gebhart/patrepeval huggingface dataset:
Metabolic pathways for activation of the antiviral agent 9-(2-phosphonylmethoxyethyl)adenine in human lymphoid cells (1995)

9-(2-Phosphonylmethoxyethyl)adenine (PMEA), the acyclic phosphonate analog of adenine monophosphate, is a promising antiviral drug with activity against herpesviruses, Epstein-Barr virus, and retroviruses, including the human immunodeficiency virus. In order to be active, it must be converted to the diphosphate derivative, the putative inhibitor of viral DNA polymerases. The metabolic pathway responsible for activation of PMEA is unclear. The metabolism of PMEA was investigated in human T-lymphoid cells (CEMss) and a PMEA-resistant subline (CEMss(r-1)) with a partial deficiency in adenylate kinase activity. Experiments with [3H]PMEA showed that extracts of CEMss phosphorylated PMEA to its mono- and diphosphate in the presence of ATP as the phosphate donor. No other nucleotides or 5-phosphoribosyl pyrophosphate displayed appreciable activity as a phosphate donor. Subcellular fractionation experiments showed that CEMss cells contained two nucleotide kinase activities, one in mitochondria and one in the cytosol, which phosphorylated PMEA. The PMEA-resistant CEMss mutant proved to have a deficiency in the mitochondrial adenylate kinase activity, indicating that this enzyme was important in the phosphorylation of PMEA. Other effective antiviral purine phosphonate derivatives of PMEA showed a profile of phosphorylating activity similar to that of PMEA. By comparison, phosphorylation of the pyrimidine analog (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine proceeded by an enzyme present in the cytosol. We conclude from these studies that adenylate kinase which has been localized in the intermembrane space of mitochondria is the major route for PMEA phosphorylation in CEMss cells but that another hitherto unidentified enzyme(s) present in the cytosol may contribute to the anabolism of the phosphonates.
Performance Characteristics of Two- and Three-Dimensional Impellers in Centrifugal Compressors (1986)

The overall performance of two- and three-dimensional impellers of a centrifugal compressor were tested and compared. A closed loop test stand with Freon gas as working fluid was employed for the experiments. The inlet and outlet velocity distribtions of all impellers were measured using three hole cobra probes. As a result, it has been revealed that three-dimensional impellers are superior to two-dimensional one in terms of efficiency, head coefficient and operating range. Further, it has also been clarified that the impeller slip factor is affected by blade angle distribution.
Massively Multilingual Neural Machine Translation (2019)

Roee Aharoni, Melvin Johnson, Orhan Firat. Proceedings of the 2019 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies, Volume 1 (Long and Short Papers). 2019.
Direct binding of polysialic acid to a brain-derived neurotrophic factor depends on the degree of polymerization (2008)

Polysialic acid (polySia) is the homopolymer of sialic acid and negatively regulates neuronal cell-cell and cell-extracellular matrix interactions through steric and repulsive hindrance due to its bulky polyanionic structure. Whether polySia also functions as a positive regulator in the nervous system through binding to specific ligands is not known. In the present study, we demonstrated that a brain-derived neurotrophic factor (BDNF) dimer binds directly to polySia to form a large complex with an M(r) greater than 2000 kDa under physiologic conditions. Although somewhat affected by the linkage and type of sialic acid components in the polySia, the complex formation is highly dependent on the polySia chain length. The minimum degree of polymerization required for the complex formation is 12. This is the first study to demonstrate the biologic significance of the degree of polySia polymerization in eukaryotes. Similar large polySia complexes form with other neurotrophic factors such as nerve growth factor, neurotrophin-3, and neurotrophin-4. Furthermore, the BDNF, after making a complex with polySia, can bind to the BDNF receptors, TrkB and p75NTR. The complex formation of BDNF with polySia upregulates growth or/and survival of neuroblastoma cells. These findings suggest that polySia functions as a reservoir of BDNF and other neurotrophic factors and may serve to regulate their local concentrations on the cell surface.
On Tail Probabilities for Martingales (1975)

