gebhart/patrepeval huggingface dataset:
Modulation of cellular senescence in fibroblasts and dermal papillae cells in vitro. (2013)

A hexapeptide (Hexapeptide-11) of structure Phe-Val-Ala-Pro-Phe-Pro (FVAPFP) originally isolated from yeast extracts and later synthesized by solid state synthesis to high purity has demonstrated an ability to influence the onset of senescence in intrinsically aged fibroblasts, extrinsically aged fibroblasts, and extrinsically aged dermal papillae cells in vitro. The mechanism of senescence control is believed to be related to the peptide's ability to reversibly downregulate ataxia telangiectasia mutated (ATM) and p53 protein expression. The importance of p53 as the gatekeeping protein for monitoring cellular DNA damage is strategic for maintaining cellular health. ATM activates p53 by direct phosphorylation, causing cells to move into senescence which effectively moves them out of reproductive processes. Technologies that can influence ATM and p53 expression may offer unique benefits for controlling cellular senescence and effectively delaying cellular aging processes. The influence on ATM and p53 expression is noted to occur in both cell lines at peptide concentrations between 0.1% and 1.0%. The implications of these effects for aging benefits for skin and hair is important as, to date, no known small peptide has been suggested to demonstrate this effect in such a reversible and dose-dependent fashion.
Low threshold miniature Q-switched Nd:MgO:LiNbO3 laser (1986)

Nd:MgO:LiNbO 3 is a high gain solid-state laser material. In addition, it allows electronic control of the emitted radiation by virtue of its electrooptic properties. We have operated a miniature Q -switched laser consisting of a single 2- × 2- × 10-mm Nd:MgO:LiNbO 3 crystal and a Brewster plate placed between two mirrors spaced by 3 cm. This laser was end pumped by a dye laser beam at 598 nm. Peak powers of 5 W have been achieved with only 0.5% output coupling. Pulses 30-ns wide (FWHM) have been observed. The absorbed pump power threshold was 10 mW. Due to the material photoconductivity, an internal electric field can be generated that screens the external voltage. This screening effect was eliminated by applying the voltage in the form of pulses of alternating polarity. The voltage switching (from ~300 V to zero) excites several acoustic resonances in the crystal (piezoelectric effect) that modulate the crystal birefringence (elastooptic effect). The resulting time-dependent cavity loss affects the time of emission of the Q -switched pulse at low pump levels. However, the acoustic resonances have no influence when pumping more than three times above threshold.
A Copper- and Amine-Free Sonogashira Reaction Employing Aminophosphines as Ligands (2004)

An efficient Pd-catalyzed Sonogashira coupling reaction was achieved in the absence of a copper salt or amine with an inorganic base and easily prepared, air-stable aminophosphine ligands in commonly used organic solvents; good to excellent yields were obtained. Under optimized reaction conditions, the Sonogashira coupling reaction occurred selectively when an enyne substrate was employed and no Heck reaction product was detected; acetone-masked acetylene and trimethylsilylacetylene can also be efficiently coupled, providing a method to make terminal alkynes.
Exciton interactions in cyanine dye–hyaluronic acid (HA) complex: reversible and biphasic molecular switching of chromophores induced by random coil-to-double-helix phase transition of HA (2004)

Reversible and biphasic switching of monomer-to-R-chiral dimer transition and R-chiral-to-S-chiral dimer transition of cyanine chromophores were demonstrated by complex formation with hyaluronic acid.
Thy‐1 as a regulator of cell‐cell and cell‐matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis (2006)

Thy-1 (CD90) is a 25-37 kDa glycosylphosphatidylinositol (GPI) -anchored glycoprotein expressed on many cell types, including T cells, thymocytes, neurons, endothelial cells, and fibroblasts. Activation of Thy-1 can promote T cell activation, and this role of Thy-1 is reviewed elsewhere. Thy-1 also affects numerous nonimmunologic biological processes, including cellular adhesion, neurite outgrowth, tumor growth, migration, and cell death. In reviewing the nonimmunologic functions of Thy-1, we discuss the phenotype of the Thy-1 null mouse, signaling pathways modulated by Thy-1, the role of the GPI anchor in Thy-1 localization to lipid rafts and signaling, and regulation of Thy-1 expression. Thy-1 is an important regulator of cell-cell and cell-matrix interactions, with important roles in nerve regeneration, metastasis, inflammation, and fibrosis.
Plasma kinetics and biodistribution of a lipid emulsion resembling low-density lipoprotein in patients with acute leukemia. (1994)

