gebhart/patrepeval huggingface dataset:
Monoclonal Antibody Analysis and Insecticidal Spectrum of Three Types of Lepidopteran-Specific Insecticidal Crystal Proteins of Bacillus thuringiensis (1988)

We have investigated the protein composition and the insecticidal spectrum of crystals of 29 Bacillus thuringiensis strains active against lepidopteran larvae. All crystals contained proteins of 130 to 140 kilodaltons (kDa) which could be grouped into three types by the molecular weight of the protoxin and the trypsin-activated core fragment. Proteins of the three types showed a characteristic insecticidal spectrum when tested against five lepidopteran species. Type A crystal proteins were protoxins of 130 or 133 kDa, which were processed into 60-kDa toxins by trypsin. Several genes encoding crystal proteins of this type have been cloned and sequenced earlier. They are highly conserved in the N-terminal half of the toxic fragment and were previously classified in three subtypes (the 4.5-, 5.3-, and 6.6-kilobase subtypes) based on the restriction map of their genes. The present study shows that different proteins of these three subtypes were equally toxic against Manduca sexta and Pieris brassicae and had no detectable activity against Spodoptera littoralis. However, the 4.5-, 5.3-, and 6.6-kilobase subtypes differed in their toxicity against Heliothis virescens and Mamestra brassicae. Type B crystal proteins consisted of 140-kDa protoxins with a 55-kDa tryptic core fragment. These were only active against one of the five insect species tested (P. brassicae). The protoxin and the trypsin-activated toxin of type C were 135- and 63-kDa proteins, respectively. Proteins of this type were associated with high toxicity against S. littoralis and M. brassicae. A panel of 35 monoclonal antibodies was used to compare the structural characteristics of crystal proteins of the three different types and subtypes. Each type of protein could be associated with a typical epitope structure, indicating an unambiguous correlation between antigenic structure and insect specificity.
Role of Macrophage Glycosaminoglycans in the Cellular Catabolism of Oxidized LDL by Macrophages (1998)

Macrophage binding sites for oxidized LDL (Ox-LDL) include class A scavenger receptors (SR-As), the CD-36 molecule, and an additional but hitherto unidentified binding site. Because cell-surface glycosaminoglycans (GAGs) were previously shown to be involved in the cellular uptake of native LDL and lipoprotein(a), several strategies to assess the participation of heparan sulfate (HS) and chondroitin sulfate (CS) in macrophage catabolism of Ox-LDL were used. First, incubation of J-774 A.1 macrophage-like cells with either heparinase or chondroitinase, or with both enzymes together, reduced the binding, uptake, and degradation of 125I-Ox-LDL by 20% to 45%, in comparison with control nontreated cells, while catabolism of 125I-labeled acetylated LDL (Ac-LDL) and native LDL were unaffected. Second, the proteoglycan (PG) cellular content was increased by cell enrichment with exogenous GAGs or by using human monocyte-derived macrophages from two patients with Sanfilippo mucopolysaccharidosis, which are characterized by cellular HS accumulation. In these macrophages, cellular uptake of 125I-Ox-LDL increased, while catabolism of 125I-Ac-LDL and native LDL were unaffected. Experiments using conditioned media from control, heparinase-digested, or chondroitinase-digested macrophages indicated that neither secreted GAGs nor released digestion products played any role in Ox-LDL catabolism. To evaluate potential interactions between cell-surface GAGs and known receptors for Ox-LDL, we used excess unlabeled Ac-LDL to block SR-As or anti-CD-36 antibodies to block CD-36, and then examined the catabolism of 125I-Ox-LDL by GAG-enriched or -depleted macrophages. Both excess unlabeled Ac-LDL and anti-CD-36 antibodies reduced 125I-Ox-LDL catabolism, but only excess unlabeled Ac-LDL completely abolished the increase in 125I-Ox-LDL catabolism on GAG enrichment of the cells, indicating a cooperation between exogenous GAGs and cell-surface SR-As in the catabolism of OX-LDL. Moreover, the addition of GAGases to macrophages that were preincubated with anti-CD-36 antibodies and excess Ac-LDL further reduced macrophage degradation of Ox-LDL in comparison with cells that were pretreated only with anti-CD-36 antibodies and Ac-LDL, indicating a more complex role for endogenous GAGs. Overall, these studies demonstrate a substantial contribution of macrophage-associated GAGs in the catabolism of Ox-LDL, which is mediated in part by a cooperation between GAGs and cell-surface SR-As.
The Global Burden of Headache: A Documentation of Headache Prevalence and Disability Worldwide (2007)

