gebhart/patrepeval huggingface dataset:
Reduced cell size, chromosomal aberration and altered proliferation rates are characteristics and confounding factors in the STHdh cell model of Huntington disease (2017)

Huntington disease is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the gene encoding the huntingtin protein. Expression of the mutant protein disrupts various intracellular pathways and impairs overall cell function. In particular striatal neurons seem to be most vulnerable to mutant huntingtin-related changes. A well-known and commonly used model to study molecular aspects of Huntington disease are the striatum-derived STHdh cell lines generated from wild type and huntingtin knock-in mouse embryos. However, obvious morphological differences between wild type and mutant cell lines exist, which have rarely been described and might not have always been considered when designing experiments or interpreting results. Here, we demonstrate that STHdh cell lines display differences in cell size, proliferation rate and chromosomal content. While the chromosomal divergence is considered to be a result of the cells' tumour characteristics, differences in size and proliferation, however, were confirmed in a second non-immortalized Huntington disease cell model. Importantly, our results further suggest that the reported phenotypes can confound other study outcomes and lead to false conclusions. Thus, careful experimental design and data analysis are advised when using these cell models.
The Methoxyallene Approach to Oxacycles. Part 2. Stereoselective Synthesis of 2,3‐Disubstituted Oxepanes. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Marine Spirotetronates: Biosynthetic Edifices That Inspire Drug Discovery (2019)

Spirotetronates are actinomyces-derived polyketides that possess complex structures and exhibit potent and unexplored bioactivities. Due to their anticancer and antimicrobial properties, they have potential as drug hits and deserve further study. In particular, abyssomicin C and tetrocarcin A have shown significant promise against antibiotic-resistant <i>S. aureus</i> and tuberculosis, as well as for the treatment of various lymphomas and solid tumors. Improved synthetic routes to these compounds, particularly the class II spirotetronates, are needed to access sufficient quantities for structure optimization and clinical applications.
Non-Nutritive Bioactive Food Constituents of Plants: Bioavailability of Flavonoids (2003)

Flavonoids are polyphenols widely distributed in the plant kingdom, and are present in fruits and vegetables regularly consumed by humans. In vitro metabolic studies of flavonoids in rat liver microsomes identified the 3',4'-dihydroxylated derivatives as the major metabolic endpoint. However, in vivo in rats almost none of this metabolite and only minor amounts of the 4'-monohydroxylated derivative was produced. Flavonoids with the 4'-monohydroxylated structure were generally not metabolised and were excreted unchanged in urine in higher amounts than other flavonoids investigated. It has for long been a controversy, whether flavonoids are absorbed as the intact glycoside or whether they have to be hydrolysed to the free aglycon prior to absorption. Recent data suggest that beta-glucosidases and maybe also lactase phlorizin hydrolase (LPH) in the small intestine are capable of hydrolysing flavonoid glucosides and these compounds are thus taken up as the free aglycon and not as the intact glycosides. LC-MS analyses of 12 dietary flavonoids in human urine showed that no flavonoid glycosides were excreted, and that the citrus flavanones and phloretin are excreted in higher amounts than the flavonols. Furthermore, total flavonoid excretion may be a useful biomarker for habitual fruit and vegetable consumption.
A disrupter of actin microfilaments impairs sulfonylurea-inhibitory gating of cardiac KATP channels (1996)

The efficacy with which sulfonylurea drugs inhibit cardiac ATP-sensitive K+ (KATP) channels is reduced during metabolic compromise and cellular contracture. Disruption of the actin microfilament network, which occurs under similar conditions, reduces the sensitivity of the channel toward intracellular ATP. To investigate whether a disrupter of actin microfilaments could also affect the responsiveness of the KATP channel to sulfonylurea drugs, single-channel currents were measured in the inside-out configuration of excised patches from guinea pig ventricular myocytes. Treatment of the internal side of patches with deoxyribonuclease (DNase) I (100 micrograms/ml), which forms complexes with G actin and prevents actin filament formation, antagonized sulfonylurea-induced inhibition of KATP channels that was coupled with a loss of sensitivity to ATP. The apparent dissociation constant and Hill coefficient for the inhibitory effect of glyburide, a prototype sulfonylurea, on KATP-channel opening were, respectively, 0.13 microM and 0.95 before and 2.7 microM and 0.98 after DNase treatment. DNase did not alter intraburst kinetic properties of the channel. When DNase was denatured or coincubated with purified actin (200 micrograms/ml), it no longer decreased glyburide-induced channel inhibition. This suggests that sulfonylurea-inhibitory gating of cardiac KATP channels may also be regulated through a mechanism involving subsarcolemmal actin microfilament networks.
A Novel Toll-Like Receptor that Recognizes Bacterial DNA (2002)

