gebhart/patrepeval huggingface dataset:
Optimization of a Pb2+-Directed Gold Nanoparticle/DNAzyme Assembly and Its Application as a Colorimetric Biosensor for Pb2+ (2004)

We previously communicated a method for directed assembly of gold nanoparticles using a Pb2+-dependent DNAzyme and demonstrated the application of this system as a colorimetric biosensor. The sensor shows high sensitivity and selectivity toward Pb2+ and undergoes a blue-to-red color transition in the presence of Pb2+. To gain a deeper insight into the analyte-directed nanomaterials assembly and sensing processes, a detailed characterization of the system has been performed. First, we found that the presence of gold nanoparticles had no effect on the Pb2+-dependent activity of the DNAzyme and the presence of DNAzyme has little effect on the melting properties of the DNA-functionalized nanoparticle aggregates, suggesting that the performance of the nanoparticle and DNAzyme systems can be optimized independently. Second, the optimal length of the DNAzyme and the alignment of the DNA-functionalized gold nanoparticles for the assembly and sensing processes have been determined to be 9 base pairs on each end for the DNAzyme, and “head-to-tail” alignment for the DNA-functionalized gold nanoparticles. Third, the optimal stoichiometry of the enzyme to the substrate strands of the DNAzyme was shown to be one to one in nanoparticle aggregates. Finally, the most favorable temperature and pH conditions for the system have also been established, with a temperature of 37 °C and pH of 6.4 to 9.2 as the best operating conditions. The study also revealed that, for most efficient assembly of nanoparticles, the DNA backbone should be rigidified by formation of a double helix with other DNA molecules. These findings allow optimization of the processes for directed assembly of nanomaterials and for colorimetric sensing.
TNF alpha as a therapeutic target in rheumatoid arthritis. (1994)

Rheumatoid arthritis (RA) is an autoimmune disease with inflammatory manifestations in the peripheral synovial joints, which are infiltrated by activated T cells, macrophages, and plasma cells. We have investigated the role of cytokines in RA and have proposed that tumour necrosis factor has a pivotal role in the pathogenesis of this disease. This chapter describes those studies, which led to the first clinical trial in RA patients using a chimeric anti TNF alpha antibody. In addition to pro-inflammatory cytokine production, at sites of inflammation such as the RA synovial joint, there is also evidence for homeostatic immunoregulatory mechanisms which include the production of cytokine inhibitors, such as soluble TNF-R and the IL-1 receptor antagonist, and cytokines with immunoregulatory properties like IL-10. The evidence for these inhibitors in RA is presented, and the relevance of this homeostatic mechanism in relation to chronic inflammatory diseases is discussed.
Molecular Mechanisms of Resistance to Human Immunodeficiency Virus Type 1 with Reverse Transcriptase Mutations K65R and K65R+M184V and Their Effects on Enzyme Function and Viral Replication Capacity (2002)

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) resistance mutations K65R and M184V result in changes in susceptibility to several nucleoside and nucleotide RT inhibitors. K65R-containing viruses showed decreases in susceptibility to tenofovir, didanosine (ddI), abacavir, and (-)-beta-D-dioxolane guanosine (DXG; the active metabolite of amdoxovir) but appeared to be fully susceptible to zidovudine and stavudine in vitro. Viruses containing the K65R and M184V mutations showed further decreases in susceptibility to ddI and abacavir but increased susceptibility to tenofovir compared to the susceptibilities of viruses with the K65R mutation. Enzymatic and viral replication analyses were undertaken to elucidate the mechanisms of altered drug susceptibilities and potential fitness defects for the K65R and K65R+M184V mutants. The relative inhibitory capacities (K(i)/K(m)) of the active metabolites of tenofovir, ddI, and DXG were increased for the RT containing the K65R mutation compared to that for the wild-type RT, but the relative inhibitory capacity of abacavir was only minimally increased. For the mutant viruses with the K65R and M184V mutations, the increase in tenofovir susceptibility compared to that of the mutants with K65R correlated with a decrease in the tenofovir inhibitory capacity that was mediated primarily by an increased K(m) of dATP. The decrease in susceptibility to ddI by mutants with the K65R and M184V mutations correlated with an increase in the inhibitory capacity mediated by an increased K(i). ATP-mediated removal of carbovir as well as small increases in the inhibitory capacity of carbovir appear to contribute to the resistance of mutants with the K65R mutation and the mutants with the K65R and M184V mutations to abacavir. Finally, both the HIV-1 K65R mutant and, more notably, the HIV-1 K65R+M184V double mutant showed reduced replication capacities and reduced RT processivities in vitro, consistent with a potential fitness defect in vivo and the low prevalence of the K65R mutation among isolates from antiretroviral agent-experienced patients.
Sparse sampling for sensing temporal data — building an optimized envelope (2016)

