gebhart/patrepeval huggingface dataset:
Progress and challenges in viral vector-mediated gene transfer to the brain. (2002)

Gene transfer into the brain allows the manipulation of transgene expression in both time and space. Recently developed gene transfer technologies allow transgenes to be expressed in any anatomically, biochemically or functionally distinct group of brain cells. Gene transfer has been used to alter the expression of neurotransmitter receptors, ion channels, signaling proteins, neuronal growth, differentiation and survival factors, and thus to modify brain anatomy, neuron physiology, behavior and pathology. However, challenges remain in making gene therapy a more widespread tool for the treatment of neurological disease. We have identified the following as areas needing development: access and delivery of viral vectors to the brain; diffusion of viral vectors and transgenes throughout large areas of brain tissue; viral vector side effects and toxicity, inflammatory and immune responses to vectors; long-term stable transgene expression; cell type-specific expression of transgenes; and the ability of the experimenter or physician to switch transgene expression 'on' and 'off' at will. In the last year, neuro-gene therapy has shown that brain defects in experimental disease models can be prevented and corrected, and that viral vectors and encoded transgenes can be made to diffuse over larger brain areas. In addition, the cause of vector-induced inflammation and immune responses have begun to be elucidated, so that rational approaches can be developed to avoid these complications. Further improvements in viral vectors will facilitate clinical trials in the near future.
Refining Noninvasive Prenatal Diagnosis with Single-Molecule Next-Generation Sequencing (2012)

The gradual elimination of risky procedures used to sample fetal material for prenatal diagnosis has been an important objective in medicine. It is often stated that more fetuses are lost due to such invasive procedures (amniocentesis and chorionic villus sampling) than are identified as carrying a chromosomal abnormality. Noninvasive prenatal diagnosis (NIPD) 2 has developed substantially since the discovery in 1997 that appreciable amounts of free fetal DNA occur in maternal plasma (1). This discovery rapidly paved the way for the detection of paternally inherited alleles in maternal blood, including, most notably, Rh D blood group, fetal sex, and single-gene disorders. For more than a decade now, NIPD has been used routinely for pregnancies in which paternally inherited alleles require detection because their inheritance would indicate a …
A direct inhibitory effect of insulin on a cytosolic proteolytic complex containing insulin-degrading enzyme and multicatalytic proteinase. (1994)

The insulin-degrading enzyme (IDE) and the multicatalytic proteinase (MCP) can be isolated as components of a cytosolic proteolytic complex. IDE is the primary enzyme involved in cellular degradation of insulin, and insulin has been shown to interact with cytosolic IDE. MCP is believed to be important in non-ubiquitin pathways of cellular protein degradation. Insulin has a dose- and time-dependent inhibitory effect on MCP degradation of N-succinyl-Leu-Leu-Val-Tyr 7-amino-4-methylcoumarin (LLVY), a substrate for MCP. Proinsulin also inhibits LLVY degradation in a dose-dependent manner. The effect of insulin is immediate as measured in a continuously monitored assay of LLVY degradation. Purification of the IDE-MCP complex using a variety of approaches, including affinity and conventional chromatography, retains the insulin effect on LLVY degradation as long as the complex remains intact. After ion-exchange chromatography, which separates IDE and MCP, insulin no longer has an inhibitory effect. Recombination of purified IDE and MCP does not restore the effect of insulin, but inclusion of additional components from the ion-exchange column does. These results support the existence of a functional cytosolic complex that contains IDE and MCP. Insulin interacts with IDE and alters the activity of MCP, suggesting a functional relationship between these two components and a mechanism for an intracellular action of insulin.
Efficacy and safety of the combination of paclitaxel and platinum in advanced thymic carcinoma (2015)

