gebhart/patrepeval huggingface dataset:
Development of a Murine Mutant Ras CD8+ CTL Peptide Epitope Variant That Possesses Enhanced MHC Class I Binding and Immunogenic Properties (1998)

We recently identified a murine mutant Ras p21 CD8+ CTL epitope reflecting residues 4 to 12, containing the mutation of Gly to Val at codon 12, that bound weakly to H-2Kd in vitro and generated a weak primary CTL response in immunized BALB/c mice. Here, we explored the hypothesis that specific modifications to the Ras4-12 peptide sequence can improve MHC binding, leading to enhanced immunogenicity without altering immune specificity. We synthesized Ras4-12 peptides in which Val at residue 12 was replaced with the more dominant H-2Kd C-terminus anchor residue Leu or Ile. In functional H-2Kd binding assays, Ras4-12(L12 or I12) peptide variants competed more effectively than the Ras4-12(V12) peptide. Ras4-12(L12 or I12) peptide variants enhanced both in vitro cytotoxicity and proliferation responses of anti-Ras4-12 CTL compared with the mutant Ras4-12(V12) peptide. Additionally, the Ras4-12(L12) peptide variant induced a quantitatively greater T cell response in vivo compared with that produced by Ras4-12(V12) as determined by IFN-gamma production. Mice immunized with Ras4-12(L12) peptide elicited CD8+ CTL activity specific for target cells presenting the Ras4-12(V12) epitope exogenously and endogenously. Moreover, both anti-Ras4-12(V12)-derived and anti-Ras4-12(L12)-derived CTL lines were similar insofar as their TCR usage and amino acid contact residues in the Ras4-12(V12) peptide. These experiments demonstrate that modifications can be introduced in tumor-specific peptide epitopes to enhance both in vitro and in vivo immunogenicity. The design of oncogene-specific peptide epitope variants as immunogens may accelerate the generation of anti-tumor T cell responses for cancer immunotherapy.
Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice. (1990)

Potentially fatal physiologic and metabolic derangements can occur in response to bacterial infection in animals and man. Recently it has been shown that alterations in the levels of circulating cytokines such as IL-6 and TNF-alpha occur shortly after bacterial challenge. To understand better the role of IL-6 in inflammation, we investigated the effects of in vivo anti-mouse IL-6 antibody treatment in a mouse model of septic shock. Rat anti-mouse IL-6 neutralizing mAb was produced from splenocytes of an animal immunized with mouse rIL-6. This mAb, MP5-20F3, was a very potent and specific antagonist of mouse IL-6 in vitro bioactivity, demonstrated using the NFS60 myelomonocytic and KD83 plasmacytoma target cell lines, and also immunoprecipitated radiolabeled IL-6. Anti-IL-6 mAb pretreatment of mice subsequently challenged with lethal doses of i.p. Escherichia coli or i.v. TNF-alpha protected mice from death caused by these treatments. Pretreatment of E. coli-challenged mice with anti-IL-6 led to an increase in serum TNF bioactivity, in comparison to isotype control antibody, implicating IL-6 as a negative modulator of TNF in vivo. Anti-TNF-alpha treatment of mice challenged i.p. with live E. coli resulted in a 70% decrease in serum IL-6 levels, determined by immunoenzymetric assay, compared to control antibody, thereby supporting a role for TNF-alpha as a positive regulator of IL-6 levels. We conclude that IL-6 is a mediator in lethal E. coli infection, and suggest that antagonists of IL-6 may be beneficial therapeutically in life-threatening bacterial infection.
ジェイムズ・K・バクスター (ニュージーランド詩人) (1994)

