gebhart/patrepeval huggingface dataset:
Identification of Non-nucleoside Human Ribonucleotide Reductase Modulators (2015)

Ribonucleotide reductase (RR) catalyzes the rate-limiting step of dNTP synthesis and is an established cancer target. Drugs targeting RR are mainly nucleoside in nature. In this study, we sought to identify non-nucleoside small-molecule inhibitors of RR. Using virtual screening, binding affinity, inhibition, and cell toxicity, we have discovered a class of small molecules that alter the equilibrium of inactive hexamers of RR, leading to its inhibition. Several unique chemical categories, including a phthalimide derivative, show micromolar IC50s and KDs while demonstrating cytotoxicity. A crystal structure of an active phthalimide binding at the targeted interface supports the noncompetitive mode of inhibition determined by kinetic studies. Furthermore, the phthalimide shifts the equilibrium from dimer to hexamer. Together, these data identify several novel non-nucleoside inhibitors of human RR which act by stabilizing the inactive form of the enzyme.
Policy-based distributed management architecture for large-scale enterprise conferencing service using SIP (2005)

Recent advances in broadband communication and computing technology have accelerated the proliferation of Internet protocol-based multimedia conferencing services in large-scale enterprises. Most of the research on session initial protocol (SIP)-based multimedia conferencing, however, has been limited in scalability due to the centralized management of conference control by a single server. In order to overcome this limitation, we have designed policy-based distributed management architecture for a large-scale enterprise conferencing service by extending the Internet Engineering Task Force's (IETF's) approach. The salient feature of the proposed management architecture is that in addition to the distribution of media processing, both participant membership control and authorization functions are dynamically distributed in accordance with the management policy in order to improve scalability. In order to implement these distributed management functions, we have extended both SIP and conference policy control protocols of the IETF. We also show the procedures for the distributed conference management using the extended SIP signaling methods. Finally, we have evaluated by simulation the performances of the proposed architecture in comparison with the centralized architecture of the IETF. The simulation results show that the proposed architecture greatly improves scalability.
Peroxisome proliferator-activated receptor-gamma ligands inhibit choroidal neovascularization. (2000)

The inhibition of VEGF-induced choroidal angiogenesis in vitro, and CNV in vivo by PPAR-gamma ligands suggests the potential application of these agents in the large group of patients with age-related macular degeneration complicated by CNV.
Controlled specific expression and purification of 6ÃHis-tagged proteins in<i>Pseudomonas</i> (1999)

The 6 x His affinity tags have proved invaluable for the exclusive purification of proteins, in Escherichia coli, of genes cloned in frame with a 6 x His tag and a strong inducible promoter. Here, we demonstrate that the system can be extended to Gram-negative bacteria other than E. coli, by the use of compatible broad-host-range plasmids. As an example, the inducible synthesis and specific purification of the Pseudomonas 6 x His-PfrA siderophore regulatory protein in Pseudomonas putida WCS358 is demonstrated.
The Irregular Z-Buffer and its Application to Shadow Mapping (2004)

It is possible that, with further structure modification, 1,2,4-triazolo[4,3-a]pyridine derivatives, which possess good herbicidal activities, may become novel lead compounds for the development of herbicides against dicotyledonous weeds.
Experimental Tissue Molding for Soft-Tissue Reconstruction (1988)

Molding of pig omentum to create external structures, such as the ear or penis, was performed using silicone rubber molds. The omentum was mobilized on its gastroepiploic pedicle and brought out through a fascial defect. The molds containing the omentum were placed beneath the skin and panniculus carnosus for 4 weeks. Split-thickness skin grafts were placed on both surfaces of the mold, and a series of synthetic materials was placed within the omentum to provide structural support. When an appropriate amount of tissue had been placed within the device, omentum took on the contour of the mold. Excessive pressure associated with swelling resulted in necrosis, while an inadequate amount of tissue gave poor contour. Omentum molded without any support material rapidly lost its contour once removed from the mold. Omentum molded in combination with a synthetic material maintained its shape up to 1 month after mold removal in a limited number of animals. This model was designed to create structures with the fine detail of a prosthesis using autologous tissue. This "prosthesis" made from living tissue could then be transferred secondarily to its recipient area by microvascular technique.
Pulse shaping in mode-locked fiber lasers by in-cavity spectral filter (2014)

