gebhart/patrepeval huggingface dataset:
Human RAD2 Homolog 1 5′- to 3′-Exo/Endonuclease Can Efficiently Excise a Displaced DNA Fragment Containing a 5′-Terminal Abasic Lesion by Endonuclease Activity (1996)

Repair of abasic lesions, one of the most common types of damage found in DNA, is crucial to an organism's well-being. Studies in vitro indicate that after apurinic-apyrimidinic endonuclease cleaves immediately upstream of a baseless site, removal of the 5'-terminal sugar-phosphate residue is achieved by deoxyribophosphodiesterase activity, an enzyme-mediated beta-elimination reaction, or by endonucleolytic cleavage downstream of the baseless sugar. Synthesis and ligation complete repair. Eukaryotic RAD2 homolog 1 (RTH1) nuclease, by genetic and biochemical evidence, is involved in repair of modified DNA. Efficient endonucleolytic cleavage by RTH1 nuclease has been demonstrated for annealed primers that have unannealed 5'-tails. In vivo, such substrate structures could result from repair-related strand displacement synthesis. Using 5'-tailed substrates, we examined the ability of human RTH1 nuclease to efficiently remove 5'-terminal abasic residues. A series of upstream primers were used to increasingly displace an otherwise annealed downstream primer containing a 5'-terminal deoxyribose-5-phosphate. Until displacement of the first annealed nucleotide, substrates resisted cleavage. With further displacement, efficient cleavage occurred at the 3'-end of the tail. Therefore, in combination with strand displacement activity, RTH1 nucleases may serve as an important alternative to other pathways in repair of abasic sites in DNA.
The Lit de Justice. Semantics, ceremonial and the Parlement of Paris 1300–1600. By Elizabeth A. R. Brown and Richard C. Famiglietti (Beihefte der Francia, 31.) Pp. 163 incl. 8 plates. Sigmaringen: Jan Thorbecke, 1994. DM 72. 3 7995 7331 3 (1996)

The Lit de Justice. Semantics, ceremonial and the Parlement of Paris 1300–1600. By Elizabeth A. R. Brown and Richard C. Famiglietti (Beihefte der Francia, 31.) Pp. 163 incl. 8 plates. Sigmaringen: Jan Thorbecke, 1994. DM 72. 3 7995 7331 3 - Volume 47 Issue 2
UK Teletext-Evolution and Potential (1979)

The development of teletext started in the UK in the early 1970's after investigation into methods of broadcasting subtitles. It was clear that it would soon be economic to build, into every television receiver, LSI circuitry to decode and to display data transmitted during the blanking intervals of the broadcast television signal. Extensive research by the BBC, the IBA and members of BREMA* led to agreement on a unified UK standard for teletext in 1974 and, after a 2 year trial, to a full public teletext service starting in November 1976.1 ,2 The evolution of this UK standard was influenced by the fundamental requirements of a practical data broadcasting service: (1) the service should provide a comprehensive range of information attractively presented, (2) access time, the delay between the viewer selecting a page and the first reception of that page,should be acceptably small, (3) data transmission should be compatible with the normal distribution network, it should have as large a service area as the colour television signal, and should not interfere with normal reception of colour television programmes,3'4 (4) the display should be easily read, (5) transmission errors should have minimnum subjective effect, (6) receivers should be low cost, (7) future options both for transmission and reception should be considered.
Modulation of specific surface receptors and activation sensitization in primary resting CD4+ T lymphocytes by the Nef protein of HIV-1 (2005)