Low-density lipoprotein (LDL) could be used as a carrier of chemotherapeutic agents to neoplastic cells that overexpress LDL receptors (rLDL), but LDL is difficult to obtain and handle. Recently, it was observed that a protein-free emulsion resembling the lipid portion of LDL (LDE) behave like native LDL when injected into the bloodstream. In this study, the evidence that LDE is taken up by rLDL was expanded by comparing LDL and LDE plasma decay curves in rabbits and by competition experiments with lymphocytes. To verify whether LDE could be removed from the plasma by neoplastic cells with increased rLDL, LDE labeled with 14Ccholesteryl ester was injected into 14 patients with acute myeloid leukemia (AML) and into 7 with acute lymphocytic leukemia (ALL). In AML rLDL expression is increased but in ALL it is normal. LDE plasma fractional clearance rate (FCR, in h-1) was calculated from the remaining radioactivity measured in plasma samples collected during 24 h following injection. LDE FCR was 3-fold greater in AML than in ALL patients 0.192 +/- 0.210 (SD) and 0.066 +/- 0.033 h-1, respectively, P < 0.035. When LDE injection was repeated in 9 AML patients in hematological remission, LDE FCR diminished 66% compared to the pretreatment values (from 0.192 +/- 0.210 to 0.065 +/- 0.038 h-1, P < 0.02), so that it could be estimated that nearly 66% of the emulsion was taken up by AML cells and only 34% by the normal tissues. As expected, LDE FCR was unchanged in 4 patients with ALL in hematological remission (0.069 +/- 0.044 h-1). Gamma camera images obtained 6 h after the injection of 99mTc-label LDE into one patient with ALL showed biodistribution similar to that of LDL. In one AML patient LDE was comparatively more concentrated over the areas corresponding to the bone marrow infiltrated by AML cells. Our results indicate that LDE FCR is increased in a disease known to contain malignant cells that overexpress rLDL, suggesting that LDE is taken up by malignant cells with increased rLDL.
Design Issues for a Dexter-based Hypermedia System (1993)

This paper discusses experiences and lessons learned from the design of an open hypermedia system, one that integrates applications and data not ''owned'' by the hypermedia. The Dexter Hypertext Reference Model was used as the basis for the design. Though our experiences were generally positive, we found the model constraining in certain ways and underdeveloped in others. For instance, Dexter argues against dangling links, but we found several situations where permitting and supporting dangling links was advisable. In Dexter, the data objects making up a component's contents are encapsulated in the component; in practice, references to objects stored apart from the hyper media structure should be allowed. We elaborate Dexter's notion of composite component to include composites that ''contain'' other components and composites with structured contents, among others. The paper also includes a critique of Dexter's notion of link directionality, proposes a distinction between marked and unmarked anchors, and discusses anchoring within a composite.
Lentiviral Vector-Mediated Delivery of Short Hairpin RNA Results in Persistent Knockdown of Gene Expression in Mouse Brain (2003)

RNA interference (RNAi) is an evolutionarily conserved mechanism of posttranscriptional gene-specific silencing. For in vivo applications, RNAi has been hampered until recently by inefficient delivery methods and by the transient nature of the gene suppression. Lentiviral vectors (LVs) hold great promise for gene therapeutic applications, pharmaceutical target validation, and functional genomics because stable gene transfer is mediated both in dividing and nondividing cells. We have used a lentiviral vector-based system for RNAi. We produced human immunodeficiency virus type 1-derived LVs encoding a short hairpin RNA specific for enhanced green fluorescent protein (EGFP) mRNA that were capable of inhibiting EGFP expression in mammalian cells. EGFP knockdown persisted after multiple passages of the cells. Of particular interest, our RNAi LVs were equally effective in suppression and prevention of EGFP expression after stereotactic injection in adult mouse brain. Therefore, we believe that the use of LVs for stable RNAi in brain will become a powerful aid to probe gene function in vivo and for gene therapy of diseases of the central nervous system.
Audio-visual based emotion recognition-a new approach (2004)