This study aimed to assess the efficacy and safety of a combination of paclitaxel and cisplatin/carboplatin for the treatment of advanced thymic carcinoma. Thirty-seven patients (23 men and 14 women, median age 47 years, performance status score ≤2) with pathologically or cytologically diagnosed advanced thymic carcinoma were recruited. Patients received 175 mg/m(2) paclitaxel on day 1 and 75 mg/m(2) cisplatin or 300 mg/m(2) carboplatin on day 2 of a 21 day cycle for at least two cycles to evaluate efficacy and adverse events. No complete response (CR) was observed; 11 patients had a partial response (PR), 16 patients had no change (NC), and 10 had progressive disease, resulting in an overall response rate of 29.7%, a stable rate of 43.2%, and a disease control rate (CR + PR + NC) of 72.9%. Grade I/II and III/IV neutropenia were observed in 21 (56.7%) and 13 (35.1%) patients, respectively. Four (10.8%) patients developed grade I/II thrombocytopenia. Grade I/II and III/IV nausea and vomiting were observed in 19 (51.2%) and five (13.5%) patients, respectively. Grade I/II liver dysfunction was observed in seven (18.9%) patients. Two patients with grade III liver dysfunction recovered after hepatoprotective treatment. The combination of paclitaxel and platinum was effective and well tolerated in patients with advanced thymic carcinoma.
Optical System with 4 ㎛ Resolution for Maskless Lithography Using Digital Micromirror Device (2010)

In the present study, an optical system is proposed for maskless lithography using a digital micromirror device (DMD). The system consists of an illumination optical system, a DMD, and a projection lens system. The illumination optical system, developed for 95% uniformity, is composed of fly's eye lens plates, a 405 nm narrow band pass filter (NBPF), condensing lenses, a field lens and a 250W halogen lamp. The projection lens system, composed of 8 optical elements, is developed for 4 <TEX>${\mu}m$</TEX> resolution. The proposed system plays a role of an optical engine for PCB and/or FPD maskless lithography. Furthermore, many problems arising from the presence of masks in a conventional lithography system, such as expense and time in fabricating the masks, contamination by masks, disposal of masks, and the alignment of masks, may be solved by the proposed system. The proposed system is verified by lithography experiments which produce a line pattern with the resolution of 4 <TEX>${\mu}m$</TEX> line width.
Design and performance of a multichannel vestibular prosthesis that restores semicircular canal sensation in rhesus monkey (2011)

In normal individuals, the vestibular labyrinths sense head movement and mediate reflexes that maintain stable gaze and posture. Bilateral loss of vestibular sensation causes chronic disequilibrium, oscillopsia, and postural instability. We describe a new multichannel vestibular prosthesis (MVP) intended to restore modulation of vestibular nerve activity with head rotation. The device comprises motion sensors to measure rotation and gravitoinertial acceleration, a microcontroller to calculate pulse timing, and stimulator units that deliver constant-current pulses to microelectrodes implanted in the labyrinth. This new MVP incorporates many improvements over previous prototypes, including a 50% decrease in implant size, a 50% decrease in power consumption, a new microelectrode array design meant to simplify implantation and reliably achieve selective nerve-electrode coupling, multiple current sources conferring ability to simultaneously stimulate on multiple electrodes, and circuitry for in vivo measurement of electrode impedances. We demonstrate the performance of this device through in vitro bench-top characterization and in vivo physiological experiments with a rhesus macaque monkey.
Xenograft Model of Progressive Human Proliferative Breast Disease (1993)

