gebhart/patrepeval huggingface dataset:
Cross‐typic specificity and immunotherapeutic potential of a human HPV16 E7‐specific CTL line (2004)

Cervical cancer (CaCx) is strongly associated with human papillomavirus (HPV) infection, particularly HPV types 16 and 18. The constitutive expression of HPV E6 and E7 proteins in CaCx makes them attractive targets for CTL based immunotherapy. However cervical carcinomas may have features, e.g., antigen processing defects, that limit the effectiveness of HPV specific CTL. Furthermore most vaccine development has concentrated on HPV type 16, and it is not clear whether such vaccines could induce CTL able to cross-react on related oncogenic HPV types, e.g., HPV31 and 52. To investigate these potentially important parameters in vitro, we used a CTL (D4) specific for HPV16 E7(11-20). D4 was able to kill a variety of HPV16+ CaCx cell lines including those with suspected (CaSki) or known antigen processing defects (C33A), and with low HPV DNA copy number (SiHa). D4 was also able to cross react on a related peptide from HPV52 E7 but not HPV31 E7. Further analysis suggested that D4 cross reactivity against related peptides was influenced both by TCR contact residues and a certain threshold for peptide binding. The HPV cross-reactivity was confirmed at the whole protein level as D4 was also able to recognize the endogenously processed forms of HPV16 and 52 E7 but not 31 E7. These results suggest that HPV16 E7(11-20) would be a useful epitope for immunotherapy in both HPV 16 and 52 tumours. Despite this, it is difficult to generate these CTL in response to vaccination, emphasizing the need for definition of novel epitopes and more efficient vaccination strategies.
ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile (2003)

The presence or absence of somatic mutations in the expressed immunoglobulin heavy chain variable regions (IgVH) of chronic lymphocytic leukemia (CLL) cells provides prognostic information. Patients whose leukemic cells express unmutated IgVH regions (Ig-unmutated CLL) often have progressive disease, whereas patients whose leukemic cells express mutated IgVH regions (Ig-mutated CLL) more often have an indolent disease. Given the difficulty in performing IgVH sequencing in a routine diagnostic laboratory, this prognostic distinction is currently unavailable to most patients. Pilot gene expression profiling studies in patients with CLL identified genes that were differentially expressed between the Ig-unmutated and Ig-mutated CLL subtypes. Here, we have profiled an expanded cohort of 107 patients and show that ZAP-70 is the gene that best distinguishes the CLL subtypes. Ig-unmutated CLL expressed ZAP-70 5.54-fold more highly than Ig-mutated CLL (P < 10(-21)). ZAP-70 expression correctly predicted IgVH mutation status in 93% of patients. ZAP-70 expression and IgVH mutation status were comparable in their ability to predict time to treatment requirement following diagnosis. In 7 patients, ZAP-70 expression and IgVH mutation status were discordant: 4 Ig-mutated CLLs had high ZAP-70 expression and 3 Ig-unmutated CLLs had low ZAP-70 expression. Among these ZAP-70 "outliers," those with Ig-mutated CLL had clinical features that are uncharacteristic of this CLL subtype: 2 required early treatment and 2 used a mutated VH3-21 gene, an IgVH gene that has been associated with progressive disease. We developed reverse transcriptase-polymerase chain reaction and immunohistochemical assays for ZAP-70 expression that can be applied clinically and would yield important prognostic information for patients with CLL.
The effect of stimulus pulse duration on selectivity of neural stimulation (1996)

