gebhart/patrepeval huggingface dataset:
Cell Therapy for Heart Failure (2013)

Despite significant therapeutic advances, the prognosis of patients with heart failure (HF) remains poor, and current therapeutic approaches are palliative in the sense that they do not address the underlying problem of the loss of cardiac tissue. Stem cell-based therapies have the potential to fundamentally transform the treatment of HF by achieving what would have been unthinkable only a few years ago-myocardial regeneration. For the first time since cardiac transplantation, a therapy is being developed to eliminate the underlying cause of HF, not just to achieve damage control. Since the initial report of cell therapy (skeletal myoblasts) in HF in 1998, research has proceeded at lightning speed, and numerous preclinical and clinical studies have been performed that support the ability of various stem cell populations to improve cardiac function and reduce infarct size in both ischemic and nonischemic cardiomyopathy. Nevertheless, we are still at the dawn of this therapeutic revolution. Many important issues (eg, mechanism(s) of action of stem cells, long-term engraftment, optimal cell type(s), and dose, route, and frequency of cell administration) remain to be resolved, and no cell therapy has been conclusively shown to be effective. The purpose of this article is to critically review the large body of work performed with respect to the use of stem/progenitor cells in HF, both at the experimental and clinical levels, and to discuss current controversies, unresolved issues, challenges, and future directions. The review focuses specifically on chronic HF; other settings (eg, acute myocardial infarction, refractory angina) are not discussed.
Thrombospondin-induced tumor cell migration: haptotaxis and chemotaxis are mediated by different molecular domains. (1987)

Thrombospondin induces the migration of human melanoma and carcinoma cells. Using a modified Boyden chamber assay, tumor cells migrated to a gradient of soluble thrombospondin (chemotaxis). Checkerboard analysis indicated that directional migration was induced 27-fold greater than stimulation of random motility. Tumor cells also migrated in a dose-dependent manner to a gradient of substratum-bound thrombospondin (haptotaxis). A series of human melanoma and carcinoma cells were compared for their relative motility stimulation by thrombospondin haptotaxis vs. chemotaxis. Some cell lines exhibited a stronger haptotactic response compared to their chemotactic response while other lines exhibited little or no migration response to thrombospondin. Human A2058 melanoma cells which exhibit a strong haptotactic and chemotactic response to thrombospondin were used to study the structural domains of thrombospondin required for the response. Monoclonal antibody C6.7, which binds to the COOH-terminal region of thrombospondin, inhibited haptotaxis in a dose-dependent optimal manner. C6.7 had no significant effect on thrombospondin chemotaxis. In contrast, monoclonal antibody A2.5, heparin, and fucoidan, which bind to the NH2-terminal heparin-binding domain of thrombospondin, inhibited thrombospondin chemotaxis but not haptotaxis. Monoclonal antibody A6.1 directed against the internal core region of thrombospondin had no significant effect on haptotaxis or chemotaxis. Synthetic peptides GRGDS (50 micrograms/ml), but not GRGES, blocked tumor cell haptotaxis on fibronectin, but had minimal effect on thrombospondin or laminin haptotaxis. The 140-kD fragment of thrombospondin lacking the heparin-binding amino-terminal region retained the property to fully mediate haptotaxis but not chemotaxis. When the COOH region of the 140-kD fragment, containing the C6.7-binding site, was cleaved off, the resulting 120-kD fragment (which retains the RGDA sequence) failed to induce haptotaxis. Separate structural domains of thrombospondin are therefore required for tumor cell haptotaxis vs. chemotaxis. This may have implications during hematogenous cancer metastases formation.
Mitochondrial and Nuclear Forms of Wnt13 Are Generated via Alternative Promoters, Alternative RNA Splicing, and Alternative Translation Start Sites (2006)