IoT systems collect vast amounts of data which can be used in order to track and analyze the structure of future recorded data. However, due to limited computational power, bandwith, and storage capabilities, this data cannot be stored as is, but rather must be reduced in such a way so that the abilities to analyze future data, based on past data, will not be compromised. We propose a parameterized method of sampling the data in an optimal way. Our method has three parameters - an averaging method for constructing an average data cycle from past observations, an envelope method for defining an interval around the average data cycle, and an entropy method for comparing new data cycles to the constructed envelope. These parameters can be adjusted according to the nature of the data, in order to find the optimal representation for classifying new cycles as well as for identifying anomalies and predicting future cycle behavior. In this work we concentrate on finding the optimal envelope, given an averaging method and an entropy method. We demonstrate with a case study of meteorological data regarding El Ninio years.
Evaluating the Efficacy and Safety of Erenumab (AMG 334) In Chronic Migraine Prevention in a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study (S52.002) (2017)

To evaluate the safety and efficacy of erenumab (AMG 334) in patients with chronic migraine (CM) (ClinicalTrials.gov NCT02066415).
TEDS rule: A molecular rationale for differential regulation of myosins by phosphorylation of the heavy chain head (1995)

Myosins are a superfamily of heteromeric, actin filament-based motors thought to be involved in a variety of actin-dependent motile processes [Pollard et al., 1991 ; Cheney and Mooseker, 19921. Myosin-mediated motility entails actin-dependent hydrolysis of ATP and, indeed, one of the defining characteristics of myosins is their ability to hydrolyze ATP in an actin-dependent fashion [Pollard et a]., 19911. At the level of primary structure, this ability is specified by the N-terminal "head" of the myosin heavy chain (Fig. The generic myosin has, in addition to the head, two other distinct functional domains-the "neck" and the "tail." The neck, which is located immediately C-terminal to the head, is the region of the heavy chain to which the light chains bind [Cheney and Mooseker, 19921. The tail, which is C-terminal to the neck, varies widely in structure and function among different myosins specifying, for example, dimerization and/or membrane binding (Fig.
A decoupled scheduled dataflow multithreaded architecture (2003)

Proposes a new approach to building multithreaded uniprocessors that become building blocks in high-end computing architectures. Our innovativeness stems from a multithreaded architecture with non-blocking threads where all memory accesses are decoupled from the thread execution. Data is pre-loaded into the thread context (registers), and all results are post-stored after the completion of the thread execution. The decoupling of memory accesses from thread execution requires a separate unit to perform the necessary pre-loads and post-stores, and to control the allocation of hardware thread contexts to enabled threads. This separation facilitates achieving high locality and minimizing the impact of distribution and hierarchy in large memory systems. The non-blocking nature of threads eliminates the need for thread switching, thus improving the overhead in scheduling threads. The functional execution paradigm eliminates complex hardware required for scheduling instructions for modern superscalar architectures. We present preliminary results obtained from Monte Carlo simulations of the proposed architectural features.
Intrinsic unstructuredness and abundance of PEST motifs in eukaryotic proteomes (2005)

