gebhart/patrepeval huggingface dataset:
High-speed electrical signaling: overview and limitations (1998)

Advances in IC fabrication technology, coupled with aggressive circuit design, have led to exponential growth of IC speed and integration levels. For these improvements to benefit overall system performance, the communication bandwidth between systems and ICs must scale accordingly. Currently, communication links in various applications approach Gbps data rates. These applications include computer-to-peripheral connections, local area networks, memory buses, and multiprocessor interconnection networks. Designers are concerned that these links will soon reach the fundamental limits of electrical signaling. In this article, we examine the limitations of CMOS implementations of highspeed links and show that the links' performance should continue to scale with technology. To handle the interconnects' finite bandwidth, however requires more sophisticated signaling methods. CMOS circuits, typically slower than circuits implemented in nonmainstream technologies, are particularly attractive for common applications because of their lower cost. The overall system cost is further reduced when signaling components are implemented as macro cells, integrated on the same die with a microprocessor or signal processing block.
Clinical Studies with Oxiracetam in Patients with Dementia of Alzheimer Type and Multi-lnfarct Dementia of Mild to Moderate Degree (1992)

The cognitive and behavioral effects and the safety of oxiracetam therapy during a placebo-controlled trial and the relevant follow-up up to 1 year in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID) of mild to moderate degree were studied. Sixty male and female outpatients participated in the double-blind, placebo-controlled, parallel-group, randomized trial, comparing the effects of oxiracetam 800 mg b.i.d. and placebo during 90 days of treatment. At the end of therapy, statistical analysis evidenced significant improvements in the group receiving oxiracetam in respect to the placebo group on Mini Mental State Examination, Auditory Continuous Performance Test, Rey's 15 Words Test, Block Tapping Test, Mattis Word Fluency, Luria Alternating Series and Instrumental Activities of Daily Living. Afterwards, 29 of the 30 patients who received oxiracetam, participated in the open follow-up study, receiving 800 mg b.i.d. oxiracetam for a total standard period of 1 year. Statistical improvements in comparison to baseline were again found on the same tests of the first 90 days (except for Rey's 15 Words Test) and on the Memory item of the Inventory of Psychic and Somatic Complaints Elderly. During the late phase of the follow-up, statistically significant worsenings in comparison to baseline were observed on Digit Span Backward, Gibson's Spiral and some non-memory items of IPSC-E. Neither severe adverse events were observed during the whole study, nor changes in routine laboratory examinations. In conclusion, in the present population of patients with mild to moderate degree dementia, the safety of 1,600 mg/day of oxiracetam also up to 1 year of treatment was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)
Induced capacitance in the squid giant axon. Lipophilic ion displacement currents. (1983)

Voltage-clamped squid giant axons, perfused internally and externally with solutions containing 10(-5) M dipicrylamine (DpA-), show very large polarization currents (greater than or equal to 1 mA/cm2) in response to voltage steps. The induced polarization currents are shown in the frequency domain as a very large voltage-and frequency-dependent capacitance that can be fit by single Debye-type relaxations. In the time domain, the decay phase of the induced currents can be fit by single exponentials. The induced polarization currents can also be observed in the presence of large sodium and potassium currents. The presence of the DpA- molecules does not affect the resting potential of the axons, but the action potentials appear graded, with a much-reduced rate of rise. The data in the time domain as well as the frequency domain can be explained by a single-barrier model where the DpA- molecules translocate for an equivalent fraction of the electric field of 0.63, and the forward and backward rate constants are equal at -15 mV. When the induced polarization currents described here are added to the total ionic current expression given by Hodgkin and Huxley (1952), numerical solutions of the membrane action potential reproduce qualitatively our experimental data. Numerical solutions of the propagated action potential predict that large changes in the speed of conduction are possible when polarization currents are induced in the axonal membrane. We speculate that either naturally occurring substances or drugs could alter the cable properties of cells in a similar manner.
Expression of the Serratia marcescens lipoproteins gene in Escherichia coli (1981)

