gebhart/patrepeval huggingface dataset:
The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor (1998)

Tumor necrosis factor (TNF) can induce a variety of cellular responses at low picomolar concentrations. This is in apparent conflict with the published dissociation constants for TNF binding to TNF receptors in the order of 100-500 pM. To elucidate the mechanisms underlying the outstanding cellular sensitivity to TNF, we determined the binding characteristics of TNF to both human TNF receptors at 37 degrees C. Calculation of the dissociation constant (Kd) from the association and dissociation rate constants determined at 37 degrees C revealed a remarkable high affinity for TNF binding to the 60-kDa TNF type 1 receptor (TNF-R1; Kd = 1.9 x 10(-11) M) and a significantly lower affinity for the 80-kDa TNF type 2 receptor (TNF-R2; Kd = 4.2 x 10(-10) M). The high affinity determined for TNF-R1 is mainly caused by the marked stability of ligand-receptor complexes in contrast to the transient interaction of soluble TNF with TNF-R2. These data can readily explain the predominant role of TNF-R1 in induction of cellular responses by soluble TNF and suggest the stability of the TNF-TNF receptor complexes as a rationale for their differential signaling capability. In accordance with this reasoning, the lower signaling capability of homotrimeric lymphotoxin, compared with TNF, correlates with a lower stability of the lymphotoxin-TNF-R1 complex at 37 degrees C.
Providing advanced security mechanism for scalable data sharing in cloud storage (2016)

Data sharing is a significant functionality in cloud storage. These cloud storage provider are answerable for keeping the data obtainable and available in addition to the physical environment protected and running. Here we can securely, efficiently, and flexibly share data with others in cloud storage. A new public-key cryptosystems is planned which create constant-size cipher texts such that efficient allocation of decryption rights for any set of cipher texts are achievable. The uniqueness means that one can aggregate any set of secret keys and make them as packed in as a single key, but encircling the power of all the keys being aggregated. This packed in aggregate key can be easily sent to others or be stored in a smart card with very restricted secure storage. In KAC, users encrypt a file with single key, that means every file have each file, also there will be aggregate keys for two or more files, which formed by using the tree structure. Through this, the user can share more files with a single key at a time.
Characterization of Molecular Features, Antigen-Binding, and in Vitro Properties of IgG and IgM Variants of 4E10, an Anti-HIV Type 1 Neutralizing Monoclonal Antibody (2004)

The human monoclonal antibody 4E10 has been generated previously by immortalization of peripheral blood cells from an HIV-1-infected individual. This antibody binds to the linear epitope NWFDIT on gp41 and exhibits exceptional neutralizing activity against a broad spectrum of primary HIV-1 isolates. In the present study, molecular features, immunoreactivity, and functional activity of 4E10 were studied. The original hybridoma-derived 4E10 was of subtype IgG(3). Analysis of the variable segment of the heavy chain (VH) demonstrated extensive somatic mutations compared to the closest homologous germline gene VH1-69. Most amino acid substitutions occurred in the complementarity-determining region (CDR) 2, characteristic for an antigen-driven somatic maturation. The heavy chain of the CDR3 (H3) is of unusual length and cannot be attributed with certainty to any specific D(H) locus. To enable mass production and to prolong the in vivo half-life, 4E10 was subsequently cloned as IgG(1) in Chinese hamster ovary (CHO) cells. In additional studies, 4E10 was class switched to the IgM isotype. Binding to the linear epitope NWFDIT was not significantly changed after the cloning procedures. However, in vitro studies revealed dramatic differences in the neutralizing potential. The antiviral activity could be greatly enhanced by change of IgG(3) to IgG(1). In contrast, the IgM isotype almost completely lost its neutralizing potential.
Revertant seedlings from crown gall tumors retain a portion of the bacterial Ti plasmid DNA sequences (1981)

