gebhart/patrepeval huggingface dataset:
Intracellular IFN- γ Production and IL-12 Serum Levels in Latent Autoimmune Diabetes of Adults (LADA) and in Type 2 Diabetes (2004)

Th1 cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), and Th1-inducing cytokines, such as IL-12, are involved in the pathogenesis of various organ-specific autoimmune diseases, including autoimmune diabetes. In this study, we investigated intracellular IFN-gamma release by T lymphocytes and IL-12 serum levels in 48 type 2 and 36 latent autoimmune diabetes of adults (LADA) diabetics and 25 control subjects in an attempt to evaluate their role in the pathogenesis of these clinical entities. Ionomycin (ION) and phorbol-12-myristate-13-acetate (PMA)-activated peripheral blood mononuclear cells (PBMCs) were stained with anti-CD4-FITC or anti-CD8-FITC and anti-IFN-gamma phycoerythrin (PE) monoclonal antibodies (mAbs) and analyzed by flow cytometry. IL-12 serum levels were determined by enzyme-linked immunosorbent assay (ELISA). In all study groups, IFN-gamma content of CD4(+) and CD8(+) lymphocytes was significantly upregulated by stimulation. Furthermore, it was observed that CD4(+) and CD8(+) lymphocytes from type 2 diabetics produced significantly lower levels of IFN-gamma compared with LADA patients and controls. However, the percentages of CD4(+)/IFN-gamma(+) and CD8(+)/IFN-gamma(+) cells from type 2 diabetics were significantly higher compared with controls. The flow cytometric picture of intracellular IFN-gamma release in LADA patients did not differ from that observed in controls. However, IL-12 serum levels in type 2 and LADA diabetics were lower than in controls. Because Th1 cytokines have been associated with the pathogenesis of autoimmune diabetes, these results preclude Th1 involvement in the autoimmune phenomena observed in LADA patients. In contrast, the low IFN-gamma levels observed in type 2 diabetics in combination with the low IL-12 serum levels might be a contributing factor in the frequently observed chronic complications in these patients.
Nuclear signaling induced by ionizing radiation involves colocalization of the activated p56/p53lyn tyrosine kinase with p34cdc2. (1996)

The Src-like protein-tyrosine kinase p56/p53lyn associates with cell membranes and transduces signals from activated cell surface receptors. In the present work, cell fractionation and confocal microscopy studies demonstrate expression of Lyn in the nucleus. We also demonstrate that exposure of intact cells to ionizing radiation is associated with selective activation of nuclear Lyn. Similar findings have been obtained following irradiation of purified nuclei. Immunoprecipitation studies of nuclear lysates demonstrate radiation-induced binding of Lyn to p34cdc2. Nuclear colocalization of Lyn with Cdc2 has been confirmed by confocal microscopy. Other studies with glutathione S-transferase-Lyn fusion proteins demonstrate that the binding of Lyn to nuclear Cdc2 is associated with inhibition of Cdc2 activity. These findings suggest that the association of activated Lyn with Cdc2 in the nucleus may contribute to regulation of a DNA damage-dependent premitotic checkpoint.
Spectral sorting of visible light using dielectric gratings (2017)

We present the concept of spectral sorting using normalized optical efficiency and systematically study the dielectric based multilayer structure for spectral sorting of visible light with silicon as the absorbing material. We show that by using grating structures, the spectral sorter structures are more efficient when the detector size is less than 1µm, enabling the shrinking of the detector size to the wavelength scale. A comprehensive design strategy is derived that could be used as a design guideline to achieve the sorting of visible light. We show that for pixel size as small as 0.5µm, optical efficiency as high as 80% could be achieved using dielectric based sorting structures.
[Improving the embryonic stem cell test (EST) by establishing molecular endpoints of tissue specific development using murine embryonic stem cells (D3 cells)]. (2002)

