gebhart/patrepeval huggingface dataset:
Characterization of CD20-Transduced T Lymphocytes as an Alternative Suicide Gene Therapy Approach for the Treatment of Graft-Versus-Host Disease (2004)

We have previously proposed the CD20 molecule as a novel suicide gene for T lymphocytes in the context of allogeneic bone marrow transplantation, because CD20 can be used both as a selection marker and as a killer gene after exposure to the anti-CD20 therapeutic antibody rituximab. We now report on preclinical studies using this novel system, in which the best transduction protocol, reproducibility, yield, feasibility, and functionality of the transduced T lymphocytes have been investigated with a large donor series. Wild-type human CD20 cDNA was transduced into human T lymphocytes, using a Moloney-derived retroviral vector. Alternative protocols were tested by employing either one or four spinoculations (in which cells are centrifuged in the presence of retroviral vector supernatant) and stimulating T cells with phytohemagglutinin (PHA) or anti-CD3/CD28. One spinoculation alone was sufficient to obtain approximately 30% CD20-positive cells within four experimental days. Four spinoculations significantly increased transduction to 60%. A small difference in transduction efficiency was observed between the two stimulation methods, with PHA being superior to anti-CD3/CD28. Transduced cells could be purified on immunoaffinity columns, with purity reaching 98% and yield being on average 50%. Finally, 86-97% of immunoselected T lymphocytes could be killed in vitro with rituximab and complement. More importantly, the CD20 transgene did not alter the functionality of T lymphocytes with respect to allogeneic recognition and cytotoxic response, anti-Epstein-Barr virus cytotoxic response, antigenic response to tetanus toxoid antigen, interleukin 2 (IL-2), IL-4, and interferon gamma production; chemotaxis in the presence of stromal cell-derived factor 1, phenotype for several activation markers including HLA-DR, CD25, CD69, and CD95, and T cell repertoire.
46.2: Invited Paper : High‐Performance LTPS Technologies for Advanced Mobile Display Applications (2007)

Abstract LTPS (Low Temperature Polycrystalline Silicon)‐TFT is ideally suited for mobile active‐matrix displays. An overview will be provided of the latest innovations underlining the unique capability of LTPS, highlighting examples from TPO's own R&amp;D, in the areas of integrated ambient light sensing, ultralow‐standby‐power memory‐in‐pixel, advanced driving schemes and pixel designs for wide viewing, high level of System‐on‐Panel integration, and high‐performance AMOLED, based on advanced and mature LTPS processes &amp; devices.
Multiparametric magnetic resonance imaging to characterize cabotegravir long‐acting formulation depot kinetics in healthy adult volunteers (2021)

MRI clearly delineated cabotegravir LA injection-site location and depot kinetics in healthy adults. Although injection-site variability was observed, drug depot surface area correlated with both plasma C<sub>max</sub> and partial AUC independently of anatomical distribution.
Radio frequency integrated circuit technology for low-power wireless communications (1998)

The radio frequency portion of a handheld wireless communications device represents a significant fraction of the battery drain of the overall unit. As a result, an intensive effort is underway on a worldwide basis to minimize the overall radio frequency power requirements. This effort has proceeded on many fronts, with the best work drawing on the multidisciplinary efforts of researchers in the communications systems, circuit design, and semiconductor technology areas. This article summarizes the significant technological challenges to the realization of low-power radio frequency circuits, and follows with a discussion of the research programs that have been put in place to address these challenges. RF transceiver architectures are discussed in particular together with performance aspects.
Norwalk Virus Shedding after Experimental Human Infection (2008)

Noroviruses are the most common cause of viral gastroenteritis in the United States. To determine the magnitude and duration of virus shedding in feces, we evaluated persons who had been experimentally infected with Norwalk virus. Of 16 persons, clinical gastroenteritis (watery diarrhea and/or vomiting) developed in 11; symptomatic illness lasted 1-2 days. Virus shedding was first detected by reverse transcription-PCR (RT-PCR) 18 hours after participant inoculation and lasted a median of 28 days after inoculation (range 13-56 days). The median peak amount of virus shedding was 95 x 10(9) (range 0.5-1,640 x 10(9)) genomic copies/g feces as measured by quantitative RT-PCR. Virus shedding was first detected by antigen ELISA approximately 33 hours (median 42 hours) after inoculation and lasted 10 days (median 7 days) after inoculation. Understanding of the relevance of prolonged fecal norovirus excretion must await the development of sensitive methods to measure virus infectivity.
Expression of the G-protein--coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells (1994)

