gebhart/patrepeval huggingface dataset:
The Selective Neurokinin 3 Antagonist AZD2624 Does Not Improve Symptoms or Cognition in Schizophrenia (2014)

Problems with the efficacy of second-generation antipsychotics on negative symptoms and cognition have highlighted the need for further development of drugs targeting central nervous system neurotransmitter systems other than dopamine. One target in development is neurokinin 3 (NK(3)) tachykinin receptors, which are coreleased and interact with dopamine. This study investigates the efficacy, tolerability, and cognitive effects of AZD2624, a selective, orally active NK(3) receptor antagonist, in symptomatic patients with schizophrenia. Patients were randomly assigned to 1 of 3 treatment groups: AZD2624 40 mg, placebo, or olanzapine 15 mg. Treatment lasted for 28 days, and the Positive and Negative Syndrome Scale, the Clinical Global Impression Severity Scale and Improvement Scales, and cognition as assessed by CogState were used as primary outcome measures. There were no significant differences in patients treated with AZD2624 versus placebo on change in Positive and Negative Syndrome Scale total score and Clinical Global Impression Severity Scale; in addition, no change in CogState measures was found. Results of the trial do not support a role for the NK(3) antagonist AZD2624 as a therapeutic treatment for acute schizophrenia when used as monotherapy.
Effect of Donepezil Hydrochloride (E2020) on Extracellular Acetylcholine Concentration in the Cerebral Cortex of Rats (1999)

Donepezil hydrochloride (donepezil), a potent and selective acetylcholinesterase inhibitor, has been developed for the treatment of Alzheimer’s disease. We studied the effect of oral administration of this drug on the extracellular acetylcholine (ACh) concentration in the cerebral cortex of rats using microdialysis. We also observed fasciculation, a peripheral cholinergic sign induced by activation of neuromuscular transmission, after oral administration of the drug as an index of peripheral cholinergic activation. Other cholinesterase inhibitors, tacrine, ENA-713 and TAK-147, were used as reference drugs. Donepezil significantly and dose-dependently increased the extracellular ACh concentration in the rat cerebral cortex within the dose range of 2.5-10 mg/kg. Tacrine, ENA-713 and TAK-147 also elevated the extracellular concentration of ACh. The minimum effective doses of donepezil, tacrine, ENA-713 and TAK-147 were ≦2.5,10, 10 and ≦ 10 mg/kg, respectively. Donepezil produced fasciculation at doses of 2.5 mg/kg and above, with a dose-dependent increase in incidence and intensity. The reference compounds also induced fasciculation in a dose-dependent manner. The threshold doses of tacrine, ENA-713 and TAK-147 for fasciculation were 5, 2.5 and 2.5 mg/kg, respectively. The values of the ratio of the minimum effective dose for the ACh-increasing action to that for the fasciculation-producing action were: donepezil, ≦1; tacrine, 2; ENA-713, 4; TAK-147, ≦4. These results indicate that orally administered donepezil has a potent and selective activity on the central cholinergic system.
Comparison of Performances of Two Commercially Available Tests, a PCR Assay and a Ligase Chain Reaction Test, in Detection of Urogenital <i>Chlamydia trachomatis</i> Infection (1998)

The diagnostic performance of a PCR test (Roche Cobas Amplicor CT/NG Test) and that of a ligase chain reaction (LCR) test (Abbott LCx Chlamydia trachomatis assay) were compared by using endocervical and urethral swab specimen culture as a reference test. First-void urine (FVU) and endocervical and urethral swab specimens were collected from 1,015 unselected patients attending a sexually transmitted disease clinic and a clinic for adolescents in Helsinki, Finland. Chlamydia trachomatis was cultured from samples from the endocervix or urethra. PCR was performed with fresh and frozen urine and the culture transport medium. LCR was performed with fresh and frozen urine and LCx swab transport medium. Diagnostic consistency and diagnostic accuracy were statistically tested. The test results were identical for 984 patients (97%). Discrepant results were observed for 31 patients. Overall, LCR and PCR showed excellent kappa coefficients of consistency for both swab and FVU specimens (0.93 and 0.95, respectively). Sixty-one patients (6%) were culture positive. Testing of FVU by LCR or PCR increased the overall positivity rates to 7.0 and 7.7%, respectively. While PCR of FVU detected the greatest number of C. trachomatis infections (sensitivity, 96.1%), for some PCR-positive FVU specimens the results could not be confirmed (specificity, 99.6%). PCR and LCR were more sensitive than culture (sensitivities, 92 and 93% versus 79% for culture) in the diagnosis of genital C. trachomatis infection. In conclusion, both tests can be recommended for use in the clinical laboratory and for the screening of asymptomatic C. trachomatis infections.
Centromere Targeting of the Chromosomal Passenger Complex Requires a Ternary Subcomplex of Borealin, Survivin, and the N-Terminal Domain of INCENP (2006)

