gebhart/patrepeval huggingface dataset:
Predicting β-turns and their types using predicted backbone dihedral angles and secondary structures (2010)

We have created an accurate predictor of beta-turns and their types. Our method, called DEBT, is available online at http://comp.chem.nottingham.ac.uk/debt/.
Alternative Adaptive Immunity in Jawless Vertebrates (2010)

Jawless vertebrates use variable lymphocyte receptors (VLRs) that are generated by RAG-independent combinatorial assembly of leucine-rich repeat cassettes for Ag recognition, instead of the Ig-based Ag receptors used by jawed vertebrates. The VLR genes encode for crescent-shaped proteins that use variable beta-strands and a C-terminal loop to bind to Ags rather than the six CDR loops used by BCRs and TCRs. VLR mAbs have been isolated recently, which enabled the structure of VLR-Ag complexes to be defined. The jawless vertebrate adaptive immune system has many similarities to the Ig-based system of jawed vertebrates, including the compartmentalized development of B-like and T-like lymphocyte lineages that proliferate and differentiate into VLR-secreting plasmacytes and proinflammatory cytokine-producing cells in response to Ags. The definition of common features of the VLR-based and Ig-based systems offers fresh insight into the evolution of adaptive immunity.
Ten novel mutations in the HEXA gene in non-Jewish Tay — Sachs patients (1993)

The heterogeneity of mutations causing Tay-Sachs disease in non-Jewish populations requires efficient techniques allowing the simultaneous screening for both known and novel mutations. beta-hexosaminidase mRNA isolated from cultured fibroblasts of 19 Tay-Sachs patients (7 with adult or late onset form of the disease and 12 with infantile Tay-Sachs disease) was amplified by cDNA-PCR in two overlapping segments spanning the entire coding sequence. We used chemical mismatch cleavage (CMC), denaturing gradient gel electrophoresis (DGGE) and direct sequencing of amplified fragments displaying a cleaved product or an altered melting behavior to screen the HEX A gene for mutations and to determine their distribution and frequency in the non-Jewish Tay-Sachs patients. These methods allowed us to identify 31 out of 38 alleles studied (82%). In addition to 9 previously described mutations (the 4 bp insertion in exon 11, G to A transitions at codons 170, 269, 482, 499 and 504, C to T transition at codon 499 and 504 and a GT to AT transition at the donor site of intron 9), we have identified 10 novel mutations. These include 1 donor splice site defect in intron 6, 8 missense mutations at non-randomly distributed conserved residues and a 2 bp deletion in exon 4. These results confirm the extreme molecular heterogeneity of mutations causing Tay-Sachs disease in non-Jewish population. The strategy used should be profitable for identifying mutations in large genes and for diagnostic purposes.
Recent Insight into the Mechanism of Gastrointestinal Tract Ulceration (1987)

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their gastrotoxic and duodenotoxic effects. A few years ago the introduction of a sustained-release form of indomethacin led to an apparently high incidence of jejunal and ileal perforations. Recently, Langman in England was able to demonstrate that the intake of some NSAIDs is related to an enhanced incidence of ileal and jejunal perforations in rats and dogs, even after parenteral or rectal administration. We have been able to show that: (i) There is a correlation between biliary excretion of NSAIDs or ester conjugates of these drugs and ileal perforations in rats. (ii) In contrast to dogs there is no (ibuprofen) or little enterohepatic circulation (diclofenac and diflunisal) in man. This agrees with the low incidence of ileal and jejunal ulcers reported with these drugs in contrast to indomethacin or piroxicam. (iii) Reduction of enterohepatic circulation of indomethacin in rats by dietary means reduces the degree of small intestinal erosions and ulcerations in parallel with the reduced biliary excretion of the drug. It may be safely assumed that the enterohepatic circulation of some NSAIDs, particularly indomethacin and piroxicam, may contribute to the reported incidence of ileal and jejunal damage caused by these drugs. These drugs may, on the other hand, have clearcut advantages as well.
Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease (2005)

