gebhart/patrepeval huggingface dataset:
Fibroblasts and myofibroblasts in wound healing (2014)

(Myo)fibroblasts are key players for maintaining skin homeostasis and for orchestrating physiological tissue repair. (Myo)fibroblasts are embedded in a sophisticated extracellular matrix (ECM) that they secrete, and a complex and interactive dialogue exists between (myo)fibroblasts and their microenvironment. In addition to the secretion of the ECM, (myo)fibroblasts, by secreting matrix metalloproteinases and tissue inhibitors of metalloproteinases, are able to remodel this ECM. (Myo)fibroblasts and their microenvironment form an evolving network during tissue repair, with reciprocal actions leading to cell differentiation, proliferation, quiescence, or apoptosis, and actions on growth factor bioavailability by binding, sequestration, and activation. In addition, the (myo)fibroblast phenotype is regulated by mechanical stresses to which they are subjected and thus by mechanical signaling. In pathological situations (excessive scarring or fibrosis), or during aging, this dialogue between the (myo)fibroblasts and their microenvironment may be altered or disrupted, leading to repair defects or to injuries with damaged and/or cosmetic skin alterations such as wrinkle development. The intimate dialogue between the (myo)fibroblasts and their microenvironment therefore represents a fascinating domain that must be better understood in order not only to characterize new therapeutic targets and drugs able to prevent or treat pathological developments but also to interfere with skin alterations observed during normal aging or premature aging induced by a deleterious environment.
Nonthermal Atmospheric Plasma Rapidly Disinfects Multidrug-Resistant Microbes by Inducing Cell Surface Damage (2012)

Plasma, a unique state of matter with properties similar to those of ionized gas, is an effective biological disinfectant. However, the mechanism through which nonthermal or "cold" plasma inactivates microbes on surfaces is poorly understood, due in part to challenges associated with processing and analyzing live cells on surfaces rather than in aqueous solution. Here, we employ membrane adsorption techniques to visualize the cellular effects of plasma on representative clinical isolates of drug-resistant microbes. Through direct fluorescent imaging, we demonstrate that plasma rapidly inactivates planktonic cultures, with >5 log(10) kill in 30 s by damaging the cell surface in a time-dependent manner, resulting in a loss of membrane integrity, leakage of intracellular components (nucleic acid, protein, ATP), and ultimately focal dissolution of the cell surface with longer exposure time. This occurred with similar kinetic rates among methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Candida albicans. We observed no correlative evidence that plasma induced widespread genomic damage or oxidative protein modification prior to the onset of membrane damage. Consistent with the notion that plasma is superficial, plasma-mediated sterilization was dramatically reduced when microbial cells were enveloped in aqueous buffer prior to treatment. These results support the use of nonthermal plasmas for disinfecting multidrug-resistant microbes in environmental settings and substantiate ongoing clinical applications for plasma devices.
AMOS: an active system for MPEG-4 video object segmentation (2002)

Object segmentation and tracking is a fundamental step for many digital video applications. In this paper, we present an active system (AMOS) which combines low level automatic region segmentation with an active method for defining and tracking high-level semantic video objects. The system contains two stages: an initial object segmentation stage where user input in the starting frame is used to create a semantic object; and an object tracking stage where underlying regions of the semantic object are tracked and grouped through successive frames. Experiments with different types of videos show very good performance.
Two-degree-of-freedom powered prosthetic wrist (2011)

Prosthetic wrists need to be compact. By minimizing space requirements, a wrist unit can be made for people with long residual limbs. This prosthetic wrist uses two motors arranged across the arm within the envelope of the hand. The drive is transmitted by a differential so that it produces wrist flexion and extension, pronation and supination, or a combination of both. As a case study, it was controlled by a single-prosthesis user with pattern recognition of the myoelectric signals from the forearm. The result is a compact, two-degree-of-freedom prosthetic wrist that has the potential to improve the functionality of any prosthetic hand by creating a hand orientation that more closely matches grasp requirements.
Identification of N-Phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine Derivatives as Novel, Potent, and Selective NF-κB Inducing Kinase (NIK) Inhibitors for the Treatment of Psoriasis (2020)

