gebhart/patrepeval huggingface dataset:
If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. (2007)

The notion that chronic stress fosters disease by activating the hypothalamic-pituitary-adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed that much of the variability is attributable to stressor and person features. Timing is an especially critical element, as hormonal activity is elevated at stressor onset but reduces as time passes. Stressors that threaten physical integrity, involve trauma, and are uncontrollable elicit a high, flat diurnal profile of cortisol secretion. Finally, HPA activity is shaped by a person's response to the situation; it increases with subjective distress but is lower in persons with posttraumatic stress disorder.
Cytokine expression by human peripheral blood dendritic cells stimulated in vitro with HIV-1 and herpes simplex virus (1996)

Dendritic cells are potent stimulators of Ag-specific T cell responses and have been implicated in the pathogenesis of HIV-1 and other viral infections. Although cytokines may be involved in both of these processes, there is little information on the expression of cytokines by human blood dendritic cells. We characterized cytokine gene and protein expression in dendritic cells that were purified from normal human PBMC by flow cytometry and stimulated in vitro for up to 24 h with HIV-1 or herpes simplex virus (HSV). The unstimulated, uncultured dendritic cells were defined by their phenotype (HLA DR+ CD3- CD19- CD16- CD56- CD14-) and distinct morphology, lack of mRNA expression for CD3, CD14 and CD19, and presence of mRNA for CD4 and CD83. The purified dendritic cells also expressed CD4 (70-90%), CD33 (36-48%), and CD11c (44-54%); lacked CD1a expression (<1%); and were potent stimulators of an allogeneic MLR. The stimulated dendritic cells expressed mRNA for IFN-alpha, IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, GM-CSF, and TNF-alpha within 4 to 12 h as determined by reverse transcription-PCR, with higher levels induced by HSV compared with HIV-1 strains IIIb or BaL. In contrast, the dendritic cells produced detectable protein only for IFN-alpha and IL-6 in response to HIV-1 or HSV, and IL-1beta in response to HSV within 24 h. There were no differences in expression of CD80 and CD86 surface molecules by dendritic cells that were either mock stimulated or stimulated with HIV-1 or HSV for 24 h. Production of IFN-alpha, IL-1beta, and IL-6 by dendritic cells may be important to the immunologic function of these cells and their role in the pathogenesis of HIV-1 and HSV infections.
Routine Isotope-Dilution Liquid Chromatography–Tandem Mass Spectrometry Assay for Simultaneous Measurement of the 25-Hydroxy Metabolites of Vitamins D2 and D3 (2005)

This simple robust interference-free LC-MS/MS assay is suitable for routine measurement of the 25-hydroxy metabolites of vitamins D2 and D3 in human serum. The assay has been in use for 9 months and has been used to assay more than 6000 routine samples.
Small animal models for the study ofClostridium difficiledisease pathogenesis (2013)

Clostridium difficile is the leading cause of bacterial antibiotic-associated diarrhoea in hospitals in the developed world. Despite this notoriety, the complex mechanisms employed by this pathogen to overcome innate host defences and induce fulminant disease are poorly understood. Various animal models have been used extensively for C. difficile research to study disease pathogenesis. Until recently, the most commonly used C. difficile disease model has utilised hamsters; however, mouse and pig models have now been developed that unravel different aspects of C. difficile pathology. This review summarises key aspects of the small animal models currently used in C. difficile studies with a specific focus on major differences between them. Furthermore, this review highlights the advantages and disadvantages of each model and illustrates that careful consideration is required when selecting models for use in C. difficile research.
The immunosuppressive and toxic effects of FK-506 are mechanistically related: pharmacology of a novel antagonist of FK-506 and rapamycin. (1992)

