gebhart/patrepeval huggingface dataset:
Phase II trial of 5-FU administered Ip to patients with refractory ovarian cancer. (1984)

A phase II study of ip 5-FU was performed in 14 patients with ovarian cancer who were refractory to systemic chemotherapy including prior iv 5-FU in 12 of the patients. 5-FU was administered via a semipermanent Tenckhoff peritoneal dialysis catheter. The starting concentration of 5-FU in the dialysate was 4 mM. The patients received eight consecutive 2-L exchanges, each of 4-hour duration, for a total of 36 hours including time for instillation and drainage. Treatment courses were repeated every 2 weeks for six cycles or until disease progression occurred. A total of 69 cycles of ip 5-FU were administered to 14 patients. There was one complete response to therapy documented by second-look laparotomy. While the response rate was only 7%, in seven of eight (88%) patients with small volume disease (tumor masses less than 2.0 cm in diameter), there was no evidence for disease progression while receiving ip 5-FU therapy. In this phase II trial, the major toxic effect of ip 5-FU was abdominal pain. While there were no cases of documented bacterial peritonitis, all of the patients experienced some degree of abdominal discomfort while receiving therapy. Fifty percent of the patients had severe abdominal pain with at least one cycle of therapy. Other toxic effects included myelosuppression, mucositis, nausea and vomiting, and skin rash. The results of this study indicate that ip 5-FU should be further evaluated in patients with ovarian cancer who have a small volume of disease and who have not had prior therapy with 5-FU.
The PI3K-Akt-mTOR pathway regulates Aβ oligomer induced neuronal cell cycle events (2009)

Accumulating evidence suggests that neurons prone to degeneration in Alzheimer's Disease (AD) exhibit evidence of re-entry into an aberrant mitotic cell cycle. Our laboratory recently demonstrated that, in a genomic amyloid precursor protein (APP) mouse model of AD (R1.40), neuronal cell cycle events (CCEs) occur in the absence of beta-amyloid (Abeta) deposition and are still dependent upon the amyloidogenic processing of the amyloid precursor protein (APP). These data suggested that soluble Abeta species might play a direct role in the induction of neuronal CCEs. Here, we show that exposure of non-transgenic primary cortical neurons to Abeta oligomers, but not monomers or fibrils, results in the retraction of neuronal processes, and induction of CCEs in a concentration dependent manner. Retraction of neuronal processes correlated with the induction of CCEs and the Abeta monomer or Abeta fibrils showed only minimal effects. In addition, we provide evidence that induction of neuronal CCEs are autonomous to primary neurons cultured from the R1.40 mice. Finally, our results also demonstrate that Abeta oligomer treated neurons exhibit elevated levels of activated Akt and mTOR (mammalian Target Of Rapamycin) and that PI3K, Akt or mTOR inhibitors blocked Abeta oligomer-induced neuronal CCEs. Taken together, these results demonstrate that Abeta oligomer-based induction of neuronal CCEs involve the PI3K-Akt-mTOR pathway.
Triazolo[4,5-d]pyrimidine Derivatives as Inhibitors of GCN2 (2014)

ADVERTISEMENT RETURN TO ISSUEPREVPatent HighlightNEXTTriazolo[4,5-d]pyrimidine Derivatives as Inhibitors of GCN2Jean-Francois Brazeau† and Gerard Rosse*†‡View Author Information† Structure Guided Chemistry, Dart Neuroscience LLC, 7473 Lusk Boulevard, San Diego, California 92121, United States‡ Adjunct Associate Professor, Department of Pharmacology and Physiology, College of Medicine, Drexel University, New College Building, 245 North 15th Street, Philadelphia, Pennsylvania 19102, United States*E-mail: [email protected]Cite this: ACS Med. Chem. Lett. 2014, 5, 4, 282–283Publication Date (Web):February 12, 2014Publication History Received31 January 2014Published online12 February 2014Published inissue 10 April 2014https://pubs.acs.org/doi/10.1021/ml500052fhttps://doi.org/10.1021/ml500052feditorialACS PublicationsCopyright © 2014 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views3198Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (218 KB) Get e-AlertscloseSUBJECTS:Assays,Cancer,Inhibitors,Peptides and proteins,Reaction products Get e-Alerts
Characterization of cspB, a Bacillus subtilis inducible cold shock gene affecting cell viability at low temperatures (1992)

