gebhart/patrepeval huggingface dataset:
Enantioselective Total Synthesis of Ecteinascidin 743 (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEnantioselective Total Synthesis of Ecteinascidin 743E. J. Corey, David Y. Gin, and Robert S. KaniaView Author Information Department of Chemistry, Harvard University Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1996, 118, 38, 9202–9203Publication Date (Web):September 25, 1996Publication History Received18 July 1996Published online25 September 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja962480thttps://doi.org/10.1021/ja962480trapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views12530Altmetric-Citations295LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Allyl group,Aromatic compounds,Hydrocarbons,Hydroxyls,Lactones Get e-Alerts
Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action (1997)

Frizzled polypeptides are integral membrane proteins that recently were shown to function as receptors for Wnt signaling molecules. Here, we report the identification of a novel, secreted 36-kDa protein that contains a region homologous to a putative Wnt-binding domain of Frizzleds. This protein, called Frizzled-related protein (FRP), was first identified as a heparin-binding polypeptide that copurified with hepatocyte growth factor/scatter factor in conditioned medium from a human embryonic lung fibroblast line. Degenerate oligonucleotides, based on the NH2-terminal sequence of the purified protein, were used to isolate corresponding cDNA clones. These encoded a 313-amino acid polypeptide, containing a cysteine-rich domain of approximately 110 residues that was 30-40% identical to the putative ligand-binding domain of Frizzled proteins. A 4.4-kb transcript of the FRP gene is present in many organs, both in the adult and during embryogenesis, and homologs of the gene are detectable in DNA from several vertebrate species. In biosynthetic studies, FRP was secreted but, like Wnts, tended to remain associated with cells. When coexpressed with several Wnt family members in early Xenopus embryos, FRP antagonized Wnt-dependent duplication of the embryonic dorsal axis. These results indicate that FRP may function as an inhibitor of Wnt action during development and in the adult.
Finding schizophrenia genes (2005)

Genetic epidemiological studies suggest that individual variation in susceptibility to schizophrenia is largely genetic, reflecting alleles of moderate to small effect in multiple genes. Molecular genetic studies have identified a number of potential regions of linkage and 2 associated chromosomal abnormalities, and accumulating evidence favors several positional candidate genes. These findings are grounds for optimism that insight into genetic factors associated with schizophrenia will help further our understanding of this disease and contribute to the development of new ways to treat it.
Reactions of Ethylenimines. IX. The Mechanisms of Ring Openings of Ethylenimines in Acidic Aqueous Solutions1 (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactions of Ethylenimines. IX. The Mechanisms of Ring Openings of Ethylenimines in Acidic Aqueous Solutions1Joseph E. Earley, Charles E. O'Rourke, Leallyn B. Clapp, John O. Edwards, and Bernard C. LawesCite this: J. Am. Chem. Soc. 1958, 80, 13, 3458–3462Publication Date (Print):July 1, 1958Publication History Published online1 May 2002Published inissue 1 July 1958https://pubs.acs.org/doi/10.1021/ja01546a062https://doi.org/10.1021/ja01546a062research-articleACS PublicationsRequest reuse permissionsArticle Views308Altmetric-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
An X-Y paint set and sperm FISH protocol that can be used for validation of cattle sperm separation procedures (2001)

X and Y chromosome paints were developed from sorted yak chromosomes for sexing cattle spermatozoa. Clear hybridization signals were obtained for every spermatozoon using a modified sperm decondensation protocol and fluorescence in situ hybridization (FISH). The procedure was evaluated using the established Beltsville sperm sexing technology, which separates spermatozoa by flow cytometry into X- and Y-bearing fractions. Close agreement was found between the assessment of sperm separation by flow cytometry and by FISH with the X-Y paint set. The FISH method is a simple, reliable and robust procedure for assessing the effectiveness of separation of X and Y spermatozoa.
Retinitis pigmentosa: clinical observations and correlations. (1983)

