gebhart/patrepeval huggingface dataset:
Upgrading of Flow Cytometric Analysis for Absolute Counts, Cytokines and Other Antigenic Molecules of Cynomolgus Monkeys(Macaca fascicularis) by Using Anti-Human Cross-Reactive Antibodies. (2000)

In order to effectively use cynomolgus monkeys as animal models for human diseases, more than 300 anti-human monoclonal antibodies (mAbs) were studied as to their cross-reaction with various antigens from cynomolgus monkeys (Macaca fascicularis). Two hundred twenty-nine of 339 (67.55%) anti-human mAbs that react with human antigens of CD-defined molecules, chemokine receptors, and T cell receptors were cross-reactive with the monkey antigens. Using the cross-reactive antibodies and the fluorescenced beads for calibration, the procedure for the absolute count of monkey lymphocyte subsets was developed and the mean values for CD4+ and CD8+ lymphocyte subsets in peripheral blood were 718 and 573/mm3, respectively. Moreover, intracellular cytokines, IL-2, IL-4 and IFN gamma, and intracellular apoptosis-related proteins, Bcl-2, FADD and active form of caspase-3 could be detected in peripheral blood mononuclear cells as well as various tissue cells. It is therefore practicable to detail the phenotype of leukocytes, assess the production of intracellular cytokines and enumerate T-lymphocyte subsets by using the cross-reactive human antibodies with respective antigens of cynomolgus monkeys.
Apoptotic Protease Activating Factor 1 (Apaf-1)–Independent Cell Death Suppression by Bcl-2 (2000)

Reportedly, antiapoptotic Bcl-2 family proteins suppress apoptosis by binding to and inhibiting members of the CED-4 family of caspase activators. To explore this question, we used embryonic stem (ES) cells in which one (-/+) or both (-/-) copies of the gene encoding apoptotic protease activating factor 1 (Apaf-1), a CED-4 homologue, were disrupted by homologous recombination. Stable clones of heterozygous (-/+) and homozygous (-/-) Apaf-1 knockout ES cells that overexpressed Bcl-2 were generated. Withdrawal of serum growth factors or stimulation of heterozygous ES cells with staurosporine (STS), ultraviolet (UV)B irradiation, etoposide (VP16), or cisplatin induced apoptosis followed by cell death (determined by failure to exclude propidium iodide dye). These cell death stimuli also induced activation of several types of caspases and loss of mitochondrial membrane potential (DeltaPsi) in heterozygous (+/-) Apaf-1 knockout ES cells. In addition, overexpression of Bcl-2 protected against these events in Apaf-1-expressing ES cells. In contrast, STS, UVB, and VP16 induced little or no caspase activation and apoptosis in homozygous (-/-) Apaf-1 knockout ES cells. Nevertheless, Apaf-1-deficient ES cells subjected to these cell death stimuli or deprived of growth factors did eventually die through a nonapoptotic mechanism associated with loss of DeltaPsi. Moreover, Bcl-2 overprotection preserved DeltaPsi, reduced the percentage of Apaf-1(-/)- ES cells undergoing cell death, and increased clonigenic survival. The extent of Bcl-2-mediated cytoprotection was not significantly different for heterozygous (-/+) versus homozygous (-/-) Apaf-1 knockout cells. Furthermore, although Bcl-2 could be readily coimmunoprecipitated with Bax, associations with Apaf-1 were undetectable under conditions where Apaf-1 interactions with procaspase-9 were observed. We conclude that Bcl-2 has cytoprotective functions independent of Apaf-1, preserving mitochondrial function through a caspase-independent mechanism.
Identification of human uroplakin II promoter and its use in the construction of CG8840, a urothelium-specific adenovirus variant that eliminates established bladder tumors in combination with docetaxel. (2002)