A new class of cold shock-induced proteins that may be involved in an adaptive process required for cell viability at low temperatures or may function as antifreeze proteins in Escherichia coli and Saccharomyces cerevisiae has been identified. We purified a small Bacillus subtilis cold shock protein (CspB) and determined its amino-terminal sequence. By using mixed degenerate oligonucleotides, the corresponding gene (cspB) was cloned on two overlapping fragments of 5 and 6 kb. The gene encodes an acidic 67-amino-acid protein (pI 4.31) with a predicted molecular mass of 7,365 Da. Nucleotide and deduced amino acid sequence comparisons revealed 61% identity to the major cold shock protein of E. coli and 43% identity to a family of eukaryotic DNA binding proteins. Northern RNA blot and primer extension studies indicated the presence of one cspB transcript that was initiated 119 bp upstream of the initiation codon and was found to be induced severalfold when exponentially growing B. subtilis cell cultures were transferred from 37 degrees C to 10 degrees C. Consistent with this cold shock induction of cspB mRNA, a six- to eightfold induction of a cspB-directed beta-galactosidase synthesis was observed upon downshift in temperature. To investigate the function of CspB, we inactivated the cold shock protein by replacing the cspB gene in the B. subtilis chromosome with a cat-interrupted copy (cspB::cat) by marker replacement recombination. The viability of cells of this mutant strain, GW1, at freezing temperatures was strongly affected. However, the effect of having no CspB in GW1 could be slightly compensated for when cells were preincubated at 10 degrees C before freezing. These results indicate that CspB belongs to a new type of stress-inducible proteins that might be able to protect B. subtilis cells from damage caused by ice crystal formation during freezing.
Ultrathin Films of Single‐Walled Carbon Nanotubes for Electronics and Sensors: A Review of Fundamental and Applied Aspects (2008)

Abstract Ultrathin films of single‐walled carbon nanotubes (SWNTs) represent an attractive, emerging class of material, with properties that can approach the exceptional electrical, mechanical, and optical characteristics of individual SWNTs, in a format that, unlike isolated tubes, is readily suitable for scalable integration into devices. These features suggest the potential for realistic applications as conducting or semiconducting layers in diverse types of electronic, optoelectronic and sensor systems. This article reviews recent advances in assembly techniques for forming such films, modeling and experimental work that reveals their collective properties, and engineering aspects of implementation in sensors and in electronic devices and circuits with various levels of complexity. A concluding discussion provides some perspectives on possibilities for future work in fundamental and applied aspects.
Effect of Penetration Enhancers on the Transdermal Delivery of Bupranolol Through Rat Skin (2005)

Bupranolol (BPL) is a suitable drug candidate for transdermal drug delivery system development based on its favorable physicochemical and pharmacokinetic properties. The effect of different penetration enhancers on the permeation of BPL across rat skin was studied using side-by-side diffusion cells. 2-Pyrrolidone (PY), 1-methyl-2-pyrrolidone (MPY), and propylene glycol (PG) at various concentrations were used as penetration enhancers along with 0.4% w/v aqueous suspension of BPL. Menthol at different concentrations in isopropanol-water (6:4) mixture also was used as an enhancer wherein BPL at 0.4% w/v was completely solubilized. Skin pretreatment studies were carried out with all the above enhancers to understand their role in the penetration enhancement effect. PY and MPY at 5% w/v concentrations increased the permeation of BPL by 3.8- and 2.4-fold, respectively, versus control (p < .01). PG at 10% and 30 w/v concentrations increased the flux of BPL by 2.5- and 5.0-fold, respectively, versus control (p < .001). Menthol at 2% w/v concentration increased the flux of BPL by 3.8-fold (p < .01) and further increase in menthol concentration significantly decreased the flux of BPL. Overall, pyrrolidones and menthol at low concentrations (5% w/v or less) and PG at 30% w/v concentration were effective as penetration enhancers for BPL.
Advances in the Management of Pediatric Asthma: A Review of Recent FDA Drug Approvals and Label Updates (2005)