To clarify the role of in vivo interferon activation in the recovery from acute hepatitis C and in the prediction of responses to interferon-alpha treatment in chronic hepatitis C, we measured concentrations of 2',5'-oligoadenylate synthetase in the serum of 14 patients with well-documented acute post-transfusion hepatitis C and 40 patients with histologically confirmed chronic hepatitis C. In the latter group, 16 received interferon-alpha treatment, while no specific treatment was given to patients with acute hepatitis C. Serum activity of 2',5'-oligoadenylate synthetase was measured in duplicate by radioimmunoassay. Four out of the 14 patients with acute hepatitis C recovered, and hepatitis in the remaining 10 became chronic. Serum 2',5'-oligoadenylate synthetase concentration in the acute stage of hepatitis was above 200 pmol/dL in all four patients who recovered and in only of two of the remaining 10 patients (p < 0.02, Fisher's exact test). The 16 chronic hepatitis C patients who received interferon-alpha treatment were classified into sustained responders, relapsed responders and nonresponders, as judged by their responses to the treatment. Among the three groups, there was no significant difference in the mean concentrations of 2',5'-oligoadenylate synthetase either before the treatment or in the peak concentrations during the treatment. We conclude that activation of in vivo interferon in the acute stage favors recovery from acute hepatitis C, and 2',5'-oligoadenylate synthetase concentration cannot predict the responses to interferon-alpha treatment in patients with chronic hepatitis C.
Instrument matrix of the four-detector photopolarimeter: physical meaning of its rows and columns and constraints on its elements (1990)

The four-detector photopolarimeter (FDP) is an arrangement of four photodetectors for measuring the state of polarization of light. The output current vector I of the FDP is related to the input Stokes vector S by I = AS, where A is the instrument matrix. The rows of A can be viewed as projection operators that determine the output currents of the detectors. This leads to the recognition of four special totally polarized input states, each of which maximizes the output of one detector. The associated four orthogonal states produce minimum signals. Because each detector is absorptive and its output is nonnegative, eight inequalities must be satisfied by the elements of A. For optically isotropic detectors, one element is identically zero and another can be made zero by an appropriate coordinate rotation. Three additional inequalities that are likely to apply are also stated. The columns of A have the following interesting meaning. The first column represents the normalized response of the FDP for incident unpolarized light or its average response to incident light polarized in any pair of orthogonal states. The second, third, and fourth columns represent the differential normalized responses of the FDP for incident light polarized in the following pairs of orthogonal states: (1) linear polarizations at 0 and 90° azimuths, (2) linear polarizations at 45° and 135° azimuths, and (3) the right and left circular polarizations, respectively. These are the same pairs of orthogonal states that are used in the phenomenological definitions of the Stokes parameters.
Local and systemic antibody responses and immunological memory in humans after immunization with cholera B subunit by different routes. (1984)

A single oral or intramuscular immunization with purified cholera B subunit induced an intestinal secretory immunoglobulin A (IgA) antitoxin response in, respectively, 10 out of 11 and 9 out of 12 Bangladeshi volunteers. The IgA titre rise in intestinal lavage fluid was similar by either route of immunization, but the duration of the response was usually longer after the oral dose. A second immunization by either route, given 25 days after the first, and a third dose (oral only), given 15 months later, resulted in intestinal immune responses which did not differ in magnitude from that induced by the initial immunization but were observed significantly earlier, usually by day 3. Both the first oral and intramuscular immunizations induced significant antitoxin titre rises, mainly IgG, in the serum in most vaccinees but the magnitude of the response was considerably higher after the intramuscular dose. Significant IgA antitoxin titre rises in saliva and breast milk were seen after both oral and intramuscular immunization.
Solvents and Self-Organization of Polymers (1996)

Solvents and Self-Organization of Polymers brings together scientists who are experts in macromolecular synthesis, the physical chemistry and the physics of polymer self-organization. The book also co
Direct-Referencing Automatic Two-Points Reticle-To-Wafer Alignment Using A Projection Column Servo System (1986)

An improved version of the Philips/ASM-L phase grating alignment system is described. The new system can be used in combination with standard, single-sided telecentric projection lenses, by using a spatial filter external to the lens. In addition, the alignment-detection has been extended to a double system which enables direct control of magnification and die rotation. Long-term frame instability and changes in environmental conditions such as temperature and barometric pressure have no influence on the overlay accuracy. The new external spatial filtering technique gives the same proven benefits as the earlier spatial filtering which was built internal to the lenses. A comparison of this alignment scheme with other methods is given, showing that this new scheme is superior in terms of dependence on external influences.
HPV Vaccination — More Answers, More Questions (2007)