Blastocyst-derived pluripotent embryonic stem (ES) cells of the mouse can be induced to differentiate in culture into a variety of cell types, including cardiac muscle cells. In the embryonic stem cell test (EST) the capacity of ES cells of the mouse cell line D3 to differentiate into contracting cardiomyocytes is used to assess the embryotoxic potential of test compounds and in addition, the effects on the viability of ES cells and differentiated mouse fibroblasts (cell line 3T3) are compared. The three endpoints are used to classify the embryotoxic potential of chemicals after 10 days of exposure: (i) the inhibition of differentiation of ES cells into cardiomyocytes (ID50) and (ii) the decrease of viability of 3T3 cells (IC503T3) and (iii) ES cells (IC50D3) in a MTT cytotoxicity test. Applying linear analysis of discriminance, a biostatistical prediction model (PM) was developed to assign test chemicals to three classes of embryotoxicity. In an international validation study funded by ECVAM it could be demonstrated that the EST can predict the embryotoxic potential of a test compound as good as frequently used mammalian systems based on pregnant animals. In a joint project with major German pharmaceutical companies we are attempting to improve the EST by establishing molecular endpoints of differentiation (e.g. cardiac, neuronal, chondrogenic) in cultured ES cells. We have studied the expression of tissue specific proteins in ES cell cultures in the presence of embryotoxic chemicals by immunofluorescent antibody techniques, e.g. FACS analysis. The other groups are focusing on endogenous gene expression in early development by RT-PCR methods or the DNA microarray technique. The results obtained recently using molecular markers specific for cardiac differentiation and employing intracellular flow cytometry for quantification will be presented. Molecular endpoints will allow improvement of the EST by measuring gene expression patterns in a small number of murine ES cells.
Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer (2007)

Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.
Combined dendritic cell- and CpG oligonucleotide-based immune therapy cures large murine tumors that resist chemotherapy (2002)

The use of dendritic cells (DC) loaded with tumor antigen is one of the most advanced approaches in cancer immunotherapy. CpG motifs within microbial DNA detected by toll-like receptor 9 are responsible for the favorable properties of CpG oligodeoxynucleotides (ODN) as immune modulators. In this study, mature antigen-pulsed DC or peritumoral injections of CpG ODN, both effective for the treatment of small established tumors, were almost ineffective against large established tumors (1-cm diameter) in a syngeneic murine colon carcinoma model. For large tumors, the antitumor activity of mature antigen-pulsed DC was strongly increased by coinjection of CpG ODN, resulting in a transient control of tumor growth. Rejection of large tumors and long-term cure of mice was achieved by combining injection of antigen-pulsed DC plus CpG ODN at a site distant to the tumor with peritumoral injections of CpG ODN. Depletion of CD8 T cells abrogated the therapeutic activity. Large numbers of DEC-205-positive DC infiltrated the tumor in treated mice. Therapy with 5-fluorouracil and leucovorin was unable to control tumors of the same size. In conclusion, we demonstrate that the immune system, provided that appropriate stimulation with DC and CpG ODN is given, has the potential to cure animals of large solid tumors in situations where even chemotherapy is not efficient.
A Practical Postscript (1986)

I have tried above all to show in this book that philosophy can have immense practical force and value in human life. But — perhaps for reasons given in the last two chapters, where we discussed our resistances to philosophy in particular and reason in general — it is clear that this view of philosophy is not properly institutionalised or put into practice. Hence the philosopher may fairly be asked some question of the general form "Assuming you are right about philosophy, what do you recommend should be done about it?"
Probing the Abilities of Synthetically Useful Serine Proteases To Discriminate between the Configurations of Remote Stereocenters Using Chiral Aldehyde Inhibitors (1996)

