gebhart/patrepeval huggingface dataset:
The acute neurotoxic effect of β-amyloid on mature cultures of rat hippocampal neurons is attenuated by the anti-oxidant U-78517F (1994)

The neuropathological characteristics of Alzheimer's disease include the selective loss of neurons and the development of senile plaques and neurofibrillary tangles. These plaques and tangles are invariably associated with deposits of an insoluble protein, beta-amyloid, and the hypothesis that the beta-amyloid is responsible for the neuronal loss in Alzheimer's disease has received considerable support. The neurotoxic action of beta-amyloid has been demonstrated in primary cultures of cortical and hippocampal neurons and in PC-12 cells. The present study reports that the neurotoxicity of beta-amyloid is reduced by the antioxidant drug U-78517F. On the basis of this observation, we suggest that the neurotoxic effect of beta-amyloid is mediated by oxygen free radicals. The clinical use of antioxidant interventions may reduce neurodegeneration and the progression of the symptoms in patients with Alzheimer's disease.
Systemic pre‐treatment with a group II mGlu agonist, LY379268, reduces hyperalgesia in vivo (2002)

1. Previous studies investigating the role of metabotropic glutamate (mGlu) receptors in nociceptive processing have been hampered by the lack of systemically active, selective, ligands. This study investigates the possible analgesic and/or anti-hyperalgesic properties of the most potent compound to date that has systemic agonist activity at group II mGlu receptors, LY379268. 2. In testing the drug in rats as an analgesic to acute noxious stimuli, LY379268 (in doses up to 3 mg kg(-1) i.p.) did not affect withdrawal latencies to either mechanical or thermal stimulation. 3. However, when a 3 mg kg(-1) dose was given prior to an intraplantar injection of carrageenan, the inflammatory hyperalgesia that developed was significantly delayed compared to saline pre-treated controls, without affecting the inflammation of the paw. A similar dose of the mGlu-inactive enantiomer, LY379267, was not anti-hyperalgesic. 4. In a model of mouse tail withdrawal to warm water, LY379268 (12 mg kg(-1) i.p.), given before a subcutaneous tail injection of capsaicin, reduced the subsequent neurogenic hyperalgesia. 5. Rota-rod testing showed that the drug did not produce a motor impairment in rats at antihyperalgesic doses. 6. The results indicate that systemic activation of this group of mGlu receptors reduces both inflammatory and neurogenic thermal hyperalgesia.
Gene-Targeting Strategies (2003)

In the early 1980s, the first demonstrations of homologous recombination in cultured mammalian cells involved recombination between two introduced plasmid molecules (e.g., see ref. 1) and proceeded to situations in which one of the plasmid molecules was randomly integrated into the genome and recombined with a second introduced plasmid. The first endogenous locus, β-globin, was targeted by Oliver Smithies in 1985 (2). The same low frequency of gene targeting (∼10-3 of the frequency of random integrations) was observed in two human somatic cell lines, only one of which expressed the target gene. This experiment was particularly significant because it demonstrated that gene expression was not a prerequisite for successful targeting. Attention then shifted from somatic cells to gene targeting in cultured mouse embryonic stem (ES) cells, because of the powerful attraction of being able to generate new strains of mice with specific genetic alterations from cultured cells manipulated in vitro. A series of experiments, using the hypoxanthine phosphoribo-syltransferase (HPRT) gene as target, evaluated the two basic types of targeting vector (insertion and replacement) that remain in current use and the requirements for successful gene targeting. Two features of the HPRT system made it particularly favorable for these early model experiments: convenient procedures exist to select either for, or against, HPRT expression in cultured cells; and the gene is X-chromosome linked so that, in male cells, only a single locus need be targeted to produce a change in phenotype that could then be selected for.
Topologically equivalent mutations causing dysfunctional coagulation factors VII (294Ala→Val) and X (334Ser→ Pro) (1994)