Uroplakins (UPs) are a group of integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. UPII gene expression is bladder specific and differentiation dependent, but very little is known about its transcription response elements. To identify the promoter elements, a DNA fragment of 2239 bp upstream of the UPII gene was amplified by PCR and linked to a promoterless firefly luciferase reporter gene. Transient transfection experiments showed that the DNA segment located between -1809 and +1 bp resulted in preferential expression in bladder carcinoma cells with negligible expression in nonurothelial cells. This promoter was engineered into adenovirus (Ad) type 5 to drive the expression of the E1A and E1B genes and to create an attenuated replication-competent Ad variant, termed CG8840. Viral replication and the cytopathic effect of CG8840 were evaluated by virus yield and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in bladder transitional cell carcinoma (TCC) cell lines RT4 and SW780; nonbladder cancer cell lines G361 (melanoma), LNCaP (prostate cancer), PA-1 (ovarian cancer), and U118 (brain cancer); and human primary cells including lung fibroblasts, bladder smooth muscle cells, and mammary epithelial cells. CG8840 replicated in and eliminated bladder TCC efficiently with high specificity (10,000:1) in comparison with nonbladder cells. The antitumor activity of CG8840 was examined in BALB/c nu/nu mice carrying s.c. human TCC xenografts. Intratumoral and i.v. administration of CG8840 in RT4 human bladder cancer xenografts caused significant (P < 0.01) inhibition of tumor growth. Synergistic antitumor efficacy was observed when CG8840 was combined with docetaxel, resulting in significant regression of RT4 bladder cancer xenograft tumors within 6 weeks after i.v. administration of CG8840 (3.33 x 10(9) plaque-forming units/animal on day 1) and docetaxel (20 mg/kg on days 2, 6, and 9). These results demonstrate the utility of the UPII promoter in the generation of urothelium-specific adenoviral vectors and provide a potential foundation for the development of bladder tumor-specific oncolytic viral therapies.
Sensors made of RNA: tailored ribozymes for detection of small organic molecules, metals, nucleic acids and proteins (2006)

Nucleic acids are well suited to serve as biosensors for the fast and reliable detection of small organic molecules, such as a number of metabolites or antibiotics, specific nucleic acid sequences, peptides, proteins or metal ions. One of the main advantages of using nucleic acids as biosensors is that they can be modulated to respond allosterically to specific effectors. Thus molecular recognition is transformed directly into a catalytic process with observable results. In particular, catalytic RNA structures, such as the hammerhead and hairpin ribozymes, have been used for biosensor engineering. The review reports on the function mode of nucleic acid biosensors and introduces recent developments and applications in the field.
Structure of Human Methionine Aminopeptidase-2 Complexed with Fumagillin (1998)

The fungal metabolite fumagillin suppresses the formation of new blood vessels, and a fumagillin analog is currently in clinical trials as an anticancer agent. The molecular target of fumagillin is methionine aminopeptidase-2 (MetAP-2). A 1.8 A resolution crystal structure of free and inhibited human MetAP-2 shows a covalent bond formed between a reactive epoxide of fumagillin and histidine-231 in the active site of MetAP-2. Extensive hydrophobic and water-mediated polar interactions with other parts of fumagillin provide additional affinity. Fumagillin-based drugs inhibit MetAP-2 but not MetAP-1, and the three-dimensional structure also indicates the likely determinants of this specificity. The structural basis for fumagillin's potency and specificity forms the starting point for structure-based drug design.
Cross-neutralizing anti-HIV-1 human single chain variable fragments(scFvs) against CD4 binding site and N332 glycan identified from a recombinant phage library (2017)

