gebhart/patrepeval huggingface dataset:
Biological Markers of Acute Kidney Injury (2011)

An abrupt change in serum creatinine, the most common indicator of acute kidney injury (AKI), is strongly linked to poor outcomes across multiple clinical settings. Despite endless attempts to distill the magnitude and timing of a changing serum creatinine into a standardized metric, singular focus on this traditional functional marker obligates the characterization of AKI to remain, at best, retrospective and causally noninformative. The resultant inability to meaningfully segregate critical aspects of injury such as type, onset, propagation, and recovery from ongoing decrements in renal function has hindered successful translation of promising therapeutics. Over the past decade, however, the emerging field of clinical proteomics reinvigorates hope of identifying novel plasma and urine biomarkers to characterize cause and course of kidney injury. Efforts to validate these markers for use in clinical studies now show early promise but face important obstacles including interpretive difficulties inherent in using serum creatinine as a sole comparator for diagnostic performance, a need to better evaluate the incremental performance of new markers above established clinical and biochemical predictors, a relative lack of power to sufficiently examine hard clinical end points, and a potential over-reliance on use alone of receiver operating curves for assessing biomarker utility. Here, we discuss efforts to address these barriers and further ascertain the clinical value of new markers.
In vitro cytotoxicity to various human tumor cell lines of a tumor cytotoxic factor(s) produced by human alveolar macrophages. (1984)

When human alveolar macrophages (AM) obtained by lavage of the lungs of healthy donors were incubated in medium with or without lipopolysaccharide (LPS) they released a factor(s) with tumor cell killing activity. This tumor cytolytic and/or cytotoxic factor(s) (TCF) was assayed by measuring its effect in inhibiting target cell growth. TCF activity was not observed in the supernatant from cultures of LPS-treated hematopoietic malignant cell lines (monocytic leukemia, B-cell leukemia and T-cell leukemia cell lines). Human TCF was significantly cytotoxic to 13 of 15 solid-tumor cell lines tested and to 7 of 9 hematopoietic malignant cell lines, but not to two different normal, nontumorigenic cell lines. TCF-rich supernatants contained low levels of interferon (IFN) activity that were not significantly cytotoxic to A-375 melanoma cells. Human TCF and IFN-alpha or IFN-beta had additive cytotoxic effects. These data suggest that human TCF released by activated human AM may be of potential use in the treatment of malignant disseminated diseases.
Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2) (2002)

The endothelium expresses a large repertoire of genes under apparent transcriptional control of biomechanical forces, many of which are neither cell-type nor flow specific. We set out to identify genes that are uniquely flow responsive in human vascular endothelial cells. Transcriptional profiling using commercial DNA microarrays identified 12 of 18 000 genes that were modulated at least 5-fold after 24 hours of steady laminar flow (25 dyne/cm(2)). After a 7-day exposure to unidirectional pulsatile flow (19 +/- 12 dyne/cm(2)), only 3 of 12 remained elevated at least 5-fold. A custom microarray of ~300 vascular cell-related gene fragments was constructed, and expression analysis revealed that many flow-induced genes are also induced by at least one of the following agents: tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), transforming growth factor-beta, vascular endothelial growth factor, or thrombin, indicating a more general role in adaptive or stress responses. Most flow-induced genes were also induced by TNF-alpha but not IL-1beta, suggesting the involvement of reactive oxygen species. A limited panel of genes that are unique for flow-exposed cultures was identified, including lung Krüppel-like factor (LKLF/KLF2) and cytochrome P450 1B1 (CYP1B1). In marked contrast, both these genes were substantially repressed by TNF-alpha. LKLF but not CYP1B1 mRNA was detected exclusively in the vascular endothelium of healthy human aorta by in situ hybridization and appeared to be flow regulated. To date LKLF is the first endothelial transcription factor that is uniquely induced by flow and might therefore be at the molecular basis of the physiological healthy, flow-exposed state of the endothelial cell.
Vascular normalization in orthotopic glioblastoma following intravenous treatment with lipid-based nanoparticulate formulations of irinotecan (Irinophore C™), doxorubicin (Caelyx®) or vincristine (2011)

The results are consistent with a partial restoration of the blood-brain barrier following treatment. Further, treatment with the selected liposomal drugs gave rise to blood vessels that were morphologically more mature and a vascular network that was more evenly distributed. Taken together the results suggest that treatment can lead to normalization of GBM blood vessel the structure and function. An in vitro assay designed to assess the effects of extended drug exposure on endothelial cells showed that selective cytotoxic activity against proliferating endothelial cells could explain the effects of liposomal formulations on the angiogenic tumor vasculature.
Bcl11a is essential for lymphoid development and negatively regulates p53 (2012)

