gebhart/patrepeval huggingface dataset:
The Amino-terminal Domain of Human STAT4 (1998)

The multifunctional signal transducer and activator of transcription (STAT) proteins relay signals from the cell membrane to the nucleus in response to cytokines and growth factors. STAT4 becomes activated when cells are treated with interleukin-12, a key cytokine regulator of cell-mediated immunity. Upon activation, dimers of STAT4 bind cooperatively to tandem interferon-gamma activation sequences (GAS elements) near the interferon-gamma gene and stimulate its transcription. The amino-terminal domain of STAT4 (STAT4(1-124)) is required for cooperative binding interactions between STAT4 dimers and activation of interferon-gamma transcription in response to interleukin-12. We have overproduced this domain of human STAT4 (hSTAT4(1-124)) in Escherichia coli and purified it to homogeneity for structural studies. The circular dichroism spectrum of hSTAT4(1-124) indicates that it has a well ordered conformation in solution. The translational diffusion constant of hSTAT4(1-124) was determined by nuclear magnetic resonance methods and found to be consistent with that of a dimer. The rotational correlation time (tauc) of hSTAT4(1-124) was estimated from 15N relaxation to be 16 ns; this value is consistent with a 29-kDa dimeric protein. These results, together with the number of signals observed in the two-dimensional 1H-15N heteronuclear single quantum coherence spectrum of uniformly 15N-labeled protein, indicate that hSTAT4(1-124) forms a stable, symmetric homodimer in solution. Cooperativity in native STAT4 probably results from a similar or identical interaction between the amino-terminal domains of adjacent dimers bound to DNA.
Mental Health and Illness in Australia: Some Contemporary Facts and Figures (2012)

We report here an acidic polysaccharide, namely RSP-3, which ameliorates acute kidney injury and is obtained from Sanguisorba officinalis. We extracted and purified two polysaccharides from this herb based on the acidity and screened them for their effect in regulating the immunological activity of macrophages. Among them, RSP-3 exhibited significant anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated macrophages by decreasing TNF-α and IL-6 levels. Subsequently, we found that RSP-3 suppressed ER stress, reduced ROS production and blocked NF-κBp65 translocation. After fully characterizing RSP-3 with a series of analytical technologies, we tested its anti-acute kidney injury (AKI) effect in vivo. In a murine AKI model induced by LPS, treatment with RSP-3 effectively ameliorated renal function. Besides, it decreased the levels of TNF-α and IL-6 in serum and reduced macrophage infiltration in injured kidney tissue. In sum, RSP-3, with a significant protective effect against AKI by showing anti-inflammatory activity, may become a meaningful drug candidate for treatment of AKI.
CD31 (PECAM‐1)‐bright cells derived from AC133‐positive cells in human peripheral blood as endothelial‐precursor cells (2003)

To clarify the process of endothelial differentiation, we isolated AC133(+) cells and induced the in vitro differentiation of these cells into endothelial cells. AC133(+) cells efficiently differentiated into endothelial cells when the cells were cultured on fibronectin-coated dishes in the presence of vascular endothelial growth factor. Time-course analysis of the alteration of endothelial markers on cultured AC133(+) cells revealed that the expression of CD31 (PECAM-1) on AC133(+) cells was the earliest marker among all of the tested markers. Based on the hypothesis that CD31 is an early indicator during the endothelial differentiation, we examined the relationship between CD31 expression and the ability to differentiate into endothelial cells in cells derived from AC133(+) cells. CD31-bright cells, which were sorted from cultured AC133(+) cells, differentiated more efficiently into endothelial cells than had CD31-positive or CD31-negative cells, suggesting that CD31-bright cells may be precursor cells for endothelial cells. In the present study, we identified CD31(+) cells derived from cultured AC133(+) cells that are able to differentiate to endothelial cells as precursor cells.
An 80 MFLOPS floating-point engine in the Intel i860 processor (2003)

The i860 processor is a 64-b microprocessor with 1.02 million transistors. It has a 64-b external data bus and a 32-b external address bus. It is fabricated with Intel's CHMOS IV technology (a 1- mu m double-metal process). The die size is approximately 10 mm*15 mm. First silicon is functional over commercial temperature and voltage ranges with an execution speed of 40 MHz. The floating-point engine consists of a pipelined adder and a pipelined multiplier, incorporates a special hardware to support the dual operation instructions, and operates synchronously with the RISC (reduced-instruction-set computer) core to execute up to three operations per clock. Its high performance lends itself well to a numeric-intensive computation environment, including vector processing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Endo/exo mechanism and processivity of family 18 chitinases produced by Serratia marcescens (2006)

