gebhart/patrepeval huggingface dataset:
Deoxygenation of Polyhydroxybenzenes:  An Alternative Strategy for the Benzene-Free Synthesis of Aromatic Chemicals (2002)

New synthetic connections have been established between glucose and aromatic chemicals such as pyrogallol, hydroquinone, and resorcinol. The centerpiece of this approach is the removal of one oxygen atom from 1,2,3,4-tetrahydroxybenzene, hydroxyhydroquinone, and phloroglucinol methyl ether to form pyrogallol, hydroquinone, and resorcinol, respectively. Deoxygenations are accomplished by Rh-catalyzed hydrogenation of the starting polyhydroxybenzenes followed by acid-catalyzed dehydration of putative dihydro intermediates. Pyrogallol synthesis consists of converting glucose into myo-inositol, oxidation to myo-2-inosose, dehydration to 1,2,3,4-tetrahydroxybenzene, and deoxygenation to form pyrogallol. Synthesis of pyrogallol via myo-2-inosose requires 4 enzyme-catalyzed and 2 chemical steps. For comparison, synthesis of pyrogallol from glucose via gallic acid intermediacy and the shikimate pathway requires at least 20 enzyme-catalyzed steps. A new benzene-free synthesis of hydroquinone employs conversion of glucose into 2-deoxy-scyllo-inosose, dehydration of this inosose to hydroxyhydroquinone, and subsequent deoxygenation to form hydroquinone. Synthesis of hydroquinone via 2-deoxy-scyllo-inosose requires 2 enzyme-catalyzed and 2 chemical steps. By contrast, synthesis of hydroquinone using the shikimate pathway and intermediacy of quinic acid requires 18 enzyme-catalyzed steps and 1 chemical step. Methylation of triacetic acid lactone, cyclization, and regioselective deoxygenation of phloroglucinol methyl ether affords resorcinol. Given the ability to synthesize triacetic acid lactone from glucose, this constitutes the first benzene-free route for the synthesis of resorcinol.
The Assurance of Reliability of Television Automation Systems (1976)

Present-day automation systems frequently use a minicomputer in an on-line mode as the primary controller. The computer system consists of three major parts: the actual computer, the software instructing it how to perform its tasks, and the peripherals that connect it to the “outside world.” The reliability of each part in a computer-controlled television switching system and the options available to assure acceptable performance under various conditions of failure are discussed.
L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. (1992)

Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.
Serial killing by cytotoxic T lymphocytes: T cell receptor triggers degranulation, re‐filling of the lytic granules and secretion of lytic proteins via a non‐granule pathway (1995)

CD8+ cytotoxic T lymphocyte (CTL) clones begin to synthesize the lytic proteins granzyme A, granzyme B and perforin after stimulation with allogeneic target cells. The lytic proteins are stored in the secretory granules which are released after cross-linking of the T cell receptor (TcR) upon target cell recognition. During lytic granule biogenesis granzyme A protein synthesis can be detected between 2 and 10 days after allogeneic stimulation of the CTL. Although granzyme A is stored in the lytic granules over this period, the majority of granzyme A synthesized is secreted directly from the CTL. TcR triggering of degranulation also results in new synthesis of the lytic proteins, which can be inhibited by cycloheximide (CHX). Some of the newly synthesized lytic proteins can be stored in the cell and refill the granules. But up to one third of granzymes A and B can be secreted directly from the CTL via the constitutive secretory pathway as shown by granzyme A enzymatic activity and immunoblots of secreted granzyme B, where one third of the protein fails to acquire the granule targeting signal. Perforin is also secreted via the constitutive pathway, both from the natural killer cell line, YT, and from CTL clones after TcR cross-linking. Constitutive secretion of the lytic proteins can be blocked by both CHX and brefeldin A (BFA). While BFA does not affect the directional killing of recognized targets, it abrogates bystander killing, indicating that bystander killing arises from newly synthesized lytic proteins delivered via a non-granule route. These results demonstrate that the perforin/granzyme-mediated lytic pathway can be maintained while CTL kill multiple targets. We show that CTL not only re-fill their granules during killing, but also secrete lytic proteins via a non-granule-mediated pathway.
In vivo alterations in cytokine production following interleukin-12 (IL-12) and anti-IL-4 antibody treatment of CB6F1 mice with chronic cutaneous leishmaniasis (1996)