BT37 is a crown gall teratoma incited on tobacco by Agrobacterium tumefaciens containing pTi-T37, a nopaline-type Ti plasmid. Treatment of this cloned tumor tissue with kinetin at 1 mg/liter results in the formation of relatively normal-appearing shoots. These shoots can be induced to root and set viable seed. In contrast to BT37 tissue, the derived tissues are not phytohormone independent and do not produce nopaline. The reverted plants, like normal tobacco plants, are susceptible to infection by A. tumefaciens. This loss of tumorous traits is accompanied by the loss of most of the Ti plasmid sequences (T-DNA) found in BT37 DNA. Southern blot analysis indicates that the revertant tissues have lost the central portion of the T-DNA, which contains the "common DNA" sequences, a highly conserved region of the Ti plasmid that has been found to be incorporated into all tumors studied. Thus, these sequences appear necessary for oncogenicity and tumor maintenance and their loss is probably directly related to tumor reversal. The reverted plants as well as the plants obtained from seed, however, do retain sequences homologous to the ends of the T-DNA present in the parental teratoma. The persistence of foreign DNA sequences during the process of meiosis and seed formation has important implications for the possibility of the genetic engineering of plants.
Recombinant human thrombopoietin: basic biology and evaluation of clinical studies (2002)

Thrombocytopenia is a common medical problem for which the main treatment is platelet transfusion. Given the increasing use of platelets and the declining donor population, identification of a safe and effective platelet growth factor could improve the management of thrombocytopenia. Thrombopoietin (TPO), the c-Mpl ligand, is the primary physiologic regulator of megakaryocyte and platelet development. Since the purification of TPO in 1994, 2 recombinant forms of the c-Mpl ligand--recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF)--have undergone extensive clinical investigation. Both have been shown to be potent stimulators of megakaryocyte growth and platelet production and are biologically active in reducing the thrombocytopenia of nonmyeloablative chemotherapy. However, neither TPO has demonstrated benefit in stem cell transplantation or leukemia chemotherapy. Other clinical studies have investigated the use of TPO in treating chronic nonchemotherapy-induced thrombocytopenia associated with myelodysplastic syndromes, idiopathic thrombocytopenic purpura, thrombocytopenia due to human immunodeficiency virus, and liver disease. Based solely on animal studies, TPO may be effective in reducing surgical thrombocytopenia and bleeding, ex vivo expansion of pluripotent stem cells, and as a radioprotectant. Ongoing and future studies will help define the clinical role of recombinant TPO and TPO mimetics in the treatment of chemotherapy- and nonchemotherapy-induced thrombocytopenia.
Robust Antitumor Effects of Combined Anti–CD4-Depleting Antibody and Anti–PD-1/PD-L1 Immune Checkpoint Antibody Treatment in Mice (2015)

Depletion of CD4(+) cells in tumor-bearing mice has strong antitumor effects. However, the mechanisms underlying these effects and the therapeutic benefits of CD4(+) cell depletion relative to other immunotherapies have not been fully evaluated. Here, we investigated the antitumor effects of an anti-CD4-depleting mAb as a monotherapy or in combination with immune checkpoint mAbs. In B16F10, Colon 26, or Lewis lung carcinoma subcutaneous tumor models, administration of the anti-CD4 mAb alone had strong antitumor effects that were superior to those elicited by CD25(+) Treg depletion or other immune checkpoint mAbs, and which were completely reversed by CD8(+) cell depletion. CD4(+) cell depletion led to the proliferation of tumor-specific CD8(+) T cells in the draining lymph node and increased infiltration of PD-1(+)CD8(+) T cells into the tumor, with a shift toward type I immunity within the tumor. Combination treatment with the anti-CD4 mAb and immune checkpoint mAbs, particularly anti-PD-1 or anti-PD-L1 mAbs, synergistically suppressed tumor growth and greatly prolonged survival. To our knowledge, this work represents the first report of robust synergy between anti-CD4 and anti-PD-1 or anti-PD-L1 mAb therapies.
RERG Is a Novel ras-related, Estrogen-regulated and Growth-inhibitory Gene in Breast Cancer (2001)