The chromosomal passenger complex (CPC), consisting of the serine/threonine kinase Aurora B, the inner centromere protein INCENP, Survivin, and Borealin/DasraB, has essential functions at the centromere in ensuring correct chromosome alignment and segregation. Despite observations that small interfering RNA-mediated knockdown of any one member of the CPC abolishes localization of the other subunits, it remains unclear how the complex is targeted to the centromere. We have now identified a ternary subcomplex of the CPC comprising Survivin, Borealin, and the N-terminal 58 amino acids of INCENP in vitro and in vivo. This subcomplex was found to be essential and sufficient for targeting to the centromere. Notably, Aurora B kinase, the enzymatic core of the CPC, was not required for centromere localization of the subcomplex. We demonstrate that CPC targeting to the centromere does not depend on CENP-A and hMis12, two core components for kinetochore/centromere assembly, and provide evidence that the CPC may be directed to centromeric DNA directly via the Borealin subunit. Our findings thus establish a functional module within the CPC that assembles on the N terminus of INCENP and controls centromere recruitment.
Examination of cyanine intercalation dyes for rapid and sensitive detection of DNA fragments by capillary electrophoresis. (1999)

Recently, a series of cyanine dyes has been developed that are reported to offer superior fluorescence upon intercalation relative to ethidium bromide (EB). The dimeric cyanine dyes, such as POPO-3 (Molecular Probes, Eugene, OR, U.S.A.), are reported to offer the highest fluorescence enhancement of the cyanine dyes. Although POPO-3 does offer an improvement in sensitivity, achieving reproducible, high-efficiency results by employing pre-column, on-column, and postcolumn labeling strategies proved to be problematic. Evaluation of the labeling rate of these dimeric dyes indicates that perhaps the most limiting factor to using this dye for rapid CE analysis of DNA fragments is the apparent slow rate at which the dye fully intercalates into the DNA structure. Use of the monomeric analog PO-PRO-3 (Molecular Probes) resulted in much better separations and low limits of defection when employed for on-column intercalation. However, we find that the kinetics are too slow to employ this dye in a sheath flow cell for postcolumn derivatization.
Molecular Genetic Evidence for Subtypes of Oligoastrocytomas (1997)

The histogenesis of oligoastrocytomas remains controversial, with some data arguing similarity of oligoastrocytomas to astrocytic tumors, and other data suggesting closer relationships with oligodendroglial neoplasms. Since the molecular genetic changes in astrocytomas differ from those of oligodendrogliomas, we characterized 120 astrocytic and oligodendroglial tumors, including 38 oligoastrocytomas, for genetic alterations that occur disproportionately between astrocytomas and oligodendrogliomas, i.e. TP53 gene mutations and allelic loss of chromosomes 1p, 17p and 19q. As previously reported, TP53 mutations were common in astrocytic gliomas, occurring in approximately half of WHO grade II and III astrocytomas, but in only 5% of WHO grades II and III oligodendrogliomas. Allelic losses of chromosomes 1p and 19q, however, were common in oligodendrogliomas (41% and 63%), but less frequent in astrocytomas (9% and 35%). Oligoastrocytomas showed TP53 mutations in 12/38 (32%) cases and allelic losses of chromosomes 1p and 19q in 52% and 70%, respectively. Most importantly, TP53 mutations and allelic losses on chromosomes 1p and 19q were inversely correlated in oligoastrocytomas (p < 0.011 and p < 0.019). These data suggest the existence of two genetic subsets of oligoastrocytomas, one genetically related to astrocytomas and the other genetically related to oligodendrogliomas. Histologically, those oligoastrocytomas with TP53 mutations were more often astrocytoma-predominant, while those with chromosome 19q loss were more often oligodendroglioma-predominant.
Comedo-Ductal carcinoma in situ: A paradoxical role for programmed cell death (2008)

