gebhart/patrepeval huggingface dataset:
B Lymphocyte Stimulator (BLyS): A Therapeutic Trichotomy for the Treatment of B Lymphocyte Diseases (2002)

B Lymphocyte Stimulator (BLyS protein) is a member of the tumor necrosis factor (TNF) family of ligands and functions as an essential in vivo regulator of B lymphocyte homeostasis. As such, changes in systemic BlyS protein expression caused by disruption of the gene encoding BLyS or administration of neutralizing soluble receptors have resulted in profound losses in mature B cell numbers and impaired humoral immunity. A similar phenotype has been observed in A/WySnJ mice that express a truncated BLyS receptor and are thus defective in BLyS signal transduction. In contrast, overexpression of BLyS protein in BLyS-transgenic mice results in B cell hyperplasia, hypergammaglobulinemia, and development of autoimmune-like disease. The ability of BLyS to regulate both the size and repertoire of the peripheral B cell compartment raises the possibility that BLyS and antagonists thereof may form the basis of a therapeutic trichotomy. As an agonist, BLyS protein may enhance humoral immunity in congenital or acquired immunodeficiencies such as those resulting from viral infection or cancer therapy. BLyS-specific antagonists (antibodies or soluble receptors) that inhibit the biological activity of BLyS may be effective therapies for those autoimmune diseases characterized by polyclonal hypergammaglobulinemia and elevated autoantibody titers. Finally, the specificity of BLyS for B-lineage cells raises the possibility that BLyS may be used as a targeting vehicle for delivery of a cytotoxic or cytolytic signal to neoplastic B-lineage cells expressing one or more of the three known BLyS receptors. This review discusses the therapeutic potential of BLyS in the context of BLyS structure, function and receptor specificity.
LOTTERYBUS: a new high-performance communication architecture for system-on-chip designs (2002)

The LOTTERYBUS architecture was designed to address the following limitations of current communication architectures: (i) lack of control over the allocation of communication bandwidth to different system components or data flows (e.g., in static priority based shared buses), leading to starvation of lower priority components in some situations, and (ii) significant latencies resulting from variations in the time-profile of the communication requests (e.g., in time division multiplexed access (TDMA) based architectures), sometimes leading to larger latencies for high-priority communications. We present two variations of LOTTERYBUS: the first is a low overhead architecture with statically configured parameters, while the second variant is a more sophisticated architecture, in which values of the architectural parameters are allowed to vary dynamically. Our experiments investigate the performance of the LOTTERYBUS architecture across a wide range of communication traffic characteristics. In addition, we also analyze its performance in a 4/spl times/4 ATM switch sub-system design. The results demonstrate that the LOTTERYBUS architecture is (i) capable of providing the designer with fine grained control over the bandwidth allocated to each SoC component or data flow, and (ii) well suited to provide high priority communication traffic with low latencies (we observed upto 85.4% reduction in communication latencies over conventional on-chip communication architectures).
CD19 chimeric antigen receptor T cell therapy for haematological malignancies (2015)

T cells can be redirected to recognize tumour antigens by genetic modification to express a chimeric antigen receptor (CAR). These consist of antibody-derived antigen-binding regions linked to T cell signalling elements. CD19 is an ideal target because it is expressed on most B cell malignancies as well as normal B cells but not on other cell types, restricting any 'on target, off tumour' toxicity to B cell depletion. Recent clinical studies involving CD19 CAR-directed T cells have shown unprecedented responses in a range of B cell malignancies, even in patients with chemorefractory relapse. Durable responses have been achieved, although the persistence of modified T cells may be limited. This therapy is not without toxicity, however. Cytokine release syndrome and neurotoxicity appear to be frequent but are treatable and reversible. CAR T cell therapy holds the promise of a tailored cellular therapy, which can form memory and be adapted to the tumour microenvironment. This review will provide a perspective on the currently available data, as well as on future developments in the field.
Structural and haemostatic features of pharmaceutical heparins from different animal sources: challenges to define thresholds separating distinct drugs (2016)