The abilities of the synthetically useful serine proteases, subtilisin Carlsberg (SC) and α-chymotrypsin (CT), to discriminate between R- and S-configurations of stereocenters remote from the catalytic site have been explored using chiral aldehyde transition state analog inhibitors as probes. The inhibitors evaluated were (R)- and (S)-3-phenylbutanal and (R)- and (S)-4-phenylpentanal, for which the stereocenters at C-3 and C-4 respectively are distant from the aldehyde functionality that interacts with the catalytic serine residue. The achiral parent compounds, 3-phenylpropanal and 4-phenylbutanal, respectively, were also assessed for reference purposes. Each aldehyde was found to be a competitive inhibitor for both enzymes, with CT being significantly more potently inhibited than SC. Within this series, the presence of an R-center methyl group improved binding significantly over that of the achiral parent aldehyde for both enzymes. In contrast, the effects on binding of S-methyl substituents in the same positions were modest, and generally somewhat deleterious. Furthermore, the greater the separation of the stereocenter from the aldehyde group, the lower the degree of configuration discrimination. The most effective inhibition, and the highest degree of remote stereocenter discrimination, observed was that by CT of (R)-3-phenylbutanal, whose KI of 8.4 μM was 61-fold lower than that of its achiral parent 3-phenylpropanal, and 88-fold lower than the KI of its S-enantiomer. Molecular mechanics and molecular dynamics calculations were performed to identify each favored aldehyde−enzyme complex and to reveal the binding and orientation differences responsible for the R- and S-enantiomer binding discriminations observed.
Prediction of antigenic determinants and secondary structures of the major AIDS virus proteins (1987)

Criteria for the design of peptide vaccines to prevent AIDS are presented. The best vaccine candidates contain both B and T lymphocyte-defined epitopes in regions conserved in sequence between viral isolates. We propose that attention should focus on proteins specified by the gag and, possibly, pol genes in addition to the env gene envelope glycoproteins being actively studied. The predictions of B- and T-epitopes are refined by consideration of secondary structure prediction and inter-isolate sequence variability to suggest peptides from env, gag and pol that would be the best vaccine candidates.
Epidemiology and clinical presentation of respiratory syncytial virus infection in a rural area of southern Mozambique (2002)

There is a substantial burden of disease attributable to RSV infection in this rural African setting, with the highest incidence and severity occurring in young infants.
Winter Wine Tourists in Canada's Niagara Region (2006)

This paper represents the first stage in a multi-se asonal investigation of peak, offpeak and shoulder season winery tourists in Canada’s Niagara region. The goal of the study reported here is to better understand the off -peak winery tourist ‐ that strange creature who chooses to visit a winery in the dead of Canadian winter. Who are these people?
Two divergently transcribed genes of Dictyostelium discoideum are cyclic AMP-inducible and coregulated during development. (1987)

The cysteine proteinase 1 (CP1) gene of Dictyostelium discoideum encodes a developmentally regulated sulfhydryl proteinase. We characterized the DNA sequences upstream of the CP1 gene and found a second developmentally regulated gene, which we term DG17. The translational open reading frame of the DG17 gene encoded a 458-amino-acid cysteine- and lysine-rich protein of unknown function. In several regions, the cysteine and lysine residues were arranged in a manner characteristic of the zinc-binding domains found in proteins which interact with nucleic acids. During normal development, the DG17 and CP1 genes are coordinately activated late in aggregation. The addition of exogenous cyclic AMP (cAMP) induced the premature expression of both mRNAs. By measuring the rate of specific mRNA synthesis in isolated nuclei, we showed that cAMP acted at the transcriptional level to activate both genes. The two genes were separated by 910 nucleotides and were divergently transcribed. The intergenic region was predominantly composed of A + T residues except for four short G-rich regions. These sequences coincided with the positions of four nuclease-hypersensitive sites, which appear during aggregation when the DG17 and CP1 genes are transcribed (J. Pavlovic, E. Banz, and R. W. Parish, Nucleic Acids Res. 14:8703-8722, 1986). Two of the G-rich regions formed the core of two almost identical 80-nucleotide repeats located 220 and 320 nucleotides upstream of the CP1 gene. Using the Dictyostelium transformation system, we showed that a restriction fragment containing the intergenic region was capable of directing bidirectional transcription in a cAMP-dependent manner.
Genome-Wide Experimental Determination of Barriers to Horizontal Gene Transfer (2007)