Using microarray analysis, we identified a unique ras superfamily gene, termed RERG (ras-related and estrogen-regulated growth inhibitor), whose expression was decreased or lost in a significant percentage of primary human breast tumors that show a poor clinical prognosis. Importantly, high RERG expression correlated with expression of a set of genes that define a breast tumor subtype that is estrogen receptor-positive and associated with a slow rate of tumor cell proliferation and a favorable prognosis for these cancer patients. RERG mRNA expression was induced rapidly in MCF-7 cells stimulated by beta-estradiol and repressed by tamoxifen treatment. Like Ras, RERG protein exhibited intrinsic GDP/GTP binding and GTP hydrolysis activity. Unlike Ras proteins, RERG lacks a known recognition signal for COOH-terminal prenylation and was localized primarily in the cytoplasm. Expression of RERG protein in MCF-7 breast carcinoma cells resulted in a significant inhibition of both anchorage-dependent and anchorage-independent growth in vitro and inhibited tumor formation in nude mice. These features of RERG are strikingly different from most Ras superfamily GTP-binding pro-teins and suggest that the loss of RERG expression may contribute to breast tumorigenesis.
Dynamics of thermally driven capillary waves for two-dimensional droplets (2010)

Capillary waves have been observed in systems ranging from the surfaces of ordinary fluids to interfaces in biological membranes and have been one of the most studied areas in the physics of fluids. Recent advances in fluorescence microscopy and imaging enabled quantitative measurements of thermally driven capillary waves in lipid monolayers and bilayers, which resulted in accurate measurements of the line tension in monolayer domains. Even though there has been a considerable amount of work on the statics and dynamics of capillary waves in three dimensions, to the best of our knowledge, there is no detailed theoretical analysis for two-dimensional droplet morphologies. In this paper, we derive the dynamic correlation function for two-dimensional fluid droplets using linear response theory and verify our results using a novel particle-based simulation technique for binary mixtures.
The Biological and Social Phenomenon of Lyme Disease (1993)

Lyme disease, unknown in the United States two decades ago, is now the most common arthropod-borne disease in the country and has caused considerable morbidity in several suburban and rural areas. The emergence of this disease is in part the consequence of the reforestation of the northeastern United States and the rise in deer populations. Unfortunately, an accurate estimation of its importance to human and animal health has not been made because of difficulties in diagnosis and inadequate surveillance activities. Strategies for prevention of Lyme disease include vector control and vaccines.
IL-12p40-Dependent Agonistic Effects on the Development of Protective Innate and Adaptive Immunity Against Salmonella Enteritidis (2001)

To study a potential IL-12p40-dependent but IL-12p75-independent agonistic activity regulating the immune response against Salmonella Enteritidis, the course of infection in IL-12p35-deficient mice (IL-12p35(-/-), capable of producing IL-12p40) was compared with that of IL-12p40(-/-) mice. Mice lacking IL-12p40 revealed a higher mortality rate and higher bacterial organ burden than mice capable of producing IL-12p40. This phenotype was found in both genetically susceptible (BALB/c, Ity(s)) and resistant mice (129Sv/Ev, Ity(r)) indicating Ity-independent mechanisms. The more effective control of bacteria in the IL-12p35(-/-) mice was associated with elevated serum IFN-gamma and TNF-alpha levels. In contrast, IL-12p40(-/-) mice showed reduced IFN-gamma production, which was associated with significantly elevated serum IgE levels. Early during infection (days 3 and 4 postinfection), as well as late (day 20 postinfection), the number of infected phagocytes was strongly increased in the absence of IL-12p40 indicating impaired bactericidal activity when IL-12p40 was missing. Liver histopathology revealed a decreased number of mononuclear granulomas in IL-12p40(-/-) mice. Depletion of CD4(+) or CD8(+) T lymphocytes in vivo suggested that both T cell subpopulations contribute to the IL-12p40-dependent protective functions. Analysis of IL-12p40 vs IL-23p19 mRNA expression revealed an up-regulation of only IL-12p40 mRNA during Salmonella infection. Together these data indicate that IL-12p40 can induce protective mechanisms during both the innate and the adaptive type 1 immune response in Salmonella infection. This novel activity of IL-12p40 complements the well described dominant and essential role of IL-12p75 in protective immunity to Salmonella infection.
Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation (2003)

