gebhart/patrepeval huggingface dataset:
Utility of an objective dyskinesia rating scale for Parkinson's disease: Inter‐ and intrarater reliability assessment (1994)

Although dyskinesia is a frequent and important problem in Parkinson's disease (PD), a reliable assessment measure has not been thoroughly developed and tested. We modified the Obeso dyskinesia scale to create an objective rating scale for dyskinesia assessment during activities of daily living. Thirteen physicians and 15 study coordinators involved in a clinical trial independently reviewed videotape segments of PD patients performing three tasks: walking, putting on a coat, and lifting a cup to the lips for drinking. Raters evaluated the severity of worst dyskinesia seen, the types of all dyskinesias seen, and the type of dyskinesia most associated with motoric disability. For all assessments, the total group showed statistically significant inter- and intrarater reliability. Physicians had a higher consistency than did coordinators, but for most measures the difference was not statistically significant. Physicians and coordinators found the scale easy to use and especially practical for rating dyskinesia severity and for identifying the most disabling dyskinesia. Dyskinesias can be assessed in clinical trials and warrant regular documentation.
Transcription of the hypersensitive site HS2 enhancer in erythroid cells. (1992)

In the human genome, the erythroid-specific hypersensitive site HS2 enhancer regulates the transcription of the downstream beta-like globin genes 10-50 kilobases away. The mechanism of HS2 enhancer function is not known. The present study employs RNA protection assays to analyze the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids. In erythroid K562 cells in which the HS2 enhancer is active, the HS2 sequence directs the synthesis of long enhancer transcripts that are initiated apparently from within the enhancer and elongated through the intervening DNA into the cis-linked CAT gene. In nonerythroid HL-60 cells in which the HS2 enhancer is inactive, long enhancer transcripts are not detectable. Splitting the HS2 enhancer between two tandem Ap1 sites abolishes the synthesis of a group of long enhancer transcripts and results in loss of enhancer function and transcriptional silencing of the cis-linked CAT gene. In directing the synthesis of RNA through the intervening DNA and the gene by a tracking and transcription mechanism, the HS2 enhancer may (i) open up the chromatin structure of a gene domain and (ii) deliver enhancer binding proteins to the promoter sequence where they may stimulate the transcription of the gene at the cap site.
A New Method for the Synthesis of Furanose Derivatives of Aldohexoses1 (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA New Method for the Synthesis of Furanose Derivatives of Aldohexoses1Paul Kohn, Rita H. Samaritano, and Leon M. LernerCite this: J. Am. Chem. Soc. 1965, 87, 23, 5475–5480Publication Date (Print):December 1, 1965Publication History Published online1 May 2002Published inissue 1 December 1965https://pubs.acs.org/doi/10.1021/ja00951a041https://doi.org/10.1021/ja00951a041research-articleACS PublicationsRequest reuse permissionsArticle Views297Altmetric-Citations52LEARN 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 Other access optionsGet e-Alertsclose Get e-Alerts
Analysis of several key active site residues of ricin A chain by mutagenesis and X-ray crystallography (1992)

Active site residues of ricin A chain were analyzed by site-directed mutagenesis and X-ray diffraction to help assess their roles in the mechanism of action of this toxic N-glycosidase enzyme. Arg180 is thought, from X-ray studies, to protonate the adenine substrate at N3; this facilitates bond cleavage and is crucial to the mechanisms of action. The residue was converted to Gln and initial rate data measured. Km for the mutant is not significantly affected, increasing only 2-fold. The kcat, however, is decreased approximately 1000-fold. This is consistent with a simple interpretation that Arg180 is involved more in transition state stabilization than in substrate binding. Tyrosines 80 and 123 are known from X-ray models to stack on either side of the substrate adenine ring. When they were each converted to serine overall activity was reduced 160- and 70-fold respectively against ribosomes from Artemia salina. These effects are each approximately 10 times greater than when the residues were previously converted to phenylalanines. Sufficient protein for the Tyr80 to Phe mutant was obtained to carry out an X-ray analysis. Together with mutagenesis data, the structure suggests that the invariance of the two active site Tyr residues is largely caused by structural stability.
Molecular definition of bovine argininosuccinate synthetase deficiency. (1989)