Transcription factors play important roles in lymphopoiesis. We have previously demonstrated that Bcl11a is essential for normal lymphocyte development in the mouse embryo. We report here that, in the adult mouse, Bcl11a is expressed in most hematopoietic cells and is highly enriched in B cells, early T cell progenitors, common lymphoid progenitors (CLPs), and hematopoietic stem cells (HSCs). In the adult mouse, Bcl11a deletion causes apoptosis in early B cells and CLPs and completely abolishes the lymphoid development potential of HSCs to B, T, and NK cells. Myeloid development, in contrast, is not obviously affected by the loss of Bcl11a. Bcl11a regulates expression of Bcl2, Bcl2-xL, and Mdm2, which inhibits p53 activities. Overexpression of Bcl2 and Mdm2, or p53 deficiency, rescues both lethality and proliferative defects in Bcl11a-deficient early B cells and enables the mutant CLPs to differentiate to lymphocytes. Bcl11a is therefore essential for lymphopoiesis and negatively regulates p53 activities. Deletion of Bcl11a may represent a new approach for generating a mouse model that completely lacks an adaptive immune system.
Cross-Protection by Infectious Bronchitis Viruses Under Controlled Experimental Conditions (2015)

Infectious bronchitis virus (IBV) cross-protection trials were performed in healthy chickens maintained under controlled environmental conditions. Chickens primed or primed and boosted with a Massachusetts (Mass)-type attenuated vaccine were subsequently challenged with either IBV Arkansas (Ark) or GA13-type virulent strains. In addition, Ark-vaccinated chickens were challenged with IBV GA13. Spike protein 1 (S1) amino acid identities between IBV vaccine and challenge strains varied from 76.0% to 77.3%. Contrary to expectations, assessments of clinical signs, viral load, and histopathology indicated a significant level of cross-protection among these antigenically distant IBV strains. Moreover, prime and booster vaccination with Mass protected against GA13 and improved protection against Ark when compared with Mass single vaccination. These results emphasize the need to include both single vaccination control groups and control groups primed and boosted with a single serotype when testing the efficacy of IBV protectotypes and/or novel IBV vaccine combinations against heterologous serotypes under controlled experimental conditions. Such controls are of distinct importance in experiments supporting the introduction of attenuated IBV vaccine strains exotic to regions, since these exotic strains may provide new genetic material for recombination and emergence of novel IBV strains.
Effect of erythrocyte storage and oxyhemoglobin affinity changes on cardiac function (1985)

Storage of blood can depress erythrocyte 2,3-diphosphoglycerate (DPG) levels and thereby increase oxyhemoglobin affinity and potentially decrease capillary-to-tissue oxygen transport. We measured myocardial function and metabolism in isolated rabbit hearts with fixed coronary flow under basal conditions and during isoproterenol stress at 37 and 30 degrees C, comparing high and low oxyhemoglobin affinity (OHA) erythrocytes. The high OHA state resulted from standard storage conditions, which caused depressed values of DPG and P50 (the oxygen tension at which hemoglobin is 50% saturated). The low OHA erythrocytes were initially stored and then underwent biochemical treatment to restore the DPG and P50 values to normal. The low OHA cells released more oxygen, and myocardial oxygen consumption and contractile function were increased relative to the high OHA cells during both the basal and stress states at both 37 and 30 degrees C. These observations may be relevant for patients with limited coronary flow when such patients receive large transfusions of stored blood.
Bone mineral density and survival of elements and element portions in the bones of the Crow Creek massacre victims (1997)

The interpretation of archaeologically-derived skeletal series is dependent on the elements and portions of elements preserved for examination. Bone and bone portion survival is affected by factors, both intrinsic and extrinsic to the elements themselves, that influence deterioration and preservation. Among the intrinsic variables, the density of the element and element portion are particularly important with respect to the degree of preservation. Recently reported bone mineral density values from a contemporary human sample are compared to the survival of prehistoric limb bones of the Crow Creek specimens, a fourteenth-century massacre skeletal series. The contemporary density values are positively correlated with Crow Creek element and element portion survival. Two calculations of bone mineral density, however, are more closely related to preservation than a third. Such density information has implications for assessing minimum number of elements and individuals and documenting taphonomic processes.
Proposal of leukotoxin, 9,10-epoxy-12-octadecenoate, as a burn toxin. (1990)