In mammalian immune system, activation of innate immunity is crucial for protecting the host from invading pathogens. The innate immune system specifically recognizes structural patterns of microbial components, which are conserved among a wide variety of microorganisms. These structural patterns are termed pathogen associated molecular patters (PAMPs), and include lipopolysaccharide (LPS), peptidoglycan (PGN), bacterial lipoproteins (BLP), mannans, and bacterial DNA (1). All of these are essential for the microbe’s survival and are not expressed on the host. The host immune system has developed the receptors that can specifically recognize PAMPs, so-called pattern recognition receptors (PRRs). As one of PRRs, Toll-like receptor (TLR) family has been well studied (2,3). TLR family has been phylogenetically conserved from insects to mammals and characterized as a type I transmembrane protein with leucine-rich repeats in the extracellular domain and a cytoplasmic Toll/interleukin (IL)-1 receptor homology (TIR) domain. So far, ten members of human TLR are identified (2). Biological functions of some TLR family members are revealed; TLR4 is responsible for the recognition of LPS and TLR2 is involved in that of PGN and BLP (3). The activation of TLRs induces recruitment of the adaptor protein MyD88 and sequential activation of signaling molecules such as IRAK (IL-1 receptor associated kinase) and TRAF6 (TNF receptor associated factor).
Homologous recombination and nonhomologous end-joining repair pathways regulate fragile site stability (2005)

Common fragile sites are specific loci that form gaps and constrictions on metaphase chromosomes exposed to replication stress, which slows DNA replication. These sites have a role in chromosomal rearrangements in tumors; however, the molecular mechanism of their expression is unclear. Here we show that replication stress leads to focus formation of Rad51 and phosphorylated DNA-PKcs, key components of the homologous recombination (HR) and nonhomologous end-joining (NHEJ), double-strand break (DSB) repair pathways, respectively. Down-regulation of Rad51, DNA-PKcs, or Ligase IV, an additional component of the NHEJ repair pathway, leads to a significant increase in fragile site expression under replication stress. Replication stress also results in focus formation of the DSB markers, MDC1 and gammaH2AX. These foci colocalized with those of Rad51 and phospho-DNA-PKcs. Furthermore, gammaH2AX and phospho-DNA-PKcs foci were localized at expressed fragile sites on metaphase chromosomes. These findings suggest that DSBs are formed at common fragile sites as a result of replication perturbation. The repair of these breaks by both HR and NHEJ pathways is essential for chromosomal stability at these sites.
Multiband Spectrum Access: Great Promises for Future Cognitive Radio Networks (2014)

Cognitive radio has been widely considered as one of the prominent solutions to tackle the spectrum scarcity. While the majority of existing research has focused on single-band cognitive radio, multiband cognitive radio represents great promises toward implementing efficient cognitive networks compared to single-based networks. Multiband cognitive radio networks (MB-CRNs) are expected to significantly enhance the network's throughput and provide better channel maintenance by reducing handoff frequency. Nevertheless, the wideband front–end and the multiband spectrum access impose a number of challenges yet to overcome. This paper provides an in-depth analysis on the recent advancements in multiband spectrum sensing techniques, their limitations, and possible future directions to improve them. We study cooperative communications for MB-CRNs to tackle a fundamental limit on diversity and sampling. We also investigate several limits and tradeoffs of various design parameters for MB-CRNs. In addition, we explore the key MB-CRNs performance metrics that differ from the conventional metrics used for single-band-based networks.
<i>XMM-Newton</i>observations of polars in low accretion states (2004)

