gebhart/patrepeval huggingface dataset:
Synthesis of Fluorescent Analogues of the Anticancer Natural Products 4-Hydroxyphenylmethylene Hydantoin and δ-Tocotrienol (2010)

4-Hydroxyphenylmethylene hydantoin (PMH, 1), isolated from the Red Sea sponge Hemimycale arabica, and delta-tocotrienol (3), isolated from the tocotrienol-rich fraction of palm oil, are important antimetastatic and antiproliferative natural products that proved effective against metastatic prostate and breast cancers, respectively. New fluorescent derivatives of PMH (2) and delta-tocotrienol (4) were synthesized by Steglich esterification. Both 2 and 4 retained good anti-migratory and antiproliferative activities, respectively. Fluorescent analogues 2 and 4 can be used for the identification of molecular targets of 1 and 3 in tumor cell cultures.
Registered Nurses and Moral Distress (2010)

Nurses spend more time with patients at the end of life than any other member of the health care team, giving them early insight into futility-of-care issues for a particular patient. Providing futile care to dying patients is a well-known source of moral distress for nurses. Traditional ethical models are not always effective in dealing with these issues. The purpose of this article was to describe moral distress that is often experienced by nurses providing care to patients at the end of life and to propose the use of a model in dealing with associated ethical dilemmas in an effort to decrease the incidence of moral distress.
Synthetic studies toward pyruvate acetal containing saccharides. Synthesis of the carbohydrate part of the Mycobacterium smegmatis pentasaccharide glycolipid and fragments thereof for the preparation of neoantigens (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic studies toward pyruvate acetal containing saccharides. Synthesis of the carbohydrate part of the Mycobacterium smegmatis pentasaccharide glycolipid and fragments thereof for the preparation of neoantigensThomas Ziegler, Elisabeth Eckhardt, and Veronique BiraultCite this: J. Org. Chem. 1993, 58, 5, 1090–1099Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published inissue 1 February 1993https://pubs.acs.org/doi/10.1021/jo00057a021https://doi.org/10.1021/jo00057a021research-articleACS PublicationsRequest reuse permissionsArticle Views395Altmetric-Citations30LEARN 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
Deep Learning for Classification of Malware System Call Sequences (2016)

The increase in number and variety of malware samples amplifies the need for improvement in automatic detection and classification of the malware variants. Machine learning is a natural choice to cope with this increase, because it addresses the need of discovering underlying patterns in large-scale datasets. Nowadays, neural network methodology has been grown to the state that can surpass limitations of previous machine learning methods, such as Hidden Markov Models and Support Vector Machines. As a consequence, neural networks can now offer superior classification accuracy in many domains, such as computer vision or natural language processing. This improvement comes from the possibility of constructing neural networks with a higher number of potentially diverse layers and is known as Deep Learning. In this paper, we attempt to transfer these performance improvements to model the malware system call sequences for the purpose of malware classification. We construct a neural network based on convolutional and recurrent network layers in order to obtain the best features for classification. This way we get a hierarchical feature extraction architecture that combines convolution of n-grams with full sequential modeling. Our evaluation results demonstrate that our approach outperforms previously used methods in malware classification, being able to achieve an average of 85.6% on precision and 89.4% on recall using this combined neural network architecture.
Pure range-only sub-sea SLAM (2004)

This paper is about using range-only data to navigate an autonomous underwater vehicle (AUV). We assume the vehicle is equipped with conventional long base line (LBL) transceiver which measures acoustic time of flights (TOFs) between vehicle and small submerged transponders. Using only range data and no prior information other than approximate water column depth, we solve for both transponder location and vehicle trajectory. Results are given using data from a AUV operating in shallow water. A ground truth comparison is made with surveyed transponder locations and trajectory estimates from an on-board Doppler/Compass/LBL derived navigation filter.
Highly fluorescent M2L4 molecular capsules with anthracene shells (2011)

