gebhart/patrepeval huggingface dataset:
Aβ-degrading enzymes: modulators of Alzheimer's disease pathogenesis and targets for therapeutic intervention (2005)

The accumulation of Aβ (amyloid β-protein) peptides in the brain is a pathological hallmark of all forms of AD (Alzheimer's disease) and reducing Aβ levels can prevent or reverse cognitive deficits in mouse models of the disease. Aβ is produced continuously and its concentration is determined in part by the activities ofseveral degradative enzymes, including NEP (neprilysin), IDE (insulin-degrading enzyme), ECE-1 (endothelinconverting enzyme 1) and ECE-2, and probably plasmin. Decreased activity of any of these enzymes due to genetic mutation, or age- or disease-related alterations in gene expression or proteolytic activity, may increase the risk for AD. Conversely, increased expression of these enzymes may confer a protective effect. Increasing Aβ degradation through gene therapy, transcriptional activation or even pharmacological activation of the Aβ-degrading enzymes represents a novel therapeutic strategy for the treatment of AD that is currently being evaluated in cell-culture and animal models. In this paper, we will review the roles of NEP, IDE, ECE and plasmin in determining endogenous Aβ concentration, highlighting recent results concerning the regulation of these enzymes and their potential as therapeutic targets.
Genotype-Selective Combination Therapies for Melanoma Identified by High-Throughput Drug Screening (2012)

We have used drug combinatorial screening to identify effective combinations for mutant BRAF melanomas, including those resistant to vemurafenib, and mutant RAS melanomas that are resistant to many therapies. Mechanisms governing the interactions of the drug combinations are proposed, and in vivo xenografts show the enhanced benefit and tolerability of a mutant RAS -selective combination, which is currently lacking in the clinic.
A Mutation-Independent Therapeutic Strategem for Osteogenesis Imperfecta (1999)

Given the genetically heterogeneous nature of many dominantly inherited disorders, it will be imperative to design mutation-independent therapeutic strategies to circumvent such heterogeneity. Intragenic polymorphism represents a genomic resource that may be harnessed in the development of allele-specific mutation-independent therapeutics. A hammerhead ribozyme, Rzpol1a1, selectively cleaves a common single-nucleotide polymorphism (SNP) of the human COL1A1 transcript (heterozygosity frequency of 2 pq = 0.4032, from Hardy-Weinberg equilibrium). One SNP variant contains a hammerhead ribozyme cleavage site, and the other does not. Kinetic evaluation shows Rzpol1a1 to be both specific and extremely efficient in vitro. Thus, a single efficient ribozyme has been characterized that should be valuable in the development of a gene therapy suitable for up to 1 in 5 dominant-negative osteogenesis imperfecta (OI) patients, where over 150 different mutations have been identified to date. Given the increasing characterization of intragenic SNP, it is predicted that such a mutation-independent strategy, based on selective silencing of mutant alleles at SNP, may become increasingly important in future genomics-driven drug development for many heterogeneous dominant disorders and complex traits.
Transvenous and Subcutaneous Electrode System for an Implantable Defibrillator, Improved on Large Pigs (1988)

The currently required surgical procedure for implantable defibrillator implantation is a limiting factor and several groups are therefore investigating transvenous approaches. Our electrode system consists of a nondistal right ventricular catheter electrode and two or three subcutaneously (SC) placed electrodes. An optimal location for these SC electrodes is important to obtain the lowest possible defibrillation threshold (DFT) by allowing a more homogeneous current distribution within the thorax. An empirical approach consists of placing randomly the SC electrodes to find out the lowest possible DFT. A mathematical approach is to calculate the SC electrode locations for an optimal electric field distribution by using magnetic resonance images of thorax cross-sections and a specially designed computer program. Our recent experimental results are based on a series of 15 pigs weighing between 60 and 102 Kg. DFT ranged between 10 and 26 joules. We conclude that an electrode system with a right ventricular electrode and two or three subcutaneous electrodes can be optimized to reach a DFT for pigs with human-near body weights which is compatible with the energy capabilities of our implantable device.
The Heat Production of Muscle and Nerve, 1848-1914 (1959)