Citrullinemia is an inborn error of metabolism due to deficiency of the urea cycle enzyme, argininosuccinate synthetase [L-citrulline:L-aspartate ligase (AMP-forming), EC 6.3.4.5]. The disease was first described in humans but was recently reported in dairy cattle in Australia. Here we report the nucleotide sequence of the normal bovine cDNA for argininosuccinate synthetase and the mutation present in animals with citrullinemia. Analysis of DNA from affected animals by Southern blotting did not readily identify the mutation in the bovine gene. RNA (Northern) blotting revealed a major reduction in the steady-state amount of mRNA in the liver of affected animals to less than 5% of controls. The bovine cDNA was cloned and sequenced and revealed 96% identity with the deduced human sequence at the amino acid level. Starting with mutant bovine liver, the mRNA was reverse-transcribed; the cDNA product was amplified with the polymerase chain reaction, cloned, and sequenced. The sequence revealed a C----T transition converting arginine-86 (CGA) to a nonsense codon (TGA). A second C----T transition represented a polymorphism in proline-175 (CCC----CCT). The mutation and the polymorphism were confirmed by amplification of genomic DNA and demonstration with restriction endonuclease enzymes of both the loss of an Ava II site in DNA from mutant animals at codon 86 and the presence or absence of a Dde I site at codon 175. The loss of the Ava II site can be used for rapid, economical, nonradioactive detection of heterozygotes for bovine citrullinemia.
Identification of immunoreactive antigens of human papillomavirus type 6b by using Escherichia coli-expressed fusion proteins (1988)

Human papillomavirus (HPVs) infect the genital epithelium and are found in proliferative lesions ranging from benign condylomata to invasive carcinomas. The immunological response to these infections is poorly understood because of the lack of purified viral antigens. In this study, bacterially derived fusion proteins expressing segments of all the major open reading frames (ORFs) of HPV type 6b (HPV-6b) have been used in Western blot (immunoblot) assays to detect antibodies directed against HPV-encoded proteins. The most striking reactivities present in sera from patients with genital warts were to the HPV-6b L1 ORF protein and, to a lesser extent, to the HPV-6b L2 ORF protein. Two cases of reactivity to HPV-6b E2 ORF were observed, but no reactivities were seen with other HPV-6b constructs. Two sera reacted with the HPV-16 L2 fusion protein, and two sera reacted with the HPV-16 E4 protein. The antibodies directed against the HPV-6b fusion proteins showed no cross-reactivity with comparable regions of the HPV-16 ORFs. This assay provides a useful approach for further studies of HPV serology.
An immuno‐dot blot assay for detection of thermostable protease from Pseudomonas sp. AFT‐36 of dairy origin (1997)

A dot-ELISA technique for the detection of Pseudomonas protease was developed using IgG of anti-Pseudomonas AFT-36 protease as capture antibody. The detection limit of protease in buffer or milk was 1.01 ng ml-1. The procedure was performed at room temperature, took about 2.5 h and was economical. Protease AFT-36 is immunologically related to five out of seven Pseudomonas spp. The results suggest that the assay could be used to detect proteases in dairy products.
L-.beta.-(2S,4S)- and L-.alpha.-(2S,4R)-dioxolanyl nucleosides as potential anti-HIV agents: asymmetric synthesis and structure-activity relationships (1993)