CB6F1 mice exhibit intermediate resistance to infection with Leishmania major compared to their highly susceptible (BALB/c) and resistant (C57BL/6) parental strains. Unlike the C57BL/6 and BALB/c strains, which rapidly develop dominant Th1- or Th2-type responses, respectively, after infection, CB6F1 mice develop responses in which both Th1- and Th2-type cytokines are elevated through at least the first month of infection before Th1 responses become dominant as cutaneous lesions gradually heal. We have examined the effects of interleukin-12 (IL-12) and/or anti-IL-4 antibody treatment on cytokine production and the course of disease in CB6F1 mice with chronic L. major infections. When administered at 1 month of infection, IL-12 treatment led to a rapid decrease in mRNA levels for IL-4 within parasitized lesions and a moderate increase in gamma interferon (IFN-gamma) transcript levels in lymph nodes draining the site of infection. When IL-12 and anti-IL-4 antibody were administered together, they induced a marked decrease in IL-4 and transforming growth factor beta mRNA expression within lesions and a more dramatic increase in lymph node IFN-gamma transcript levels within 4 days after treatment. In comparison, similar treatment of infected BALB/c mice led to only a moderate increase in IFN-gamma transcripts but no decrease in mRNA levels for Th2-type cytokines. Treatment of CB6F1 mice with either IL-12 or anti-IL-4 antibody had no significant effect on the subsequent course of infection, whereas combined IL-12 plus anti-IL-4 treatment resulted in a decrease in lesion size and parasite numbers and a shift towards a Th1-dominant response. These results suggest that the immediate effects of cytokine or anti-cytokine therapy may be predictive of the long-term effects on the course of infection and that down-regulation of Th-2 type cytokines may be critical to the development of a Th1-dominant response.
Dutch Normal-Pressure Hydrocephalus Study: prediction of outcome after shunting by resistance to outflow of cerebrospinal fluid (1997)

The authors examined whether measurement of resistance to outflow of cerebrospinal fluid (Rcsf) predicts outcome after shunting for patients with normal-pressure hydrocephalus (NPH). In four centers 101 patients (most of whom had idiopathic NPH) who fulfilled strict entry criteria underwent shunt placement irrespective of their level of Rcsf obtained by lumbar constant flow infusion. Gait disturbance and dementia were quantified by using an NPH scale and the patient's level of disability was assessed by using the modified Rankin scale (mRS). In addition the Modified Mini-Mental State Examination was performed. Patients were assessed prior to and 1, 3, 6, 9, and 12 months after surgery. Primary outcome measures were based on differences between the preoperative and last NPH scale scores and mRS grades. Improvement was defined as a change measuring at least 15% in the NPH scale score and at least one mRS grade. Intention-to-treat analysis of all patients at 1 year yielded improvement for 57% in NPH scale score and 59% in mRS grade. Efficacy analysis, excluding serious events and deaths that were unrelated to NPH, was performed for 95 patients. Improvement rose to 76% in NPH scale score and 69% in mRS grade. Six cut-off levels of Rcsf were related to improvement in NPH scale score using two-by-two tables. Positive predictive values were approximately 80% for an Rcsf of 10, 12, or 15 mm Hg/ml/minute, 92% for an Rcsf of 18 mm Hg/ml/minute, and 100% for an Rcsf of 24 mm Hg/ml/minute. Negative predictive values were low. More important was the highest likelihood ratio of 3.5 for an Rcsf of 18 mm Hg/ml/minute. Extensive comorbidity was a major prognostic factor. Measurement of Rcsf reliably predicts outcome if the limit for shunting is raised to 18 mm Hg/ml/minute. At lower Rcsf values the decision depends mainly on the extent to which clinical and computerized tomography findings are typical of NPH.
RHEOLOGICAL PROPERTIES OF AQUEOUS AGAROSE‐GELATIN GELS (1980)

ABSTRACT Melting temperatures were determined for 1‐5% agarose gels, 7.5‐40% gelatin gels and mixed gels of different concentrations of the two hydro‐colloids. The dynamic viscoclastic constants were also quantified at 0.05 HZ for mixed gels containing 0.5% agarose and 2.5–20% gelatin. In single component gels, the melting temperature increased with hydrocolloid concentration. The melting temperature of gelatin gels was lower than that of agarose gels (22–31°C vs 69–80°C) and less concentration dependent. The melting temperature of mixed gels was more similar to that of agarose gels at low (2.5–6.25%) gelatin concentrations and more similar to that of gelatin gels at high (7.5–20%) gelatin concentrations. The storage modulus decreased with increasing temperature indicating that the thermal rupturing of the noncovalent crosslinks in the gels was stronger than the entropic behavior of the network. The temperature dependence of the storage modulus and of the dynamic viscosity increased with gelatin concentration. Based on these results and on the determination of the activation energy it is concluded that, in mixed agarose/gelatin gels, the two species form individual networks which interfere with one another at high concentrations.
Anatomy of an engineered NAD‐binding site (1994)