Progression of proliferative breast disease has been associated with increased risk for development of invasive carcinoma. Cell lines have been developed to facilitate the study of this process. Human cell line MCF1OA originated from spontaneous immortalization of breast epithelial cells obtained from a patient with fibrocystic disease, and cell lines MCF1OAneoN and MCF1OAneoT were created by stable transfection of these cells with the neomycin-resistance gene and either the HRAS gene or the mutated T-24 HRAS gene, respectively. Our goal was to develop an experimental model of progressive human proliferative breast disease. MCF1OA, MCF1OAneoN, and MCF1OAneoT cells were injected subcutaneously into the dorsal flank of male nude/beige (C57/BALB/c nu/nu bg/ bg) mice (12 mice for each cell type). These mice were examined periodically for formation and persistence or growth of palpable nodules. One mouse per group was killed 1 week after cell injection; thereafter, mice were observed as long as possible. Cells were recovered from palpable lesions by enzymatic dissociation of the excised lesions. Cells re-established in tissue culture from a week-14 tumor (MCF1OAneoT.TG1) were injected into 12 male nude/beige mice. Southern blot hybridization analysis of the HRAS gene locus and cytogenetic analyses were performed. Transplanted MCF1OA and MCF1OAneoN cells formed transient, small palpable nodules that regressed and disappeared during the 4th and 5th weeks. In 10 of the 12 mice, T-24 HRAS genetransfected MCF1OA cells (MCF1OAneoT) formed small, flat nodules that persisted for at least 1 year. Three of these xenografts became carcinomas. One (removed 7 weeks after transplantation) was an undifferentiated carcinoma composed of polygonal cells with large, vesicular nuclei and numerous mitoses. The second (removed after 14 weeks) was an invasive squamous cell carcinoma. The third (removed after 56 weeks) was a moderately differentiated adenocarcinoma. Initially, xenografts of MCF1OAneoT.TG1 cells showed intraductal proliferative changes; after 23 weeks, the lesions showed histologic features resembling those seen in atypical hyperplasia of the human breast, and later lesions showed characteristics of carcinoma in situ. The MCF1O lineage of cells of three MCF1OAneoT.TG1 xenografts was confirmed by DNA fmgerpnnting and karyotype analysis. MCF1OAneoT and MCF1OAneoT.TG1 comprise a transplantable xenograft model that produces a broad spectrum of human proliferative breast disease. The reproducible establishment of representative stages In early breast cancer progression from the MCF1O model offers a new opportunity to analyze critical events of carcinogenesis and progression in breast cancer. [J NatI Cancer Inst 85:1725–1732, 1993
Report of the First Case of Invasive Fungal Sinusitis Caused by Scopulariopsis acremonium (1998)

Scopulariopsis acremonium is a species of saprophytic fungus not previously reported to cause invasive disease in humans, although invasive infections from other species of Scopulariopsis have been reported and are reviewed. Deep infection with this fungus is associated with a high mortality rate. Invasive fungal sinusitis, in general, is a potentially fatal disease that typically affects immunocompromised patients, such as those receiving intensive chemotherapy or undergoing bone marrow transplantation. We report a case of invasive fungal sinusitis caused by Scopulariopsis acremonium in a patient with leukemia, who was successfully treated with amphotericin B, itraconazole, endoscopic sinus surgery, and granulocyte colony-stimulating factor.
Conservation of methane from Colorado's mined/minable coal beds: a feasibility study (1980)

Coal bed methane, a well documented hazard in coal mines, is also a potential energy source. In Colorado, an estimated resource of 38.8 TCF may exist in the Green River, Raton Mesa, San Juan River, and Uinta coal regions. Methane content for minable coalbeds ranges from 0 to near 500 cubic feet of gas per ton of coal. The presence of coal bed methane depends on geologic factors, while development of coal bed methane depends on geologic, mining, economic, and legal factors which must be considered in determining the feasibility of a coal degasification project. Vertical, horizontal, and directional hole degasification methods are summarized, and a case study of the Hawk's Nest Mine area, Somerset, Colorado, is included. 157 references, 29 figures, 15 tables.
Classification of human ovarian tumors using multivariate data analysis of polypeptide expression patterns (2000)

Large amounts of data on quantitative gene expression are generated by procedures such as 2-DE analysis of proteins or cDNA microarrays. Quantitative molecular variation may potentially be used for the development of methods for the classification of tumors. We used here the statistical concepts of principal components analysis (PCA) and partial least square analysis (PLS) in an attempt to type ovarian tumors. Using a set of 170 polypeptides, 22 tumors were used to establish a model ("learning set") for classification into 3 groups (benign/borderline/malignant). Eighteen tumors were then used to test the model. Six of 8 carcinomas and 3 of 4 borderline tumors were correctly classified. Two of 6 benign lesions were correctly classified, 3 were classified as borderline and 1 as carcinoma. We conclude that it may be possible to classify tumors according to their constitutive protein expression profile using multivariate analysis, thus making classification by artificial intelligence a future possibility.
Chemical and Photochemical Ligation of Oligonucleotide Blocks (1997)

Abstract Several efficient means for joining oligonucleotides in dilute solution by non-natural internucleotide bridges are discussed. It is also shown that an oligonucleotide containing a -OP(O)(O−)S- link can hnction as an effective template in PCR amplification and that oligonucleotide probes containing stilbenedicarboxamide groups can serve in monitoring the presence of mismatched bases in an oligonucleotide target.
Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes (2018)

These data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG.
Upregulation of hyaluronan and its binding receptors in an experimental model of chronic cyclosporine nephropathy (2009)