In 1848 Helmholtz' published the first recorded experiments on the heat production of isolated muscle (30). Using three thermocouples in series with a galvanometer, he measured the rise of temperature in prolonged contrac­ tions of the muscles of a frog's leg. He was then 27 years old and still in the Prussian Army Medical Service, though he was allowed to retire later in the same year. In 1847 he had published his famous monograph Ueber die
Deposition of MnO Anode and MnO<sub>2</sub> Cathode Thin Films by Plasma Enhanced Atomic Layer Deposition Using the Mn(thd)<sub>3</sub> Precursor (2015)

Atomic layer deposition (ALD) of a wide range of Mn oxides (MnO to MnO2) is demonstrated by combining the Mn(thd)3 (tris(2,2,6,6-tetramethyl-3,5-heptanedionato)manganese) precursor with different types of plasma activated reactant gases. Typical ALD behavior is found with hydrogen, ammonia, and water plasma, with a fully precursor controlled temperature window (from 140 to 250 °C) and constant growth rate (0.022 ± 0.001 nm/cycle). A purely ligand-exchange chemistry would predict Mn2O3 films with the transition metal in the +III state. However, it is found that the nature of the processgas or -plasma, more specific its oxidizing/reducing character, largely determines the oxidation state of the grown films. Our approach provides an effective method for the deposition of MnO2(+IV), Mn3O4(+II/+III), and MnO(+II) based on the Mn(thd)3(+III) precursor. All as-deposited films are found to be smooth (<1.2 nm rms roughness), crystalline and with <6% impurities. The resulting films are tested as lithium-ion battery electrodes, showing the MnO2 and the MnO films as possible candidate thin-film cathode and anode, respectively.
Potential Use of Phytate as an Antioxidant in Cooked Meats (2002)

TRADITIONALLY, phytate (myo-inositol hexakisphosphate; InsP6) has beenconsidered a food toxicant in animal feed and in human diets, due to its
powerful chelating ability, resulting in lower bioavailability of zinc, calcium,
and iron. More recently, however, phytate has been recognized as a natural seed
antioxidant, capable of chelating ionic iron and preventing iron catalysis of lipid
oxidation [1]. With recognition of the antioxidant properties of phytate, several
groups have investigated the possible use of phytate as an antioxidant in muscle
foods [2-4]. A major concern with phytate addition to foods is the possible
impairment of mineral absorption. However, a number of studies now indicate
that iron and zinc absorption is not impaired in meat-based diets containing
phytate [5-7]. This chapter will review phytate as an antioxidant in meat systems, meat-phytate interactions on mineral absorption, and effects of phytate
on product cost and acceptability.
The kinetics and mechanism of caffeine infusion from coffee: The effect of particle size (1984)

Abstract Measurements have been made of the rate of infusion of caffeine into distilled water from medium roast Kenyan Arabica coffee beans and from eight sieved fractions of the ground beans at 25.8°C. The first‐order rate constants increased dramatically as the particle size decreased. For one of the size fractions the rate constants were then measured at various temperatures up to 84.1°C and were found to rise eight‐fold over this temperature interval. The partition coefficients of caffeine between ground beans and water were also determined. These results, interpreted by a new steady‐state theory of extraction, show that the rate‐determining step in the infusion is diffusion of caffeine through the swollen coffee particles. The low magnitude of the diffusion coefficient and its high activation energy demonstrate that caffeine diffusion within the bean particles is a hindered process.
Reduced complexity MMSE detection for BLAST architectures (2004)

