gebhart/patrepeval huggingface dataset:
Purification and characterization of a coenzyme‐A‐dependent succinate‐semialdehyde dehydrogenase from Clostridium kluyveri (1993)

Cell extracts of Clostridium kluyveri, grown on ethanol plus succinate contained a succinyl-CoA:CoA transferase (0.28 U/mg), a coenzyme-A-dependent succinate-semialdehyde dehydrogenase (0.73 U/mg) and a NAD(+)-dependent 4-hydroxybutyrate dehydrogenase (0.25 U/mg). The semialdehyde dehydrogenase, which catalyzed the NADPH-dependent reduction of succinyl-CoA to succinate semialdehyde, was purified 59-fold to homogeneity. A molecular mass of 115000 Da was determined for the native enzyme; SDS/PAGE revealed one protein band at 55,000, indicating that the active form is a dimer. The enzyme was highly specific for succinyl-CoA and succinate semialdehyde. The pH optimum was 7.0 for the reduction of succinyl-CoA, and 8.5 for the reverse reaction. Km values were determined for both the forward and reverse directions. The kinetic data suggest a ping-pong mechanism.
The Pathogenesis of Biliary Atresia: Evidence for a Virus-Induced Autoimmune Disease (2007)

Biliary atresia is a mystifying cause of neonatal cholestasis, manifested by progressive inflammation and fibrosis of both the extrahepatic and intrahepatic bile ducts. It is a devastating disease that leads to cirrhosis and the need for liver transplantation in the majority of children. The etiology is unknown, and one theory is that it may involve a primary perinatal hepatobiliary viral infection and a secondary generation of an autoimmune-mediated bile duct injury. This review will outline the evidence from both human and murine studies supporting a potential cholangiotropic viral infection as the initiator of bile duct injury in biliary atresia and the role of the adaptive immune response and autoimmunity in progression of disease. Delineating the pathways of immune and autoimmune-mediated bile duct injury within biliary atresia could stimulate development of new medical interventions aimed at suppressing the specific immune response, decreasing the inflammatory damage to bile ducts, and delaying or negating the need for liver transplantation.
Uterine Vein Infusion of Interferon Tau (IFNT) Extends Luteal Life Span in Ewes1 (2009)

Interferon tau (IFNT) from the ovine conceptus has paracrine actions on the endometrium that alter release of prostaglandin F(2alpha) (PGF) and protect the corpus luteum (CL). Antiviral activity in uterine vein blood and expression of interferon-stimulated genes (ISGs) in CL is greater in pregnant than in nonpregnant ewes. We hypothesized that IFNT contributes to antiviral activity in uterine vein blood and has endocrine actions on the CL. Preadsorption of IFNT with antiserum against recombinant ovine (ro) IFNT revealed that antiviral activity in uterine vein blood from pregnant ewes was mediated by IFNT. Endocrine actions of IFNT were examined after infusing either roIFNT or bovine serum albumin (BSA; 200 microg/24 h; mini-osmotic pump) into the uterine vein of nonpregnant ewes from Day 10 to Day 11 postestrus. The abundance of ISG15 mRNA and protein was greater in CL (P < 0.05) from ewes receiving 24-h roIFNT infusion compared to that from ewes receiving 24-h BSA infusion. Injection of PGF at 12 h following insertion of mini-osmotic pumps resulted in a decline in serum progesterone concentrations 6 through 12 h later in BSA-infused ewes; however, in roIFNT-infused ewes, a similar decline in progesterone concentrations at 6 h was followed by recovery to control values at 12 h. Ewes then received infusions (200 microg/day) of either roIFNT or BSA for 7 days beginning on Day 10 of the estrous cycle. All BSA-infused ewes returned to estrus by Day 19, whereas 80% of roIFNT-infused ewes maintained luteal-phase concentrations of progesterone through Day 32. In conclusion, IFNT is released from the uterus into the uterine vein and acts through an endocrine mechanism to induce ISGs in the CL and delay luteolysis.
Modulation of Heterogeneous Electron-Transfer Dynamics Across the Electrode/Monolayer Interface (2004)