These findings suggest that upregulation of HA and its binding receptors are involved in interstitial fibrosis in chronic CsA-induced renal injury.
Integrin‐mediated calcium signaling and regulation of cell adhesion by intracellular calcium (1997)

Integrins are ubiquitous trans-membrane adhesion molecules that mediate the interaction of cells with the extracellular matrix (ECM). Integrins link cells to the ECM by interacting with the cell cytoskeleton. In cases such as leukocyte binding, integrins mediate cell-cell interactions and cell-ECM interactions. Recent research indicates that integrins also function as signal transduction receptors, triggering a number of intracellular signaling pathways that regulate cell behavior and development. A number of integrins are known to stimulate changes in intracellular calcium levels, resulting in integrin activation. Although changes in intracellular calcium regulate a vast number of cellular functions, this review will discuss the stimulation of calcium signaling by integrins and the role of intracellular calcium in the regulation of integrin-mediated adhesion.
SACRAL ROOT NEUROMODULATION IN IDIOPATHIC NONOBSTRUCTIVE CHRONIC URINARY RETENTION (1998)

Sacral root neuromodulation is an appealing, successful modality for nonobstructive urinary retention. Only patients who have a good response to percutaneous nerve evaluation are candidates for implantation. The high efficacy in patients who undergo implantation, relative simplicity of the procedure and low complication rate make this a treatment breakthrough in this difficult group.
Expression and Function of Lysophosphatidic Acid LPA1 Receptor in Prostate Cancer Cells (2006)

The bioactive phospholipid lysophosphatidic acid (LPA) promotes cell proliferation, survival, and migration by acting on cognate G protein-coupled receptors named LPA(1), LPA(2), and LPA(3). We profiled gene expression of LPA receptors in androgen-dependent and androgen-insensitive prostate cancer cells and found that LPA(1) gene is differentially expressed in androgen-insensitive and LPA-responsive but not androgen-dependent and LPA-resistant cells. In human prostate specimens, expression of LPA(1) gene was significantly higher in the cancer compared with the benign tissues. The androgen-dependent LNCaP cells do not express LPA(1) and do not proliferate in response to LPA stimulation, implying LPA(1) transduces cell growth signals. Accordingly, stable expression of LPA(1) in LNCaP cells rendered them responsive to LPA-induced cell proliferation and decreased their doubling time in serum. Implantation of LNCaP-LPA(1) cells resulted in increased rate of tumor growth in animals compared with those tumors that developed from the wild-type cells. Growth of LNCaP cells depends on androgen receptor activation, and we show that LPA(1) transduces Galphai-dependent signals to promote nuclear localization of androgen receptor and cell proliferation. In addition, treatment with bicalutamide inhibited LPA-induced cell cycle progression and proliferation of LNCaP-LPA(1) cells. These results suggest the possible utility of LPA(1) as a drug target to interfere with progression of prostate cancer.
IgG glycosylation analysis (2009)

Abstract A multitude of monoclonal IgG antibodies directed against a variety of therapeutic targets is currently being developed and produced by biotechnological companies. The biological activity of IgGs is modulated by the N ‐glycans attached to the fragment crystallizable (Fc) part. For example, lack of core‐fucoses on these N ‐glycans may lead to a drastic enhancement of antibody‐mediated cellular cytotoxicity. Moreover, sialylation of Fc N ‐glycans determines the immunosuppressive properties of polyclonal IgG from human blood, which stimulates research into Fc glycosylation of human plasma IgG in various disease settings. This review presents and evaluates the different approaches which are used for IgG glycosylation analysis: N ‐glycans may be enzymatically or chemically released from purified IgG, prior to chromatographic or mass spectrometric analysis. Moreover, IgGs may be treated with endoproteinases such as trypsin, followed by glycosylation analysis at the glycopeptide level, which is generally accomplished by HPLC with ESI‐MS. Alternatively, intact IgGs or fragments thereof obtained by enzymatic cleavages in the hinge region and by reduction may be analyzed by a large number of analytical techniques, including MS and chromatography or CE.
Potassium Fluoride on Alumina: Dry Synthesis of 3-Arylidene-1,3-Dihydro-indol-2-one Under Microwave Irradiation (1998)