More than 50% of HIV-1 infection globally is caused by subtype_C viruses. Majority of the broadly neutralizing antibodies (bnAbs) targeting HIV-1 have been isolated from non-subtype_C infected donors. Mapping the epitope specificities of bnAbs provides useful information for vaccine design. Recombinant antibody technology enables generation of a large repertoire of monoclonals with diverse specificities. We constructed a phage recombinant single chain variable fragment (scFv) library with a diversity of 7.8 × 10<sup>8</sup> clones, using a novel strategy of pooling peripheral blood mononuclear cells (PBMCs) of six select HIV-1 chronically infected Indian donors whose plasma antibodies exhibited potent cross neutralization efficiency. The library was panned and screened by phage ELISA using trimeric recombinant proteins to identify viral envelope specific clones. Three scFv monoclonals D11, C11 and 1F6 selected from the library cross neutralized subtypes A, B and C viruses at concentrations ranging from 0.09 μg/mL to 100 μg/mL. The D11 and 1F6 scFvs competed with mAbs b12 and VRC01 demonstrating CD4bs specificity, while C11 demonstrated N332 specificity. This is the first study to identify cross neutralizing scFv monoclonals with CD4bs and N332 glycan specificities from India. Cross neutralizing anti-HIV-1 human scFv monoclonals can be potential candidates for passive immunotherapy and for guiding immunogen design.
Rabies virulence: effect on pathogenicity and sequence characterization of rabies virus mutations affecting antigenic site III of the glycoprotein (1985)

Using four neutralizing monoclonal antibodies which presumably bind to the same antigenic site on the CVS glycoprotein (antigenic site III as defined by cross-neutralization tests), we isolated 58 mutants of the CVS strain of rabies virus. These mutants were highly resistant to the selecting antibodies and grew efficiently in cell cultures. We classified them into five groups on the basis of the pattern of resistance to the four antibodies. We determined pathogenicities of the mutants for adult mice by intracerebral inoculation. Group 2 mutants were nonpathogenic or had attenuated pathogenicity. On the contrary, mutants from the other groups were pathogenic, causing paralysis and death as does CVS. We determined the nucleotide alterations of representative mutants from each group by using the dideoxy method of RNA sequencing. In the glycoproteins of eight nonpathogenic or attenuated mutants, we identified an amino acid substitution at position 333. Arginine 333 was replaced by either glutamine or glycine. In the glycoprotein of eight pathogenic mutants, we identified an amino acid substitution at lysine 330, asparagine 336, or isoleucine 338. Thus, although all substitutions affected neutralization and were located close to each other in the glycoprotein sequence, only substitutions at position 333 affected pathogenicity.
Hypotension as a Risk Factor for Acute Kidney Injury in ICU Patients. (2010)

In the context of critical illness, hypotension may be associated with acute kidney injury (AKI). Using the MIMIC II database, we studied the risk of AKI in ICU patients as a function of both the severity and duration of hypotension. Multivariate logistical regression was performed to find correlations between hypotension and AKI. Minimum mean arterial blood pressure (MAP) and the amount of time MAP was below a range of hypotension thresholds in a target 48-hour window (prior to AKI onset) were used as primary predictive variables in the multivariate model. Our results indicate that the risk of AKI was related to the severity of hypotension with an odds ratio (OR) of 1.03, 95% CI 1.02-1.04 (p < 0.0001) per 1 mmHg decrease in minimum MAP ≥ 80 mmHg. For each additional hour MAP was less than 70, 60, 50 mmHg, the risk of AKI increased by 2% (OR 1.02, 95% CI 1.00-1.03, p = 0.0034), 5% (OR 1.05, 95% CI 1.02-1.08, p = 0.0028), and 22% (OR 1.22, 95% CI 1.04-1.43, p = 0.0122) respectively.
Biologically Active Compounds from Aphyllophorales (Polypore) Fungi (2004)