FK-506 inhibits Ca(2+)-dependent transcription of lymphokine genes in T cells, and thereby acts as a powerful immunosuppressant. However, its potential therapeutic applications may be seriously limited by several side effects, including nephrotoxicity and neurotoxicity. At present, it is unclear whether these immunosuppressive and toxic effects result from interference with related biochemical processes. FK-506 is known to interact with FK-binding protein-12 (FKBP-12), an abundant cytosolic protein with cis-trans peptidyl-prolyl isomerase activity (PPIase) activity. Because rapamycin (RAP) similarly binds to FKBP-12, although it acts in a manner different from FK-506, by inhibiting T cell responses to lymphokines, such an interaction with FKBP-12 is not sufficient to mediate immunosuppression. Recently, it was found that the complex of FKBP-12 with FK-506, but not with RAP, inhibits the phosphatase activity of calcineurin. Here, we used L-685,818, the C18-hydroxy, C21-ethyl derivative of FK-506, to explore further the role of FKBP-12 in the immunosuppressive and toxic actions of FK-506. Although L-685,818 bound with high affinity to FKBP-12 and inhibited its PPIase activity, it did not suppress T cell activation, and, when complexed with FKBP-12, did not affect calcineurin phosphatase activity. However, L-685,818 was a potent antagonist of the immunosuppressive activity of both FK-506 and RAP. Moreover, L-685,818 did not induce any toxicity in dogs and rats or in a mouse model of acute FK-506 nephrotoxicity, but it blocked the effect of FK-506 in this model. Therefore, FK-506 toxicity involves the disruption of biochemical mechanisms related to those implicated in T cell activation. Like immunosuppression, this toxicity is not due to the inhibition of the PPIase activity of FKBP-12, but may be linked to the inhibition of the phosphatase activity of calcineurin by the drug FKBP-12 complex.
Simultaneous optimization and evaluation of multiple dimensional queries (1998)

Database researchers have made significant progress on several research issues related to multidimensional data analysis, including the development of fast cubing algorithms, efficient schemes for creating and maintaining precomputed group-bys, and the design of efficient storage structures for multidimensional data. However, to date there has been little or no work on multidimensional query optimization. Recently, Microsoft has proposed “OLE DB for OLAP” as a standard multidimensional interface for databases. OLE DB for OLAP defines Multi-Dimensional Expressions (MDX), which have the interesting and challenging feature of allowing clients to ask several related dimensional queries in a single MDX expression. In this paper, we present three algorithms to optimize multiple related dimensional queries. Two of the algorithms focus on how to generate a global plan from several related local plans. The third algorithm focuses on generating a good global plan without first generating local plans. We also present three new query evaluation primitives that allow related query plans to share portions of their evaluation. Our initial performance results suggest that the exploitation of common subtask evaluation and global optimization can yield substantial performance improvements when relational database systems are used as data sources for multidimensional analysis.
Optical bistability in finite-size nonlinear bidimensional photonic crystals doped by a microcavity (2000)

We numerically demonstrate the existence of optical bistability in a finite-size nonlinear bidimensional photonic crystal doped by a microcavity. The numerical results are obtained by a rigorous theory of diffraction. We provide a theoretical model allowing to predict and explain the bistability phenomena from the resonances of the structure.
A textual object management system (1992)

Computer programs that access significant amounts of text usually include code that manipulates the textual objects that comprise it. Such programs include electronic mail readers, typesetters and, in particular, full-text information retrieval systems. Such code is often unsatisfying in that access to textual objects is either efficient, or flexible, but not both. A programming language like Awk or Perl provides very general facilities for describing textual objects, but at the cost of rescanning the text for every textual object. At the other extreme, full-text information retrieval systems usually offer access to a very limited number of kinds of textual objects, but this access is very efficient. The system described in this paper is a programming tool for managing textual objects. It provides a great deal of flexibility, giving access to very complex document structure, with a large number of constituent kinds of textual objects. Further, it provides access to these objects very efficiently, both in terms of time and auxiliary space, by being very careful to access secondary storage only when absolutely necessary.
β2-Microglobulin as a Biomarker in Peripheral Arterial Disease (2007)

In PAD patients, circulating B2M is elevated and correlates with the severity of disease independent of other risk factors. These findings might provide a needed biomarker for PAD and new insight into its pathophysiology. Further studies in other populations are needed to confirm the utility of measuring B2M in cardiovascular disease risk assessment.
The Trifunctional Antibody Ertumaxomab Destroys Tumor Cells That Express Low Levels of Human Epidermal Growth Factor Receptor 2 (2009)