Spontaneously adsorbed monolayers of [Os(bpy)24bptCl](PF6) have been formed on platinum microelectrodes. bpy is 2,2‘-bipyridyl, and 4bpt is 3,5-bis(pyridin-4-yl)-1,2,4-triazole. These monolayers exhibit well-defined, almost ideal electrochemical responses over a wide range of voltammetric scan rates and in a wide range of electrolytic solutions. The surface coverage of these monolayer films is consistent with that expected for a close-packed monolayer, in which the area of occupation is governed by the area of the redox-active headgroup rather than by the bridging ligand. The differential capacitance of the monolayer-modified interface is 18 ± 3 μF cm-2 compared to 35 ± 3 μF cm-2 for an unmodified surface. Consistent with the observation that the formal potential of the Os2+/3+ process shifts by less than 30 mV upon immobilization, these data suggest that the monolayers are well solvated. The dependence of the differential capacitance on solution pH reveals that the pKa of the triazole bridge within the monolayer, 8.9 ± 0.3, is indistinguishable from that found in solution. Chronoamperometry, conducted on a nanosecond time scale, reveals that the redox switching mechanism involves hole rather than electron transfer. Significantly, upon protonation of the 4bpt bridging ligand, the standard heterogeneous hole transfer rate constant decreases from 1.60 to 0.2 × 106 s-1 for the reduction mechanism and from 2.7 to 0.05 × 106 s-1 for the oxidation process. These observations are consistent with the redox mechanism occurring via a hole-transfer process, the rate of which depends on the energy difference between the metal d π orbitals and the HOMO of the bridge. Protonation of the bridging ligand increases this energy gap, resulting in an overall decrease in the rate of the redox reaction.
Activation and Involvement of p38 Mitogen-activated Protein Kinase in Glutamate-induced Apoptosis in Rat Cerebellar Granule Cells (1997)

In the mammalian central nervous system glutamate is the major excitatory neurotransmitter and plays a crucial role in plasticity and toxicity of certain neural cells. We found that glutamate stimulated activation of p38 and stress-activated protein kinase (SAPK, also known as c-Jun N-terminal kinase (JNK)), two subgroup members of the mitogen-activated protein kinase superfamily in matured cerebellar granule cells. The p38 activation was largely mediated by N-methyl-D-aspartate receptors. Furthermore, we have revealed a novel signaling pathway, that is, Ca2+-mediated activation of p38 in glutamate-treated granule cells. The glutamate concentration effective for inducing apoptosis correlated with that for inducing p38 activation. SB203580, a specific inhibitor for p38, inhibited glutamate-induced apoptosis. Thus p38 might be involved in glutamate-induced apoptosis in cerebellar granule cells.
Event Representations for Automated Story Generation with Deep Neural Nets (2018)

Automated story generation is the problem of automatically selecting a sequence of events, actions, or words that can be told as a story. We seek to develop a system that can generate stories by learning everything it needs to know from textual story corpora. To date, recurrent neural networks that learn language models at character, word, or sentence levels have had little success generating coherent stories. We explore the question of event representations that provide a mid-level of abstraction between words and sentences in order to retain the semantic information of the original data while minimizing event sparsity. We present a technique for preprocessing textual story data into event sequences. We then present a technique for automated story generation whereby we decompose the problem into the generation of successive events (event2event) and the generation of natural language sentences from events (event2sentence). We give empirical results comparing different event representations and their effects on event successor generation and the translation of events to natural language.
Comparing the Effectiveness of Polymer Debriding Devices Using a Porcine Wound Biofilm Model (2016)