Biomarkers to assist in the diagnosis and medical management of Alzheimer disease (AD) are a pressing need. We have employed a proteomic approach, microcapillary liquid chromatography mass spectrometry of proteins labeled with isotope-coded affinity tags (ICAT), to quantify relative changes in the proteome of human cerebrospinal fluid (CSF) obtained from the lumbar cistern. Using CSF from well-characterized AD patients and age-matched controls at 2 different institutions, we quantified protein concentration ratios of 42% of the 390 CSF proteins that we have identified and found differences > or = 20% in over half of them. We confirmed our findings by western blot and validated this approach by quantifying relative levels of amyloid precursor protein and cathepsin B in 17 AD patients and 16 control individuals. Quantitative proteomics of CSF from AD patients compared to age-matched controls, as well as from other neurodegenerative diseases, will allow us to generate a roster of proteins that may serve as specific biomarker panels for AD and other geriatric dementias.
Specific expression of a novel cell wall hydroxyproline-rich glycoprotein gene in lateral root initiation. (1989)

A gene encoding a novel cell wall hydroxyproline-rich glycoprotein (HRGPnt3) was isolated from a genomic library of tobacco. The deduced protein (620 amino acids, Mr, 65,406) contains an amino-terminal hydrophobic signal peptide, is highly basic, and is rich in proline, although characteristic Ser-Pro4 repeats are found only beyond residue 204. At the carboxyl terminus, there is a 34-amino-acid unit repeated three times. Arginine is the predominant basic amino acid rather than lysine, as in other HRGPs. A second gene homologous to HRGPnt3 was revealed by Southern blot hybridization of tobacco genomic DNA. Northern blot hybridization identified a 1.9-kb transcript present at low levels in roots. To determine the underlying spatial pattern of expression, the HRGPnt3 promoter and the first 27 nucleotides of the open reading frame were fused to the beta-glucuronidase (GUS) reporter gene and transformed back into tobacco. Histochemical localization of GUS activity showed that the HRGPnt3 promoter was transiently induced in the pericycle and endodermis, specifically in the discrete, small subset of cells involved in the initiation of lateral roots. This pattern of expression, in cells destined to form the tip of the emerging lateral root, indicates that the encoded cell wall protein has a specialized structural function, possibly in the mechanical penetration of the cortex and epidermis of the main root, and that the HRGPnt3 promoter responds to an early morphogenetic signal for lateral root induction.
Design, Synthesis, and Biological Evaluation of Enantiomeric β‐N‐Acetylhexosaminidase Inhibitors LABNAc and DABNAc as Potential Agents against Tay‐Sachs and Sandhoff Disease (2009)

N-Acetylhexosaminidases are of considerable importance in mammals and are involved in various significant biological processes. In humans, deficiencies of these enzymes in the lysosome, resulting from inherited genetic defects, cause the glycolipid storage disorders Tay-Sachs and Sandhoff diseases. One promising therapy for these diseases involves the use of beta-N-acetylhexosaminidase inhibitors as chemical chaperones to enhance the enzyme activity above sub-critical levels. Herein we describe the synthesis and biological evaluation of a potent inhibitor, 2-acetamido-1,4-imino-1,2,4-trideoxy-L-arabinitol (LABNAc), in a high-yielding 11-step procedure from D-lyxonolactone. The N-benzyl and N-butyl analogues were also prepared and found to be potent inhibitors. The enantiomers DABNAc and NBn-DABNAc were synthesised from L-lyxonolactone, and were also evaluated. The L-iminosugar LABNAc and its derivatives were found to be potent noncompetitive inhibitors of some beta-N-acetylhexosaminidases, while the D-iminosugar DABNAc and its derivatives were found to be weaker competitive inhibitors. These results support previous work postulating that D-iminosugar mimics inhibit D-glycohydrolases competitively, and that their corresponding L-enantiomers show noncompetitive inhibition of these enzymes. Molecular modelling studies confirm that the spatial organisation in enantiomeric inhibitors leads to a different overlay with the monosaccharide substrate. Initial cell-based studies suggest that NBn-LABNAc can act as a chemical chaperone to enhance the deficient enzyme's activity to levels that may cause a positive pharmacological effect. LABNAc, NBn-LABNAc, and NBu-LABNAc are potent and selective inhibitors of beta-N-acetylhexosaminidase and may be useful as therapeutic agents for treating adult Tay-Sachs and Sandhoff diseases.
Hepatitis B Virus Immunopathogenesis (1995)