This study, which is a part of the initiative 'Lifting The Burden: The Global Campaign to Reduce the Burden of Headache Worldwide', assesses and presents all existing evidence of the world prevalence and burden of headache disorders. Population-based studies applying International Headache Society criteria for migraine and tension-type headache, and also studies on headache in general and 'chronic daily headache', have been included. Globally, the percentages of the adult population with an active headache disorder are 46% for headache in general, 11% for migraine, 42% for tension-type headache and 3% for chronic daily headache. Our calculations indicate that the disability attributable to tension-type headache is larger worldwide than that due to migraine. On the World Health Organization's ranking of causes of disability, this would bring headache disorders into the 10 most disabling conditions for the two genders, and into the five most disabling for women.
Necessary and sufficient conditions for a maximal ergodic theorem along subsequences (1987)

Abstract Let T be an ergodic measure preserving point transformation from a probability space X onto itself. Assume that is an increasing sequence of subsets of the positive integers. Conditions are given which are sufficient for the ergodic maximal function associated with these subsets to be weak type ( p, p ). These conditions are shown to be both necessary and sufficient for a larger two-sided maximal function. The conditions are in the form of covering lemmas for the integers.
Fluorescence lifetime imaging by time‐correlated single‐photon counting (2003)

We present a time-correlated single photon counting (TCPSC) technique that allows time-resolved multi-wavelength imaging in conjunction with a laser scanning microscope and a pulsed excitation source. The technique is based on a four-dimensional histogramming process that records the photon density over the time of the fluorescence decay, the x-y coordinates of the scanning area, and the wavelength. The histogramming process avoids any time gating or wavelength scanning and, therefore, yields a near-perfect counting efficiency. The time resolution is limited only by the transit time spread of the detector. The technique can be used with almost any confocal or two-photon laser scanning microscope and works at any scanning rate. We demonstrate the application to samples stained with several dyes and to CFP-YFP FRET.
The Gastrins: Their Production and Biological Activities (2001)

Gastric epithelial organization and function are controlled and maintained by a variety of endocrine and paracrine mediators. Peptides encoded by the gastrin gene are an important part of this system because targeted deletion of the gene, or of the gastrin-CCKB receptor gene, leads to decreased numbers of parietal cells and decreased gastric acid secretion. Recent studies indicate that the gastrin precursor, preprogastrin, gives rise to a variety of products, each with a distinctive spectrum of biological activity. The conversion of progastrin to smaller peptides is regulated by multiple mechanisms including prohormone phosphorylation and secretory vesicle pH. Progastrin itself stimulates colonic epithelial proliferation; biosynthetic intermediates (Gly-gastrins) stimulate colonic epithelial proliferation and gastric epithelial differentiation; and C-terminally amidated gastrins stimulate colonic proliferation, gastric epithelial proliferation and differentiation, and acid secretion. The effects of progastrin-derived peptides on gastric epithelial function are mediated in part by release of paracrine factors that include histamine, epidermal growth factor (EGF)-receptor ligands, and Reg. The importance of the appropriate regulation of this system is shown by the observation that prolonged moderate hypergastrinemia in transgenic mice leads to remodelling of the gastric epithelium, and in the presence of Helicobacter, to gastric cancer.
Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAF1/CIP1, expression in the absence of p53. (1994)

