gebhart/patrepeval huggingface dataset:
Data from Association of AXL and PD-L1 Expression with Clinical Outcomes in Patients with Advanced Renal Cell Carcinoma Treated with PD-1 Blockade (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;A minority of patients currently respond to single-agent immune-checkpoint blockade (ICB), and strategies to increase response rates are urgently needed. AXL is a receptor tyrosine kinase commonly associated with drug resistance and poor prognosis in many cancer types, including in clear-cell renal cell carcinoma (ccRCC). Recent experimental cues in breast, pancreatic, and lung cancer models have linked AXL with immune suppression and resistance to antitumor immunity. However, its role in intrinsic and acquired resistance to ICB remains largely unexplored.&lt;/p&gt;Experimental Design:&lt;p&gt;In this study, tumoral expression of AXL was examined in ccRCC specimens from 316 patients who were metastatic receiving the PD-1 inhibitor nivolumab in the GETUG AFU 26 NIVOREN trial after failure of antiangiogenic therapy. We assessed associations between AXL and patient outcomes following PD-1 blockade, as well as the relationship with various markers, including PD-L1; VEGFA; the immune markers CD3, CD8, CD163, and CD20; and the mutational status of the tumor-suppressor gene von Hippel-Lindau (VHL).&lt;/p&gt;Results:&lt;p&gt;Our results show that high AXL-expression level in tumor cells is associated with lower response rates and a trend to shorter progression-free survival following anti–PD-1 treatment. AXL expression was strongly associated with tumor–PD-L1 expression, especially in tumors with VHL inactivation. Moreover, patients with tumors displaying concomitant PD-L1 expression and high AXL expression had the worst overall survival.&lt;/p&gt;Conclusions:&lt;p&gt;Our findings propose AXL as candidate factor of resistance to PD-1 blockade, and provide compelling support for screening both AXL and PD-L1 expression in the management of advanced ccRCC.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related commentary by Hahn et al., p. 6619&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Cover Picture: Extremely Tight Binding of a Ruthenium Complex to Glycogen Synthase Kinase 3 (ChemBioChem 18/2008) (2008)

The cover picture shows the binding of a ruthenium half-sandwich complex to the ATP binding site of glycogen synthase kinase 3 (GSK-3) and how its structure and potency evolved from a brief structure–activity relationship. With a binding constant (Ki) of, at most, 5 pM, this organometallic compound is several orders of magnitude more potent than the natural product staurosporine, which itself served as an inspiration for the design. The crystal structure of the organoruthenium inhibitor with GSK-3 demonstrates that the metal itself is not involved in any direct interactions with the active site of GSK-3, but solely serves as a structural center. Further details can be found in the article by E. Meggers, et al. on p. 2933 ff.
Synthesis and Dual-Mode Electrochromism of Anisotropic Monoclinic Nb12O29 Colloidal Nanoplatelets (2020)

Transition metal oxide nanocrystals with dual-mode electrochromism hold promise for smart windows enabling spectrally selective solar modulation. We have developed the colloidal synthesis of anisotropic monoclinic Nb12O29 nanoplatelets (NPLs) to investigate the dual-mode electrochromism of niobium oxide nanocrystals. The precursor for synthesizing NPLs was prepared by mixing NbCl5 and oleic acid to form a complex that was subsequently heated to form an oxide-like structure capped by oleic acid, denoted as niobium oxo cluster. By initiating the synthesis using niobium oxo clusters, preferred growth of NPLs over other polymorphs was observed. The structure of the synthesized NPLs was examined by X-ray diffraction in conjunction with simulations, revealing that the NPLs are monolayer monoclinic Nb12O29, thin in the [100] direction and extended along the b and c directions. Besides having monolayer thickness, NPLs show decreased intensity of Raman signal from Nb-O bonds with higher bond order when compared to bulk monoclinic Nb12O29, as interpreted by calculations. Progressive electrochemical reduction of NPL films led to absorbance in the near-infrared region (stage 1) followed by absorbance in both the visible and near-infrared regions (stage 2), thus exhibiting dual-mode electrochromism. The mechanisms underlying these two processes were distinguished electrochemically by cyclic voltammetry to determine the extent to which ion intercalation limits the kinetics, and by verifying the presence of localized electrons following ion intercalation using X-ray photoelectron spectroscopy. Both results support that the near-infrared absorption results from capacitive charging and the onset of visible absorption in the second stage is caused by ion intercalation.
Modality Agnostic Model for Spatial Resolution in Mass Spectrometry Imaging: Application to MALDI MSI Data (2021)