Abstract Aldehydes (2) or ketones (4) were condensed with 1,3-dihydro-indol-2-one (1) in presence of potassium fluoride on alumina without solvent under focused microwave irradiation.
Structure and Activity of Diphtheria Toxin (1971)

Abstract The activity of diphtheria toxin in catalyzing transfer of the adenosine diphosphate ribose moiety of NAD+ into covalent linkage with the mammalian peptidyl transfer RNA translocation factor, transferase II, is dependent upon exposure of the toxin to thiols. The toxin is almost completely inactive when assayed in the absence of thiols, but may be maximally activated by treatment with 50 mm dithiothreitol for 10 min. The activation process has been correlated with certain structural features of the toxin. Studies involving electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate have led us to conclude that toxin consists of a mixture of two similar proteins of molecular weight about 63,000. One consists of intact, 63,000-dalton polypeptide chains (intact toxin), while the other (nicked toxin) consists of two fragments of 24,000 and 39,000 daltons (A and B, respectively) linked by at least one disulfide bridge. Treatment of toxin with thiols results in dissociation of the latter into Fragments A and B. Fragment A is enzymically active, and probably accounts for all the activity of thiol-treated toxin. Fragment B is almost certainly devoid of activity for reasons which are discussed, although this has not been demonstrated experimentally. Intact toxin appears to be inactive before or after treatment with dithiothreitol. In the accompanying paper we show that intact toxin is a precursor of nicked toxin, and may be converted into the latter by treatment with trypsin.
Control speculation in multithreaded processors through dynamic loop detection (2002)

This paper presents a mechanism to dynamically detect the loops that are executed in a program. This technique detects the beginning and the termination of the iterations and executions of the loops without compiler/user intervention. We propose to apply this dynamic loop detection to the speculation of multiple threads of control dynamically obtained from a sequential program. Based an the highly predictable behavior of the loops, the history of the past executed loops is used to speculate the future instruction sequence. The overall objective is to dynamically obtain coarse grain parallelism (at the thread level) that can be exploited by a multithreaded architecture. We show that for a 4-context multithreaded processor the speculation mechanism provides around 2.6 concurrent threads in average.
Purine nucleoside phosphorylase from human erythrocytes: physicochemical properties of the crystalline enzyme (1978)

The major physicochemical properties of human erythrocytic purine nucleoside phosphorylase (PNPase) have been described. The molecular weight, estimated by ultracentrifugation, molecular sieving and sucrose density gradient centrifugation, ranged from 87 000 to 92 000. Other physical constants of erythrocytic PNPase were: sedimentation coefficent (s20, w), 5.4 S obtained by sedimentation analysis and 5.5 S by the sucrose density gradient procedure; Stokes radius, 38 A; calculated diffusion coefficient (D20, w), 5.7 X 10(-7) cm2 s-1; frictional ration, 1.29; and partial specific volume calculated from amino acid analysis, 0.73 cm3 g-1. The CD spectra of the human erythrocytic and bovine spleen PNPases were almost identical and indicated a very low alpha-helical content. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicated that the molecular weight of the PNPase subunit is 30 000 +/- 500. These results corroborate earlier reports that the native enzyme is a homologous trimer. Comparative studies with crystalline bovine spleen PNPase confirmed that it is also a trimer but is somewhat smaller than the human erythrocytic enzyme with a molecular weight of about 86 000.
Joint channel and echo impulse response shortening on digital subscriber lines (1996)

A new scheme for joint shortening of two long impulse responses using a single finite impulse response (FIR) equalizer is presented. The optimum settings, in the mean square error (MSE) sense, of the equalizer and the two (unit-tap constrained) shortened impulse responses are derived. The main application of interest is joint shortening of the channel and echo impulse responses for high-speed transmission on digital subscriber lines.
IC202A, a New Siderophore with Immunosuppressive Activity Produced by Streptoalloteichus sp. 1454-19. I. Taxonomy, Fermentation, Isolation and Biological Activity. (1999)

IC202A, a new immunosuppressive compound, was isolated from the culture filtrate of Streptoalloteichus sp. 1454-19. It showed a suppressive effect on mixed lymphocyte culture reaction with an IC50 value of 3.6 microg/ml and mitogen induced lymphocyte blastogenesis in vitro.