Journal Article Topologically equivalent mutations causing dysfunctional coagulation factors VII (294Ala→Val) and X (334Ser→ Pro) Get access F. Bernardi, F. Bernardi * *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Castaman, G. Castaman 1Divisione di Ematologia-Centro Regionale Studio Malattie Emorragiche e TromboticheOspedale S.Bortolo, Vicenza, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Redaelll, R. Redaelll 2Divisione di Ematologia, Ospedale NiguardaMilano, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Pinotti, M. Pinotti Search for other works by this author on: Oxford Academic PubMed Google Scholar B. Lunghl, B. Lunghl Search for other works by this author on: Oxford Academic PubMed Google Scholar F. Rodeghlero, F. Rodeghlero 1Divisione di Ematologia-Centro Regionale Studio Malattie Emorragiche e TromboticheOspedale S.Bortolo, Vicenza, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Marchetti G. Marchetti Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 3, Issue 7, July 1994, Pages 1175–1177, https://doi.org/10.1093/hmg/3.7.1175 Published: 01 July 1994 Article history Received: 24 February 1994 Revision received: 05 May 1994 Accepted: 05 May 1994 Published: 01 July 1994
ZD6474: an Agent That Selectively Targets Both VEGFR Tyrosine Kinase and EGFR Tyrosine Kinase (2006)

ZD6474は，細胞増殖に関わる二つの重要なシグナル伝達経路に選択的に作用する新規の小分子化合物で，血管内皮増殖因子受容体（VEGFR）チロシンキナーゼを阻害することで，腫瘍の血管新生を抑制し，あわせて上皮増殖因子受容体（EGFR）チロシンキナーゼを阻害することで，腫瘍の増殖を直接抑制する．1日1回の経口投与により広範囲の移植ヒト腫瘍モデルに対し優れた増殖抑制効果を示した．本邦および米国/オーストラリアで実施された二つの第I相試験の結果，ZD6474の忍容性は概ね良好であった．主な有害事象として，皮疹，下痢，高血圧，無症候性のQT延長が認められた．また，本邦の第I相試験では，非小細胞肺癌患者9例中4例に奏効例が認められた．ZD6474の第II相試験として，非小細胞肺癌患者および小細胞肺癌患者を対象に，ZD6474単独療法および化学療法剤との併用療法による検討が行われ，非小細胞肺癌患者を対象に実施されたゲフィチニブ（イレッサTM）と比較するZD6474単独療法の第II相試験およびZD6474とドセタキセルの併用療法による第II相試験において，主要評価項目である無増悪生存期間の改善が認められた．
High-Efficiency Transduction of Freshly Isolated Human Tumor Cells Using Adenoviral Interleukin-2 Vectors (1996)

Tumor cells genetically modified to express immunostimulatory molecules can produce high levels of antitumor immunity in rodent models. Although a number of clinical trials are currently in progress to assess the value of the approach in human disease, almost all require ex vivo transduction of cultured tumor cells with retroviral vectors. This process is not feasible for many human malignancies, hampering clinical evaluation of the approach. We have used an E1a,1b/E3 deletion mutant of adenovirus containing either the lacZ or the human interleukin-2 (IL-2) gene to transduce human neuroblastoma cells. This vector transduces fresh neuroblastoma cells and neuroblastoma cell lines with an efficiency of 80-90%, compared to an efficiency of 0-14% obtained with retroviral vectors. Cells transduced with the IL-2 adenovector produce up to 12,000 pg of IL-2/10(6) cells/24 hr. IL-2 adenovector-transduced neuroblasts are immunostimulatory; when they are cultured with patient lymphocytes, they increase the proportion of DR+ T cells and generate major histocompatibility complex (MHC) unrestricted cytotoxic effector cells active against parental (nontransduced) tumor cells. We conclude that IL-2 adenovector can be used to transduce freshly isolated human tumor cells efficiently, which will then produce immunomodulatory quantities of the cytokine. The use of adenoviral rather than retroviral vectors facilitates preparation of human tumor "vaccines" and these vectors are now being used in our clinical study of neuroblastoma patients.
Dyssynchrony Indices To Predict Response to Cardiac Resynchronization Therapy (2010)

These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.
Enzyme-linked immunosorbent assay for shigella toxin (1986)

