gebhart/patrepeval huggingface dataset:
G-Quadruplex Structures Formed by Expanded Hexanucleotide Repeat RNA and DNA from the Neurodegenerative Disease-Linked C9orf72 Gene Efficiently Sequester and Activate Heme (2014)

The expansion of a (G(4)C(2))n repeat within the human C9orf72 gene has been causally linked to a number of neurodegenerative diseases, most notably familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies have shown that the repeat expansion alters gene function in four ways, disrupting the gene's normal cellular roles and introducing toxic gain of function at the level of both DNA and RNA. (G(4)C(2))n DNA, as well as the RNA transcribed from it, are found to fold into four-stranded G-quadruplex structures. It has been shown that the toxicity of the RNA G-quadruplexes, often localized in intracellular RNA foci, lies in their ability to sequester many important RNA binding proteins. Herein we propose that a distinct toxic property of such RNA and DNA G-quadruplexes from the C9orf72 gene may arise from their ability to bind and oxidatively activate cellular heme. We show that G-quadruplexes formed by both (G(4)C(2))(4) RNA and DNA not only complex tightly with heme but also enhance its intrinsic peroxidase and oxidase propensities. By contrast, the antisense (C(4)G(2))(4) RNA and DNA neither bind heme nor influence its oxidative activity. Curiously, the ability of C9orf72 DNA and transcripts to bind and activate heme mirror similar properties that have been reported for the Aβ peptide and its oligomers in Alzheimer's disease neurons. It is therefore conceivable that C9orf72 RNA G-quadruplex tangles play roles in sequestering intracellular heme and promoting oxidative damage in ALS and FTD analogous to those proposed for Aβ peptide and its tangles in Alzheimer's Disease. Given that neurodegenerative diseases in general are characterized by mitochondrial and respiratory malfunctions, the role of C9orf72 DNA and RNA in heme sequestration as well as its inappropriate activation in ALS and FTD neurons may warrant examination.
Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study (2008)

Long-term treatment with febuxostat resulted in durable maintenance of sUA < 6.0 mg/dl for most subjects. There was nearly complete abolition of gout flares in patients completing the study. Baseline tophi resolved in a majority of subjects.
Escherichia coli sister chromosome separation includes an abrupt global transition with concomitant release of late-splitting intersister snaps (2011)

The basis for segregation of sister chromosomes in bacteria is not established. We show here that two discrete ~150-kb regions, both located early in the right replichore, exhibit prolonged juxtaposition of sister loci, for 20 and 30 min, respectively, after replication. Flanking regions, meanwhile, separate. Thus, the two identified regions comprise specialized late-splitting intersister connections or snaps. Sister snap loci separate simultaneously in both snap regions, concomitant with a major global nucleoid reorganization that results in emergence of a bilobed nucleoid morphology. Split snap loci move rapidly apart to a separation distance comparable with one-half the length of the nucleoid. Concomitantly, at already split positions, sister loci undergo further separation to a comparable distance. The overall consequence of these and other effects is that thus far replicated sister chromosomes become spatially separated (individualized) into the two nucleoid lobes, while the terminus region (and likely, all unreplicated portions of the chromosome) moves to midcell. These and other findings imply that segregation of Escherichia coli sister chromosomes is not a smooth continuous process but involves at least one and likely, two major global transition(s). The presented patterns further suggest that accumulation of internal intranucleoid forces and constraining of these forces by snaps play central roles in global chromosome dynamics. They are consistent with and supportive of our previous proposals that individualization of sisters in E. coli is driven primarily by internally generated pushing forces and is directly analogous to sister individualization at the prophase to prometaphase transition of the eukaryotic cell cycle.
Advances in the development of universal influenza vaccines (2012)

Despite the widespread availability and use of influenza vaccines, influenza still poses a considerable threat to public health. Vaccines against seasonal influenza do not offer protection against pandemic viruses, and vaccine efficacy against seasonal viruses is reduced in seasons when the vaccine composition is not a good match for the predominant circulating viruses. Vaccine efficacy is also reduced in older adults, who are one of the main target groups for vaccination. The continual threat of pandemic influenza, with the known potential for rapid spread around the world and high mortality rates, has prompted researchers to develop a number of novel approaches to providing immunity to this virus, focusing on target antigens which are highly conserved between different influenza A virus subtypes. Several of these have now been taken into clinical development, and this review discusses the progress that has been made, as well as considering the requirements for licensing these new vaccines and how they might be used in the future.
Serum interleukin (IL)‐1, IL‐2, sIL‐2Ra, IL‐6 and thrombopoietin levels in patients with chronic myeloproliferative diseases (2005)