Heparins extracted from different animal sources have been conventionally considered effective anticoagulant and antithrombotic agents despite of their pharmacological dissimilarities. We performed herein a systematic analysis on the physicochemical properties, disaccharide composition, in vitro anticoagulant potency and in vivo antithrombotic and bleeding effects of several batches of pharmaceutical grade heparins obtained from porcine intestine, bovine intestine and bovine lung. Each of these three heparin types unambiguously presented differences in their chemical structures, physicochemical properties and/or haemostatic effects. We also prepared derivatives of these heparins with similar molecular weight differing exclusively in their disaccharide composition. The derivatives from porcine intestinal and bovine lung heparins were structurally more similar with each other and hence presented close anticoagulant activities whereas the derivative from bovine intestinal heparin had a higher proportion of 6-desulfated α-glucosamine units and about half anticoagulant activity. Our findings reasonably indicate that pharmaceutical preparations of heparin from different animal sources constitute distinct drugs, thus requiring specific regulatory rules and therapeutic evaluations.
Purification of Mutacin III from Group III Streptococcus mutans UA787 and Genetic Analyses of Mutacin III Biosynthesis Genes (1999)

Previously, members of our group reported the isolation and characterization of mutacin II from Streptococcus mutans T8 and the genetic analyses of the mutacin II biosynthesis genes (J. Novak, P. W. Caufield, and E. J. Miller, J. Bacteriol. 176:4316-4320, 1994; F. Qi, P. Chen, and P. W. Caufield, Appl. Environ. Microbiol. 65:652-658, 1999; P. Chen, F. Qi, J. Novak, and P. W. Caufield, Appl. Environ. Microbiol. 65:1356-1360, 1999). In this study, we cloned and sequenced the mutacin III biosynthesis gene locus from a group III strain of S. mutans, UA787. DNA sequence analysis revealed eight open reading frames, which we designated mutR, -A, -A', -B, -C, -D, -P, and -T. MutR bears strong homology with MutR of mutacin II, while MutA, -B, -C, -D, -P, and -T are counterparts of proteins in the lantibiotic epidermin group. MutA' has 60% amino acid identity with MutA and therefore appears to be a duplicate of MutA. Insertional inactivation demonstrated that mutA is an essential gene for mutacin III production, while mutA' is not required. Mutacin III was purified to homogeneity by using reverse-phase high-pressure liquid chromatography. N-terminal peptide sequencing of the purified mutacin III determined mutA to be the structural gene for prepromutacin III. The molecular mass of the purified peptide was measured by laser disorption mass spectrophotometry and found to be 2,266.43 Da, consistent with our supposition that mutacin III has posttranslational modifications similar to those of the lantibiotic epidermin.
A Multicenter Clinical Trial of a Biosynthetic Skin Replacement, Dermagraft-TC, Compared with Cryopreserved Human Cadaver Skin for Temporary Coverage of Excised Burn Wounds (1997)

This multicenter study compared the use of a biosynthetic human skin substitute with frozen human cadaver allograft for the temporary closure of excised burn wounds. Dermagraft-TC (Advanced Tissue Sciences, Inc.) (DG-TC) consists of a synthetic material onto which human neonatal fibroblasts are cultured. Burn wounds in 66 patients with a mean age of 36 years and a mean burn size of 44% total body surface area (28% total body surface area full-thickness) were surgically excised. Two comparable sites, each approximately 1% total body surface area in size, were randomized to receive either DG-TC or allograft. Both sites were then treated in the same manner. When clinically indicated (> 5 days after application) both skin replacements were removed, and the wound beds were evaluated and prepared for grafting. DG-TC was equivalent or superior to allograft with regard to autograft take at postautograft day 14. DG-TC was also easier to remove, had no epidermal slough, and resulted in less bleeding than did allograft while maintaining an adequate wound bed. Overall satisfaction was better with DG-TC.
POVERTY IN INDIA 1951-1994: TRENDS AND DECOMPOSITIONS (1997)

