gebhart/patrepeval huggingface dataset:
Structural and biological characterization of NOS inhibitors with antimicrobial properties (585.5) (2014)

Nitric oxide produced by bacterial nitric oxide synthase (bNOS) protects Gram‐positive pathogens Bacillus anthracis and Staphylococcus aureus against oxidative stress and a wide variety of antibiotics. Recently, we demonstrated that co‐treatment with NOS inhibitors increases the killing efficacy of a common antimicrobial (1) . Taking an interdisciplinary approach using microbial in vitro assays, spectroscopic binding analyses, enzyme kinetics and X‐ray crystal structures we have identified a series of lead inhibitors for future structure‐based drug design. Crystal structures of lead bNOS inhibitors have revealed an unprecedented mode of binding to the bacterial NOS that has not been previously observed in mammalian homologs. Continued exploitation of this novel‐binding mode will be imperative for rationally designing a potent and selective bNOS inhibitor. Grant Funding Source : National Institute of Health
Centrosomal-ciliary geneCEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis (2007)

Mutations in the centrosomal-ciliary gene CEP290/NPHP6 are associated with Joubert syndrome and are the most common cause of the childhood recessive blindness known as Leber congenital amaurosis (LCA). An in-frame deletion in Cep290 shows rapid degeneration in the rod-rich mouse retina. To explore the mechanisms of the human retinal disease, we studied CEP290-LCA in patients of different ages (7-48 years) and compared results to Cep290-mutant mice. Unexpectedly, blind CEP290-mutant human retinas retained photoreceptor and inner laminar architecture in the cone-rich central retina, independent of severity of visual loss. Surrounding the cone-rich island was photoreceptor loss and distorted retina, suggesting neural-glial remodeling. The mutant mouse retina at 4-6 weeks of age showed similar features of retinal remodeling, with altered neural and synaptic laminae and Muller glial activation. The visual brain pathways in CEP290-LCA were anatomically intact. Our findings of preserved foveal cones and visual brain anatomy in LCA with CEP290 mutations, despite severe blindness and rapid rod cell death, suggest an opportunity for visual restoration of central vision in this common form of inherited blindness.
Analysis of symbol-design strategies for intrapulse radar-embedded communications (2015)

The design of communication symbols that may be embedded on an intrapulse basis into the backscatter generated by a high-power, pulsed radar is considered. This framework requires the asynchronous detection of transmitted symbols in a high-interference environment that degrades the capabilities of conventional intercept receivers. The impact of symbol design and filter structure upon the successful detection of covert symbols by the intended receiver and a hypothetical partially clairvoyant intercept receiver is examined.
Zoom Rendering: Improving 3-D Rendering Performance with 2-D Operations (1996)

We propose a new method to accelerate rendering during the interactive visualization of complex scenes. The method is applicable if the cost of per-pixel processing is high compared to simple frame buffer transfer operations, as supported by low-end graphics systems with high-performance CPUs or 2-D graphics accelerators. In this case rendering an appropriately down-scaled image and then enlarging it allows a trade-off of rendering speed and image quality. Using this method, more uniform frame rates can be achieved and the dynamic viewing error can be reduced.
The role of tumour necrosis factor- and tumour necrosis factor receptor signalling in inflammation-associated systemic genotoxicity (2011)

Chronic inflammatory diseases are characterised by systemically elevated levels of tumour necrosis factor (TNF)-α, a proinflammatory cytokine with pleiotropic downstream effects. We have previously demonstrated increased genotoxicity in peripheral leukocytes and various tissues in models of intestinal inflammation. In the present study, we asked whether TNF-α is sufficient to induce DNA damage systemically, as observed in intestinal inflammation, and whether tumour necrosis factor receptor (TNFR) signalling would be necessary for the resultant genotoxicity. In the wild-type mice, 500 ng per mouse of TNF-α was sufficient to induce DNA damage to multiple cell types and organs 1-h post-administration. Primary splenic T cells manifested TNF-α-induced DNA damage in the absence of other cell types. Furthermore, TNFR1(-/-)TNFR2(-/-) mice demonstrated decreased systemic DNA damage in a model of intestinal inflammation and after TNF-α injection versus wild-type mice, indicating the necessity of TNFR signalling. Nuclear factor (NF)-κB inhibitors were also able to decrease damage induced by TNF-α injection in wild-type mice. When TNF-α administration was combined with interleukin (IL)-1β, another proinflammatory cytokine, DNA damage persisted for up to 24 h. When combined with IL-10, an anti-inflammatory cytokine, decreased genotoxicity was observed in vivo and in vitro. TNF-α/TNFR-mediated signalling is therefore sufficient and plays a large role in mediating DNA damage to various cell types, subject to modulation by other cytokines and their mediators.
Clinical efficacy of acid water on distal lower extremity osteomyelitis (2013)