Comedo-DCIS is a histologic subtype of preinvasive breast neoplasia that is characterized by prominent apoptotic cell death and has greater malignant potential than other DCIS subtypes. We investigated the mechanisms of apoptosis in comedo-DCIS and its role in conversion of comedo-DCIS to invasive cancer. Clinical comedo-DCIS excisions and the MCF10DCIS.com human breast cancer model which produces lesions resembling comedo-DCIS were analyzed. Apoptotic luminal and myoepithelial cells were identified by TUNEL and reactivity to cleaved PARP antibody and cell death assessed by Western blotting, Mitocapture and immunohistochemical assays. MCF10DCIS.com cells undergo spontaneous apoptosis in vitro, both in monolayers and multicellular spheroids; it is associated with increased mitochondrial membrane permeability, increase in Bax/Bcl-2 ratio and occurs via caspase-9-dependent p53-independent pathway. This suggests that apoptosis is stromal-independent and that the cells are programmed to undergo apoptosis. Immunostaining with cleaved PARP antibody showed that myoepithelial apoptosis occurs before lesions progress to comedo-DCIS in both clinical comedo-DCIS and in vivo MCF10DCIS.com lesions. Intense staining for MMP-2, MMP-3, MMP-9 and MMP-11 was observed in the stroma and epithelia of solid DCIS lesions prior to conversion to comedo-DCIS in clinical and MCF10DCIS.com lesions. Gelatin zymography showed higher MMP-2 levels in lysates and conditioned media of MCF10DCIS. com cells undergoing apoptosis. These data suggest that signals arising from the outside (microenvironmental) and inside (internal genetic alterations) of the duct act in concert to trigger apoptosis of myoepithelial and luminal epithelial cells. Our findings implicate spontaneous apoptosis in both the etiology and progression of comedo-DCIS. It is possible that spontaneous apoptosis facilitates elimination of cells thus permitting expansion and malignant transformation of cancer cells that are resistant to spontaneous apoptosis.
3D soundfield reproduction using higher order loudspeakers (2013)

Three dimensional surround sound reproduction over large areas is a prevailing challenge due to the enormous numbers of loudspeakers required. In this paper, we propose an array of higher order loudspeakers which provide a mode matching solution to the problem based on 3D wavefield translation. It is shown that for a given bandwidth, the use of L <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> order sources significantly brings down the minimum loudspeaker requirement by a factor of 1=(L + 1) <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Furthermore, the array is shown to be capable of exterior field cancellation, increasing its performance in echoing environments. Design examples are given for interior field, exterior field and interior and exterior combined field reproduction.
How Copyleft Uses License Rights to Succeed in the Open Source Software Revolution and the Implications for Article 2B (1999)

The computer industry moves from one “next great thing” to the next “next great thing” with amazing speed. Graphical user interface, object-oriented programming, client-server computing, multimedia software, Java applets, the network computer, and the Internet have all been hailed as technological breakthroughs at one time or another. Some of these promising developments fizzle, some evolve and succeed slowly, and some revolutionize the industry overnight. Led by a group of software developers known as “hackers,” the latest “next great thing” is “open source” software.

The word “source” refers to software in source code form. Source code is the collection of instructions a computer programmer writes to tell a computer what to do. A programmer writes source code in a certain programming language, such as Basic, Pascal, C++, or Java. The source code is understandable to anyone proficient in that language. Using a software tool, source code is converted into a form called binary or executable code that a computer can execute.

The word “open” in the context of open source software refers to source code that is freely available and modifiable. Most software publishers distribute their software to the mass market in binary form only. They treat source code as a trade secret and license it selectively on a confidential basis.

The open source software movement claims at least two major advantages over traditional commercially developed software. First, hackers claim that by making source code widely available and freely modifiable, programmers can develop higher quality software and fix bugs faster than commercial software developers. Second, they believe that products based on open source software will be relatively inexpensive compared to traditional commercial software. Hackers think they have started a revolution that will overtake the leading commercial software publishers of today.