The study of unfolded protein regions has gained importance because of their prevalence and important roles in various cellular functions. These regions have characteristically high net charge and low hydrophobicity. The amino acid sequence determines the intrinsic unstructuredness of a region and, therefore, efforts are ongoing to delineate the sequence motifs, which might contribute to protein disorder. We find that PEST motifs are enriched in the characterized disordered regions as compared with globular ones. Analysis of representative PDB chains revealed very few structures containing PEST sequences and the majority of them lacked regular secondary structure. A proteome-wide study in completely sequenced eukaryotes with predicted unfolded and folded proteins shows that PEST proteins make up a large fraction of unfolded dataset as compared with the folded proteins. Our data also reveal the prevalence of PEST proteins in eukaryotic proteomes (approximately 25%). Functional classification of the PEST-containing proteins shows an over- and under-representation in proteins involved in regulation and metabolism, respectively. Furthermore, our analysis shows that predicted PEST regions do not exhibit any preference to be localized in the C terminals of proteins, as reported earlier.
Immunomodulatory actions of xanthines and isoenzyme selective phosphodiesterase inhibitors. (1995)

Theophylline and related xanthines have been used in the treatment of airways diseases such as bronchial asthma for over 50 years. The therapeutic effectiveness of this class of drugs was traditionally thought to be derived from their ability to elicit bronchodilation, however evidence is accumulating to suggest that theophylline in particular possesses immunomodulatory and anti-inflammatory activity. The molecular mechanisms of action of theophylline have not yet been clarified, although several putative mechanisms of action have been proposed. One of these suggests that theophylline via non-selective inhibition of the phosphodiesterase (cAMP) and cyclic guanosine monophosphate (cGMP) levels resulting in relaxation of airway smooth muscle and inhibition of inflammatory cell activation. To date seven different families of the PDE enzyme have been defined according to a variety of criteria including substrate specificity, sensitivity to selective inhibitors and the effect of allosteric modulators. The type IV isoenzyme is the predominant isoenzyme in most inflammatory cells. This article reviews some of the in vitro, in vivo and clinical studies which have demonstrated that theophylline and selective PDE inhibitors possess anti-inflammatory and immunomodulatory activity.
Enhanced Production of (R)-1,2-Propanediol by Metabolically Engineered Escherichia coli (2000)

1,2-Propanediol (1,2-PD) is a major commodity chemical currently derived from propylene. Previously, we have demonstrated the production of enantiomerically pure (R)-1,2-propanediol from glucose by an engineered E. coli expressing genes for NADH-linked glycerol dehydrogenase and methylglyoxal synthase. In this work, we investigate three methods to improve 1,2-PD in E. coli. First, we investigated improving the host by eliminating production of a byproduct, lactate. To do this, we constructed strains with mutations in two enzymes involved in lactate production, lactate dehydrogenase and glyoxalase I. (Surprisingly, when mutations were made in its ability to produce lactate, one strain of E. coli [MM294], produced a small amount of 1,2-PD without any added genes.) Second, we constructed a complete pathway to 1,2-PD from the glycolytic intermediate, dihydroxyacetone phosphate. Our previous 1, 2-PD producing strains relied on at least one endogenous E. coli activity and only produced 0.7 g/L of 1,2-PD. The complete pathway involved the coexpression of methylglyoxal synthase (mgs), glycerol dehydrogenase (gldA), and either yeast alcohol dehydrogenase (adhI) or E. coli 1,2-propanediol oxidoreductase (fucO). Third, we investigated bioprocessing improvements by carrying out a fed-batch fermentation with the best engineered strain (expressing mgs, gldA, and fucO). A final titer of 4.5 g/L of (R)-1,2-PD was produced, with a final yield of 0.19 g of 1,2-PD per gram of glucose consumed. This work provides a basis for further strain and process improvement.
In Vivo Magnetic Resonance Evaluation of Atherosclerotic Plaques in the Human Thoracic Aorta (2000)

This study demonstrates that noninvasive MR evaluation of the aorta compares well with TEE imaging for the assessment of atherosclerotic plaque thickness, extent, and composition. This MR method may prove useful for the in vivo study of aortic atherosclerosis.
Cloning of Components of a Novel Subthreshold-Activating K+Channel with a Unique Pattern of Expression in the Cerebral Cortex (1999)