Choice of stimulus parameters is an important consideration in the design of neural prosthetic systems. The objective of this study was to determine the effect of rectangular stimulus pulsewidth (PW) on the selectivity of peripheral nerve stimulation. Computer simulations using a cable model of a mammalian myelinated nerve fiber indicated that shorter PW's increased the difference between the threshold currents of fibers lying at different distances from an electrode. Experimental measurements of joint torque generated by peripheral nerve stimulation demonstrated that shorter PW's generated larger torques before spillover and created a larger dynamic range of currents between threshold and spillover. Thus, shorter PW's allowed more spatially selective stimulation of nerve fibers. Analysis of the response of a passive cable model to different duration stimuli indicated that PW dependent contributions of distributed sources to membrane polarization accounted for the observed differences in selectivity.
Human catecholamine sulfotransferase (SULT1A3) pharmacogenetics: functional genetic polymorphism (2003)

Sulfotransferase (SULT) 1A3 catalyzes the sulfate conjugation of catecholamines and structurally related drugs. As a step toward studies of the possible contribution of inherited variation in SULT1A3 to the pathophysiology of human disease and/or variation in response to drugs related to catecholamines, we have resequenced all seven coding exons, three upstream non-coding exons, exon-intron splice junctions and the 5'-flanking region of SULT1A3 using DNA samples from 60 African-American (AA) and 60 Caucasian-American (CA) subjects. Eight single nucleotide polymorphisms (SNPs) were observed in AA and five in CA subjects, including one non-synonymous cSNP (Lys234Asn) that was observed only in AA subjects with an allele frequency of 4.2%. This change in amino acid sequence resulted in only 28 +/- 4.5% (mean +/- SEM) of the enzyme activity of the wild-type (WT) sequence after transient expression in COS-1 cells, with a parallel decrease (54 +/- 2.2% of WT) in level of SULT1A3 immunoreactive protein. Substrate kinetic studies failed to show significant differences in apparent Km values of the two allozymes for either dopamine (10.5 versus 10.2 micro m for WT and variant, respectively) or the cosubstrate 3'-phosphoadenosine 5'-phosphosulfate (0.114 versus 0.122 micro m, respectively). The decrease in level of immunoreactive protein in response to this single change in amino acid sequence was due, at least in part, to accelerated SULT1A3 degradation through a proteasome-mediated process. These observations raise the possibility of ethnic-specific inherited alterations in catecholamine sulfation in humans.
Foamy Virus Envelope Glycoprotein-Mediated Entry Involves a pH-Dependent Fusion Process (2003)

In general, enveloped viruses use two different entry strategies and are classified accordingly into pH-dependent and pH-independent viruses. Different members of the retrovirus family use one or the other strategy. Little is known about the uptake of foamy viruses (FV), a special group of retroviruses, into the target cells. In this study, we examined the pH dependence of FV entry by analyzing FV envelope glycoprotein (Env)-mediated infection of target cells with murine leukemia virus or FV vector pseudotypes in the presence of various lysosomotropic agents. Similar to vesicular stomatitis virus glycoprotein G (VSV-G)-mediated uptake, FV Env-mediated entry was inhibited by various lysosomotropic agents, suggesting a pH-dependent endocytic pathway. However, in contrast to its effect on VSV-G pseudotypes, chloroquine failed to reduce the infectivity of FV Env pseudotypes, implying that the pathway is different from that of VSV-G. Glycoproteins of various other FV species showed inhibition profiles similar to that of the prototype FV (PFV) Env. Analysis of the pH dependence of the FV Env-mediated fusion process in a cell-to-cell fusion assay revealed an induction of syncytium formation by a short exposure to acidic pH, peaking around pH 5.5. Interestingly, of all FV Env species analyzed, only the PFV Env had a significant fusion activity at neutral pH. Taken together, these data suggest a pH-dependent endocytic pathway for infection of target cells by FV.
Increasing the capacity of GSM cellular radio using adaptive antennas (1996)

