gebhart/patrepeval huggingface dataset:
Molecular Cloning and Expression of the Novel Fungal -Glucosidase Genes from Humicola grisea and Trichoderma reesei (1999)

A novel fungal beta-glucosidase gene (bgl4) and its homologue (bgl2) were cloned from the cellulolytic fungi Humicola grisea and Trichoderma reesei, respectively. The deduced amino acid sequences of H. grisea BGL4 and T. reesei BGL2 comprise 476 and 466 amino acids, respectively, and share 73.1% identity. These beta-glucosidases show significant homology to plant beta-glucosidases belonging to the beta-glucosidase A (BGA) family. Both genes were expressed in Aspergillus oryzae, and the recombinant beta-glucosidases were purified. Recombinant H. grisea BGL4 is a thermostable enzyme compared with recombinant T. reesei BGL2. In addition to beta-glucosidase activity, recombinant H. grisea BGL4 showed a significant level of beta-galactosidase activity, while recombinant T. reesei BGL2 showed weak beta-galactosidase activity. Cellulose saccharification by Trichoderma cellulases was improved by the addition of recombinant H. grisea BGL4.
Identification of the Amino Acid Residues Conferring Substrate Specificity uponSelenomonas ruminantiumLysine Decarboxylase (1999)

Lysine decarboxylase (LDC, EC 4.1.1.18) from Selenomonas ruminantium has decarboxylating activities towards both L-lysine and L-ornithine with similar K(m) and Vmax. Here, we identified four amino acid residues that confer substrate specificity upon S. ruminantium LDC and that are located in its catalytic domain. We have succeeded in converting S. ruminantium LDC to an enzyme with a preference in decarboxylating activity for L-ornithine when the four-residue of LDC were replaced by the corresponding residues of mouse ornithine decarboxylase (EC 4.1.1.17).
Incremental methods for FSM traversal (2002)

Computing the set of reachable states of a finite state machine, is an important component of many problems in the synthesis and formal verification of digital systems. The process of design is usually iterative, and the designer may modify and recompute information many times, and reachability is called each time the designer modifies the system because current methods for reachability analysis are not incremental. Unfortunately, the representation of the reachable states that is currently used in synthesis and verification, is inherently non updatable (O. Coudert and J.C. Madre, 1990). We solve this problem by presenting alternate ways to represent the reachable set, and incremental algorithms that can update the new representation each time the designer changes the system. The incremental algorithms use the reachable set computed at a previous iteration, and information about the changes to the system to update it, rather than compute the reachable set from the beginning. This results in computational savings, as demonstrated by the results.
Probing peptide backbone function in bombesin. A reduced peptide bond analogue with potent and specific receptor antagonist activity. (1988)

Each peptide bond CONH group in the most important COOH-terminal octapeptide region of [Leu14]bombesin was replaced by a CH2NH group using recently developed rapid solid-phase methods. The resulting analogues were then examined for amylase releasing activity in guinea pig pancreatic acini and for their ability to inhibit binding of [125I-Tyr4]bombesin to acinar cells. Replacement of the Trp8-Ala9, Gly11-His12, and His12-Leu13 peptide bonds resulted in about 1000-, 200-, and 300-fold losses in both amylase releasing activity and binding affinity. The Val10-Gly11 replacement, however, retained 30% potency relative to the parent peptide. Ala9-Val10 and Leu13-Leu14 bond replacement analogues exhibited no detectable amylase releasing activity but were still able to bind to acini with Kd values of 1060 and 60 nM, respectively (compared to 15 nM for [Leu14]bombesin itself). Subsequently, both analogues were demonstrated to be competitive inhibitors of bombesin-stimulated amylase release with IC50 values of 937 and 35 nM, respectively. [Leu14-psi-CH2NH-Leu13]Bombesin exhibits a 100-fold improvement in binding affinity compared to previously reported bombesin receptor antagonists and showed no affinity for substance P receptors. It was also a potent inhibitor of bombesin-stimulated growth of murine Swiss 3T3 cells with an IC50 of 18 nM. In terms of a bombesin receptor-binding conformation, these results may aid in the delineation of intramolecular hydrogen-bonding points and the eventual design of improved, conformationally restricted analogues.
The sequence element of the internal ribosome entry site and a 25-kilodalton cellular protein contribute to efficient internal initiation of translation of hepatitis C virus RNA (1997)