The G-protein-coupled receptor BLR1 related to receptors for chemokines and neuropeptides has been identified as the first lymphocyte-specific member of the gene family characterized by seven transmembrane-spanning regions. Using a high-affinity anti-BLR1 monoclonal antibody (MoAb) and three-color flow cytometry it is shown that BLR1 expression on peripheral blood cells is limited to B cells and to a subset of CD4+ (14%) and CD8+ (2%) lymphocytes. T cells expressing BLR1 were positive for CD45R0, were negative for interleukin-2 receptors, show high levels of CD44, and show low levels of L-selectin. The majority of CD4+ cells originating from secondary lymphatic tissue, but none of cord blood- derived T cells, express BLR1. These observations suggest that BLR1 is a marker for memory T cells. Furthermore, BLR1 expression was detected on all CD19+ peripheral or tonsillar B lymphocytes, but only on a fraction of cord blood cells and bone marrow cells expressing CD19, sIgM, or sIgD. Interestingly, activation of both mature B and T cells by CD40 MoAb and CD3 MoAb, respectively, led to complete downregulation of BLR1. These data suggest that the G-protein-coupled receptor BLR1 is involved in functional control of mature recirculating B cells and T- helper memory cells participating in cell migration and cell activation.
A 320 MFLOPS CMOS floating-point processing unit for superscalar processors (1993)

A CMOS pipelined floating-point processing unit (FPU) for superscalar processors is described. It is fabricated using a 0.5 mu m CMOS triple-metal-layer technology on a 61 mm/sup 2/ die. The FPU has two execution modes to meet precise scientific computations and real-time applications. It can start two FPU operations in each cycle, and this achieves a peak performance of 160 MFLOPS double or single precision with an 80 MHz clock. Furthermore, the original computation mode, twin single-precision computation, double the peak performance and delivers 320 MFLOPS single precision. Its full bypass reduces the latency of operations, including load and store, and achieves an effective throughput even in nonvectorizable computations. An out-of-order completion is provided by using a new exception prediction method and a pipeline stall technique.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification of recurrent regions of copy-number variants across multiple individuals (2010)

The proposed methods for identifying common CNV regions in multiple individuals perform well compared to existing methods. The identified common regions can be used for downstream analyses such as group comparisons in association studies.
Phosphate availability affects the thylakoid lipid composition and the expression of SQD1 , a gene required for sulfolipid biosynthesis in Arabidopsis thaliana (1998)

Photosynthetic membranes of higher plants contain specific nonphosphorous lipids like the sulfolipid sulfoquinovosyl diacylglycerol in addition to the ubiquitous phospholipid phosphatidylglycerol. In bacteria, an environmental factor that drastically affects thylakoid lipid composition appears to be the availability of phosphate. Accordingly, we discovered an increase in the relative amount of sulfolipid and a concomitant decrease in phosphatidylglycerol in Arabidopsis thaliana grown on medium with reduced amounts of phosphate, as well as in the pho1 mutant of A. thaliana deficient in phosphate transport. To investigate the molecular basis of the observed change in lipid composition, we isolated a cDNA of A. thaliana, designated SQD1, that encodes a protein involved in sulfolipid biosynthesis as suggested by three lines of evidence. First, the cDNA shows high sequence similarity to bacterial sqdB genes known to be essential for sulfolipid biosynthesis; second, the SQD1 gene product is imported into chloroplasts where sulfolipid biosynthesis takes place; and third, transgenic plants expressing SQD1 in antisense orientation show a reduction in sulfolipid content. In the pho1 mutant as well as in wild-type plants grown under reduced phosphate availability, increased amounts of SQD1 mRNA and SQD1 protein are detected, suggesting that the increase in sulfolipid content under phosphate limitation is the result of an increased expression of at least one gene required for sulfolipid biosynthesis in A. thaliana. It is suggested that a certain amount of anionic thylakoid lipid is maintained by substituting sulfolipid for phosphatidylglycerol under reduced phosphate availability.
Strategies for the Efficient Recovery of Agaricus Bisporus Homokaryons (1992)

Click to increase image sizeClick to decrease image sizeKey Words: Agaricus bisporusallozymesbreedinggeneticshomokaryon identificationintramixis
Tridegin, a new peptidic inhibitor of factor XIIIa, from the blood-sucking leech Haementeria ghilianii (1997)