The lipoprotein gene (lpp) of Serratia marcescens was cloned in a lambda phage vector (K. Nakamura and M. Inouye, Proc. Natl. Acad. Sci. U.S.A. 77: 1369-1373, 1980). This lpp gene was recloned in plasmid vectors pBR322 and pSC101. When a lipoprotein-deficient (lpp) mutant of Escherichia coli was transformed with pBR322 carrying the S. marcescens lpp gene, cells became nonleaky for ribonuclease, resistant to ethylenediaminetetraacetic acid, and sensitive to globomycin. The lipoprotein was found exclusively in the outer membrane fraction. These results indicate that the S. marcescens lipoprotein was normally secreted across the cytoplasmic membrane, modified, and assembled in the E. coli outer membrane. The amount of the free-form lipoprotein produced in this system was three times higher than that produced in lpp + C. coli cells, whereas there was no difference in the amount of the bound-form lipoprotein. On the other hand, lpp E. coli cells which harbored pSC101 carrying the S. marcescens lpp gene produced only one-third of the free-form lipoprotein produced in lpp E. coli cells which harbored pSC101 carrying the E. coli lpp gene. One of the major factors causing this difference in efficiency of gene expression between the lpp genes of S. marcescens and E. coli appears to be a deletion mutation at the transcription termination region found in the cloned S. marcescens lpp gene. The functional half-life of the S. marcescens lpp messenger ribonucleic acid in E. coli was found to be found half that of the E. coli lpp messenger ribonucleic acid.
Ultra Wide Band radio in Distributed Wireless Networks (2006)

The material of this book chapter covers the topics presented within the corresponding IEEE ISCAS 2006 tutorial, and in particular it focuses on the following items: the UWB radio signal and its spectral characteristics, power issues and current standardization trends, multi user interference in impulse radio UWB networks, ranging and positioning with UWB, medium access control for UWB networks, location-aware UWB routing algorithms and metrics, and finally introducing cognitive principles in UWB networks
Role of the phosphoinositide 3‐kinase p110δ in generation of type 2 cytokine responses and allergic airway inflammation (2007)

Phosphoinositide 3-kinases (PI3K) regulate immune activation via their roles in signal transduction of multiple classes of receptors. Here, we examined the effect of genetic inactivation of the hemopoietic cell-restricted PI3K isoform p110delta on systemic cytokine and chemokine responses and allergic airway inflammation. We found that type 2 cytokine responses (IL-4, IL-5 and IL-13) are significantly decreased in p110delta mutants, whereas type 1 cytokine responses (IFN-gamma and CXCL10) were robust. Elevated IFN-gamma production during the primary response to ovalbumin (OVA) was associated with reduced production of the regulatory cytokine IL-10. IFN-gamma and IL-10 production normalized after secondary OVA immunization; however, type 2 cytokine production was persistently reduced. Type 2 cytokine-dependent airway inflammation elicited by intranasal challenge with OVA was dramatically reduced, with reduced levels of eosinophil recruitment and mucus production observed in the lungs. Induction of respiratory hyper-responsiveness to inhaled methacholine, a hallmark of asthma, was markedly attenuated in p110delta-inactivated mice. Adoptive transfer of OVA-primed splenocytes from normal but not p110delta-inactivated mice could induce airway eosinophilia in naive, airway-challenged recipient mice. These data demonstrate a novel functional role for p110delta signaling in induction of type 2 responses in vivo and may offer a new therapeutic target for Th2-mediated airway disease.
Link between the Ubiquitin Conjugation System and the ISG15 Conjugation System: ISG15 Conjugation to the UbcH6 Ubiquitin E2 Enzyme (2005)

ISG15 is a ubiquitin-like protein that is upregulated on treatment with interferon. ISG15 is considered to be covalently conjugated to cellular proteins through a sequential reaction similar to that of the ubiquitin conjugation system consisting of E1/E2/E3 enzymes: UBE1L and UbcH8 have been reported to function as E1 and E2 enzymes, respectively, for ISG15 conjugation. Several cellular proteins have been identified as targets for ISG15 conjugation, but the roles of ISG15 conjugation remain unclear. In this study, we found that UbcH6 and UbcH8, E2 enzymes for ubiquitin conjugation, are covalently modified by ISG15. We also found that UbcH6 is capable of forming a thioester intermediate with ISG15 through Cys131. We determined that the Lys136 residue near the catalytic site Cys131 is the ISG15 conjugation site in UbcH6. We isolated ISG15-modified and unmodified UbcH6 proteins, and analyzed their abilities to form thioester intermediates with ubiquitin. A ubiquitin thioester intermediate was detected in the case of unmodified UbcH6, but not in that of ISG15-modified UbcH6, strongly suggesting that ISG15 conjugation to UbcH6 suppresses its ubiquitin E2 enzyme activity. Thus, we provide evidence for a link between the ubiquitin conjugation system and the ISG15 conjugation system.
Assembly of high-affinity insulin receptor agonists and antagonists from peptide building blocks (2003)