The availability of a “cancer vaccine” has elicited enormous enthusiasm from the medical community and the public, culminating in advocacy for mandatory vaccination against human papillomavirus (HPV) and a recommendation from the Centers for Disease Control and Prevention (CDC) that 30 million girls and women between the ages of 11 and 26 years in the United States be vaccinated.1 Previous reports2,3 showed a remarkable 100% efficacy of a quadrivalent vaccine targeting HPV types 6, 11, 16, and 18 on outcomes related to vaccine HPV types in women with no evidence of previous exposure to those types. Since HPV types . . .
Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase (1992)

The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a key mediator of the antiviral and antiproliferative effects of interferons (IFNs). Studies examining the physiological function of the kinase suggest that it participates in cell growth and differentiation by regulating protein synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and in vivo result in phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in malignant transformation, suggesting that dsRNA-PK may function as a suppressor of cell proliferation and tumorigenesis.
Role of Carnitine Palmitoyltransferase I in the Control of Ketogenesis in Primary Cultures of Rat Astrocytes (1998)

The role of carnitine palmitoyltransferase I (CPT-I) in the control of ketogenesis was studied in primary cultures of rat astrocytes. Ketone bodies were the major product of [14C]palmitate oxidation by cultured astrocytes, whereas CO2 made a minor contribution to the total oxidation products. Using tetradecylglycidate as a specific, cell-permeable inhibitor of CPT-I, a flux control coefficient of 0.77 +/- 0.07 was calculated for CPT-I over the flux of [14C]palmitate to ketone bodies. CPT-I from astrocytes was sensitive to malonyl-CoA (IC50 = 3.4 +/- 0.8 microM) and cross-reacted on western blots with an antibody raised against liver CPT-I. On the other hand, astrocytes expressed significant acetyl-CoA carboxylase (ACC) activity, and consequently they contained considerable amounts of malonyl-CoA. Western blot analysis of ACC isoforms showed that ACC in astrocytes--like in neurons, liver, and white adipose tissue--mostly comprised the 265-kDa isoform, whereas the 280-kDa isoform--which was highly expressed in skeletal muscle--showed much lower abundance. Forskolin was used as a tool to study the modulation of the ketogenic pathway in astrocytes. Thus, forskolin decreased in parallel ACC activity and intracellular malonyl-CoA levels, whereas it stimulated CPT-I activity and [14C]palmitate oxidation to both ketone bodies and CO2. Results show that in cultured astrocytes (a) CPT-I exerts a very high degree of control over ketogenesis from palmitate, (b) the ACC/malonyl-CoA/CPT-I system is similar to that of liver, and (c) the ACC/malonyl-CoA/CPT-I system is subject to regulation by cyclic AMP.
Efficacy of DA-7218, a New Oxazolidinone Prodrug, in the Treatment of Experimental Actinomycetoma Produced by Nocardia brasiliensis (2008)

Two recently synthesized oxazolidinones: (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyloxazolidin-2-one (DA-7157) and its corresponding pro-drug (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl) methyl disodium phosphate (DA-7218), have shown very good activity against several Gram positive bacteria, including Nocardia and Mycobacterium. In the present work we evaluated the therapeutic in vivo effects of DA-7218 on Nocardia brasiliensis. We first determined the plasma concentration of the prodrug in BALB/c mice using several doses and then tested its activity in an in vivo experimental actinomycetoma murine model. At the end of treatment, there was a statistically significant difference between the three drug receiving groups (25, 12.5 and 5 mg/kg) and the control group(saline solution) (p=0.001), proving that DA-7218 is effective for the treatment of experimental murine actinomycetoma. This compound could be a potential option for patients affected with mycetoma by Nocardia brasiliensis.
Monocyte-derived CXCL7 peptides in the marrow microenvironment (2006)