1. Crude salivary gland extract of the giant Amazon leech, Haementeria ghilianii, contains an inhibitor of plasma factor XIIIa. 2. The inhibitory agent was purified to homogeneity by anion-exchange, cation-exchange, gel-filtration and reverse-phase chromatography to yield a single band on SDS/PAGE with an apparent molecular mass of 7.3 kDa. It has been named tridegin. 3. Micro-sequencing of proteolytic fragments showed tridegin to be a peptide of 66 amino acids. The sequence is unique with little similarity to other leech-derived proteins. 4. Inhibition of plasma factor XIIIa activity was confirmed by four independent methods: tridegin increased the solubility of fibrin clots in urea, inhibited ammonia produced from the incorporation of ethylamine into casein, inhibited the incorporation of 5'-(biotinamido)pentylamine into casein and prevented gamma-dimer formation in clotting fibrinogen. 5. The IC50 of tridegin (approx. 9.2 nM) is very close to the concentration of factor XIIIa used in the assay and in fact depends on its concentration. This is the most potent inhibitor of factor XIIIa yet described. 6. Tridegin also inhibits platelet factor XIIIa (factor XIIIAa) with a similar potency to that of the plasma enzyme. 7. Tridegin also inhibits tissue transglutaminase but with lower potency and independently of the enzyme concentration. 8. Tridegin appears to be specific for transglutaminases, since it has no effect on the coagulation times of human plasma, on thrombin or factor Xa. Moreover it has no effect on other thiol-containing enzymes and has no ability to digest fibrinogen or cleave the isopeptide substrate, L-gamma-glutamyl-4-nitroanilide.
Updated research nosology for HIV-associated neurocognitive disorders (2007)

In 1991, the AIDS Task Force of the American Academy of Neurology published nomenclature and research case definitions to guide the diagnosis of neurologic manifestations of HIV-1 infection. Now, 16 years later, the National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke have charged a working group to critically review the adequacy and utility of these definitional criteria and to identify aspects that require updating. This report represents a majority view, and unanimity was not reached on all points. It reviews our collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neurocognitive impairment to categorize individuals with subclinical impairment. An algorithm is proposed to assist in standardized diagnostic classification of HAND.
Ichthyosis in Sjögren–Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion (2010)

Sjögren-Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren-Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum-stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren-Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.
Biochemical and Immunological Characterization of Recombinant Allergen Lol p 1 (1997)

Pollen from perennial rye grass (Lolium perenne), a major cause of type-I allergy worldwide, contains a complex mixture of allergenic proteins among which Lol p 1 is one of the most important. We describe the expression, purification and characterization of a recombinant Lol p 1 overproduced in Escherichia coli. The recombinant allergen, expressed in high yields and purified in milligram amounts, bound to specific IgE antibodies from human sera, induced histamine release from sensitized human basophils, and elicited rabbit antisera that recognize specifically recombinant Lol p 1 and natural Lol p 1 of pollen extract. Recombinant Lol p 1 was used to develop ImmunoCAP assays for analysis of 150 sera that were Radioallergosorbent test positive to L. perenne pollen. In 130 of them (87%) the assay detected a significant level of IgE antibodies to Lol p 1, reaching on average 37% of the level obtained with a test for IgE to the whole grass pollen extract. To map epitopes on Lol p 1, we produced three deletion mutants [des-(116-240)-Lol p 1, des-(1-88)-Lol p 1 and des-(133-189)-Lol p 1], which were efficiently expressed in bacteria. These all showed a strong reactivity with the specific rabbit IgG antibodies, but lacked most or all the allergenic properties of recombinant Lol p 1. A study of the antigenic structure of Lol p 1 was performed using the three deletion mutants and a set of 17-18-residue overlapping synthetic peptides covering the whole allergen sequence. The results indicate that human IgE and rabbit IgG antibodies bind to distinct regions of Lol p 1, and that at least some important IgE epitopes are mainly conformational. The findings suggest that recombinant allergens constitute useful reagents for further development of serological diagnosis of allergy, and that it should be possible to produce immunogenic fragments of allergenic proteins without allergenic properties.
Objective non‐invasive assessment of patch tests with the laser Doppler perfusion scanning technique (1999)

The laser Doppler perfusion scanning technique is an objective, non-invasive assessment method that may be used to assess patch tests. The purpose of this paper is to focus on its clinical use in individuals with light skin, tested with non-pigmented test materials. A laser Doppler perfusion imager PIM 1.0 (LDPI) is used to study different set-ups of the instrument that may affect readings. These set-ups are studied through simulated light-absorbing patch tests. The results have served as a base for clinical experiments comparing visual and LDPI assessments of normal skin, irritant patch-test reactions, and more than 25,000 allergic patch-test assessments of reactions of different intensities and control patches. This paper reviews the clinical experiments to suggest a set-up of the LDPI for patch-test readings. Such a set-up makes it possible to compare intra- and inter-individual test results and to obtain meaningful assessment values among users. Some subject-related factors that may affect reading results are studied, and the effect of non-subject related factors on readings are considered. Use of the technique is illustrated by images of perfusion and a perfusion profile of a patch-test reaction followed over time.
Modulation of antibody galactosylation through feeding of uridine, manganese chloride, and galactose (2011)