We have made a series of snap-shot observations of 37 polars using XMM-Newton. We found that 16 of these systems were in a low, or much reduced, accretion state. Of those, 6 were not detected in X-rays. This suggests that in any survey of polars, around half will be in a low accretion state. We tested if there was a bias towards certain orbital periods: this is not the case. Of the 10 systems which were detected at low, but significant rates in X-rays, 8 showed significant variability in their X-ray light curves. This implies that non-uniform accretion still takes place during low accretion epochs. The bolometric luminosity of these systems is ~10^30 ergs s, two orders of magnitude less than for systems in a high accretion state. The X-ray spectra show no evidence of a distinct soft X-ray component. However, the X-ray and UV data imply that such a low temperature component exists: its temperature is low enough for its flux distribution to move outside the bandpass of the X-ray instruments.
HCCI Operation of a Passenger Car DI Diesel Engine with an Adjustable Valve Train (2006)

&lt;div class="htmlview paragraph"&gt;One of the problems encountered when operating Diesel engines in HCCI mode is a too early start of combustion, due to the low ignition resistance of Diesel fuels. Correct phasing of the combustion process requires a lower in-cylinder temperature during compression. One possibility of regulating the temperature is to adjust the intake valve closing timing and thus the effective compression ratio.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;A single cylinder research engine, configured as a passenger car type DI Common Rail Diesel engine, was fitted with a fully adjustable hydraulic valve train, which allowed free settings of the valve timing events. Premixed combustion was achieved by injecting the fuel during the compression stroke, prior to ignition, in multiple steps. Different combinations of intake valve closing timing and external EGR were tested as well as the possibility to use internal EGR for combustion control. The results showed that accurate control of Diesel HCCI combustion phasing and rate is possible when valve timing can be freely adjusted.&lt;/div&gt;
Definition of reprogramming stages by &lt;i&gt;Oct4&lt;/i&gt;-GFP activation and transgene silencing. (2015)

&lt;p&gt;A, B) Correlation of OCT4 protein with the &lt;i&gt;Oct4&lt;/i&gt;-GFP reporter expression (A) and the transgenic dTOMATO silencing (B), respectively, was investigated by flow cytometry in hOKSM.idTomato-transduced cells at different time points of reprogramming (day 4–12). Untransduced, unstained MEFs served as gating control. C) Expression characteristic of OCT4 protein, &lt;i&gt;Oct4&lt;/i&gt;-GFP and SSEA1 as observed in established iPSC clones (passage 9). D) &lt;i&gt;Oct4&lt;/i&gt;-GFP expression and transgenic dTOMATO silencing showed distinct expression characteristics in the course of reprogramming. dTOMATO expression was detectable early during reprogramming, followed by Tom&lt;sup&gt;+&lt;/sup&gt;/GFP&lt;sup&gt;+&lt;/sup&gt; and Tom&lt;sup&gt;−&lt;/sup&gt;/GFP&lt;sup&gt;−&lt;/sup&gt; intermediate stages, ultimately resulting in a Tom&lt;sup&gt;−&lt;/sup&gt;/GFP&lt;sup&gt;+&lt;/sup&gt; fraction.&lt;/p&gt;
Loop engineering in the thermophile cellobiohydrolase, Cel7A from Rasamsonia emersonii: Effects on activity and substrate interactions (2016)

Cel7A cellobiohydrolases perform processive hydrolysis on one strand of cellulose, which is threaded through the enzyme’s substrate binding tunnel. The tunnel structure results from a groove in the catalytic
domain, which is covered by a number of loops. These loops have been identified as potential targets for engineering of this industrially important enzyme family, but only few systematic studies on this have been
made. In the current work we study two Asn residues in the B2 loop of the thermostable Cel7A from Rasamsonia emersonii. We found that Asn194 and particularly Asn197 promoted substrate binding, and the replacement of one
or both of these.

