gebhart/patrepeval huggingface dataset:
Regulatory landscape of Runx2 and Sp7 in osteoblast and chondrocyte lineages: Recent findings from next‐generation sequencer‐based studies (2023)

Abstract Mouse genetic studies have revealed that Runx2 and Sp7 act as master regulators in skeletal development. Numerous mechanistic studies have also uncovered how these two transcription factors execute key gene regulatory programs for the specification and differentiation of the two skeletal cell lineages, osteoblasts, and chondrocytes. The emergence of next‐generation sequencer (NGS)‐based techniques has shifted the research focus from the local actions of Runx2 and Sp7 to their comprehensive actions on the entire genome in cells of interest. NGS‐based studies have elucidated the gene‐regulatory landscapes of Runx2 and Sp7 in osteoblast and chondrocyte lineages, demonstrating that Runx2 and Sp7 exert their cell‐type‐specific functions through cell‐type‐specific modes of action. NGS‐based techniques are expected to continue evolving and providing high‐resolution, genome‐scale datasets. Ongoing accumulation of such data will enhance our understanding of gene‐regulatory networks in skeletal development and maintenance, and assist in the modeling of skeletal disorders and the development of novel therapeutic strategies.
Semaphorin-7a reverses the ERF-induced inhibition of EMT in Ras-dependent mouse mammary epithelial cells (2012)

Epithelial-to-mesenchymal transition (EMT) is a key process in cancer progression and metastasis, requiring cooperation of the epidermal growth factor/Ras with the transforming growth factor-β (TGF-β) signaling pathway in a multistep process. The molecular mechanisms by which Ras signaling contributes to EMT, however, remain elusive to a large extent. We therefore examined the transcriptional repressor Ets2-repressor factor (ERF)-a bona fide Ras-extracellular signal-regulated kinase/mitogen-activated protein kinase effector-for its ability to interfere with TGF-β-induced EMT in mammary epithelial cells (EpH4) expressing oncogenic Ras (EpRas). ERF-overexpressing EpRas cells failed to undergo TGF-β-induced EMT, formed three-dimensional tubular structures in collagen gels, and retained expression of epithelial markers. Transcriptome analysis indicated that TGF-β signaling through Smads was mostly unaffected, and ERF suppressed the TGF-β-induced EMT via Semaphorin-7a repression. Forced expression of Semaphorin-7a in ERF-overexpressing EpRas cells reestablished their ability to undergo EMT. In contrast, inhibition of Semaphorin-7a in the parental EpRas cells inhibited their ability to undergo TGF-β-induced EMT. Our data suggest that oncogenic Ras may play an additional role in EMT via the ERF, regulating Semaphorin-7a and providing a new interconnection between the Ras- and the TGF-β-signaling pathways.
FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF, FLOT therapy for locally advanced esophageal carcinoma (JCOG1804E)—Short-term results for cohorts C and D. (2022)

286 Background: The standard neoadjuvant chemotherapy (NAC) in Japan for locally advanced esophageal squamous cell carcinoma (ESCC) consists of CDDP + 5-FU (CF). Recently, neoadjuvant DTX plus CF (DCF) therapy has shown promising efficacy for locally advanced ESCC. In addition, immune checkpoint inhibitors (ICIs) have demonstrated a survival benefit in ESCC and potential as an NAC in several cancers, including lung, breast, skin, and bladder. We previously reported that neoadjuvant CF plus nivolumab (Nivo) therapy was tolerable and showed promising efficacy for ESCC; however, the efficacy of ICI with DCF as an NAC and the safety of subsequent surgery for ESCC patients remain unclear. Methods: FRONTiER is a multi-cohort phase I study designed to evaluate the safety and efficacy of ICI combined with NAC in ESCC. The eligibility criteria were histologically proven ESCC with cT1N1-3M0 or cT2-3N0-3M0 (8th-UICC TNM classification), patient age of 20-75 years, PS ≤1, and no prior cancer therapies. The primary endpoint was the incidence of dose-limiting toxicities (DLT) from the initial dose to the 30th postoperative day. This study contained 5 experimental cohorts: cohort C received 3 courses of DTX (70 mg/m 2 ), CDDP (70 mg/m 2 ), and Nivo (360 mg/body) on day 1 and 5-FU (750 mg/m 2 ) on days 1–5 every three weeks. Cohort D received one administration of Nivo (240 mg/body) 2 weeks before chemotherapy followed by the same regimen as cohort C. Results: Twelve patients were enrolled in cohort C (n = 6) and D (n = 6) (median age [range]: 60 [31-74] years, PS 0/1: 11/1, clinical stage I/II/III/IVA: 2/2/7/1). Only one patient in cohort D developed DLT (grade 3 dyspnea and rash); no other DLT were seen. Grade ≥3 adverse events were neutropenia (n = 1), leukopenia (n = 7), anorexia (n = 3), hyponatremia (n = 2), febrile neutropenia (n = 1), nausea (n = 1), and lymphopenia (n = 1) during NAC, and lung infection (n = 2), peritoneal infection (n = 1), anemia (n = 1), lymph leakage (n = 1), vagal reflex (n = 1), dyspnea (n = 1), rash (n = 1), septic shock (n = 1), pleural effusion (n = 1), and pneumatosis intestinalis (n = 1) during the postoperative period. No treatment-related deaths were observed. All patients received 3 courses of NAC, and 11 patients (91.7%) achieved an R0 resection without treatment interruption. One patient (16.7%) in cohort C and 3 patients (50.0%) in cohort D achieved pathological complete responses. Conclusions: Neoadjuvant DCF + Nivo with/without prior Nivo administration followed by surgery for locally advanced ESCC was well tolerated and showed an extremely promising efficacy. Clinical trial information: NCT03914443.
Automatic Loop Parallelization via Compiler Guided Refactoring (2011)