The effects of pathogenic organisms on host intestinal epithelial cells are vast. Innumerable signalling pathways are triggered leading ultimately to drastic changes in physiological functions. Here, the ways in which enteric bacterial pathogens utilise and impact on the three major physiological functions of the intestinal epithelium are discussed: alterations in the structure and function of the tight junction barrier, induction of fluid and electrolyte secretion, and activation of the inflammatory cascade. This field of investigation, which was virtually non-existent a decade ago, has now exploded, thus rapidly expanding our understanding of bacterial pathogenesis. Through increased delineation of the ways in which microbes alter host physiology, we simultaneous gain insight into the normal regulatory mechanisms of the intestinal epithelium.
Disnes: a distributed network emulation systeva for gigabit networks (1994)

This paper describes the DIStributed Network Emulation Sys tem (DISNES) modeling architecture for a gigabit per second Lo cal Area Network (LAN). The emulation of networks is an im portant capability for rapidly bringing new network technology to market because it allows for the simultaneous research and devel opment of network hardware and software. A modular, object oriented strategy is employed to model network components fea turing different functionalities. The distributed emulation system has demonstrated its usefulness by allowing the rapid development of a network management interface and a model for network man agement information. In particular, DISNES incorporates an ex perimental portion of the Internet Management Information Base (IMIB), operated through the Simple Network Management Pro tocol (SNMP), which defines objects for managing Permanent Vir tual Circuit (PVC) parameters on Asynchronous Transfer Mode (ATM) switches. The flexibility of DISNES makes it especially suitable for the development of distributed networked protocols and applications.
Gene Correction of a Duchenne Muscular Dystrophy Mutation by Meganuclease-Enhanced Exon Knock-In (2013)

Duchenne muscular dystrophy (DMD) is a severe inherited, muscle-wasting disorder caused by mutations in the DMD gene. Gene therapy development for DMD has concentrated on vector-based DMD minigene transfer, cell-based gene therapy using genetically modified adult muscle stem cells or healthy wild-type donor cells, and antisense oligonucleotide-induced exon-skipping therapy to restore the reading frame of the mutated DMD gene. This study is an investigation into DMD gene targeting-mediated correction of deletions in human patient myoblasts using a target-specific meganuclease (MN) and a homologous recombination repair matrix. The MN was designed to cleave within DMD intron 44, upstream of a deletion hotspot, and integration-competent lentiviral vectors expressing the nuclease (LVcMN) were generated. MN western blotting and deep gene sequencing for LVcMN-induced non-homologous end-joining InDels (microdeletions or microinsertions) confirmed efficient MN expression and activity in transduced DMD myoblasts. A homologous repair matrix carrying exons 45-52 (RM45-52) was designed and packaged into integration-deficient lentiviral vectors (IDLVs; LVdRM45-52). After cotransduction of DMD myoblasts harboring a deletion of exons 45 to 52 with LVcMN and LVdRM45-52 vectors, targeted knock-in of the RM45-52 region in the correct location in DMD intron 44, and expression of full-length, correctly spliced wild-type dystrophin mRNA containing exons 45-52 were observed. This work demonstrates that genome surgery on human DMD gene mutations can be achieved by MN-induced locus-specific genome cleavage and homologous recombination knock-in of deleted exons. The feasibility of human DMD gene repair in patient myoblasts has exciting therapeutic potential.
ChemInform Abstract: Luminescence Properties of Thiol‐Stabilized CdTe Nanocrystals. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Distinguishing dose from defocus for in-line lithography control (1999)

Manufacturing control of a lithographic process must guarantee that the pattern features on a masking level stay within a common process window, the focus-exposure space over which all pattern tolerances are met. To do so at focus latitudes below 1 micrometers , simultaneous determination and correction of dose and defocus error is required. In-line metrology practice has been to measure a single pattern attribute, usually the dimension of the smallest feature, at each of several locations on a wafer. Since the measurement of one pattern attribute, regardless of its accuracy or precision, cannot distinguish two variables - this approach is inherently inadequate for lithography control. We demonstrate how dose and defocus can be derived from the attributes of dual-tone, optically measurable targets on product wafers. Our method is applied to the in-line control of sub-0.25 micrometers step-and-scan lithography.
PRAD-1/cyclin D1 gene overexpression in chronic lymphoproliferative disorders: a highly specific marker of mantle cell lymphoma (1994)