Wnt proteins play a key role in cell survival, cell proliferation, and cell fate during development. In endothelial cells, we identified the expression of Wnt13A, Wnt13B, and Wnt13C mRNAs, which are generated by alternative promoters and alternative RNA splicing. Wnt13A and Wnt13B proteins differ only in their N-terminal sequences. Wnt13A, a typical Wnt, is N-glycosylated and localized in the endoplasmic reticulum, with only a small fraction being secreted. Wnt13B proteins appear as a protein doublet, L-Wnt13B and S-Wnt13B, which are neither N-glycosylated nor secreted. Wnt13B proteins localized mainly to mitochondria, as demonstrated using detection in mitochondria enriched fractions and colocalization with Mitotracker and HSP60. A nuclear localization was also observed in 20% of Wnt13B-expressing cells. Both the N-terminal hydrophobic stretch (residues 1-17) and alpha-helix (residues 26-50) were the main determinants for Wnt13B mitochondrial targeting. Serial deletions of Wnt13B N-terminal sequences abolished its association with mitochondria and favored instead a nuclear localization. The production of S-Wnt13B was independent of the mitochondrial targeting but dependent on an alternative translation start corresponding to Met(74) in L-Wnt13B. The same translation start is used in Wnt13C mRNA to encode a protein undistinguishable from S-Wnt13B. S-Wnt13B when expressed alone localized to the nucleus like Wnt13C, whereas L-Wnt13B localized to mitochondria. Wnt13 nuclear forms increased the beta-catenin/T-cell factor activity in HEK293 cells and increased apoptosis in bovine aortic endothelial cells. Altogether our results demonstrate that, in addition to alternative promoters and RNA splicing, an alternative translation start in Wnt13B and Wnt13C mRNAs increases the complexity of both human wnt13 expression and functions.
Non‐motor parkinsonian pathology in aging A53T α‐Synuclein mice is associated with progressive synucleinopathy and altered enzymatic function (2013)

Aging, the main risk factor for Parkinson's disease (PD), is associated with increased α-synuclein levels in substantia nigra pars compacta (SNc). Excess α-synuclein spurs Lewy-like pathology and dysregulates the activity of protein phosphatase 2A (PP2A). PP2A dephosphorylates many neuroproteins, including the catecholamine rate-limiting enzyme, tyrosine hydroxylase (TH). A loss of nigral dopaminergic neurons induces PD movement problems, but before those abnormalities occur, behaviors such as olfactory loss, anxiety, and constipation often manifest. Identifying mouse models with early PD behavioral changes could provide a model in which to test emerging therapeutic compounds. To this end, we evaluated mice expressing A53T mutant human (A53T) α-synuclein for behavior and α-synuclein pathology in olfactory bulb, adrenal gland, and gut. Aging A53T mice exhibited olfactory loss and anxiety that paralleled olfactory and adrenal α-synuclein aggregation. PP2A activity was also diminished in olfactory and adrenal tissues harboring insoluble α-synuclein. Low adrenal PP2A activity co-occurred with TH hyperactivity, making this the first study to link adrenal synucleinopathy to anxiety and catecholamine dysregulation. Aggregated A53T α-synuclein recombinant protein also had impaired stimulatory effects on soluble recombinant PP2A. Collectively, the data identify an excellent model in which to screen compounds for their ability to block the spread of α-synuclein pathology associated with pre-motor stages of PD.
High performance 300mm backside illumination technology for continuous pixel shrinkage (2011)

Backside Illumination (BSI) sensor with excellent optical performance has become the main-stream CMOS image sensor process. This work addressed the key factors and issues for 300mm BSI technology, including wafer distortion, silicon thickness variation, backside junction formation and dielectric film structure, thermal annealing and so on. It is demonstrated that with the optimized key process, a high performance 0.9um BSI pixel with low noise can be fabricated.
Kinetic Studies of Carboxypeptidase Y<subtitle>I. Kinetic Parameters for the Hydrolysis of Synthetic Substrates<xref ref-type="fn" rid="fn1"><sup>1</sup></xref></subtitle> (1975)

Kinetic parameters for carboxypeptidase Y [EC 3.4.12.1], characterized as a nonspecific enzyme, are given for the hydrolysis of a series of acylated peptides, acylated amino acid esters, and amides. We confirmed that the enzyme released COOH-terminal proline and beta-alanine at an appreciable rate, as well as neutral amino acids with aromatic and aliphatic side chains at a very high speed. The rates of hydrolysis of ester and amide substrates were compatible with those produced by chymotrypsin [EC 3.4.21.1]. Stereospecificity was also demonstrated by the failure to hydrolyze peptide, ester, amide, and anilide substrates containing a D-amino acid. The effects of pH, solvents, and salt concentrations on the kinetic parameters of hydrolysis of peptide and ester substrates are also described.
Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax® (2007)

