gebhart/patrepeval huggingface dataset:
Predominant Autoantibody Production by Early Human B Cell Precursors (2003)

During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.
Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors (2008)

There is currently no known genetic disease linked to prolactin (Prl) or its receptor (PrlR) in humans. Given the essential role of this hormonal system in breast physiology, we reasoned that genetic anomalies of Prl/PrlR genes may be related to the occurrence of breast diseases with high proliferative potential. Multiple fibroadenomas (MFA) are benign breast tumors which appear most frequently in young women, including at puberty, when Prl has well-recognized proliferative actions on the breast. In a prospective study involving 74 MFA patients and 170 control subjects, we identified four patients harboring a heterozygous single nucleotide polymorphism in exon 6 of the PrlR gene, encoding Ile(146)-->Leu substitution in its extracellular domain. This sole substitution was sufficient to confer constitutive activity to the receptor variant (PrlR(I146L)), as assessed in three reconstituted cell models (Ba/F3, HEK293 and MCF-7 cells) by Prl-independent (i) PrlR tyrosine phosphorylation, (ii) activation of signal transducer and activator of transcription 5 (STAT5) signaling, (iii) transcriptional activity toward a Prl-responsive reporter gene, and (iv) cell proliferation and protection from cell death. Constitutive activity of PrlR(I146L) in the breast sample from a patient was supported by increased STAT5 signaling. This is a unique description of a functional mutation of the PrlR associated with a human disease. Hallmarks of constitutive activity were all reversed by a specific PrlR antagonist, which opens potential therapeutic approaches for MFA, or any other disease that could be associated with this mutation in future.
New methods of pain measurement and their application to pain control. (1978)

Recent pain research advances show promise in their application to the relief of acute and chronic clinical dental pain. Regional electroanalgesia, or transcutaneous electrical stimulation, has been used successfully in the treatment of pain associated with peripheral nerve injuries. Electrical stimulation of teeth also may prove useful as a pain control technique during operative dentistry procedures. Another exciting research finding is the discovery of endogenous or natural pain-suppressing pathways in the brain. There are recent demonstrations that natural-occurring opiate-like compounds and receptors exist in the brain. The elucidation of stimuli and behavioral responses which will activate these specific descending pain control pathways may lead to exciting new methods of pain relief. Thus, both regional electroanalgesia and the discovery of endogenous pain-suppressing pathways offer the possibility of the future expanded use of non-pharmacological pain control techniques. The proper evaluation of new pain control techniques requires the development of better methods of measuring and assessing the multidimensional aspects of the pain experience. Category scales which scale the suprathreshold range of pain from threshold to tolerance levels can be used with both experimental and clinical pain. Sensory Decision Theory has been applied to the analysis of categorical pain responses. This method distinguishes between sensitivity to stimulus intensity and response bias, or the patient's willingness to report a given intensity as painful. Another promising method for scaling pain is the use of ratio-scaling methods with verbal pain descriptors. Verbal descriptors of pain may provide the best method of scaling different dimensions of the pain experience. Reliable and objective descriptor scales have been developed which separate pain along two dimensions: sensory intensity and affect, or unpleasantness. By using cross-modality matching procedures, specific numerical values can be calculated for each verbal descriptor. These scales have been used to measure the intensity and unpleasantness associated with tooth pulp evoked experimental and clinical pain, and should be extremely useful in the evaluation of acute and chronic dental pain. They will be important experimental and clinical adjuncts in determining the efficacy of non-pharmacological pain control methods such as regional electroanalgesia, biofeedback, relaxation-suggestion and hypnosis.
Effects of TH1 and TH2 cytokines on CD8+ cell response against human immunodeficiency virus: implications for long-term survival. (1995)

