gebhart/patrepeval huggingface dataset:
Dynamic pressure-flow relationships of brain blood flow in the monkey (1974)

✓ Pressure-flow data are presented for the brain vascular bed in the rhesus monkey. These data are obtained at fixed levels of vasomotor tone. Resultant flow curves are called the “dynamic pressure-flow relationships” (DPFR). In the experimental model, arterial pressures are oscillated with a sinusoidal pump at frequencies exceeding the vasomotor response lag time. The resultant DPFR curves are discussed. A model is presented to show that changes in vasomotor tone cause a vertical shift of the DPFR. Changes in vascular bed resistance cause a change in the slope of the DPFR (▵P/▵F).
Red hot [light emitting diodes] (2003)

Light-emitting diodes are ubiquitous in today's high-tech world. But no matter what their application or color, their origin can be traced to the red LED created in 1962 by Nick Holonyak Jr., the winner of this year's IEEE Medal of Honor. The article describes Holonyak's career and the work which produced the first LED, and shows how his influence permeates the industry today.
Structure of Cinaciguat (BAY 58–2667) Bound to Nostoc H-NOX Domain Reveals Insights into Heme-mimetic Activation of the Soluble Guanylyl Cyclase (2010)

Heme is a vital molecule for all life forms with heme being capable of assisting in catalysis, binding ligands, and undergoing redox changes. Heme-related dysfunction can lead to cardiovascular diseases with the oxidation of the heme of soluble guanylyl cyclase (sGC) critically implicated in some of these cardiovascular diseases. sGC, the main nitric oxide (NO) receptor, stimulates second messenger cGMP production, whereas reactive oxygen species are known to scavenge NO and oxidize/inactivate the heme leading to sGC degradation. This vulnerability of NO-heme signaling to oxidative stress led to the discovery of an NO-independent activator of sGC, cinaciguat (BAY 58-2667), which is a candidate drug in clinical trials to treat acute decompensated heart failure. Here, we present crystallographic and mutagenesis data that reveal the mode of action of BAY 58-2667. The 2.3-A resolution structure of BAY 58-2667 bound to a heme NO and oxygen binding domain (H-NOX) from Nostoc homologous to that of sGC reveals that the trifurcated BAY 58-2667 molecule has displaced the heme and acts as a heme mimetic. Carboxylate groups of BAY 58-2667 make interactions similar to the heme-propionate groups, whereas its hydrophobic phenyl ring linker folds up within the heme cavity in a planar-like fashion. BAY 58-2667 binding causes a rotation of the alphaF helix away from the heme pocket, as this helix is normally held in place via the inhibitory His(105)-heme covalent bond. The structure provides insights into how BAY 58-2667 binds and activates sGC to rescue heme-NO dysfunction in cardiovascular diseases.
Molecular components and assembly of mu.surrogate light chain complexes in pre-B cell lines. (1994)

We describe the molecular components, subunit assembly, and cell surface expression of mu-chain complexes in mu+kappa- pre-B cell lines as revealed by two-dimensional gel electrophoresis. The mu-chain complexes of these cell lines contain several previously unreported components, p42(6.4), p39(6.7), p18(8.6), and p14(7.0), in addition to lambda 5, VpreB1, VpreB3 (formerly named 8HS20), MB-1(Ig-alpha), and B29(Ig-beta). These new components are not detected in mu+kappa+ immature B cell lines. The mu-chain associates with lambda 5, VpreB3, and p56(5.0) at an early phase of assembly, preceding the association of other molecules. mu-Associated VpreB3 decreased during assembly as the association of VpreB1 became dominant, suggesting that the change in the ratio of these two VL-like surrogate light chains is involved in the mechanism of assembly. Lambda 5, VpreB1, p56(5.0), p32(5.0), p36(5.5), and p14(7.0) were shown to be expressed on the cell surface in association with mu-chain. The association of the other molecules with mu-chain is most likely restricted to the intracellular compartment. An interaction between VpreB1 and VpreB3 was also suggested. These findings might be important for understanding the function of mu-chain complexes in pre-B cells. A possible signaling mechanism of mu/surrogate light chain complexes is discussed.
SNAS: Stochastic Neural Architecture Search (2018)