Image resolution in mass spectrometry imaging (MSI) is governed by the sampling probe, the motion of the stage relative to the probe, and the noise inherent for the sample and instrumentation employed. A new image formation model accounting for these variables is presented here. The model shows that the size of the probe, stage velocity, and the rate at which the probe consumes material from the surface govern the amount of blur present in the image. However, the main limiting factor for resolution is the signal-to-noise ratio (SNR). To evaluate blurring and noise effects, a new computational method for measuring lateral resolution in MSI is proposed. A spectral decomposition of the observed image signal and noise is used to determine a resolution number. To evaluate this technique, a silver step edge was prepared. This device was imaged at different pixels sizes using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). A modulation transfer function (MTF) and a noise power spectrum (NPS) were computed for each single-ion image, and resolution was defined as the point of intersection between the MTF and the NPS. Finally, the algorithm was also applied to a MALDI MSI tissue data set.
Light Extraction in GaInN Light-Emitting Diodes using Diffuse Omnidirectional Reflectors (2006)

A theoretical and experimental analysis of light extraction in GaInN light-emitting diodes (LEDs) employing diffuse omnidirectional reflectors is presented. The diffuse omnidirectional reflector consists of GaN, a Ni/Au current spreading layer, a SiO2 layer roughened by Ar ion etching, and a Ag layer. Randomly distributed polystyrene spheres are used as an etch mask. The diffusely reflected power is enhanced by two orders of magnitude for a roughened reflector surface compared with a planar surface. The GaInN LEDs with diffuse omnidirectional reflectors show a higher light output (&gt;3.3%) and a lower angular dependence of emission than LEDs with specular reflectors. The enhancement is attributed to reduced trapping of light within the high-index GaN semiconductor. (c) 2005 The Electrochemical Society.
Thermal Analysis of Degradation in Ga2O3–In2O3–ZnO Thin-Film Transistors (2008)

Degradation of Ga2O3–In2O3–ZnO (GIZO) thin-film transistors (TFTs), which are promising for driving circuits of next-generation displays, was studied. We found a degradation mode that was not observed in silicon TFTs. A parallel shift without any change of the transfer curve was observed under gate voltage stress. Judging from the bias voltage dependences we confirmed that the mode was mainly dominated by a vertical electric field. Thermal distribution was measured to analysis the degradation mechanism. Joule heating caused by drain current was observed; however, a marked acceleration of degradation by drain bias was not found. Therefore, we concluded that Joule heating did not accelerate degradation. Recovery of electrical properties independent of stress voltage were observed.
Mechanism of non-catalytic chemical vapor deposition growth of all-inorganic CsPbX3 (X = Br, Cl) nanowires (2021)

Non-catalytic chemical vapor deposition growth of CsPbX<sub>3</sub> (X = Br, Cl) nanowires on both amorphous and crystalline substrates through nucleation and physiological transformations: ‘nanoparticles → capsules → dumbbells → coalescence of dumbbells → NWs’.
Effect of combining glucocorticoids with Compound A on glucocorticoid receptor responsiveness in lymphoid malignancies (2018)

Glucocorticoids (GCs) are a cornerstone in the treatment of lymphoid malignancies such as multiple myeloma (MM) and acute lymphoblastic leukemia (ALL). Yet, prolonged GC use is hampered by deleterious GC-related side effects and the emergence of GC resistance. To tackle and overcome these GC-related problems, the applicability of selective glucocorticoid receptor agonists and modulators was studied, in search of fewer side-effects and at least equal therapeutic efficacy as classic GCs. Compound A (CpdA) is a prototypical example of such a selective glucocorticoid receptor modulator and does not support GR-mediated transactivation. Here, we examined whether the combination of CpdA with the classic GC dexamethasone (Dex) may improve GC responsiveness of MM and ALL cell lines. We find that the combination of Dex and CpdA does not substantially enhance GC-mediated cell killing. In line, several apoptosis hallmarks, such as caspase 3/7 activity, PARP cleavage and the levels of cleaved-caspase 3 remain unchanged upon combining Dex with CpdA. Moreover, we monitor no additional inhibition of cell proliferation and the homologous downregulation of GR is not counteracted by the combination of Dex and CpdA. In addition, CpdA is unable to modulate Dex-liganded GR transactivation and transrepression, yet, Dex-mediated transrepression is also aberrant in these lymphoid cell lines. Together, transrepression-favoring compounds, alone or combined with GCs, do not seem a valid strategy in the treatment of lymphoid malignancies.
Prevalence of ventriculomegaly in association with myelomeningocele: correlation with gestational age and severity of posterior fossa deformity. (1994)