We present a comparative study of ChiA, ChiB, and ChiC, the three family 18 chitinases produced by Serratia marcescens. All three enzymes eventually converted chitin to N-acetylglucosamine dimers (GlcNAc2) and a minor fraction of monomers. ChiC differed from ChiA and ChiB in that it initially produced longer oligosaccharides from chitin and had lower activity towards an oligomeric substrate, GlcNAc6. ChiA and ChiB could convert GlcNAc6 directly to three dimers, whereas ChiC produced equal amounts of tetramers and dimers, suggesting that the former two enzymes can act processively. Further insight was obtained by studying degradation of the soluble, partly deacetylated chitin-derivative chitosan. Because there exist nonproductive binding modes for this substrate, it was possible to discriminate between independent binding events and processive binding events. In reactions with ChiA and ChiB the polymer disappeared very slowly, while the initially produced oligomers almost exclusively had even-numbered chain lengths in the 2-12 range. This demonstrates a processive mode of action in which the substrate chain moves by two sugar units at a time, regardless of whether complexes formed along the way are productive. In contrast, reactions with ChiC showed rapid disappearance of the polymer and production of a continuum of odd- and even-numbered oligomers. These results are discussed in the light of recent literature data on directionality and synergistic effects of ChiA, ChiB and ChiC, leading to the conclusion that ChiA and ChiB are processive chitinases that degrade chitin chains in opposite directions, while ChiC is a nonprocessive endochitinase.
RNA synthesized in calicivirus-infected cells is atypical of picornaviruses (1977)

RNA labeled with [3H]uridine from Vero cells infected with San Miguel sea lion virus in the presence of actinomycin D was analyzed by glycerol density gradient sedimentation and polyacrylamide gel electrophoresis. The predominant single-stranded RNA (36S, 2.6 x 10(6) molecular weight) was genome size. There was also a prominent 22S, 1.1 x 10(6)-molecular weight, single-stranded component and one or more double-stranded or partially double-stranded classes. Replicative forms, sedimenting at 18S, contained single-stranded RNA corresponding to the larger-molecular-weight class. All classes of intracellular RNA and virion RNA were polyadenylated. These findings and results with pig kidney cells infected with vesicular exanthema of swine virus and feline cells infected with feline calicivirus indicate that caliciviruses exhibit a strategy of replication different from typical picornaviruses and supports removal of the caliciviruses from the family Picornaviridae.
Probiotic modulation of symbiotic gut microbial–host metabolic interactions in a humanized microbiome mouse model (2008)

The transgenomic metabolic effects of exposure to either Lactobacillus paracasei or Lactobacillus rhamnosus probiotics have been measured and mapped in humanized extended genome mice (germ-free mice colonized with human baby flora). Statistical analysis of the compartmental fluctuations in diverse metabolic compartments, including biofluids, tissue and cecal short-chain fatty acids (SCFAs) in relation to microbial population modulation generated a novel top-down systems biology view of the host response to probiotic intervention. Probiotic exposure exerted microbiome modification and resulted in altered hepatic lipid metabolism coupled with lowered plasma lipoprotein levels and apparent stimulated glycolysis. Probiotic treatments also altered a diverse range of pathways outcomes, including amino-acid metabolism, methylamines and SCFAs. The novel application of hierarchical-principal component analysis allowed visualization of multicompartmental transgenomic metabolic interactions that could also be resolved at the compartment and pathway level. These integrated system investigations demonstrate the potential of metabolic profiling as a top-down systems biology driver for investigating the mechanistic basis of probiotic action and the therapeutic surveillance of the gut microbial activity related to dietary supplementation of probiotics.
The RASSF1A Tumor Suppressor Blocks Cell Cycle Progression and Inhibits Cyclin D1 Accumulation (2002)