Objective To evaluate the clinical efficacy of acid water on distal lower extremity chronic osteomyelitis.Methods Between July 2011 and November 2012,11 patients with lots of exudates of chronic osteomyelitis were treated in our hospital.After the focus of infection was debrided completely,they were treated with acid water.As soon as the wound surface was clear and the surface was covered with granulating tissue,the wounds were treaded with secondary directly sutured or closed by skin transplantation.Results The exudates and the area of the wound were both decreased after rinsed and soaked in acid water for 10-25 days,with an average of 19 days.The wound was covered by second suture or flap transplantation.After of followed-up of 6-18 months,all 11 cases of chronic osteomyelitis were healed with no recurrence.Conclusions Application of acid water in treatment of osteomyelitis is effective and feasible,it has low medical cost,with good social and economic benefits,and provides a new option for the treatment of chronic osteomyelitis of the distal limbs.

Key words: 
Chronic osteomyelitis ;  Acid water;  Treatment
Pathophysiology of anthracycline cardiotoxicity (2016)

Anthracyclines (ANTs) are powerful drugs that have reduced the mortality of cancer patients. However, their use is limited by the development of cardiotoxicity (CTX), which is dose dependent and may lead to left ventricular dysfunction and heart failure. Although various strategies have been suggested to reduce the negative effects of ANTs, CTX is still an important unresolved clinical issue. This may be due at least partly to the incomplete characterization of the molecular and cellular mechanisms of ANT-induced CTX. In addition, although various forms of cardiac damage have been demonstrated with the use of these drugs in experimental studies, it is not yet clear how these translate to the clinical setting. Appropriate characterization of potential candidates for ANT-based therapies is essential to decide whether to administer these drugs. Hopefully, new information from genetic profiling will help to identify patients who are at high risk of developing CTX.
Deletion of chromosome arm 17p dna sequences in pediatric high‐grade and juvenile pilocytic astrocytomas (1995)

In adults, loss of heterozygosity for DNA on 17p has been shown in high-grade anaplastic astrocytomas (AAs) and glioblastomas multiforme (GMs), and mutation of the TP53 tumor suppressor gene has been reported in all grades of astrocytomas. Little is known, however, about 17p deletion and TP53 mutation in juvenile pilocytic astrocytomas (JPAs), the most common low-grade tumors seen in children. To elucidate the genetic characteristics of pediatric high-grade astrocytomas and JPAs, we performed restriction fragment length polymorphism analysis with probes derived from 17p and TP53 mutational studies in 28 tumor specimens. Telomeric chromosome arm 17p markers 144-D6 and ABR were lost in 6 (75%) of 8 informative tumors classified as high-grade (7 AAs, 1 GM) and in 2 (10%) of 20 informative JPAs. Loss of 17p probes centromeric to the TP53 gene were also detected in 3 AAs and 5 JPAs. Four of the 6 (66%) JPAs with losses of 17p DNA sequences recurred rapidly despite aggressive therapy, whereas only 5 of the other 14 (36%) recurred. Mutation of the TP53 gene was detected by polymerase chain reaction and denaturing gradient gel electrophoresis in only 1 JPA and 1 AA. These tumors were also examined for MDM2 gene amplification as an alternate inactivation mechanism for TP53 gene function: no instances of alteration were identified. These results suggest that a gene or genes in addition to TP53 on 17p may be involved in the etiology or progression of high-grade astrocytomas and aggressive JPAs in children.(ABSTRACT TRUNCATED AT 250 WORDS)
Spironucleus mitochondrial remnants suggest that hydrogenosomes are ancient organelles (2012)