Theoretical and experimental studies have shown that layered space-time architectures like the BLAST system can exploit the capacity advantage of multiple antenna systems in rich-scattering environments. We present a new efficient algorithm for detecting such architectures with respect to the MMSE criterion. This algorithm utilizes a sorted QR decomposition of the channel matrix and leads to a simple successive detection structure. The algorithm needs only a fraction of the computational effort compared to the standard V-BLAST algorithm and achieves the same bit error performance.
Mobile Enabled Large Scale Wireless Sensor Networks (2006)

The combined and separated research advancement in the fields of sensing, communication, and computing have driven the research efforts in wireless sensor networks (WSN) in recent years. According to the traditional definition of WSNs, a dense, static, and prohibitively expensive sensor deployment is implicitly required, which has limited the feasibility of WSNs in nonmilitary approaches. Aside from stationary sensor and sink deployment, the introduction of mobility of mobile terminals into WSNs can be leveraged to alleviate the burden of certain static sinks in order for efficient information repository, dissemination and sharing. In fact, the rapid development of diverse short distance wireless communication methods, such as Bluetooth and Zigbee, have not only popularized multi-radio functioned mobile devices, but also found their potential applications via WSN networking. To realize the goal of large scale wireless sensor network deployment, in this paper, we introduce an architecture of multi-radio enabled mobile wireless sensor network (MEMOSEN), which has taken the heterogeneity and mobility of sensors and sinks into account. The capacity gain and topology dynamics due to mobility in MEMOSEN have been addressed. The design challenges and potential applications of MEMOSEN have been analyzed as well.
A hypoxic consensus operator and a constitutive activation region regulate the ANB1 gene of Saccharomyces cerevisiae. (1990)

We have identified a consensus operator sequence, YYYATTGTTCTC, which mediates the repression imposed by the ROX1 factor upon the members of the hypoxic gene regulon, which includes ANB1, HEM13, COX5b, and CYC7. The members of the regulon were repressed with widely varying stringency, and the variation was correlated with the number and fidelity of operator sequences observed. ANB1 had two operators operating with unequal efficiency, each containing two copies of the operator sequence. Synthetic operator sequences introduced into an operator deletion were effective as monomers but much more so as dimers, consistent with cooperativity. The native operators both imposed ROX1 repression on the GAL1 gene, in either orientation, but the synthetic operators did not, indicating that the sequence context may be important. The repression and activation of ANB1 are independent spatially and functionally, since deletion of the operators did not reduce expression and since both the operator and activation regions functioned separately in the GAL1 UAS. The ANB1 UAS was constitutive, containing several elements distributed over a 300-bp region. There were two dT-rich segments, one of 51 bp and one of 165 bp, the latter capable of activating transcription by itself. Flanking segments containing GRF2 (REB1) and ABF1 (GF1) sites may contribute to activation but were not essential. The UAS showed a strongly preferred orientation.
[Utilization of melanin precursors for experimental chemotherapy of malignant melanoma]. (1984)

Melanin synthesis is a metabolic pathway unique and specific to melanocytes. It occurs by conversion of tyrosine to dopa and dopaquinone in the presence of tyrosinase. It is highly accelerated in malignant melanoma with a marked increase of tyrosinase activity. This study summarizes the recent progress in experimental chemotherapeutic approaches to malignant melanoma by utilizing melanin precursors, and presents our current results. Our studies indicated (a) that hydroquinone and 4-isopropylcatechol are selectively toxic to melanocytes and melanoma cells, (b) that their actions are mediated through tyrosinase, and (c) that dopa is selectively and highly incorporated into melanoma cells and melanocytes depending on the tyrosinase activity. In addition, our new compounds, i.e., 4-S-cysteinylphenol and 4-S-cysteaminylphenol were highly toxic to melanoma cells, increasing the life span of B16 melanoma bearing mice and decreasing melanoma growth in C57 BL mice. Other synthetic compounds, e.g., cysteinylcatechols and their devivatives, were, however, not toxic to melanoma cells. 4-S-cysteinylphenol and 4-S-cysteaminylphenol appeared to exert their cytotoxicity through the action of tyrosinase present in melanoma cells, thus providing a kind of "guided missile" approach to melanoma chemotherapy.
DNA‐binding activity of the A‐factor receptor protein and its recognition DNA sequences (1997)