The melanoma differentiation associated gene, mda-6, which is identical to the P53-inducible gene WAF1/CIP1, encodes an M(r) 21,000 protein (p21) that can directly inhibit cell growth by repressing cyclin dependent kinases. mda-6 was identified using subtraction hybridization by virtue of its enhanced expression in human melanoma cells induced to terminally differentiate by treatment with human fibroblast interferon and the anti-leukemic compound mezerein (Jiang and Fisher, 1993). In the present study, we demonstrate that mda-6 (WAF1/CIP1) is an immediate early response gene induced during differentiation of the promyelocytic HL-60 leukemia cell line along the granulocytic or macrophage/monocyte pathway. mda-6 gene expression in HL-60 cells is induced within 1 to 3 h during differentiation along the macrophage/monocyte pathway evoked by 12-0-tetradecanoyl phorbol-13-acetate (TPA) or 1,25-dihydroxyvitamin D3 (Vit D3) or the granulocytic pathway produced by retinoic acid (RA) or dimethylsulfoxide (DMSO). Immunoprecipitation analyses using an anti-p21 antibody indicate a temporal induction of p21 protein following treatment with TPA, DMSO or RA. A relationship between rapid induction of mda-6 gene expression and differentiation is indicated by a delay in this expression in an HL-60 cell variant resistant to TPA-induced growth arrest and differentiation. A similar delay in mda-6 gene expression is not observed in Vit D3 treated TPA-resistant variant cells that are also sensitive to induction of monocytic differentiation. Since HL-60 cells have a null-p53 phenotype, these results demonstrate that p21 induction occurs during initiation of terminal differentiation in a p53-independent manner. In this context, p21 may play a more global role in growth control and differentiation than originally envisioned.
The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study. (2000)

The protein c-erbB-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsies from women diagnosed with malignant tumors. Present studies suggest that soluble fragments of the c-erbB-2 oncogene may be released from the cell surface and become detectable in patients with carcinoma of the breast. Consequently, the purpose of this study was to assay the c-erbB-2 protein in the saliva and serum of women with and without carcinoma of the breast and to determine whether the protein possesses any diagnostic value. To determine the diagnostic utility of this oncogene, the soluble form of the c-erbB-2 protein was assayed in the saliva and serum using ELISA in three different groups of women. The three groups consisted of 57 healthy women, 41 women with benign breast lesions, and 30 women diagnosed with breast cancer. To compare the relative diagnostic utility of the c-erbB-2 protein, CA 15-3 was also measured. The CA 15-3 measurements served as a "gold standard" by which to compare the c-erbB-2 protein's diagnostic effectiveness. We found c-erbB-2 protein in the saliva and serum of all three groups of women. The salivary and serological levels of c-erbB-2 in the cancer patients, however, were significantly higher (P < 0.001) than the salivary and serum levels of healthy controls and benign tumor patients. Additionally, the c-erbB-2 protein was found to be equal to or to surpass the ability of CA 15-3 to detect patients with carcinoma. The results of the pilot study suggest that the c-erbB-2 protein may have potential use in the initial detection and/or follow-up screening for the recurrence of breast cancer in women.
Wideband 15&#x2013;50GHz symmetric multi-section coupled line quadrature hybrid based on surface micromachining technology (2012)

This paper demonstrates a quadrature hybrid developed using the surface micromachining technology PolyStrata™. Circuit model designs are optimized over 15–50GHz and a full-wave 3D model is tuned computationally to better approximate ideal performance. The full-wave results show misbalances below 0.5dB and 5° for magnitude and phase, respectively. Designed device is fabricated and good agreement with simulations is obtained.
Membrane protein purification and crystallization : a practical guide (2003)

I. Strategies and Techniques Purification Strategies for Membrane Proteins. Chromatographic Techniques and Basic Operations in Membrane Protein Purification. Production and purification of recombinant membrane proteins. SDS Electrophoresis Techniques. Blue-Native Electrophoresis. Preparative Isoelectric Focussing. Membrane protein crystallization. II. Discussion of Selected Isolation Protocols Lipid Dependent Inactivation and Reactivation of Bovine complex III. Purification of affinity-epitope tagged G-protein coupled receptors. Purification of NhaA, the Na+/H+ Antiporter of Escherichia coli for 3D or 2D Crystallization. Purification of the yeast cytochrome bc1 complex. III. Crystallization of Membrane Proteins Antibody fragment-mediated crystallization of membrane proteins. Crystallization of Wolinella succinogenes quinol:fumarate reductase. Ba3-type cytochrome-c oxidase from Thermus thermophilus: purification, crystallization, and crystal transformation. Two-dimensional crystallization of membrane proteins: a practical guide. In cubo crystallization of membrane proteins.
Human Astrovirus Coat Protein Inhibits Serum Complement Activation via C1, the First Component of the Classical Pathway (2007)