A series of <i>N</i>-phenyl-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-4-amine derivatives with NF-κB inducing kinase (NIK) inhibitory activity were obtained through structure-based drug design and synthetic chemistry. Among them, 4-(3-((7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-4-yl)amino)-4-morpholinophenyl)-2-(thiazol-2-yl)but-3-yn-2-ol (<b>12f</b>) was identified as a highly potent NIK inhibitor, along with satisfactory selectivity. The pharmacokinetics of <b>12f</b> and its ability to inhibit interleukin 6 secretion in BEAS-2B cells were better than compound <b>1</b> developed by Amgen. Oral administration of different doses of <b>12f</b> in an imiquimod-induced psoriasis mouse model showed effective alleviation of psoriasis, including invasive erythema, swelling, skin thickening, and scales. The underlying pathological mechanism involved attenuation of proinflammatory cytokine and chemokine gene expression, and the infiltration of macrophages after the treatment of <b>12f</b>. This work provides a foundation for the development of NIK inhibitors, highlighting the potential of developing NIK inhibitors as a new strategy for the treatment of psoriasis.
CD44 and its Role in Inflammation and Inflammatory Diseases (2009)

The cell adhesion molecule CD44 is expressed on the majority of immune cells and is responsible for mediating adhesion to the extracellular matrix glycosaminoglycan, hyaluronan. The binding of CD44 to hyaluronan is induced on T lymphocytes after activation by antigen and on monocytes after stimulation by inflammatory agents. Under inflammatory conditions, CD44 on endothelial cells presents hyaluronan to CD44 on activated T lymphocytes and mediates a rolling interaction under flow conditions. This rolling interaction together with chemokine signaling upregulates integrin-mediated adhesion, which induces cell arrest and leads to subsequent migration to the inflammatory site. Studies with monoclonal antibodies against CD44 in mouse models of chronic inflammatory disease showed reduced disease severity attributed to reduced leukocyte recruitment. More recent investigations, taking advantage of the availability of CD44 null mice, further established a role for CD44 in leukocyte recruitment to inflammatory sites. These studies also revealed a role for CD44 in limiting the inflammatory response and resolving inflammation in models of lung injury and hepatitis. Here we describe the contributions of CD44 and hyaluronan to an inflammatory response and discuss the role of CD44 in both promoting and resolving inflammation in various mouse models of inflammatory disease.
Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C. (1994)

The present studies were undertaken to characterize further the potential role of protein kinase C (PKC) in the regulation of apoptosis in HL-60 promyelocytic leukemia cells. The capacity of acute exposure to specific and nonspecific pharmacological inhibitors of PKC to promote apoptotic DNA fragmentation was examined both quantitatively and qualitatively and correlated with effects on cellular differentiation and proliferation. Incubation of HL-60 cells for 6 h with chelerythrine and calphostin C (highly specific inhibitors that act at the regulatory domain) or H7 and gossypol (nonspecific inhibitors that act at the PKC catalytic domain) produced concentration-dependent increases in DNA fragmentation. Induction of DNA fragmentation by chelerythrine, calphostin C, and gossypol was biphasic, resulting in a sharp decline in effect at concentrations above 5 microM, 0.1 microM, and 100 microM, respectively, whereas maximal and more stable effects were observed in response to H7 (100 microM). A 6-h exposure to staurosporine, a nonspecific but potent PKC inhibitor, failed to induce DNA fragmentation at concentrations generally used to achieve maximal inhibition of enzyme activity (e.g., 50 nM) but promoted fragmentation at considerably higher concentrations (e.g., > or = 200 nM). In contrast, 6-h exposures to the nonspecific protein kinase inhibitor hypericin (0.1 to 100 microM) or to the nonspecific inhibitor of protein kinase A, HA1004 (50 microM), were without effect on DNA fragmentation. DNA obtained from cells exposed to chelerythrine (5 microM), calphostin C (100 nM), H7 (50 microM), gossypol (50 microM), and staurosporine (200 nM)--but not hypericin (25 microM)--exhibited clear evidence of internucleosomal DNA cleavage on agarose gel electrophoresis; moreover, these cells exhibited the classical morphological features of apoptosis (cell shrinkage, nuclear condensation, and the formation of apoptotic bodies). All of the PKC inhibitors that induced apoptosis, and one of the inhibitors that did not (hypericin), substantially inhibited HL-60 cell clonogenicity at the concentrations evaluated. None of the agents tested induced cellular maturation as assessed by nonspecific esterase and nitro-blue tetrazolium positivity. DNA fragments obtained from cells exposed to specific and nonspecific PKC inhibitors possessed predominantly 5'-phosphate termini, consistent with the action of a Ca(2+)-/Mg(2+)-dependent endonuclease. Finally, Northern blot analysis revealed that exposure to calphostin C at a concentration that induced apoptosis (100 nM) failed to alter expression of bcl-2, an oncogene known to block apoptosis in both lymphoid and myeloid leukemia cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Light adaptation in the primate retina: Analysis of changes in gain and dynamics of monkey retinal ganglion cells (1990)