We numerically show the possibility of pulse shaping in a passively mode-locked fiber laser by inclusion of a spectral filter into the laser cavity. Depending on the amplitude transfer function of the filter, we are able to achieve various regimes of advanced temporal waveform generation, including ones featuring bright and dark parabolic-, flat-top-, triangular- and saw-tooth-profiled pulses. The results demonstrate the strong potential of an in-cavity spectral pulse shaper for controlling the dynamics of mode-locked fiber lasers.
The DEK oncoprotein is a Su(var) that is essential to heterochromatin integrity (2011)

Heterochromatin integrity is crucial for genome stability and regulation of gene expression, but the factors involved in mammalian heterochromatin biology are only incompletely understood. Here we identify the oncoprotein DEK, an abundant nuclear protein with a previously enigmatic in vivo function, as a Suppressor of Variegation [Su(var)] that is crucial to global heterochromatin integrity. We show that DEK interacts directly with Heterochromatin Protein 1 α (HP1α) and markedly enhances its binding to trimethylated H3K9 (H3K9me3), which is key for maintaining heterochromatic regions. Loss of Dek in Drosophila leads to a Su(var) phenotype and global reduction in heterochromatin. Thus, these findings show that DEK is a key factor in maintaining the balance between heterochromatin and euchromatin in vivo.
Critical role of parathyroid hormone (PTH) receptor-1 phosphorylation in regulating acute responses to PTH (2013)

Agonist-induced phosphorylation of the parathyroid hormone (PTH) receptor 1 (PTHR1) regulates receptor signaling in vitro, but the role of this phosphorylation in vivo is uncertain. We investigated this role by injecting "knock-in" mice expressing a phosphorylation-deficient (PD) PTHR1 with PTH ligands and assessing acute biologic responses. Following injection with PTH (1-34), or with a unique, long-acting PTH analog, PD mice, compared with WT mice, exhibited enhanced increases in cAMP levels in the blood, as well as enhanced cAMP production and gene expression responses in bone and kidney tissue. Surprisingly, however, the hallmark hypercalcemic and hypophosphatemic responses were markedly absent in the PD mice, such that paradoxical hypocalcemic and hyperphosphatemic responses were observed, quite strikingly with the long-acting PTH analog. Spot urine analyses revealed a marked defect in the capacity of the PD mice to excrete phosphate, as well as cAMP, into the urine in response to PTH injection. This defect in renal excretion was associated with a severe, PTH-induced impairment in glomerular filtration, as assessed by the rate of FITC-inulin clearance from the blood, which, in turn, was explainable by an overly exuberant systemic hypotensive response. The overall findings demonstrate the importance in vivo of PTH-induced phosphorylation of the PTHR1 in regulating acute ligand responses, and they serve to focus attention on mechanisms that underlie the acute calcemic response to PTH and factors, such as blood phosphate levels, that influence it.
Integrated monitoring application of patient progression: Clubfoot patient progression as case study (2015)

Clubfoot is a complex deformity found in one in a thousand children. It frequently causes disability - either from the original deformity or because of secondary conditions and problems associated with treatment. Recently, many pedorthsis supporting orthotics deformity in a foot have been evolved. Unfortunately, such pedorthsis need patients to involve in many doctor visits. The advance in wearable technology gives clinicians the tools they need to provide the best possible care to their patients, In the past year, several wearable devices, apps, and other forms of mobile technology have emerged that aim to track your health and overall well-being. In this paper an integrated remote monitoring application called FARH for clubfoot patient progression will be proposed. Farah requires only a single lightweight chipset that can be integrated unobtrusively into a comfortable shoe without hindering daily-living activities. The key advantages of this system include the capability of being used in unconstrained environments, with different footwear conditions, and on different walking surfaces. Moreover, a real time analysis of data describing a certain patient case based on analysis of foot pressure distribution in conjunction with alarming system in case of mistaken walk is also provided. Monitoring progression through automatic collection and analysis of data over time periods will highly support both patients and doctor in charge. Extension to remotely monitor other trackable disease is also included.
Clinical application in oral surgery and basic researchs of Nd-YAG laser with handpieces designed for dentistry (1985)