The human immunodeficiency virus type 1 (HIV-1) pathogenicity factor Nef increases viral replication in vivo. In immortalized cell lines, Nef affects the cell surface levels of multiple receptors and signal transduction pathways. Resting CD4+ T lymphocytes are important targets for HIV-1 infection in vivo-they actively transcribe and express HIV-1 genes and contribute to the local viral burden and long-lived viral reservoirs in patients undergoing antiretroviral therapy. In vitro, this primary cell type has, however, thus far been highly refractory to experimental manipulation, and the biological activities exerted by HIV-1 Nef in these cells are largely unknown. Using nucleofection for gene delivery, we find that Nef induces a drastic and moderate down-regulation of CD4 and major histocompatibility complex type 1 (MHC-I), respectively, but does not alter surface levels of other receptors, the down-modulation of which has been reported in cell line studies. In contrast, Nef markedly up-regulated cell surface levels of the MHC-II invariant chain CD74. The effect of Nef on these three surface receptors was also detected upon HIV-1 infection of activated primary CD4+ T lymphocytes. Nef expression alone was insufficient to activate resting CD4+ T lymphocytes, but Nef modestly enhanced the responsiveness of cells to exogenous T cell activation. Consistent with such a signal transduction activity, a subpopulation of Nef localized to lipid raft clusters at the plasma membrane. This study establishes the analysis of Nef functions in these primary HIV target cells. Our data support the involvement of modulation of a defined set of cell surface receptors and sensitization to activation rather than an autonomous activation function in the role of Nef in HIV-1 pathogenesis.
Activation of p38 Mitogen-Activated Protein Kinase Drives Dendritic Cells to Become Tolerogenic inRetTransgenic Mice Spontaneously Developing Melanoma (2009)

Our data show a critical role of constitutively activated p38 MAPK in the acquirement of tolerogenic pattern by DCs during melanoma progression that contributes to the suppression of antitumor T-cell immune responses. We suggest that new strategies of melanoma immunotherapy can include inhibitors of p38 MAPK activity in DCs.
Multimodal human-computer interaction for crisis management systems (2003)

This paper presents a multimodal crisis management system (XISM). It employs processing of natural gesture and speech commands elicited by a user to efficiently manage complex dynamic emergency scenarios on a large display. The developed prototype system demonstrates the means of incorporating unconstrained free-hand gestures and speech in a real-time interactive interface. This paper provides insights into the design aspects of the XISM system. In particular, it addresses the issues of extraction and fusion of gesture and speech modalities to allow more natural interactive behavior. Performance characteristics of the current prototype and considerations for future work are discussed. A series of studies indicated positive response with respect to ease of interacting with the current system.
Neutralizing Antibodies Against Adeno-Associated Viral Capsids in Patients with mut Methylmalonic Acidemia (2016)

Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut(0)) or partial (mut(-)) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals, especially those with mut(0) MMA, has led centers to use elective liver transplantation as a treatment for these patients. We have previously demonstrated the efficacy of systemic adeno-associated viral (AAV) gene delivery as a treatment for MMA in a murine model and therefore sought to survey AAV antibody titers against serotypes 2, 8, and 9 in a group of well-characterized MMA patients, accrued via a dedicated natural history study ( clinicaltrials.gov ID: NCT00078078). Plasma samples provided by 42 patients (8 mut(-) and 34 mut(0); 10 had received organ transplantation), who ranged in age between 2 and 31 years, were analyzed to examine AAV2 (n = 35), AAV8 (n = 41), and AAV9 (n = 42) antibody titers. In total, the seroprevalence of antibodies against AAV2, AAV8, or AAV9 was 20%, 22%, and 24%, respectively. We observed a lower-than-expected seropositivity rate (titers ≥1:20) in the pediatric MMA patients (2-18 years) for both AAV2 (p < 0.05) and AAV8 (p < 0.01) neutralizing antibodies (NAbs) compared with historical controls. Those with positive NAb titers were typically older than 18 years (p < 0.05 all serotypes) or had received solid organ transplantation (p < 0.01 AAV8, AAV9). The mut(0) patients who had not been transplanted (n = 24)-that is, the subset with the greatest need for improved treatments-represented the seronegative majority, with 21 out of 24 patients lacking Abs against all AAV capsids tested. The unexpected lack of NAbs against AAV in this patient population has encouraging implications for systemic gene delivery as a treatment for mut MMA.
Systemic and intracardiac vascular endothelial growth factor and angiopoietin‐1 and ‐2 levels in coronary artery disease: Effects of angioplasty (2007)