The diplomonads are a diverse group of eukaryotic microbes found in oxygen limited environments such as the intestine of animals were they may cause severe disease. Among them, the prominent human parasite Giardia intestinalis non-invasively colonizes the small intestine of humans and animals where it induces the gastrointestinal disease giardiasis. Two of the eight genetic groups of G. intestinalis, assemblage A and B, are known to infect humans and have zoonotic potential. At the start of project, genome scale data from assemblage B-H was either sparse or entirely missing.In this thesis, genome sequencing was performed on the assemblage B isolate GS (Paper I) and the P15 isolate (Paper III) of the hoofed-animals specific assemblage E to investigate the underlying components of phenotypic diversity in Giardia. Comparisons to assemblage A isolate WB revealed large genomic differences; entirely different repertoires of surface antigens, genome rearrangements and isolate specific coding sequences of potential bacterial origin. We established that genomic differences are also manifested at the transcriptome level (Paper VIII). In a follow up analysis (Paper IV) we concluded that the Giardia assemblages are largely reproductively isolated. The large genomic differences observed between Giardia isolates can explain the phenotypic diversity of giardiasis.The adaptation of diplomonads was further studied in Spironucleus barkhanus (Paper II), a fish commensal of grayling, that is closely related to the fish pathogen Spironucleus salmonicida, causative agent of systemic spironucleosis in salmonid fish. We identified substantial genomic differences in the form of divergent genome size, primary sequence divergence and evidence of allelic sequence heterozygosity, a feature not seen in S. salmonicida.We devised a transfection system for S. salmonicida (Paper VI) and applied it to the study of the mitochondrial remnant organelle (Paper VII). Our analyses showed that S. salmonicida harbor a hydrogenosome, an organelle with more metabolic capabilities than the mitosome of Giardia. Phylogenetic reconstructions of key hydrogenosomal enzymes showed an ancient origin, indicating a common origin to the hydrogenosome in parabasilids and diplomonads.In conclusion, the thesis has provided important insights into the adaptation of diplomonads in the present and the distant past, revealing hidden diversity.
Preclinical efficacy studies using HuMax-Axl-ADC, a novel antibody-drug conjugate targeting Axl-expressing solid cancers. (2015)

3066 Background: HuMax-Axl-ADC is an antibody-drug conjugate (ADC) that specifically targets Axl-expressing tumor cells. Aberrant expression of Axl, a receptor tyrosine kinase, has been described in solid and hematological malignancies, in both primary tumors and metastasis. Expression and activation of Axl is associated with poor clinical prognosis in cancers of the lung, pancreas, esophagus and breast. Moreover, Axl expression has been implicated in resistance to both chemotherapy and targeted therapy. Although the mechanism behind Axl activation in cancer is not fully understood, activation through the Axl ligand Gas6 has been implicated in at least some cancers. At the cellular level, Axl is involved in tumor cell adherence, migration and epithelial-to-mesenchymal transition. Methods: A panel of Axl-specific ADCs was generated by conjugating human Axl antibodies with the microtubule disrupting agent monomethyl auristatin E (MMAE), through a protease-cleavable linker. Axl-ADCs were functionally characterized in vitro, and the anti-tumor activity was tested in vivo using xenograft models. Results: Axl-ADCs demonstrated high affinity binding to Axl and efficiently induced cytotoxicity in vitro, which was dependent on both Axl expression and conjugation with MMAE. In a lung cancer xenograft model, Axl ADCs were shown to have potent anti-tumor activity in vivo. The most potent Axl-ADCs, including HuMax-Axl-ADC, induced complete tumor regression upon treatment with a single dose of 1 mg/kg. HuMax-Axl-ADC also strongly inhibited tumor growth in a xenograft model that showed high endogenous expression of Gas6. This is in line with our observation that HuMax-Axl-ADC does not compete with Gas6 for Axl binding. Importantly HuMax-Axl-ADC was able to induce tumor regression in PDX models that, similar to many human tumor biopsies, showed Axl expression in only a subpopulation of tumor cells Conclusions: HuMax-Axl-ADC is a novel ADC that shows potent anti-tumor activity in solid cancer xenograft models. The results obtained in preclinical studies support further development of HuMax-Axl-ADC for the treatment of solid cancers.
ChemInform Abstract: UNEXPECTED REACTIONS OF PERFLUOROALKYNYLMAGNESIUM HALIDES (1976)