As the OSADA dental Nd-YAG laser apparatus with changeable four handpieces was offered, we have used to several oral tissues of rabbits and observed the histological changes of irradiated tissues. Thermal changes were also observed by SANEI non-contact infrared rays thermotracer. On clinicaly, we used this apparatus for oral surgery of 60 cases including 37 tumors, 19 cases of cystic lesions, 4 cases of mucosal lesions and others.We recognized this apparatus is convenient for oral use.
Partial task assignment of task graphs under heterogeneous resource constraints (2003)

This paper presents a novel partial assignment technique (PAT) that decides which tasks should be assigned to the same resource without explicitly defining assignment of these tasks to a particular resource. Our method simplifies the assignment and scheduling steps while imposing a small or no penalty on the final solution quality. This technique is specially suited for problems which have different resources constraints. Our method does not cluster tasks into a new task, as typical clustering techniques do, but specifies which tasks need to be executed on the same processor.Our experiments have shown that PAT, which may produce non linear groups of tasks, gives better results than linear clustering when multi-resource constraints are present. Linear clustering was proved to be optimal comparing to all other clusterings for problems with timing constraints only. In this paper, we show that, if used for multi-resource synthesis problem, as it is often used nowadays, linear clustering will produce inferior solutions.
Low Temperature Properties of the Magnetic Semiconductor TmTe (1998)

The magnetic susceptibility, elastic constant, specific heat and magnetization of the magnetic semiconductor TmTe have been measured in detail. A phase transition which is likely to be an antiferro quadrupolar ordering was found to occur at 1.8 K. The specific heat measurements under magnetic fields along the three main crystal axes revealed the unusual characters of this phase transition. The ( H - T ) phase diagram below 5 T is very similar to that of the antiferro quadrupolar ordering in CeB 6 . Above 5 T, however, the phase line for H ∥[100] begins to close toward T =0 K. The physical properties in the paramagnetic region at high temperatures are discussed in the mean field approximation. The theoretical fitting of the elastic softening indicates the antiferro inter-ionic quadrupolar interactions. However, the mean field theory can not explain the specific heat results.
Detailed Structural Characterization of Unbound Protein Phosphatase 1 Inhibitors (2008)

Protein phosphatase 1 (PP1) is an essential and ubiquitous serine/threonine protein phosphatase that is regulated by more than 100 known inhibitor and targeting proteins. It is currently unclear how protein inhibitors distinctly and specifically regulate PP1 to enable rapid responses to cellular alterations. We demonstrate that two PP1 inhibitors, I-2 and DARPP-32, belong to the class of intrinsically unstructured proteins (IUPs). We show that both inhibitors have distinct preferences for transient local and long-range structure. These preferences are likely their structural signature for their interaction with PP1. Furthermore, we show that upon phosphorylation of Thr(34) in DARPP-32, which turns DARPP-32 into a potent inhibitor of PP1, neither local nor long-range structure of DARPP-32 is altered. Therefore, our data suggest a role for these transient three-dimensional topologies in binding mechanisms that enable extensive contacts with PP1's invariant surfaces. Together, these interactions enable potent and selective inhibition of PP1.
Non-steroidal mineralocorticoid receptor antagonists (2007)

The mineralocorticoid hormone aldosterone is essential in regulating the body's salt and water balance. However, abnormal activation of the mineralocorticoid receptor (MR) by elevated levels of aldosterone and salt imbalance cause hypertension and other effects detrimental to the cardiovascular system. Thus, MR antagonists are expected to be beneficial to patients with high blood pressure and other cardiovascular diseases, such as heart failure. Until recently, only steroidal MR antagonists have been developed for therapeutic use. However, due to complexity in chemical synthesis, limited scope for selectivity versus other steroid hormone receptors, and undesirable physical and chemical properties, appropriate steroidal compounds have been difficult to identify and develop. Despite > 40 years of research, only two major steroidal MR antagonists, spironolactone and eplerenone, have been brought to the market for the treatment of hypertension and heart failure. Novel classes of non-steroidal MR antagonists have just begun to emerge over the past few years. This review summarizes the existing information available on non-steroidal MR antagonists from patent applications and the scientific literature published since 2003.
Substrate reuse for epitaxial llift-off of III-V solar cellls (2007)