Human epidermal growth factor receptor 2 (HER2/neu) is an important target for the treatment of the breast cancers in which it is overexpressed. However, no approved anti-HER2/neu therapy is available for the majority of breast cancer patients, who express HER2/neu at low levels (with scores of 1+ or 2+/fluorescence in situ hybridization-negative). The trifunctional antibody ertumaxomab targets HER2/neu, CD3, and activating Fcgamma receptors. In presence of ertumaxomab, tri-cell complexes consisting of tumor cells, T cells, and accessory cells form to cause tumor cell lysis. In a phase I trial with metastatic breast cancer patients, ertumaxomab could be applied safely and resulted in radiographically confirmed clinical responses. In this study, we compare ertumaxomab- and trastuzumab-mediated killing of cancer cell lines that express HER2/neu at low and high levels. Under optimal conditions for trastuzumab-mediated destruction of HER2/neu-overexpressing cells, only ertumaxomab was able to mediate the elimination of tumor cell lines that express HER2/neu at low levels (1+). Ertumaxomab-mediated activity was accompanied by a Th1-based cytokine release, a unique mode of action of trifunctional antibodies. Competitive binding studies with trastuzumab and 520C9 mapped the binding site of ertumaxomab to the extracellular regions II and III of the HER2/neu ectodomain. This site is distinct from the binding site of trastuzumab, so that HER2/neu-expressing tumor cells can be eliminated by ertumaxomab in the presence of high amounts of trastuzumab. The ability of ertumaxomab to induce cytotoxicity against various tumor cell lines, including those with low HER2/neu antigen density, may provide a novel therapeutic option for breast cancer patients who are not eligible for trastuzumab treatment.
Cerebral restorative plasticity from normal ageing to brain diseases: A "never ending story" (2010)

Brain plasticity can be considered the main result of brain communication with the 'external' and 'internal' environment. Learning new skills as well as endogenous brain function recovery following a lesion are based on neural plasticity, a dynamic phenomenon occurring in response to modification of conscious and pre- or sub-conscious experiences as they progressively stabilize at the synaptic and neural networks level. In spite of previously accepted theory, brain plasticity occurs throughout lifespan being an inner property of the system. Different models of brain plasticity are examined in relation with different modifications of the CNS: healthy brain ageing, neurodegenerative disorders, ischemic stroke and multiple sclerosis. A clarification of advantageous as well as of aberrant brain plasticity mechanisms in pathological conditions may help to improve the development of rehabilitation methods to better address and facilitate such processes.
The gene stlA encodes a phenylalanine ammonia-lyase that is involved in the production of a stilbene antibiotic in Photorhabdus luminescens TT01 (2005)

Photorhabdus is a genus of Gram-negative bacteria from the family Enterobacteriaceae. Members of Photorhabdus have a complex life cycle during which the bacterium has a pathogenic interaction with insect larvae whilst also maintaining a mutualistic relationship with nematodes from the family Heterorhabditidae. During growth in the insect, Photorhabdus bacteria produce a broad-spectrum antibiotic identified as 3,5-dihydroxy-4-isopropylstilbene (ST). The biochemical pathway responsible for the production of this antibiotic has not been characterized. In this report, a mutant strain of Photorhabdus luminescens subsp. laumondii TT01, BMM901, has been isolated, by transposon mutagenesis, that is unable to produce the ST antibiotic. Using in silico studies, feeding experiments and biochemical analyses, it is shown that the gene mutated in this strain, stlA, encodes phenylalanine ammonia-lyase (PAL). PAL catalyses the non-oxidative deamination of l-phenylalanine to trans-cinnamic acid and the enzyme is ubiquitous in plants, where it is involved in the production of phenylpropanoids such as lignin and phytoalexins. However, this is the first report of PAL activity in a member of the Proteobacteria.
Characterization of the blast cells in acute leukemia with translocation (4;11): report of eight additional cases and of one case with a variant translocation. (1987)