Emotion recognition is one of the latest challenges in intelligent human/computer communication. Most of the previous work on emotion recognition focused on extracting emotions from visual or audio information separately. A novel approach is presented in this paper, including both visual and audio from video clips, to recognize the human emotion. The facial animation parameters (FAPs) compliant facial feature tracking based on active appearance model is performed on the video to generate two vector stream which represent the expression feature and the visual speech one. Combined with the visual vectors, the audio vector is extracted in terms of low level features. Then, a tripled hidden Markov model is introduced to perform the recognition which allows the state asynchrony of the audio and visual observation sequences while preserving their natural correlation over time. The experimental results show that this approach outperforms only using visual or audio separately.
Antitumor activity of indomethacin in mice bearing advanced colon 26 carcinoma compared with those with early transplants. (1989)

The antitumor activity of indomethacin (IND) was investigated in mice bearing advanced colon 26 adenocarcinoma compared with its early transplants. Treatment with 0.001% IND in drinking water retarded the growth of tumor when commenced at Day 1 after the tumor inoculation. The suppression of the tumor growth by IND continued up to 4 to 5 weeks as long as the size of the tumor remained small. On the other hand, IND given to mice bearing a large burden of the tumor at 2 weeks after the inoculation had facilitated the tumor growth. IND reduced tumor-associated PGE2 production in mice bearing either small or large burdens of the tumors. These results indicate that the antitumor activity of IND depends on tumor size and therefore is not simply associated with the reduction of PGE2 levels. We found that colon 26 caused changes in parameters reported for tumor cachexia, such as weight loss, wasting of muscle and adipose tissues and hypoglycemia, when it grew to around 1 g at 2-3 weeks after the tumor inoculation. IND given to the mice with large burdens of colon 26 alleviated the cachexia of the mice, resulting in the increase of the survival time even though the growth of the tumor had been facilitated. It is possible that IND affects the tumor growth and survival by reversing tumor-induced disorders in homeostasis.
Silicon microring resonators with 1.5-μm radius (2008)

We demonstrate a junction between a silicon strip waveguide and an ultra-compact silicon microring resonator that minimizes spurious light scattering and increases the critical dimensions of the geometry. We show cascaded silicon microring resonators with radii around 1.5 microm and effective mode volumes around 1.0 microm(3) that are critically coupled to a waveguide with coupled Q's up to 9,000. The radius of 1.5 microm is smaller than the operational wavelength, and is close to the theoretical size limit of the silicon microring ring resonator for the same Q. The device is fabricated with a widely-available SEM-based lithography system using a stitch-free design based on a U-shaped waveguide.
简·方达——好莱坞不老红星的传奇一生 (2014)

她，出身在演艺世家，童年的不幸让她饱受挫折，却从未磨灭她生活的勇气；她，曾获奥斯卡两届影后的殊荣，精湛而率真的演技使她成为好莱坞的常青树；她，是20世纪80年代的健身皇后，一生都在追求着完美；她，更是热心公益的慈善大使，把温暖带给了无数人。她，就是简·方达。她曾说过：“年龄大的人也有他们的精彩，只有没自信的人才会害怕变老，只要你不生活在焦虑或者恐惧之中，你就能自由自在，变得越来越有活力。”自信而坚强的她，美得如此闪耀。
Chemical Structures and Bioactivities of Sulfated Polysaccharides from Marine Algae (2011)

Sulfated polysaccharides and their lower molecular weight oligosaccharide derivatives from marine macroalgae have been shown to possess a variety of biological activities. The present paper will review the recent progress in research on the structural chemistry and the bioactivities of these marine algal biomaterials. In particular, it will provide an update on the structural chemistry of the major sulfated polysaccharides synthesized by seaweeds including the galactans (e.g., agarans and carrageenans), ulvans, and fucans. It will then review the recent findings on the anticoagulant/antithrombotic, antiviral, immuno-inflammatory, antilipidemic and antioxidant activities of sulfated polysaccharides and their potential for therapeutic application.
Testosterone Dose-Dependently Increases Maximal Voluntary Strength and Leg Power, but Does Not Affect Fatigability or Specific Tension (2003)