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of shigella toxin. For the assay, a mouse monoclonal antibody against the B subunit of the toxin and a rabbit polyclonal antibody against the holotoxin were employed. The monoclonal antibody was used to coat wells of a microtiter plate, and the polyclonal antibody preparation was used as the detecting antibody. The amount of bound polyclonal antibody was determined by using a goat anti-rabbit immunoglobulin G-alkaline phosphatase conjugate and substrate. The ELISA was able to detect as little as 12 pg (0.06 ng/ml) of shigella toxin. The assay was specific for shigella toxin, not detecting a variety of other bacterial enterotoxins and lethal toxins. The ELISA values correlated well with cytotoxin activity during toxin purification. Shigella toxin was detected by ELISA and by immunoblot analysis in human fecal specimens from persons with S. dysenteriae infections, demonstrating that this toxin is produced in vivo.
Phencyclidine (angel dust)/sigma "opiate" receptor: visualization by tritium-sensitive film. (1981)

[3H]Phencyclidine ([3H]PCP) binds specifically to an apparently single class of binding sites on slide-mounted sections of rat olfactory bulb (Kd = 46 nM; Bmax = 10.5 fmol per slice). Bound [3H]PCP can be displaced by nonradioactive PCP and a series of its analogs with relative potencies that correlate closely (P less than 0.001) with values determined in a rat discrimination test that utilized PCP as a cue. Although morphine, naloxone, and opiate peptides do not displace bound [3H]PCP, psychotomimetic benzomorphans, classed as "sigma opiates," are quite potent displacers in vitro and have PCP-like behavioral properties in vivo. These results suggest that phencyclidine and the sigma opiates act at the same sites. [3H]PCP binding sites were visualized by using tritium-sensitive LKB film analyzed by computerized densitometry and color coding. The [3H]PCP binds most densely to cortical areas, diffusely in neocortex, and somewhat heterogeneously in the laminae of the hippocampal formation and dentate gyrus. Most of the brainstem and spinal cord show low specific [3H]PCP binding, with gray matter generally showing more binding than white.
Development and Application of a High-Throughput HIV Type 1 Genotyping Assay to Identify CRF02_AG in West/West Central Africa (2004)

In West/West Central Africa, CRF02_AG is the most prevalent HIV-1 strain and circulates in the milieu of rare subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs). The molecular complexity of HIV-1 epidemics in this region and the need to extensively sample large populations, such as in the case of vaccine trials, pose seemingly conflicting requirements between full-genome sequencing and high-throughput low-resolution assays. Here we describe the development and evaluation of a multiregion hybridization assay (MHAcrf02) for the efficient genotyping of CRF02_AG in West/West Central Africa. Subtype A, G, and CRF02_AG-specific fluorescent probes were designed flanking five recombination breakpoints in CRF02_AG and were used in real-time PCRs. A panel representing West/West Central African HIV-1 genetic diversity was evaluated by MHAcrf02. The sample set, previously characterized by full-genome sequencing, included CRF02_AG and CRF02_AG-containing recombinants (n = 28), other subtypes, CRFs, and URFs (n = 34). DNA from peripheral blood mononuclear cells, cocultures, and plasmids was used as template. When the patterns of probe reactivity were evaluated. CRF02_AG was identified with a 100% specificity and sensitivity. In conclusion, MHAcrf02 will permit more efficient characterization of HIV-1 in West/West Central Africa, where CRF02_AG is an important strain. Together with other regional genotyping assays MHAcrf02 will contribute to the development of a global picture of HIV-1 diversity and geographic distribution, providing a strong foundation for intervention, including vaccine development.
Forensics-as-a-Service (FaaS): Computer Forensic Workflow Management and Processing Using Cloud (2013)

Abstract—Digital forensics is a critical technology for obtaining evidences in crime investigation. Nowadays, the overwhelming magnitude of data and the lack of easy-to-deploy software are among the major obstacles in the field of digital forensics. Cloud computing, which is designed to support large scale data pro-cessing on commodity hardware, provides a solution. However, to support forensic examination efficiently using cloud, one has to overcome many challenges such as lack of understanding and experiences on configuring and using digital forensic analytic tools by the investigators, and lack of interoperability among the forensic data processing software. To address these challenges and to leverage the emerging trends of service based computing, we proposed and experimented with a domain specific cloud environment for supporting forensic applications. We designed a cloud based framework for dealing with large volume of forensic data, sharing interoperable forensic software, and providing tools for forensic investigators to create and customize forensic data processing workflows. The experimental results show that the proposed approaches can significantly reduce forensic data analysis time by parallelizing the workload. The overhead for the investigators to design and configure complex forensic workflows is greatly minimized. The proposed workflow management solu-tion can save up to 87 % of analysis time in the tested scenarios. Keywords—cloud computing; digital forensics I.
Leukemia relapse after allogeneic bone marrow transplantation: a review (1994)