M(2)L(4) molecular capsules self-assembled from M(II) ions (where M = Zn, Ni, and Pd) and bent bidentate ligands constructed from anthracene fluorophores. The Ni(II) and Zn(II) capsules exhibited weak to strong blue emission unlike traditional Pd(II) cages and capsules.
Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014)

Exposure to total body irradiation (TBI) induces not only acute hematopoietic radiation syndrome but also long-term or residual bone marrow (BM) injury. This residual BM injury is mainly attributed to permanent damage to hematopoietic stem cells (HSCs), including impaired self-renewal, decreased long-term repopulating capacity, and myeloid skewing. These HSC defects were associated with significant increases in production of reactive oxygen species (ROS), expression of p16(Ink4a) (p16) and Arf mRNA, and senescence-associated β-galacotosidase (SA-β-gal) activity, but not with telomere shortening or increased apoptosis, suggesting that TBI induces residual BM injury via induction of HSC premature senescence. This suggestion is supported by the finding that SA-β-gal(+) HSC-enriched LSK cells showed more pronounced defects in clonogenic activity in vitro and long-term engraftment after transplantation than SA-β-gal(-) LSK cells isolated from irradiated mice. However, genetic deletion of p16 and/or Arf had no effect on TBI-induced residual BM suppression and HSC senescence, because HSCs from irradiated p16 and/or Arf knockout (KO) mice exhibited changes similar to those seen in HSCs from wild-type mice after exposure to TBI. These findings provide important new insights into the mechanism by which TBI causes long-term BM suppression (eg, via induction of premature senescence of HSCs in a p16-Arf-independent manner).
Efficiency of Doherty RF Power-Amplifier Systems (1987)

A Doherty system combines the outputs of two or more linear RF power amplifiers (PAs) through an impedance-inverting coupler such as a quarter-wave transmission line. At low output levels, the first PA operates linearly, reaching saturation (and maximum efficiency) at some transition voltage below the system peak-output voltage. At higher output levels, the first PA remains saturated and the second PA operates linearly. The instantaneous efficiency and power characteristics of a Doherty system are derived using ideal class-B RF PAs so that the results can easily be scaled for use with real-world PAs. The average efficiency and maximum-efficiency transition points are then determined for a variety of amplitude-modulated signals. The Doherty amplifier can be considerably more efficient than a conventional class-B linear PA. For example, the 28-and 8.9-percent average efficiencies of a class-B PA with Rayleigh-distri buted envelopes with 10-and 20-dB peak-to-average ratios are improved to 60 and 48 percent, respectively, by a two-stage Doherty system. The addition of a third stage further improves the efficiencies to 70 and 66 percent, respectively.
Computer simulation of the binding of naphthyridinomycin and cyanocycline A to DNA (1991)

Cyanocycline A was found to have a pKa of 6.6. Protonation of N14 was established by 1H NMR spectroscopy. In strongly acidic solution the oxazolidine ring opened irreversibly. A model was derived for the binding of naphthyridinomycin and cyanocycline A to the hexanucleotide duplex d(ATGCAT)2, by using the molecular mechanics and dynamics modules of AMBER 3.0. It involved protonation on the oxazolidine-ring nitrogen, reduction of the quinone ring to a hydroquinone, formation of an iminium ion with loss of the C7 substituent, noncovalent binding in the minor groove with the hydroquinone ring in the 3'-direction from guanine, and covalent binding to the 2-amino group of this guanine with C7 adopting the R configuration. This model is consistent with the experimental evidence on the DNA binding of these drugs. An alternative binding mode based on opening of the oxazolidine ring and alkylation at C3a also was feasible according to molecular mechanics calculations. The geometry of naphthyridinomycin does not permit interstrand cross-linking involving both C3a and C7, but formation of a cross-link to protein appears possible. When the covalent naphthyridinomycin-d(ATGCAT)2 models were refined in the presence of water and counterions, the models with the most favorable net binding enthalpies were the same as those produced by simulation in vacuum. Qualitative estimates of the relative entropy changes resulting from adduct formation were based on the number of ordered (hydrogen bonded) water molecules released from d(ATGCAT)2 and from the drug. In all cases but one, d(ATGCAT)2 loses five water molecules. It loses six in the C3a covalent model with 5',S geometry. Naphthyridinomycin hydroquinone loses up to two water molecules, depending on the particular adduct. The 3',R model was again favored for the C7 covalent adduct. Among the C3a covalent models, the one with 5',R geometry lost the second most water molecules, but it had the best binding enthalpy.
Copper tolerance of the thermoacidophilic archaeon Sulfolobus metallicus: possible role of polyphosphate metabolism (2005)