The t(11;14)(q13;q32) translocation and its molecular counterpart bcl-1 rearrangement are frequently associated with mantle cell lymphomas (MCLs) and only occasionally with other variants of B-cell lymphoid malignancies. This translocation seems to activate the expression of PRAD-1/cyclin D1 gene located downstream from the major breakpoint cluster region of this rearrangement. However, the possible overexpression of this gene in other lymphoproliferative disorders independently of bcl-1 rearrangement is unknown. We have examined the overexpression of PRAD-1 gene in a large series of 142 lymphoproliferative disorders including 20 MCLs by Northern blot analysis. Cytogenetic and/or bcl-1 rearrangement analysis with 2 probes (MTC, p94PS) were performed in 28 cases. Strong PRAD-1 overexpression was observed in 19 of the 20 MCLs including 3 gastrointestinal forms and 4 blastic variants. t(11;14) and/or bcl-1 rearrangement was detected in 6 of the 12 MCLs examined. No correlation was found between the different levels of mRNA expression and the pathologic characteristics of the lymphoma. Among chronic lymphoproliferative disorders other than MCL, only 1 atypical chronic lymphocytic leukemia (CLL) with a t(11;14) translocation and bcl-1 rearrangement and the 2 hairy cell leukemias (HCLs) analyzed showed upregulation of PRAD-1 gene. The expression in the 2 HCLs was lower than in MCL, and no bcl-1 rearrangement was observed. These findings indicate that PRAD-1 overexpression is a highly sensitive and specific molecular marker of MCL but it may also be upregulated in some B-CLLs and in HCL.
CXCL8 and Its Cognate Receptors in Melanoma Progression and Metastasis (2009)

The incidence of melanoma is rising at an alarming rate and we are still awaiting an effective treatment for this malignancy. In its early stage, melanoma can be cured by surgical removal, but once metastasis has occurred there is no effective treatment. Recent findings have suggested multiple functional implications of CXCL8 and its cognate receptors, CXCR1 and CXCR2, in melanoma pathogenesis, thus underscoring their importance as targets for cancer therapy. This review provides an update on the roles of CXCL8 and its receptors in melanoma progression and metastasis.
Isolation and characterization of Borna disease agent cDNA clones. (1990)

Borna disease (BD) is a neurologic syndrome characterized by behavioral disturbances and the accumulation of specific proteins in limbic system neurons. A viral etiology has been proposed because BD can be induced in birds, rodents, and primates by inoculation with filtered brain homogenates from animals with BD. We report here the isolation and preliminary characterization of cDNA clones from a rat with BD. These clones hybridized to specific transcripts in BD rat brain and arrested in vitro translation of BD proteins. In situ hybridization experiments using RNA probes prepared from these clones showed an abundance of these transcripts in limbic system neurons. Northern (RNA) hybridizations using these RNA probes indicated that the BD agent is probably a virus with major transcripts of 8.5, 2.1, and 0.8 kilobases.
Cytomegalovirus (CMV) retinitis and CMV antigenemia as a clue to impaired adrenocortical function in patients with AIDS (1997)

The adrenal gland is most frequently affected by CMV in AIDS patients. Our result suggests that CMV retinitis or CMV-Ag positivity independently serve as an indication of possible adrenal dysfunction.
Definitive Treatment of Combat Casualties at Military Medical Centers (2006)

More than 9,000 casualties have been evacuated during the current conflict, and more than 40,000 orthopaedic surgical procedures have been performed. The most severely injured patients are treated in the United States at military medical centers. Individualized reconstructive plans are developed, and patients are treated with state-of-the-art techniques. Rehabilitation includes the assistance of the physical medicine and rehabilitation, physical therapy, and occupational therapy services, as well as, when necessary, psychiatric or other services. The extreme challenges of treating war-related soft-tissue defects include neurovascular injuries, burns, heterotopic ossification, infection, prolonged recovery, and persistent pain. Such injuries do not allow full restoration of function. Because of such devastating injuries, and despite use of up-to-date methods, outcomes can be less than optimal.