Eight new cases (five adults and three children) of acute leukemia characterized by the presence in bone marrow cells of a t(4;11)(q21;q23)and one similar case, a child, with a t(1;11)(p32;q23) are reported. All patients were diagnosed as having acute lymphoblastic leukemia (ALL) with high-risk features. Immunologically the blast cells of the nine cases showed a strikingly consistent immature lymphoid phenotype, i.e., TdT+, HLA-DR+, B4(CD19)+, CALLA(CD10)-, Smlg-, cmu-, BA-2(CD9)+ corresponding to a "null ALL." In addition, six of nine cases expressed the myeloid marker VIM-D5(CD15). By double immunofluorescence staining it was determined that the VIM-D5(CD15) antigen was expressed by terminal deoxynucleotidyl transferase-positive blast cells, excluding the possibility of double leukemia. In five cases investigation of the Ig heavy chain genes by Southern blot analysis showed clonal rearrangement of both Ig heavy chain gene alleles. These data suggest that the blast cells involved in t(4;11) leukemia represent early B-cell progenitors with "aberrant" expression of myelomonocytic features, possibly related to the 11q23 breakpoint.
Hepatocyte Growth Factor/Scatter Factor Blocks the Mitochondrial Pathway of Apoptosis Signaling in Breast Cancer Cells (2001)

The cytokine hepatocyte growth factor/scatter factor (HGF/SF) has been found to protect a variety of epithelial and cancer cell types against cytotoxicity and apoptosis induced by DNA damage, but the specific apoptotic signaling events and the levels at which they are blocked by HGF/SF have not been identified. We found that treatment of MDA-MB-453 human breast cancer cells with adriamycin (also known as doxorubicin, a DNA topoisomerase IIalpha inhibitor) induced a series of time-dependent events, including the mitochondrial release of cytochrome c and apoptosis-inducing factor, mitochondrial membrane depolarization, activation of a set of caspases (caspase-9, -3, -7, -2, and -8), cleavage of poly(ADP-ribose) polymerase (PARP), and up-regulation of expression of the Fas ligand. All of these events were blocked by preincubation of the cells with HGF/SF. In contrast, the pan-caspase inhibitor benzyloxycarbonyl-VAD-fluoromethylketone blocked some of these events (e.g. caspase-3 activation and PARP cleavage) but did not block cytochrome c release or mitochondrial depolarization. These findings suggest that HGF/SF functions, in part, upstream of the mitochondria to block mitochondrial apoptosis signaling, prevent activation of multiple caspases, and protect breast cancer cells against apoptosis.
Anti-Inflammatory Triterpenes from Pistacia terebinthus Galls (2002)

From the galls of Pistacia terebinthus we obtained an extract that proved to be effective against chronic and acute inflammation. Now we report on the isolation and identification of three triterpenes: two tirucallane-type lanostanoids and one oleanane, which we have identified as masticadienonic acid (1), masticadienolic acid (2), and morolic acid (3), respectively. All of them showed effectiveness on the mouse ear inflammation induced by repeated applications of 12-O-tetradecanoylphorbol 13-acetate and on the phospholipase A2-induced foot paw edema. The pharmacological activity of the compounds was ratified by a histological study of the ear samples. In addition, they inhibited leukotriene B4 production in rat polymorphonuclear leukocytes stimulated with calcium ionophore A 23187.
Design and Conduct of Clinical Trials in Hormone Replacement Therapy (2001)

Postmenopausal hormone replacement therapy represents an area of outstanding importance in preventive medicine that greatly affects personal well-being as well as public health. The number of women living in the United States who are 50 years or older has been estimated at nearly 50 million. Many of those women are likely to be eligible for postmenopausal hormone replacement, which may consist either of estrogen replacement therapy (ERT) in women without a uterus or, more frequently, estrogen/progestin combination therapy (HRT) in women with a uterus. This chapter first presents an overview of general regulatory requirements pertaining to the design and conduct of clinical studies in support of marketing approval for a drug product. These requirements include, but are not restricted to, studies in HRT. The chapter next discusses the design and conduct of clinical trials in support of marketing approval for the indications: treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy; prevention of osteoporosis; and protection by adjunctive progestin against estrogen-induced endometrial hyperplasia/cancer in women with a uterus. Finally, data related to the potential cardioprotective action of HRT and its protection against Alzheimer's disease and colon cancer are discussed.
IUPHAR-DB: An Open-Access, Expert-Curated Resource for Receptor and Ion Channel Research (2011)