Watch a martingale with uniformly bounded increments until it first crosses the horizontal line of height $a$. The sum of the conditional variances of the increments given the past, up to the crossing, is an intrinsic measure of the crossing time. Simple and fairly sharp upper and lower bounds are given for the Laplace transform of this crossing time, which show that the distribution is virtually the same as that for the crossing time of Brownian motion, even in the tail. The argument can be adapted to extend inequalities of Bernstein and Kolmogorov to the dependent case, proving the law of the iterated logarithm for martingales. The argument can also be adapted to prove Levy's central limit theorem for martingales. The results can be extended to martingales whose increments satisfy a growth condition.
Functions of intermediate filaments in neuronal development and disease (2003)

Five major types of intermediate filament (IF) proteins are expressed in mature neurons: the three neurofilament proteins (NF-L, NF-M, and NF-H), alpha-internexin, and peripherin. While the differential expression of IF genes during embryonic development suggests potential functions of these proteins in axogenesis, none of the IF gene knockout experiments in mice caused gross developmental defects of the nervous system. Yet, deficiencies in neuronal IF proteins are not completely innocuous. Substantial developmental loss of motor axons was detected in mice lacking NF-L and in double knockout NF-M;NF-H mice, supporting the view of a role for IFs in axon stabilization. Moreover, the absence of peripherin resulted in approximately 30% loss of small sensory axons. Mice lacking NF-L had a scarcity of IF structures and exhibited a severe axonal hypotrophy, causing up to 50% reduction in conduction velocity, a feature that would be very detrimental for large animal species. Unexpectedly, the NF-M rather than NF-H protein turned out to be required for proper radial growth of large myelinated axons. Studies with transgenic mice suggest that some types of IF accumulations, reminiscent of those found in amyotrophic lateral sclerosis (ALS), can have deleterious effects and even cause neurodegeneration. Additional evidence for the involvement of IFs in pathogenesis came from the recent discovery of neurofilament gene mutations linked to ALS and Charcot-Marie-Tooth disease (CMT2E). Conversely, we discuss how certain types of perikaryal neurofilament aggregates might confer protection in motor neuron disease.
Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicity (2005)

Severe combined immunodeficiency (SCID) caused by mutations in RAG1 or RAG2 genes is characterized by a complete block in T- and B-cell development. The only curative treatment is allogeneic hematopoietic stem cell transplantation, which gives a high survival rate (90%) when an HLA-genoidentical donor exists but unsatisfactory results when only partially compatible donors are available. We have thus been interested in the development of a potential alternative treatment by using retroviral gene transfer of a normal copy of RAG1 cDNA. We show here that this approach applied to RAG-1-deficient mice restores normal B- and T-cell function even in the presence of a reduced number of mature B cells. The reconstitution is stable over time, attesting to a selective advantage of transduced progenitors. Notably, a high transgene copy number was detected in all lymphoid organs, and this was associated with a risk of lymphoproliferation as observed in one mouse. Altogether, these results demonstrate that correction of RAG-1 deficiency can be achieved by gene therapy in immunodeficient mice but that human application would require the use of self-inactivated vector to decrease the risk of lymphoproliferative diseases.
Microfluidic micropipette aspiration for measuring the deformability of single cells (2012)