A number of growth factors are involved in clonal haematopoietic expansion and their clinical significance in patients with chronic myeloproliferative diseases requires further evaluation. Using enzyme-linked immunosorbent assays, we analysed serum levels of interleukin (IL)-1a, IL-1b, IL-2, IL-6, the soluble IL-2 receptor alpha (sIL-2Ra), and thrombopoietin (TPO), in 25 individuals with myelofibrosis with myeloid metaplasia (MMM), 40 with essential thrombocythaemia (ET), eight with polycythaemia vera (PV), 10 patients with chronic myeloid leukaemia (CML) and 27 normal controls. These were correlated with clinicopathological characteristics including overall survival, and histopathological bone marrow features, including angiogenesis. The serum derived from patients with MMM, ET, PV and CML contained significantly higher IL-2 and sIL-2Ra than healthy subjects, while IL-6 levels were higher only in MMM and CML than controls. IL-2, sIL-2Ra and IL-6 levels were raised during the transformation phase of CML, during progression of MMM to AML, and ET and PV to myelofibrosis (P < 0.001). There was a positive correlation between IL-2, sIL-2Ra, IL-6 and angiogenesis in bone marrow samples. Cytokines may be useful markers for predicting clinical evolution, reflecting increased angiogenesis. This requires further evaluation to guide diagnostic and therapeutic options.
AET vs. AED: Unsupervised Representation Learning by Auto-Encoding Transformations rather than Data (2019)

The success of deep neural networks often relies on a large amount of labeled examples, which can be difficult to obtain in many real scenarios. To address this challenge, unsupervised methods are strongly preferred for training neural networks without using any labeled data. In this paper, we present a novel paradigm of unsupervised representation learning by Auto-Encoding Transformation (AET) in contrast to the conventional Auto-Encoding Data (AED) approach. Given a randomly sampled transformation, AET seeks to predict it merely from the encoded features as accurately as possible at the output end. The idea is the following: as long as the unsupervised features successfully encode the essential information about the visual structures of original and transformed images, the transformation can be well predicted. We will show that this AET paradigm allows us to instantiate a large variety of transformations, from parameterized, to non-parameterized and GAN-induced ones. Our experiments show that AET greatly improves over existing unsupervised approaches, setting new state-of-the-art performances being greatly closer to the upper bounds by their fully supervised counterparts on CIFAR-10, ImageNet and Places datasets.
Channel characterization and modeling for Ka-band very small aperture terminals (1997)

An increasing number of commercial applications are being promoted for future Ka-band satellite communication systems. Many of these systems will involve low-margin very small aperture terminals (VSATs). These systems are subject to important atmospheric propagation degradations that affect the quality of transmission and the link availability. The objective of this paper is to characterize the Ka-band channel and evaluate the performance degradation in VSATs resulting from atmospheric propagation, impairments. In particular microwave propagation through a turbulent atmosphere is discussed, and the statistical characterization and modeling of tropospheric scintillation is reviewed. Moreover, the paper extends the method proposed by Filip and Vilar (1990) for the long-term characterization and modeling of the combined effect of rain impairments and scintillation. Specifically, the increase in noise temperature during rain events is added to the Filip-Vilar model. This leads to a five-parameter global fading distribution that is used to predict typical Ka-band satellite link outage time, the mathematical formalism is illustrated by applying the method to the selected case of the Advanced Communications Technology Satellite (ACTS)-Georgia Tech experimental downlink. Numerical results confirm that both rain impairments and scintillation are important factors in the design of Ka-band VSAT systems.
Quantitative determination of optical transmission through subwavelength slit arrays in Ag films: Role of surface wave interference and local coupling between adjacent slits (2008)

Measurement of the transmitted intensity from a coherent monomode light source through a series of subwavelength slit arrays in Ag films, with varying array pitch and number of slits, demonstrates enhancement (suppression) by factors of as much as 6 (9) when normalized to the transmission efficiency of an isolated slit. Pronounced minima in the transmitted intensity are observed at array pitches corresponding to ${\ensuremath{\lambda}}_{\mathrm{SPP}}$, $2{\ensuremath{\lambda}}_{\mathrm{SPP}}$, and $3{\ensuremath{\lambda}}_{\mathrm{SPP}}$, where ${\ensuremath{\lambda}}_{\mathrm{SPP}}$ is the wavelength of the surface plasmon polariton (SPP). The position of these minima arises from destructive interference between incident propagating waves and pi-phase-shifted SPP waves. Increasing the number of slits to four or more does not increase appreciably the per-slit transmission intensity. A simple interference model fits well the measured transmitted intensity profile.
Increased Accumulation of Trehalose in Rhizobia Cultured under 1% Oxygen (1990)