There were no differences in indices of angiogenesis when aortic root, coronary ostium, coronary sinus, and femoral vein levels of VEGF and angiopoietins are compared, suggesting that peripheral blood measurements of these indices are comparable to intracardiac levels. Although no immediate effects were observed in soluble VEGF levels, PCI affected intracardiac angiopoietin-1 with a systemic release of angiopoietin-2. Further investigations are necessary to determine the relative systemic and intracardiac effects of the angiopoietins in vascular remodelling post PCI.
LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction (2006)

Low-density lipoprotein receptor-related protein 4 (Lrp4) is a member of a family of structurally related, single-pass transmembrane proteins that carry out a variety of functions in development and physiology, including signal transduction and receptor-mediated endocytosis. Lrp4 is expressed in multiple tissues in the mouse, and is important for the proper development and morphogenesis of limbs, ectodermal organs, lungs and kidneys. We show that Lrp4 is also expressed in the post-synaptic endplate region of muscles and is required to form neuromuscular synapses. Lrp4-mutant mice die at birth with defects in both presynaptic and postsynaptic differentiation, including aberrant motor axon growth and branching, a lack of acetylcholine receptor and postsynaptic protein clustering, and a failure to express postsynaptic genes selectively by myofiber synaptic nuclei. Our data show that Lrp4 is required during the earliest events in postsynaptic neuromuscular junction (NMJ) formation and suggest that it acts in the early, nerveindependent steps of NMJ assembly. The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes.
Poly(A) . Poly(U) as Adjuvant in Cancer Treatment Distribution and Pharmacokinetics in Rabbits (1985)

Rabbits were injected with poly(A).poly(U) and the metabolic fate and stability studied using scintigraphic techniques, radioactive counting, and subcellular fractionation. The complex has a very long lifetime (measured in days) in both liver and spleen, the major locations of concentration in the animal, with about nine times more per gram of tissue in the spleen compared with the liver. In spleen cells the material is about equally divided between nuclei and cytoplasm. The polymer is slowly degraded to shorter molecules in these cells but, even 1 week after injection, significant amounts of apparently intact polynucleotide complex can be detected in both cellular fractions.
Aberrant splicing at catalytic site as cause of infantile onset glycogen storage disease type II (GSDII): Molecular identification of a novel IVS9 (+2GT?GC) in combination with rare IVS10 (+1GT?CT) (2001)

Glycogen storage disease type II (GSDII) results from deleterious mutations in acid alpha-glucosidase gene. To date several mutant alleles have been studied including missense and nonsense mutations, insertions, small and large deletions as well as splice site mutations. Apart from IVS1 (- 13-->G), 525delT, and Delta18, the other mutations are rare and often unique to single patients. Moreover, the molecular findings also observed in the different ethnic groups makes it difficult to attempt to correlate genotype and phenotype to explain the origin of clinical variability. Even though there are no conclusive genotype phenotype correlations, the in frame splice site mutations identified up until now have been found associated with the juvenile/adult onset of GSDII. In this study we describe a novel in frame splicing defect, IVS9 (+2GT-->GC), identified in combination with the rare IVS10 (+1GT-->CT) mutation in a patient with classic infantile GSDII disease. Because both mutations occur at the catalytic site region, it is likely that the alteration of both catalytic function and steric conformation of the enzyme may be responsible for the most severe form of the disease.
Manufacture of Passive Dynamic Ankle–Foot Orthoses Using Selective Laser Sintering (2008)

Ankle-foot orthosis (AFO) designs vary in size, shape, and functional characteristics depending on the desired clinical application. Passive Dynamic (PD) Response ankle-foot orthoses (PD-AFOs) constitute a design that seeks to improve walking ability for persons with various neuromuscular disorders by passively (like a spring) providing variable levels of support during the stance phase of gait. Current PD-AFO manufacturing technology is either labor intensive or not well suited for the detailed refinement of PD-AFO bending stiffness characteristics. The primary objective of this study was to explore the feasibility of using a rapid freeform prototyping technique, selective laser sintering (SLS), as a PD-AFO manufacturing process. Feasibility was determined by replicating the shape and functional characteristics of a carbon fiber AFO (CF-AFO). The study showed that a SLS-based framework is ideally suited for this application. A second objective was to determine the optimal SLS material for PD-AFOs to store and release elastic energy; considering minimizing energy dissipation through internal friction is a desired material characteristic. This study compared the mechanical damping of the CF-AFO to PD-AFOs manufactured by SLS using three different materials. Mechanical damping evaluation ranked the materials as Rilsan D80 (best), followed by DuraForm PA and DuraForm GF. In addition, Rilsan D80 was the only SLS material able to withstand large deformations.
Lysophospholipid Receptors: Signaling and Biology (2004)