In the present work, for the first time thin-film GaAs solar cells lifted-off from reused GaAs wafers are presented. Thin-films with a diameter of 2 inch were used to fabricate six cell string demonstrators. The thin-film solar cells deposited on and lifted-off from new substrates show excellent properties. The cells from reused substrates show a somewhat lower efficiency due to a non-optimized wafer re-preparation procedure.
Pure astrocyte cultures derived from cells isolated from mature brain (1988)

Enriched preparations of oligodendrocytes, isolated either from adult bovine brain or from 30-day-old rat brain, eventually yield cultures in MEM-15% calf serum that contain, in addition to oligodendrocytes, proliferating astrocytes and variable numbers of fibroblast-like cells. If these cultures are switched to a serum-free defined medium during the 1st week, mixed cultures containing only oligodendrocytes and astrocytes are obtained. Bovine cultures can be replated and purified by selective adhesion to yield cultures that are greater than 99% astrocytes; similar procedures were not successful with rat cultures. Cytoskeletal preparations of the purified astrocyte cultures from mature bovine brain contain both vimentin and glial fibrillary acidic protein (GFAP), but vimentin is by far the major intermediate filament protein. Thus, the intermediate filament composition of these astrocytes is similar to that of astrocytes in primary cultures obtained from neonatal rat brain. Immunofluorescent studies of these cultures at 24 hr in vitro show that there are no GFAP+ cells in cultures of either species; the bovine cultures contain greater than 95% GC+ cells; and the rat cultures contain 90% GC+ cells. After a few days in vitro flat cells appear that are vimentin+/GFAP-/GC-. In serum-free medium these cells eventually become vimentin+/GFAP+. We propose that the astrocytes that grow in these cultures arise from a population of glial precursor cells, which are present even in adult brain and are isolated together with oligodendroglia, and that they do not derive from contaminating mature astrocytes. Thus, the astrocytes in our cultures may have the same origin as astrocytes grown in culture from dissociated neonatal brain.
Combination Immune Therapies to Enhance Anti-Tumor Responses by NK Cells (2013)

Natural killer (NK) cells are critical innate immune lymphocytes capable of destroying virally infected or cancerous cells through targeted cytotoxicity and further assisting in the immune response by releasing inflammatory cytokines. NK cells are thought to contribute to the process of tumor killing by certain therapeutic monoclonal antibodies (mAb) by directing antibody-dependent cellular cytotoxicity (ADCC) through FcγRIIIA (CD16). Numerous therapeutic mAb have been developed that target distinct cancer-specific cell markers and may direct NK cell-mediated ADCC. Recent therapeutic approaches have combined some of these cancer-specific mAb with additional strategies to optimize NK cell cytotoxicity. These include agonistic mAb targeting NK cell activating receptors and mAbs blocking NK cell inhibitory receptors to enhance NK cell functions. Furthermore, several drugs that can potentiate NK cell cytotoxicity through other mechanisms are being used in combination with therapeutic mAb. In this review, we examine the mechanisms employed by several promising agents used in combination therapies that enhance natural or Ab-dependent cytotoxicity of cancer cells by NK cells, with a focus on treatments for leukemia and multiple myeloma.
Oxidation Mechanism of As(III) in the UV/TiO<sub>2</sub> System:  Evidence for a Direct Hole Oxidation Mechanism (2005)