Forfattere: Trine Holst Sorensen, Michael S. Windahl, Jeppe Kari, Johan Olsen Kim
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Effects of gymnemic acid concentration and time since exposure on intensity of simple tastes: A test of the biphasic model for the action of gymnemic acid (1982)

At several intervals following exposure to gymnemic acid, subjects judged the sweetness, bitterness, saltiness, and sourness of simple taste stimuli. The experiment was expressly designed to test Kennedy and Halpern's (1980) biphasic model for the action of gymnemic acid. The model predicts selective suppression of sweet taste immediately following exposure to gymnemic acid but nonselective disruption of tastes with the passage of time. The data show dramatic reductions in sweet taste which recover with time but no reductions in bitterness, saltiness, or sourness at any time following exposure to any of a wide range of gymnemic acid concentrations.
Bispecific T-Cell Engager -Armored Chimeric Antigen Receptor T Cells Overcome Antigen Escape From EGFRvIII-Targeted Therapy For Glioblastoma (2019)

INTRODUCTION: Immune therapy with T cells engineered to express chimeric antigen receptors (CARs) represents a promising therapy for patients with glioblastoma (GBM). However, clinical responses have been limited due to heterogeneous target antigen expression and outgrowth of tumors lacking the antigen targeted by CAR T cells directed against a single target. In clinical studies with CART-EGFRvIII, EGFRvIII-targeted T cells successfully localized to the brain tumor microenvironment, but ultimately failed to prevent disease progression with post-treatment specimens demonstrating high levels of wild-type EGFR despite reduced expression of EGFRvIII. METHODS: We developed a novel bicistronic CAR construct engineered for local delivery of bispecific T-cell engagers (BiTEs) that target residual tumor. Specifically, EGFRvIII-targeted CAR T cells were engineered to secrete BiTEs against wild-type EGFR, which is frequently amplified and overexpressed in GBM. RESULTS: Human T cells were efficiently transduced with the dual CART.BiTE transgene. These modified cells secreted biologically active EGFR-specific BiTEs that not only redirected CAR T cells but also recruited and activated untransduced bystander T cells against wild-type EGFR. Recapitulating clinical data, EGFRvIII CAR T cells were unable to completely treat tumors with heterogenous EGFRvIII expression, leading to outgrowth of EGFRvIII-negative, EGFR-positive GBM. Conversely, CART.BiTE cells cured mice even in the setting of antigen-loss, against heterogeneous and well-established intracerebral tumors in mice. Unlike CAR T cells directly targeting EGFR, which caused toxicity in human skin grafts in vivo, secreted BiTE-EGFR was both locally effective and did not result in toxicity against grafted human skin. CONCLUSION: This is the first instance in which CARs and BiTEs have been combined into a single platform of immune therapy. Our results demonstrate that CARs and BiTEs can be combined strategically to mitigate antigen heterogeneity in GBM and also provide a unique T-cell-based delivery method for BiTEs to tumors in the brain.
Limiting dilution analysis of ontogeny of self- and allo-reactive thymocytes of C57BL/6J mouse. (1990)

In the present study, functional development of mouse fetal through neonatal to adult thymocytes was analyzed by limiting dilution assay (LDA) in terms of allo-reactivity and self-reactivity. Self-reactive PTL-p were always much less than those of allo-reactive PTL-p at all ages examined in this study. These results imply that thymocyte proliferation is not predominantly driven by responses to self antigens in the thymus, and that self-reactive thymocytes do not develop prior to allo-reactive thymocytes during thymic ontogeny. It is unlikely that most of such proliferating, murine early fetal thymocytes are self-reactive; allo-reactive cells are unlikely to have been derived from self-reactive cells during T cell development.
Fabrication of thin ferroelectric Hf<sub>0.5</sub>Zr<sub>0.5</sub>O<sub>2</sub> films by millisecond flash lamp annealing (2023)

Abstract We used millisecond flash lamp annealing (FLA) to form thin ferroelectric Hf 0.5 Zr 0.5 O 2 (HZO) films with thicknesses of less than 10 nm and with remanent polarization up to 30 μ C cm −2 . A clear dependency of the polarization on the annealing temperature and time was observed, indicating that the precise management of the thermal budget is a key factor in forming ferroelectric HZO. We also show and compare the process windows within which ferroelectricity in 10 and 5 nm samples is obtained. The results show that a high thermal budget is necessary for thinner samples. We examined the endurance characteristics and a greater endurance compared to rapid thermal annealing treatment was observed with more than 10 10 cycles without breakdown confirmed in 5 nm thick samples. The data indicates that there is the possibility of further thickness scaling whilst retaining highly durable characteristics for films annealed by FLA.
CCDC 900883: Experimental Crystal Structure Determination (2013)