In order to study the structure-activity relationships of L-(2S,4S)- and L-(2S,4R)-dioxolanyl nucleoside as potential anti-HIV agents, various enantiomerically pure L-(2S,4S)- and (2S,4R)-dioxolanylpyrimidine and -purine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear (PBM) cells. The enantiomerically pure key intermediate 8 has been synthesized in six steps from 1,6-anhydro-beta-L-gulose (2), and compound 8 was condensed with 5-substituted pyrimidines, 6-chloropurine, and 2,6-disubstituted purine to obtain various dioxolanylpyrimidine and -purine nucleosides, respectively. Among the compound synthesized, 5-fluorocytosine derivative 29 was found to exhibit the most potent anti-HIV activity (EC50 = 0.0012 microM) although it was toxic (IC50 = 10.0 microM). The order of anti-HIV potency of pyrimidine analogues was as follows: 5-fluorocytosine (beta-isomer) > cytosine (beta-isomer) > 5-fluorocytosine (alpha-isomer) > 5-iodocytosine (beta-isomer) > cytosine (alpha-isomer) > 5-bromocytosine (beta-isomer) > thymine (beta-isomer) > 5-methylcytosine (alpha-isomer) > 5-iodocytosine (alpha-isomer) > 5-chlorocytosine (beta-isomer). The anti-HIV potency of purine analogues was found to be in the following decreasing order: 2,6-diaminopurine (beta-isomer) > 2-chloroadenine (alpha-isomer) > 2-fluoroadenine (beta-isomer) > adenine (beta-isomer) > 2-amino-6-chloropurine (alpha-isomer) > 2-amino-6-chloropurine (beta-isomer) > guanine (beta-isomer) > 2-fluoroadenine (alpha-isomer) > adenine (alpha-isomer) > 2,6-diaminopurine (alpha-isomer) > N6-methyladenine (beta-isomer). It is interesting to note that the alpha-5-fluorocytosine analogue exhibited an excellent anti-HIV activity (EC50 = 0.063 microM) without cytotoxicity up to 100 microM in PBM cell.
The clinically active BTK inhibitor PCI-32765 targets B-cell receptor– and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia (2012)

Small-molecule drugs that target the B-cell antigen receptor (BCR) signalosome show clinical efficacy in the treatment of B-cell non-Hodgkin lymphoma. These agents, including the Bruton tyrosine kinase (BTK) inhibitor PCI-32765, display an unexpected response in patients with chronic lymphocytic leukemia (CLL): a rapid and sustained reduction of lymphadenopathy accompanied by transient lymphocytosis, which is reversible upon temporary drug deprivation. We hypothesized that this clinical response reflects impaired integrin-mediated adhesion and/or migration. Here, we show that PCI-32765 strongly inhibits BCR-controlled signaling and integrin α(4)β(1)-mediated adhesion to fibronectin and VCAM-1 of lymphoma cell lines and primary CLL cells. Furthermore, PCI-32765 also inhibits CXCL12-, CXCL13-, and CCL19-induced signaling, adhesion, and migration of primary CLL cells. Our data indicate that inhibition of BTK by PCI-32765 overcomes BCR- and chemokine-controlled integrin-mediated retention and homing of malignant B cells in their growth- and survival-supporting lymph node and bone marrow microenvironment, which results in clinically evident CLL regression.
Retentive Multipotency of Adult Dorsal Root Ganglia Stem Cells (2009)