We construct a new time series of poverty measures for both rural and urban India from 1951 to 1994. The results show that there was little progress in reducing poverty until the mid-1970s, and that there has been a marked downward trend since then. It took nearly 30 years for India&amp;apos;s poverty measures to fall appreciably below their levels in the early 1950s. Measures of the depth and severity of poverty show a more marked decline over the period than does the headcount index. More than three-fourths of the decline in national poverty measures is attributable to the decline in rural poverty. Both growth in mean consumption and redistribution contributed to the decline in national poverty.
High temperature superconducting compounds 2 (1990)

This book presents a symposium on high temperature superconducting compounds. It includes papers in the areas of fundamental understanding of the subject and of novel processing approaches to increase the critical current density by alleviating the weak link problems and by enhancing flux pinning. The authors have elaborated on the present understanding of various aspects of the critical current density in the oxide superconductors. The major subjects covered include weak link phenomena, flux creep and processing approaches. Progress on the thin film fabrication is presented. Major trends include the epitaxial deposition of films to enhance critical current density and the deposition of films at low temperatures. The subjects discussed include melt texturing and fabrication of wires/tapes/filaments.
Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. (1986)

Deficiency of the enzyme adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4; ADA) leads to severe combined immunodeficiency, a disorder that potentially could be corrected by gene transfer into hematopoietic cells. We have constructed retroviruses containing human ADA cDNA and a dominant selectable marker, a mutated dihydrofolate reductase gene (DHFR*) encoding methotrexate resistance. Human ADA cDNA was inserted alone (DHFR*-ADA) or with a simian virus 40 (SV40) promoter (DHFR*-SVADA). Although NIH 3T3 cells infected with either construct produced human ADA activity, substantially greater levels were attained with DHFR*-SVADA. Infection of murine lymphoid cells in culture with DHFR*-SVADA led to expression of human enzyme at a level well above the mouse endogenous level. ADA activity was also increased after infection of a human ADA-deficient B-cell line. Lethally irradiated mice that were reconstituted with syngeneic marrow infected with the DHFR*-SVADA virus contained unrearranged, integrated proviral DNA in total spleen DNA or in spleen hematopoietic stem cell (CFU-S)-derived colonies. Nevertheless, no human ADA was detectable. RNA analysis showed relatively low and variable expression from the retroviral long terminal repeat, and no detectable expression from the internal SV40 promoter. These data suggest that intrinsic biologic differences exist between cultured cells and CFU-S in vivo.
A synthetic alanyl-initiator tRNA with initiator tRNA properties as determined by flourescence measurements: comparison to a synthetic alanyl-elongator tRNA (1991)

Two synthetic tRNAs have been generated that can be enzymatically aminoacylated with alanine and have AAA anticodons to recognize a poly(U) template. One of the tRNAs (tRNA(eAla/AAA)) is nearly identical to Escherichia coli elongator tRNA(Ala). The other has a sequence similar to Escherichia coli initiator tRNA(Met) (tRNA(iAla/AAA)). Although both tRNAs can be used in poly(U)-directed nonenzymatic initiation at 15 mM Mg2+, only the elongator tRNA can serve for peptide elongation and polyalanine synthesis. Only the initiator tRNA can be bound to 30S ribosomal subunits or 70S ribosomes in the presence of initiation factor 2 (IF-2) and low Mg2+ suggesting that it can function in enzymatic peptide initiation. A derivative of coumarin was covalently attached to the alpha amino group of alanine of these two Ala-tRNA species. The fluorescence spectra, quantum yield and anisotropy for the two Ala-tRNA derivatives are different when they are bound to 70S ribosomes (nonenzymatically in the presence of 15 mM Mg2+) indicating that the local environment of the probe is different. Also, the effect of erythromycin on their fluorescence is quite different, suggesting that the probes and presumably the alanine moiety to which they are covalently linked are in different positions on the ribosomes.
Formation of amyloid aggregates from human lysozyme and its disease‐associated variants using hydrostatic pressure (2004)