We propose Stochastic Neural Architecture Search (SNAS), an economical end-to-end solution to Neural Architecture Search (NAS) that trains neural operation parameters and architecture distribution parameters in same round of back-propagation, while maintaining the completeness and differentiability of the NAS pipeline. In this work, NAS is reformulated as an optimization problem on parameters of a joint distribution for the search space in a cell. To leverage the gradient information in generic differentiable loss for architecture search, a novel search gradient is proposed. We prove that this search gradient optimizes the same objective as reinforcement-learning-based NAS, but assigns credits to structural decisions more efficiently. This credit assignment is further augmented with locally decomposable reward to enforce a resource-efficient constraint. In experiments on CIFAR-10, SNAS takes less epochs to find a cell architecture with state-of-the-art accuracy than non-differentiable evolution-based and reinforcement-learning-based NAS, which is also transferable to ImageNet. It is also shown that child networks of SNAS can maintain the validation accuracy in searching, with which attention-based NAS requires parameter retraining to compete, exhibiting potentials to stride towards efficient NAS on big datasets. We have released our implementation at https://github.com/SNAS-Series/SNAS-Series.
Drug targeting of a peptide radiopharmaceutical through the primate blood-brain barrier in vivo with a monoclonal antibody to the human insulin receptor. (1997)

Peptide radiopharmaceuticals are potential imaging agents for brain disorders, should these agents be enabled to undergo transport through the blood-brain barrier (BBB) in vivo. Radiolabeled Abeta1-40 images brain amyloid in tissue sections of Alzheimer's disease autopsy brain, but this peptide radiopharmaceutical cannot be used to image brain amyloid in vivo owing to negligible transport through the BBB. In these studies, 125I-Abeta1-40 was monobiotinylated (bio) and conjugated to a BBB drug delivery and brain targeting system comprised of a complex of the 83-14 monoclonal antibody (mAb) to the human insulin receptor, which is tagged with streptavidin (SA). A marked increase in rhesus monkey brain uptake of the 125I-bio-Abeta1-40 was observed after conjugation to the 8314-SA delivery system at 3 h after intravenous injection. In contrast, no measurable brain uptake of 125I-bio-Abeta1-40 was observed in the absence of a BBB drug delivery system. The peptide radiopharmaceutical was degraded in brain with export of the iodide radioactivity, and by 48 h after intravenous injection, 90% of the radioactivity was cleared from the brain. In conclusion, these studies describe a methodology for BBB drug delivery and brain targeting of peptide radiopharmaceuticals that could be used for imaging amyloid or other brain disorders.
Discriminative learning for differing training and test distributions (2007)

We address classification problems for which the training instances are governed by a distribution that is allowed to differ arbitrarily from the test distribution---problems also referred to as classification under covariate shift. We derive a solution that is purely discriminative: neither training nor test distribution are modeled explicitly. We formulate the general problem of learning under covariate shift as an integrated optimization problem. We derive a kernel logistic regression classifier for differing training and test distributions.
Tissue-type plasminogen activator promotes murine myofibroblast activation through LDL receptor–related protein 1–mediated integrin signaling (2007)

The activation of interstitial fibroblasts to become alpha-SMA-positive myofibroblasts is an essential step in the evolution of chronic kidney fibrosis, as myofibroblasts are responsible for the production and deposition of the ECM components that are a hallmark of the disease. Here we describe a signaling pathway that leads to this activation. Tissue-type plasminogen activator (tPA) promoted TGF-beta1-mediated alpha-SMA and type I collagen expression in rat kidney interstitial fibroblasts. This fibrogenic effect was independent of its protease activity but required its membrane receptor, the LDL receptor-related protein 1 (LRP-1). In rat kidney fibroblasts, tPA induced rapid LRP-1 tyrosine phosphorylation and enhanced beta1 integrin recruitment by facilitating the LRP-1/beta1 integrin complex formation. Blockade or knockdown of beta1 integrin abolished type I collagen and alpha-SMA expression. Furthermore, inhibition of the integrin-linked kinase (ILK), a downstream effector of beta1 integrin, or disruption of beta1 integrin/ILK engagement, abrogated the tPA action, whereas ectopic expression of ILK mimicked tPA in promoting myofibroblast activation. In murine renal interstitium after obstructive injury, tPA and alpha-SMA colocalized with LRP-1, and tPA deficiency reduced LRP-1/beta1 integrin interaction and myofibroblast activation. These findings show that tPA induces LRP-1 tyrosine phosphorylation, which in turn facilitates the LRP-1-mediated recruitment of beta1 integrin and downstream ILK signaling, thereby leading to myofibroblast activation. This study implicates tPA as a fibrogenic cytokine that promotes the progression of kidney fibrosis.
The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review (2020)