Preservation of neural stem cells (NSCs) in the adult peripheral nervous system (PNS) has recently been confirmed. However, it is not clear whether peripheral NSCs possess predestined, bona fide phenotypes or a response to innate developmental cues. In this study, we first demonstrated the longevity, multipotency, and high fidelity of sensory features of postmigrating adult dorsal root ganglia (aDRG) stem cells. Derived from aDRG and after 4-5 years in culture without dissociating, the aDRG NSCs were found capable of proliferation, expressing neuroepithelial, neuronal, and glial markers. Remarkably, these aDRG NSCs expressed sensory neuronal markers vesicular glutamate transporter 2 (VGluT2--glutamate terminals), transient receptor potential vanilloid 1 (TrpV1--capsaicin sensitive), phosphorylated 200 kDa neurofilaments (pNF200--capsaicin insensitive, myelinated), and the serotonin transporter (5-HTT), which normally is transiently expressed in developing DRG. Furthermore, in response to neurotrophins, the aDRG NSCs enhanced TrpV1 expression upon exposure to nerve growth factor (NGF), but not to brain-derived neurotrophic factor (BDNF). On the contrary, BDNF increased the expression of NeuN. Third, the characterization of aDRG NSCs was demonstrated by transplantation of red fluorescent-expressing aDRG NSCs into injured spinal cord. These cells expressed nestin, Hu, and beta-III-tubulin (immature neuronal markers), GFAP (astrocyte marker) as well as sensory neural marker TrpV1 (capsaicin sensitive) and pNF200 (mature, capsaicin insensitive, myelinated). Our results demonstrated that the postmigrating neural crest adult DRG stem cells not only preserved their multipotency but also were retentive in sensory potency despite the age and long-term ex vivo status.
Tailored cloze: improved with classical item analysis techniques (1988)

This study investigates the possibility that the reliability and validity of a cloze procedure can be improved by applying traditional item analysis and selection techniques. Students in a single level (n = 89) at the Guangzhou English Language Centre (People's Republic of China) were chosen for this study because previous experience and research had indicated that cloze tests gene rally produce low reliability and validity coefficients in samples wherein the range of ESL proficiencies is limited. This turned out to be the case when a 399-word every seventh word deletion cloze passage with 50 items was administered to this group. The study was designed such that 250 of the poten tial items in this passage could be piloted and item analyzed. The results of the item analysis were used to select the 'best' items on the basis of item facility and discrimination indices. The resulting 50 item 'tailored cloze' was then read ministered to the same group and the results for the original version of the cloze test were compared to those for the tailored version. These results indicate statistically significant and meaningful improvements in test quality due to the revision. The dispersion of scores, reliability and validity were all substantially improved by the item analysis and selection processes. The article concludes with discussion of the implications of these findings.
Flow Cytometry: A Practical Approach (1994)

Introduction to the principles of flow cytometry An introduction to fluorescence technology Preparing suspensions of single cells Flow sorting Immunofluorescence of surface markers Measurement of cytoplasmic and nuclear antigens Analysis of DNA - general methods Analysis of DNA-measurement of cell kinetics by the bromodeoxyuridine/anti-bromodeoxyuridine method Analysis of cell proliferation using the bromodeoxyuridine-Hoechst ethidium bromide method Chromosome analysis and sorting Intracellular ionized calcium, magnesium, membrane potential and pH Flow cytometry of RNA content Measurement of dynamic cellular events Further applications to cell biology.
High-speed optical modulation based on carrier depletion in a silicon waveguide (2007)

We present a high-speed and highly scalable silicon optical modulator based on the free carrier plasma dispersion effect. The fast refractive index modulation of the device is due to electric-field-induced carrier depletion in a Silicon-on-Insulator waveguide containing a reverse biased pn junction. To achieve high-speed performance, a travelling-wave design is used to allow co-propagation of electrical and optical signals along the waveguide. We demonstrate high-frequency modulator optical response with 3 dB bandwidth of ~20 GHz and data transmission up to 30 Gb/s. Such high-speed data transmission capability will enable silicon modulators to be one of the key building blocks for integrated silicon photonic chips for next generation communication networks as well as future high performance computing applications.
On the Irregular Nonbinary QC-LDPC-Coded Hybrid Multidimensional OSCD-Modulation Enabling Beyond 100 Tb/s Optical Transport (2013)

As a solution to limited bandwidth and high energy consumption of information infrastructure as well as heterogeneity of optical networks, a hybrid multidimensional coded modulation scheme is proposed employing all available electrical and optical degrees of freedom. Electrical basis functions are based on either modified orthogonal polynomials or prolate spheroidal wave functions, while optical ones on polarization and spatial mode states. The proposed scheme is both multi-Tb/s and beyond 100 Tb/s enabling technology. Additionally, the proposed scheme provides the adaptive, software-defined, and dynamic allocation of bandwidth with fine granularity. The adaptive coding is based on irregular nonbinary quasi-cyclic LDPC codes, providing record net coding gains.
Metabotropic Glutamate 5 Receptor Blockade Alleviates Akinesia by Normalizing Activity of Selective Basal-Ganglia Structures in Parkinsonian Rats (2003)