Abstract Während das Magnesiumacetylid (II) nur im Fall von X=Br mit Acetanhydrid (I) neben (IV) das Acetylid (III) bildet, entsteht aus (VI) mit (II) statt des erwarteten Acetylids (V) ausschließlich der Enoläther (VII).
Investigations on packet error rate of variable spreading and chip repetition factors (VSCRF)-CDMA wireless access in reverse link multi-cell environment (2005)

We apply the symbol repetition principle to the chip sequence after spreading in VSCRF-CDMA wireless access in a multi-cell environment employing one-cell frequency reuse with strong cochannel interference (CCI) from adjacent cells. More specifically, we compare three wireless access schemes: VSCRF-CDMA; DS-CDMA with adaptive transmission timing control (ATTC) achieving orthogonality among dominant paths of simultaneously accessing users; interleaved frequency division multiple access (IFDMA) only employing symbol repetition from the viewpoint of the achievable PER considering the CCI from the surrounding cells. Simulation results show that VSCRF-CDMA improves the required average received signal energy per symbol-to-interference power spectrum density ratio by approximately 1.0 and 4.0 dB compared to DS-CDMA with ATTC and IFDMA, respectively, where four simultaneously accessing users exist in the target and dominant interfering cells, respectively, in a six-path exponentially decayed Rayleigh fading channel. Consequently, VSCRF-CDMA is effective in autonomously achieving a higher link capacity in a multi-cell environment because it makes full use of the respective advantages of spreading and chip repetition.
Temperature-dependent interactions between hydrophobically modified ethyl(hydroxyethyl)cellulose and methyl nanocellulose (2019)

The temperature-dependent association between methyl nanocellulose and hydrophobically modified ethyl(hydroxyethyl)cellulose (EHEC) was determined. Methyl nanocellulose was mixed under different concentrations with EHEC in aqueous media. The hydrophobic association, cloud point and temperature-dependent flocculation were studied using turbidity, rheometry and laser diffraction analysis. The phase separation of EHEC samples containing different amounts of methyl nanocellulose in 1.0 wt% solution was measured between 20 and 70 °C, showing that the cloud point of the solutions increased with increasing nanocellulose content. An increase in the low shear viscosity and gelation behavior of the mixture with the highest methyl nanocellulose content in conjunction with changes in cloud point indicated that the hydrophobic nanocellulose strengthened the hydrophobic association and the gel network. A bimodal particle size distribution was observed for both the pure EHEC and hydrophobically modified nanocellulose reference solutions, whereas the mixture had a trimodal particle size distribution when being diluted. The colloidal stability and re-structuring mechanism of the dilute methyl nanocellulose suspension after shear and the role of birefringence are discussed.
White‐emitting OLED devices in an RGBW format with microelement white subpixels (2010)

Abstract— OLED devices with an RGBW pixel format using an unpatterned white emitter have the potential to provide very good efficiency and color gamut while enabling lower‐cost and large‐format manufacturing. However, the white subpixel often has unacceptably large color shifts with viewing angle. Furthermore, for some architectures such as top‐emitting microcavity devices, it can even be difficult to produce a white subpixel with good on‐axis color. In this paper, we describe the use of a white subpixel made up of a combination of differently tuned microelements and demonstrate how such an approach can overcome these problems. By carefully tuning the color and areas of each of the microelements in the white subpixel, we can trade off between better on‐axis color, less color change with angle, and higher efficiency. Furthermore, it was demonstrated that an RGBW top‐emitter microcavity device with a microelement white subpixel can achieve an increase in both power efficiency and color gamut relative to a conventional RGBW bottom‐emitter non‐microcavity device.
Management of dyslipidemia in the elderly population (2010)

The elderly population is increasing worldwide. Despite a major decrease in deaths from coronary heart disease (CHD), this malady remains the major cause of death in elderly men and women. In this paper, we review the role of dyslipidemia as a major known risk factor in the pathogenesis of CHD, age-related changes in lipoprotein metabolism, and differences in changes in lipids that occur in men and women during aging. Next we provide an overview of the available studies and recommendations from ATP III. Finally, we comment on the screening and management, cost and side effects of therapy as it applies to an aging population.
Generation of Human B-Cell Lines Dependent on CD40-Ligation and Interleukin-4 (2015)

OPINION article Front. Immunol., 11 February 2015Sec. B Cell Biology Volume 6 - 2015 | https://doi.org/10.3389/fimmu.2015.00055
Transactional coordination agents for composite systems (2003)