Insulin is thought to elicit its effects by crosslinking the two extracellular alpha-subunits of its receptor, thereby inducing a conformational change in the receptor, which activates the intracellular tyrosine kinase signaling cascade. Previously we identified a series of peptides binding to two discrete hotspots on the insulin receptor. Here we show that covalent linkage of such peptides into homodimers or heterodimers results in insulin agonists or antagonists, depending on how the peptides are linked. An optimized agonist has been shown, both in vitro and in vivo, to have a potency close to that of insulin itself. The ability to construct such peptide derivatives may offer a path for developing agonists or antagonists for treatment of a wide variety of diseases.
Derivatives of 17-Phenyl-18,19,20-trinorprostaglandin F2.alpha. Isopropyl Ester: Potential Antiglaucoma Agents (1995)

The 15R and 15S epimers of a series of phenyl substituted analogs of 17-phenyl-18,19,20-trinorprostaglandin F2 alpha isopropyl ester [(15S)-3] have been synthesized. The intraocular pressure (IOP) lowering effects and potential side effects of these novel derivatives have been studied in cats and rabbits. In addition, the effects of selected analogues on IOP have been studied in monkeys. Furthermore, we have hydrolyzed some of the isopropyl esters and assessed the ability of the resulting carboxylic acids to contract the cat iris sphincter muscle in vitro. In general, the 15S-derivatives were more active than the 15R-epimers. Derivatives substituted with an acetyl group in the benzene ring appeared to have a better side effect profile as compared to (15S)-3. Furthermore, substitution with an aromatic moiety had a dramatic effect on the activity in that the resulting compounds reduced IOP in cats but had little effect on the pupil diameter. Thus, the activity profile of (15S)-3 may be changed by the introduction of substituents in the benzene ring.
Investigation of colorectal cancer in accordance with consensus molecular subtype classification (2020)

The classification of colorectal cancer (CRC) plays a pivotal role in predicting a patient's prognosis and determining treatment strategies. The consensus molecular subtype (CMS) classification system was constructed by analyzing genetic information from 18 CRC data sets, containing 4151 CRC samples. CRC was classified into four subtypes with distinct molecular and biological characteristics: CMS1 (microsatellite instability immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal). Since their designation in 2015, these classifications have been applied to basic and translational research of CRC, with the hope that understanding these subsets will influence a clinician's approach to therapeutic treatment and improve clinical outcomes. We reviewed CRC investigations in accordance with CMSs published in the last 5 years to further explore the clinical significance of these subtypes and identify underlying trends that may direct relevant future research. We determined that CMSs linked common features of CRC cell lines and PDX models in various studies. Furthermore, associations between prognosis and clinicopathological findings, including pathological grade and the stage of carcinogenesis, tumor budding, and tumor location, were correlated with CMS classification. Novel prognostic factors were identified, and the relationship between chemotherapeutic drug resistance and CMS has been fortified by our compilation of research; thus, indicating that this review provides advanced insight into clinical questions and treatment strategies for CRC.
. Blood, Blood, Blood (2006)

The audiocassette Marj az–Zahur begins with the words, “Blood, blood, blood”, and thereafter manages to repeat the word about forty times. Everyone talked about blood during the intifada. There was blood everywhere. Demonstrators were shot every other day; collaborators were killed, their tortured bodies dumped in the street in front of mosques. The blood and wounds of martyrs were commonly displayed and photographed. It was also blood that prevented negotiations, compromise of any sort, as in the Hamas message, “The blood of martyrs will not be wasted on the negotiation table”. The zeal was such that some actively invited their own bloodletting.
A point mutation of the Na+/H+ exchanger gene (NHE1) and amplification of the mutated allele confer amiloride resistance upon chronic acidosis. (1993)