For many parallel applications, performance relies not on instruction-level parallelism, but on loop-level parallelism. Unfortunately, many modern applications are written in ways that obstruct automatic loop parallelization. Since we cannot identify sufficient parallelization opportunities for these codes in a static, off-line compiler, we developed an interactive compilation feedback system that guides the programmer in iteratively modifying application source, thereby improving the compiler’s ability to generate loop-parallel code. We use this compilation system to modify two sequential benchmarks, finding that the code parallelized in this way runs up to 8.3 times faster on an octo-core Intel Xeon 5570 system and up to 12.5 times faster on a quad-core IBM POWER6 system. Benchmark performance varies significantly between the systems. This suggests that semi-automatic parallelization should be combined with target-specific optimizations. Furthermore, comparing the first benchmark to hand-parallelized, hand-optimized pthreads and OpenMP versions, we find that code generated using our approach typically outperforms the pthreads code (within 93-339%). It also performs competitively against the OpenMP code (within 75-111%). The second benchmark outperforms hand-parallelized and optimized OpenMP code (within 109-242%).
Graphene Quantum Dots Based Systems As HIV Inhibitors (2018)

Graphene quantum dots (GQD) are the next generation of nanomaterials with great potential in drug delivery and target-specific HIV inhibition. In this study we investigated the antiviral activity of graphene based nanomaterials by using water-soluble GQD synthesized from multiwalled carbon nanotubes (MWCNT) through prolonged acidic oxidation and exfoliation and compared their anti-HIV activity with that exerted by reverse transcriptase inhibitors (RTI) conjugated with the same nanomaterial. The antiretroviral agents chosen in this study, CHI499 and CDF119, belong to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI). From this study emerged the RTI-conjugated compound GQD-CHI499 as a good potential candidate for HIV treatment, showing an IC<sub>50</sub> of 0.09 μg/mL and an EC<sub>50</sub> value in cell of 0.066 μg/mL. The target of action in the replicative cycle of HIV of the drug conjugated samples GQD-CHI499 and GQD-CDF119 was also investigated by a time of addition (TOA) method, showing for both conjugated samples a mechanism of action similar to that exerted by NNRTI drugs.
Cloning and Sequence Analysis of Multiple Splice Variants of Lactate Dehydrogenase C in Yak Testes (2008)

Lactate dehydrogenase C (LDH-C) has been reported to play a role in the energy metabolism of mammal spermatozoa. However, the functions and expression patterns of LDH-C still remain unclear. In order to elucidate the functions and expression patterns of LDH-C, we cloned the cDNA of yak LDH-C. Total RNA was extracted from yak testes and reverse transcribed and amplified by PCR. The full length open reading frame (ORF) of LDH-C and its five splice variants were obtained. The full length ORF contained 999 bp encoding a 332-amino-acid protein that showed 100% identity with bovine LDH-C. Compared with the full length ORF of LDH-C, the five variants used the same start codon as the full length ORF and encoded 5 putative proteins. In detail, variants 1 (missing the coding sequence of exon 6 and 7) and 2 (missing the coding sequence of exon 7) bear the entire nicotinamide-adenine dinucleotide (NAD) binding domain and an active site. Variants 3 (missing the first 42 nuleotides of exon 4) and 4 (missing the coding sequences of exons 5, 6 and 7) lack part of the NAD binding domain but contained the entire active site. Variant 5 (missing the coding sequence of exons 4 and 7) lacks a large part of the NAD binding domain and the entire active site. Native polyacrylamide gel electrophoresis was performed to determine if the splice variants can be translated into proteins. However, native PAGE detected no specific bands from yak testes and bovine spermatozoa. This study suggests the alternative splicing of LDH-C is ubiquitous in bovine testes and might be involved in regulation of LDH-C expression. The findings also help to elucidate the functions of LDH-C.
Possibility of hard-target lidar detection of a biogenic volatile organic compound, α-pinene gas, over forest areas (2001)