Testosterone supplementation in men increases fat-free mass, but whether measures of muscle performance, such as maximal voluntary strength, power, fatigability, or specific tension, are improved has not been determined. Furthermore, the extent to which these measures of muscle performance are related to testosterone dose or circulating concentration is unknown. To examine the relationship between testosterone dose and muscle performance, 61 healthy, eugonadal young men (aged 18-35 yr) were randomized to 1 of 5 groups, each receiving a long-acting GnRH agonist to suppress endogenous testosterone production plus weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate for 20 wk. These doses produced mean nadir testosterone concentrations of 253, 306, 542, 1345, and 2370 ng/dl, respectively. Maximal voluntary muscle strength and fatigability were determined by a seated leg press exercise. Leg power was measured using a validated leg power instrument. Specific tension was estimated by the ratio of one repetition maximum muscle strength to thigh muscle volume determined by magnetic resonance imaging. Testosterone administration was associated with a dose-dependent increase in leg press strength and leg power, but muscle fatigability did not change significantly during treatment. Changes in leg press strength were significantly correlated with total (r = 0.46; P = 0.0005) and free (r = 0.38; P = 0.006) testosterone as was leg power (total testosterone: r = 0.38; P = 0.007; free testosterone: r = 0.35; P = 0.015), but not muscle fatigability. Serum IGF-I concentrations were not significantly correlated with leg strength, power, or fatigability. Specific tension did not change significantly at any dose. We conclude that the effects of testosterone on muscle performance are specific; it increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. The changes in leg strength and power are dependent on testosterone dose and circulating testosterone concentrations and exhibit a log-linear relationship with serum total and free testosterone. Failure to observe a significant testosterone dose relationship with fatigability suggests that testosterone does not affect this component of muscle performance and that different components of muscle performance are regulated by different mechanisms.
Superfamily 2 helicases (2012)

Superfamily 2 helicases are involved in all aspects of RNA metabolism, and many steps in DNA metabolism. This review focuses on the basic mechanistic, structural and biological properties of each of the families of helicases within superfamily 2. There are ten separate families of helicases within superfamily 2, each playing specific roles in nucleic acid metabolism. The mechanisms of action are diverse, as well as the effect on the nucleic acid. Some families translocate on single-stranded nucleic acid and unwind duplexes, some unwind double-stranded nucleic acids without translocation, and some translocate on double-stranded or single-stranded nucleic acids without unwinding.
Antigenic and structural properties of the hemagglutinin-neuraminidase glycoprotein of human parainfluenza virus type 3: sequence analysis of variants selected with monoclonal antibodies which inhibit infectivity, hemagglutination, and neuraminidase activities (1987)

The hemagglutinin-neuraminidase (HN) gene sequence was determined for 16 antigenic variants of human parainfluenza virus type 3 (PIV3). The variants were selected by using monoclonal antibodies (MAbs) to the HN protein which inhibit neuraminidase, hemagglutination, or both activities. Each variant had a single-point mutation in the HN gene, coding for a single amino acid substitution in the HN protein. Operational and topographic maps of the HN protein correlated well with the relative positions of the substitutions. There was little correlation between the cross-reactivity of a MAb with the bovine PIV3 HN and the amount of amino acid homology between the human and bovine PIV3 HN proteins in the regions of the epitopes, suggesting that many of the epitopes are conformational in nature. Computer-assisted analysis of the HN protein predicted a secondary structure composed primarily of hydrophobic beta sheets interconnected by random hydrophilic coil structures. The HN epitopes were located in predicted coil regions. Epitopes recognized by MAbs which inhibit neuraminidase activity of the virus were located in a region which appears to be structurally conserved among several paramyxovirus HN proteins and which may represent the sialic cid-binding site of the HN molecule.
Mammalian Target of Rapamycin (mTOR) Inhibitors as Anti-Cancer Agents (2004)