Composite systems are collections of autonomous, heterogeneous and distributed software applications. In these systems, data dependencies are continuously violated by local operations, and therefore coordination processes are necessary to guarantee overall correctness and consistency. Such coordination processes must be endowed with some form of execution guarantees, which require the participating subsystems to have certain database functionality (such as atomicity of local operations, order preservation, and either compensation of operations or the deferment of their commit). However, this functionality is not present in many applications and must be implemented by a transactional coordination agent coupled with the application. In this paper, we discuss the requirements to be met by the applications and their associated transactional coordination agents. We identify a minimal set of functionalities which the applications must provide in order to participate in transactional coordination processes, and we also discuss how the missing database functionality can be added to arbitrary applications using transactional coordination agents. Then, we identify the structure of a generic transactional coordination agent and provide an implementation example of a transactional coordination agent tailored to SAP R/3.
Metallcarbonyl‐Synthesen, X: Synthese neuer Niob‐ und Tantal‐Halbsandwichkomplexe. Molekülstruktur der Stammverbindung (η5‐C5H5)Nb(CO)4 (1981)

Abstract Die Halbsandwich‐Komplexe (η‐ 5 C 5 H 4 CH 3 )Nb(CO) 4 ( 3a ), [η 5 ‐C 5 (CH 3 ) 5 ]Nb(CO) 4 ( 3b ), (η 5 ‐C 5 H 4 CH 3 )Ta(CO) 4 ( 3c ) und [η 5 ‐C 5 (CH 3 ) 5 ]Ta(CO) 4 ( 3d ) sind durch reduzierende Hochdruckcarbonylierung der entsprechenden Nb V ‐bzw. Ta V ‐vorstufen (η 5 ‐C 5 R 4 R′)MCl 4 ( 2a ‐ d ) synthetisierbar. Die Reduzierbarkeit der Halogeno‐Komplexe, 2a – d , wird durch sukzessive Einführung von Methyl‐Substituenten in den Cyclopentadienyl‐Ring erleichtert und ist bei den Niob‐Verbindungen mit milderen Reduktionsmitteln als bei den analogen Tantal‐Komplexen möglich. Bei der Photolyse von 3a – d in Tetrahydrofuran entstehen die Solvens‐Komplexe (η 5 ‐C 5 R 4 R′)M(CO) 3 (THF) ( 4a – d ). Die Stammsubstanz (η 5 ‐C 5 H 5 )Nb(CO) 4 ( 1 ) wurde röntgenstrukturanalytisch untersucht und besitzt eine unverzerrt tetragonal‐pyramidale Molekülstruktur.
Structural Changes and Transitional Behavior Studied from Both Micro- and Macroscale in the High-Energy Electron-Irradiated Poly(vinylidene fluoride−trifluoroethylene) Copolymer (2001)

The microstructural changes in high-energy electron-irradiated poly(vinylidene fluoride−trifluoroethylene) 68/32 mol % copolymer have been studied by X-ray diffraction, FTIR spectroscopy, and differential scanning calorimetry. The macroscopic polarization response in these materials was investigated by examining the dielectric and polarization behavior in a broad temperature and frequency range. It was found that besides reducing crystallinity in the copolymer film, irradiation produces significant changes in the ferroelectric-to-paraelectric phase transition behavior. The irradiation leads to a reduction in the polar domain size to below a critical size (a few nanometers), resulting in the instability of the macroscopic ferroelectric state and transforming the structure of the crystalline region in the copolymer from a polar all-trans ferroelectric to a nonpolar state represented by a trans−gauche conformation. However, a reentrant polarization hysteresis was observed in the copolymers irradiated with higher doses (>75 Mrad). Therefore, there is an optimized dose that generates a copolymer with a nonpolar structure but relatively high crystallinity whose electromechanical performance is the best. In the copolymers in this optimum dose range, FT-IR data revealed that there is not much change in the molecular conformation with temperature, even as the temperature passes through the dielectric peak, indicating that there is no symmetry breaking in both the macroscale and local level. Although the lattice spacing of the crystalline region along the molecular chain direction discontinuously changes between two special cases, the interchain spacing continuously changes with the irradiation dose, reflecting a strong intrachain coupling between the nonpolar and polar regions. On the other hand, the X-ray data reveal that the crystalline size perpendicular to the polymer chain does not change with irradiation until at doses exceeding 85 Mrad.