Horizontal gene transfer, in which genetic material is transferred from the genome of one organism to that of another, has been investigated in microbial species mainly through computational sequence analyses. To address the lack of experimental data, we studied the attempted movement of 246,045 genes from 79 prokaryotic genomes into Escherichia coli and identified genes that consistently fail to transfer. We studied the mechanisms underlying transfer inhibition by placing coding regions from different species under the control of inducible promoters. Our data suggest that toxicity to the host inhibited transfer regardless of the species of origin and that increased gene dosage and associated increased expression may be a predominant cause for transfer failure. Although these experimental studies examined transfer solely into E. coli, a computational analysis of gene-transfer rates across available bacterial and archaeal genomes supports that the barriers observed in our study are general across the tree of life.
c-erbB-2 sensing using AlGaN∕GaN high electron mobility transistors for breast cancer detection (2008)

Antibody-functionalized, Au-gated AlGaN∕GaN high electron mobility transistors (HEMTs) were used to detect c-erbB-2, which is a breast cancer marker. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN∕GaN HEMT drain-source current showed a rapid response of less than 5s when target c-erbB-2 antigen in a buffer at clinically relevant concentrations was added to the antibody-immobilized surface. We could detect a range of concentrations from 16.7to0.25μg∕ml. These results clearly demonstrate the promise of portable electronic biological sensors based on AlGaN∕GaN HEMTs for breast cancer screening.
A microstructure for interfacing with neurons: the neurochip (2002)

A new type of multielectrode array for studies of cultured neural networks is described. It is a silicon microstructure, a "neurochip", which embodies wells on the surface of a chip that are designed to contain single neurons. Each well has a platinized gold electrode which can be used for stimulating a neuron in the well or for recording from it. Each well is covered with a structure which provides tunnels through which axons and dendrites can grow out and a central hole through which the neurons can be loaded into the well. The processes thus trap the cells in the wells. The first application of this method is described: A4/spl times/4 array of wells spaced 100 /spl mu/m apart. Results are described which show long term survival and outgrowth of neurons from the wells, and the use of well electrodes to both record and stimulate electrical activity of individual neurons.
Prognostic significance of expression of CCL5/RANTES receptors in patients with gastric cancer (2008)

Tumor expression of CCR3 and/or CCR5 (receptors for CCL5) is associated with a lower survival rate in patients with gastric cancer.
Twelve-Month Health Care Use and Mortality in Commercially Insured Young People With Incident Psychosis in the United States (2017)

The hugely elevated mortality observed here underscores that young people experiencing psychosis warrant intensive clinical attention-yet we found low rates of pharmacotherapy and limited use of psychosocial treatment. These patterns reinforce the importance of providing coordinated, proactive treatment for young people with psychosis in US community settings.
Peroxiredoxin 4: a multifunctional biomarker worthy of further exploration (2011)

Currently, there is much interest in identifying clinically relevant biomarkers, as they have the potential to be high utility non-invasive tools for early diagnosis and reliable patient monitoring in numerous conditions. Since its discovery almost 15 years ago, research on the ubiquitous antioxidant enzyme peroxiredoxin 4 (Prx4) has culminated in the recognition that Prx4 levels are different in blood drawn from the healthy general population and patients with acute or chronic diseases. In this commentary, the most striking research data from different in vitro approaches, animal models and human observational studies are discussed collectively, highlighting the clinical importance of Prx4 as a multifunctional staging and prognosis biomarker. In this context, the oxidative state of patients may be reflected by intra- and extracellular Prx4 levels, redox state, oligomerization and nitro-oxidative modifications of the enzyme. A consolidated model of the potential role and origin of circulating Prx4 is presented to stimulate further investigations in light of the current biomarker situation.
Experimental therapy with tissue kallikrein against cerebral ischemia (2006)