Children have the highest prevalence of asthma of any age group. In the United States during 2001, there were 12.6 million physician and hospital outpatient visits for asthma treatment, of which almost 5 million involved children 18 years and younger. Therapeutic advances in pediatric asthma could improve patient outcomes and potentially reduce the burden on health care systems. Efforts to obtain efficacy and safety data in pediatric populations and develop pediatric formulations of asthma treatments have been encouraged by the FDA and clinicians. This article reviews the newest additions to asthma therapies approved for use in children, including an inhaled corticosteroid, some long-acting beta2-agonists, some leukotriene-receptor blockers, and a single-isomer, short-acting beta2-agonist.
Termination of transcription in bacteriophage lambda. Heterogeneous, 3'-terminal oligo-adenylate additions and the effects of rho factor. (1975)

RNA transcripts were synthesized in vitro from a lambda DNA template with purified Escherichia coli RNA polymerase either in the presence or absence of the protein termination factor, rho. The products were initially characterized by electrophoresis on polyacrylamide slab gels, and two of the lower molecular weight discrete species (6 S and 4 S RNA) were further characterized by standard two-dimensional "fingerprint" analysis. Production of the 4 S RNA was strongly affected by the presence of rho, whereas production of the 6 S RNA species was relatively unaffected by rho. 3'-Terminal oligonucleotide fragments were then selectively isolated on columns of dihydroxyboryl-substituted cellulose from these transcripts. Sequence analysis of these oligonucleotide products indicated: (a) that all of the transcripts examined possess similar degrees of 3'-terminal sequence heterogeneity which consisted predominantly of the addition of 1 to 5 adenylate residues to the 3'-terminus of the transcript; and (b) that rho factor-enhanced termination results in a definite structural change in the nucleotide sequence with which an RNA molecule can terminate.
PANIC-ATTAC: A Mouse Model for Inducible and Reversible β-Cell Ablation (2008)

The PANIC-ATTAC mouse may be used as an animal model of inducible and reversible beta-cell ablation and therefore has applications in many areas of diabetes research that include identification of beta-cell precursors, evaluation of glucotoxicity effects in diabetes, and examination of pharmacological interventions.
Isolation of an aminoglycoside hypersensitive mutant and its application in screening. (1986)

An aminoglycoside hypersensitive mutant, Kp-126, was isolated from the aminoglycoside-resistant strain, Kp-8, of Klebsiella pneumoniae through selection using sorbistin, a non-aminocyclitol-aminoglycoside antibiotic. The mutant Kp-126 was approximately 100-fold more sensitive to sorbistin than the parent strain Kp-8. The mutant also showed hypersensitivity to various aminocyclitol-aminoglycoside antibiotics. K. pneumoniae Kp-126 was used in screening and a new aminoglycoside antibiotic, 3,3'-neotrehalosadiamine (BMY-28251), was discovered in the fermentation broths of soil isolate strain of Bacillus pumilus.
Biosensors: the new wave in cancer diagnosis (2010)

The earlier cancer can be detected, the better the chance of a cure. Currently, many cancers are diagnosed only after they have metastasized throughout the body. Effective, accurate methods of cancer detection and clinical diagnosis are urgently needed. Biosensors are devices that are designed to detect a specific biological analyte by essentially converting a biological entity (ie, protein, DNA, RNA) into an electrical signal that can be detected and analyzed. The use of biosensors in cancer detection and monitoring holds vast potential. Biosensors can be designed to detect emerging cancer biomarkers and to determine drug effectiveness at various target sites. Biosensor technology has the potential to provide fast and accurate detection, reliable imaging of cancer cells, and monitoring of angiogenesis and cancer metastasis, and the ability to determine the effectiveness of anticancer chemotherapy agents. This review will briefly summarize the current obstacles to early detection of cancer and the expanding use of biosensors as a diagnostic tool, as well as some future applications of biosensor technology.
Observation of extremely long electron-spin-relaxation times inp-type δ-doped GaAs/AlxGa1−xAs double heterostructures (1993)