The A-factor receptor protein (ArpA) containing an alpha-helix-turn-alpha-helix DNA-binding consensus sequence at its N-terminal portion plays a key role in the regulation of secondary metabolism and cell differentiation in Streptomyces griseus. A binding site forming a palindrome 24bp in length was initially recovered from a pool of random-sequence oligonucleotides by rounds of a binding/immunoprecipitation/amplification procedure with histidine-tagged ArpA and anti-ArpA antibody. By means of further binding/gel retardation/amplification experiments on the basis of the recovered sequence, a 22 bp palindromic binding site with the sequence 5'-GG(T/C)CGGT(A/T)(T/C)G(T/G)-3' as one half of the palindrome was deduced as a consensus sequence recognized and bound by ArpA. ArpA did not bind to the binding site in the presence of its ligand, A-factor. In addition, exogenous addition of A-factor to the ArpA-DNA complex induced immediate release of ArpA from the DNA. All of these data are consistent with the idea, obtained from previous genetic studies, that ArpA acts as a repressor-type regulator for secondary metabolism and cellular differentiation by preventing the expression of a certain key gene(s) during the early growth phase. A-factor, produced in a growth-dependent manner, releases ArpA from the DNA, thus switching on the expression of the key gene(s), leading to the onset of secondary metabolism and aerial mycelium formation.
Traitement des glaucomes par la brimonidine : (Alphagan® 0,2 %) (2000)

PURPOSE: The main purpose of our study was to assess the systemic safety of brimonidine tartrate 0.2%, an alpha 2 highly selective agonist in patients with glaucoma or ocular hypertension Material-Methods: Brimonidine was administered alone or in combination in 128 patients suffering from glaucoma or ocular hypertension in order to improve the IOP effect and/or to replace a drug which prescription was limited due to its secondary effects. In addition to the standard follow up and IOP reduction evaluation, our study was focused on the appreciation of the systemic tolerance to brimonidine. RESULTS: The average age of our patients was 65.2 +/- 13.8 years and the mean follow up was 4.5 +/- 3.4 months. Brimondine was administered in monotherapy in 15 patients (7.8%) and in combination with another drug in the others (92.2%), the combination with a beta-blocking agent being the most frequent combination. 113 among the 128 patients suffered from POAG. 51.6% of patients described systemic side effects at various degrees (drowsiness, fatigue, general uneasiness, mouth dryness.). All these systemic side effects were significantly more frequent in patients older than 60 years (p<0.05). They did not seem to be influenced by an intercurrent illness or a systemic concurrent treatment with drugs potentially acting with the noradrenergic transmission (monoamine oxydase inhibitors, tricyclic antidepressants, mianserine, alpha-sympatholytics.). Brimonidine was interrupted in 82 patients (64.1%) secondary to a systemic intolerance in 21 patients, an allergic blepharo-conjunctivitis in 12 patients, and a non optimal IOP reduction in 42 patients. Considering the all patients and treatments, IOP dropped from 20.5 +/- 3.6mmHg to 19.8 +/- 4.6mmHg at the last examination (p<0.05). In bitherapies, the observed IOP reduction was not significantly different from the one achieved with the previous association. CONCLUSION: Our medium-term results have shown that brimonidine was an efficient ocular hypotensive agent and had a satisfactory ocular tolerance in nearly all the patients. However, its systemic tolerance appeared to be less favourable than previously reported. A systematic eyelid closure and punctal occlusion following each instillation is advisable in older patients.
Possible health impact of animal oestrogens in food (2001)