The fact that another revolution has begun in the computer industry is not a surprise. The surprise is that licensing, known as “copyleft,” is at the heart of the revolution. This Article examines the origins and continuing momentum of the open source revolution. It then discusses the principles of open source licensing and why licensing is central to the open source revolution. The Article concludes by discussing the implications that copyleft licensing principles have for proposed Article 2B of the Uniform Commercial Code (“UCC”), a provision that would govern software licenses. The Article points out that in order to foster innovative developments such as the open source revolution, Article 2B needs to, among other things, validate the enforceability of standard-form mass-market licenses, preserve the ability of software developers to freely allocate risk, and provide sensible contract default rules.
Innovative Water Shutoff Solutions Using Coiled Tubing Conveyed Inflatable Devices (2002)

Abstract With water production continuing to increase from mature reservoirs and the need to enhance hydrocarbon recovery from these reservoirs economically using existing wellbores, the requirement for innovative thru-tubing zonal isolation solutions has never been greater. Due to the complexity of the completion design and reservoir in mature fields, the benefits of high-expansion plugging devices and coiled tubing conveyance for chemical placement have become increasingly important. Thru-tubing inflatable technology has, for some time now, been providing high-expansion devices to pass through the existing completion and isolate in the liner or casing below. However, as reservoirs deplete and remedial work such as re-perforation is performed, the conditions in which these tools are required to perform are becoming ever more challenging. This paper will focus on two coiled tubing water shutoff interventions using thru-tubing inflatable technology in conjunction with cement or chemical placement. In these interventions, the wellbore conditions were considered particularly challenging – sub-hydrostatic bottomhole pressure, multiple perforated intervals and an existing zonal isolation device in the form of a straddle. These case histories will be examined in detail, with emphasis on the pre-job planning, equipment selection, operational procedures, lessons learnt and post job results.
Hydrolysis of Maltoheptaose in Flow through Silicon Wafer Microreactors Containing Immobilised α‐Amylase and Glycoamylase (2006)

Abstract In this study a silicon micro immobilised enzyme reactor (μIMER) has been applied for hydrolysis of maltoheptaose as a model maltodextrin and starch using immobilised μ‐amylase (from Aspergillus oryzae ) and glycoamylase (from Aspergillus niger ). The influence of several parameters was investigated such as immobilisation chemistry, buffer constituents, pH, temperature, flow rate and substrate concentration. The conversion efficiency profile of the substrate was measured and the long‐term stability of the reactor was tested. For separation and detection of the formed hydrolysis products, high‐performance anion‐exchange chromatography with pulsed amperometric detection (HPAEC‐PAD) was used. The results show that the μIMERs can also be used for hydrolysis of starch and also additionally be connected directly on‐line with, e.g., liquid chromatography, making it possible to perform on‐line characterisation and analysis of starch hydrolysis products.
Bacteriophage Therapy To Reduce <i>Campylobacter jejuni</i> Colonization of Broiler Chickens (2005)

Colonization of broiler chickens by the enteric pathogen Campylobacter jejuni is widespread and difficult to prevent. Bacteriophage therapy is one possible means by which this colonization could be controlled, thus limiting the entry of campylobacters into the human food chain. Prior to evaluating the efficacy of phage therapy, experimental models of Campylobacter colonization of broiler chickens were established by using low-passage C. jejuni isolates HPC5 and GIIC8 from United Kingdom broiler flocks. The screening of 53 lytic bacteriophage isolates against a panel of 50 Campylobacter isolates from broiler chickens and 80 strains isolated after human infection identified two phage candidates with broad host lysis. These phages, CP8 and CP34, were orally administered in antacid suspension, at different dosages, to 25-day-old broiler chickens experimentally colonized with the C. jejuni broiler isolates. Phage treatment of C. jejuni-colonized birds resulted in Campylobacter counts falling between 0.5 and 5 log10 CFU/g of cecal contents compared to untreated controls over a 5-day period postadministration. These reductions were dependent on the phage-Campylobacter combination, the dose of phage applied, and the time elapsed after administration. Campylobacters resistant to bacteriophage infection were recovered from phage-treated chickens at a frequency of <4%. These resistant types were compromised in their ability to colonize experimental chickens and rapidly reverted to a phage-sensitive phenotype in vivo. The selection of appropriate phage and their dose optimization are key elements for the success of phage therapy to reduce campylobacters in broiler chickens.
Hippocampal-Dependent Antidepressant Action of the H<sub>3</sub>Receptor Antagonist Clobenpropit in a Rat Model of Depression (2015)