Lysophospholipids (LPs), such as lysophosphatidic acid and sphingosine 1-phosphate, are membrane-derived bioactive lipid mediators. LPs can affect fundamental cellular functions, which include proliferation, differentiation, survival, migration, adhesion, invasion, and morphogenesis. These functions influence many biological processes that include neurogenesis, angiogenesis, wound healing, immunity, and carcinogenesis. In recent years, identification of multiple cognate G protein-coupled receptors has provided a mechanistic framework for understanding how LPs play such diverse roles. Generation of LP receptor-null animals has allowed rigorous examination of receptor-mediated physiological functions in vivo and has identified new functions for LP receptor signaling. Efforts to develop LP receptor subtype-specific agonists/antagonists are in progress and raise expectations for a growing collection of chemical tools and potential therapeutic compounds. The rapidly expanding literature on the LP receptors is herein reviewed.
Stable hybridoma cultivation in a pilot‐scale acoustic perfusion system: Long‐term process performance and effect of recirculation rate (2005)

Perfusion systems have the possibility to be operated continuously for several months. It is important that the performance of the cell retention device does not limit the operation time of a perfusion process used in the production of active pharmaceutical ingredients. Therefore, the aim of this study was to investigate the reliability and long-term stability of an acoustic perfusion process using the 200 L/d BioSep. As the BioSep is an external device, it is possible that dependent on the recirculation rate nutrient gradients occur in the external loop, which could affect the cell metabolism. Therefore, the effect of possible nutrient gradients on cell metabolism, viability and productivity was studied by varying the recirculation rate. In this study, it is shown that a perfusion process using a pilot-scale acoustic cell-retention device (200 L/d) is reliable and simple to operate, resulting in a stable 75-day cultivation of a hybridoma cell line producing a monoclonal antibody. The recirculation rate had a significant effect on the oxygen concentration in the external loop, with oxygen being depleted within the cell-retention device at recirculation rates below 6 m3/m(reactor)3.d (=600 L/d). The oxygen depletion at low circulation rates correlated with a slightly increased lactate production rate. For all other parameters no effect of the recirculation rate was observed, including cell death measured through the release of lactate dehydrogenase and specific productivity. A maximum specific productivity of 12 pg/cell.d was reached.
A Map-Reduce Method for Training Autoencoders on Xeon Phi (2015)

The stacked autoencoder is a deep learning model that consists of multiple autoencoders. This model has been widely applied in numerous machine learning applications. A significant amount of effort has been made to increase the size of the deep learning model with respect to the size of the training dataset and the parameter of the model to improve performance. However, training a large deep learning model is highly time consuming. Recent studies have applied the CPU cluster with thousands of machines as well as the single GPU or the GPU cluster, to train large scale deep learning models. As a high-performance coprocessor like GPU, the Xeon Phi can be an alternative tool for training large scale deep learning models on a single machine. The Xeon Phi can be recognized as a small cluster which features about 60 cores, and each core supports four hardware threads. Massive parallelism offsets the low computing capacity of every core, but challenges an efficient parallel autoencoders design. In this paper, we analyze the training algorithm of autoen-coders based on the matrix operation and point out the thread oversubscription problem, which results in performance degradation. Based on the observation, we propose our map-reduce implementation of autoencoders on the Xeon Phi coprocessor. Our basic idea is to parallelize multiple autoencoder model replicas with bulk synchronous parallel (BSP) communication model where the parameters are updated after the computations of all replicas are completed. Each thread is responsible for one model replica, and all replicas work together on the same mini-batch. This data parallelism method is suitable for training autoencoders on the Xeon Phi, and can extend to asynchronous parallel training method without thread oversubscription. In our experiment the speedup is four times higher than that of sequential implementation. Enlarging the size of the autoencoder model, our method still gets stable speedup.
Viral vectors: a look back and ahead on gene transfer technology. (2013)