The responses of monkey retinal ganglion cells to sinusoidal stimuli of various temporal frequencies were measured and analyzed at a number of mean light levels. Temporal modulation tuning functions (TMTFs) were measured at each mean level by varying the drift rate of a sine-wave grating of fixed spatial frequency and contrast. The changes seen in ganglion cell temporal responses with changes in adaptation state were similar to those observed in human subjects and in turtle horizontal cells and cones tested with sinusoidally flickering stimuli; "Weber's Law" behavior was seen at low temporal frequencies but not at higher temporal frequencies. Temporal responses were analyzed in two ways: (1) at each light level, the TMTFs were fit by a model consisting of a cascade of low- and high-pass filters; (2) the family of TMTFs collected over a range of light levels for a given cell was fit by a linear negative feedback model in which the gain of the feedback was proportional to the mean light level. Analysis (1) revealed that the temporal responses of one class of monkey ganglion cells (M cells) were more phasic at both photopic and mesopic light levels than the responses of P ganglion cells. In analysis (2), the linear negative feedback model accounted reasonably well for changes in gain and dynamics seen in three P cells and one M cell. From the feedback model, it was possible to estimate the light level at which the dark-adapted gain of the cone pathways in the primate retina fell by a factor of two. This value was two to three orders of magnitude lower than the value estimated from recordings of isolated monkey cones. Thus, while a model which includes a single stage of negative feedback can account for the changes in gain and dynamics associated with light adaptation in the photopic and mesopic ranges of vision, the underlying physical mechanisms are unknown and may involve elements in the primate retina other than the cone.
Rhodanine and Thiohydantoin Derivatives for Detecting Tau Pathology in Alzheimer’s Brains (2011)

A novel series of rhodanin (RH) and thiohydantoin (TH) derivatives were designed and synthesized for detecting tau pathology in the brains of patients with Alzheimer's disease (AD). In experiments in vitro using tau and β-amyloid (Aβ) aggregates, the TH derivative, TH2, showed high specific binding to tau aggregates. In hippocampal sections obtained from AD patients, TH2 intensely stained neurofibrillary tangles. In experiments using normal mice, [(125)I]TH2 showed good uptake (1.54%ID/g, 2 min postinjection) into and a rapid washout (0.25%ID/g, 60 min postinjection) from the brain. [(123)I]TH2 should be further investigated as a potential imaging agent for detecting tau pathology.
The mtr locus is a two-gene operon required for transcription attenuation in the trp operon of Bacillus subtilis. (1990)

We have cloned and characterized the mtr operon of Bacillus subtilis. This operon encodes a presumed RNA-binding regulatory protein that is required for attenuation control of the trp operon. We have shown that the mtr operon consists of two structural genes, mtrA and mtrB, predicted to encode 22-kDa and 8-kDa polypeptides, respectively. MtrB shows homology with RegA, an RNA-binding regulatory protein of bacteriophage T4. The lesions in several mtr mutants were localized to mtrB or the putative mtr promoter. Several mtrB alleles were dominant to mtr+, suggesting that the regulatory factor is a multimeric protein. The in vivo action of the mtrA and mtrB gene products was analyzed in an E. coli strain containing a trpE-lacZ gene fusion under control of the B. subtilis trp promoter/attenuator region. Both MtrA and MtrB were necessary for regulation of beta-galactosidase production.
Functional Characterization of an Isoform-Selective Inhibitor of PI3K-p110β as a Potential Anticancer Agent (2012)

We report the first functional characterization of a p110β-selective inhibitor, KIN-193, that is efficacious as an antitumor agent in mice. We show that this class of inhibitor holds great promise as a pharmacologic agent that could be used to address the potential therapeutic benefit of treating p110β-dependent PTEN-deficient human tumors.
MEMS single-pole double-throw (SPDT) X and K-band switching circuits (2002)

