Testing for Web Applications (2013)

This paper deals with an original approach to automate Model-Based Vulnerability Testing (MBVT) for Web applications, which aims at improving the accuracy and precision of vulnerability testing. Today, Model-Based Testing techniques are mostly used to address functional features. The adaptation of such techniques for vulnerability testing defines novel issues in this research domain. In this paper, we describe the principles of our approach, which is based on a mixed modeling of the application under test: the specification indeed captures some behavioral aspects of the Web application, and includes vulnerability test purposes to drive the test generation algorithm. This approach is illustrated with the widely-used DVWA example.
ENDOPHYTIC BACTERIA FROM SEEDS OFNICOTIANA TABACUMCAN REDUCE CADMIUM PHYTOTOXICITY (2008)

Although endophytic bacteria seem to have a close association with their host plant, little is known about the influence of seed endophytic bacteria on initial plant development and on their interactions with plants under conditions of metal toxicity. In order to further elucidate this close relationship, we isolated endophytic bacteria from surface sterilized Nicotiana tabacum seeds that were collected from plants cultivated on a cadmium-(Cd) and zinc-enriched soil. Many of the isolated strains showed Cd tolerance. Sterilely grown tobacco plants were inoculated with either the endogenous microbial consortium, composed of cultivable and noncultivable strains; single strains; or defined consortia of the most representative cultivable strains. Subsequently, the effects of inoculation of endophytic bacteria on plant development and on metal and nutrient uptake were explored under conditions with and without exposure to Cd. In general, seed endophytes were found to have a positive effect on plant growth, as was illustrated by an increase in biomass production under conditions without Cd. In several cases, inoculation with endophytes resulted in improved biomass production under conditions of Cd stress, as well as in a higher plant Cd concentration and total plant Cd content compared to noninoculated plants. These results demonstrate the beneficial effects of seed endophytes on metal toxicity and accumulation, and suggest practical applications using inoculated seeds as a vector for plant beneficial bacteria.
Nonvolatile Static Random Access Memory Using Resistive Switching Devices: Variable-Transconductance Metal–Oxide–Semiconductor Field-Effect-Transistor Approach (2010)

In this paper, we present a variable-transconductance ( g m ) metal–oxide–semiconductor field-effect-transistor (VGm-MOSFET) architecture using a nonpolar resistive switching device (RSD) for nonvolatile bistable circuit applications. The architecture can be achieved by connecting an RSD to the source terminal of an ordinary MOSFET. The current drive capability of the VGm-MOSFET can be modified by resistance states of the connected RSD, which is a very useful function for nonvolatile bistable circuits, such as nonvolatile static random access memory (NV-SRAM) and nonvolatile flip-flop (NV-FF). NV-SRAM can be easily configured by connecting two additional VGm-MOSFETs to the storage nodes of a standard SRAM cell. Using our developed SPICE macromodel for nonpolar RSDs, successful circuit operations of the proposed NV-SRAM cell were confirmed.