It has been postulated that inorganic polyphosphate (polyP) and transport of metal-phosphate complexes could participate in heavy metal tolerance in some bacteria. To study if such a system exists in archaea, the presence of polyP was determined by the electron energy loss spectroscopy (EELS) procedure and quantified by using specific enzymic methods in Sulfolobus acidocaldarius, Sulfolobus metallicus and Sulfolobus solfataricus. All three micro-organisms synthesized polyP during growth, but only S. metallicus greatly accumulated polyP granules. The differences in the capacity to accumulate polyP between these archaea may reflect adaptive responses to their natural environment. Thus, S. metallicus could grow in and tolerate up to 200 mM copper sulfate, with a concomitant decrease in its polyP levels with increasing copper concentrations. On the other hand, S. solfataricus could not grow in or tolerate more than 1-5 mM copper sulfate, most likely due to its low levels of polyP. Shifting S. metallicus cells to copper sulfate concentrations up to 100 mM led to a rapid increase in their exopolyphosphatase (PPX) activity which was concomitant in time with a decrease in their polyP levels and a stimulation of phosphate efflux. Furthermore, copper in the range of 10 microM greatly stimulated PPX activity in cell-free extracts from S. metallicus. The results strongly suggest that a metal tolerance mechanism mediated through polyP is functional in members of the genus Sulfolobus. This ability to accumulate and hydrolyse polyP may play an important role not only in the survival of these micro-organisms in sulfidic mineral environments containing high toxic metals concentrations, but also in their applications in biomining.
SNPdetector: A Software Tool for Sensitive and Accurate SNP Detection (2005)

Identification of single nucleotide polymorphisms (SNPs) and mutations is important for the discovery of genetic predisposition to complex diseases. PCR resequencing is the method of choice for de novo SNP discovery. However, manual curation of putative SNPs has been a major bottleneck in the application of this method to high-throughput screening. Therefore it is critical to develop a more sensitive and accurate computational method for automated SNP detection. We developed a software tool, SNPdetector, for automated identification of SNPs and mutations in fluorescence-based resequencing reads. SNPdetector was designed to model the process of human visual inspection and has a very low false positive and false negative rate. We demonstrate the superior performance of SNPdetector in SNP and mutation analysis by comparing its results with those derived by human inspection, PolyPhred (a popular SNP detection tool), and independent genotype assays in three large-scale investigations. The first study identified and validated inter- and intra-subspecies variations in 4,650 traces of 25 inbred mouse strains that belong to either the Mus musculus species or the M. spretus species. Unexpected heterozygosity in CAST/Ei strain was observed in two out of 1,167 mouse SNPs. The second study identified 11,241 candidate SNPs in five ENCODE regions of the human genome covering 2.5 Mb of genomic sequence. Approximately 50% of the candidate SNPs were selected for experimental genotyping; the validation rate exceeded 95%. The third study detected ENU-induced mutations (at 0.04% allele frequency) in 64,896 traces of 1,236 zebra fish. Our analysis of three large and diverse test datasets demonstrated that SNPdetector is an effective tool for genome-scale research and for large-sample clinical studies. SNPdetector runs on Unix/Linux platform and is available publicly (http://lpg.nci.nih.gov).
Adaptive impedance matching (2002)