A single administration of VM is capable of inducing an effective CTL response to multiple tumor-associated antigens. The responses generated were able to reject 6-day old B16-F10 tumors.
Improving the Adversarial Robustness and Interpretability of Deep Neural Networks by Regularizing Their Input Gradients (2018)

Deep neural networks have proven remarkably effective at solving many classification problems, but have been criticized recently for two major weaknesses: the reasons behind their predictions are uninterpretable, and the predictions themselves can often be fooled by small adversarial perturbations. These problems pose major obstacles for the adoption of neural networks in domains that require security or transparency. In this work, we evaluate the effectiveness of defenses that differentiably penalize the degree to which small changes in inputs can alter model predictions. Across multiple attacks, architectures, defenses, and datasets, we find that neural networks trained with this input gradient regularization exhibit robustness to transferred adversarial examples generated to fool all of the other models. We also find that adversarial examples generated to fool gradient-regularized models fool all other models equally well, and actually lead to more "legitimate," interpretable misclassifications as rated by people (which we confirm in a human subject experiment). Finally, we demonstrate that regularizing input gradients makes them more naturally interpretable as rationales for model predictions. We conclude by discussing this relationship between interpretability and robustness in deep neural networks.
Migraine practice patterns among neurologists (2004)

Educational initiatives aiming to increase the awareness of the Guidelines among neurologists should highlight the full range of migraine symptoms that support the diagnosis, appropriate use of neuroimaging, indications for preventive treatments, issues of triptan cardiovascular safety, and preventing rebound headaches.
A Multicenter Study of the Efficacy and Safety of Sustained Release GH in the Treatment of Naive Pediatric Patients with GH Deficiency (2001)

Treatment of naive children with GH deficiency has relied upon long-term replacement therapy with daily injections of GH. The daily schedule may be inconvenient for patients and their caregivers, possibly promoting nonadherence with the treatment regimen or premature termination of treatment. We studied a new sustained release GH formulation, administered once or twice monthly, to determine its efficacy and safety in this population. Seventy-four prepubertal patients with documented GH deficiency were randomized to receive sustained release recombinant human GH at either 1.5 mg/kg once monthly or 0.75 mg/kg twice monthly by sc injection in a 6-month open-label study. Efficacy was determined by growth data from 69 patients completing 6 months and 56 patients completing 12 months in an extension study. Growth rates were significantly increased over baseline and were similar for the two dosage groups. The mean (+/-SD) annualized growth rate (pooled data) was 8.4 +/- 2.1 cm/yr at 6 months, and the growth rate was 7.8 +/- 1.8 at 12 months compared with 4.5 +/- 2.3 at baseline. Standardized height, bone age, and predicted adult height assessments demonstrated catch-up growth without excessive skeletal maturation. Injection site-related events (including pain, erythema, and nodules) were the most commonly reported adverse events; no serious adverse events related to treatment were reported. Laboratory studies documented no accumulation of trough GH or IGF-I levels during treatment, nor did glucose intolerance or persistent hyperinsulinism develop. Sustained release recombinant human GH is safe and effective for long-term GH replacement in children with GH deficiency. Patients achieved similar growth velocities when sustained release GH was given once or twice monthly. The enhanced convenience of this dosage form may result in greater long-term adherence to the treatment regimen.
Interplay of Fiber Non-Linearity and Optical Filtering in Ultra-Dense WDM (2002)

An experimental study is presented on the interaction between optical filtering and self-phase modulation induced spectral broadening and distortion in 25 and 50 GHz channel spacing WDM transmission with 10 Gb/s bit rate per channel.
Culture-Dependent and Culture-Independent Characterization of Microbial Assemblages Associated with High-Temperature Petroleum Reservoirs (2000)