The prevalence of VM in fetuses with myelomeningoceles varies with both GA and the severity of the associated PF deformity. These observations may provide additional prognostic information once a myelomeningocele is detected at sonography.
A novel mechanism for the regulation of osteoblast differentiation: Transcription of periostin, a member of the fasciclin I family, is regulated by the bHLH transcription factor, twist (2002)

Periostin is a secreted protein that is highly expressed in early osteoblastic cells in vitro and in periosteum and periodontal ligament tissues in vivo. It is known that periostin supports cellular adhesion and spreading in vitro. Although, the mechanisms of transcriptional regulation of periostin are poorly understood, gene-profiling data have revealed that overexpression of Twist, a basic helix-loop-helix (bHLH) transcription factor, resulted in increased periostin expression as validated by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses. Twist is an important transcription factor for cell type determination and differentiation and has been shown to play an important regulatory role in early osteogenesis. In situ hybridization of mouse calvarial bones indicated that periostin and Twist mRNA are co-localized at the osteogenic fronts of calvarial bones. To characterize the 5' flanking region of the periostin gene, primer extension was carried out to identify the transcription start site, and DNA sequence analysis confirmed the presence of a 'Twist-box' response element. The results of electrophoretic mobility shift assay (EMSA) using nuclear extracts of MC3T3-E1 cells revealed that Twist bound to the Twist-box sequence on the periostin promoter. In vivo footprinting experiments using ligation-mediated PCR (LM-PCR) indicated that the Twist-box sequence was protected in undifferentiated MC3T3-E1 preosteoblasts but not in differentiated MC3T3-E1 osteoblasts. To determine whether Twist actually regulates the periostin expression, 293T cells were transiently co-transfected with the periostin promoter construct and the human Twist expression vector. Reporter analysis indicated that the periostin promoter activities were enhanced by overexpression of Twist. These data suggest that Twist can bind to the periostin promoter in undifferentiated preosteoblasts and up-regulate periostin expression, consistent with the up-regulation of periostin expression by Twist as observed in the gene-profiling data.
On the inadequacy of link connectivity monitoring (2008)

Internet backbone networks are constantly evolving along several dimensions such as technology, protocols, and features. The rapid rate of this evolution often places a tremendous amount of burden on network operators and router vendors to cope with both unanticipated as well as complicated failure scenarios. While routing protocols are designed to detect these failures and respond by switching to alternate paths, we argue that current routing protocols (e.g., OSPF) do not completely verify all data plane paths properly. Thus, there potentially exist failure scenarios that are not detected by them and thereby recover from. To alleviate this problem, we show how a simple extension to OSPF, wherein each router injects probes to a 2-hop neighbor, can easily verify all the data plane forwarding paths within the adjacent router. While we point out the extension in the context of OSPF, we believe our approach is generally applicable to other control plane protocols as well. Using Rocketfuel topologies, we quantify the resulting overhead of injecting these 2-hop probes for routers in real ISPs.
Definition of an Uptake Pharmacophore of the Serotonin Transporter Through 3D-QSAR Analysis (2005)