This thesis presents the results of a study of 384 eyes of 192 patients with a mean age of 39.1 years who presented with typical retinitis pigmentosa. The major findings are outlined below, together with suggested hypotheses: Cataract was found in 46.4% of the eyes. Among these, 93.6% showed posterior subcapsular opacification. The incidence of cataract increased with age. The vitreous degeneration that is characteristic of the RP syndrome and begins in childhood was described as showing dust-like, particulate matter throughout the gel; posterior vitreous separation; formation of a posterior matrix of coarse, white, interconnected strands and opacities; and final collapse of the residual gel. Ultrastructural studies of vitreous material from eight eyes revealed that the particles were isolated pigment granules and the coarse strands were composed of condensed collagen fibers. Notwithstanding the vitreous degeneration and prevalence of myopia in RP, neurosensory retinal breaks and/or rhegmatogenous detachment were found in only 7 (1.8%) of the 384 eyes studied. Premature separation of the vitreous from the retina, absence of lattice retinal degeneration, and perhaps a stronger than normal RPE-neurosensory retinal bond are thought to be possible protective factors. Rather than searching for a "toxin," elaborated by diseased retina, that causes vitreous degeneration and cataract formation, it is suggested that the ocular media be studied for an absence of moieties that are normally produced by healthy retina for vitreous and lens maintenance. The classic criteria for diagnosis of RP were met by 96.3% of eyes that showed retinal vascular attenuation and by 52.0% that showed pallor of the optic disc. Less frequent manifestations included solitary retinal hemorrhage, peripheral microaneurysms, telangiectasia, and fluorescein leakage at the macula and disc. Seven additional cases with a Coats'-like retinal detachment were added to the 14 already presented in the literature. Two of the seven had autosomal dominant RP, the first such cases reported. The vascular malformations and detachments were most often inferior. Unlike typical Coats' syndrome, the condition was usually bilateral, showed no sex preference, and appeared to affect older individuals.(ABSTRACT TRUNCATED AT 400 WORDS)
Complement‐mediated lysis of type‐C virus: Effect of primate and human sera on various retroviruses (1978)

Abstract Antibody‐independent complement‐mediated lysis of type‐C RNA tumor viruses (retroviruses) was measured in the sera of humans and other primates using the reverse transcriptase release assay. In this assay, preincubated mixtures of test serum and virus are assayed for the presence of viral reverse transcriptase released from disrupted virions. Serum decomplemented by heating possesses no such activity. Sera containing non‐specific heat‐labile factors inhibitory to the reverse transcriptase release assay are excluded from consideration. According to this assay, both normal and leukemic human sera, as well as sera from several other primate species including apes, Old World monkeys and New World monkeys, are all capable of lysing both endogenous and infectious primate and murine type‐C viruses. At least two non‐primate species (cat and rabbit) also possess this activity, although several other non‐primates do not. There is no appreciable viral specificity; each test serum possessing complement‐mediated virolytic activity can lyse all classes of retroviruses against which it is tested. Those primate species which spontaneously release retroviruses (baboon, squirrel monkey), as well as those primate species which are infected with exogenous retroviruses (rhesus, gibbon ape), are all capable of lysing their respective viruses. In addition, the relative efficiency of complement‐mediated viral lysis correlates better with primate phylogeny than with the relative ease of type‐C virus release or transmission. This would seem to suggest that complement‐mediated viral lysis does not, in fact, play a primary role in blocking the release or transmission of type‐C viruses among primates.
Analysis of Newly Identified and Rare Synonymous Genetic Variants in the RET Gene in Patients with Medullary Thyroid Carcinoma in Polish Population (2017)

Gain-of-function germline mutations of the RET proto-oncogene are responsible for initiation of carcinogenesis within the thyroid gland and development of hereditary form of medullary thyroid carcinoma and MEN2 syndrome. Genotype-phenotype correlations are established for most RET mutations, but the importance of the synonymous changes in this gene remains debatable. We aimed to analyze RET gene variants in Polish population. Genetic testing for the RET gene variants was performed with standard methods in 585 people aged 1-85, including 448 patients with medullary thyroid carcinoma and 131 of their first- and second-degree relatives, as well as six patients suspected of MTC/MEN2. Besides the most frequent synonymous changes, p.Leu769Leu, p.Ser836Ser, and p.Ser904Ser, four rare changes-c.1827C>T (p.Cys609Cys), c.2364C>T (p.Ile788Ile), c.2418C>T (p.Tyr806Tyr), and c.2673G>A (p.Ser891Ser)-were found in the RET gene, in the Polish population. Two of the rare changes, p.Cys609Cys and p.Ile788Ile, had not been previously described. The frequency of molecular synonymous variants in the general population was evaluated by testing 400 anonymous blood samples of neonates. Our findings may contribute to a better understanding of the genetic diversity of the RET gene and the involvement of synonymous variants in this diversity.
Flow Cytometric Analysis of Phosphorylated Histone H2AX Following Exposure to Ionizing Radiation in Human Microvascular Endothelial Cells (2006)