Potassium channels that are open at very negative membrane potentials govern the subthreshold behavior of neurons. These channels contribute to the resting potential and help regulate the degree of excitability of a neuron by affecting the impact of synaptic inputs and the threshold for action potential generation. They can have large influences on cell behavior even when present at low concentrations because few conductances are active at these voltages. We report the identification of a new K(+) channel pore-forming subunit of the ether-à-go-go (Eag) family, named Eag2, that expresses voltage-gated K(+) channels that have significant activation at voltages around -100 mV. Eag2 expresses outward-rectifying, non-inactivating voltage-dependent K(+) currents resembling those of Eag1, including a strong dependence of activation kinetics on prepulse potential. However, Eag2 currents start activating at subthreshold potentials that are 40-50 mV more negative than those reported for Eag1. Because they activate at such negative voltages and do not inactivate, Eag2 channels will contribute sustained outward currents down to the most negative membrane potentials known in neurons. Although Eag2 mRNA levels in whole brain appear to be low, they are highly concentrated in a few neuronal populations, most prominently in layer IV of the cerebral cortex. This highly restricted pattern of cortical expression is unlike that of any other potassium channel cloned to date and may indicate specific roles for this channel in cortical processing. Layer IV neurons are the main recipient of the thalamocortical input. Given their functional properties and specific distribution, Eag2 channels may play roles in the regulation of the behavioral state-dependent entry of sensory information to the cerebral cortex.
Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma (2005)

We report four young women who developed acute psychiatric symptoms, seizures, memory deficits, decreased level of consciousness, and central hypoventilation associated with ovarian teratoma (OT) and cerebrospinal fluid (CSF) inflammatory abnormalities. Three patients recovered with treatment of the tumor or immunosuppression and one died of the disorder. Five other OT patients with a similar syndrome and response to treatment have been reported. Our patients' serum or CSF showed immunolabeling of antigens that were expressed at the cytoplasmic membrane of hippocampal neurons and processes and readily accessed by antibodies in live neurons. Immunoprobing of a hippocampal-expression library resulted in the isolation of EFA6A, a protein that interacts with a member of the two-pore-domain potassium channel family and is involved in the regulation of the dendritic development of hippocampal neurons. EFA6A-purified antibodies reproduced the hippocampal immunolabeling of all patients' antibodies and colocalized with them at the plasma membrane. These findings indicate that in a young woman with acute psychiatric symptoms, seizures, and central hypoventilation, a paraneoplastic immune-mediated syndrome should be considered. Recognition of this disorder is important because despite the severity of the symptoms, patients usually recover. The location and function of the isolated antigen suggest that the disorder is directly mediated by antibodies.
Singapore Genome Variation Project: A haplotype map of three Southeast Asian populations (2009)

The Singapore Genome Variation Project (SGVP) provides a publicly available resource of 1.6 million single nucleotide polymorphisms (SNPs) genotyped in 268 individuals from the Chinese, Malay, and Indian population groups in Southeast Asia. This online database catalogs information and summaries on genotype and phased haplotype data, including allele frequencies, assessment of linkage disequilibrium (LD), and recombination rates in a format similar to the International HapMap Project. Here, we introduce this resource and describe the analysis of human genomic variation upon agglomerating data from the HapMap and the Human Genome Diversity Project, providing useful insights into the population structure of the three major population groups in Asia. In addition, this resource also surveyed across the genome for variation in regional patterns of LD between the HapMap and SGVP populations, and for signatures of positive natural selection using two well-established metrics: iHS and XP-EHH. The raw and processed genetic data, together with all population genetic summaries, are publicly available for download and browsing through a web browser modeled with the Generic Genome Browser.
Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes (2009)

TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC.
Directed Evolution of E. coli Alkaline Phosphatase Towards Higher Catalytic Activity (2003)