Formation of amyloid deposits from the Ile56Thr or Asp67His variants of human lysozyme is a hallmark of autosomal hereditary systemic amyloidosis. It has recently been shown that amyloid fibrils can be formed in vitro from wild-type (WT), I56T, or D67H lysozyme variants upon prolonged incubation at acidic pH and elevated temperatures (1). Here, we have used hydrostatic pressure as a tool to generate amyloidogenic states of WT and variant lysozymes at physiological pH. WT or variant lysozyme samples were initially compressed to 3.5 kbar (at 57 degrees C, pH 7.4). Decompression led to the formation of amyloid fibrils, protofibrils, or globular aggregates, as indicated by light scattering, thioflavin T fluorescence, and transmission electron microscopy analysis. Increased 1-anilinonaphthalene-8-sulfonate binding to the proteins was also observed, indicating exposure of hydrophobic surface area. Thus, pressure appears to induce a conformational state of lysozyme that aggregates readily upon decompression. These results support the notion that amyloid aggregation results from the formation of partially unfolded protein conformations and suggest that pressure may be a useful tool for the generation of the amyloidogenic conformations of lysozyme and other proteins.
Profound Normovolemic Hemodilution (1996)

Previous systematic investigations of the hemostatic effects of normovolemic hemodilution (NHD) have not explored the influence of hematocrits less than 20% in humans or animals.However, clinical interest in maximizing the perioperative conservation of erythrocytes may involve profound NHD beyond traditionally accepted empiric end points. We report here on coagulation data in eight healthy adolescent patients undergoing profound NHD in concert with surgical correction of idiopathic scoliosis, and in 29 swine undergoing experimental stepwise NHD until death. Blood was replaced with 5% albumin in 0.9% saline in our patients, and with 5% albumin in lactated Ringer's solution in our pigs. A 75% blood volume exchange in our patients yielded a platelet count (PLT) of 158 +/- 26 times 103/micro Liter, fibrinogen concentration (FIB), 50 +/- 7 mg/dL, prothrombin time (PT), 25.4 +/- 2.6 s, activated partial thromboplastin time (aPTT), 87 +/- 15 s, and a nadir hemoglobin of 2.8 +/- 0.2 g/dL; however, global oxygen delivery as assessed by body oxygen consumption remained adequate. Coagulation during the experimental porcine hemodilution was assessed by measuring PLT, FIB, PT, and aPTT, as well as by measurement of coagulation factor activities. In neither species did clinically significant thrombocytopenia (PLT < 100 times 103/micro Liter) become manifest prior to clinical or other laboratory evidence of coagulopathy. Rather, a combined deficiency of coagulation factors explains the coagulopathy developing during NHD in both patients and swine. Abnormal hemostasis develops prior to compromise of global tissue oxygenation, assessed by mixed venous oxygen saturation and total body oxygen consumption, during NHD in healthy patients anesthetized as described. Therefore, NHD may be more limited by preservation of normal coagulation than of global oxygen delivery and consumption. (Anesth Analg 1996;83:459-65)
Inactivation of the Type II Receptor Reveals Two Receptor Pathways for the Diverse TGF-β Activities (1993)

Transforming growth factor-beta (TGF-beta) is a multifunctional protein that regulates cell proliferation and differentiation and extracellular matrix production. Although two receptor types, the type I and type II receptors, have been implicated in TGF-beta-induced signaling, it is unclear how the many activities of TGF-beta are mediated through these receptors. With the use of cells overexpressing truncated type II receptors as dominant negative mutants to selectively block type II receptor signaling, the existence of two receptor pathways was shown. The type II receptors, possibly in conjunction with type I receptors, mediate the induction of growth inhibition and hypophosphorylation of the retinoblastoma gene product pRB. The type I receptors are responsible for effects on extracellular matrix, such as the induction of fibronectin and plasminogen activator inhibitor I, and for increased JunB expression. Selective inactivation of the type II receptors alters the TGF-beta response in a similar manner to the functional inactivation of pRB, suggesting a role for pRB in the type II, but not the type I, receptor pathway.
Toxicological considerations when creating nanoparticle-based drugs and drug delivery systems (2011)

Nanotechnology has significant potential for advancing therapeutic efficacy and imaging in cancer; however, these agents can be toxic. Therefore, toxicity needs to be considered when selecting nanoparticles for a particular application. Methods for assessing nanoparticle toxicity need to be improved and standardized across all nanotechnology platforms in order to speed up the application of nanoparticle use in humans.
Mussel Adhesion: Finding the Tricks Worth Mimicking (2005)