Highly specific signal transduction inhibitors are being developed as anti-cancer agents against an array of molecular targets, with the promise of increased selectivity and lower toxicity than classic cytotoxic chemotherapy agents. Rapamycin and its analogues are a promising class of novel therapeutics that specifically inhibit signaling from the serine-threonine kinase, mammalian target of rapamycin (mTOR). mTOR is a key intermediary in multiple mitogenic signaling pathways and plays a central role in modulating proliferation and angiogenesis in normal tissues and neoplastic processes. Rapamycin potently inhibits T-cell proliferation, and is approved for clinical use as an immuno-suppressant following kidney transplantation. Hyperactivation of mTOR signaling has been implicated in tumorigenesis, and promising pre-clinical studies in several tumor types suggest that the anti-proliferative and anti-angiogenic properties of rapamycin may be useful in cancer therapy. These studies have led to several clinical trials evaluating the safety and efficacy of rapamycin analogs in cancer therapy. The goal of this article is to review the mechanism of action of rapamycin as an anti-cancer agent, and to review the clinical experience with rapamycin and rapamycin analogs as immunosuppressive and anti-neoplastic therapeutic agents.
Molecular Interactions of the Gating Modifier Toxin ProTx-II with Nav1.5 (2007)

Voltage-gated Na(+) channels are critical components in the generation of action potentials in excitable cells, but despite numerous structure-function studies on these proteins, their gating mechanism remains unclear. Peptide toxins often modify channel gating, thereby providing a great deal of information about these channels. ProTx-II is a 30-amino acid peptide toxin from the venom of the tarantula, Thrixopelma pruriens, that conforms to the inhibitory cystine knot motif and which modifies activation kinetics of Na(v) and Ca(v), but not K(v), channels. ProTx-II inhibits current by shifting the voltage dependence of activation to more depolarized potentials and, therefore, differs from the classic site 4 toxins that shift voltage dependence of activation in the opposite direction. Despite this difference in functional effects, ProTx-II has been proposed to bind to neurotoxin site 4 because it modifies activation. Here, we investigate the bioactive surface of ProTx-II by alanine-scanning the toxin and analyzing the interactions of each mutant with the cardiac isoform, Na(v)1.5. The active face of the toxin is largely composed of hydrophobic and cationic residues, joining a growing group of predominantly K(v) channel gating modifier toxins that are thought to interact with the lipid environment. In addition, we performed extensive mutagenesis of Na(v)1.5 to locate the receptor site with which ProTx-II interacts. Our data establish that, contrary to prior assumptions, ProTx-II does not bind to the previously characterized neurotoxin site 4, thus making it a novel probe of activation gating in Na(v) channels with potential to shed new light on this process.
Paraphrase Generation with Deep Reinforcement Learning (2017)

Automatic generation of paraphrases from a given sentence is an important yet challenging task in natural language processing (NLP), and plays a key role in a number of applications such as question answering, search, and dialogue. In this paper, we present a deep reinforcement learning approach to paraphrase generation. Specifically, we propose a new framework for the task, which consists of a \textit{generator} and an \textit{evaluator}, both of which are learned from data. The generator, built as a sequence-to-sequence learning model, can produce paraphrases given a sentence. The evaluator, constructed as a deep matching model, can judge whether two sentences are paraphrases of each other. The generator is first trained by deep learning and then further fine-tuned by reinforcement learning in which the reward is given by the evaluator. For the learning of the evaluator, we propose two methods based on supervised learning and inverse reinforcement learning respectively, depending on the type of available training data. Empirical study shows that the learned evaluator can guide the generator to produce more accurate paraphrases. Experimental results demonstrate the proposed models (the generators) outperform the state-of-the-art methods in paraphrase generation in both automatic evaluation and human evaluation.
The JAK-STAT Signaling Pathway: Input and Output Integration (2007)

Universal and essential to cytokine receptor signaling, the JAK-STAT pathway is one of the best understood signal transduction cascades. Almost 40 cytokine receptors signal through combinations of four JAK and seven STAT family members, suggesting commonality across the JAK-STAT signaling system. Despite intense study, there remain substantial gaps in understanding how the cascades are activated and regulated. Using the examples of the IL-6 and IL-10 receptors, I will discuss how diverse outcomes in gene expression result from regulatory events that effect the JAK1-STAT3 pathway, common to both receptors. I also consider receptor preferences by different STATs and interpretive problems in the use of STAT-deficient cells and mice. Finally, I consider how the suppressor of cytokine signaling (SOCS) proteins regulate the quality and quantity of STAT signals from cytokine receptors. New data suggests that SOCS proteins introduce additional diversity into the JAK-STAT pathway by adjusting the output of activated STATs that alters downstream gene activation.