The RASSF1A locus at 3p21.3 is epigenetically inactivated at high frequency in a variety of solid tumors. Expression of RASSF1A is sufficient to revert the tumorigenicity of human cancer cell lines. We show here that RASSF1A can induce cell cycle arrest by engaging the Rb family cell cycle checkpoint. RASSF1A inhibits accumulation of native cyclin D1, and the RASSF1A-induced cell cycle arrest can be relieved by ectopic expression of cyclin D1 or of other downstream activators of the G(1)/S-phase transition (cyclin A and E7). Regulation of cyclin D1 is responsive to native RASSF1A activity, because RNA interference-mediated downregulation of endogenous RASSF1A expression in human epithelial cells results in abnormal accumulation of cyclin D1 protein. Inhibition of cyclin D1 by RASSF1A occurs posttranscriptionally and is likely at the level of translational control. Rare alleles of RASSF1A, isolated from tumor cell lines, encode proteins that fail to block cyclin D1 accumulation and cell cycle progression. These results strongly suggest that RASSF1A is an important human tumor suppressor protein acting at the level of G(1)/S-phase cell cycle progression.
Effect of hyperthermia on the radiosensitivity of normal and malignant cells in mice (1976)

The effect of systemic hyperthermia on the in vivo radiation response of normal and malignant mouse cells was evaluated. X-irradiation of L1210 cells and Ehrlich ascites cells at body temperatures above 41 degrees C resulted in strongly enhanced tumor cell death. The magnitude of this thermal effect increased with increasing temperatures. Hypoxic tumor cells were particularly sensitive to combined heat-radiation treatment. L1210 leukemia cells did not become resistant to the sensitizing effects of hyperthermia even after repeated heat exposures over several transplant generations. The sensitizing action of hyperthermia varied with different heating strategies. Heating before or during irradiation did not materially alter the radiation response of tumor cells. Maximal potentiation of radiation damage was achieved only when the tumorous mice were subjected to at least 20 minutes heat incubation after irradiation. LD studies on ICR mice revealed that moderate hyperthermia (41.5 degrees C) does not alter the radiation response of normal body tissues. These findings indicate that it is possible to devise hyperthermic treatment regimens that drastically enhance radiation-induced tumor cell death in vivo without reducing the radioresistance of normal tissues.
CXCR3+CCR5+ T cells and autoimmune diseases: guilty as charged? (2014)

Prior to the 1990s, genetic analyses indicated that many autoimmune diseases are driven by T cell responses; however, the identity of the pathogenic T cell populations responsible for dysfunctional autoimmune responses remained unclear. Some 20 years ago, the discovery of numerous chemokines and their receptors along with the development of specific mAbs to these provided a distinct advance. These new tools revealed a remarkable dichotomy and disclosed that some chemokine receptors guided the constitutive migration of T cells through lymphoid tissues, whereas others, such as CCR5 and CXCR3, guided effector and memory T cell migration to inflammatory lesions. These T cell markers enabled a new understanding of immune responses and the types of T cells involved in different inflammatory reactions.
A Security Evaluation of DNSSEC with NSEC3. (2010)

Domain Name System Security Extensions (DNSSEC) and Hashed Authenticated Denial of Existence (NSEC3) are slated for adoption by important parts of the DNS hierarchy, including the root zone, as a solution to vulnerabilities such as ”cache-poisoning” attacks. We study the security goals and operation of DNSSEC/NSEC3 using Mur’, a finite-state enumeration tool, to analyze security properties that may be relevant to various deployment scenarios. Our systematic study reveals several subtleties and potential pitfalls that can be avoided by proper configuration choices, including resource records that may remain valid after the expiration of relevant signatures and potential insertion of forged names into a DNSSEC-enabled domain via the opt-out option. We demonstrate the exploitability of DNSSEC opt-out options in an enterprise setting by constructing a browser cookie-stealing attack on a laboratory domain. Under recommended configuration settings, further Mur’ model checking finds no vulnerabilities within our threat model, suggesting that DNSSEC with NSEC3 provides significant security benefits.
Abstract 2637: Hsp90 inhibitor STA-9090 enhances the activity of standard of care therapies in erlotinib-sensitive and -resistant NSCLC models (2010)