The diuretic drug amiloride and its 5-amino substitute N5-methyl-N5-propylamiloride (MPA) are potent inhibitors of the growth factor-activatable Na+/H+ exchanger isoform 1 (NHE1). This inhibitor competes with Na+, presumably by interacting with the ion-transport site of the NHE molecule. As an approach to identify this site, we previously reported the use of a specific H(+)-killing selection technique for isolating amiloride-resistant variants of Chinese hamster lung fibroblasts. After long-term selection, two variants, AR40 and AR300, 100- and 1000-fold, respectively, resistant to MPA, were isolated. By comparing NHE1 cDNA sequences of parental and two variant cell lines, we show that the 1000-fold resistance to MPA results from two sequential genetic events. (i) In one AR40 allele a point mutation, Phe-167--> Leu, occurs in the middle of the fourth putative transmembrane segment of NHE1. Producing this mutant protein from human NHE1 cDNA by site-directed mutagenesis increased the Ki for MPA by 30-fold, as seen in AR300 cells. (ii) An approximately 10-fold amplification of the mutated allele, which contributes to the acquired MPA resistance, accounts for the Vmax increase. Mutating a close residue, Phe-165--> Tyr, increased by 40-fold the Ki for amiloride and reduced Na+ transport rate 3- to 4-fold, indicating that we have identified a critical domain of the NHE molecule that controls amiloride binding and Na+ transport. Interestingly, the epithelial amiloride-resistant NHE isoforms that occurred naturally possess some of the amino acid substitutions described here.
Prevalence of Sexually Transmitted Disease Infection in Women Alleging Rape (1992)

During a 2-year period ending in October, 1989, 110 women who claimed to have been raped were treated at the sexually transmitted disease clinic at Birmingham General Hospital. A total of 22 sexually transmitted infections were found in 14 (13%) women, of which Chlamydia trachomatis (in 8%) and Trichomonas vaginalis (in 6%) were the most frequently found pathogens. In none of these patients was it possible to determine whether infection resulted from rape or from voluntary intercourse with another person. The high prevalence of infection found in this study and in previous studies indicates that all women alleging rape should be investigated at a sexually transmitted disease clinic.
Simple testing can prevent most critical failures: an analysis of production failures in distributed data-intensive systems (2014)

Large, production quality distributed systems still fail periodically, and do so sometimes catastrophically, where most or all users experience an outage or data loss. We present the result of a comprehensive study investigating 198 randomly selected, user-reported failures that occurred on Cassandra, HBase, Hadoop Distributed File System (HDFS), Hadoop MapReduce, and Redis, with the goal of understanding how one or multiple faults eventually evolve into a user-visible failure. We found that from a testing point of view, almost all failures require only 3 or fewer nodes to reproduce, which is good news considering that these services typically run on a very large number of nodes. However, multiple inputs are needed to trigger the failures with the order between them being important. Finally, we found the error logs of these systems typically contain sufficient data on both the errors and the input events that triggered the failure, enabling the diagnose and the reproduction of the production failures.We found the majority of catastrophic failures could easily have been prevented by performing simple testing on error handling code - the last line of defense - even without an understanding of the software design. We extracted three simple rules from the bugs that have lead to some of the catastrophic failures, and developed a static checker, Aspirator, capable of locating these bugs. Over 30% of the catastrophic failures would have been prevented had Aspirator been used and the identified bugs fixed. Running Aspirator on the code of 9 distributed systems located 143 bugs and bad practices that have been fixed or confirmed by the developers.
Diagnostic efficacy of computer extracted image features in optical coherence tomography of the precancerous cervix (2010)

The diagnostic efficacy of CADx in OCT imaging to differentiate high-grade CIN from normal/low grade CIN is demonstrated. The high specificity of OCT with CADx suggests further investigation as an effective secondary screening tool when combined with a highly sensitive primary screening tool.
Two Methods of Whole-Genome Amplification Enable Accurate Genotyping Across a 2320-SNP Linkage Panel (2004)