Spin-relaxation dynamics of electrons have been studied in p-type \ensuremath{\delta}-doped GaAs:Be/${\mathrm{Al}}_{\mathit{x}}$${\mathrm{Ga}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$As double heterostructures by time-resolved photoluminescence polarization measurements. A relaxation time of \ensuremath{\simeq}20 ns has been observed which is two orders of magnitude longer than that reported for corresponding acceptor concentrations in homogeneously doped GaAs. This enhancement, which arises from a drastic reduction of the electron-hole wave-function overlap, demonstrates that electron-hole scattering with a simultaneous exchange interaction dominates spin relaxation at low temperatures.
A Genome-Wide Study of Cytogenetic Changes in Colorectal Cancer Using SNP Microarrays: Opportunities for Future Personalized Treatment (2012)

In colorectal cancer (CRC), chromosomal instability (CIN) is typically studied using comparative-genomic hybridization (CGH) arrays. We studied paired (tumor and surrounding healthy) fresh frozen tissue from 86 CRC patients using Illumina's Infinium-based SNP array. This method allowed us to study CIN in CRC, with simultaneous analysis of copy number (CN) and B-allele frequency (BAF)--a representation of allelic composition. These data helped us to detect mono-allelic and bi-allelic amplifications/deletion, copy neutral loss of heterozygosity, and levels of mosaicism for mixed cell populations, some of which can not be assessed with other methods that do not measure BAF. We identified associations between CN abnormalities and different CRC phenotypes (histological diagnosis, location, tumor grade, stage, MSI and presence of lymph node metastasis). We showed commonalities between regions of CN change observed in CRC and the regions reported in previous studies of other solid cancers (e.g. amplifications of 20q, 13q, 8q, 5p and deletions of 18q, 17p and 8p). From Therapeutic Target Database, we identified relevant drugs, targeted to the genes located in these regions with CN changes, approved or in trials for other cancers and common diseases. These drugs may be considered for future therapeutic trials in CRC, based on personalized cytogenetic diagnosis. We also found many regions, harboring genes, which are not currently targeted by any relevant drugs that may be considered for future drug discovery studies. Our study shows the application of high density SNP arrays for cytogenetic study in CRC and its potential utility for personalized treatment.
Modulating the potency of an activator in a yeast in vitro transcription system. (1994)

The intrinsic stimulatory potential or potency of a eukaryotic gene activator is controlled by the interaction between the activation domain and the transcriptional machinery. To further understand this interaction, we undertook a biochemical study to identify parameters that could be used to modulate activator potency. We considered how varying the number of activation domains, their flexibility, and the number of promoter sites affects potency in a yeast nuclear extract. The effects of GAL4 derivatives bearing either one, two, or four herpes simplex virus VP16 activation domains (amino acids 413 to 454) were measured on DNA templates containing one or two GAL4 sites in a Saccharomyces cerevisiae nuclear extract. We found that multimerized VP16 activation domains acted synergistically to increase the potency of the activators. The spacing between the activation domains was critical, such that the increased flexibility imparted by a protein linker contributed to increased activator potency. With highly potent activators, the levels of transcription stimulated on a single site were saturating, whereas the stimulatory effect of weaker activators increased with the number of sites. We discuss how these biochemical studies relate to the mechanism of gene activation and synergy in a yeast in vitro system.
Why Did Tarenflurbil Fail in Alzheimer's Disease? (2009)