The coenzyme specificity of Escherichia coli glutathione reductase was switched from NADP to NAD by modifying the environment of the 2'-phosphate binding site through a set of point mutations: A179G, A183G, V197E, R198M, K199F, H200D, and R204P (Scrutton NS, Berry A, Perham RN, 1990, Nature 343:38-43). In order to analyze the structural changes involved, we have determined 4 high-resolution crystal structures, i.e., the structures of the wild-type enzyme (1.86 A resolution, R-factor of 16.8%), of the wild-type enzyme ligated with NADP (2.0 A, 20.8%), of the NAD-dependent mutant (1.74 A, 16.8%), and of the NAD-dependent mutant ligated with NAD (2.2 A, 16.9%). A comparison of these structures reveals subtle differences that explain details of the specificity change. In particular, a peptide rotation occurs close to the adenosine ribose, with a concomitant change of the ribose pucker. The mutations cause a contraction of the local chain fold. Furthermore, the engineered NAD-binding site assumes a less rigid structure than the NADP site of the wild-type enzyme. A superposition of the ligated structures shows a displacement of NAD versus NADP such that the electron pathway from the nicotinamide ring to FAD is elongated, which may explain the lower catalytic efficiency of the mutant. Because the nicotinamide is as much as 15 A from the sites of the mutations, this observation reminds us that mutations may have important long-range consequences that are difficult to anticipate.
Use of synthetic oligonucleotide probes complementary to genes for human HLA-DR alpha and beta as extension primers for the isolation of 5'-specific genomic clones. (1983)

We have synthesized 175-nucleotide-long probes for the DNA of human histocompatibility antigens HLA-DR alpha and beta by extending on poly(A)+ mRNA from B-cell lines with short synthetic deoxyribonucleotide primers complementary to the predicted nucleotide sequence of the NH2 terminus of both polypeptides. The synthesis of the probe for the alpha-chain DNA was a two-step process starting with 11-mers which were extended by dideoxynucleotide chain termination experiments to a 20-mer of predicted sequence. The synthesized 20-mer was then used to generate a 175-nucleotide cDNA probe which was shown to encode the appropriate amino acids for the alpha chain and was used to select a human genomic DNA clone containing the coding sequences for HLA-DR alpha. For the beta polypeptide an 18-mer homologous to the NH2-terminal sequence of a cDNA clone from another B-cell line was used to extend on poly(A)+ mRNA isolated from a B-cell line. Preliminary sequence analysis of a 175-base-long extension product indicates a match of the cDNA sequence to the published sequence of a clone for HLA-DR beta. Information from these extension experiments helps to establish the sensitivity and specificity of the primer extension method.
Neural Network Matrix Factorization (2015)

Data often comes in the form of an array or matrix. Matrix factorization techniques attempt to recover missing or corrupted entries by assuming that the matrix can be written as the product of two low-rank matrices. In other words, matrix factorization approximates the entries of the matrix by a simple, fixed function---namely, the inner product---acting on the latent feature vectors for the corresponding row and column. Here we consider replacing the inner product by an arbitrary function that we learn from the data at the same time as we learn the latent feature vectors. In particular, we replace the inner product by a multi-layer feed-forward neural network, and learn by alternating between optimizing the network for fixed latent features, and optimizing the latent features for a fixed network. The resulting approach---which we call neural network matrix factorization or NNMF, for short---dominates standard low-rank techniques on a suite of benchmark but is dominated by some recent proposals that take advantage of the graph features. Given the vast range of architectures, activation functions, regularizers, and optimization techniques that could be used within the NNMF framework, it seems likely the true potential of the approach has yet to be reached.
Convenient general method for the preparation of primary alkyllithiums by lithium-iodine exchange (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConvenient general method for the preparation of primary alkyllithiums by lithium-iodine exchangeWilliam F. Bailey and Eric R. PunzalanCite this: J. Org. Chem. 1990, 55, 19, 5404–5406Publication Date (Print):September 1, 1990Publication History Published online1 May 2002Published inissue 1 September 1990https://pubs.acs.org/doi/10.1021/jo00306a021https://doi.org/10.1021/jo00306a021research-articleACS PublicationsRequest reuse permissionsArticle Views2875Altmetric-Citations219LEARN 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
Follicle‐stimulating hormone receptor polymorphisms in a population of infertile women (2005)

The results show that Ser/Ser-680 predominates in the studied infertile population. Furthermore, women with normal ovarian reserve and the Ser/Ser FSH receptor variant had significantly higher FSH levels, compared to women with Asn/Asn and Asn/Ser variants. FSH receptor genotyping may, thus, be interesting as an adjunct indicator of ovarian reserve for infertile women undergoing assisted reproduction, and may be helpful in the determination of the starting dosage of FSH in in vitro fertilization.
Semiparametric Latent Factor Models (2005)