Recent investigations of oil reservoirs in a variety of locales have indicated that these habitats may harbor active thermophilic prokaryotic assemblages. In this study, we used both molecular and culture-based methods to characterize prokaryotic consortia associated with high-temperature, sulfur-rich oil reservoirs in California. Enrichment cultures designed for anaerobic thermophiles, both autotrophic and heterotrophic, were successful at temperatures ranging from 60 to 90 degrees C. Heterotrophic enrichments from all sites yielded sheathed rods (Thermotogales), pleomorphic rods resembling Thermoanaerobacter, and Thermococcus-like isolates. The predominant autotrophic microorganisms recovered from inorganic enrichments using H(2), acetate, and CO(2) as energy and carbon sources were methanogens, including isolates closely related to Methanobacterium, Methanococcus, and Methanoculleus species. Two 16S rRNA gene (rDNA) libraries were generated from total community DNA collected from production wellheads, using either archaeal or universal oligonucleotide primer sets. Sequence analysis of the universal library indicated that a large percentage of clones were highly similar to known bacterial and archaeal isolates recovered from similar habitats. Represented genera in rDNA clone libraries included Thermoanaerobacter, Thermococcus, Desulfothiovibrio, Aminobacterium, Acidaminococcus, Pseudomonas, Halomonas, Acinetobacter, Sphingomonas, Methylobacterium, and Desulfomicrobium. The archaeal library was dominated by methanogen-like rDNAs, with a lower percentage of clones belonging to the Thermococcales. Our results strongly support the hypothesis that sulfur-utilizing and methane-producing thermophilic microorganisms have a widespread distribution in oil reservoirs and the potential to actively participate in the biogeochemical transformation of carbon, hydrogen, and sulfur in situ.
The Insulin/Akt Signaling Pathway Is Targeted by Intracellular β-Amyloid (2009)

Intraneuronal beta-amyloid (Abeta(i)) accumulates early in Alzheimer's disease (AD) and inclusion body myositis. Several organelles, receptor molecules, homeostatic processes, and signal transduction components have been identified as sensitive to Abeta. Although prior studies implicate the insulin-PI3K-Akt signaling cascade, a specific step within this or any essential metabolic or survival pathway has not emerged as a molecular target. We tested the effect of Abeta42 on each component of this cascade. In AD brain, the association between PDK and Akt, phospho-Akt levels and its activity were all decreased relative to control. In cell culture, Abeta(i) expression inhibited both insulin-induced Akt phosphorylation and activity. In vitro experiments identified that beta-amyloid (Abeta), especially oligomer preparations, specifically interrupted the PDK-dependent activation of Akt. Abeta(i) also blocked the association between PDK and Akt in cell-based and in vitro experiments. Importantly, Abeta did not interrupt Akt or PI3K activities (once stimulated) nor did it affect more proximal signal events. These results offer a novel therapeutic strategy to neutralize Abeta-induced energy failure and neuronal death.
<title>Robust photopolymers for MCM, board, and backplane optical interconnects</title> (1998)

A robust polymeric waveguide technology is proposed for affordable optoelectronic interconnects in massively parallel processing applications. We have developed high-performance organic polymeric materials that can be readily made into both multimode and single-mode optical waveguide structures of controlled numerical aperture and geometry. These materials are formed from highly-crosslinked acrylate monomers with specific linkages that determine properties such as flexibility, toughness, loss, and stability against yellowing. These monomers are intermiscible, providing for precise adjustment of the refractive index from 1.30 to 1.60. Waveguides are formed lithographically, with the liquid monomer mixture polymerizing upon illumination in the UV via either mask exposure or laser direct-writing. A wide range of rigid and flexible substrates can be used, including glass, quartz, oxidized silicon, glass-filled epoxy printed circuit board substrate, and flexible polyimide film. Our waveguides are low loss (0.02 dB/cm at 840 nm) as well as temperature resistant (over 65 years at 100 degree(s)C) and humidity resistant (no effect on unpackaged guides after 600 hours at 85 degree(s)C 85% RH), enabling use in a variety of demanding applications. We discuss the use of these materials on multi-chip modules, boards, and backplanes. Waveguiding structures measuring tens of inches in length can be produced on backplanes, and guides that are meters long can be laser-written on rolls of plastic. We also discuss the fabrication of symmetrically-clad flexible strips of waveguide arrays that are compatible with MT- type connectors.
Identification of thiols and glutathione conjugates of depsipeptide FK228 (FR901228), a novel histone protein deacetylase inhibitor, in the blood (2003)

Four glutathione (GSH) conjugates and two thiols were detected when depsipeptide FK228, formerly FR901228, a naturally occurring potent histone deacetylase (HDAC) inhibitor, was incubated in rat or human plasma in the presence of GSH. Their structures were elucidated by the high-performance liquid chromatography/electrospray ionization multi-stage mass spectrometry (HPLC/ESI-MS(n)) technique, and in some cases confirmed by accurate mass measurement. These products were also detected in rat and human blood homogenates following their incubation with FK228, but were not detected in GSH solution alone. A possible scheme for its formation is proposed. One of the thiols has recently been found to be more active as a histone deacetylase inhibitor than the parent compound.
Possible association between statin use and bowel dysmotility: Table 1 (2012)