The capacity of mobile cellular radio networks can be considerably increased if a higher level of cochannel interference can be tolerated. An adaptive antenna combines the outputs of an array of elements to maximise the wanted signal and suppress interfering signals. The author proposes an adaptive antenna algorithm suitable for GSM and the urban multipath environment. The algorithm is based on iterative reference signal reconstruction from the GSM training sequence. The average error rate is obtained by simulation for four equal power interfering signals and an urban GSM multipath model. An adaptive antenna can only practically be deployed at the base station. Realising its gains in a real network on both the up and downlinks requires, for the downlink, a number of techniques. This is discussed and a concept of how the full capacity gains can be achieved in an evolutionary manner on both links is proposed. The concept is equally applicable to the DCS 1800 and DCS 1900 systems based on GSM.
Dipeptidyl peptidase I is enriched in granules of in vitro- and in vivo-activated cytotoxic T lymphocytes (1993)

Recent studies have suggested that dipeptidyl peptidase I (DPPI) is the major post-translational processing enzyme responsible for generating activated myeloid and lymphoid granule serine proteases. The current studies assessed the relative levels of DPPI and granzyme A (BLT esterase) in B6 anti-H-2d-specific CTL generated in mixed lymphocyte cultures (in vitro-activated CTL), by infusion of B6 spleen cells into irradiated H-2d mice (graft-vs-host, GVH CTL) or by 1 degree and 2 degrees peritoneal immunization of B6 mice with P815 (H-2d) cells (PE CTL). In contrast to low levels of DPPI activity in unstimulated CD4+ spleen T cells, both unstimulated CD8+ spleen T cells and in vitro-activated CTL populations were several-fold enriched in DPPI activity, while PE CTL and GVH CTL expressed even higher levels of DPPI. Depletion of DPPI-enriched cells by treatment with Leu-Leu-OMe resulted in loss of cytolytic effector function from each CTL population. However, PE CTL and GVH CTL were more sensitive to the toxicity of Leu-Leu-OMe than were in vitro-activated CTL. While standard BLT esterase assays detected much higher levels of this serine protease activity in GVH CTL or in vitro-activated CTL than in PE CTL, levels of BLT esterase activity significantly above the basal levels present in unstimulated CD8+ or CD4+ T lymphocytes were found in association with immunoreactive granzyme A in lysates of PE CTL. In both PE CTL and in vitro-activated CTL, DPPI and BLT esterase activity co-localized in the granule fraction of cell lysates, and similar percentages of total cellular BLT esterase and DPPI were exocytosed upon cross-linking of surface CD3. Thus, both in vivo- and in vitro-activated CTL were found to possess functional granules containing readily detectable albeit somewhat different levels of DPPI and granzyme A activity.
Joint frequency offset estimation and interference cancellation for MIMO-OFDM systems [mobile radio] (2005)

Synchronization and equalization in wireless multi-user MIMO-OFDM (multiple-input multiple-output orthogonal frequency division multiplexing) systems is important for next generation wireless communication. This paper proposes a new algorithm for joint frequency offset estimation and equalizer training for the uplink of a multi-user MIMO-OFDM system where each user employs spatial multiplexing. A new two-stage receiver structure is adopted, which consists of an initial space-time equalization for suppressing the co-channel interference (CCI), shortening the channel, and mitigating asynchronicity, followed by parallel equalization and detection in the frequency domain. The effects of frequency offset for each transmit data stream can be adjusted after the space-time equalization. Simulations show good performance in terms of bit error rate and mean square error for the frequency offset estimation.
Ru x Cr 1−x / Ta underlayer for Co-alloy perpendicular magnetic recording (2002)

The effects of the RuxCr1−x/Ta underlayer on the microstructural and magnetic properties of CoCrPtB perpendicular films were investigated. The hcp RuxCr1−x (0002) texture was observed to grow perpendicular to the film plane with narrow rocking curves of 2°–3°. High-resolution transmission electron microscopy indicated epitaxial growth of the CoCrPtB on top of the RuxCr1−x/Ta underlayer. In-plane x-ray diffraction scans indicate that as the Cr atomic composition increases in the RuxCr1−x underlayer, the a-lattice parameter was found to contract more closely matching the CoCrPtB a-lattice parameter [measured with (112̄0)]. In addition, the rocking curves for the CoCrPtB (0002)-texture induced by the (0002) textured RuxCr1−x buffer showed narrowing peaks (4.5°–3.5°) as the Cr concentration increased from 0% to 40%.
Design and study of peptide‐ligand affinity chromatography adsorbents: Application to the case of trypsin purification from bovine pancreas (1997)