<b>Objective:</b> Debridement to remove necrotic and/or infected tissue and promote active healing remains a cornerstone of contemporary chronic wound management. While there has been a recent shift toward less invasive polymer-based debriding devices, their efficacy requires rigorous evaluation. <b>Approach:</b> This study was designed to directly compare monofilament debriding devices to traditional gauze using a wounded porcine skin biofilm model with standardized application parameters. Biofilm removal was determined using a surface viability assay, bacterial counts, histological assessment, and scanning electron microscopy (SEM). <b>Results:</b> Quantitative analysis revealed that monofilament debriding devices outperformed the standard gauze, resulting in up to 100-fold greater reduction in bacterial counts. Interestingly, histological and morphological analyses suggested that debridement not only removed bacteria, but also differentially disrupted the bacterially-derived extracellular polymeric substance. Finally, SEM of post-debridement monofilaments showed structural changes in attached bacteria, implying a negative impact on viability. <b>Innovation:</b> This is the first study to combine controlled and defined debridement application with a biologically relevant <i>ex vivo</i> biofilm model to directly compare monofilament debriding devices. <b>Conclusion:</b> These data support the use of monofilament debriding devices for the removal of established wound biofilms and suggest variable efficacy towards biofilms composed of different species of bacteria.
Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism (2015)

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit.
Identified Sources and Targets of Slow Inhibition in the Neocortex (2003)

There are two types of inhibitory postsynaptic potentials in the cerebral cortex. Fast inhibition is mediated by ionotropic gamma-aminobutyric acid type A (GABA(A)) receptors, and slow inhibition is due to metabotropic GABA(B) receptors. Several neuron classes elicit inhibitory postsynaptic potentials through GABA(A) receptors, but possible distinct sources of slow inhibition remain unknown. We identified a class of GABAergic interneurons, the neurogliaform cells, that, in contrast to other GABA-releasing cells, elicited combined GABA(A) and GABA(B) receptor-mediated responses with single action potentials and that predominantly targeted the dendritic spines of pyramidal neurons. Slow inhibition evoked by a distinct interneuron in spatially restricted postsynaptic compartments could locally and selectively modulate cortical excitability.
Demonstration of Four Immunoassay Formats Using the Array Biosensor (2002)

The ability of a fluorescence-based array biosensor to measure and quantify the binding of an antigen to an immobilized antibody has been demonstrated using the four different immunoassay formats: direct, competitive, displacement, and sandwich. A patterned array of antibodies specific for 2,4,6-trinitrotoluene (TNT) immobilized onto the surface of a planar waveguide and used to measure signals from different antigen concentrations simultaneously. For direct, competitive, and displacement assays, which are one-step assays, measurements were obtained in real time. Dose-response curves were calculated for all four assay formats, demonstrating the array biosensor's ability to quantify the amount of antigen present in solution.
A Structural Approach into Human Tryptophan Hydroxylase and its Implications for the Regulation of Serotonin Biosynthesis (2001)

Tryptophan hydroxylase (TPH) catalyzes the 5-hydroxylation of tryptophan, which is the first step in the biosynthesis of indoleamines (serotonin and melatonin). Serotonin functions mainly as a neurotransmitter, whereas melatonin is the principal hormone secreted by the pineal gland. TPH belongs to the family of the aromatic amino acid hydroxylases, including phenylalanine hydroxylase (PAH) and tyrosine hydroxylase (TH), which all have a strict requirement for dioxygen, non-heme iron (II) and tetrahydrobiopterin (BH4). During the last three years there has been a formidable increase in the amount of structural information about PAH and TH, which has provided new insights into the active site structure, the binding of substrates, inhibitors and pterins, as well as on the effect of disease-causing mutations in these hydroxylases. Although structural information about TPH is not yet available, the high sequence homology between the three mammalian hydroxylases, notably at the catalytic domains, and the similarity of the reactions that they catalyze, indicate that they share a similar 3D-structure and a common catalytic mechanism. Thus, we have prepared a model of the structure of TPH based on the crystal structures of TH and PAH. This structural model provides a frame for understanding the specific interactions of TPH with L-tryptophan and substrate analogues, BH4 and cofactor analogues, L-DOPA and catecholamines. The interactions of these ligands with the enzyme are discussed focusing on the physiological and pharmacological regulation of serotonin biosynthesis, notably by tryptophan supplementation therapy and substitution therapy with tetrahydrobiopterin analogues (positive effects), as well as the effect of catecholamines on TPH activity in L-DOPA treated Parkinson's disease patients (enzyme inhibition).
Use of Copy Number Deletion Polymorphisms to Assess DNA Chimerism (2014)