Abstract BACKGROUND: Heat shock protein 90 (Hsp90) is a molecular chaperone that regulates the folding, stability and activity of many kinases and signal transduction proteins that are critical for the proliferation and survival of cancer cells. These Hsp90 client proteins include wild type and drug-resistant forms of such clinically important drug targets as: BCR-ABL, BRAF, EGFR, HER2, KIT, MET and VEGFR1. STA-9090 is a highly potent and less toxic, next-generation Hsp90 inhibitor that is structurally unrelated to first-generation agents such as 17-AAG and IPI-504. STA-9090 induces proteasome-mediated degradation of Hsp90 client proteins preferentially in cancer versus normal cells, resulting in cell cycle arrest and apoptosis. STA-9090 is currently being evaluated in multiple Phase 1/2 clinical trials in sold tumor and hematologic malignancies, including an open-label, multi-center Phase 2 trial in patients with advanced NSCLC harboring wild type or activated forms of EGFR or KRAS. In anticipation of conducting clinical trials combining STA-9090 with therapeutic agents commonly employed to treat NSCLC, we have examined the ability of STA-9090 to enhance the in vitro and in vivo activity of paclitaxel, docetaxel, erlotinib and bevacizumab in preclinical models of lung cancer. RESULTS: In vitro cytotoxicity studies were conducted with the erlotinib-sensitive HCC827 (expressing EGFRdel746–750) and erlotinib-resistant NCI-H1975 (expressing EGFRL858R/T790M) NSCLC cell lines. Using the median-effect method of Chau and Talalay, STA-9090 was found to significantly enhance the in vitro cytotoxicity of the taxanes, paclitaxel and docetaxel, with combination index (CI) values ranging from 0.3-0.7, which is indicative of synergy rather than additive or antagonistic effects. Similarly, STA-9090 also displayed synergy (0.4-0.8 CI) with the EGFR inhibitor erlotinib against erlotinib-sensitive cells, but as expected, not against erlotinib-resistant cells. Consistent with these results, STA-9090 enhanced the in vivo efficacy of concomitantly dosed paclitaxel and docetaxel in the HCC827 and NCI-H1975 xenograft models. Further, STA-9090 also enhanced the in vivo efficacy of the anti-VEGF monoclonal antibody bevacizumab in these models. These combinations did not result in significant additional toxicity relative to the single agents alone, and pharmacokinetic analyses demonstrated that these findings were not due to drug-drug interactions. CONCLUSIONS: Our results demonstrate that STA-9090 potently synergizes with paclitaxel, docetaxel, erlotinib and bevacizumab, which are widely employed to treat NSCLC in the clinic. Hsp90 inhibition using STA-9090 represents a novel and promising approach to combination therapy for NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2637.
Nucleosides. 133. Synthesis of 5-alkenyl-1-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)cytosines and related pyrimidine nucleosides as potential antiviral agents (1985)

The synthesis of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)cytosines with a halovinyl or vinyl substituent at C-5 was accomplished from the corresponding 5-iodo (FIAC, 1) and/or 5-chloromercuri nucleoside analogues with use of Li2PdCl4- and Pd(OAc)2-mediated coupling reactions. Thiation of the benzoylated derivative of the 5-ethyluracil nucleoside 3 followed by S-methylation and then ammonolysis provided 5-ethyl-2'-fluoro-ara-C. 5-Ethynyl-2'-fluoro-ara-C (19a) and 5-ethynyl-2'-fluoro-ara-U (19b) were also obtained from the persilylated 5-iodo nucleosides 1 and 16, respectively, by PdII/CuI catalyzed coupling with (trimethylsilyl)acetylene. With use of selective sugar deprotection of the initial coupling products with H2O/Me2SO, the corresponding 5-[2-(trimethylsilyl)ethynyl] derivatives 18a and 18b could be isolated. Most of the new compounds showed activity in vitro against both HSV-1 and HSV-2, as did the known corresponding 5-alkenyluracil nucleosides synthesized earlier. The 5-vinylcytosine and -uracil nucleosides 10 and 24, respectively, were highly effective against HSV-1 (ED90 = 0.40 and 0.043 microM, respectively) and HSV-2 (ED90 = 0.59 and 0.56 microM, respectively). Unlike BVDU, the 2'-fluoroarabinosyl derivatives of 5-(halovinyl)cytosine and -uracil showed activity against both types of herpes simplex virus. The therapeutic indices of these compounds are in some cases superior to those of 2'-fluoro-5-methyl-ara-U (FMAU, 2). Moderate antileukemic activity was observed in vitro for the 5-alkynyl and 5-vinyl compounds. The competition of these compounds with thymidine for viral-induced thymidine kinases was also studied.
Tunable high Q narrow-band triplexer (2009)