It is postulated that toxic substances (burn toxin) synthesized in burned skin are transferred into general circulation and cause multiple organ failure. We found a highly cytotoxic substance, leukotoxin, a linoleate epoxide, exists in burned skin. Leukotoxin, as the name indicates, was synthesized by leukocytes from linoleate as a substrate. The aim of this study is to evaluate the possibility of leukotoxin as a burn toxin. We studied plasma leukotoxin level of four patients with extensive burns (over 50% of body surface area) and examined coagulation studies in these patients. We detected considerable amounts of leukotoxin (11.4 nmol/ml-37.0 nmol/ml) in all patients. Leukotoxin was not detected in the control subjects. Pulmonary edema, cardiac failure, and coagulation abnormalities were found in these patients. Exogeneously administered leukotoxin induced similar pathological conditions in experimental animals to those observed in patients with extensive burns. Hence, it is concluded that leukotoxin is a responsible substance as a burn toxin.
Soluble Erythropoietin Receptor Contributes to Erythropoietin Resistance in End-Stage Renal Disease (2010)

These observations suggest that sEpoR levels may contribute to erythropoietin resistance in end stage renal disease, and that sEpoR production may be mediated by pro-inflammatory cytokines.
Standing Genetic Variation in Contingency Loci Drives the Rapid Adaptation of Campylobacter jejuni to a Novel Host (2011)

The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10(-/-) mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64 Mb genome to 200-500 X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host.
Diagnosis of invasive candidiasis by a dot immunobinding assay for Candida antigen detection (1993)

A dot immunobinding assay which uses a polyclonal rabbit anti-Candida immunoglobulin G as the primary antibody and colloidal gold coated with goat anti-rabbit immunoglobulin G as the secondary antibody for the detection of Candida cytoplasmic antigens is described. It was able to detect as little as 1 ng of total Candida protein per ml when a cytoplasmic extract of Candida albicans was seeded into buffer and 10 ng/ml when the same extract was seeded into pooled human serum. Serial serum samples from four groups of patients were assayed for Candida antigen: (i) 22 patients with candidemia, (ii) 16 patients at high risk for invasive candidiasis, (iii) 3 patients with other deep mycoses, and (iv) 50 hospitalized patients at low risk for serious Candida infection. Of the 22 candidemic patients, 19 had invasive candidiasis and 3 had transient candidemia. Antigenemia was detected in 16 of the 19 patients with invasive candidiasis (including patients with C. albicans, Candida tropicalis, Candida glabrata, Candida krusei, and Candida parapsilosis) and in 4 of 16 patients at high risk for invasive candidiasis. There was no detectable antigen in 12 high-risk control patients, 3 patients with transient candidemia, 3 patients with other deep mycoses, and 50 relatively low-risk patients. The sensitivity for detecting invasive disease in candidemic patients and specificity for all patients studied were 84.2 and 94.4%, respectively. The positive predictive value was 80%; the negative predictive value was 95.7%. The sensitivity for neutropenic patients with invasive disease was 85.7%. This assay is rapid and accurate and appears to be useful in identifying candidemic patients with invasive candidiasis.
Implication of the proliferation and apoptosis associated CSE1L/CAS gene for breast cancer development. (2001)

The CSEIL/CAS protein (CAS) is a Ran-binding protein with a function as a nuclear transport (export) factor. CSEIL/CAS, similar to Ran and other ran-binding proteins, plays at the same time an important role in the mitotic spindle checkpoint, which assures genomic stability during cell division. This checkpoint is frequently disturbed in neoplasms of various origin, including breast, hepatic and colonic tumors. CAS is located on chromosome 20ql3 and amplified in several cell lines, including breast, colon and bladder cancer. MEKl phosphorylation is known to be a reason for different CAS localization and activity. We evaluated the expression of CAS in 50 benign and malignant tumors of the breast by immunohistochemistry. Benign lesions of the breast (n=13) revealed a weak, predominantly cytoplasmatic CAS positivity. In ductal and lobular in situ carcinomas (n=17), 70-90% of the tumor cells were positive for anti-CAS staining which was predominantly cytoplasmatic. In invasive ductal and lobular carcinomas (n =20), 70-90% of the tumor cells stained positive with anti-CAS in a predominantly nuclear pattern. Different localization of CAS might affect its role not only for chromosome segregation, proliferation and apoptosis, but also its function in nuclear transport of proteins like retinoblastoma-gene-product, p53 and BRCAl. A different regulation in this checkpoint might contribute to the invasive potential in malignant carcinomas of the breast. Alteration of CAS-activity, possibly via MEKl-inhibition, might therefore be a possible option for breast cancer therapy.
Accurate modelling and inversion of electrical resistivity data in the presence of metallic infrastructure with known location and dimension (2015)