A LLOGENEIC BONE MARROW transplantation (BMT) is an effective treatment for hematologic malignancies.' More than 5,000 transplants are performed yearly worldwide. The increasing use of human leukocyte antigen (HLA) nonidentical donors, and HLA-matched unrelated donors will assure the continued growth in the use of this therapeutic modality.'
The CRY1 gene in Chlamydomonas reinhardtii: structure and use as a dominant selectable marker for nuclear transformation. (1994)

We have cloned and sequenced the CRY1 gene, encoding ribosomal protein S14 in Chlamydomonas reinhardtii, and found that it is highly similar to S14/rp59 proteins from other organisms, including mammals, Drosophila melanogaster, and Saccharomyces cerevisiae. We isolated a mutant strain resistant to the eukaryotic translational inhibitors cryptopleurine and emetine in which the resistance was due to a missense mutation (CRY1-1) in the CRY1 gene; resistance was dominant in heterozygous stable diploids. Cotransformation experiments using the CRY1-1 gene and the gene for nitrate reductase (NIT1) produced a low level of resistance to cryptopleurine and emetine. Resistance levels were increased when the CRY1-1 gene was placed under the control of a constitutive promoter from the ribulose bisphosphate carboxylase/oxygenase small subunit 2 (RBCS2) gene. We also found that the 5' untranslated region of the CRY1 gene was required for expression of the CRY1-1 transgene. Direct selection of emetine-resistant transformants was possible when transformed cells were first induced to differentiate into gametes by nitrogen starvation and then allowed to dedifferentiate back to vegetative cells before emetine selection was applied. With this transformation protocol, the RBCS2/CRY1-1 dominant selectable marker gene is a powerful tool for many molecular genetic applications in C. reinhardtii.
The integration of optical flow and deformable models with applications to human face shape and motion estimation (1996)

We present a formal methodology for the integration of optical flow and deformable models. The optical flow constraint equation provides a non-holonomic constraint on the motion of the deformable model. In this augmented system, forces computed from edges and optical flow are used simultaneously. When this dynamic system is solved, a model-based least-squares solution for the optical flow is obtained and improved estimation results are achieved. The use of a 3-D model reduces or eliminates problems associated with optical flow computation. This approach instantiates a general methodology for treating visual cues as constraints on deformable models. We apply this framework to human face shape and motion estimation. Our 3-D deformable face model uses a small number of parameters to describe a rich variety of face shapes and facial expressions. We present experiments in extracting the shape and motion of a face from image sequences.
Survival estimates for 683 patients starting dialysis from 1970 through 1989: identification of risk factors for survival. (1994)

Survival estimates were performed on 683 chronic dialysis patients who started dialysis from 1970 through 1989 and followed through 1991. Patients were grouped by dialysis type, renal diagnosis, start-year group and age at start. During these 20 entry, years, the median starting age rose from 47 to 61 years. Patients with a renal diagnosis of diabetes mellitus or renal vascular disease increased to 41% of those starting dialysis during the last 8 years of study. Survival analysis for all of the 683 patients revealed a 51-month median survival and a 43% and 23% 5- and 10-year survival estimates, respectively. There was nearly a fourfold rise in the risk ratio as age increased from the youngest to oldest age groups. Home hemodialysis patients had the longest survival, 89% at 5 years; patients on CAPD had a 56% 5-year survival. In-center hemodialysis patients had a median survival of 48 months and a 5-year survival of 39%. Pairwise comparisons of the renal diagnostic groups found patients with polycystic kidneys, interstitial disease and chronic glomerulonephritis to have better survival than patients with diabetes mellitus, renal vascular disease or the "other" diagnoses (log-rank test, p < 0.001). Survival analyses showed age, renal diagnosis, race, type of dialysis and dialysis modality switch to be important predictors of survival. The results of the survival estimates, gross mortality rates and standardized mortality ratios were used as guides to the adequacy of dialysis and quality of care delivered for the years 1989 through 1992.
Time Prediction of Mouse-based Cursor Movements (2001)