CD8+ cells from long-term survivors [LTS; infected with human immunodeficiency virus (HIV) for 10 or more years and having CD4+ cell counts of > or = 500 cells per microliters] have a 3-fold greater ability to suppress HIV replication than do CD8+ cells from patients who have progressed to disease (progressors) during the same time period. A change in the pattern of cytokines produced in the host from those that typically favor cell-mediated immunity (T helper 1, TH1 or type 1) to those that down-regulate it (T helper 2, TH2 or type 2) was investigated as a cause of this reduced CD8+ cell anti-HIV function. Treatment of CD8+ cells from LTS with the TH1 cytokine interleukin (IL)-2 enhanced their anti-HIV activity, whereas exposure of these cells to TH2 cytokines IL-4 or IL-10 reduced their ability to suppress HIV replication and to produce IL-2. IL-2 could prevent and reverse the inhibitory effects of IL-4 and IL-10. Moreover, prolonged exposure of CD8+ cells from some progressors to IL-2 improved the ability of these cells to suppress HIV replication. These observations support previous findings suggesting that strong CD8+ cell responses play an important role in maintaining an asymptomatic state in HIV infection. The data suggest that the loss of CD8+ cell suppression of HIV replication associated with disease progression results from a shift in cytokine production within the infected host from a TH1 to a TH2 pattern. Modulation of these cytokines could provide benefit to HIV-infected individuals by improving their CD8+ cell anti-HIV activity.
Projection-based head-mounted displays for wearable computers (2004)

The projection based head-mounted display (HMD) constitutes a new paradigm in the field of wearable computers. Expanding on our previous projection based HMD, we developed a wearable computer consisting of a pair of miniature projection lenses combined with a beam splitter and miniature displays. Such wearable computer utilizes a novel conceptual design encompassing the integration of phase conjugate material (PCM) packaged inside the HMD. Some of the applications benefiting from this innovative wearable HMD are for government agencies and consumers requiring mobility with a large field-of-view (FOV), and an ultra-light weight headset. The key contribution of this paper is the compact design and mechanical assembly of the mobile HMD.
Glutathione-ascorbic acid antioxidant system in animals (1994)

strong evolutionary link between GSH and eukaryotic aerobic metabolism that is reflected in the function of GSH in protection against oxygen toxicity (2). GSH is not required in the diet of animals but is synthesized in virtually all animal cells' by the sequential actions of two enzymes: y-glutamylcysteine synthetase and GSH synthetase. A useful approach to understanding the func- tions of a cellular component such as GSH is to remove it and to determine the consequences of its deletion. GSH deficiency can be produced
Preparation of Potent Cytotoxic Ribonucleases by Cationization:  Enhanced Cellular Uptake and Decreased Interaction with Ribonuclease Inhibitor by Chemical Modification of Carboxyl Groups (2001)

Carboxyl groups of bovine RNase A were amidated with ethylenediamine (to convert negative charges of carboxylate anions to positive ones), 2-aminoethanol (to eliminate negative charges), and taurine (to keep negative charges), respectively, by a carbodiimide reaction. Human RNase 1 was also modified with ethylenediamine. Surprisingly, the modified RNases were all cytotoxic toward 3T3-SV-40 cells despite their decreased ribonucleolytic activity. However, their enzymatic activity was not completely eliminated by the presence of excess cytosolic RNase inhibitor (RI). As for native RNase A and RNase 1 which were not cytotoxic, they were completely inactivated by RI. More interestingly, within the cytotoxic RNase derivatives, cytotoxicity correlated well with the net positive charge. RNase 1 and RNase A modified with ethylenediamine were more cytotoxic than naturally occurring cytotoxic bovine seminal RNase. An experiment using the fluorescence-labeled RNase derivatives indicated that the more cationic RNases were more efficiently adsorbed to the cells. Thus, it is suggested that the modification of carboxyl groups could change complementarity of RNase to RI and as a result endow RNase cytotoxicity and that cationization enhances the efficiency of cellular uptake of RNase so as to strengthen its cytotoxicity. The finding that an extracellular human enzyme such as RNase 1 could be effectively internalized into the cell by cationization suggests that cationization is a simple strategy for efficient delivery of a protein into cells and may open the way of the development of new therapeutics.
Isocitrate Dehydrogenase Mutations Are Rare in Pheochromocytomas and Paragangliomas (2009)