The purification of trypsin from bovine pancreas was employed in a case study concerning the design and optimization of peptide-ligand adsorbents for affinity chromatography. Four purpose-designed tripeptide-ligands were chemically synthesized (>95% pure), exhibiting an Arg residue as their C-terminal (site P1) for trypsin bio-recognition, a Pro or Ala in site P2, and a Thr or Val in site P3. Each tripeptide-ligand was immobilized via its N-terminal amino group on Ultrogel A6R agarose gel, which was previously activated with low concentrations of cyanuric chloride (10.5 to 42.5 μmol/g gel). Well over 90% of the peptide used was immobilized. Three different concentrations were investigated for every immobilized tripeptide-ligand, 3.5, 7.0, and 14 μmol/g gel. The KD values of immobilized tripeptide-trypsin complexes were determined as well as the purifying performance and the trypsin-binding capacity of the affinity adsorbents. The KD values determined were in good agreement with the trypsin purification performance of the respective affinity adsorbents. The tripeptide sequence H-TPR-OH displayed the highest affinity for trypsin (KD 8.7 μM), whereas the sequence H-TAR-OH displayed the lowest (KD 38 μM). Dipeptide-ligands have failed to bind trypsin. When the ligand H-TPR-OH was immobilized via its N-terminal on agarose, at a concentration of 14 μmol/g gel, it produced the most effective affinity chromatography adsorbent. This adsorbent exhibited high trypsin-binding capacity (approximately 310,000 BAEE units/mL of adsorbent); furthermore, it purified trypsin from pancreatic crude extract to a specific activity of 15,200 BAEE units/mg (tenfold purification), and 82% yield. © 1997 John Wiley & Sons, Inc.
Measurement and Analysis of Extracellular Acid Production to Determine Glycolytic Rate (2015)

Extracellular measurement of oxygen consumption and acid production is a simple and powerful way to monitor rates of respiration and glycolysis(1). Both mitochondrial (respiration) and non-mitochondrial (other redox) reactions consume oxygen, but these reactions can be easily distinguished by chemical inhibition of mitochondrial respiration. However, while mitochondrial oxygen consumption is an unambiguous and direct measurement of respiration rate(2), the same is not true for extracellular acid production and its relationship to glycolytic rate (3-6). Extracellular acid produced by cells is derived from both lactate, produced by anaerobic glycolysis, and CO2, produced in the citric acid cycle during respiration. For glycolysis, the conversion of glucose to lactate(-) + H(+) and the export of products into the assay medium is the source of glycolytic acidification. For respiration, the export of CO2, hydration to H2CO3 and dissociation to HCO3(-) + H(+) is the source of respiratory acidification. The proportions of glycolytic and respiratory acidification depend on the experimental conditions, including cell type and substrate(s) provided, and can range from nearly 100% glycolytic acidification to nearly 100% respiratory acidification (6). Here, we demonstrate the data collection and calculation methods needed to determine respiratory and glycolytic contributions to total extracellular acidification by whole cells in culture using C2C12 myoblast cells as a model.
Tuning nonlinearity, dynamic range, and frequency of nanomechanical resonators (2006)

We explore an electrostatic mechanism for tuning the nonlinearity of nanomechanical resonators and increasing their dynamic range for sensor applications. We also demonstrate tuning the resonant frequency of resonators both upward and downward. A theoretical model is developed that qualitatively explains the experimental results and serves as a simple guide for design of tunable nanomechanical devices.
Low-Power HeNe Laser Treatment of Venous Leg Ulcers (1991)