The growth of rhizobia under 1% O(2) induced the accumulation of alpha,alpha-trehalose, and the effect of low O(2) was independent of medium composition and Rhizobium species. Trehalose concentration in cells declined rapidly when microaerobic cultures were supplied with 21% O(2). Trehalose formation in nodules may be induced by the microaerobic environment.
Understanding electronic commerce (1997)

In five years or less, analysts say, sales transactions on the Internet will total $100 billion annually. In short, online commerce is big and it's coming fast - and here's the book that shows you how to understand and profit from it. This invaluable overview includes: basics - how electronic commerce works in the real world; strategies - the mind set of companies that will get the most from electronic commerce; consumer applications - credit cards, digital money, and more; business applications - purchase orders, invoices, and other large transactions; case studiesinsightful snapshots of electronic commerce innovatively applied; security - its paramount importance and the five things it requires; and the future - from electronic agents to microcash and microtransactions. This book is for technology-savvy executives, group managers, entrepreneurs, corporate planners, information systems professionals, and anyone else who wants to master the new technology.
Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer (2015)

ANZCTR 12610000509066 . Date of Registration: June 21, 2010.
Multiantigen/multiepitope–directed immune-specific suppression of “complex autoimmune encephalomyelitis” by a novel protein product of a synthetic gene (2002)

Systemic administration of antigen/peptide for peripheral T cell tolerance has long been investigated as a potential approach to therapy of autoimmune diseases. The multiple antimyelin T cell reactivities likely to be associated with multiple sclerosis (MS) impose major difficulties in devising such an immune-specific therapeutic approach to the disease, because targeting T cells specific for a single autoantigen/epitope is unlikely to be sufficiently effective. Here, we present a pilot study on the possibility of concomitantly inhibiting multiple potentially pathogenic antimyelin T cell reactivities by tolerogenic administration of an artificial "multiantigen/multiepitope" protein. A synthetic gene was constructed to encode selected disease-relevant epitopes of myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG). The protein product, hmTAP (synthetic human multitarget autoantigen protein), was adequately processed for antigenic presentation of the relevant integral epitopes, in vitro and in vivo. Systemic administration of hmTAP not only suppressed and treated experimental autoimmune encephalomyelitis (EAE) initiated by autoreactivity to a PLP epitope, but also abrogated complex EAE transferred by multispecific line T cells reactive against encephalitogenic epitopes of MBP, PLP, and MOG. These data indicate that multiantigen/multiepitope-directed therapy of complex autoimmune diseases is effective and can be mediated by the protein product of a specifically designed synthetic gene.
The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic (2018)

Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive place due to their unique antiviral potency, high specificity, and low toxicity in antiretroviral combination therapies used to treat HIV. Until now, >50 structurally diverse classes of compounds have been reported as NNRTIs. Among them, six NNRTIs were approved for HIV-1 treatment, namely, nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETR), rilpivirine (RPV), and doravirine (DOR). In this perspective, we focus on the six NNRTIs and lessons learned from their journey through development to clinical studies. It demonstrates the obligatory need of understanding the physicochemical and biological principles (lead optimization), resistance mutations, synthesis, and clinical requirements for drugs.
Antiviral Activity, Safety, and Pharmacokinetics of Bictegravir as 10-Day Monotherapy in HIV-1–Infected Adults (2017)

BIC is a novel, potent, unboosted INSTI that demonstrated rapid, dose-dependent declines in HIV-1 RNA after 10 days of monotherapy. BIC was well tolerated, and displayed rapid absorption and a half-life supportive of once-daily therapy in HIV-infected subjects.
Online Multi-Object Tracking with Dual Matching Attention Networks (2019)

In this paper, we propose an online Multi-Object Tracking (MOT) approach which integrates the merits of single object tracking and data association methods in a unified framework to handle noisy detections and frequent interactions between targets. Specifically, for applying single object tracking in MOT, we introduce a cost-sensitive tracking loss based on the state-of-the-art visual tracker, which encourages the model to focus on hard negative distractors during online learning. For data association, we propose Dual Matching Attention Networks (DMAN) with both spatial and temporal attention mechanisms. The spatial attention module generates dual attention maps which enable the network to focus on the matching patterns of the input image pair, while the temporal attention module adaptively allocates different levels of attention to different samples in the tracklet to suppress noisy observations. Experimental results on the MOT benchmark datasets show that the proposed algorithm performs favorably against both online and offline trackers in terms of identity-preserving metrics.
Hardware supported persistent object address translation (2017)