3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are a class of drug that has been proven to be effective in lowering serum lipid levels. Although generally well-tolerated side effects from this class of drug have been noted to include liver dysfunction, renal failure and myopathy. Statins are also known to effect nitric oxide levels through upregulation of nitric oxide synthase. There is some evidence to imply that nitric oxide acts on inhibitory nerves in the colon to produce impaired motility. The authors present a case of recurrent colonic dilatation and volvulus which was initially treated with a sigmoid colectomy. Unfortunately symptoms persisted and a trial of the omission of statins was undertaken resulting in symptomatic relief. Following admission into hospital, statins were inadvertently restarted which caused the symptoms to reoccur. The statin was discontinued and upon review several months later the patient reported symptomatic benefit.
BCL6 Is Required for Differentiation of Ig-Like Transcript 3-Fc–Induced CD8+ T Suppressor Cells (2010)

Ig-like transcript 3 (ILT3) is an inhibitory receptor expressed by tolerogenic dendritic cells. When human CD8(+) T cells are allostimulated in the presence of recombinant ILT3-Fc protein, they differentiate into antigenic specific T suppressor (Ts) cells that inhibit CD4 and CD8 T cell effector function both in vitro and in vivo. ILT3-Fc-induced CD8(+) Ts cells express high amounts of BCL6 that are crucial to their function. Knockdown of BCL6 from unprimed human T cells prevents their differentiation into Ts cells, whereas ex vivo overexpression of BCL6 converts CD8(+) T cells into Ts cells. NOD/SCID mice transplanted with human pancreatic islets and humanized by injection of human PBMCs tolerate the graft and develop BCL6(high) CD8(+) Ts cells when treated with ILT3-Fc before or after the onset of rejection. This indicates that ILT3-Fc acts through BCL6 and is a potent immunosuppressive agent for reversing the onset of allo- or possibly autoimmune attacks against pancreatic islets.
Bridged Triarylamines:  A New Class of Heterohelicenes (2003)

A series of bridged triarylamines, which constitute a new class of heterohelicenes, have been synthesized using a simple three-step procedure. These compounds are shown to be highly luminescent chromophores and are capable of being oxidized. The solid-state structures of these helicenes show a tendency for pi-stacking interactions into an overall zigzag motif.
Effect of Renal Nerve Stimulation on Renal Blood Flow Autoregulation and Antinatriuresis During Reductions in Renal Perfusion Pressure (1981)

Renal nerve stimulation increases renal vascular resistance and decreases glomerular filtration rate and urinary sodium excretion. The purpose of this study was to determine whether neurally mediated changes in renal vascular resistance, glomerular filtration rate, and urinary sodium excretion at control renal perfusion pressure modified the autoregulation of renal blood flow and glomerular filtration rate and the antinatriuresis observed during reductions in renal perfusion pressure in pentobarbital-anesthetized dogs. Renal blood flow, glomerular filtration rate, and urinary sodium excretion were determined during stepwise reductions in renal perfusion pressure from 137 to 55 mm Hg (suprarenal aortic constriction) before and during electrical stimulation of the renal nerve at 0.5, 1.0, 2.0, and 4.0 Hz. In the absence of renal nerve stimulation, renal blood flow and glomerular filtration rate remained constant until renal perfusion pressure was reduced to 70 and 85 mm Hg, respectively. Urinary sodium excretion decreased linearly as renal perfusion pressure decreased. Renal nerve stimulation at 0.5, 1.0, 2.0, and 4.0 Hz increased renal vascular resistance and decreased glomerular filtration rate and urinary sodium excretion. These frequencies of renal nerve stimulation, however, did not alter the decreases in renal vascular resistance and glomerular filtration rate or the antinatriuretic response to stepwise reductions in renal perfusion pressure to 55 mm Hg. These data demonstrate that increased renal vascular resistance at either the afferent or efferent arteriole does not change the responses of these vessels to reductions in renal perfusion pressure. Renal nerve stimulation at frequencies which decrease urinary sodium excretion at control renal perfusion pressure also does not enhance the antinatriuretic response to reductions in renal perfusion pressure.