gebhart/patrepeval huggingface dataset:
Cytokine circuits in brain. Implications for AIDS dementia complex. (1994)

This chapter has summarized studies showing that cells of the immune system and glial cells of the CNS use many of the same cytokines as communication signals. Activated astrocytes and microglia are the principal sources of these cytokines in the CNS, although oligodendrocytes are capable of expressing IL-1 and TGF-beta. There is a complex circuitry of interactions mediated by cytokines, especially in the event of blood-brain barrier damage and lymphoid/mononuclear cell infiltration into the CNS. Infiltrating activated macrophages produce cytokines such as IL-1, TNF-alpha, and IL-6, which would trigger glial cells to produce their own cytokines. The activation of astrocytes and microglia to secrete proinflammatory cytokines such as IL-1, TNF-alpha, IL-6, and GM-CsF may contribute to the propagation of intracerebral immune and inflammatory responses initiated by immune cells, as well as enhancement of HIV-1 expression in the CNS. The cytokine cascades ongoing in the CNS could ultimately be suppressed due to the presence of immunosuppressive cytokines such as TGF-beta. Whether immune and inflammatory responses within the CNS are propagated or suppressed depends on a number of parameters, including (a) the activational status of these cells, (b) cytokine receptor levels on glial and immune cells, (c) the presence of cytokines with both immune-enhancing and immune-suppressing effects (IFN-gamma, IL-1, TNF-alpha, IL-6, TGF-beta, CsFs), (d) the concentration and location of these cytokines in the CNS, and (e) the temporal sequence in which a particular cell is exposed to numerous cytokines (see Fig. 1). The ultimate outcome of immunologic and inflammatory events in the CNS, as well as HIV expression, will be determined, in part, by an interplay of the above parameters.
Serum Fatty Acids and the Risk of Coronary Heart Disease (1995)

To examine the relation between serum fatty acids and coronary heart disease (CHD), the authors conducted a nested case-control study of 94 men with incident CHD and 94 men without incident CHD who were enrolled in the Usual Care group of the Multiple Risk Factor Intervention Trial between December 1973 and February 1976. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and examined their association with CHD. In all multivariate models, levels of the cholesterol ester saturated fatty acid palmitic acid (16:0) were directly associated with CHD risk (standardized odds ratio = 1.68; 95% confidence interval 1.10-2.55 in the model that adjusted for total plasma cholesterol level). Levels of the phospholipid omega-3 fatty acid docosapentaenoic acid (22:5) were inversely associated with CHD risk in the two multivariate models that controlled for the effects of total plasma cholesterol level or high density lipoprotein cholesterol to total plasma cholesterol ratio (standardized odds ratio = 0.58; 95% confidence interval 0.38-0.89 in the first model that controlled for total plasma cholesterol level). In contrast to the first two multivariate models, levels of the docosahexaenoic acid (22:6) were inversely associated with CHD risk in a third multivariate model that controlled for the effects of high density lipoprotein cholesterol to low density lipoprotein cholesterol ratio (standardized odds ratio = 0.57; 95% confidence interval 0.36-0.90). These findings are consistent with other evidence indicating that saturated fatty acids are directly correlated with CHD and that omega-3 polyunsaturated fatty acids are inversely correlated with CHD. Because these associations were present after adjustment for blood lipid levels, other mechanisms, such as a direct effect on blood clotting, may be involved.
N‐Acetyl lysyl‐tRNA synthetases evolved by a CcdB‐based selection possess N‐acetyl lysine specificity in vitro and in vivo (2012)

Posttranslational modifications play a crucial role in modulating protein structure and function. Genetic incorporation of unnatural amino acids into a specific site of a protein facilitates the systematic study of protein modifications including acetylation. We here report the directed evolution of pyrrolysyl-tRNA synthetase (PylRS) from Methanosarcina mazei to create N-acetyl lysyl-tRNA synthetases (AcKRSs) using a new selection system based on the killing activity of the toxic ccdB gene product. The amino acid specificity of these and of published AckRSs was tested in vitro and in vivo, and the enzyme-kinetic properties of the AckRSs were evaluated for the first time.
Study of Sonic hedgehog signaling pathway related molecules in gastric carcinoma (2006)