In many applications, it is desirable to synthesize an adaptive impedance to match some "real world" system, so that when the target impedance changes, the matching impedance tracks this change and maintains a close match. In this paper we present a scheme for adaptive impedance matching formulated in the Model Reference Adaptive Systems' Control (MRAS) framework. The Model Reference adaptive controller can be implemented using Adaptive Delta-Sigma Filters to improve the performance-to-cost ratio due to their inherent oversampling. We will refer to this combined framework for adaptive impedance matching as MRAS/AIM.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
P3–127: Social vulnerability predicts cognitive decline in a prospective cohort of older Canadians (2006)

Some social factors, including social engagement, social networks, and socioeconomic status, have been associated with cognitive decline. These findings have been somewhat limited by the consideration of single social factors in isolation rather than taking potentially interacting social factors into account. Additionally, measurement of cognitive decline has been problematic. We aimed to investigate whether social vulnerability, defined using a social vulnerability index that takes many social factors into account, is associated with cognitive decline at five–year follow–up. In the Canadian Study of Health and Aging, baseline social vulnerability and cognitive trajectory were known for 2468 older adults aged 70+. In measuring social vulnerability, 40 variables relating to social factors were identified and each response was scored as 0 if the “deficit” was absent and 1 if it was present, with intermediate values for ordered response categories. A social vulnerability index was constructed for each individual using the sum of 40 deficit scores. Cognitive decline was defined as a ≥10 point decline in the Modified Mini–Mental State Exam (3MS). A more conservative definition, requiring a decline of ≥17 points on the 3MS was also investigated, based on the most conservative published estimate of a meaningful difference. Associations of social vulnerability with five–year cognitive decline, adjusting for age, sex, and frailty, were analyzed using logistic regression. Mean social vulnerability was 9.9 out of 40 possible deficits (SD 3.5, range 2.2–27.2). 365 individuals (14% of the total sample) experienced a decline of ≥10 points on the 3MS. Adjusting for age, sex, and frailty, each additional social deficit was associated with increased odds of cognitive decline (OR 1.06, 95% CI:1.02–1.10). Using a more conservative definition of cognitive decline, 147 individuals (6% of the sample) experienced a decline of ≥17 points on the 3MS and the association with social vulnerability remained (OR 1.09, 95% CI:1.03–1.14). Increasing social vulnerability, defined using a social vulnerability index that takes many social factors into account, was associated with increased odds of cognitive decline in this study of older Canadians.
LSD1: Biologic Roles and Therapeutic Targeting (2016)

LSD1 (KDM1A; BHC110; AOF2) was the first protein reported to exhibit histone demethylase activity and has since been shown to have multiple essential roles in mammalian biology. Given its enzymatic activity and its high-level expression in many human malignancies, a significant recent focus has been the development of pharmacologic inhibitors. Here we summarize structural and biochemical knowledge of this important epigenetic regulator, with a particular emphasis on the functional and preclinical studies in oncology that have provided justification for the evaluation of tranylcypromine derivative LSD1 inhibitors in early phase clinical trials.
Prospects for the manufacture of red cells for transfusion (2010)

Whilst red cell transfusion is a well established cellular therapy, the problems of insufficiency of supply, transfusion transmitted infections and the requirement for immunological matching persist. The possibility of generating large numbers of O Rh D negative red cells at Good Manufacturing Practice grade as a route to circumvent these issues is therefore an attractive proposition. Significant numbers of erythrocytes can be generated from somatic haematopoietic stem cells, but it seems unlikely that these can provide sufficient volumes for large scale manufacture. However, human embryonic stem cells (hESC) and, potentially, induced pluripotent stem cells (iPSC), may provide a route to this objective. Red cell transfusion is an attractive goal for pluripotent stem cell-derived therapeutics because it is a well-characterised single cell suspension that lacks nucleated cells and has a low expression of human leucocyte antigen molecules, but many challenges remain in translating this cellular therapy to the clinic.
Treatment of Murine Lupus with CTLA4Ig (1994)