We propose a semiparametric model for regression problems involving multiple response variables. The model makes use of a set of Gaussian processes that are linearly mixed to capture dependencies that may exist among the response variables. We propose an efficient approximate inference scheme for this semiparametric model whose complexity is linear in the number of training data points. We present experimental results in the domain of multi-joint robot arm dynamics.
Polymer-encapsulated cells genetically modified to secrete human nerve growth factor promote the survival of axotomized septal cholinergic neurons. (1994)

Effective treatments for neurodegenerative disorders are limited by our inability to alter the progression of the diseases. A number of proteins have specific neuroprotective activities in vitro; however, the delivery of these factors into the central nervous system over the long term at therapeutic levels has been difficult to achieve. BHK cells engineered to express and release human nerve growth factor were encapsulated in an immunoisolation polymeric device and transplanted into both fimbria-fornix-lesioned rat brains and naive controls. In the lesioned rat brain, chronic delivery of human nerve growth factor by the encapsulated BHK cells provided nearly complete protection of axotomized medial septal cholinergic neurons. Human nerve growth factor continued to be released by encapsulated cells upon removal from the aspirative site after 3 weeks or from normal rat striatum after 3 and 6 months in vivo. Long-term encapsulated cell survival was confirmed by histologic analysis. This encapsulated xenogeneic system may provide therapeutically effective amounts of a number of neurotrophic factors, alone or in combination, to virtually any site within the body.
Correlation of the primary Gleason pattern on prostate needle biopsy with clinico-pathological factors in Gleason 7 tumors. (2004)

Among patients with Gleason 7 adenocarcinoma of the prostate, the biopsy-derived primary Gleason pattern does not appear to correlate with important clinical and pathologic outcomes. The utility of distinguishing a primary Gleason pattern on needle biopsy among patients with Gleason 7 tumors remains unclear given the limited and conflicting literature addressing this issue.
Extracting the hysteresis loops of magnetic interfaces from optical second-harmonic intensity measurements (2007)

Surface- and interface-sensitive optical techniques, such as optical second-harmonic generation (SHG), allow the buried interfacial structure of centrosymmetric materials to be explored through thin capping layers, and magnetic SHG (MSHG) extends this to magnetic interfaces. However, the variation of the MSHG intensity with magnetic field does not measure hysteresis loops directly, because the loops are displaced by an amount dependent on the crystallographic response and its phase difference with respect to the magnetic response, and also because there is a quadratic magnetization contribution to the SH intensity that may be significant. Two new procedures are reported for extracting hysteresis loops directly from the MSHG intensity. The first is applicable to all magnetic interfaces, including exchange-biased structures, where the saturation magnetization for positive and negative magnetic fields is equal and opposite. The second applies to all centrosymmetric hysteresis loops. These procedures correct for the quadratic response, allowing experimental geometries to be chosen that maximize the magnetic contribution, thus improving the signal-to-noise ratio and the sensitivity of the technique.
Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. (1992)

Nonenzymatic glycosylation of proteins, as occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation end products of proteins (AGEs), which can bind to endothelial cells, thereby altering cellular function in a manner which could contribute to the pathogenesis of diabetic angiopathy. In this report, we describe the isolation of two endothelial cell surface-associated proteins which mediate, at least in part, the interaction of AGEs with endothelium. Based on pilot studies demonstrating AGE binding activity with comparable characteristics in bovine endothelial cell and lung extracts, the material from lung was sequentially subjected to chromatography on hydroxylapatite, fast protein liquid chromatography Mono S, and gel filtration. Two distinct polypeptides, approximately 35 and approximately 80 kDa, were purified to homogeneity, each of which bound AGEs as demonstrated by competitive binding assays using cellular binding proteins immobilized on a plastic surface. NH2-terminal sequence analysis indicated that the approximately 35-kDa protein was novel, whereas the NH2-terminal sequence of the approximately 80-kDa protein was identical to that of lactoferrin. Immunocytologic studies using polyclonal antibody prepared to each of the purified polypeptides demonstrated the presence of immunoreactive material on the surface of bovine endothelial cells maintained under serum-free conditions. Furthermore, immunoelectron microscopic studies with antibodies to the approximately 35- and approximately 80-kDa AGE-binding proteins conjugated to different size colloidal gold particles confirmed the presence of the target antigens on the cell surface and suggested that they were closely associated. IgG purified from polyclonal antisera to either the 35- or 80-kDa AGE-binding proteins blocked the binding of 125I-AGE-albumin to the cell surface. These results indicate that endothelial cells express specific cell surface molecules which mediate AGE-endothelial interaction. These polypeptides represent a novel class of cell surface acceptor molecules for glucose-modified proteins which may promote degradation and/or transcytosis of the ligand, and modulation of cellular function.