瞄准：学习声音的刺猬的表示小径相关的分子，声音的刺猬(嘘) 和在胃的癌的 Gli1。方法：在包括非癌的胃的纸巾的 56 个胃的标本的嘘的表示，胃的腺癌，胃的有鳞的房间癌被 RT-PCR，原位杂交和免疫组织化学检测。Gli1 的表示被原位杂交观察。结果：嘘和 Gli1 表示的积极的率是 0.0% ， 0.0% 在非癌的胃的纸巾当它是 66.7% 时， 57.8% 分别地在胃的腺癌，和 100% ， 100% 分别地在里面胃的有鳞的房间癌。在非癌的胃的纸巾和胃的癌(P<0.05 ) 之间有有效差量。当表示在胃的粘蛋白的腺癌是不在的时，在胃的管状的腺癌的嘘和 Gli1 的提高的表示与糟糕区分的肿瘤被联系。结论：在胃的腺癌和胃的有鳞的房间癌的嘘和 Gli1 的提高的表示显示出在胃的致癌作用的细胞的增长发信号的激活的嘘的参与。它建议表明基因的嘘可以是为胃的肿瘤诊断和治疗的新、好的目标基因。
Quantifying the Potential Benefit of Overlapping Communication and Computation in Large-Scale Scientific Applications (2006)

The design and implementation of a high performance communication network are critical factors in determining the performance and cost-effectiveness of a large-scale computing system. The major issues center on the trade-off between the network cost and the impact of latency and bandwidth on application performance. One promising technique for extracting maximum application performance given limited network resources is based on overlapping computation with communication, which partially or entirely hides communication delays. While this approach is not new, there are few studies that quantify the potential benefit of such overlapping for large-scale production scientific codes. We address this with an empirical method combined with a network model to quantify the potential overlap in several codes and examine the possible performance benefit. Our results demonstrate, for the codes examined, that a high potential tolerance to network latency and bandwidth exists because of a high degree of potential overlap. Moreover, our results indicate that there is often no need to use fine-grained communication mechanisms to achieve this benefit, since the major source of potential overlap is found in independent work-computation on which pending messages does not depend. This allows for a potentially significant relaxation of network requirements without a consequent degradation of application performance
Numerical Modeling of Facial Aging (1998)

Facial aging is a biological phenomenon. Skin properties change with time, and gravity and facial expressions exert mechanical deformation. Knowledge of these alterations may suggest ways to reverse them by identifying the corresponding distortional forces. The aim of this study was to determine a pattern of change for parameters of the face during the aging process, based on the numerical fitting of measures from a sample of patients. The first aspect of this study was to define adequate facial parameters and means of measuring them. Subsequently, each parameter was defined individually, and these data were analyzed as a set. The sample for the research was restricted to a group of 40 white female patients with a history of limited exposure to the sun, with ages ranging from 25 to 65. The reason for choosing this sample was the availability of frontal pattern photographs at different ages. The parameters for each patient were measured at two different ages. A strong correlation was found between age and behavior of the parameters. This aging model can be verified qualitatively by comparing photographs of a patient with manipulated photographs simulating aging. The quantitative verification of the model was done through the comparison of the measured and the predicted parameters.
Widespread Translational Control of Fibrosis in the Human Heart by RNA-Binding Proteins (2019)

We reveal widespread translational effects of transforming growth factor β1 and define novel posttranscriptional regulatory networks that control the fibroblast-to-myofibroblast transition. These networks are active in human heart disease, and silencing of hub genes limits fibroblast activation. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure.
Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-γ-induced class II transactivator (2003)