This contribution highlights efforts by the International Union of Basic and Clinical Pharmacology (IUPHAR) Nomenclature Committee (NC-IUPHAR) to classify human receptors and ion channels, to document their properties, and to recommend ligands that are useful for characterization. This effort has inspired the creation of an online database (IUPHAR-DB), which is intended to provide free information to all scientists, summarized from primary literature by experts.
Identification of Hck Inhibitors As Hits for the Development of Antileukemia and Anti‐HIV Agents (2013)

Hematopoietic cell kinase (Hck) is a member of the Src family of non-receptor protein tyrosine kinases. High levels of Hck are associated with drug resistance in chronic myeloid leukemia. Furthermore, Hck activity has been connected with HIV-1. Herein, structure-based drug design efforts were aimed at identifying novel Hck inhibitors. First, an in-house library of pyrazolo[3,4-d]pyrimidine derivatives, which were previously shown to be dual Abl and c-Src inhibitors, was analyzed by docking studies within the ATP binding site of Hck to select the best candidates to be tested in a cell-free assay. Next, the same computational protocol was applied to screen a database of commercially available compounds. As a result, most of the selected compounds were found active against Hck, with Ki values ranging from 0.14 to 18.4 μM, confirming the suitability of the computational approach adopted. Furthermore, selected compounds showed an interesting antiproliferative activity profile against the human leukemia cell line KU-812, and one compound was found to block HIV-1 replication at sub-toxic concentrations.
A relational database schema on the transactional key-value store scalaris (2014)

Distributed key-value stores are horizontally scalable by design. However, structured data with links between values may raise hotspots or bottlenecks caused by popular keys and large index objects. These hotspots typically reduce the scalability of the key-value store, especially for operations changing data. Relational database management systems, on the other hand, are designed to handle relational data efficiently, but generally do not scale horizontally in a cost-efficient way. Combining the best of both worlds, would be great. With a wiki as a demonstrator, we map a relational database schema to a distributed transactional key-value store. This includes solutions for typical constraints key-value stores impose on applications due to their limited query expressibility. It also includes the mapping of dependent tables and secondary indices to a single key-value namespace. We evaluate and identify hotspots and bottlenecks and propose improved mappings. We reduce the effects of the most prominent hotspots, i.e. secondary indices, by applying advanced partitioning schemes which both reduce the size of the indices and allow more concurrent write accesses in transactional contexts. These optimisations are generic and help to map relational schemas and corresponding applications to transactional key-value stores in a way to preserve their horizontal scalability. With our data models for key-value stores, we get the best of two worlds for the wiki application: a horizontally scalable database serving a moderately complex relational schema. Our optimisations give up to 96% fewer transaction aborts for data change operations and an up to 25-fold latency improvement for the overall operations mix, i.e. reading, changing, and creating data, compared to the basic mapping, when replaying an access trace of the Wikipedia on our system.
Tailoring the Morphology of Carbon Nanotube Arrays: From Spinnable Forests to Undulating Foams (2009)

Directly spinning carbon nanotube (CNT) fibers from vertically aligned CNT arrays is a promising way for the application of CNTs in the field of high-performance materials. However, most of the reported CNT arrays are not spinnable. In this work, by controlling catalyst pretreatment conditions, we demonstrate that the degree of spinnability of CNTs is closely related to the morphology of CNT arrays. Shortest catalyst pretreatment time led to CNT arrays with the best spinnability, while prolonged pretreatment resulted in coarsening of catalyst particles and nonspinnable CNTs. By controlling the coalescence of catalyst particles, we further demonstrate the growth of undulating CNT arrays with uniform and tunable waviness. The CNT arrays can be tuned from well-aligned, spinnable forests to uniformly wavy, foam-like films. To the best of our knowledge, this is the first systematical study on the correlation between catalyst pretreatment, CNT morphology, and CNT spinnability.