The interaction of B7-related molecules on antigen-presenting cells with CD28 or CTLA-4 antigens on T cells provides a second signal for T cell activation. Selection inhibition of the B7-CD28 or B7-CTLA-4 interactions produces antigen-specific T cell unresponsiveness in vitro and suppresses immune function in vivo. To determine whether selective inhibition of the B7-CD28 or B7-CTLA-4 interactions could suppress spontaneous autoimmune disease, a B7-binding protein was generated by genetic fusion of the extracellular domain of murine CTLA-4 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody (muCTLA4Ig). In lupus-prone NZB/NZW filial generation (F1) mice, treatment with muCTLA4Ig blocked autoantibody production and prolonged life, even when treatment was delayed until the most advanced stage of clinical illness. These findings suggest a possible role for human CTLA4Ig in the treatment of autoimmune diseases in humans.
Calcium‐Dependent Dissociation of Synaptotagmin from Synaptic SNARE Complexes (2000)

The formation of the synaptic core (SNARE) complex constitutes a crucial step in synaptic vesicle fusion at the nerve terminal. The interaction of synaptotagmin I with this complex potentially provides a means of conferring Ca2+-dependent regulation of exocytosis. However, the subcellular compartments in which interactions occur and their modulation by Ca2+ influx remain obscure. Sodium dodecyl sulfate (SDS)-resistant core complexes, associated with synaptotagmin I, were enriched in rat brain fractions containing plasma membranes and docked synaptic vesicles. Depolarization of synaptosomes triggered [3H]GABA release and Ca2+-dependent dissociation of synaptotagmin from the core complex. In perforated synaptosomes, synaptotagmin dissociation was induced by Ca2+ (30-300 microM) but not Sr2+ (1 mM); it apparently required intact membrane bilayers but did not result in disassembly of trimeric SNARE complexes. Synaptotagmin was not associated with unstable v-SNARE/t-SNARE complexes, present in fractions containing synaptic vesicles and cytoplasm. These complexes acquired SDS resistance when N-ethylmaleimide-sensitive fusion protein (NSF) was inhibited with N-ethylmaleimide or adenosine 5'-O-(3-thiotriphosphate), suggesting that constitutive SNARE complex disassembly occurs in undocked synaptic vesicles. Our findings are consistent with models in which the Ca2+ triggered release of synaptotagmin precedes vesicle fusion. NSF may then dissociate ternary core complexes captured by endocytosis and recycle/prime individual SNARE proteins.
Insulin‐associated weight gain in diabetes – causes, effects and coping strategies (2006)

Insulin therapy or intensification of insulin therapy commonly results in weight gain in both type 1 and type 2 diabetes. This weight gain can be excessive, adversely affecting cardiovascular risk profile. The spectre of weight gain can increase diabetic morbidity and mortality when it acts as a psychological barrier to the initiation or intensification of insulin, or affects adherence with prescribed regimens. Insulin-associated weight gain may result from a reduction of blood glucose to levels below the renal threshold without a compensatory reduction in calorie intake, a defensive or unconscious increase in calorie intake caused by the fear or experience of hypoglycaemia, or the 'unphysiological' pharmacokinetic and metabolic profiles that follow subcutaneous administration. There is, however, scope for limiting insulin-associated weight gain. Strategies include limiting dose by increasing insulin sensitivity through diet and exercise or by using adjunctive anorectic or insulin-sparing pharmacotherapies such as pramlintide or metformin. Insulin replacement regimens that attempt to mimic physiological norms should also enable insulin to be dosed with maximum efficiency. The novel acylated analogue, insulin detemir, appears to lack the usual propensity for causing weight gain. Elucidation of the pharmacological mechanisms underlying this property might help clarify the mechanisms linking insulin with weight regulation.