Single-pole double-throw (SPDT) X and K-band circuit designs incorporating low-loss microelectromechanical shunt capacitive switches are reported. The switches incorporate highly inductive connecting beams which aid in further increasing the isolation at the desired operational RF frequency. Measurements show an isolation of better than 40 dB at both 7 and 20 GHz. Insertion loss was measured at -0.95 dB at 7 GHz and -0.69 dB at 20 GHz for the two respective designs.
NPAT links cyclin E–Cdk2 to the regulation of replication-dependent histone gene transcription (2000)

In eukaryotic cells, histone gene expression is one of the major events that mark entry into S phase. While this process is tightly linked to cell cycle position, how it is regulated by the cell cycle machinery is not known. Here we show that NPAT, a substrate of the cyclin E-Cdk2 complex, is associated with human replication-dependent histone gene clusters on both chromosomes 1 and 6 in S phase. We demonstrate that NPAT activates histone gene transcription and that this activation is dependent on the promoter elements (SSCSs) previously proposed to mediate cell cycle-dependent transcription. Cyclin E is also associated with the histone gene loci, and cyclin E-Cdk2 stimulates the NPAT-mediated activation of histone gene transcription. Thus, our results both show that NPAT is involved in a key S phase event and provide a link between the cell cycle machinery and activation of histone gene transcription.
Inhibition of Plasminogen Activator Inhibitor-1 (2008)

The present study demonstrates beneficial in vitro and in vivo effects of novel PAI-1 inhibitors. Our methodology proves to be a useful tool to obtain effective inhibitors of serpin activity.
Systemic combined melatonin–mitochondria treatment improves acute respiratory distress syndrome in the rat (2014)

Despite high in-hospital mortality associated with acute respiratory distress syndrome (ARDS), there is no effective therapeutic strategy. We tested the hypothesis that combined melatonin-mitochondria treatment ameliorates 100% oxygen-induced ARDS in rats. Adult male Sprague-Dawley rats (n = 40) were equally categorized into normal controls, ARDS, ARDS-melatonin, ARDS with intravenous liver-derived mitochondria (1500 μg per rat 6 hr after ARDS induction), and ARDS receiving combined melatonin-mitochondria. The results showed that 22 hr after ARDS induction, oxygen saturation (saO2 ) was lowest in the ARDS group and highest in normal controls, significantly lower in ARDS-melatonin and ARDS-mitochondria than in combined melatonin-mitochondria group, and significantly lower in ARDS-mitochondria than in ARDS-melatonin group. Conversely, right ventricular systolic blood pressure and lung weight showed an opposite pattern compared with saO2 among all groups (all P < 0.001). Histological integrity of alveolar sacs showed a pattern identical to saO2 , whereas lung crowding score exhibited an opposite pattern (all P < 0.001). Albumin level and inflammatory cells (MPO+, CD40+, CD11b/c+) from bronchoalveolar lavage fluid showed a pattern opposite to saO2 (all P < 0.001). Protein expression of indices of inflammation (MMP-9, TNF-α, NF-κB), oxidative stress (oxidized protein, NO-1, NOX-2, NOX-4), apoptosis (mitochondrial Bax, cleaved caspase-3, and PARP), fibrosis (Smad3, TGF-β), mitochondrial damage (cytochrome C), and DNA damage (γ-H2AX+) exhibited an opposite pattern compared to saO2 in all groups, whereas protein (HO-1, NQO-1, GR, GPx) and cellular (HO-1+) expressions of antioxidants exhibited a progressively increased pattern from normal controls to ARDS combined melatonin-mitochondria group (all P < 0.001). In conclusion, combined melatonin-mitochondrial was superior to either treatment alone in attenuating ARDS in this rat model.
A Novel Peptide Specifically Binding to Interleukin-6 Receptor (gp80) Inhibits Angiogenesis and Tumor Growth (2005)