This review describes biologically active natural products isolated from Aphyllophorales, many of which are known as polypores. Polypores are a large group of terrestrial fungi of the phylum Basdiomycota (basidiomycetes), and they along with certain Ascomycota are a major source of pharmacologically active substances. There are about 25 000 species of basidiomycetes, of which about 500 are members of the Aphyllophorales, a polyphyletic group that contains the polypores. Many of these fungi have circumboreal distributions in North America, Europe, and Asia and broad distributions on all inhabited continents and Africa; only a small number of the most common species with the most obvious fruiting bodies (basidiocarps) have been evaluated for biological activity. An estimated 75% of polypore fungi that have been tested show strong antimicrobial activity, and these may constitute a good source for developing new antibiotics. Numerous compounds from these fungi also display antiviral, cytotoxic, and/or antineoplastic activities. Additional important components of this vast arsenal of compounds are polysaccharides derived from the fungal cell walls. These compounds have attracted significant attention in recent years because of their immunomodulatory activities, resulting in antitumor effects. These high molecular weight compounds, often called biological response modifiers (BRM), or immunopotentiators, prevent carcinogenesis, show direct anticancer effects, and prevent tumor metastasis. Some of the protein-bound polysaccharides from polypores and other basidiomycetes have found their way to the market in Japan as anticancer drugs. Finally, numerous compounds with cardiovascular, phytotoxic, immunomodulatory, analgesic, antidiabetic, antioxidant, insecticidal, and nematocidal activities, isolated from polypores, are also presented. In fact many of the fungi mentioned in this paper have long been used in herbal medicine, including polypores such as Ganoderma lucidum (Reishi or Ling Zhi), Laetiporus sulphureus (Chicken-of-the-Woods), Trametes versicolor (Yun Zhi), Grifola umbellata (Zhu Lin), Inonotus obliquus (Chaga), and Wolfiporia cocos (Hoelen).
Application of the scaled subprofile model to functional imaging in neuropsychiatric disorders: A principal component approach to modeling brain function in disease (1994)

Abstract Recent advances in functional neuroimaging have presented a challenge to traditional statistical methods in characterizing the effects of neuropsychiatric illness on brain function. The most common approach for analyzing regional group differences has relied on t‐tests with significance thresholds selected to reduce the potential effect of multiple statistical tests. Regional covariance analysis offers an alternative to this threshold‐based, group difference approach by identifying the functional interactions among brain regions that can be spatially distributed throughout the brain. The Scaled Subprofile Model (SSM) is one form of regional covariance analysis that has been applied to the study of patient groups. Based on a modified principal component analysis, the SSM offers a method for modeling regionally specific patterns of brain function whose expression can be evaluated between groups and validated against clinical measures of patient disease severity and neuropsychological test scores. We review the application of the SSM, to date, in studies of the effects of neurological and psychiatric illness on brain function, including a discussion of SSM methodology and its application to the study of resting state functional neuroimaging in patient groups. SSM analyses applied to studies of Alzheimer's disease, Parkinson's disease, major depressive disorder, AIDS dementia complex, and neoplastic disease each identified functionally specific topographic effects that were associated with clinical disease severity. The results of the SSM analyses suggest that neuropsychiatric disorders may alter functional networks or systems of neural activity in ways that can be expressed as regional covariance patterns in resting functional imaging data. © 1994 Wiley‐Liss, Inc.
THE ORGANISATIONAL GOALS OF SOCIAL ENTREPRENEURS: HOW SOCIAL ARE THEY? (2009)

There is an increasing consensus among academics that the common denominator of ‘social entrepreneurs’ is their adherence to a ‘dominant social mission’. The extent to which social entrepreneurs actually adhere to socially oriented goals and values is largely taken for granted and treated as a black box. Building on established theoretical constructs, this paper develops a number of measures that can potentially contribute to our understanding of how ‘social’ social entrepreneurs really are. More specifically, we empirically test four potential measures of “social proclivity” in a well defined sample of social ventures, performing confirmatory factor analysis (CFA) (N~270). CFA points to high reliability and validity for the measures of each of the four constructs and supports the existence of a higher order construct “social proclivity”. Further, results show that social entrepreneurs display strong social as well as economic motives, providing an empirical base for actually capturing the dual-bottom line that characterises these enterprises.
Taxonomy of the papillose Euphorbia [Tithymalus] longecornuta complex (Euphorbiaceae) of northern Mexico (2011)