The CND qPCR technique is suitable for measurement of chimerism for monitoring of rejection in allogeneic organ transplantation and quantification of the cell-free fetal DNA fraction in maternal plasma samples used for noninvasive prenatal genetic testing.
αvβ3-Integrin antagonists inhibit thrombin-induced proliferation and focal adhesion formation in smooth muscle cells (2003)

Alphavbeta3-integrin antagonists reduced neointimal formation following vascular injury in eight different animal models. Because alpha-thrombin contributes to neointimal formation, we examined the hypothesis that alphavbeta3-integrins influence alpha-thrombin-induced signaling. Cultured rat aortic smooth muscle cells (RASMC) expressed alphavbeta3-integrins as demonstrated by immunofluorescence microscopy and fluorescence-activated cell sorting analysis. Proliferative responses to alpha-thrombin were partially inhibited by anti-beta3-integrin monoclonal antibody F11 and by cyclic RGD peptides. Immunofluorescence microscopy showed that alpha-thrombin stimulated a rapid increase in the formation of focal adhesions as identified by vinculin staining and that this effect was partially inhibited by alphavbeta3 antagonists. Beta3-integrin staining was diffuse in quiescent RASMC and did not concentrate at sites of focal adhesions following thrombin treatment. Alpha-thrombin elicited a time-dependent increase in activation of c-Jun NH2-terminal kinase-1 (JNK1) and in tyrosine phosphorylation of focal adhesion kinase (FAK). Alphavbeta3-integrin antagonists partially inhibited increases in JNK1 activity but had no effect on FAK phosphorylation. In SMC isolated from beta3-integrin-deficient mice, focal adhesion formation was impaired in response to thrombin but not sphingosine-1-phosphate, a potent activator of Rho. In summary, alphavbeta3-integrins play an important role in alpha-thrombin-induced proliferation and focal adhesion formation in RASMC.
One pot synthesis of self-assembled V2O5 nanobelt membrane via capsule-like hydrated precursor as improved cathode for Li-ion battery (2011)

A novel self-assembled V2O5 nanobelt membrane was successfully fabricated for the first time. The synthesis strategy is based on the earlier one-pot formation of V2O5·xH2O capsule-like nanobelt membranevia the mediated hydrogen bonding action. The as-made V2O5 nanobelt membrane can be directly integrated into Li-ion batteries serving as a cathode, which exhibit the enhanced electrochemical performance when cycled, including good rate capability, high specific capacity, great cyclability, stability and reliability.
Mobile IP telephony: mobility support of SIP (2003)

The Internet has recently become the most important, most popular way of communication. A significant new feature of the Internet is the support of telephony. Two main competing signaling protocol standards have been developed for this purpose: H.323, proposed by the ITU, and SIP, proposed by the IETF. Another new feature for the Internet is the support of terminal mobility. The IETF efforts in this field have resulted in the Mobile IP standard. Liao (1999) has shown that Mobile IP does not provide fast enough handoffs to support voice communications. Liao has also demonstrated how H.323 may be extended to offer a solution. In this paper we address several major issues for supporting mobility on SIP. We detail the mechanisms for extending SIP to support location management, registration of roaming mobiles, and handoffs. The mechanisms are either extensions of existing SIP, or based on Mobile IP, and thus may be readily employed over the Internet. We believe that the work presented here is an important step towards supporting mobile telephony over the Internet.
Neurogenesis in Postnatal Rat Spinal Cord: A Study in Primary Culture (1997)