Approximately 5% of the world population is infected by the hepatitis B virus (HBV) that causes a necroinflammatory liver disease of variable duration and severity. Chronically infected patients with active liver disease carry a high risk of developing cirrhosis and hepatocellular carcinoma. The immune response to HBV-encoded antigens is responsible both for viral clearance and for disease pathogenesis during this infection. While the humoral antibody response to viral envelope antigens contributes to the clearance of circulating virus particles, the cellular immune response to the envelope, nucleocapsid, and polymerase antigens eliminates infected cells. The class I- and class II-restricted T cell responses to the virus are vigorous, polyclonal, and multispecific in acutely infected patients who successfully clear the virus, and the responses are relatively weak and more narrowly focused in chronically infected patients who do not. The pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response to HBV has been demonstrated by the induction of a severe necroinflammatory liver disease following the adoptive transfer of HBsAg-specific CTL into HBV transgenic mice, and by the noncytolytic suppression of viral gene expression and replication in the same animals by a posttranscriptional mechanism mediated by interferon gamma, tumor necrosis factor alpha, and interleukin 2. The dominant cause of viral persistence during HBV infection is the development of a weak antiviral immune response to the viral antigens. While neonatal tolerance probably plays an important role in viral persistence in patients infected at birth, the basis for poor responsiveness in adult-onset infection is not well understood and requires further analysis. Viral evasion by epitope inactivation and T cell receptor antagonism may contribute to the worsening of viral persistence in the setting of an ineffective immune response, as can the incomplete downregulation of viral gene expression and the infection of immunologically privileged tissues. Chronic liver cell injury and the attendant inflammatory and regenerative responses create the mutagenic and mitogenic stimuli for the development of DNA damage that can cause hepatocellular carcinoma. Elucidation of the immunological and virological basis for HBV persistence may yield immunotherapeutic and antiviral strategies to terminate chronic HBV infection and reduce the risk of its life-threatening sequellae.
Extending the boolean and vector space models of information retrieval with p-norm queries and multiple concept types (1983)

Information retrieval systems accept user queries and respond by identifying documents presumed to be relevant to those queries. Boolean logic is commonly employed as the query language, but an alternate scheme based on the vector space model has been investigated. Automatic indexing methods allow questions and documents to be represented by weighted vectors, and searching yields a ranked list of documents in decreasing order of query-document similarity. Both the Boolean logic and vector space approaches are special cases of the very general p-norm model developed by Wu.
In this thesis, analytical results help explain the ranking behavior of p-norm queries. Four experimental test collections are employed to prove that interpreting Boolean queries with p-norm techniques leads to substantial improvements in retrieval effectiveness. Several procedures are described to automatically construct Boolean queries from short lists of words. An algorithm based on probability theory which utilizes relevance feedback information to produce even more effective Boolean or p-norm queries is also specified and validated by experimental tests; one of the essential innovations is to control query construction by allowing the searcher to specify the desired number of retrieved documents.
The vector space model is extended to allow separate handling of other types of concepts beyond those derived from textual words or assigned descriptors. Citation, cocitation, and bibliographic coupling data as well as factual information normally handled by database management systems are easily incorporated. Clustered search and feedback processes are improved by utilizing combinations of these concept types, as shown by preliminary experimental studies with collections in computer and information science.
P-norm queries and multiple concept types are both handled by an updated SMART system implemented using relational database and statistical processing packages. This integrated system should facilitate further research as well as be adaptable to retrieval applications for office and bibliographic information.
Pathophysiology of Adult Obstructive Sleep Apnea (2008)

Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive narrowing or collapse of the pharyngeal airway during sleep. The disorder is associated with major comorbidities including excessive daytime sleepiness and increased risk of cardiovascular disease. The underlying pathophysiology is multifactorial and may vary considerably between individuals. Important risk factors include obesity, male sex, and aging. However, the physiological mechanisms underlying these risk factors are not clearly understood. This brief review summarizes the current understanding of OSA pathophysiology in adults and highlights the potential mechanisms underlying the principal risk factors. In addition, some of the pathophysiological characteristics associated with OSA that may modulate disease severity are illustrated. Finally, the potential for novel treatment strategies, based on an improved understanding of the underlying pathophysiology, is also discussed with the ultimate aim of stimulating research ideas in areas where knowledge is lacking.
Mesh-based content routing using XML (2001)

We have developed a new approach for reliably multicasting time-critical data to heterogeneous clients over mesh-based overlay networks. To facilitate intelligent content pruning, data streams are comprised of a sequence of XML packets and forwarded by application-level XML routers. XML routers perform content-based routing of individual XML packets to other routers or clients based upon queries that describe the information needs of downstream nodes. Our PC-based XML router prototype can route an 18 Mbit per second XML stream.Our routers use a novel Diversity Control Protocol (DCP) for router-to-router and router-to-client communication. DCP reassembles a received stream of packets from one or more senders using the first copy of a packet to arrive from any sender. When each node is connected to n parents, the resulting network is resilient to (n − 1) router or independent link failures without repair. Associated mesh algorithms permit the system to recover to (n − 1) resilience after node and/or link failure. We have deployed a distributed network of XML routers that streams real-time air traffic control data. Experimental results show multiple senders improve reliability and latency when compared to tree-based networks.
Soft-error characteristics in bipolar memory cells with small critical charge (1991)

The alpha-particle-induced soft-error mechanism in a high-speed bipolar static RAM (SRAM) which is used for mainframe computers is investigated using a three-dimensional (3-D) device and a circuit simulator. It is shown that a constant critical charge for the memory cell does not exist. This is because the memory cell's soft-error sensitivities to the charges collected at the base and collector of the cell transistor are different due to the difference in time constants of the base and collector. To take into account this sensitivity difference in the soft-error rate simulation, an effective-charge model is proposed. This model incorporates weight coefficients that express the memory cell's soft-error sensitivities to the charges collected at the base and collector. Accelerated soft-error rates of the 4-kb SRAMs are simulated using the effective-charge model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ChemInform Abstract: Chemotherapeutic Agents. Part 14. Synthesis of π‐Deficient Pyrimidines Linked with π‐Rich Heterocycles as Antimicrobial Agents. (1989)

Abstract The 2‐thiouracils (I) are used as starting materials for a series of title compounds.
Induction of Cachexia in Mice by Systemically Administered Myostatin (2002)

Mice and cattle with genetic deficiencies in myostatin exhibit dramatic increases in skeletal muscle mass, suggesting that myostatin normally suppresses muscle growth. Whether this increased muscling results from prenatal or postnatal lack of myostatin activity is unknown. Here we show that myostatin circulates in the blood of adult mice in a latent form that can be activated by acid treatment. Systemic overexpression of myostatin in adult mice was found to induce profound muscle and fat loss analogous to that seen in human cachexia syndromes. These data indicate that myostatin acts systemically in adult animals and may be a useful pharmacologic target in clinical settings such as cachexia, where muscle growth is desired.
Risks of Mortality, Myocardial Infarction, Bleeding, and Stroke Associated With Therapies for Age-Related Macular Degeneration (2010)

Bevacizumab and ranibizumab use was not associated with increased risks of mortality, myocardial infarction, bleeding, or stroke compared with photodynamic therapy or pegaptanib use.
Review article: selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases (2014)

The pro-inflammatory influence of HDACs in the gut has been confirmed, but mostly in murine studies. Considerably more human data are required to permit development of selective HDAC inhibitors for IBD treatment. Inhibition of key HDAC isoforms in combination with modulation of HDAC-regulatory miRNAs has potential as a novel therapeutic approach.
M-ary Detection and q-ary Decoding in Large-Scale MIMO: A Non-Binary Belief Propagation Approach (2013)