The marrow microenvironment consists of several different interacting cell types, including hematopoietic-derived monocyte/macrophages and nonhematopoietic-derived stromal cells. Gene-expression profiles of stromal cells and monocytes cultured together differ from those of each population alone. Here, we report that CXCL7 gene expression, previously described as limited to the megakaryocyte lineage, is expressed by monocytes cocultured with stromal cells. CXCL7 gene expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and secretion of protein was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot. At least 2 stromal-derived activities, one yet to be identified, were required for optimal expression of CXCL7 by monocytes. NAP-2, the shortest form of CXCL7 detected in the coculture media, was confirmed to decrease the size and number of CFU-Meg colonies. The propeptide LDGF, previously reported to be mitogenic for fibroblasts, was not secreted by stimulated monocytes. The recombinant form of LDGF produced in a prokaryotic expression system did not have biologic activity in our hands. The monocytic source of CXCL7 was also detected by immunohistochemistry in normal bone marrow biopsies, indicating an in vivo function. We conclude that stromal-stimulated monocytes can serve as an additional source for CXCL7 peptides in the microenvironment and may contribute to the local regulation of megakaryocytopoiesis.
Force sensing with temperature self-compensated based on a loop thin-wall section beam (2005)

A novel method about force sensing with temperature self-compensated based on a loop thin-wall section beam is proposed and demonstrated. Two identical fiber Bragg gratings are rigidly affixed on the outer surface of the beam with the positional angle difference between the two gratings of 90/spl deg/. The wavelength space between the two reflected peaks of the gratings is proportional to the force and insensitive to temperature when the direction of the force and one of the two gratings are located along a diameter; therefore, the force sensing with temperature self-compensated can be achieved.
Strain-dependent Differences in LTP and Hippocampus-dependent Memory in Inbred Mice (2000)

Many studies have used "reverse" genetics to produce "knock-out" and transgenic mice to explore the roles of various molecules in long-term potentiation (LTP) and spatial memory. The existence of a variety of inbred strains of mice provides an additional way of exploring the genetic bases of learning and memory. We examined behavioral memory and LTP expression in area CA1 of hippocampal slices prepared from four different inbred strains of mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms-+(Ter?)/J. We found that LTP induced by four 100-Hz trains of stimulation was robust and long-lasting in C57BL/6J and DBA/2J mice but decayed in CBA/J and 129/SvEms-+(Ter?)/J mice. LTP induced by one 100-Hz train was significantly smaller after 1 hr in the 129/SvEms-+(Ter?)/J mice than in the other three strains. Theta-burst LTP was shorter lasting in CBA/J, DBA/2J, and 129/SvEms-+(Ter?)/J mice than in C57BL/6J mice. We also observed specific memory deficits, among particular mouse strains, in spatial and nonspatial tests of hippocampus-dependent memory. CBA/J mice showed defective learning in the Morris water maze, and both DBA/2J and CBA/J strains displayed deficient long-term memory in contextual and cued fear conditioning tests. Our findings provide strong support for a genetic basis for some forms of synaptic plasticity that are linked to behavioral long-term memory and suggest that genetic background can influence the electrophysiological and behavioral phenotypes observed in genetically modified mice generated for elucidating the molecular bases of learning, memory, and LTP.
BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers (2009)

BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers.
In vivo evaluation of pyridoxalated-polymerized hemoglobin solution. (1984)

Previous evaluations of stroma free hemoglobin solutions (SFHS) revealed two problems, a low P50 (13 to 15 torr) which theoretically limits oxygen off-loading to tissues, and a short intravascular half time of only 3.5 hours. To correct these problems the hemoglobin molecule was pyridoxalated and polymerized to raise the P50 (20 to 22 torr) and to increase the plasma half-disappearance time to 25 hours. In the current investigation, rats exchange transfused to 75 per cent of their initial blood volume with SFHS exhibited centrilobular liver necrosis 12 and 24 hours after the transfusion as a result of the hypovolemic state induced by the hemoglobin diuresis. In contrast, animals administered pyridoxalated polymerized hemoglobin solution (Pr-Pl-Hb) displayed a normal hepatic morphologic finding. Renal morphologic findings in the two groups were similar except for the smaller quantities of hemoglobin observed in the proximal and distal tubules of Pr-Pl-Hb animals. This finding may be a result of the slower degradation of Pr-Pl-Hb in the intravascular compartment. Renal function in Pr-Pl-Hb remained normal after exchange transfusion, while the BUN in SFHS treated animals increased significantly due to the state of dehydration. Thus, Pr-P1-Hb represents an improvement over the previously tested SFHS in both P50 and intravascular half-time and, because of lowered osmotic and oncotic activities, it may be used in higher concentration to improve oxygen carrying capacity.
Novel VEGF-independent Strategies Targeting Tumor Vasculature: Clinical Aspects (2012)