Glutamate overactivity within the basal ganglia has been shown to be central to the expression of motor symptoms in advanced stages of Parkinson's disease, and metabotropic glutamate receptors (mGluRs) represent promising targets for new therapeutic strategies in this pathology. Little is known, however, about the cellular and behavioral changes occurring in the early stages of the disease when dopamine depletion is moderate. Here, we report that rats with partial bilateral dopamine lesions exhibit akinetic deficits associated with dramatically increased neuronal metabolic activity in selective structures of the basal ganglia such as the subthalamic nucleus and the substantia nigra pars reticulata, but not in the entopeduncular nucleus. Furthermore, chronic treatment with the mGluR5 antagonist 2-methyl-6-(phenylethylnyl)-pyridine alleviated the akinesia and was associated with a normalization of the activity of these two overactive structures. These data stress the therapeutic potential of mGluR5 antagonists in the treatment of parkinsonian patients in the early stages of the disease.
Statistics of random spikes in the intensity of stimulated Raman scattering: initiation by spatially distributed fluctuations (1993)

The statistical properties of spikes in the intensity of stimulated Raman scattering and investigated. The number of spikes taking place up to a given moment in time and the distribution of the temporal durations and the amplitudes of the spikes are calculated for the case in which the spikes are initiated by a spatially distributed polarization fluctuation.
Multigene Engineering of Triacylglycerol Metabolism Boosts Seed Oil Content in Arabidopsis (2014)

Increasing the yield of oilseed crops is an important objective for biotechnologists. A number of individual genes involved in triacylglycerol metabolism have previously been reported to enhance the oil content of seeds when their expression is altered. However, it has yet to be established whether specific combinations of these genes can be used to achieve an additive effect and whether this leads to enhanced yield. Using Arabidopsis (Arabidopsis thaliana) as an experimental system, we show that seed-specific overexpression of WRINKLED1 (a transcriptional regulator of glycolysis and fatty acid synthesis) and DIACYLGLYCEROL ACYLTRANSFERASE1 (a triacylglycerol biosynthetic enzyme) combined with suppression of the triacylglycerol lipase SUGAR-DEPENDENT1 results in a higher percentage seed oil content and greater seed mass than manipulation of each gene individually. Analysis of total seed yield per plant suggests that, despite a reduction in seed number, the total yield of oil is also increased.
A Natural Product Telomerase Activator As Part of a Health Maintenance Program (2010)

Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. In January, 2007, a commercial health maintenance program, PattonProtocol-1, was launched that included a natural product-derived telomerase activator (TA-65®, 10-50 mg daily), a comprehensive dietary supplement pack, and physician counseling/laboratory tests at baseline and every 3-6 months thereafter. We report here analysis of the first year of data focusing on the immune system. Low nanomolar levels of TA-65® moderately activated telomerase in human keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of TA-65® were achieved in pilot human pharmacokinetic studies with single 10- to 50-mg doses. The most striking in vivo effects were declines in the percent senescent cytotoxic (CD8(+)/CD28(-)) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p = not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months (p = 0.028 and 0.00013, respectively). Most of these decreases were seen in cytomegalovirus (CMV) seropositive subjects. In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months was measured. Although mean telomere length did not increase, there was a significant reduction in the percent short (<4 kbp) telomeres (p = 0.037). No adverse events were attributed to PattonProtocol-1. We conclude that the protocol lengthens critically short telomeres and remodels the relative proportions of circulating leukocytes of CMV(+) subjects toward the more "youthful" profile of CMV(-) subjects. Controlled randomized trials are planned to assess TA-65®-specific effects in humans.