The serotonergic system plays a critical role in a wide variety of physiological and behavioral processes. Dysregulation of the tightly controlled extracellular concentration of serotonin (5-hydroxytryptamine, 5-HT) appears to be at the origin of a host of metabolic and psychiatric disorders. Since the plasma membrane 5-HT transporter (SERT) is the major protagonist in regulating extracellular 5-HT concentration, SERT is the target of most drugs interacting with the serotonergic system. Unfortunately, some of the drugs towards SERT (e.g. amphetamine derivatives) interfere with cell homeostasis leading to cell toxicity. Developing new SERT ligands devoid of any side-effect represents a major priority in the treatment of 5-HT-associated pathologies. Here, we report structure-activity relationships (SAR) and three-dimensional QSAR (3D-QSAR) studies of a library of 121 compounds including 5-HT analogs, harmanes, benzothiazoles, indanones, amphetamine derivatives and substrate-type 5-HT releasers, with the goal of identifying the structural determinants crucial for SERT uptake. In the absence of data about the bioactive form of 5-HT, conformational analysis of 5-HT was performed using quantum chemistry calculations. This led to three 5-HT stable conformers with anti, -gauche and +gauche side-chain conformation. These conformers, used as templates for superimposition with all the library compounds, enabled the design of a reliable 6-points pharmacophore representative of SERT uptake activity. Molecular dynamics (MD) simulations performed with compounds that are efficiently, moderately, poorly or not transported by SERT allowed to assess the validity of our pharmacophore. Altogether, our data provide for the first time a reliable pharmacophore of SERT uptake activity, which may help to the design of new drugs targeting SERT.
Advancement into the Arctic Region for Bioactive Sponge Secondary Metabolites (2011)

Porifera have long been a reservoir for the discovery of bioactive compounds and drug discovery. Most research in the area has focused on sponges from tropical and temperate waters, but more recently the focus has shifted to the less accessible colder waters of the Antarctic and, to a lesser extent, the Arctic. The Antarctic region in particular has been a more popular location for natural products discovery and has provided promising candidates for drug development. This article reviews groups of bioactive compounds that have been isolated and reported from the southern reaches of the Arctic Circle, surveys the known sponge diversity present in the Arctic waters, and details a recent sponge collection by our group in the Aleutian Islands, Alaska. The collection has yielded previously undescribed sponge species along with primary activity against opportunistic infectious diseases, malaria, and HCV. The discovery of new sponge species and bioactive crude extracts gives optimism for the isolation of new bioactive compounds from a relatively unexplored source.
Mechanistic clues to the protective effect of chrysin against doxorubicin-induced cardiomyopathy: Plausible roles of p53, MAPK and AKT pathways (2017)

Doxorubicin (DOX) is the mainstay chemotherapeutic agent against a variety of human neoplasmas. However, its clinical utility is limited by its marked cardiotoxicity. Chrysin, is a natural flavone which possesses antioxidant, anti-inflammatory and anti-cancer properties. The current study aimed to investigate the potential protective effect of chrysin against DOX-induced chronic cardiotoxicity and the underlying molecular mechanisms. Male Sprague-Dawley rats were treated with either DOX (5 mg/kg, once a week) and/or chrysin (50 mg/kg, four times a week) for four weeks. Chrysin prevented DOX-induced cardiomyopathy which was evident by conduction abnormalities, elevated serum CKMB and LDH and histopathological changes. Chrysin also ameliorated DOX-induced oxidative stress by decreasing lipid peroxidation and upregulating the antioxidant enzymes. Moreover, chrysin attenuated DOX-induced apoptosis via decreasing expression of p53, Bax, Puma, Noxa, cytochrome c and caspase-3 while increasing expression of Bcl-2. DOX induced activation of MAPK; p38 and JNK and increased expression of NF-κB. Meanwhile, DOX suppressed AKT pathway via decreasing expression of its upstream activator VEGF and increasing expression of PTEN. Conversely, chrysin effectively neutralised all these effects. Collectively, these findings indicate that chrysin effectively protected against DOX-induced cardiomyopathy via suppressing oxidative stress, p53-dependent apoptotic pathway, MAPK and NF-κB pathways while augmenting the VEGF/AKT pathway.
<title>An efficient approach for video information retrieval</title> (2005)