Expansion of the pool of tumor necrosis factor (TNF)-alpha-producing T cells is instrumental for the bone loss induced by estrogen deficiency, but the responsible mechanism is unknown. Here we show that ovariectomy up-regulates IFN-gamma-induced class II transactivator, a multitarget immune modulator, resulting in increased antigen presentation by macrophages, enhanced T cell activation, and prolonged lifespan of active T cells. Up-regulation of class II transactivator derives from increased production of IFN-gamma by T helper 1 cells, resulting from enhanced secretion of IL-12 and IL-18 by macrophages. The resulting T cell expansion and bone loss are prevented in vivo by both blockade of antigen presenting cell-induced T cell activation, and silencing of IFN-gamma receptor signaling. Thus, increased IFN-gamma-induced class II transactivator expression and the resulting enhanced T cell proliferation and lifespan are critical to the bone wasting effect of estrogen deficiency.
Early Enhanced Glucose Uptake in Human Cytomegalovirus-infected Cells (1984)

The uptake rate of some sugars was demonstrated in human embryo fibroblasts following infection by human cytomegalovirus (HCMV) and a significant increase in glucose uptake was demonstrated. Quantitative and sequential analysis of glucose uptake during the HCMV replication cycle showed that the enhanced uptake began during the first 20 h after infection and occurred even when a high glucose level was constantly present in the medium. The increase in sugar uptake requires an active viral genome, de novo protein synthesis and seems to be dependent only on the early transcription of the viral genome, as it did occur when replication of the viral genome was limited (non-permissive cells or cells infected in the presence of DNA synthesis inhibitors).
Broadly Protective Adenovirus-Based Multivalent Vaccines against Highly Pathogenic Avian Influenza Viruses for Pandemic Preparedness (2013)

Recurrent outbreaks of H5, H7 and H9 avian influenza viruses in domestic poultry accompanied by their occasional transmission to humans have highlighted the public health threat posed by these viruses. Newer vaccine approaches for pandemic preparedness against these viruses are needed, given the limitations of vaccines currently approved for H5N1 viruses in terms of their production timelines and the ability to induce protective immune responses in the absence of adjuvants. In this study, we evaluated the feasibility of an adenovirus (AdV)-based multivalent vaccine approach for pandemic preparedness against H5, H7 and H9 avian influenza viruses in a mouse model. Replication-defective AdV vectors expressing hemagglutinin (HA) from different subtypes and nucleoprotein (NP) from one subtype induced high levels of humoral and cellular immune responses and conferred protection against virus replication following challenge with H5, H7 and H9 avian influenza virus subtypes. Inclusion of HA from the 2009 H1N1 pandemic virus in the vaccine formulation further broadened the vaccine coverage. Significantly high levels of HA stalk-specific antibodies were observed following immunization with the multivalent vaccine. Inclusion of NP into the multivalent HA vaccine formulation resulted in the induction of CD8 T cell responses. These results suggest that a multivalent vaccine strategy may provide reasonable protection in the event of a pandemic caused by H5, H7, or H9 avian influenza virus before a strain-matched vaccine can be produced.
Knowledge-Intensive Conversational Case-Based Reasoning in Software Component Retrieval (2006)

Case based reasoning (CBR) is a problem solving method that reuses the previous problem solving experiences (represented as cases) to solve the new problem. As a type of interactive CBR, conversational CBR has been proposed to help users construct their problem descriptions incrementally through a mixed-initiative question-answering sequence. In software component retrieval, users meet the difficulty in well-defining their component queries. As a solution to release this difficulty, we proposed and implemented a conversational component retrieval model (CCRM) using a knowledge-intensive conversational CBR method in the thesis.\n\nThe research activities and contributions followed two directions: theoretical research on conversational CBR to provide an efficient and natural conversation process, and applying and adapting conversational CBR to support software component retrieval.\n\nIn the theoretical research direction, we first provided a framework to classify the similarity methods in CBR from the perspective of what features were taken into account during the similarity calculation, and further analyzed and illustrated that the query-biased similarity methods (only considering the features appearing in the query during the similarity calculation) were more suitable for conversational CBR applications. A knowledge-intensive conversational CBR method was designed that was able to utilize the general domain knowledge to improve the efficiency and naturalness of the conversation process. Four knowledge-intensive question selection tasks, including the feature inferencing, the integrated question ranking, the consistent question clustering, and the coherent question sequencing, were identified and handled in this method. We also proposed a lazy dialog learning mechanism that could continuously improve the performance of conversational CBR.\n\nFollowing the conversational component retrieval application direction, we reviewed and analyzed the current software component retrieval methods and proposed a conversational component retrieval model. In order to represent both the software components and the component queries as cases, it is necessary for a case to have multiple values on some features (generalized cases). In the research, we analyzed the feasibilities and discussed the methods to extend conversational CBR to support generalized cases from three aspects: the case representation, the similarity calculation metric, and the question selection method. At the end, a knowledge-intensive conversational software component retrieval system (TrollCCRM), enhanced by the above research findings, was implemented and evaluated on the image processing software component retrieval application.\n\nThe evaluation results so far gave us positive results that the TrollCCRM system provided an efficient and natural conversation process guiding users to find their desired software components.
Design and fabrication of blazed binary diffractive elements with sampling periods smaller than the structural cutoff (1999)