We present a microfluidic technique for measuring the deformability of single cells using the pressure required to deform such cells through micrometre-scale tapered constrictions. Our technique is equivalent to whole-cell micropipette aspiration, but involves considerably simpler operation, less specialized equipment, and less technical skill. Single cells are infused into a microfluidic channel, and then deformed through a series of funnel-shaped constrictions. The constriction openings are sized to create a temporary seal with each cell as it passes through the constriction, replicating the interaction with the orifice of a micropipette. Precisely controlled deformation pressures are generated using an external source and then attenuated 100 : 1 using an on-chip microfluidic circuit. Our apparatus is capable of generating precisely controlled pressures as small as 0.3 Pa in a closed microchannel network, which is impervious to evaporative losses that normally limit the precision of such equipment. Intrinsic cell deformability, expressed as cortical tension, is determined from the threshold deformation pressure using the liquid-drop model. We measured the deformability of several types of nucleated cells and determined the optimal range of constriction openings. The cortical tension of passive human neutrophils was measured to be 37.0 ± 4.8 pN μm(-1), which is consistent with previous micropipette aspiration studies. The cortical tensions of human lymphocytes, RT4 human bladder cancer cells, and L1210 mouse lymphoma cells were measured to be 74.7 ± 9.8, 185.4 ± 25.3, and 235.4 ± 31.0 pN μm(-1) respectively. The precision and usability of our technique demonstrates its potential as a biomechanical assay for wide-spread use in biological and clinical laboratories.
The Herpes Simplex Virus Type 1 U <sub>S</sub> 11 Protein Interacts with Protein Kinase R in Infected Cells and Requires a 30-Amino-Acid Sequence Adjacent to a Kinase Substrate Domain (2002)

ABSTRACT The herpes simplex virus type 1 γ 1 34.5 gene product precludes the host-mediated protein shutoff response induced by activated protein kinase R (PKR). Earlier studies demonstrated that recombinant viruses lacking the γ 1 34.5 gene (Δγ 1 34.5) developed secondary mutations that allowed earlier U S 11 expression and enabled continued protein synthesis. Further, in vitro studies demonstrated that a recombinant expressed U S 11 protein binds PKR, blocks the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF-2α) by activated PKR, and, if provided prior to PKR activation, precluded PKR autophosphorylation. The present study furthers the hypothesis that early U S 11 production precludes PKR-mediated host protein shutoff by demonstrating that (i) U S 11 and PKR interact in the context of viral infection, (ii) this interaction is RNA dependent and requires a 30-amino-acid domain (amino acids 91 to 121) in the carboxyl domain of the U S 11 protein, (iii) the proteins biochemically colocalize in the S100 ribosomal fraction, and (iv) there is a PKR substrate domain immediately adjacent to the binding domain. The results suggest that the U S 11 interaction with PKR at the ribosome is RNA dependent and that the U S 11 protein contains a substrate domain with homology to eIF-2α in close proximity to an essential binding domain.
Combined Routing Scheduling for Spatial TDMA in Multihop Ad hoc Networks (2002)

Multihop ad hoc radio networks can potentially provide low cost, reliable and easily deployed wireless communications for both civilian and military applications. Using a store and forward procedure, with half-duplex transceivers, communication between nodes that are beyond direct radio range is enabled. There are a variety of multiple access protocols applicable to this type of system. Spatial Time Division Multiple Access (STDMA) is a conflict free MAC protocol where links or nodes are scheduled to transmit in periodical slots. This paper analyze the performance of a novel routing and scheduling strategy to create the link transmission schedule in STDMA, named Reuse Adaptive Minimum Hop Algorithm (RA-MHA). RA-MHA uses the set of Minimum hop paths between sources and destinations as well as previously suggested schedule strategies in order to assign link transmissions. The behavior of RA-MHA is compared against the classical STDMA approach through simulations using omnidirectional and Adaptive Beam Forming Antennas. The use of directional antenna patterns reduces the Multiple Access Interference and RA-MHA produces substantial improvement in throughput and packet delay.
Stem cell therapy for faecal incontinence: Current state and future perspectives (2018)