A switchless bank of three tunable bandpass filters is demonstrated which can be used as a triplexer over a large tuning range. Three high Q narrow-band evanescent-mode cavity filters are integrated in a single substrate using an input feed-line network to achieve multi-band operation. Using shorted feed-lines for magnetic field coupling allows the out of band impedance to be dominated by the reactance of the feed-lines. The feed-lines are then designed to have high out of band impedance over the tuning range. A three-way switchless filter bank is presented in the 1.7 GHz-3.4 GHz range maintaining less than 4 dB loss for 14 MHz-31 MHz 3-dB bandwidth over most of the tuning range. The filter bank is fabricated in one low-loss Rogers TMM3 substrate using standard PCB processing, and commercially available 0.5 mm thick piezoelectric actuators are used for the electrical tuning.
An experiential, social network‐based approach to direct marketing (2009)

Purpose Direct marketing faces challenges and opportunities associated with the emergence of social network media. Companies need to address target audiences both directly and also indirectly through social media. The purpose of this paper is to provide a review of the changing media landscape of direct marketing, and proposes a model of direct and indirect targeting of buyers. Design/methodology/approach A conceptual model is presented which brings together the needs of producers, sellers and communities. Customer experience is used as an integrative framework for reconciling the sometimes differing needs of these groups. Findings The literature is reviewed, noting changes in media habits. Previous studies of social network users provide a picture of the benefits sought by members of online communities. Originality/value Assessment of direct marketing has traditionally emphasised cognitive and behavioural metrics. This paper has proposed an experiential framework which may be more difficult to measure, but evidence is presented that emotions associated with use of social network web sites may be more important as a key success factor for direct marketing.
Strategies for the identification of interacting proteins. (1993)

Many problems in modern biology involve complex arrays of interacting protein and, in some cases, RNA molecules. The initial challenge facing investigators is to identify the important players that drive the process under study. This difficult task is ameliorated somewhat by the development of methods designed to keep pace with the magnitude of this challenge. I have outlined a few of these approaches at the cutting edge of cloning interacting proteins. A perhaps more daunting prospect is to dissect the important molecules once they are in hand, to identify key interactions, and, ultimately, to move to an understanding of function in cells. For this, of course, all of the tools of genetics, biochemistry, and molecular biology, extant and yet to be developed, will have to be tapped.
Insecticidal and synergistic effects of Majorana hortensis essential oil and some of its major constituents (2009)

Abstract The essential oil from leaves of Majorana hortensis Moench (Lamiaceae) was isolated by hydrodistillation with a yield of 1.6% (wt/wt). The insecticidal activity of the oil was evaluated against fourth instars of Spodoptera littoralis Boisduval (Lepidoptera: Noctuidae) and adults of Aphis fabae L. (Hemiptera: Aphididae). The oil showed a remarkable toxic effect against S. littoralis in a topical application assay (LD 50 = 2.48 μg per larva) and in a residual film assay (LC 50 = 3.14 g/l). The oil of M. hortensis also exhibited a pronounced toxic effect against A. fabae adults with LC 50 values of 1.86 and 2.27 g/l in rapid dipping and residual film assays, respectively. Gas chromatography‐mass spectrometry analyses of M. hortensis essential oils revealed the presence of 31 compounds and the main components were terpinen‐4‐ol (30.0%), γ‐terpinene (11.3%), and trans ‐sabinene hydrate (10.8%). Repeated column chromatography of M. hortensis oil on silica gel led to the isolation of two major constituents, which were characterized based on 1 H‐nuclear magnetic resonance and mass spectrometric data, as terpinen‐4‐ol and γ‐terpinene. These two components were examined for their insecticidal and synergistic activities towards S. littoralis and A. fabae . Terpinen‐4‐ol and γ‐terpinene exhibited a significant insecticidal activity against both insects, but γ‐terpinene was more toxic than terpinen‐4‐ol. When tested in a binary mixture with the synthetic insecticides profenofos and methomyl, it was found that both compounds enhanced the insecticidal activity of these insecticides by two‐ to threefold. These results show that terpinen‐4‐ol and γ‐terpinene have a synergistic effect on the insecticidal activities of synthetic insecticides profenofos and methomyl.