ABSTRACT The byssus is a holdfast structure that allows the marine mussel (Mytilus) to adopt a sessile mode of life even in the most wave-swept habitats. The success of byssus as an adaptation for attachment is at least in part responsible for the fouling caused by these organisms, but it has also provided inspiration for the design of underwater adhesives and coatings. A valuable bio-inspired concept emerging from mussel adhesion is that of polymers with catecholic and phosphate functionalities for robust underwater surface coupling. Prepolymer processing by complex coacervation for good spreading and functional gradients is also likely to find applications.
A method for relative position tracking of vehicles using optical navigation technology (2007)

Abstract:- This paper proposes a new and unique as well as cost effective solution for applications which require high accuracy relative tracking and for which GPS solutions are cost excessive or inappropriate.
SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. (2003)

The purpose of this study was to evaluate the activity of the indolinone kinase inhibitor SU11248 against the receptor tyrosine kinase KIT in vitro and in vivo, examine the role of KIT in small cell lung cancer (SCLC), and anticipate clinical utility of SU11248 in SCLC. SU11248 is an oral, multitargeted tyrosine kinase inhibitor with direct antitumor and antiangiogenic activity through targeting platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor, KIT, and FLT3 receptors. Treatment of the KIT-expressing SCLC-derived NCI-H526 cell line in vitro with SU11248 resulted in dose-dependent inhibition of stem cell factor-stimulated KIT phosphotyrosine levels and proliferation. The biological significance of KIT inhibition was evaluated in vivo by treating mice bearing s.c. NCI-H526 tumors with SU11248 or another structurally unrelated KIT inhibitor, STI571 (Gleevec), which is also known to inhibit Bcr-Abl and PDGFRbeta. SU11248 treatment resulted in significant tumor growth inhibition, whereas inhibition from STI571 treatment was less dramatic. Both compounds reduced phospho-KIT levels in NCI-H526 tumors, with a greater reduction by SU11248, correlating with efficacy. Likewise, phospho-PDGFRbeta levels contributed by tumor stroma and with known involvement in angiogenesis were strongly inhibited by SU11248 and less so by STI571. Because platinum-based chemotherapy is part of the standard of care for SCLC, SU11248 was combined with cisplatin, and significant tumor growth delay was measured compared with either agent alone. These results expand the profile of SU11248 as a KIT signaling inhibitor and suggest that SU11248 may have clinical potential in the treatment of SCLC via direct antitumor activity mediated via KIT as well as tumor angiogenesis via vascular endothelial growth factor receptor FLK1/KDR and PDGFRbeta.
CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance (2014)

The majority of non-small cell lung cancer (NSCLC) patients harbor EGFR-activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with EGFR mutations are refractory to EGFR-TKIs. Resistance to EGFR inhibitors reportedly involves SRC activation and induction of epithelial-to-mesenchymal transition (EMT). Here, we have demonstrated that overexpression of CRIPTO1, an EGF-CFC protein family member, renders EGFR-TKI-sensitive and EGFR-mutated NSCLC cells resistant to erlotinib in culture and in murine xenograft models. Furthermore, tumors from NSCLC patients with EGFR-activating mutations that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1 compared with tumors from patients that were sensitive to EGFR-TKIs. Primary NSCLC cells derived from a patient with EGFR-mutated NSCLC that was intrinsically erlotinib resistant were CRIPTO1 positive, but gained erlotinib sensitivity upon loss of CRIPTO1 expression during culture. CRIPTO1 activated SRC and ZEB1 to promote EMT via microRNA-205 (miR-205) downregulation. While miR-205 depletion induced erlotinib resistance, miR-205 overexpression inhibited CRIPTO1-dependent ZEB1 and SRC activation, restoring erlotinib sensitivity. CRIPTO1-induced erlotinib resistance was directly mediated through SRC but not ZEB1; therefore, cotargeting EGFR and SRC synergistically attenuated growth of erlotinib-resistant, CRIPTO1-positive, EGFR-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome intrinsic EGFR-inhibitor resistance in patients with CRIPTO1-positive, EGFR-mutated NSCLC.