Although it is well-known that As(III) is oxidized to As(V) in the UV/TiO2 system, the main oxidant for that reaction is still not clear. Accordingly, the present study aims at reinvestigating the TiO2-photocatalyzed oxidation mechanism of As(III). We performed a series of As(II) oxidation experiments by using UV-C/H2O2 and UV-A/TiO2, focusing on the effects of competing compounds. The experiment with UV-C/H2O2 indicated that HO2*/O2-* is not an effective oxidant of As(III) in the homogeneous phase. The effects of oxalate, formate, and Cu(II) on the photocatalytic oxidation of As(III) contradicted the controversial hypothesis that HO2*/ O2-* is the main oxidant of As(III) in the UV/TiO2 system. The effect of As(III) on the TiO2-photocatalyzed oxidations of benzoate, terephthalate, and formate was also incompatible with the superoxide-based As(II) oxidation mechanism. Instead, the experimental observations implied that OH* and/or the positive hole are largely responsible forthe oxidation of As(III) in the UV/TiO2 system. To determine which species plays a more significant role, the effects of methanol and iodide were tested. Since excess methanol did not retard the oxidation rate of As(III), OH* seems not to be the main oxidant. Therefore, the best rationale regarding the oxidation mechanism of As(III) in the UV/TiO2 system seems to be the direct electron transfer between As(III) and positive holes. Only with this mechanism, it was possible to explain the data of this study. Besides the mechanistic aspect, an application method for this technology was sought. The usage of UV/TiO2 for oxidizing As(II) requires a posttreatment in which both As(V) and TiO2 should be removed from water. For this objective, we applied FeCl3 and AIK(SO4)2 as coagulants, and the result implied that the combined usage of TiO2 and coagulation might be a feasible solution to treat arsenic contamination around the world.
Borna Disease Virus Matrix Protein Is an Integral Component of the Viral Ribonucleoprotein Complex That Does Not Interfere with Polymerase Activity (2006)

We have recently shown that the matrix protein M of Borna disease virus (BDV) copurifies with the affinity-purified nucleoprotein (N) from BDV-infected cells, suggesting that M is an integral component of the viral ribonucleoprotein complex (RNP). However, further studies were hampered by the lack of appropriate tools. Here we generated an M-specific rabbit polyclonal antiserum to investigate the intracellular distribution of M as well as its colocalization with other viral proteins in BDV-infected cells. Immunofluorescence analysis revealed that M is located both in the cytoplasm and in nuclear punctate structures typical for BDV infection. Colocalization studies indicated an association of M with nucleocapsid proteins in these nuclear punctate structures. In situ hybridization analysis revealed that M also colocalizes with the viral genome, implying that M associates directly with viral RNPs. Biochemical studies demonstrated that M binds specifically to the phosphoprotein P but not to N. Binding of M to P involves the N terminus of P and is independent of the ability of P to oligomerize. Surprisingly, despite P-M complex formation, BDV polymerase activity was not inhibited but rather slightly elevated by M, as revealed in a minireplicon assay. Thus, unlike M proteins of other negative-strand RNA viruses, BDV-M seems to be an integral component of the RNPs without interfering with the viral polymerase activity. We propose that this unique feature of BDV-M is a prerequisite for the establishment of BDV persistence.
Occluded Pedestrian Detection Through Guided Attention in CNNs (2018)

Pedestrian detection has progressed significantly in the last years. However, occluded people are notoriously hard to detect, as their appearance varies substantially depending on a wide range of occlusion patterns. In this paper, we aim to propose a simple and compact method based on the FasterRCNN architecture for occluded pedestrian detection. We start with interpreting CNN channel features of a pedestrian detector, and we find that different channels activate responses for different body parts respectively. These findings motivate us to employ an attention mechanism across channels to represent various occlusion patterns in one single model, as each occlusion pattern can be formulated as some specific combination of body parts. Therefore, an attention network with self or external guidances is proposed as an add-on to the baseline FasterRCNN detector. When evaluating on the heavy occlusion subset, we achieve a significant improvement of 8pp to the baseline FasterRCNN detector on CityPersons and on Caltech we outperform the state-of-the-art method by 4pp.
Applicability evaluation of service feature enhancement using the partial-file "plug-in" modification technique (2002)

This paper evaluates the applicability of the plug-in mechanism of the nonstop service enhanceable software (NOSES) platform. Plug-in is a dynamic partial-file modification technique that does not affect calls in service in a communication switching system. To apply plug-in program modification widely, the static and dynamic properties of the modified software must be considered. The evaluated applicability of plug-in based on case studies and field data was about 60% for service feature additions modifications. Thus, plug-in is effective for file maintenance of switching systems.