IDH mutations are very rare in paragangliomas and pheochromocytomas and do not appear to play an important role in oncogenic HIF activation known to be present in these tumors.
Pixel-selected ray tracing (1991)

An acceleration method based on an idea that T. Whitted (Commun. ACM, vol.23, no.6 pp.343-349, June 1980) presented on ray tracing is discussed. He proposed making antialiased images by hierarchical adaptive oversampling. The present authors use hierarchical adaptive undersampling to reduce the number of pixels whose intensity must be calculated by ray tracing. To implement pixel-selected ray tracing (PSRT), homogeneous regions in images must first be found. Generally, adaptive undersampling can result in some image-quality defects, because small objects and parts of thin or wedge-shaped objects may disappear when they are located between the initially sampled pixels. PSRT has an improved algorithm that uses pixels with the correct object information from among the sampled pixels to find pixels with erroneous color and correct them. Moreover, PRST uses ray-object intersection trees for precise classification of the homogeneity of regions and for fast intensity calculation in homogeneous regions. Experimental results are presented. They show that PSRT is two to nine times faster than standard ray tracing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A 10/30 MHz Fast Reference-Tracking Buck Converter With DDA-Based Type-III Compensator (2014)

A 10/30 MHz voltage-mode controlled buck converter with a wide duty-cycle range is presented. A high-accuracy delay-compensated ramp generator using only low-speed comparators but can work up to 70 MHz is proposed. By using a differential difference amplifier (DDA), a new Type-III compensator is proposed to reduce the chip area of the compensator by 60%. Moreover, based on the unique structure of the proposed compensator, an end-point prediction (EPP) scheme is also implemented to achieve fast reference-tracking responses. The converter was fabricated in a 0.13 μm standard CMOS process. It achieves wide duty-cycle ranges of 0.75 and 0.59 when switching at 10 MHz and 30 MHz with peak efficiencies of 91.8% and 86.6%, respectively. The measured maximum output power is 3.6 W with 2.4 V output voltage and 1.5 A load current. With a constant load current of 500 mA, the up-tracking speeds for switching frequencies of 10 MHz and 30 MHz are 1.67 μs/V and 0.67 μs/V, respectively. The down-tracking speeds for 10 MHz and 30 MHz are 4.44 μs/V and 1.56 μs/V, respectively.
Stability of freeze-dried vaginalLactobacillusstrains in the presence of different lyoprotectors (2009)

The industrial use of lactic acid bacteria as probiotic cultures depends on the preservation techniques employed, which are required to guarantee stable cultures in terms of viability and functional activity. The aim of this study was to evaluate the effects of 12% lactose and 12% sucrose suspended in water or reconstituted skim milk on the survival and expression of beneficial characteristics during freeze-drying and subsequent storage of 6 vaginal lactobacilli strains. A cubic polynomial model was also used for the first time to evaluate the effects of different protectors on survival behavior during storage. Different survival patterns were observed among the strains considered. The presence of both lactose and sucrose in water or in 6% skim milk as the suspension medium proved to be effective in maintaining a high degree of survival and expression of potentially probiotic characteristics (production of antimicrobial substances or auto-aggregation capabilities) of most strains after lyophilization and long-term storage. This study constitutes a valuable step to obtain concentrated cultures with the highest stability of microorganisms for pharmaceutical purposes.
An unmodified anticarcinoma antibody, BR96, localizes to and inhibits the outgrowth of human tumors in nude mice. (1992)