The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (<i>n</i> = 8 in glioblastoma and <i>n</i> = 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients.
The relationship between angiogenesis and cyclooxygenase‐2 expression in prostate cancer (2005)

These data suggest that COX-2 drives tumour spread in prostate cancer by means other than the promotion of angiogenesis.
The Efficiency of a DTPA-Based Solvent in the Dissolution of Barium Sulfate Scale Deposits (1995)

Abstract This paper describes kinetic experiments to determine the rate at which Ba ions are mobilized from crystalline barium sulfate into aqueous solution by a solvent in which the active ingredient is a strong chelating agent for Ba ions (DTPA - diethylene triamine pentaacetic acid). The experiments define the temperature dependence and hence the activation energy of the dissolution process, the surface area dependence and most importantly the dependence on the concentration of the DTPA in solution. In a 0.05M DTPA solution the dissolution rate of barium sulfate is highly temperature dependent with an activation energy of ~45kJ mol-1. This value suggests that the rate is controlled by the desorption of a Ba-DTPA surface complex. Surface complexation is further identified as the key to barium sulfate dissolution by the observation that over the concentration range 0.5M to 0.05M DTPA the initial dissolution rate is inversely related to the DTPA concentration. The activation energy remains unaltered but the absolute dissolution rate is increased. In other words, a 0.05M DTPA solution is more efficient as a solvent than a 0.5M solution. This unexpected result is interpreted in terms of a passivation of the barium sulfate surface by the formation of a surface complex layer at high DTPA concentrations.
Identification of a novel biomarker gene set with sensitivity and specificity for distinguishing between allograft rejection and tolerance#* (2011)

Here we examined whether the expression of a novel immunoregulatory gene set could be used to predict outcomes in murine models of rapamycin-induced cardiac tolerance, spontaneous hepatic tolerance, and cardiac rejection. The expression of the immunoregulatory gene set was assessed with the GeXP multiplex reverse-transcription polymerase chain reaction (RT-PCR) analysis system, and it was correlated to the pathological and biochemical parameters of the allografts. In rejecting cardiac grafts, the increased expression of an inflammatory set of genes, which included CD45, CD4, CD25, suppressor of cytokine signaling 2, cytotoxic T lymphocyte-associated protein 4 (CTLA4), selectin lymphocyte, interferon-γ (IFN-γ), programmed cell death 1 (Pdcd1), and granzyme B (Gzmb), was seen 8 days after transplantation along with histological evidence of severe allograft rejection. In tolerant cardiac allografts, the expression of fibrinogen-like protein 2 (Fgl2), Pdcd1, killer cell lectin-like receptor G1 (Klrg1), CTLA4, and lymphocyte-activation gene 3 was associated with tolerance. In a model of liver allograft tolerance, the increased expression of lectin galactose-binding soluble 1, Fgl2, CD39, phosphodiesterase 3B, Klrg1, forkhead box P3 (Foxp3), and transforming growth factor β as well as the inflammatory set of genes was observed 8 to 14 days after transplantation (ie, when there was severe inflammatory injury). At a later time when the liver allografts had been fully accepted and were histologically normal, the expression of the inflammatory set of genes returned to the baseline, but the expression of the tolerogenic set of genes was still increased. Genes that were expressed in tolerant cardiac and liver allografts included Fgl2, Klrg1, and Foxp3, whereas genes associated with rejection included CD25, Gzmb, and IFN-γ. Our data indicate that monitoring the graft expression of a novel biomarker gene set with the GeXP multiplex RT-PCR analysis system may allow differentiation between rejection and tolerance.
Antisense technologies (2003)