Translation of hepatitis C virus (HCV) RNA is initiated by internal entry of ribosomes into the 5' noncoding region (NCR). This process depends on genomic elements within the 5' NCR called the internal ribosome entry site (IRES) and may involve host factors. The alpha-branch structure (nucleotides 47 to 67) of the HCV IRES is considered a cis-acting element critical for translation initiation because it is indispensable for translation in vitro (S. Fukushi, K. Katayama, C. Kurihara, N. Ishiyama, F. B. Hoshino, T. Ando, and A. Oya, Biochem. Biophys. Res. Commun. 199:425-432, 1994). In order to further characterize the function of the alpha-branch, we determined whether sequence exchange within the alpha-branch had any effect on translation initiation. An in vitro translation study revealed that the stem sequences of this region played an important role in efficient IRES function. In addition to several HeLa cell proteins, which had a binding affinity for the 5' NCR, a novel 25-kDa protein that specifically interacted with the HCV IRES was discovered. The binding affinity of the 25-kDa protein for the 5' NCR was correlated with the efficiency of translation initiation of HCV RNA, indicating a critical role for the 25-kDa protein in HCV translation.
Psychological Well-Being before and after Growth Hormone Treatment in Adults with Growth Hormone Deficiency (1990)

The effect of recombinant-DNA human growth hormone treatment on psychological well-being and quality of life was studied in adults with GH deficiency (GHD). 24 adults who satisfied strict criteria for GHD took part in a double-blind, placebo-controlled, 6-month trial. Quality of life assessments were performed at entry, 1 and 6 months by means of self-rating questionnaires. This study reports significantly lower scores on quality of life assessment in the GH-deficient patients at entry compared with matched controls, indicating that this population may be psychologically compromised. Preliminary analysis of treatment results shows that after 6 months, those patients receiving active treatment experienced less perceived illness than the placebo group. Significant psychological improvements were noted in the patients' perception of their energy level and mood.
Combining metagenomics, metatranscriptomics and viromics to explore novel microbial interactions: towards a systems-level understanding of human microbiome (2015)

The advances in experimental methods and the development of high performance bioinformatic tools have substantially improved our understanding of microbial communities associated with human niches. Many studies have documented that changes in microbial abundance and composition of the human microbiome is associated with human health and diseased state. The majority of research on human microbiome is typically focused in the analysis of one level of biological information, i.e., metagenomics or metatranscriptomics. In this review, we describe some of the different experimental and bioinformatic strategies applied to analyze the 16S rRNA gene profiling and shotgun sequencing data of the human microbiome. We also discuss how some of the recent insights in the combination of metagenomics, metatranscriptomics and viromics can provide more detailed description on the interactions between microorganisms and viruses in oral and gut microbiomes. Recent studies on viromics have begun to gain importance due to the potential involvement of viruses in microbial dysbiosis. In addition, metatranscriptomic combined with metagenomic analysis have shown that a substantial fraction of microbial transcripts can be differentially regulated relative to their microbial genomic abundances. Thus, understanding the molecular interactions in the microbiome using the combination of metagenomics, metatranscriptomics and viromics is one of the main challenges towards a system level understanding of human microbiome.
The roles of FPGAs in reprogrammable systems (1998)

Reprogrammable systems based on field programmable gate arrays are revolutionizing some forms of computation and digital logic. As a logic emulation system, they provide orders of magnitude faster computation than software simulation. As a custom-computing machine, they achieve the highest performance implementation for many types of applications. As a multimode system, they yield significant hardware savings and provide truly generic hardware. In this paper, we discuss the promise and problems of reprogrammable systems. This includes an overview of the chip and system architectures of reprogrammable systems as well as the applications of these systems. We also discuss the challenges and opportunities of future reprogrammable systems.
Fault tolerant energy aware data dissemination protocol in sensor networks (2004)