We applied a flow cytometric method to quantify IR-induced histone H2AX phosphorylation at serine 139 (gammaH2AX) and compared those values to those obtained using a standard microscopy based foci counting method. After PFA fixation, methanol permeabilization was suitable for both FITC- or Alexa647-gammaH2AX. In contrast, Alexa647-gammaH2AX was not suitable for ethanol permeabilization. Antibody concentrations at 1-2 microg/ml yielded the highest gammaH2AX positive percentage for both antibodies. Without DAPI staining, gammaH2AX formation can be measured as a relative fold increase. Values determined by bivariant flow cytometric analysis and those obtained using microscopic foci formation exhibited a good quantitative correlation. Values obtained by both methods could vary according to the gating or threshold setting used. gammaH2AX positive cells increased as a function of radiation dose (2-16 Gy) followed by a dose-dependent decay. The free radical scavenger N-acetyl-L-cysteine (NAC), if administered at a concentration of 4 mM 30 min before IR, was effective in reducing IR-induced gammaH2AX formation in all phases of the cell cycle. We have developed a simplified and quantitative flow cytometry based method to measure IR-induced gammaH2AX in cells and demonstrated strong correlation to values obtained by a standard automated digital microscopic foci analysis along with NIH ImageJ custom macro software.
Proteolytic Processing of the p75 Neurotrophin Receptor and Two Homologs Generates C-Terminal Fragments with Signaling Capability (2003)

The 75 kDa neurotrophin receptor (p75NTR) and two neurotrophin receptor homologs (NRH1, NRH2) constitute a subfamily of the nerve growth factor/tumor necrosis factor receptor superfamily. NRH1 coexists with p75NTR in fish, amphibians, and birds but is absent in mammals, whereas NRH2 exists only in mammals. Unlike p75NTR and NRH1, NRH2 lacks a canonical extracellular ligand binding domain. The similarity of NRH2 to the product of metalloproteinase cleavage of p75NTR prompted us to examine the cleavage of p75NTR in greater detail. p75NTR, NRH1, and NRH2 undergo multiple proteolytic cleavages that ultimately release cytoplasmic fragments. For p75NTR, cleavage in the extracellular domain by a PMA-inducible membrane metalloproteinase is followed by cleavage within or near the transmembrane domain, releasing the intracellular domain into the cytoplasm. This processing resembles the alpha- and gamma-secretase-mediated processing of beta-amyloid precursor protein and the similar processing of Notch. Although neurotrophins did not regulate p75NTR processing, the alpha- and gamma-secretase-mediated cleavage of p75 is modulated by receptor tyrosine kinases (Trks) TrkA and TrkB but not TrkC. Surprisingly, although NRH1 and NRH2 also undergo proteolytic cytoplasmic release of intracellular domains, a different protease mediates the cleavage. Furthermore, whereas the p75NTR soluble intracellular domain accumulates only in the presence of proteasome inhibitors, the equivalent fragment of NRH2 is stable and localizes in the nucleus. Because soluble intracellular domains of p75NTR and NRH2 were found to activate NF-kappaB in concert with TNF receptor associated factor 6 (TRAF6), we propose that cleavage of these proteins may serve conserved cytoplasmic and nuclear signaling functions through distinct proteases.
The diffusion and thermal diffusion of hydrogen-deuterium, with a note on the thermal diffusion of hydrogen-helium (1941)

Abstract The diffusion coefficient D12 has been determined for hydrogen-deuterium and is found to be in close agreement with the value predicted by the classical theory. The case is one of particular interest because the diffusing molecules have the same size and the same molecular field. The thermal separation in mixtures of this pair of gases has also been measured. As the molecules are of the same size, the thermal separation is due entirely to difference in mass. By using Chapman’s theory, the value of the repulsive force index (v12) is deduced. By combining the values of v12 and D12, the repulsive force constant k12 can be determined, and so the complete law of force operating in collisions between unlike molecules can be obtained. On classical considerations this law of force would apply to either gas separately. Measurements of thermal separation in mixtures of hydrogen-helium have also been made and the value of v12 determined. It is shown that this pair of molecules is 'harder’ than hydrogen-deuterium. Comparison is made with earlier results of Elliott and Masson.
Surface plasmon broadening for arbitrary shape nanoparticles: A geometrical probability approach (2003)

A geometrical probability measure is proposed for calculating the effective conduction electron mean free path of an arbitrary shape convex particle. It is shown that the plasmon widths determined from this mean free path are consistent with exact quantum mechanical widths for simple particle shapes. We use the mean free path formula to evaluate size and shape dependent dielectric functions and extinction spectra for silver spheroids, square prisms, truncated tetrahedrons, and cylinders.
Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds (2013)