Oestrogens govern reproductive functions in vertebrates, and are present in all animal tissues. The theoretical maximum daily intake (TMDI) of oestradiol-17beta by consumption of cattle meat is calculated to be 4.3 ng. Following the use of oestradiol-containing growth-promoting agents, TMDI is increased by a factor of 4.6 to 20 ng oestradiol-17beta, assuming that single dosage and 'good animal husbandry' are observed. Pork and poultry probably contain similar amounts of oestrogens as untreated cattle. The mean concentration of oestradiol-17beta in whole milk is estimated at 6.4 pg/ml. Scarce data available on eggs report up to 200 pg/g oestradiol-17beta. The risk evaluation of oestrogenic growth-promoting agents is limited by analytical uncertainties. Residues of oestradiol-17alpha and the importance of oestrogen conjugates are widely unknown. The performance of mass spectrometry still needs to be improved for confirmation of oestrogen concentrations in most food. At present, the potential relevance of oestradiol acyl esters, the actual daily production rate of oestradiol in prepubertal children, and the role of oestradiol metabolites in cancer are obscure. The presence of different cytoplasmic oestrogen receptor subtypes and potential oestradiol effects in non-reproductive functions require further examination.
Kernel approximate Bayesian computation in population genetic inferences (2013)

Approximate Bayesian computation (ABC) is a likelihood-free approach for Bayesian inferences based on a rejection algorithm method that applies a tolerance of dissimilarity between summary statistics from observed and simulated data. Although several improvements to the algorithm have been proposed, none of these improvements avoid the following two sources of approximation: 1) lack of sufficient statistics: sampling is not from the true posterior density given data but from an approximate posterior density given summary statistics; and 2) non-zero tolerance: sampling from the posterior density given summary statistics is achieved only in the limit of zero tolerance. The first source of approximation can be improved by adding a summary statistic, but an increase in the number of summary statistics could introduce additional variance caused by the low acceptance rate. Consequently, many researchers have attempted to develop techniques to choose informative summary statistics. The present study evaluated the utility of a kernel-based ABC method [Fukumizu, K., L. Song and A. Gretton (2010): "Kernel Bayes' rule: Bayesian inference with positive definite kernels," arXiv, 1009.5736 and Fukumizu, K., L. Song and A. Gretton (2011): "Kernel Bayes' rule. Advances in Neural Information Processing Systems 24." In: J. Shawe-Taylor and R. S. Zemel and P. Bartlett and F. Pereira and K. Q. Weinberger, (Eds.), pp. 1549-1557., NIPS 24: 1549-1557] for complex problems that demand many summary statistics. Specifically, kernel ABC was applied to population genetic inference. We demonstrate that, in contrast to conventional ABCs, kernel ABC can incorporate a large number of summary statistics while maintaining high performance of the inference.
Specification of security constraint in UML (2001)

In recent years various initiatives for solving the problem of security in databases have arisen. However, all of them have been only partial solutions which resolved isolated problems. Consequently, a global solution to the problem has not been reached yet. We believe that a methodological approach in which security is taken into consideration from the earliest stages of the development process of the databases is the best strategy. The authors present a language for specifying security constraints in models of classes, which is one step to a complete methodology for the development of secure multilevel databases. This language is called OSCL (Object Security Constraint Language). OSCL is based on the constraint language OCL (Object Constraint Language), which is used by the current standard of modeling, UML (Unified Modeling Language).
The Action of Hydroxylamine and Hydrazine on Acetylenic Thioamides (1937)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Action of Hydroxylamine and Hydrazine on Acetylenic ThioamidesDavid E. WorrallCite this: J. Am. Chem. Soc. 1937, 59, 5, 933–934Publication Date (Print):May 1, 1937Publication History Published online1 May 2002Published inissue 1 May 1937https://pubs.acs.org/doi/10.1021/ja01284a048https://doi.org/10.1021/ja01284a048research-articleACS PublicationsRequest reuse permissionsArticle Views122Altmetric-Citations16LEARN 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