Euphorbia longecomuta is the earliest (first proposed in 1890) of four species in northern Mexico, all belonging to the Tithymalus group, which possess papillose leaves, stems, or cyathia.An additional two species (E.ivanjohnstonii and E. pinkavana) were subsequently proposed by M.C.Johnston, and a fourth (E.creberrima) by the late Rogers McVaugh.The taxonomy of the group is discussed and a key to the taxa presented.Euphorbia ivanjohnstonii forma longifolia B.L. Turner, forma nov.. is proposed and a photograph of the holotype is provided, along with a map showing distributions of the taxa concerned.KEY WORDS: Euphorbiaceae.Euphorbia
Configurable string matching hardware for speeding up intrusion detection (2005)

Signature-based Intrusion Detection Systems (IDSs) monitor network traffic for security threats by scanning packet payloads for attack signatures. IDSs have to run at wire speed and need to be configurable to protect against emerging attacks. In this paper we consider the problem of string matching which is the most computationally intensive task in IDS. A configurable string matching accelerator is developed with the focus on increasing throughput while maintaining the configurability provided by the software IDSs. Our preliminary results suggest that the hardware accelerator offers an overall system performance of up to 14Gbps.
A novel human tyrosine kinase gene inducible in T cells by interleukin 2 (1993)

We have cloned a novel human protein tyrosine kinase gene specific to T cells by the polymerase chain reaction method. This gene encodes a 620 amino-acid polypeptide including a catalytic domain for tyrosine kinase, an SH2 domain and an SH3 domain, seemingly belonging to the src family. However, characteristics of a long unique N-terminal stretch and lack of a myristylation site at the N-terminus and of a kinase regulatory tyrosine residue in the C-terminus classify this molecule into a new subfamily comprising recently cloned mouse tec, itk/tsk and human atk/bpk genes. This gene was transcriptionally induced in normal T cells by interleukin 2 stimulation. These results suggest the crucial roles of this gene in T cell proliferation and differentiation.
Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts (1989)

A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum. These results demonstrate the potential of DMM to facilitate engraftment in unsensitized mice in which the host stem cells may compete with donor type cells; the use of DMM to create models in which mechanisms of immune rejection can be studied without interference due to stem cell competition; and that bone marrow allograft rejection may be overcome by increasing the bone marrow inoculum in these stringent models.
A high performance fast search algorithm for block matching motion estimation (1997)

In this paper, we introduce a new fast search block matching motion estimation algorithm with high performance. Based on the center-biased characteristic for most of the video sequences, the proposed algorithm can jointly minimize the error image and total number of bits spent on the motion vectors with much reduced computational complexity. Simulation results show that the proposed algorithm can produce high performance with high speed-up ratio, especially for stationary or quasi-stationary video sequences.
Dependence of ultrasonic attenuation and absorption in dog soft tissues on temperature and thermal dose (1997)

The effect of temperature and thermal dose (equivalent minutes at 43 degrees C) on ultrasonic attenuation in fresh dog muscle, liver, and kidney in vitro, was studied over a temperature range from room temperature to 70 degrees C. The effect of temperature on ultrasonic absorption in muscle was also studied. The attenuation experiments were performed at 4.32 MHz, and the absorption experiments at 4 MHz. Attenuation and absorption increased at temperatures higher than 50 degrees C, and eventually reached a maximum at 65 degrees C. The rate of change of tissue attenuation as a function of temperature was between 0.239 and 0.291 Np m-1 MHz-1 degree C-1 over the temperature range 50-65 degrees C. A change in attenuation and absorption was observed at thermal doses of 100-1000 min, where a doubling of these loss coefficients was observed over that measured at 37 degrees C, presumably the result of changes in tissue composition. The maximum attenuation or absorption was reached at thermal dosages on the order of 10(7) min. It was found that the rate at which the thermal dose was applied (i.e., thermal dose per min) plays a very important role in the total attenuation absorption. Lower thermal dose rates resulted in larger attenuation coefficients. Estimation of temperature-dependent absorption using a bioheat equation based thermal model predicted the experimental temperature within 2 degrees C.