There has been a lot of disappointment surrounding the recent failure of the largest ever study in patients with Alzheimer's disease (AD) with tarenflurbil, a compound believed to modulate the activity of gamma-secretase, the pivotal enzyme that generates the amyloid-beta (A beta) peptide from the amyloid-beta protein precursor. What are the reasons for this setback after the previous apparently encouraging results in a Phase II study? A straightforward explanation of this failure is that the gamma-secretase is not the right target for therapy or that, in general, blocking A beta does not produce clinical benefits in AD. If one still accepts a physiopathological role of A beta in AD, tarenflurbil could not be the right compound because of its weak pharmacological activity as an A beta(1-42) lowering agent and its poor brain penetration. In addition, based on previous negative results with several anti-inflammatory drugs in AD, it is hypothesized that the residual anti-inflammatory activity of tarenflurbil may have a detrimental effect on disease progression.
Self-triggered Asynchronous Optical Sampling Terahertz Spectroscopy using a Bidirectional Mode-locked Fiber Laser (2018)

We report a self-triggered asynchronous optical sampling terahertz spectroscopy system based on a single bidirectional mode-locked fiber laser and plasmonics-enhanced photoconductive nanoantennas. The fiber laser generates two optical mutually coherent pulse trains with a stable repetition rate difference, enabling time-domain terahertz spectroscopy without using any mechanical delay line, stabilization electronics, or external trigger. The resolved terahertz spectra over a 0.1-2 THz frequency range and a 30-second measurement time show more than a 70-dB dynamic range, revealing water absorption lines matching the HITRAN database, through a light-weight and compact spectroscopy setup.
Selectivity of SSRIs: individualising patient care through rational treatment choices (2004)

Despite a common mode of action [inhibition of the 5-hydroxytryptamine (5-HT) neuronal reuptake transporter], proven antidepressant efficacy and a similar range of indications (depression and a variety of anxiety disorders), the unique secondary binding properties of each selective serotonin reuptake inhibitor (SSRI) account for clinically significant differences in tolerability and side-effect profiles, particularly in some patients. Secondary properties within the class of SSRIs include some combination of actions at noradrenergic, dopaminergic, muscarinic cholinergic, histaminergic and sigma receptors. In addition, most SSRIs inhibit at least one of the cytochrome P450 enzymes, resulting in potential pharmacokinetic interactions with co-prescribed drugs. Although secondary properties of SSRIs can be associated with side effects, sometimes these same actions can be harnessed to good therapeutic effect through rational, informed treatment choices. In this way, agents that more consistently cause central nervous system activation (such as fluoxetine and sertraline) can be used to boost energy in patients whose depression is accompanied by fatigue and apathy, while the anxiolytic, sedative properties of others (particularly paroxetine and fluvoxamine) can be beneficial in patients with insomnia and agitation. When secondary properties are experienced as undesirable side effects, agents with greater selectivity for the serotonin transporter and without significant secondary binding properties, such as citalopram and escitalopram, may be desirable. This article explains how an understanding of the secondary binding properties of the SSRIs can guide individualised treatment across the spectrum of depressive and anxious states.
C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice* (2009)

Our results show that post-traumatic administration of C1-INH attenuates neuro-behavioral deficits and histological damage associated with traumatic brain injury.
The planar light waveguide type optical amplifier fabricated by sputtering method (1999)

The planar light waveguide type optical amplifier was designed and fabricated. For the fabrication of optical amplifier, the core layer of Er-doped SiO/sub 2/ glass was deposited onto the silica cladding layer by the RF sputtering method with a deposition rate 55 /spl Aring//min. The average Er concentration of the deposited film was 0.77 wt%. Using an input signal power 20 dBm of a laser diode with 1546 nm wavelength, the gain of the optical amplifier was 5 dB with an incident pump power of 200 mW.
TCP fast open (2011)

Today's web services are dominated by TCP flows so short that they terminate a few round trips after handshaking; this handshake is a significant source of latency for such flows. In this paper we describe the design, implementation, and deployment of the TCP Fast Open protocol, a new mechanism that enables data exchange during TCP's initial handshake. In doing so, TCP Fast Open decreases application network latency by one full round-trip time, decreasing the delay experienced by such short TCP transfers.