Spinal cord injuries result in paralysis, because when damaged neurons die they are not replaced. Neurogenesis of electrophysiologically functional neurons occurred in spinal cord cultured from postnatal rats. In these cultures, the numbers of immunocytochemically identified neurons increased over time. Additionally, neurons identified immunocytochemically or electrophysiologically incorporated bromodeoxyuridine, confirming they had differentiated from mitotic cells in vitro. These findings suggest that postnatal spinal cord retains the capacity to generate functional neurons. The presence of neuronal precursor cells in postnatal spinal cord may offer new therapeutic approaches for restoration of function to individuals with spinal cord injuries.
Enhancing passive UHF RFID backscatter energy using chirp spread spectrum signals and channel shortening (2016)

Performance of passive ultrahigh frequency radio-frequency identification (UHF RFID) systems depends on the energy level of the backscattered signal from the RF tag to the RFID reader. In the indoor environment, the transmitted signals are corrupted by the multi-path channels fading that reduce the energy of the backscatter signal and modify the waveform of the continuous wave (CW) that result a short read range. Chirp spread spectrum (CSS) signals and channel shortening (CS) techniques are used separately to combat the effect of the multi-path channel fading in different contexts. In this paper, we propose two methods that use jointly CSS and CS in the multiple-input single-output (MISO) passive UHF RFID system that employs multiple antennas at the reader and one antenna at the tag First method increases significantly the received energy on the tag. The harvest energy ensures the backscatter communication from tag to reader. Second method offers a good trade-off between maintaining of high received energy and preserving the main characteristics of the waveform of the CSS, on the tag. This method is required to ensure a secured communication between reader and tag.
Structure-based Design of Novel Small-Molecule Inhibitors of Plasmodium falciparum (2010)

Malaria is endemic in most developing countries, with nearly 500 million cases estimated to occur each year. The need to design a new generation of antimalarial drugs that can combat the most drug-resistant forms of the malarial parasite is well recognized. In this study, we wanted to develop inhibitors of key proteins that form the invasion machinery of the malarial parasite. A critical feature of host-cell invasion by apicomplexan parasites is the interaction between the carboxy terminal tail of myosin A (MyoA) and the myosin tail interacting protein (MTIP). Using the cocrystal structure of the Plasmodium knowlesi MTIP and the MyoA tail peptide as input to the hybrid structure-based virtual screening approach, we identified a series of small molecules as having the potential to inhibit MTIP-MyoA interactions. Of the initial 15 compounds tested, a pyrazole-urea compound inhibited P. falciparum growth with an EC(50) value of 145 nM. We screened an additional 51 compounds belonging to the same chemical class and identified 8 compounds with EC(50) values less than 400 nM. Interestingly, the compounds appeared to act at several stages of the parasite's life cycle to block growth and development. The pyrazole-urea compounds identified in this study could be effective antimalarial agents because they competitively inhibit a key protein-protein interaction between MTIP and MyoA responsible for the gliding motility and the invasive features of the malarial parasite.
CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2 (2003)

The control of dendritic cell (DC) migration is pivotal for the initiation of cellular immune responses. When activated with inflammatory stimuli, the chemokine receptor CCR7 is up-regulated on DCs. Activated DCs home to lymphoid organs, where the CCR7 ligands CCL19 and CCL21 are expressed. We previously found that human monocyte-derived DCs (MoDCs) exclusively migrated to CCL19 and CCL21 when matured in the presence of prostaglandin (PG) E2. Because PGE2 did not alter CCR7 cell surface expression, we examined whether PGE2 may exert its effect by coupling CCR7 to signal transduction modules. Indeed, stimulation with CCR7 ligands led to enhanced phosphatidylinositol-3-kinase-mediated phosphorylation of protein kinase B when MoDCs were matured in the presence of PGE2. Moreover, CCL19/CCL21-induced intracellular calcium mobilization in MoDCs occurred only when PGE2 was present during maturation. MoDC migration to CCL19 and CCL21 was dependent on phospholipase C and intracellular calcium flux but not on phosphatidylinositol-3 kinase. Hence, our data provide insight into CCL19/CCL21-triggered signal transduction pathways and identify a novel function for PGE2 in controlling the migration of mature MoDCs by facilitating CCR7 signal transduction.