Faecal continence is a complex function involving different organs and systems. Faecal incontinence is a common disorder with different pathogeneses, disabling consequences and high repercussions for quality of life. Current management modalities are not ideal, and the development of new treatments is needed. Since 2008, stem cell therapies have been validated, 36 publications have appeared (29 in preclinical models and seven in clinical settings), and six registered clinical trials are currently ongoing. Some publications have combined stem cells with bioengineering technologies. The aim of this review is to identify and summarise the existing published knowledge of stem cell utilization as a treatment for faecal incontinence. A narrative or descriptive review is presented. Preclinical studies have demonstrated that cellular therapy, mainly in the form of local injections of muscle-derived (muscle derived stem cells or myoblasts derived from them) or mesenchymal (bone-marrow- or adipose-derived) stem cells, is safe. Cellular therapy has also been shown to stimulate the repair of both acute and subacute anal sphincter injuries, and some encouraging functional results have been obtained. Stem cells combined with normal cells on bioengineered scaffolds have achieved the successful creation and implantation of intrinsically-innervated anal sphincter constructs. The clinical evidence, based on adipose-derived stem cells and myoblasts, is extremely limited yet has yielded some promising results, and appears to be safe. Further investigation in both animal models and clinical settings is necessary to drawing conclusions. Nevertheless, if the preliminary results are confirmed, stem cell therapy for faecal incontinence may well become a clinical reality in the near future.
Proteolytic Activation of Respiratory Syncytial Virus Fusion Protein (2001)

The F (fusion) protein of the respiratory syncytial viruses is synthesized as an inactive precursor F(0) that is proteolytically processed at the multibasic sequence KKRKRR(136) into the subunits F(1) and F(2) by the cellular protease furin. This maturation process is essential for the F protein to gain fusion competence. We observed that proteolytic cleavage additionally occurs at another basic motif, RARR(109), that also meets the requirements for furin recognition. Cleavage at both sites leads to the removal from the polypeptide chain of a glycosylated peptide of 27 amino acids. When the sequence RARR(109) was changed to NANR(109) or to RANN(109) by site-directed mutagenesis, cleavage by furin was completely prevented. Although the mutants were still processed at position Arg(136), they did not show any syncytia formation. Proteolytic cleavage of the modified motifs was achieved by treatment of transfected cells with trypsin converting the F mutants into their fusogenic forms. Our findings indicate that both furin consensus sequences have to be cleaved in order to activate the fusion protein.
Ultra Short Term Analysis of Heart Rate Variability using Normal Sinus Rhythm and Atrial Fibrillation ECG Data (2007)

Heart rate variability (HRV) analysis is well established as a quantitative predictor of clinical cardiac events. To provide reliable assessment of HRV in mobile settings, short duration ECG recordings may be analyzed since the conventional five min measurement might be inadequately long. In this study, HRV features were calculated in variable time lengths of long term mobile ECG data. The ultra short term HRV features as reliable as five min measurement were found using Kruskal-Wallis test (p>0.05). However, these HRV features may not have any clinical relevance. Thus, two sets of HRV features were calculated from varying lengths of normal sinus rhythm and atrial fibrillation ECG data. Finally, ultra short term HRV features were obtained from the shortest ECG data segments that produced significant differences between the two sets of HRV features. These results suggested that we could assess the cardiac activity of individuals accurately and conveniently by ultra short term ECG recordings from mobile sensors.
A simple and economical direct agglutination test for serodiagnosis and sero-epidemiological studies of visceral leishmaniasis (1986)

A simple and economical direct agglutination test for the detection of visceral leishmaniasis is described. Trypsin-treated, Coomassie Brilliant Blue-stained, formalin-preserved promastigotes were used as antigen in re-usable V-well microtitre plates. In 21 patients with recent kala-azar, titres of 1:51200 or higher were found. Cured kala-azar patients treated 4 to 14 months before testing, showed titres in the range of 1:3,200 to greater than 1:51,200. Healthy and diseased controls had titres below 1:1,600 with the exception of African trypanosomiasis patients who showed titres of 1:200 to 1:12,800, overlapping with the titres of cured kala-azar patients. Where trypanosomiasis is not a consideration, a titre of 1:1,600 could be considered indicative of visceral leishmaniasis, the sensitivity and specificity were then 100%. The test was applied to sera of 280 inhabitants of Baringo District, a known focus of visceral leishmaniasis in Kenya. When treated cases were included, the test showed a sensitivity of 100% and specificity of 99.3%. This test could be used in district hospitals and health centres in endemic areas as an aid in diagnosis of kala-azar and in the field for sero-epidemiological studies.
<i>By the Bomb's Early Light: American Thought and Culture at the Dawn of the Atomic Age</i> (1987)