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
A Policy-based Orchestration Plane For The Autonomic Management Of Future Networks (2009)

International audience
Additive global cerebral blood flow normalization in arterial spin labeling perfusion imaging (2015)

To determine how different methods of normalizing for global cerebral blood flow (gCBF) affect image quality and sensitivity to cortical activation, pulsed arterial spin labeling (pASL) scans obtained during a visual task were normalized by either additive or multiplicative normalization of modal gCBF. Normalization by either method increased the statistical significance of cortical activation by a visual stimulus. However, image quality was superior with additive normalization, whether judged by intensity histograms or by reduced variability within gray and white matter.
Jones Fracture in the Elite Athlete: Patient Reported Outcomes following Fixation with BMAC (2018)

Objectives: Jones’ fractures, 5 th metatarsal metaphyseal-diaphyseal junction fractures, are a debilitating injury for the elite athlete, particularly in cutting/pivoting sports. These injuries are usually managed surgically due to the high rate of nonunion and re-fracture. Despite primary screw fixation, delayed union and nonunion are not uncommon. Bone marrow aspirate concentrate (BMAC), an autologous source of hematopoietic and mesenchymal stem cells, has been used to augment healing due to the poor healing potential in the watershed region. We hypothesize that open reduction internal fixation (ORIF) augmented with BMAC will improve patient-reported outcome measures following Jones’ fractures in athletes. Methods: This study was a prospectively collected and maintained review of elite athletes that underwent intramedullary screw fixation augmented with BMAC for Jones’ fractures at an academic medical institution. All patients were evaluated preoperatively and postoperatively to assess differences in patient reported outcomes including VAS, PROMIS, FAAM, SF-12 scores, return to play, and complications. Student’s t test was used in statistical comparison of the preoperative and postoperative outcome scores. P &lt; 0.05 was considered significant. Results: A total of 41 elite athletes were treated with ORIF with BMAC for a Jones fracture with a mean age of 25.59 years (range 19-42). There were 26 (63%) males and 15 females included in the study. Type of athlete ranged across the following sport activities: football, basketball, soccer, volleyball. Of note, patients had significantly improved with lower visual analog score for pain (mean Δ3.56, p= 0.001), higher FAAM scores (mean Δ 43.6, p&lt; 0.001), and PASS scores (increased from 11% to 85%, p&lt; 0.001) at 6 months. Additionally, patients showed improvement in SF12, PROMIS10, and FAAM scores at 12 months, although this was not statistically significant due to insufficient follow up at this time. The average numbers of days lost to competition was 131 days. All patients that have returned to elite competitive sport activity report minimal to no pain. Conclusion: Intramedullary screw fixation of Jones’ fractures with BMAC results in optimal surgical outcomes in the elite athlete. The use of patient reported outcomes continues to be a focus of quality measures and should guide clinical decision making for surgical intervention, return to play, and to assess impact of treatment. A higher powered and long-term study with validated patient-reported outcomes is needed to confirm our observations.
MMSE Equalization for Bandwidth-Efficient Multicarrier Systems (2006)

Multicarrier systems, used in many of today's communications standards like 802.11b, are very prominent candidates for future mobile communication systems. Complex modulated transmultiplexer filter banks (Tzannes et al., 1994) providing improved frequency responses in comparison to orthogonal frequency division multiplex (OFDM) are proposed without a cyclic prefix. For the sake of increased bandwidth efficiency, they require an equalizer which mitigates the distortion of the frequency selective transmission channel. An efficient implementation of these transmultiplexer filter banks leads to discrete Fourier transformation (DFT) transmultiplexer filter banks. The advantages of such modifications with respect to OFDM are discussed and the results for the design of the required channel equalizer are presented