No matter what their origin, strain and family, viruses have evolved exquisite strategies to reach and penetrate specific target cells where they hijack the cellular machinery to express viral genes and produce progeny particles. The ability to deliver and express genetic information to cells is the basis for exploiting viruses as "Trojan horses" to genetically modify the natural cell target or, upon manipulation of the viral receptor to retarget the virus, to genetically engineer different cell types. This process, known as transduction, is accomplished using viral vectors derived from parental wild type viruses whose viral genes, essential for replication and virulence, have been replaced with the heterologous gene(s) required for cell manipulation. Rearrangement of the viral genome to impede replication or generation of infectious virions but maintaining the ability to deliver nucleic acids has been the object of intense research since the early 1980s. Technological advances and the ever-growing knowledge of molecular virology and virus-host cell relationships have constantly improved the safety profile of viral vectors that are now used in vitro and in vivo to study cellular gene function, correct genetic defects (gene therapy), express therapeutic proteins, vaccinate against infectious agents and tumors, produce experimental animal models, and for other purposes. This review illustrates the strategies used to generate some of the most used viral vectors, and their advantages, limitations and principal applications.
Overdiagnosis Due to Prostate-Specific Antigen Screening: Lessons From U.S. Prostate Cancer Incidence Trends (2002)

Among men with prostate cancer that would be detected only at autopsy, these rates correspond to overdiagnosis rates of, at most, 15% in whites and 37% in blacks. The observed trends in prostate cancer incidence are consistent with considerable overdiagnosis among PSA-detected cases. However, the results suggest that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing.
Fusion of ETV6 to Neurotrophin-3 Receptor TRKC in Acute Myeloid Leukemia With t(12;15)(p13;q25) (1999)

Chromosome translocations involving band 12p13 are known to be involved in a variety of hematologic malignancies, some of them resulting in rearrangement of the ETV6/TEL gene. Applying the fluorescence in situ hybridization (FISH) method, we found a cryptic translocation t(12;15)(p13;q25) in an adult acute myeloid leukemia (AML) patient. Hybridization with cosmid probes showed that the ETV6 gene was rearranged in this translocation. A patient-specific cDNA library was screened with ETV6 cDNA, and a novel fusion transcript was identified between the ETV6 and TRKC/NTRK3 gene located on 15q25. TRKC is a receptor tyrosine kinase that is activated by neurotrophin-3 (NT-3). It is known to be expressed broadly in neural tissues but not in hematologic cells, so far. ETV6-TRKC chimeric transcript encoded the pointed (PNT) domain of the ETV6 gene that fused to the protein-tyrosine kinase (PTK) domain of the TRKC gene. Two types of fusion transcript were determined, one that included the entire PTK domain of TRKC and the other in which the 3'-terminal 462 bp of TRKC was truncated within the PTK domain. Western blot analysis showed the expression of both chimeric proteins of 52 and 38 kD in size. Our results suggest that chimeric PTK expressed in the leukemic cells may contribute to cellular transformation by abnormally activating TRK signaling pathways. Moreover, this is the first report on truncated neurotrophin receptors associated in leukemia.
EFFECTS OF VARIATIONS OF OCCUPANT BEHAVIOR ON RESIDENTIAL BUILDING NET ZERO ENERGY PERFORMANCE (2011)

The objective of the work is to identify the types of occupant-driven residential behaviour variations that most significantly impact a designer’s ability to predict energy consumption and peak electrical demand of a house. The study compares the sensitivities of results for a typical house and compares with a house designed to achieve net zero energy consumption, where occupant-driven loads are more influential. The results, generated using EnergyPlus, suggest that cooling setpoints and lighting power have the most influence for a typical house, while plug loads and schedule randomization have more influence over the net zero energy house.