AbstractDirected evolution was used to enhance the catalytic activity of E. coli alkaline phosphatase (EAP). Through two rounds of error-prone PCR and one round of DNA shuffling followed by a rapid, sensitive screening procedure, several improved variants were obtained. Their enzymatic kinetic properties, thermal stabilities and possible mechanism for the improvement were investigated. In 1.0 M Tris buffer, the specific activity of the most active EAP variant S2163 was 1500 units/mg protein, showing it to be 3.6 times more active than the D101S parent enzyme and ∼40 times more active than the wild-type EAP. At the same time, the Km value of the S2163 variant decreased to 1491 μM from the 2384 μM of the D101S. As a result, the kcat/Km ratio of this variant showed a 5.8-fold enhancement over that of D101S parent enzyme. Three activating amino acid substitutions, K167R, G180S and S374C, which were located far away from the center of the catalytic pocket, were identified by sequencing the genes encoding evolved enzymes. Possible explanations for the improvement of activity were analyzed.KeywordsDirected EvolutionError-prone PcrDna ShufflingE. Coli Alkaline PhosphataseCatalytic ActivityNon-active Site
Nanostructured black silicon and the optical reflectance of graded-density surfaces (2009)

We fabricate and measure graded-index “black silicon” surfaces and find the underlying scaling law governing reflectance. Wet etching (100) silicon in HAuCl4, HF, and H2O2 produces Au nanoparticles that catalyze formation of a network of [100]-oriented nanopores. This network grades the near-surface optical constants and reduces reflectance to below 2% at wavelengths from 300 to 1000 nm. As the density-grade depth increases, reflectance decreases exponentially with a characteristic grade depth of about 1/8 the vacuum wavelength or half the wavelength in Si. Observation of Au nanoparticles at the ends of cylindrical nanopores confirms local catalytic action of moving Au nanoparticles.
Adenoviral Gene Delivery for HIV-1 Vaccination (2005)

The AIDS epidemic continues to spread throughout nations of Africa and Asia and is by now threatening to undermine the already frail infrastructure of developing countries in Sub-Saharan Africa that are hit the hardest. The only option to stem this epidemic is through inexpensive and efficacious vaccines that prevent or at least blunt HIV-1 infections. Despite decades of pre-clinical and clinical research such vaccines remain elusive. Most anti-viral vaccines act by inducing protective levels of virus-neutralizing antibodies. The envelope protein of HIV-1, the sole target of neutralizing antibodies, is constantly changing due to mutations, B cell epitopes are masked by heavy glycosylation and the protein's structural unfolding upon binding to its CD4 receptor and chemokine co-receptors. Efforts to induce broadly cross-reactive virus-neutralizing antibodies able to induce sterilizing or near sterilizing immunity to HIV-1 have thus failed. Studies have indicated that cell-mediated immune responses and in particular CD8+ T cell responses to internal viral proteins may control HIV-1 infections without necessarily preventing them. Adenoviral vectors expressing antigens of HIV-1 are eminently suited to stimulate potent CD8+ T cell responses against transgene products, such as antigens of HIV-1. They performed well in pre-clinical studies in rodents and nonhuman primates and are currently in human clinical trials. This review summarizes the published literature on adenoviral vectors as vaccine carriers for HIV-1 and discusses advantages and disadvantages of this vaccine modality.
Power optimized mode selection for H.263 video coding and wireless communications (2002)

We study how to use the H.263 video communications standard efficiently to save the total consumed energy of a mobile unit in cellular networks. Particularly, we study the computational power dissipation of various operation modes available in the H.263 coding standard. We show how to achieve low power consumption in a mobile unit by judiciously selecting the operating mode of H.263 in response to the mobile environment changes (e.g., slow fading and path loss), while maintaining a good video quality level. Our preliminary results show that a mobile with the proposed method consumes 10% less energy than a mobile that comes with the most efficient power-rate mode (with a search window size of 8) of H.263 video coding in one-hour mobile communication simulation. It even saves around 32% energy over a mobile operating with an advanced coding method (using four negotiating options).