Antisense agents are valuable tools to inhibit the expression of a target gene in a sequence-specific manner, and may be used for functional genomics, target validation and therapeutic purposes. Three types of anti-mRNA strategies can be distinguished. Firstly, the use of single stranded antisense-oligonucleotides; secondly, the triggering of RNA cleavage through catalytically active oligonucleotides referred to as ribozymes; and thirdly, RNA interference induced by small interfering RNA molecules. Despite the seemingly simple idea to reduce translation by oligonucleotides complementary to an mRNA, several problems have to be overcome for successful application. Accessible sites of the target RNA for oligonucleotide binding have to be identified, antisense agents have to be protected against nucleolytic attack, and their cellular uptake and correct intracellular localization have to be achieved. Major disadvantages of commonly used phosphorothioate DNA oligonucleotides are their low affinity towards target RNA molecules and their toxic side-effects. Some of these problems have been solved in 'second generation' nucleotides with alkyl modifications at the 2' position of the ribose. In recent years valuable progress has been achieved through the development of novel chemically modified nucleotides with improved properties such as enhanced serum stability, higher target affinity and low toxicity. In addition, RNA-cleaving ribozymes and deoxyribozymes, and the use of 21-mer double-stranded RNA molecules for RNA interference applications in mammalian cells offer highly efficient strategies to suppress the expression of a specific gene.
?-sheet breaker peptide inhibitor of Alzheimer's amyloidogenesis with increased blood-brain barrier permeability and resistance to proteolytic degradation in plasma (1999)

Short synthetic peptides homologous to the central region of Abeta but bearing proline residues as beta-sheet blockers have been shown in vitro to bind to Abeta with high affinity, partially inhibit Abeta fibrillogenesis, and redissolve preformed fibrils. While short peptides have been used extensively as therapeutic drugs in medicine, two important problems associated with their use in central nervous system diseases have to be addressed: (a) rapid proteolytic degradation in plasma, and (b) poor blood-brain barrier (BBB) permeability. Recently, we have demonstrated that the covalent modification of proteins with the naturally occurring polyamines significantly increases their permeability at the BBB. We have extended this technology to iAbeta11, an 11-residue beta-sheet breaker peptide that inhibits Abeta fibrillogenesis, by covalently modifying this peptide with the polyamine, putrescine (PUT), and evaluating its plasma pharmacokinetics and BBB permeability. After a single intravenous bolus injection in rats, both 125I-YiAbeta11 and 125I-PUT-YiAbeta11 showed rapid degradation in plasma as determined by trichloroacetic acid (TCA) precipitation and paper chromatography. By switching to the all D-enantiomers of YiAbeta11 and PUT-YiAbeta11, significant protection from degradation by proteases in rat plasma was obtained with only 1.9% and 5.7% degradation at 15 min after intravenous bolus injection, respectively. The permeability coefficient x surface area product at the BBB was five- sevenfold higher in the cortex and hippocampus for the 125I-PUT-D-YiAbeta11 compared to the 125I-D-YiAbeta11, with no significant difference in the residual plasma volume. In vitro assays showed that PUT-D-YiAbeta11 retains its ability to partially inhibit Abeta fibrillogenesis and dissolve preformed amyloid fibrils. Because of its five- to sevenfold increase in permeability at the BBB and its resistance to proteolysis in the plasma, this polyamine-modified beta-sheet breaker peptide may prove to be an effective inhibitor of amyloidogenesis in vivo and, hence, an important therapy for Alzheimer's disease.
Serum neuron specific enolase – a novel indicator for neuropsychiatric systemic lupus erythematosus? (2015)

Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE.
The Management of Gout (1996)

We now have sufficient knowledge to be able to identify the factors contributing to hyperuricemia in most patients with gout. Some of these factors, such as obesity, a high-purine diet, regular alcohol consumption, and diuretic therapy, may be correctable. In patients with persistent hyperuricemia, regular medication should lower the serum urate concentration to an optimal level. The continuing challenge is to educate patients about correctable factors and the importance of regular medication and ensure their compliance so that attacks of gout do not recur.
Optimal Detection of Fetal Chromosomal Abnormalities by Massively Parallel DNA Sequencing of Cell-Free Fetal DNA from Maternal Blood (2011)

Massively parallel sequencing is capable of detecting multiple fetal chromosomal abnormalities from maternal plasma when an optimized algorithm is used.
Characterization of Hydrogenase from the Hyperthermophilic Archaebacterium, Pyrococcus furiosus (1989)