Through process transfer and optimization for increased antibody production to 3 g/L for a GS-CHO cell line, an undesirable drop in antibody Fc galactosylation was observed. Uridine (U), manganese chloride (M), and galactose (G), constituents involved in the intracellular galactosylation process, were evaluated in 2-L bioreactors for their potential to specifically increase antibody galactosylation. These components were placed in the feed medium at proportionally increasing concentrations from 0 to 20 × UMG, where a 1× concentration of U was 1 mM, a 1× concentration of M was 0.002 mM, and a 1× concentration of G was 5 mM. Antibody galactosylation increased rapidly from 3% at 0× UMG up to 21% at 8× UMG and then more slowly to 23% at 20× UMG. The increase was primarily due to a shift from G0F to G1F, with minimal impact on other glycoforms or product quality attributes. Cell culture performance was largely not impacted by addition of up to 20× UMG except for suppression of glucose consumption and lactate production at 16 and 20× UMG and a slight drop in antibody concentration at 20× UMG. Higher accumulation of free galactose in the medium was observed at 8× UMG and above, coincident with achieving the plateau of maximal galactosylation. A concentration of 4× UMG resulted in achieving the target of 18% galactosylation at 2-L scale, a result that was reproduced in a 1,000-L run. Follow-up studies to evaluate the addition of each component individually up to 12× concentration revealed that the effect was synergistic; the combination of all three components gave a higher level of galactosylation than addition of the each effect independently. The approach was found generally useful since a second cell line responded similarly, with an increase in galactosylation from 5% to 29% from 0 to 8× UMG and no further increase or impact on culture performance up to 12× UMG. These results demonstrate a useful approach to provide exact and specific control of antibody galactosylation through manipulation of the concentrations of uridine, manganese chloride, and galactose in the cell culture medium.
Internal Friction in Solids. I. Theory of Internal Friction in Reeds (1937)

In a vibrating reed opposite sides have dilations of opposite signs. Thus when one side is heated the other is cooled. At low frequencies the vibrations are isothermal. At high frequencies they are adiabatic. At intermediate frequencies they are of a hybrid type accompanied by internal friction. In this paper this internal friction is calculated solely from thermodynamical considerations. It is predicted that the internal friction associated with this hybrid type of vibration is of a larger order of magnitude than that due to all other causes.
Therapeutic Strategies Based on Glucagon-Like Peptide 1 (2004)

Glucagon-like peptide (GLP)-1 is an incretin hormone with potent glucose-dependent insulinotropic and glucagonostatic actions, trophic effects on the pancreatic beta-cells, and inhibitory effects on gastrointestinal secretion and motility, which combine to lower plasma glucose and reduce glycemic excursions. Furthermore, via its ability to enhance satiety, GLP-1 reduces food intake, thereby limiting weight gain, and may even cause weight loss. Taken together, these actions give GLP-1 a unique profile, considered highly desirable for an antidiabetic agent, particularly since the glucose dependency of its antihyperglycemic effects should minimize any risk of severe hypoglycemia. However, its pharmacokinetic/pharmacodynamic profile is such that native GLP-1 is not therapeutically useful. Thus, while GLP-1 is most effective when administered continuously, single subcutaneous injections have short-lasting effects. GLP-1 is highly susceptible to enzymatic degradation in vivo, and cleavage by dipeptidyl peptidase IV (DPP-IV) is probably the most relevant, since this occurs rapidly and generates a noninsulinotropic metabolite. Strategies for harnessing GLP-1's therapeutic potential, based on an understanding of factors influencing its metabolic stability and pharmacokinetic/pharmacodynamic profile, have therefore been the focus of intense research in both academia and the pharmaceutical industry. Such strategies include DPP-IV-resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation of the peptide.
A randomised controlled trial comparing Mediwrap® heat retention and forced air warming for maintaining normothermia in thoracic surgery☆ (2009)

Hypothermia is one of the common complications in the perioperative period. Currently, normothermia is maintained with forced air warming (FAW) or passive heat retention methods. We compared the efficacy of the Mediwrap blanket with FAW in maintaining normothermia during intra-operative period in thoracic surgery in a prospective randomised controlled trial on 30 patients. Core temperature was measured at 30-min intervals in the perioperative period and the time taken to attain baseline in the postoperative periods in the two groups was compared. There was no difference in core temperatures between the groups during pre- and intra-operative period, with mean+/-S.D. final core temperatures of 36.2+/-0.6 degrees C with Mediwrap and 36+/-0.9 degrees C with the FAW blanket. However, the postoperative core temperatures were significantly higher in the Mediwrap group. The time required to reach baseline temperature was lower in the Mediwrap group with a mean+/-S.D. of 66+/-66 min as compared to 161+/-108 min in the FAW group. The Mediwrap blanket is as effective as the FAW blanket in maintaining core body temperature during thoracotomy when applied thirty minutes before the surgery.