The antitumor effects of an unmodified murine monoclonal antibody, BR96, were examined in nude mice bearing human lung adenocarcinoma xenografts. BR96, a murine IgG3 that internalizes and is cytotoxic to cells expressing the antigen in vitro, also elicits strong antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity effector functions. Its in vivo antitumor effects were compared with those of its F(ab')2 fragments, a mouse-human chimeric form, and an IgG1 class switched variant of the original (IgG3) BR96. Antitumor effects were observed with antigen-positive tumor lines (but not with tumors which did not bind with BR96) and correlated with the levels of antigen expression as detected in vitro. The chimeric form of BR96 gave the strongest antitumor effects, followed by the murine IgG3, while limited effects were seen with the IgG1 and with F(ab')2 fragments of BR96, indicating that Fc-dependent host effector functions are primarily responsible for its in vivo activity. The antitumor effects observed were modest unless the antibody treatment was started on the day following tumor grafting.
Nanoparticles disguised as red blood cells to evade the immune system (2012)

The development of nanoparticle platforms with long in vivo circulation half-life has long been one of the major goals in the field of cancer drug delivery. Long-circulating nanoparticles can more effectively localize to the tumor site through either passive or active targeting mechanisms. The current gold standard for bestowing long-circulating attributes involves the use of PEG, which surrounds the particles with a hydration layer and thereby prevents recognition by the mononuclear phagocyte system. Recently, a new strategy for synthesizing biomimetic nanoparticles has been inspired by the body's own long-circulating entities, red blood cells (RBCs). Such a system disguises drug nanocarriers as 'self' using membrane materials directly derived from RBCs. This method has been demonstrated to prolong particle systemic circulation half-life beyond that of the corresponding PEGylated systems. The RBC membrane-coated nanoparticles present a major breakthrough in drug delivery technology and show great promise for clinical applications. Herein we highlight the significance and the unique features of this nature-inspired nanoparticle platform and offer opinions on its future prospects.
Improved Synthetic Methods of Firefly Luciferin Derivatives for Use in Bioluminescent Analysis of Hydrolytic Enzymes; Carboxylic Esterase and Alkaline Phosphatase (1992)

Abstract Improved synthetic methods of firefly luciferin derivatives, such as 6-O-alkanoylluciferins and 6-O-phosphonoluciferin, are described. These derivatives proved to be useful as substrates for the bioluminescent assay of hydrolytic enzymes such as carboxylic esterase and alkaline phosphatase. The synthetic methods previously reported gave fairly low yields because of direct derivatization of unstable luciferin itself and are difficult to be applied to large-scale synthesis because of unavoidable HPLC purification. We first modified the hydroxyl group of 2-cyano-6-hydroxybenzothiazole and then condensed the resulting stable products with d-cysteine to give the appropriate derivatives in good yields without HPLC purification. 6-O-Phosphonoluciferin was unstable as free acid form but stable as its sodium salt.
Identification of NF‐κB Modulation Capabilities within Human Intestinal Commensal Bacteria (2011)

The intestinal microbiota plays an important role in modulation of mucosal immune responses. To seek interactions between intestinal epithelial cells (IEC) and commensal bacteria, we screened 49 commensal strains for their capacity to modulate NF-κB. We used HT-29/kb-seap-25 and Caco-2/kb-seap-7 intestinal epithelial cells and monocyte-like THP-1 blue reporter cells to measure effects of commensal bacteria on cellular expression of a reporter system for NF-κB. Bacteria conditioned media (CM) were tested alone or together with an activator of NF-κB to explore its inhibitory potentials. CM from 8 or 10 different commensal species activated NF-κB expression on HT-29 and Caco-2 cells, respectively. On THP-1, CM from all but 5 commensal strains stimulated NF-κB. Upon challenge with TNF-α or IL-1β, some CM prevented induced NF-κB activation, whereas others enhanced it. Interestingly, the enhancing effect of some CM was correlated with the presence of butyrate and propionate. Characterization of the effects of the identified bacteria and their implications in human health awaits further investigations.
A SCANDINAVIAN TWO-CENTER STUDY OF BMA 031 IN STEROID-RESISTANT REJECTION OF RENAL GRAFTS (1993)