Clinical observations have suggested that low-energy lasers, mainly helium-neon (HeNe) lasers, might stimulate wound healing. A controlled study of the effects of low-power HeNe laser was performed in conjunction with a standard treatment for healing chronic venous leg ulcers on 46 patients divided randomly into two groups. All patients received standard treatment (paste-impregnated bandage and a self-adhesive elastic bandage) plus either HeNe laser (wave-length, 632.8 nm; beam power, 6 mW; continuous emission, energy density, 4 J/cm2) or placebo HeNe laser twice weekly for 12 weeks. The areas of healing were examined and compared percentage-wise after 2, 4, 6, 8, and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the HeNe group compared with the placebo group.
Importance of primer selection for the detection of hepatitis C virus RNA with the polymerase chain reaction assay. (1992)

We compared four primer sets from conserved regions of the hepatitis C virus (HCV) genome for their ability to detect HCV RNA in a "nested" cDNA polymerase chain reaction assay on sera from 114 anti-HCV antibody-positive individuals from around the world. The different primer sets had equivalent sensitivity, detecting less than 1 chimpanzee ID50 (dose that infects 50%) when tested against reference strain H of HCV. We tested equal amounts of RNA extracted from the serum of each individual with the four primer sets. The set derived from two highly conserved domains within the 5' noncoding (NC) region of the HCV genome, which also share significant similarity with Pestivirus 5' NC sequences, was the most effective at detecting HCV RNA. All samples positive for HCV RNA with any other primer set were also positive with the primer set from the 5' NC region, and the latter was at least 3 times more likely to detect HCV infection than a primer set from within the nonstructural protein 3-like gene region (P less than 0.001). We had no false positive results in greater than 500 negative controls interspersed among the test samples. The 5' NC region primer set detected HCV-specific RNA, verified by high-stringency Southern blot hybridization and DNA sequencing, in 100% of 15 acute and 33 chronic non-A, non-B hepatitis patients from the United States, Europe, and Asia and 10 hepatocellular carcinoma patients from Africa and Asia that tested negative for the hepatitis B virus-encoded surface antigen. In conclusion, use of an appropriate primer set is crucial for detecting HCV RNA in the serum of infected individuals.
[The cellular reaction to heat shock: the physiological aspect]. (1994)

This review regards the basic manifestations of cell response to heat-shock (HS): formation of resistance increase or acquired tolerance, and contribution of stress proteins (SP) to this reaction. This to great extent nonspecific increase in heat-shock cell resistance is based on two processes: a) an increase in the initial heat resistance of cell functions which results from enhancing of resistance of native efficient state of cell protein macromolecules to denaturating agents; b) stimulation of cell repair capacity that is expressed as an increase in the rate of cell function restoration in the case of its equal extent of damage in trained and untrained cells, and as expansion of the repairable zone (the interval of temperatures within the limits of which the function is inhibited completely, but reversibly after certain duration of heating). Stimulation of cell repair capacity is due to a more rapid renativation or substitution of proteins modified by stress. Both the processes (a and b) provide the ability of trained cells to function under higher temperature, compared to untrained ones. This review shows that heating, as well as any other denaturating agent as an inadequate stimulant, can give rise to synthesis of new proteins and other metabolites or to enhance running synthesis of substances. The fact of protein synthesis stimulation does not provide grounds to attribute an adaptive function to these proteins. SP are unable to increase the initial heat-resistance of cell functions, but participation of some SP (chaperons) in stimulation of cell repair capacity is highly probable. In the same time the repair of heat injured cells can take place without protein synthesis. In some cases the acquired tolerance remains for several weeks after HS. A comparison of cell responses to HS and to medium temperature increase within the tolerant limits (temperature adjustment) shows that their adaptive mechanisms are evidently different, although the increase in the initial heat resistance of some functions and stimulation of cell repair capacity take place under the temperature adjustment.