In the last decades, the active research in the field of tumor angiogenesis has led to the development of a class of agents providing an effective inhibition of neo-vessel formation through the blockade of VEGF related pathways. More recently, the identification of other factors involved in tumor angiogenesis, such as platelet-derived growth factor, fibroblast growth factor and Angiopoietins has emphasized the need to develop agents targeting multiple pro-angiogenic pathways. Although contrasting data are currently available regarding the clinical efficacy of multikinase inhibitors, Sunitinib, Sorafenib and Pazopanib have displayed encouraging results, and have fuelled further evaluations. Moreover, definitive data are also eagerly awaited regarding the clinical role of angiopoietins inhibitors. On the other hand, the existence of morphological, functional and architectural differences between normal and tumor vasculature has provided solid basis for the development of a novel class of compounds, known as Vascular Disrupting Agents (VDAs) able to selectively disrupt existing tumor vessels. After initial concerns related to the potential development of severe cardiovascular toxicities, further clinical investigations have shown a safe toxicity profile for these agents. Moreover, despite the discouraging data on dolostatin-10 and ASA404, several VDAs, including CAP4, Ombrabulin and Pinabulin have already shown promising activity in phase I-II clinical trials warranting more advanced evaluations. In this review we aimed at summarizing the most relevant VEGF-independent strategies targeting tumor vasculature, focusing on the clinical development of novel antiangiogenic agents including multikinase and angiopoietins inhibitors as well as VDAs.
Voice Activity Detection Based on Auto-Correlation Function Using Wavelet Transform and Teager Energy Operator (2006)

In this paper, a new robust wavelet-based voice activity detection (VAD) algorithm derived from the discrete wavelet transform (DWT) and Teager energy operation (TEO) processing is presented. We decompose the speech signal into four subbands by using the DWT. By means of the multi-resolution analysis property of the DWT, the voiced, unvoiced, and transient components of speech can be distinctly discriminated. In order to develop a robust feature parameter called the speech activity envelope (SAE), the TEO is then applied to the DWT coefficients of each subband. The periodicity of speech signal is further exploited by using the subband signal auto-correlation function (SSACF) for. Experimental results show that the proposed SAE feature parameter can extract the speech activity under poor SNR conditions and that it is also insensitive to variable-level of noise.
Triple-push oscillator approach: theory and experiments (2001)

This paper presents the theory and experiments of the triple-push oscillator approach. This oscillator architecture is combined with three identical oscillator subcircuits. An analytical mode analysis is used to describe the behavior of all modes. As will be shown, odd-mode currents in each oscillator subcircuit have a 120/spl deg/ phase shift to one another and thus produce in-phase combining for the third harmonic. The time domain analysis was performed to simulate a triple-push oscillator, showing that the phenomenon of 120/spl deg/ phase shift exists among each oscillator subcircuit. To prove this concept, a 4.9-GHz hybrid bipolar junction transistor (BJT) circuit and a 28.4-GHz heterojunction bipolar transistor (BJT) MMIC chip were demonstrated. The measured results showed that the 4.9-GHz BJT triple-push oscillator delivered an output power of 1.0 dBm at 4.9 GHz with 12.0-dB fundamental rejection, and the 28.4-GHz HBT MMIC chip exhibited a measured center frequency at 28.4 GHz with an output power of -15.4 dBm, while the output powers of the fundamental and the second harmonic signals were suppressed to -21 and -34 dBm.
Thermal Expansion of Confined Water (2009)

Dilatometric measurement of the thermal expansion of water in porous silica shows that the expansion coefficient increases systematically as the pore size decreases below about 15 nm. This behavior is quantitatively reproduced by molecular dynamics (MD) simulations based on a new dissociative potential. According to MD, the structure of the water is modified within approximately 6 A of the pore wall, so that it resembles bulk water at a higher pressure. On the basis of this observation, it is possible to account for the measured expansion, as the thermal expansion coefficient of bulk water increases with temperature over the range considered in this study.