Clobenpropit's antidepressant effects and the enhanced synaptic plasticity require hippocampal H1R and H2R activation, suggesting that clobenpropit acts through disinhibition of histamine release. Clobenpropit reverses memory deficits and increases hippocampal GluN2A expression without modifying anxiety-related phenotypes or EPSCs in CA1 pyramidal neurons.
Activation of p21‐activated protein kinase α (αPAK) by hyperosmotic shock in neonatal ventricular myocytes (1997)

The p21-activated protein kinases (PAKs) may participate in signalling from Cdc42/Rac1 to the stress-regulated MAPKs (SAPKs/JNKs and p38-/HOG-1-related-MAPKs). We characterized the expression and regulation of alpha PAK in cultured ventricular myocytes. alpha PAK was specifically immunoprecipitated from myocyte extracts. High basal alpha PAK activity was detected in unstimulated myocytes. Its activity was increased rapidly (<30 s) by hyperosmotic shock in the presence of okadaic acid, and was maximal by 3 min (187 +/- 7% relative to unstimulated cells). Endothelin-1 and interleukin-1beta, which also activate SAPKs/JNKs, did not increase alpha PAK activity and presumably act through different PAK isoforms or other mechanisms.
Low-flux neutron imaging (1973)

Judicious use of scintillation screens greatly improves the capabilities for low-flux neutron imaging. Room temperature, cooled /sup 6/LiF-- ZnS(Ag) and gadolinium oxysulfide (Gd/sub 2/O/sub 2/S: Tb) were evaluated for direct exposures, and x-ray intensifying screens were evaluated with dysprosium and europium transfer screens. Although gadolinium oxysulfide provides improved resolution, it requires seven times the imaging time of /sup 6/LiF-- ZnS(Ag). Studies indicate that use of intensifying screens during transfer processes decreases the flux for a given density by about 30% and provides contrast enhancement. It was shown that cooling of scintillator-film combinations reduces reciprocity failure effects and in these experiments decreased direct exposure times (Gd/sub 2/O/sub 2/S: Tb) by up to 80%. (auth)
Cloning of a cDNA encoding rat intestinal fatty acid binding protein. (1984)

Intestinal fatty acid binding protein mRNA is one of the most abundant mRNA species in the rat small intestinal epithelium. RNA transfer blot analyses disclosed that the mRNA encoding intestinal fatty acid binding protein is approximately equal to 900 nucleotides long and not represented in liver RNA. We have identified 564 nucleotides of this mRNA, including 12 nucleotides of the 5' nontranslated region, the coding portion, and 155 nucleotides of the 3' nontranslated domain. The primary translation product encoded by this mRNA contains 132 amino acids and has a Mr of 15,062. The derived protein sequence was verified by automated sequential Edman degradation of the intact polypeptide isolated from a wheat germ cell-free system. The in vitro product is NH2-terminally acetylated, a finding that is consistent with its ultimate cytoplasmic destination. Comparison of the amino acid sequence of this protein with liver fatty acid binding protein, a polypeptide specified by the most abundant small intestinal epithelial mRNA, revealed significant homology and similarity in the predicted secondary structures of their NH2-terminal domains.
GridVine: An Infrastructure for Peer Information Management (2007)

GridVine is a semantic overlay infrastructure based on a peer-to-peer (P2P) access structure. Built following the principle of data independence, it separates a logical layer - in which data, schemas, and schema mappings are managed - from a physical layer consisting of a structured P2P network supporting decentralized indexing, key load-balancing, and efficient routing. The system is decentralized, yet fosters semantic interoperability through pair-wise schema mappings and query reformulation. GridVine's heterogeneous but semantically related information sources can be queried transparently using iterative query reformulation. The authors discuss a reference implementation of the system and several mechanisms for resolving queries collaboratively.