Originally published in 1985, By the Bomb's Early Light is the first book to explore the cultural 'fallout' in America during the early years of the atomic age. Paul Boyer argues that the major aspects of the long-running debates about nuclear armament and disarmament developed and took shape soon after the bombing of Hiroshima. The book is based on a wide range of sources, including cartoons, opinion polls, radio programs, movies, literature, song lyrics, slang, and interviews with leading opinion-makers of the time. Through these materials, Boyer shows the surprising and profoundly disturbing ways in which the bomb quickly and totally penetrated the fabric of American life, from the chillingly prophetic forecasts of observers like Lewis Mumford to the Hollywood starlet who launched her career as the 'anatomic bomb.' In a new preface, Boyer discusses recent changes in nuclear politics and attitudes toward the nuclear age.
Extracting deep bottleneck features using stacked auto-encoders (2013)

In this work, a novel training scheme for generating bottleneck features from deep neural networks is proposed. A stack of denoising auto-encoders is first trained in a layer-wise, unsupervised manner. Afterwards, the bottleneck layer and an additional layer are added and the whole network is fine-tuned to predict target phoneme states. We perform experiments on a Cantonese conversational telephone speech corpus and find that increasing the number of auto-encoders in the network produces more useful features, but requires pre-training, especially when little training data is available. Using more unlabeled data for pre-training only yields additional gains. Evaluations on larger datasets and on different system setups demonstrate the general applicability of our approach. In terms of word error rate, relative improvements of 9.2% (Cantonese, ML training), 9.3% (Tagalog, BMMI-SAT training), 12% (Tagalog, confusion network combinations with MFCCs), and 8.7% (Switchboard) are achieved.
Effect of mulberry leaf extract with enriched 1-deoxynojirimycin content on postprandial glycemic control in subjects with impaired glucose metabolism (2011)

Long-term ingestion of mulberry leaf extract with enriched DNJ content could result in improved postprandial glycemic control in individuals with impaired glucose metabolism. These trials were registered with UMIN (no. UMIN000003154 and UMIN000003155). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00101.x, 2011).
Pur-1, a zinc-finger protein that binds to purine-rich sequences, transactivates an insulin promoter in heterologous cells. (1992)

Purine-rich stretches of nucleotides (GAGA boxes) are often found just upstream of transcription start sites in many genes, including insulin. Mutational analysis suggests that the GAGA box plays an important role in transcription of the rat insulin I gene. We identify here at least four different proteins that bind specifically to the insulin GAGA box. Using a GAGA oligonucleotide, we have isolated a cDNA encoding a sequence-specific protein from a HIT (hamster insulinoma cell line) lambda gt11 library. This protein, which we designate Pur-1 (for purine binding), binds to the GAGA boxes of the rat insulin I and II genes and the human islet amyloid polypeptide gene. Pur-1 is a potent transactivator in both pancreatic and nonpancreatic cells. Furthermore, Pur-1 is able to activate an intact insulin promoter in HeLa cells, where it is normally inactive.
A Binary Integer Decimal-based Multiplier for Decimal Floating-Point Arithmetic (2007)

Demand for Decimal Floating-Point (DFP) arithmetic is increasing because global business, e-commerce, financial applications, and the standards and laws that govern them require it. The IEEE P754 Draft Standard for Floating-point Arithmetic specifies formats and operations for DFP numbers. In this paper, we present an IEEE P754-compliant multiplier that operates on values that use the binary encoding of DFP numbers, commonly referred to as the Binary Integer Decimal (BID) encoding. Our BID-based DFP multiplier uses high-speed binary hardware, has variable latency, and is optimized for the common case that the product does not need to be rounded. Our multiplier also uses a novel technique that estimates the number of product digits that needed to be rounded in parallel with the significand multiplication. In this design, a single multiplier is used to multiply the significands and round the product. We believe this the first hardware design of a DFP multiplier for BID-encoded numbers.