Human astroviruses (HAstVs) belong to a family of nonenveloped, icosahedral RNA viruses that cause noninflammatory gastroenteritis, predominantly in infants. Eight HAstV serotypes have been identified, with a worldwide distribution. While the HAstVs represent a significant public health concern, very little is known about the pathogenesis of and host immune response to these viruses. Here we demonstrate that HAstV type 1 (HAstV-1) virions, specifically the viral coat protein (CP), suppress the complement system, a fundamental component of the innate immune response in vertebrates. HAstV-1 virions and purified CP both suppress hemolytic complement activity. Hemolytic assays utilizing sera depleted of individual complement factors as well as adding back purified factors demonstrated that HAstV CP suppresses classical pathway activation at the first component, C1. HAstV-1 CP bound the A chain of C1q and inhibited serum complement activation, resulting in decreased C4b, iC3b, and terminal C5b-9 formation. Inhibition of complement activation was also demonstrated for HAstV serotypes 2 to 4, suggesting that this phenomenon is a general feature of these human pathogens. Since complement is a major contributor to the initiation and amplification of inflammation, the observed CP-mediated inhibition of complement activity may contribute to the lack of inflammation associated with astrovirus-induced gastroenteritis. Although diverse mechanisms of inhibition of complement activation have been described for many enveloped animal viruses, this is the first report of a nonenveloped icosahedral virus CP inhibiting classical pathway activation at C1.
Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma. (2016)

8006 Background: Despite recent progress, MM remains incurable, hence the need for agents with novel mechanisms of action. Marine-derived plitidepsin targets eEF1A2, a protein overexpressed in MM. Plitidepsin/dexamethasone showed activity in a phase I/II trial conducted in relapsed or refractory MM. Moreover, plitidepsin exhibited synergism with bortezomib and lenalidomide in human MM cell lines and tumor samples. Methods: Relapsed and/or refractory MM patients were included if they had ECOG PS≤2 and CrCL>30 ml/min. Prior hematopoietic stem cell transplantation (HSCT) and previous treatment with bortezomib or other PIs and IMIDs was allowed. Primary objective: identification of the recommended dose (RD) for po dexamethasone (days 1,8,15,22)/s.c. bortezomib (days 1,4,8,11)/i.v. plitidepsin (days 1,15) administered every 4 weeks across 3 dose levels (DLs): DL1: 40 mg/1.0 mg/m2/4.0 mg/m2, DL2: 40mg/1.3mg/m2/4.0mg/m2 and DL3: 40mg/1.3mg/m2/5.0mg/m2. Secondary objectives: evaluation of efficacy and overall safety. Results: Twenty patients were enrolled. Median age was 65, median number of prior regimens was 3.5 (range, 1-10) and 9 patients had undergone HSCT. No dose-limiting toxicities (DLTs) were observed (n=20), therefore the RD was established at DL3. Hematological toxicity was manageable; grade 3-4 events included anemia (25%), neutropenia (25%) and thrombocytopenia (60%). Non-hematological toxicity was mainly mild. Out of 18 patients evaluable for efficacy, 15(83%) had received bortezomib and lenalidomide and 7/15 patients were refractory to lenalidomide. Overall response rate (ORR):56%, including 2 complete responses (11%), 4 very good partial responses (22%), 4 partial responses (22%) (one of them in a patient triple refractory to bortezomib, lenalidomide and pomalidomide) and 3 minimal responses (17%). Clinical benefit: 72%, median PFS: 8.3 months, PFS6months: 58% and DOR 6months: 90% (10 patients are still on-treatment). Conclusions: the RD for dexamethasone/bortezomib/plitidepsin at the tested schedule was established at 40 mg/1.3 mg/m2/5 mg/m2. An ORR of 56% was observed, including ≥ VGPR:33%. The drug combination was well tolerated. Clinical trial information: NCT02100657.
Modern organic chemistry, by John D. Roberts and Marjorie C. Caserio, W. A. Benjamin, Inc., New York, N. Y., 1967. XXII + 844 pp. Price $10.75 (1968)

No Abstract.
DNA-Based Immunotherapeutics For Allergic Disease (2002)