In this paper, we propose a non-binary belief propagation approach (NB-BP) for detection of $M$-ary modulation symbols and decoding of $q$-ary LDPC codes in large-scale multiuser MIMO systems. We first propose a message passing based symbol detection algorithm which computes vector messages using a scalar Gaussian approximation of interference, which results in a total complexity of just $O(KN\sqrt{M})$, where $K$ is the number of uplink users and $N$ is the number of base station (BS) antennas. The proposed NB-BP detector does not need to do a matrix inversion, which gives a complexity advantage over MMSE detection. We then design optimized $q$-ary LDPC codes by matching the EXIT charts of the proposed detector and the LDPC decoder. Simulation results show that the proposed NB-BP detection-decoding approach using the optimized LDPC codes achieve significantly better performance (by about 1 dB to 7 dB at $10^{-5}$ coded BER for various system loading factors with number of users ranging from 16 to 128 and number of BS antennas fixed at 128) compared to using linear detectors (e.g., MMSE detector) and off-the-shelf $q$-ary irregular LDPC codes. Also, even with estimated channel knowledge (e.g., with MMSE channel estimate), the performance of the proposed NB-BP detector is better than that of the MMSE detector.
MINING MEDLINE: ABSTRACTS, SENTENCES, OR PHRASES? (2001)

A growing body of works address automated mining of biochemical knowledge from digital repositories of scientific literature, such as MEDLINE. Some of these works use abstracts as the unit of text from which to extract facts. Others use sentences for this purpose, while still others use phrases. Here we compare abstracts, sentences, and phrases in MEDLINE using the standard information retrieval performance measures of recall, precision, and effectiveness, for the task of mining interactions among biochemical terms based on term co-occurrence. Results show statistically significant differences that can impact the choice of text unit.
Sub-Nanosecond Time of Flight on Commercial Wi-Fi Cards (2015)

The time-of-flight of a signal captures the time it takes to propagate from a transmitter to a receiver. Time-of-flight is perhaps the most intuitive method for localization using wireless signals. If one can accurately measure the time-of-flight from a transmitter, one can compute the transmitter's distance simply by multiplying the time-of-flight by the speed of light. Today, GPS, the most widely used outdoor localization system, localizes a device using the time-of-flight of radio signals from satellites. However, applying the same concept to indoor localization has proven difficult. Systems for localization in indoor spaces are expected to deliver high accuracy (e.g., a meter or less) using consumer-oriented technologies (e.g., Wi-Fi on one's cellphone). Unfortunately, past work could not measure time-of-flight at such an accuracy on Wi-Fi devices. As a result, over the years, research on accurate indoor positioning has moved towards more complex alternatives such as employing large multi-antenna arrays to compute the angle-of-arrival of the signal. These new techniques have delivered highly accurate indoor localization systems. Despite these advances, time-of-flight based localization has some of the basic desirable features that state-of-the-art indoor localization systems lack. In particular, measuring time-of-flight does not require more than a single antenna on the receiver. In fact, by measuring time-of-flight of a signal to just two antennas, a receiver can intersect the corresponding distances to locate its source. Thus, a receiver can locate a wireless transmitter with no support from the surrounding infrastructure. This is quite unlike current indoor localization systems, which require multiple access points at known locations, to find the distance between a pair of mobile devices. Furthermore, each of these access points need to have many antennas -- far beyond what is supported in commercial Wi-Fi devices.
Angiogenic Factors in Endometriosis (2002)

Similar to tumor metastases, endometriotic implants require neovascularization to establish, grow, and invade. The peritoneal environment is ideally suited to provide a proangiogenic milieu. Nevertheless, endometriotic lesions are found only in a minority of reproductive-age women (approximately 10%) with retrograde menstruation. In this paper, we review the major cytokines, growth factors, steroid hormones, and eicosanoids responsible for angiogenesis in endometriosis. We postulate that interference with angiogenic principles expressed in the peritoneum may constitute novel therapeutic opportunities for the prevention, amelioration, or treatment of pelvic endometriosis.