Electrical resistivity tomography (ERT) has been widely used in environmental applications to study processes associated with subsurface contaminants and contaminant remediation. Anthropogenic alterations in subsurface electrical conductivity associated with contamination often originate from highly industrialized areas with significant amounts of buried metallic infrastructure. The deleterious influence of such infrastructure on imaging results generally limits the utility of ERT where it might otherwise prove useful for subsurface investigation and monitoring. In this manuscript we present a method of accurately modelling the effects of buried conductive infrastructure within the forward modelling algorithm, thereby removing them from the inversion results. The method is implemented in parallel using immersed interface boundary conditions, whereby the global solution is reconstructed from a series of well-conditioned partial solutions. Forward modelling accuracy is demonstrated by comparison with analytic solutions. Synthetic imaging examples are used to investigate imaging capabilities within a subsurface containing electrically conductive buried tanks, transfer piping, and well casing, using both well casings and vertical electrode arrays as current sources and potential measurement electrodes. Results show that, although accurate infrastructure modelling removes the dominating influence of buried metallic features, the presence of metallic infrastructure degrades imaging resolution compared to ERT imaging in the absence of infrastructure. However, it is possible to rectify this degradation in resolution through appropriate placement of electrodes.
Polynucleotide:adenosine glycosidase activity of ribosome-inactivating proteins: effect on DNA, RNA and poly(A) (1997)

Ribosome-inactivating proteins (RIP) are a family of plant enzymes for which a unique activity was determined: rRNAN-glycosidase at a specific universally conserved position, A4324in the case of rat ribosomes. Recently we have shown that the RIP from Saponaria officinalis have a much wider substrate specificity: they are actually polynucleotide:adenosine glycosidases. Here we extend studies on substrate specificity to most known RIP: 52 purified proteins, both type 1 (single-chain) and type 2 (two chain, an enzymatic chain and a lectin chain) were examined for adenine release on various substrates including RNAs from different sources, DNA, and poly(A). All RIP depurinated extensively DNA and some released adenine from all adenine-containing polynucleotides tested. From experimental evidence the entire class of plant proteins, up to now called ribosome-inactivating proteins, may be classified as polynucleotide:adenosine glycosidases. The newly identified substrates may be implicated in the biological role(s) of RIP.
Atomic physicochemical parameters for three dimensional structure directed quantitative structure-activity relationships. 4. Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibiotics (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAtomic physicochemical parameters for three dimensional structure directed quantitative structure-activity relationships. 4. Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibioticsVellarkad N. Viswanadhan, Arup K. Ghose, Ganapathi R. Revankar, and Roland K. RobinsCite this: J. Chem. Inf. Comput. Sci. 1989, 29, 3, 163–172Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/ci00063a006https://doi.org/10.1021/ci00063a006research-articleACS PublicationsRequest reuse permissionsArticle Views3558Altmetric-Citations969LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Ligand Binding Stepwise Disrupts Water Network in Thrombin: Enthalpic and Entropic Changes Reveal Classical Hydrophobic Effect (2012)

Well-ordered water molecules are displaced from thrombin's hydrophobic S3/4-pocket by P3-varied ligands (Gly, d-Ala, d-Val, d-Leu to d-Cha with increased hydrophobicity and steric requirement). Two series with 2-(aminomethyl)-5-chlorobenzylamide and 4-amidinobenzylamide at P1 were examined by ITC and crystallography. Although experiencing different interactions in S1, they display almost equal potency. For both scaffolds the terminal benzylsulfonyl substituent differs in binding, whereas the increasingly bulky P3-groups address S3/4 pocket similarly. Small substituents leave the solvation pattern unperturbed as found in the uncomplexed enzyme while increasingly larger ones stepwise displace the waters. Medium-sized groups show patterns with partially occupied waters. The overall 40-fold affinity enhancement correlates with water displacement and growing number of van der Waals contacts and is mainly attributed to favorable entropy. Both Gly derivatives deviate from the series and adopt different binding modes. Nonetheless, their thermodynamic signatures are virtually identical with the homologous d-Ala derivatives. Accordingly, unchanged thermodynamic profiles are no reliable indicator for conserved binding modes.
[Role of CTHRC1 in proliferation, migration and invasion of human colorectal cancer cells]. (2015)

CTHRC1 is up-regulated in colorectal cancer tissues and SW620 and LoVo cells to promote the cell proliferation, migration, invasion and colony formation. CTHRC1 can enhance epithelial-mesenchymal transition of colorectal cancer cells by activating ERK1/2 to promote tumor cell metastasis and invasion.