In this paper we present a data dissemination protocol for efficiently distributing data through a sensor network in the face of node and link failures. Our work is motivated by the SPIN protocol which uses metadata negotiation to minimize data transmissions. We propose a protocol called shortest path minded SPIN (SPMS) in which every node has a zone defined by its maximum transmission radius. A data source node advertises the availability of data to all the nodes in its zone. Any interested node requests the data and gets sent the data using multi-hop communication via the shortest path. The failure of any node in the path is detected and recovered using backup routes. We build simulation models to compare SPMS against SPIN. The simulation results show that SPMS reduces the delay over 10 times and consumes 30% less energy in the static failure free scenario. Even with the addition of mobility, SPMS outperforms SPIN by energy gains between 5% and 21%. An analytical model is also constructed to compare the two protocols under a simplified topology.
Stochastic resonance and phase shifts in superparamagnetic particles (1995)

In single-domain particles magnetic moments behave as overdamped rotary oscillators with a potential \ensuremath{\propto}${\mathrm{cos}}^{2}$\ensuremath{\vartheta}. Thus they make a well-understandable object for studies of stochastic resonance (SR). With a numerically exact approach, we analyze magnetic SR in superparamagnetic assemblies including a situation when an external field creates a controllable inequaliity of the potential-well depths.
Abstractive Summarization: A Survey of the State of the Art (2019)

The focus of automatic text summarization research has exhibited a gradual shift from extractive methods to abstractive methods in recent years, owing in part to advances in neural methods. Originally developed for machine translation, neural methods provide a viable framework for obtaining an abstract representation of the meaning of an input text and generating informative, fluent, and human-like summaries. This paper surveys existing approaches to abstractive summarization, focusing on the recently developed neural approaches.
The tularaemia vaccine (1994)

Tularaemia is a disease caused by the facultative intracellular bacterium Francisella tularensis. Vaccination resulting in protective immunity is induced by live vaccine only. Such vaccination can be performed by scarification utilizing the live vaccine strain of F. tularensis (F. tularensis LVS), which results in good but not complete protection. Humoral as well as cell-mediated immunity are induced by vaccination and it has been shown that cell-mediated immunity is a prerequisite for protection. Since the live vaccine strain is attenuated and the genetic background of attenuation is unknown it is important to consider process parameters so that the immunogenicity of the vaccine is preserved.
158-µJ pulses from a single-transverse-mode, large-mode-area erbium-doped fiber amplifier (1997)

We report the amplification of 10-100-pJ semiconductor diode pulses to an energy of 158 microJ and peak powers >100 kW in a multistage fiber amplifier chain based on a single-mode, large-mode-area erbium-doped amplifier design. To our knowledge these results represent the highest single-mode pulse energy extracted from any doped-fiber system.
Progressive supranuclear palsy (Steele-Richardson-Olszewski disease) (1999)

Progressive supranuclear palsy is a neurodegenerative disease which affects the brainstem and basal ganglia. Patients present with disturbance of balance, a disorder of downward gaze and L-DOPA-unresponsive parkinsonism and usually develop progressive dysphagia and dysarthria leading to death from the complications of immobility and aspiration. Treatment remains largely supportive but, potentially, treatments based on cholinergic therapy may be useful. As in Alzheimer's disease, the neuronal degeneration is associated with the deposition of hyperphosphorylated tau protein as neurofibrillary tangles but there are important distinctions between the two diseases. Evidence from familial fronto-temporal dementia with parkinsonism linked to chromosome 17 suggests that tau protein deposition is a primary pathogenic event in some neurodegenerative diseases. The understanding of the mechanism of tau deposition in progressive supranuclear palsy is likely to be of importance in unravelling its aetiology.
Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion (2006)