Allergic diseases are a growing health concern in industrialized countries. Despite a number of effective therapeutic options for the prevention and treatment of the pathophysiologic responses that occur upon allergen exposure, the induction of true allergen desensitization remains an elusive therapeutic goal. Only immunotherapy (IT) has been shown to have any effect on the underlying hypersensitivities, which mediate allergic responses and traditional protein based allergen IT has a limited scope of efficacy. However, a number of reagents collectively termed DNA based immunotherapeutics have proven highly effective in both the prevention and reversal of Th2 mediated hypersensitivity states in mouse models of allergic disease. Four basic DNA based immunotherapeutic modalities have been used for these studies. These include immunization with gene vaccines, allergen mixed with immunostimulatory oligodeoxynucleotide (ISS-ODN), and physical allergen:ISS-ODN conjugates (AIC), as well as immunomodulation with ISS-ODN alone. This chapter will provide a framework for understanding the application of these DNA based immunotherapeutic strategies to the treatment of allergic disease.
Antitumor Synergism and Enhanced Survival with a Tumor Vasculature–Targeted Enzyme Prodrug System, Rapamycin, and Cyclophosphamide (2017)

Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with Annexin A1 or Annexin A5. Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart nonnative methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of nontoxic selenomethionine. The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of nonnative proteins and/or DNA required with other enzyme prodrug systems. The enzyme fusion exhibits strong and stable <i>in vitro</i> binding with dissociation constants in the nanomolar range for both human and mouse breast cancer cells and in a cell model of tumor vascular endothelium. Daily administration of the therapy suppressed growth of highly aggressive triple-negative murine 4T1 mammary tumors in immunocompetent BALB/cJ mice and MDA-MB-231 tumors in SCID mice. Treatment did not result in the occurrence of negative side effects or the elicitation of neutralizing antibodies. On the basis of the vasculature-targeted nature of the therapy, combinations with rapamycin and cyclophosphamide were evaluated. Rapamycin, an mTOR inhibitor, reduces the prosurvival signaling of cells in a hypoxic environment potentially exacerbated by a vasculature-targeted therapy. IHC revealed, unsurprisingly, a significant hypoxic response (increase in hypoxia-inducible factor 1 α subunit, HIF1A) in the enzyme prodrug-treated tumors and a dramatic reduction of HIF1A upon rapamycin treatment. Cyclophosphamide, an immunomodulator at low doses, was combined with the enzyme prodrug therapy and rapamycin; this combination synergistically reduced tumor volumes, inhibited metastatic progression, and enhanced survival. <i>Mol Cancer Ther; 16(9); 1855-65. ©2017 AACR</i>.
A Transgenic Model to Analyze the Immunoregulatory Role of IL-10 Secreted by Antigen-Presenting Cells (1999)

IL-10 is a cytokine secreted by a wide variety of cells type that has pleiotropic stimulatory and suppressive activities on both lymphoid and myeloid cells in vitro. To analyze the consequences of high IL-10 secretion by APCs in immune responses, we produced transgenic mice expressing human IL-10 directed by the MHC class II Ea promoter. Despite alterations in the development of T and B cells, no gross abnormalities were detected in peripheral lymphocyte populations or serum Ig levels. However, when immunized using conditions that give either a Th2-type or a Th1-type response, IL-10 transgenic mice failed to mount a significant T or B cell immune response to OVA. IL-10 transgenic mice were also highly susceptible to infection with intracellular pathogens like Listeria monocytogenes or Leishmania major, in contrast to IL-10 transgenic mice, where the transgene was express in T cells. Finally, the recently described stimulatory effect of IL-10 on CD8+ T cells was confirmed by the ability of IL-10 transgenic mice to limit the growth of immunogenic tumors by a CTL-mediated mechanism. These results demonstrate, that, depending on the type of immune response, IL-10 can mediate immunosuppressive or immunostimulatory activities in vivo.
Surface-Enhanced Raman Detection of 2,4-Dinitrotoluene Impurity Vapor as a Marker To Locate Landmines (2000)

Time, cost, and casualties associated with demining efforts underscore the need for improved detection techniques. Reduction in the number of false positives by directly detecting the explosive material, rather than casing material, is desirable. The desired field sensor must, at a minimum, demonstrate reproducibility, the necessary level of sensitivity, portability, instrumental stability, and fast system response times. Ideally, vibrational spectroscopic techniques have the potential to remove false positives, since every chemical has a unique bond structure. Herein, we demonstrate the capabilities of surface-enhanced Raman spectroscopy to detect the chemical vapor signature emanating from buried TNT-based landmines. We present reproducible results obtained from blind tests controlled by the Defense Advanced Research Projects Agency (DARPA) that demonstrate vapor detection of 2,4-dinitrotoluene at concentration levels of 5 ppb or less. The results presented used acquisition times of 30 s on a fieldable system and showed that SERS can be a significant improvement over current landmine detection methods.