BMA 031 (Behring Monoclonal Antibody) was given to 25 renal graft recipients with biopsy-proven steroid-resistant rejections. A dose of 50 mg of BMA 031 was given i.v. on 7 consecutive days concomitantly with a standard triple-drug regimen. No premedication was administered before the first BMA 031 dose. After the first dose, 7 patients experienced moderate fever (< 39 degrees C), 5 patients had high fever (> 39 degrees C), 4 patients had nausea/vomiting, 3 diarrhea, 1 headache, and 1 hypertension. These reactions were seen only after the first dose except for 1 patient who developed urticaria on days 3-4. All the rejection episodes were reversed or partially reversed. Twenty-one patients experienced re-rejections 3-46 days after the last BMA 031 dose, and were treated with methylprednisolone and/or rabbit antihuman thymocyte globulin. Seven patients lost their grafts within 1 year (28%), including 2 patients who died of infection with a functioning graft. BMA 031 seems to be a safe drug with only few mild side effects, and it effectively reverses steroid-resistant rejections. Re-rejections were frequent, but mostly reversible.
Albendazole sensitizes cancer cells to ionizing radiation (2011)

Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted.
A nurse prescriber's guide to the legal implications of parental responsibility (2005)

Parental responsibility is described by the Children Act 1989 as all the rights, powers and duties a parent has over a child and its property. Those rights include the right to consent to treatment for a child right up until the child's eighteenth birthday. It is essential, therefore, that nurse prescribers are aware of who has parental responsibility for a child in their care and the extent to which parental responsibility allows a parent to refuse treatment for a child.
Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease. (1997)

The in vivo patterns of CPP32 (Caspase-3) gene expression were determined using an immunohistochemical approach and paraffin-embedded normal human tissues. A rabbit polyclonal antiserum was generated against recombinant human CPP32 protein and shown to be specific by immunoblot analysis of various human tissues and cell lines. CPP32 immunoreactivity was selectively found in certain cell types and was typically present within the cytosol, although occasional cells also contained nuclear immunostaining. CPP32 immunostaining was easily detected, for example, in epidermal keratinocyes, cartilage chondrocytes, bone osteocytes, heart myocardiocytes, vascular smooth muscle cells, bronchial epithelium, hepatocytes, thymocytes, plasma cells, renal tubule epithelium, spermatogonia, prostatic secretory epithelial cells, uterine endometrium and myometrium, mammary ductal epithelial cells, and the gastrointestinal epithelium of the stomach, intestine, and colon. In contrast, little or no CPP32 immunoreactivity was observed in endothelial cells, alveolar pneumocytes, kidney glomeruli, mammary myoepithelial cells, Schwann cells, and most types of brain and spinal cord neurons. Consistent with a role for CPP32 in apoptotic cell death, clear differences in the relative intensity of CPP32 immunostaining were noted in some shorter-lived types of cells compared to longer-lived, including (a) germinal center (high) versus mantle zone (low) B lymphocytes within the secondary follicles of lymph nodes, spleen, and tonsils; (b) mature neutrophils (high) versus myeloid progenitor cells (low) in bone marrow; (c) corpus luteal cells (high) versus follicular granulosa cells (low) in the ovary; and (d) prostate secretory epithelial cells (high) versus basal cells (low). These findings establish for the first time the cell type- and differentiation-specific patterns of expression of an interleukin-1beta converting enzyme/CED-3 (Caspase) family protease.
Design and control of a robotic finger for prosthetic hands (2003)

Considers design and control of a robotic finger for prosthetic hands. A linkage driven robotic finger actuated by single motor is developed such that the motion of the robotic finger is very close to the motion of a human finger. The signal measured from strain gauges attached to the tendon of the hand is used as a position command to control the motion of the robotic finger. The results of simulation and experiment are presented to show that the proposed robotic finger is fit for a prosthetic hand.