Today, more and more video information can be accessed through internet, satellite, etc.. Retrieving specific video information from large-scale video database has become an important and challenging research topic in the area of multimedia information retrieval. Generally, video retrieval can be categorized by the retrieval of video shot and retrieval of video clip. Up to now, few approaches can support both shot retrieval and clip retrieval efficiently. In this paper, we introduce a new high-dimensional index structure OVA-File, which is a variant of VA-File. In OVA-File, the approximations close to each other in data space are stored in close positions of the approximation file. The benefit is that only a part of approximations near the query vector need to be visited to get the approximate query result. Then, both shot query algorithm and video clip query algorithm are proposed to support video information retrieval efficiently. The experimental results showed that the queries based on OVA-File were much faster than that based on VA-File with small loss of result quality.
Serotonin-Bradykinin Synergism in the Mammalian Capillary Bed. (1967)

The synergistic action of 5-HT and bradykinin in the rat mesenteric microcirculation was shown: a) not to be mediated through other dilator or constrictor amines or vasoactive polypeptides; b) to be dependent upon the venular constrictor action of 5-HT; and c) it was proposed that rhexis of postcapillary collecting venules is brought about by a local increase of intravascular pressure as a consequence of severe venular constriction.
Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts. (1994)

Nucleotide-excision repair is the repair system for removing bulky lesions from DNA. Humans deficient in this repair pathway suffer from xeroderma pigmentosum (XP), a disease characterized by photodermatoses, including skin cancers. At the cellular level, XP patients fail to remove cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts induced by UV light, as well as other bulky DNA lesions caused by various genotoxic agents. XP cells are not particularly sensitive to ionizing radiation or to alkylating agents that cause mostly nonbulky DNA lesions. Therefore, it has generally been assumed that the human nucleotide-excision repair enzyme (excinuclease) is specific for bulky adducts. To determine the substrate range of human excinuclease we used the highly sensitive excision assay and tested bulky adducts, synthetic apurinic/apyrimidinic sites, N6-methyladenine, O6-methylguanine, and mismatches as potential substrates. We found that all of these "lesions" were removed by human excinuclease, although with vastly different efficiencies.
Smectic Liquid Crystal Defects for Self‐Assembling of Building Blocks and Their Lithographic Applications (2011)

Abstract Recently, it has been reported that liquid crystal (LC) defects can be used to create highly periodic templates by controlling the surface anchoring and the elastic properties of LC molecules. The self‐assembled defect ordering of the LC materials takes advantage of the ability to achieve fast stabilization of molecular ordering and structure due to the reversible and non‐covalent interactions of the LC molecules. In this Featre Article, the defect structures of liquid crystalline materials will be demonstrated by the surface anchoring and elastic properties. A particular focus are the focal conic domains (FCDs) that are commonly observed in SmA liquid crystals and their lamellar lyotropic counterparts, which form periodic defect ordered structures. In addition, methodologies for creating lithographic templates from the defect order will be described. Finally, the review closes with a discussion of toric focal conic domain arrays that have been fabricated in this manner and used for various applications.
Innentitelbild: Molecular Bases for Anesthetic Agents: Halothane as a Halogen‐ and Hydrogen‐Bond Donor (Angew. Chem. 36/2019) (2019)

Halothan, ein häufig genutztes Anästhetikum, kann gleichzeitig als Wasserstoffbrücken- und Halogenbrückendonor im Festkörper und in Lösung fungieren, wie S. V. Rosokha, G. Resnati et al. in ihrer Zuschrift auf S. 12586 zeigen. Beide Wechselwirkungen involvieren funktionelle Gruppen, die auch in Zellmembranen vorhanden sind, wahrscheinlichen Zielstrukturen von Halothan im menschlichen Körper. Die Fähigkeit des Agens, mehrzähnig zu koordinieren, erklärt sein eudismisches Verhältnis.
Channel Reordering with Time-shifted Streams to Improve Channel Change Latency in IPTV Networks (2011)

In IPTV networks, channel change latency is considered as a major obstacle in achieving broadcast-level quality video delivery. Because of the bandwidth limitations observed at the client side, users typically have access to a limited number of channels. As a result, channel change requests oftentimes need to go through the network, thereby leading to significant delays. In this paper, we address this problem by proposing a resource-efficient time-shifted channel reordering mechanism to minimize the channel change latency. The proposed framework exploits the differing key-frame delivery times for the adjacent sessions to dynamically arrange the switching order during the surfing periods. The simulation results show that, with the proposed framework, more than 50% improvement can be achieved in channel change latency without introducing any overhead in the network.