Comprehensive genome scans involving many thousands of SNP assays will require significant amounts of genomic DNA from each sample. We report two successful methods for amplifying whole-genomic DNA prior to SNP analysis, multiple displacement amplification, and OmniPlex technology. We determined the coverage of amplification by analyzing a SNP linkage marker set that contained 2320 SNP markers spread across the genome at an average distance of 2.5 cM. We observed a concordance of >99.8% in genotyping results from genomic DNA and amplified DNA, strongly indicating the ability of both methods used to amplify genomic DNA in a highly representative manner. Furthermore, we were able to achieve a SNP call rate of >98% in both genomic and amplified DNA. The combination of whole-genome amplification and comprehensive SNP linkage analysis offers new opportunities for genetic analysis in clinical trials, disease association studies, and archiving of DNA samples.
4-1BB engagement costimulates NKT cell activation and enhances airway hyperreactivity and airway inflammation mediated by NKT cells (88.19) (2007)

Abstract Multiple studies have demonstrated that 4-1BB (CD137), a member of the TNF receptor superfamily, is expressed in several immune cells, including activated T cells. However, the expression and the potential roles of 4-1BB on CD1d-restricted invariant NKT (iNKT) cell have not fully characterized. In this study, it was demonstrated that 4-1BB on iNKT cells was consititutively expressed, and the expressions was increased by TCR engagement. Also, 4-1BB signaling provided by 3H3, an anti-4-1BB agonistic mAb, promoted iNKT cells activation, resulting in enhanced proliferation and cytokine production of iNKT cells driven by alpha-galactosylcerimide (alpha-GalCer) or anti-CD3 mAb in vitro. Administration of 3H3 further increased IL-4 and IFN-gamma levels in serum induced by alpha-GalCer administration in vivo. When 3H3 and alpha-GalCer were intranasally co-administrated, airway hyperreacitivity and inflammatory cell accumulation were severely aggravated. In conclusion, 4-1BB on iNKT cell functions as a costimulatory molecule, and facilitates the induction of more severe airway hyperreacitivity and inflammatory cell accumulation in NKT cell-mediated airway inflammation.
Maturation in Vitro of Pig Oocytes in Protein-Free Culture Media: Fertilization and Subsequent Embryo Development in Vitro1 (1998)

In the present study, attempts were made to develop a protein-free (PF) in vitro maturation (IVM) system for pig oocytes and to examine subsequent embryo development after in vitro fertilization. In experiment 1, four IVM media were tested: 1) control: North Carolina State University (NCSU) 23+10% porcine follicular fluid; 2) PF-NCSU: NCSU 23+0.1% polyvinyl alcohol (PVA)+1% amino acids; 3) PF-TCM: Tissue culture medium (TCM) 199+PVA; and 4) PF-WM: PF-Waymouth MB 752/1 medium (WM)+PVA. Oocytes were cultured in the respective media containing eCG and hCG (10 IU/ml each) for 20-22 h and then without hormonal supplements for an additional 20-22 h. After culture, the degree of cumulus expansion and frequency of nuclear maturation were determined. Some oocytes were coincubated with frozen-thawed spermatozoa for 5-6 h in modified Tris-buffered medium containing caffeine and BSA. In experiment 2, oocytes were matured in control, PF-TCM, and PF-WM, fertilized in vitro, and cultured for 144 h in NSCU 23+BSA. Fewer (p < 0.01) oocytes reached metaphase II stage in PF-NCSU (45% vs. 80-85%) than in the other media. Oocytes matured in control medium showed the most cumulus expansion, followed by those in PF-TCM and PF-WM; those in PF-NCSU showed very slight expansion. A lower (p < 0.05) penetration rate was obtained for oocytes matured in PF-NCSU than in the control medium (59% vs. 81%). In contrast to those in control (96%) and PF-TCM (93%), oocytes in PF-WM (65%) showed a lower male pronuclear formation. Compared to that in the control, a significantly lower (p < 0.05) cleavage rate was also observed for oocytes matured in PF-WM. Similar proportions of embryos developed to the blastocyst stage when oocytes were matured in control (22%) and PF-TCM (13%). These results indicate that pig oocytes can be successfully matured in a protein-free medium with subsequent development to the blastocyst stage.