Emerging non-volatile main memory technologies create a new opportunity for writing programs with a large, byte-addressable persistent storage that can be accessed through regular memory instructions. These new memory-as-storage technologies impose significant challenges to current programming models. In particular, some emerging persistent programming frameworks, like the NVM Library (NVML), implement relocatable persistent objects that can be mapped anywhere in the virtual address space. To make this work, persistent objects are referenced using object identifiers (ObjectID), rather than pointers, that need to be translated to an address before the object can be read or written. Frequent translation from ObjectID to address incurs significant overhead.
Photodegradable Hydrogels for Dynamic Tuning of Physical and Chemical Properties (2009)

We report a strategy to create photodegradable poly(ethylene glycol)-based hydrogels through rapid polymerization of cytocompatible macromers for remote manipulation of gel properties in situ. Postgelation control of the gel properties was demonstrated to introduce temporal changes, creation of arbitrarily shaped features, and on-demand pendant functionality release. Channels photodegraded within a hydrogel containing encapsulated cells allow cell migration. Temporal variation of the biochemical gel composition was used to influence chondrogenic differentiation of encapsulated stem cells. Photodegradable gels that allow real-time manipulation of material properties or chemistry provide dynamic environments with the scope to answer fundamental questions about material regulation of live cell function and may affect an array of applications from design of drug delivery vehicles to tissue engineering systems.
Parallel analysis of genetic selections using whole genome oligonucleotide arrays (1998)

Thousands of genes have recently been sequenced in organisms ranging from Escherichia coli to human. For the majority of these genes, however, available sequence does not define a biological role. Efficient functional characterization of these genes requires strategies for scaling genetic analyses to the whole genome level. Plasmid-based library selections are an established approach to the functional analysis of uncharacterized genes and can help elucidate biological function by identifying, for example, physical interactors for a gene and genetic enhancers and suppressors of mutant phenotypes. The application of these selections to every gene in a eukaryotic genome, however, is generally limited by the need to manipulate and sequence hundreds of DNA plasmids. We present an alternative approach in which identification of nucleic acids is accomplished by direct hybridization to high-density oligonucleotide arrays. Based on the complete sequence of Saccharomyces cerevisiae, high-density arrays containing oligonucleotides complementary to every gene in the yeast genome have been designed and synthesized. Two-hybrid protein-protein interaction screens were carried out for S. cerevisiae genes implicated in mRNA splicing and microtubule assembly. Hybridization of labeled DNA derived from positive clones is sufficient to characterize the results of a screen in a single experiment, allowing rapid determination of both established and previously unknown biological interactions. These results demonstrate the use of oligonucleotide arrays for the analysis of two-hybrid screens. This approach should be generally applicable to the analysis of a range of genetic selections.
Calcitonin gene-related peptide: a potent dilator of human epicardial coronary arteries. (1986)

To investigate the action of calcitonin gene-related peptide (CGRP) on human epicardial coronary arteries, six patients received intracoronary CGRP at doses of 50,100, and 200 ng/min. The effect of CGRP was measured angiographically with a computerized analysis system. A dose-dependent increase in coronary arterial diameter was observed. At the highest dose there were 34%, 7%, 38%, and 40% mean increases in the diameters of the circumflex, proximal, mid, and distal left anterior descending arteries, respectively. No further increase in diameter was found after a subsequent dose of 1 mg intracoronary isosorbide dinitrate. Prior infusion of CGRP did not prevent coronary arterial spasm induced by ergonovine in two patients with variant angina, but a subsequent bolus of CGRP partially relieved the spasm. We propose that CGRP has a role in the regulation of coronary vascular smooth muscle tone.
Tuber-Specific Silencing of the Acid Invertase Gene Substantially Lowers the Acrylamide-Forming Potential of Potato (2010)

Some popular processed foods including French fries contain small amounts of toxic acrylamide. Efforts to lower the accumulation of this reactive compound by modifying the production process have a negative effect on sensory characteristics and are not broadly applicable. This study optimized a method developed more than a decade ago to lower the accumulation of the acrylamide precursors glucose and fructose in cold-stored tubers. In contrast to the original application, which lowered hexose content by one-third through constitutive expression of an antisense copy of the cold-inducible acid invertase (Inv) gene, the current approach was based on tuber-specific expression of an Inv-derived inverted repeat. Stored tubers of transgenic plants contained as little as 2% of the reducing sugars that accumulated in controls. This decline in glucose and fructose formation is counterbalanced by increased sucrose and starch levels. However, it did not trigger any phenotypic changes and also did not affect the formation of free asparagine, ascorbic acid, phenylalanine, and chlorogenic acid. Importantly, French fries from the low-invertase tubers contained up to 8-fold reduced amounts of acrylamide. Given the important role of processed potato products in the modern Western diet, a replacement of current varieties with the low-hexose potatoes would reduce the average daily intake of acrylamide by one-fourth.