Tissue kallikrein is a serine proteinase capable of cleaving kininogen substrate to produce the potent vasodilator kinin peptide. Kinin mediates a complex set of physiological actions through its receptor signaling. Systemic delivery of the kallikrein gene in an adenoviral vector significantly reduced stroke-induced mortality rate, blood pressure elevation, and aortic hypertrophy in hypertensive Dahl-salt sensitive rats fed a high salt diet. Using a focal cerebral ischemic rat model induced by middle cerebral artery occlusion, intravenous or intracerebroventricular kallikrein gene delivery significantly reduced ischemia/repefusion (I/R)-induced neurological deficits, cerebral infarction, neuronal and glial cell apoptosis, and inflammatory cell infiltration, while promoting angiogenesis and neurogenesis in the ischemic brain. A continuous infusion of a sub-depressor dose of tissue kallikrein protein through implanted minipump decreased I/R-induced neurological dysfunction and cerebral infarction, inflammation and oxidative stress independent of kallikrein's blood pressure-lowering effect. Moreover, kallikrein offered neuroprotection even when delivered at one day after the onset of stroke. Kallikrein's protective effects were blocked by the kinin B2 receptor antagonist icatibant. The role of the kinin B2 receptor in mediating the protective effect against ischemic brain injury was further confirmed by increases in mortality rate and post-ischemic brain injury in kinin B2 receptor-deficient mice. Taken together, these results suggest a novel function of kallikrein as an anti-inflammatory and anti-oxidative agent in protecting the brain against ischemic stroke-induced injuries. These findings also raise the possibility that tissue kallikrein may have value in the treatment of acute ischemic stroke.
Structural Determinants of Ion Flow Through Recombinant Glutamate Receptor Channels (1991)

Functional glutamate receptor (GluRs) were transiently expressed in cultured mammalian cells from cloned complementary DNAs encoding GluR-A, -B, -C, or -D polypeptides. The steady-state current-voltage (I-V) relations of glutamate- and kainate-induced currents through homomeric channels fell into two classes: channels composed of either the GluR-A, -C, and -D subunits showed doubly rectifying I-V curves, and channels composed of the GluR-B subunits displayed simple outward rectification. The presence of GluR-B subunits in heteromeric GluRs determined the I-V behavior of the resulting channels. Site-directed mutagenesis identified a single amino acid difference (glutamine to arginine) in the putative transmembrane segment TM2 responsible for subunit-specific I-V relationships. The properties of heteromeric wild-type and mutant GluRs revealed that the dominance of GluR-B is due to the arginine residue in the TM2 region.
The stages of disc degeneration as revealed by discograms (1986)

One hundred and thirty-nine discs from cadaveric lumbar spines were injected with a mixture of radio-opaque fluid and dye. Discograms were taken and the discs were then sectioned in the sagittal plane. Examination of the sections revealed that injected fluid did not at first mix with the disc matrix but pushed it aside to form pools of injected fluid. The location of these pools, and hence the appearance of a discogram, depended on the stage of degeneration of the disc. It is concluded that useful clinical information can be obtained from discograms.
Generating Vesicular Stomatitis Virus Pseudotype Bearing the Severe Acute Respiratory Syndrome Coronavirus Spike Envelope Glycoprotein for Rapid and Safe Neutralization Test or Cell‐Entry Assay (2006)

We generated a recombinant vesicular stomatitis virus (VSV) pseudotype (VSV Delta G*SG) by replacing the envelope G gene with the GFP gene and complementing with spike glycoprotein (S) of SARS-CoV in trans. The neutralization and infection blocking tests showed that the VSV Delta G*SG and SARS-CoV reacted similarly to SARS-CoV specific antiserum, suggesting the VSVDelta G*SG can be a safe replacement of the live SARS-CoV for neutralization test and cell-entry assay.
New theoretical analysis of the LRRM calibration technique for vector network analyzers (2001)

In this paper, a new theoretical analysis of the four-standards line-reflect-reflect-match (LRRM) vector network-analyzer (VNA) calibration technique is presented. As a result, it is shown that the reference-impedance (to which the LRRM calibration is referred) cannot generally be defined whenever nonideal standards are used. Based on this consideration, a new algorithm to determine the on-wafer match standard is proposed that improves the LRRM calibration accuracy. Experimental verification of the new theory and algorithm using on-wafer calibrations up to 40 GHz is given.
Small ischemic brain lesions after cardiac valve replacement detected by diffusion-weighted magnetic resonance imaging: relation to neurocognitive function☆ (2005)

Following cardiac valve replacement, new small ischemic brain lesions were detected by diffusion-weighted MRI. Neurocognitive decline was present early after operation, but resolved within 4 months. A correlation of new ischemic lesions to postoperative cognitive dysfunction or clinical variables was not found.