We report here on the theoretical performance of blazed binary diffractive elements composed of pillars carefully arranged on a two-dimensional grid whose period is smaller than the structural cutoff. These diffractive elements operate under unpolarized light. For a given grating geometry, the structural cutoff is a period value above which the grating no longer behaves like a homogeneous thin film. Because the grid period is smaller than this value, effective-medium theories can be fully exploited for the design, and straightforward procedures are obtained. The theoretical performance of the blazed binary elements is investigated through electromagnetic theories. It is found that these elements substantially outperform standard blazed échelette diffractive elements in the resonance domain. The increase in efficiency is explained by a decrease of the shadowing effect and by an unexpected sampling effect. The theoretical analysis is confirmed by experimental evidence obtained for a 3λ-period prismlike grating operating at 633 nm and for a 20°-off-axis diffractive lens operating at 860 nm.
Interleukin-1-mediated PGE2 production and sphingomyelin metabolism. Evidence for the regulation of cyclooxygenase gene expression by sphingosine and ceramide. (1992)

We recently demonstrated that sphingosine enhances interleukin-1 beta (IL-1)-mediated prostaglandin E2 (PGE2) production in human dermal fibroblasts (Ballou, L. R., Barker, S. C., Postlethwaite, A. E., and Kang, A. H. (1990) J. Immunol. 145, 4245-4251). Because sphingosine and ceramide are interconvertable, we extended previous studies by treating cells with C2-ceramide (C2-cer), a membrane-soluble analogue of ceramide, and found that C2-cer stimulates IL-1-mediated PGE2 production to the same degree as sphingosine. In an effort to elucidate the mechanistic basis by which sphingosine and C2-cer affect PGE2 production, we examined the effect of these molecules on the expression of genes encoding cyclooxygenase (EC 1.14.99.1, Cox) and phospholipase A2 (EC 3.1.1.4, PLA2), the rate-limiting enzymes in PGE2 biosynthesis. We found that sphingosine and C2-cer treatment resulted in an 8-fold induction of Cox mRNA within 1-2 h which declined thereafter; concomitant changes in Cox protein were also observed. In contrast, expression of phospholipase A2 remained unaltered. We also found that IL-1-mediated PGE2 production was dramatically enhanced in cells treated simultaneously with sphingomyelinase which led us to directly test the effect of IL-1 on sphingomyelin turnover. IL-1 treatment induced the hydrolysis of a significant fraction of prelabeled sphingomyelin which was accompanied by increased levels of intracellular ceramide. Taken together, our results suggest that enhanced Cox expression may account for the observed enhancement of IL-1-mediated PGE2 production by sphingosine and C2-cer. These data also suggest that endogenous sphingomyelin metabolites, generated in response to IL-1, may play an important role in IL-1 signal transduction.
Retrospective on the Future of Polyelectrolyte Multilayers (2009)

The layer-by-layer, or multilayer, method of thin film growth has evolved into a widely-used enabling technology. Starting in the mid 1990's, an exponentially increasing number of publications on the topic, many appearing in this Journal, have shown how multilayers may be adapted to passive and active coatings, devices and architectures. Looking forward, this Perspective briefly summarizes some of the most promising emerging ideas and applications.
ATAXIA-TELANGIECTASIA AND THE NIJMEGEN BREAKAGE SYNDROME: Related Disorders But Genes Apart (1997)