The archaebacterium, Pyrococcus furiosus, grows optimally at 100 degrees C by a fermentative type metabolism in which H2 and CO2 are the only detectable products. The organism also reduces elemental sulfur (S0) to H2S. Cells grown in the absence of S0 contain a single hydrogenase, located in the cytoplasm, which has been purified 350-fold to apparent homogeneity. The yield of H2 evolution activity from reduced methyl viologen at 80 degrees C was 40%. The hydrogenase has a Mr value of 185,000 +/- 15,000 and is composed of three subunits of Mr 46,000 (alpha), 27,000 (beta), and 24,000 (gamma). The enzyme contains 31 +/- 3 g atoms of iron, 24 +/- 4 g atoms of acid-labile sulfide, and 0.98 +/- 0.05 g atoms of nickel/185,000 g of protein. The H2-reduced hydrogenase exhibits an electron paramagnetic resonance (EPR) signal at 70 K typical of a single [2Fe-2S] cluster, while below 15 K, EPR absorption is observed from extremely fast relaxing iron-sulfur clusters. The oxidized enzyme is EPR silent. The hydrogenase is reversibly inhibited by O2 and is remarkably thermostable. Most of its H2 evolution activity is retained after a 1-h incubation at 100 degrees C. Reduced ferredoxin from P. furiosus also acts as an electron donor to the enzyme, and a 350-fold increase in the rate of H2 evolution is observed between 45 and 90 degrees C. The hydrogenase also catalyzes H2 oxidation with methyl viologen or methylene blue as the electron acceptor. The temperature optimum for both H2 oxidation and H2 evolution is greater than 95 degrees C. Arrhenius plots show two transition points at approximately 60 and approximately 80 degrees C independent of the mode of assay. That occurring at 80 degrees C is associated with a dramatic increase in H2 production activity. The enzyme preferentially catalyzes H2 production at all temperatures examined and appears to represent a new type of "evolution" hydrogenase.
CONCRETE REINFORCED WITH FIBROUS WIRE (1971)

THE PRESENT STATE OF KNOWLEDGE IN USING SMALL LENGTHS OF CHOPPED WIRE TO ENHANCE CERTAIN PROPERTIES OF CONCRETE IS SUMMARIZED. A SYSTEMATIC APPROACH TO MIX DESIGN AND MEASUREMENT OF THE ENSUING MATERIAL PROPERTIES IS NEEDED. IMPORTANT POINTS EMERGED: WIRE FIBER INCLUSION HAS A MARKED EFFECT ON WORKABILITY, THIN SECTIONS SHOW CONSIDERABLE STRENGTH IMPROVEMENTS, IMPROVEMENTS ARE NOTED IN IMPACT RESISTANCE AND THERMAL CONDUCTIVITY, AND STEEL FIBER INCLUSION INCREASES BOTH THE MATERIAL AND THE HANDLING COSTS OF THE CONCRETE. /AUTHOR/
Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo. (1989)

We have isolated a series of sublines of the hormone-dependent MCF-7 human breast cancer cell line after selection both in vivo and in vitro for growth in the presence of subphysiological concentrations of estrogens. These sublines represent a model system for study of the processes leading to hormonal autonomy. The cells form growing tumors in ovariectomized athymic nude mice in the absence of estrogen supplementation but retain some responsivity to estrogen as determined by stimulation of the rate of tumor growth in vivo and by induction of progesterone receptor. An ovarian-independent but hormone-responsive phenotype may occur early in the natural progression to hormone-independent and unresponsive growth in breast cancer. We observed no change in the affinity or decrease in the level of expression of estrogen receptors and progesterone receptors among the sublines and the parental cells. Epidermal growth factor receptors are not overexpressed in ovarian-independent cells. Thus, altered hormone receptor expression may be a late event in the acquisition of a hormone-independent and unresponsive phenotype. Sublines isolated by in vivo but not in vitro selection are more invasive than the parental cells both in vivo and across an artificial basement membrane in vitro. Thus, as yet unknown tumor-host interactions may be important in the development of an invasive phenotype. Furthermore, acquisition of the ovarian-independent and invasive phenotypes can occur independently.