Experimental and clinical findings support the essential role of interleukin (IL)-6 in the pathogenesis of various human cancers and provide a rationale for targeted therapeutic investigations. A novel peptide, S7, which selectively binds to IL-6 receptor (IL-6R) alpha chain (gp80) and broadly inhibits IL-6-mediated events, was identified using phage display library screening. The synthetic S7 peptide specifically bound to soluble IL-6R as well as cognate human IL-6R alpha, resulting in a dose-dependent blockade of the interaction between IL-6 and IL-6R alpha. S7 peptide prevents IL-6-mediated survival signaling and sensitizes cervical cancer cells to chemotherapeutic compounds in vitro. The in vitro analysis of antiangiogenic activity showed that S7 peptide substantially inhibits IL-6-induced vascular endothelial growth factor-A expression and angiogenesis in different cancer cell lines. Furthermore, S7 peptide was bioavailable in vivo, leading to a significant suppression of IL-6-induced vascular endothelial growth factor-mediated cervical tumor growth in severe combined immunodeficient mice. These observations show the feasibility of targeting IL-6/IL-6R interaction using the small peptide and highlight its potential in the clinical applications.
The Neurochemical and Metabolic Cascade Following Brain Injury: Moving from Animal Models to Man (1995)

Experimental traumatic brain injury produces a series of cellular events contributing to a neurochemical and neurometabolic cascade. This cascade is defined by the release of neurotransmitters resulting in a massive ionic flux, which, consequently, produces an increase in glycolysis. This increase in glycolysis is followed by a metabolic diaschisis, which is related to the degree and extent of behavioral deficits. Clinical efforts have now determined that a similar cascade occurs in human head injury, validating the animal model as well as providing new assessment strategies for the management and treatment of brain injury.
What's between simulation and formal verification? (2002)

This embedded tutorial surveys some possibilities for verification techniques that combine conventional simulation and ideas, techniques, and algorithms from formal verification, to obtain better functional test coverage of large designs.
Role of nonhistone proteins in the chromosomal events of mitosis (1994)

This review is concerned with the role of chromosomal nonhistone proteins in three important aspects of mitotic events: chromosome condensation, sister chromatid separation at the metaphase:anaphase transition, and interactions between the chromosomes and cytoskeleton that occur during construction of the mitotic spindle and cleavage furrow. Emphasis will be given to the potential roles of topoisomerase II and the chromosome passenger proteins in these events. Other important aspects of mitotic events such as the regulation of the G2-->M transition, the structural changes that affect the nuclear envelope and other organelles during mitosis, and the mechanism of chromosome movement will not be considered here. Despite long histories of often elegant experimentation, all three of our chosen subjects remain areas of lively, ongoing controversy. Thus, although recent advances appear to have taken us many steps closer to an understanding of the underlying mechanisms, we suspect that final answers will be some time in coming.
Learning to Transduce with Unbounded Memory (2015)

Recently, strong results have been demonstrated by Deep Recurrent Neural Networks on natural language transduction problems. In this paper we explore the representational power of these models using synthetic grammars designed to exhibit phenomena similar to those found in real transduction problems such as machine translation. These experiments lead us to propose new memory-based recurrent networks that implement continuously differentiable analogues of traditional data structures such as Stacks, Queues, and DeQues. We show that these architectures exhibit superior generalisation performance to Deep RNNs and are often able to learn the underlying generating algorithms in our transduction experiments.
The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion (1996)

We have studied an acute promyelocytic leukemia (APL) patient with a variant t(5;17)(q32;q12). This translocation fuses the gene for the nucleolar phosphoprotein nucleophosmin (NPM) to the retinoic acid receptor alpha (RARA). Two alternatively spliced transcripts are expressed, which differ in 129 bases immediately upstream of the RARA sequence. The NPM sequences contained in the shorter NPM-RAR cDNA are identical to the NPM sequences contained in the NPM-ALK fusion gene expressed in t(2;5) lymphomas. The RARA sequences are the same as the RARA sequences found in the PML-RAR and PLZF-RAR fusion seen in t(15;17) and t(11;17) APL, respectively. Both NPM-RAR transcripts fuse NPM and RARA sequence in the same reading frame, to generate translation products of 57 kD and 62 kD. Both NPM-RAR proteins are expressed in the patient's leukemic cells, along with wild-type RARA derived from the uninvolved allele. In transcriptional assays using a retinoic acid response element reporter construct, both NPM-RAR fusion proteins act as retinoic acid-dependent transcriptional activators. This case defines a third class of APL rearrangements, all of which generate fusion proteins of RARA.