Gene mutations provide valuable clues to cellular metabolism. In humans such insights come mainly from genetic disorders. Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are two distinct but closely related, single gene disorders that highlight a complex junction of several signal transduction pathways. These pathways appear to control defense mechanisms against specific types of damage to cellular macromolecules, and probably regulate the processing of certain types of DNA damage or normal intermediates of DNA metabolism. A-T is characterized primarily by cerebellar degeneration, immunodeficiency, genome instability, clinical radiosensitivity, and cancer predisposition. NBS shares all these features except cerebellar deterioration. The cellular phenotypes of A-T and NBS are almost indistinguishable, however, and include chromosomal instability, radiosensitivity, and defects in cell cycle checkpoints normally induced by ionizing radiation. The recent identification of the gene responsible for A-T, ATM, has revealed its product to be a large, constitutively expressed phosphoprotein with a carboxy-terminal region similar to the catalytic domain of phosphatidylinositol 3-kinases (PI 3-kinases). ATM is a member of a family of proteins identified in various organisms, which share the PI 3-kinase domain and are involved in regulation of cell cycle progression and response to genotoxic agents. Some of these proteins, most notably the DNA-dependent protein kinase, have an associated protein kinase activity, and preliminary data indicate this activity in ATM as well. Mutations in A-T patients are null alleles that truncate or destabilize the ATM protein. Atm-deficient mice recapitulate the human phenotype with slower nervous-system degeneration. Two ATM interactors, c-Abl and p53, underscore its role in cellular responses to genotoxic stress. The complexity of ATM's structure and mode of action make it a paradigm of multifaceted signal transduction proteins involved in many physiological pathways via multiple protein-protein interactions. The as yet unknown NBS protein may be a component in an ATM-based complex, with a key role in sensing and processing specific DNA damage or intermediates and signaling their presence to the cell cycle machinery.
Expression of a soluble and functional form of the human beta 2 integrin CD11b/CD18. (1991)

Polymorphonuclear cells and monocytes (phagocytes) are a critical component of host defense against infections. However, these cells also play a significant role in host tissue damage in many noninfectious diseases, such as ischemia-reperfusion injury syndromes and rejection of transplanted organs. The leukocyte adhesion molecule family CD11/CD18 (beta 2 integrins) is critical to the function of polymorphonuclear cells and monocytes in inflammation and injury. Inherited deficiency of CD11/CD18 impairs phagocyte chemotaxis, adhesion and transmigration across endothelium, and clearance of invading microorganisms through phagocytosis and cell-mediated killing. Furthermore, murine monoclonal antibodies directed against the CD11b/CD18 (CR3) heterodimer have been shown to reduce, by 50%-80%, phagocyte-mediated ischemia-reperfusion injury in several organ systems, such as the myocardium, liver, and gastrointestinal tract and to inhibit development of insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice. Expression of CD11b/CD18 in a soluble and functional form might therefore be potentially useful as an anti-inflammatory agent. We have now expressed a recombinant soluble heterodimeric form of this human beta 2 integrin, normally expressed as two noncovalently associated membrane-bound subunits. The secreted receptor exhibited direct and specific binding to its ligand, iC3b, the major complement C3 opsonin, and inhibited binding of polymorphonuclear cells to recombinant interleukin 1-activated endothelium.
Gamma-hydrobutyric acid (GHB) and its chemical modifications: a review of the GHBergic system. (2005)

Gamma-hydroxybutyric acid (GHB) is a naturally occurring substance with function of an inhibitory neurotransmitter in the central nervous system in mammals. GHB can be used as a medicine in narcolepsy (Xyrem) and for general anesthesia (sodium oxybate). It is also a popular drug of abuse, causing coma, addiction and severe withdrawal syndrome, and, therefore, demanding thorough studies on the GHBergic system and expanded research on toxicology of this compound. The aim of this review is to present the proved and some suggested mechanisms of its action from pharmacological point of view, which may help to properly treat intoxication or other pathological states caused by GHB ingestion. Some new GHB derivatives studied for analogous action and their present use are also described.