Mitochondria are increasingly recognized as lynchpins in the evolution of cardiac injury during ischemia and reperfusion. This review addresses the emerging concept that modulation of mitochondrial respiration during and immediately following an episode of ischemia can attenuate the extent of myocardial injury. The blockade of electron transport and the partial uncoupling of respiration are two mechanisms whereby manipulation of mitochondrial metabolism during ischemia decreases cardiac injury. Although protection by inhibition of electron transport or uncoupling of respiration initially appears to be counterintuitive, the continuation of mitochondrial oxidative phosphorylation in the pathological milieu of ischemia generates reactive oxygen species, mitochondrial calcium overload, and the release of cytochrome c. The initial target of these deleterious mitochondrial-driven processes is the mitochondria themselves. Consequences to the cardiomyocyte, in turn, include oxidative damage, the onset of mitochondrial permeability transition, and activation of apoptotic cascades, all favoring cardiomyocyte death. Ischemia-induced mitochondrial damage carried forward into reperfusion further amplifies these mechanisms of mitochondrial-driven myocyte injury. Interruption of mitochondrial respiration during early reperfusion by pharmacologic blockade of electron transport or even recurrent hypoxia or brief ischemia paradoxically decreases cardiac injury. It increasingly appears that the cardioprotective paradigms of ischemic preconditioning and postconditioning utilize modulation of mitochondrial oxidative metabolism as a key effector mechanism. The initially counterintuitive approach to inhibit mitochondrial respiration provides a new cardioprotective paradigm to decrease cellular injury during both ischemia and reperfusion.
Disparate Distribution of 16 Candidate Single Nucleotide Polymorphisms Among Racial and Ethnic Groups of Pediatric Heart Transplant Patients (2006)

African-Americans have a genetic background that may predispose to proinflammatory/lower regulatory environment, reduced drug exposure and immunosuppressive efficacy. In this ongoing multicenter study, these gene polymorphisms differences among ethnic/racial groups are being documented so that therapeutic strategies can be devised to optimize outcomes for pediatric transplant recipients.
BCR-ABL inactivates cytosolic PTEN through Casein Kinase II mediated tail phosphorylation (2015)

The tumor suppressive function of PTEN is exerted within 2 different cellular compartments. In the cytosol-membrane, it negatively regulates PI3K-AKT pathway through the de-phosphorylation of phosphatidylinositol (3,4,5)-triphosphate (PIP3), therefore blocking one of the major signaling transduction pathways in tumorigenesis. In the nucleus, PTEN controls genomic stability and cellular proliferation through phosphatase independent mechanisms. Importantly, impairments in PTEN cellular compartmentalization, changes in protein levels and post-transductional modifications affect PTEN tumor suppressive functions. Targeting mechanisms that inactivate PTEN promotes apoptosis induction of cancer cells, without affecting normal cells, with appealing therapeutic implications. Recently, we have shown that BCR-ABL promotes PTEN nuclear exclusion by favoring HAUSP mediated PTEN de-ubiquitination in Chronic Myeloid Leukemia. Here, we show that nuclear exclusion of PTEN is associated with PTEN inactivation in the cytoplasm of CML cells. In particular, BCR-ABL promotes Casein Kinase II-mediated PTEN tail phosphorylation with consequent inhibition of the phosphatase activity toward PIP3. Targeting Casein Kinase II promotes PTEN reactivation with apoptosis induction. We therefore propose a novel BCR-ABL/CKII/PTEN pathway as a potential target to achieve synthetic lethality with tyrosine kinase inhibitors.
Surgical Stabilization of the Equine Cervical Spine (1979)