Recent experimental evidence suggests that transcellular propagation of fibrillar protein aggregates drives the progression of neurodegenerative diseases in a prion-like manner. This phenomenon is now well described in cell and animal models and involves the release of protein aggregates into the extracellular space. Free aggregates then enter neighboring cells to seed further fibrillization. The mechanism by which aggregated extracellular proteins such as tau and α-synuclein bind and enter cells to trigger intracellular fibril formation is unknown. Prior work indicates that prion protein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface to transmit pathologic processes. Here, we find that tau fibril uptake also occurs via HSPG binding. This is blocked in cultured cells and primary neurons by heparin, chlorate, heparinase, and genetic knockdown of a key HSPG synthetic enzyme, Ext1. Interference with tau binding to HSPGs prevents recombinant tau fibrils from inducing intracellular aggregation and blocks transcellular aggregate propagation. In vivo, a heparin mimetic, F6, blocks neuronal uptake of stereotactically injected tau fibrils. Finally, uptake and seeding by α-synuclein fibrils, but not huntingtin fibrils, occurs by the same mechanism as tau. This work suggests a unifying mechanism of cell uptake and propagation for tauopathy and synucleinopathy.
Carotid artery stenting (2003)

Two major randomised trials concerning the surgical treatment of carotid artery stenosis showed that carotid endarterectomy is superior to medical treatment in reducing the overall risk of stroke in symptomatic or asymptomatic patients.w1–4 The first phase of the North American endarterectomy trial (NASCET)w1 confirmed the superiority for symptomatic severe (lumen diameter reduction > 70%) carotid stenoses while the second phase of the NASCET trial showed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis (50–70%).w4 The asymptomatic carotid study (ACAS) showed a reduction in stroke rate after carotid endarterectomy also in asymptomatic patients with carotid stenoses > 60%.w2

Although carotid endarterectomy is nowadays considered the gold standard for the treatment of carotid occlusive disease, the approach is not without complications. In the NASCET study population, 5.8% of patients suffered from perioperative death and stroke. When the attention is focused on routine clinical practice without strict patient selection criteria, or if a neurological audit is performed by independent neurologists, the incidence of major events can easily double.1

Since the first percutaneous transluminal carotid angioplasty was performed by Kerber in 1980,w5 the rapid improvement in interventional technology and materials has transformed a technique initially developed as a palliative treatment in inoperable patients into a therapeutic alternative option to surgery.w6–9 The main concern has always been the safety of such intervention in terms of cerebral embolisation, a frequent event during the procedure detected by transcranial Doppler monitoring, diffusion weighted magnetic resonance, and retinal fluoangioscopy even in asymptomatic patients.w10 w11 This may be explained by the presence of thrombotic material in carotid plaques frequently observed during surgical exploration.w12 Preliminary studies evaluating the safety and efficacy of carotid angioplasty showed a higher incidence of stroke and death compared to carotid endarterectomy.w7 w13–15 One …
Avanti 3: A Randomized, Double-Blind Trial to Compare the Efficacy and Safety of Lamivudine plus Zidovudine versus Lamivudine plus Zidovudine plus Nelfinavir in HIV-1-Infected Antiretroviral-Naive Patients (2001)

The objective of our randomized, multicentre, double-blind, placebo-controlled study was to investigate the safety, tolerability, and antiretroviral and immunological effect of double and triple combination therapy regimens. A total of 105 antiretroviral therapy-naive patients were randomized to receive either zidovudine (300 mg twice per day) plus lamivudine (150 mg twice per day) plus nelfinavir placebo (three times per day) (n=52), or zidovudine/lamivudine (dose as before) plus nelfinavir (750 mg three times per day) (n=53) for 28 weeks. After this time, patients were allowed to switch to open-label zidovudine/lamivudine/nelfinavir. The overall log10 reduction from baseline in plasma HIV-1 RNA was significantly greater in the zidovudine/lamivudine/nelfinavir group than the zidovudine/lamivudine group (P=0.001; median treatment difference, -1.01 log10 copies/ml; 95% confidence interval -1.23 to -0.79), as measured by the average area under the curve minus baseline over 28 weeks. Increases from baseline in CD4 cell counts were statistically significantly greater in the zidovudine/ lamivudine/nelfinavir group (101.5 cells/ml) than the zidovudine/lamivudine group (47.0 cells/ml; P=0.027) at week 28. Of note, the addition of nelfinavir from weeks 28-52 led to an increase in the proportion of subjects with plasma HIV-1 RNA <400 copies/ml from 17% (9/52 patients on zidovudine/lamivudine) to 50% (13/26 patients who switched to zidovudine/lamivudine/nelfinavir). Incidence of drug-related adverse events was similar in the two groups, except for nausea (more common in zidovudine/lamivudine group; 40 versus 17%) and diarrhoea (more common in zidovudine/lamivudine/nelfinavir group; 45 versus 14%). In conclusion, our study confirms the efficacy of triple combination therapy with two nucleoside analogues and a protease inhibitor compared with double-nucleoside therapy. Interestingly, the addition of nelfinavir to zidovudine/lamivudine, even after 6 months of double nucleoside therapy, led to a substantial virological benefit that was sustained over 24weeks in a subset of patients.