This paper addresses the prediction of movement time of mouse-based cursor transfers between objects in a graphical user interface. We present the data from an experimental study aimed at obtaining an appropriate model for movement time prediction. As can be seen from the data, Fitts ’ law which is widely used as a predictor for such movements fails with our data. This is not only for low values of Fitts ’ index of difficulty as known from the literature, but also for small target areas like radio buttons, combo boxes, and buttons on toolbars such as typically occurring with graphical user interfaces. We present a new power model for movement time prediction derived from our data and compare this model to other models from the literature.
Glyceryl Methacrylate Hydrogel as a Vitreous Implant (1968)

Glyceryl methacrylate (GMA) hydrogel was used as a vitreous implant in 15 rabbit eyes which have been observed for seven months and are still being followed. The dehydrated gel was placed into the vitreous cavity through a small incision at the pars plana ciliaris. Inside the eye the implant swelled by absorbing available intraocular fluid. The final volume of the hydrogel, which can be calculated in advance, was about 32 times bigger than that of the dry implant. The softness of the GMA hydrogel approximated that of the vitreous gel with refractive index, specific gravity, and permeability to water very close to that of the vitreous body. The implants were well tolerated with little or no inflammatory reaction. No complications were observed to result from the presence of the implant inside the eye.
Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP‐ribose) polymerase‐1/2 inhibitors (2005)

Two classes of quinazolinone derivatives and quinoxaline derivatives were identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1) and (PARP-2) inhibitors, respectively. In PARP enzyme assays using recombinant PARP-1 and PARP-2, quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2. SBDD analysis via a combination of X-ray structural study and homology modeling suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2.
CHILD MAURICE (2014)

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Neuropathological spectrum of synucleinopathies (2003)

Synucleinopathies comprise a diverse group of neurodegenerative proteinopathies that share common pathological lesions composed of aggregates of conformational and posttranslational modifications of alpha-synuclein in selected populations of neurons and glia. Abnormal filamentous aggregates of misfolded alpha-synuclein protein are the major components of Lewy bodies, dystrophic (Lewy) neurites, and the Papp-Lantos filaments in oligodendroglia and neurons in multiple system atrophy linked to degeneration of affected brain regions. The synucleinopathies include (1) Lewy body disorders and dementia with Lewy bodies, (2) multiple system atrophy (MSA), and (3) Hallervorden-Spatz disease. (1) The pathological diagnosis of Lewy body disorders and dementia with Lewy bodies is established by validated consensus criteria based on semiquantitative assessment of subcortical and cortical Lewy bodies as their common hallmarks. They are accompanied by subcortical multisystem degeneration with neuronal loss and gliosis with or without Alzheimer pathologic state. Lewy bodies also occur in numerous other disorders, including pure autonomic failure, neuroaxonal dystrophies, and various amyloidoses and tauopathies. (2) Multiple system atrophy, a sporadic, adult-onset degenerative movement disorder of unknown cause, is characterized by alpha-synuclein-positive glial cytoplasmic and rare neuronal inclusions throughout the central nervous system associated with striatonigral degeneration, olivopontocerebellar atrophy, and involvement of medullar and spinal autonomic nuclei. (3) In neurodegeneration with brain iron accumulation type I, or Hallervorden-Spatz disease, alpha-synuclein is present in axonal spheroids and glial and neuronal inclusions. While the identity of the major components of Lewy bodies suggests that a pathway leading from normal soluble to abnormal misfolded filamentous proteins is central for their pathogenesis, regardless of the primary disorder, there are conformational differences in alpha-synuclein between neuronal and glial aggregates, showing nonuniform mapping for its epitopes. Despite several cellular and transgenic models, it is not clear whether inclusion body formation is an adaptive/neuroprotective or a pathogenic reaction/process generated in response to different, mostly undetermined, functional triggers linked to neurodegeneration.