The Cloward technique for intervertebral fusion was utilized on 12 horses ranging from 3 months to 2 years of age. Of the 12 horses, 9 had been diagnosed as having equine cervical vertebral malformation (CVM) or “wobbles,” and 3 were normal controls. A large hole was drilled from the ventral border of the vertebral bodies spanning the intervertebral disc and the vertebral end plates of the 2 articulating vertebrae. Frozen homologous bone dowels of slightly larger diameter from equine cadaver ilia were inserted in the holes. No adverse postoperative complication arose. Clinical improvement was seen in all horses with CVM. Three months postoperatively, partial or complete fusion was evident radiographically in 11 of the 12 horses. Necropsies were performed 3–6 months postoperatively to evaluate the quality of the fusion. Cadaver manipulation demonstrated reduced intervertebral movement at the operative site in all cases. The articulations of the equine cervical spine can be operatively fused by the Cloward technique, and surgically induced trauma is minimal. This technique can be used for stabilizing subluxations and may be applicable for treating fractures and osteolytic processes that have weakened vertebrae.
Strain and Model Differences in Behavioral Outcomes after Spinal Cord Injury in Rat (2001)

Spinal cord injury (SCI) results in loss of function below the level of injury and the development of chronic central pain (CCP) syndromes. Since different strains may develop and express chronic pain behaviors differently, we evaluated behavioral outcomes (locomotor recovery and the development of mechanical and thermal allodynia) in three commonly used strains of rats (Long-Evans, Wistar, and Sprague-Dawley) using two models of SCI. The two models examined were contusion at T10 (NYU impactor, 12.5 mm height) and the T13 hemisection. Mechanical stimulation (von Frey filaments) revealed significantly lower baseline responses for Long-Evans rats and significantly higher baseline paw withdrawal latencies to thermal stimulation for Wistar rats compared to the other strains. Following contusion SCI, Long-Evans rats had the highest percentage of animals that developed mechanical allodynia (73%), while Sprague-Dawley rats had the highest percentages (75%) following hemisection SCI. Interestingly, the Sprague-Dawley rats had the highest percentage (87%) to develop thermal allodynia following contusion SCI, while 100% of both Long-Evans and Sprague Dawley rats developed thermal allodynia in the hemisection model. Locomotor recovery after SCI was similar for each model in that Long-Evans rats recovered slower and to a lesser extent than the other strains. In each model, Sprague-Dawley rats recovered faster and achieved greater function. Overall, the hemisection model produced a larger percentage of animals that developed CCP and had greater responses to mechanical stimulation. Thus, it appears that strain selection has a greater impact on locomotor recovery and model selection has a greater impact on the development of CCP following SCI. Furthermore, these results suggest that genetic factors may play a role in recovery following SCI.
In vitro pharmacological characterization of TKI-28, a broad-spectrum tyrosine kinase inhibitor with anti-tumor and anti-angiogenic effects (2005)

Tyrosine kinases are used as important biomarkers in many tumor types. Preclinical and clinical anti-tumor studies have shown that broadly acting tyrosine kinase inhibitors may be more useful than specific inhibitors, since the former might overcome redundancies and crosstalk in tumor cell growth signaling pathways. Here, we aim to identify a novel potent tyrosine kinase inhibitor. Computer modeling of the pyrido-pyrimidine class compound, TKI-28(6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidine-7-one), predicted that the compound would dock well in the ATP pocket of the ErbB-2 tyrosine kinase, yielding a high binding affinity for ErbB receptors. Biochemical studies revealed that TKI-28 potently inhibited the activities of tyrosine kinases such as ErbB-2, EGFR, KDR, PDGFRbeta, c-kit and c-Src, but had little effect on Flt-1 in cell-free system. TKI-28 also efficiently blocked autophosphorylation of the listed receptor tyrosine kinases, and subsequently downregulated phosphorylation of many downstream signaling proteins at the cellular level. TKI-28 exhibited a more potent anti-proliferative activity against EGF- and neuregulin-stimulated SK-OV-3 cells versus serum-stimulated cells, accompanied by apparent induction of apoptosis. Finally, TKI-28 was found to possess anti-angiogenic effects, characterized by inhibition of cell proliferation driven by EGF, VEGF and PDGF, as well as decreased cell migration and tube formation in HMECs. These results collectively highlight the pharmacological characteristics of TKI-28 as a broad-spectrum tyrosine kinase inhibitor, suggesting that it has great potential as an anti-cancer and anti-angiogenesis agent.