The absorption spectrum of alpha-pinene gas, a biogenic volatile organic compound, was directly measured with a pulsed mid-infrared laser. The maximum absorption wavelength was found to be ~3.42 mum, and an absorption cross section of 4.8 x 10(-23) m(2) molec(-1) was obtained. A simple theoretical calculation with the measured spectral data showed that several hundreds of parts in 10(12) (ppt) of alpha-pinene gas in forest-mountain areas over a range of ~10 km were detectable by a long-path-averaged hard-target absorption lidar. Requirements for system development were also discussed.
Diagnostic Methods for and Clinical Pictures of Polyomavirus Primary Infections in Children, Finland (2014)

We used comprehensive serodiagnostic methods (IgM, IgG, and IgG avidity) and PCR to study Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus infections in children observed from infancy to adolescence. Comparing seroconversion intervals with previous and subsequent intervals, we found that primary infections with these 2 viruses were asymptomatic in childhood.
A New Approach for Single Antenna INS Alignment in Multirotors Allows Aaster Time-to-Application (2022)

GNSS/INS integration systems are increasingly used in the navigation of Unmanned Aerial Vehicles. To decrease the size and weight, single antenna GNSS is usually favorable in many UAV applications. To reach optimal accuracy, the system should be initialized properly. However, a single antenna GNSS/INS system cannot directly measure the initial heading of the UAV, without additional sensors such as a magnetometer or gyrocompass. Course over ground computation is also not feasible for vehicles like multirotors where the direction of motion is not aligned to the vehicle body axis. This paper proposes a new real-time approach for initial attitude estimation of a multirotor using a single-antenna GNSS and a MEMS IMU. An array of strapdown navigators with random initial headings are spread in the environment and after a short period with sufficient motion, the best-fit navigator is determined and its attitude states are used to initialize the GNSS/INS fusion filter. This approach provides accurate initial attitude angles in a few tens of seconds, which is important due to the limited operational time of small UAVs. In addition, the proposed approach does not require a complicated process to be performed by the user at the UAV start-up, i.e., any dynamic motion during the alignment phase is sufficient to reach the proper heading accuracy. Since this is a purely algorithmic approach, it does not require any additional sensor.
Radical Transversal Lightlike Submanifolds of Indefinite Para-Sasakian Manifolds (2014)

Abstract In this paper, we study radical transversal lightlike submanifolds and screen slant radical transversal lightlike submanifolds of indefinite para-Sasakian manifolds giving some non-trivial examples of these submanifolds. Integrability conditions of distributions D and RadTM on radical transversal lightlike submanifolds and screen slant radical transversal lightlike submanifolds of indefinite para-Sasakian manifolds, have been obtained. We also study totally contact umbilical radical transversal lightlike submanifolds of indefinite para-Sasakian manifolds.
Estimation of Base Flow in Drainage Channels in Two Tile Drained Watersheds in Illinois (2005)

A study to determine the base flow components in drainage channels was undertaken in two watershedsnamely Big Ditch (Site A) and Embarras (Site B) in Champaign County, Illinois. Two channel sections were selected in thetwo watersheds and rectangular cutthroat flumes were installed at upstream and downstream ends in the channel sections.The stream segment (194 m long) in Site A had two tile outlets draining into it. The stream segment (183 m long) in Site Bdid not have any tile drain. Flow rates were measured at each of the flumes and tile outlets at 15 minute intervals. Twelvepiezometers were installed on both sides of each of the channel sections to monitor the water table elevations in order toestimate the base flow to the channels.<br><br>Hydrographs were developed for storm events of different intensities for the flumes and tile outlets starting from March04 toDecember04. In total, twenty four hydrographs were studied. A mass balance approach was used to estimate the baseflow volume per unit length of the channels. Dupuit equation was also applied to determine the base flow in three transectsin the stream sections during base flow periods.<br><br>It was observed that the base flow rate was predominantly dependent on the antecedent moisture conditions, rainfalldistribution, the types of soil in the watersheds and plant water uptake.
Does TCPC power loss really affect exercise capacity? (2015)

The Authors’ reply 

We read with interest the response1 to our study.2 The authors speculate: “What if indexed power loss (iPL) is dependent on body surface area (BSA)?” We wish to make the following points in response:

1. The data extracted from our paper2 that includes 30 patients shows no statistically significant correlation (p=0.167) between iPL and BSA (see online supplementary figure). This clarifies the speculation and supports our conclusion: ‘iPL correlates with exercise capacity’. We believe this is not surprising given …
New Oxide Ceramic Developed for Superior High-Temperature Wear Resistance (2003)

Ceramics, for the most part, do not have inherently good tribological properties. For example friction coefficients in excess of 0.7 have been reported for silicon nitride sliding on silicon nitride or on bearing steel (ref. 1). High friction is always accompanied by considerable wear. Despite their inherently poor tribological properties, the high strength and high toughness of silicon nitride (Si3N4) ceramics has led to their successful use in tribological applications (refs. 1 to 4). The upper temperature limit for the application of Si3N4 as wear-resistant material is limited by reaction with the tribological environment (ref. 3). Silicon nitride is known to produce a thin silicon dioxide film with easy shear capability that results in low friction and low wear in a moist environment (ref. 5). At elevated temperatures, the removal of the reaction product that acts as lubricant causes the friction coefficient to increase and, consequently, the wear performance to become poor. New materials are sought that will have wear resistance superior to that of Si3N4 at elevated temperatures and in harsh environments. A new class of oxide ceramic materials has been developed with potential for excellent high-temperature wear resistance. The new material consists of a multicomponent oxide with a two-phase microstructure, in which the wear resistance of the mixed oxide is significantly higher than that of the individual constituents. This is attributed to the strong constraining effects provided by the interlocking microstructures at different length scales, to the large aspect ratio of the phases, to the strong interphase bonding, and to the residual stresses. Fretting wear tests were conducted by rubbing the new ceramic material against boron carbide (B4C). The new ceramic material produced a wear track groove on B4C, suggesting significantly higher wear resistance for the oxide ceramic. The new material did not suffer from any microstructural degradation after the wear test. The wear rate of the new ceramic material at 600 C was determined to be on the order of 10-10 mm3/N-m, which is 3 to 5 orders of magnitude lower than that for the current state-of-theart wear-resistant materials (Si3N4and B4C). The friction coefficient of the new ceramic materials is on the order of 0.4, which is significantly lower than that of silicon nitride. This new class of oxide materials has shown considerable potential for applications requiring high wear resistance at high temperatures and in harsh environments. New understanding of the wear behavior of ceramic materials is emerging as a result of the surprisingly high wear resistance of two-phase oxide ceramics. There is excellent potential for further improvements in the wear resistance of oxide ceramics through optimizing the microstructure and altering the crystallographic properties of specific oxide materials as a second phase to reduce the coefficient of friction at elevated temperatures.
4-Tritylbenzoic acid. A molecular scaffold for wheel-and-axle host–guest inclusion compounds with a supramolecular axis (2000)

4-Tritylbenzoic acid crystallises via the carboxy dimer supramolecular synthon to produce a wheel-and-axle host lattice that includes different aromatic solvents in its microporous framework. The clathrate structures were characterised by single crystal X-ray diffraction. Solvents like xylenes, chlorobenzene and anisole are included in a channel of cross-sectional area 42 Å2 with 2∶1 host–guest stoichiometry while mesitylene occupies a channel of 71 Å2 as a 1∶1 clathrate. The host architecture is robust and yet adaptive. The carboxy dimer synthon together with the phenyl–phenyl interactions (edge-to-face, ef and offset face-to-face, off) produce recurring, zigzag tapes of wheel-and-axle supermolecules. A plethora of aromatic ef and off motifs in the intra- and inter-tape regions modulate the cavity area to accommodate solvents of different size/shape. The ability to tune the pore volume and still retain the target wheel-and-axle topology is a notable feature in this family of isomorphous structures. The unsolvated acid adopts a different crystal packing with the triphenylmethyl groups filling the voids in the structure.
The Effect of Perceived Locomotor Constraints on Distance Estimation (1990)

Two experiments were conducted to examine the ways in which the visual estimation of distance to a target is affected by constraints perceived to be placed on the subsequent locomotion to the target without vision. We hypothesized that an appraisal of impending effort would play a role in ascertaining the distance to be walked. In Experiment 1, the amount of resistance to walking was variable and unpredictable. One group of subjects performed against relatively low resistance, whereas another group performed against substantially greater resistance. In the low-resistance condition, no significant differences in CE, VE, time to target, or number of steps to target were found between any of the eight combinations of predictable or unpredictable resistances during walking. In the high-resistance condition, however, significant differences were found for CE and number of strides to target when resistance varied unpredictably during walking. Experiment 2 was similar in design but required subjects to walk with combinations of normal or short steps after they had viewed the target knowing only the gait type that would be used to begin locomotion. No differences in CE, VE, or time to target were found between four different combinations of gait type and predictability, under subjectively controlled conditions. When the step constraints were externally imposed, however, differences were found for CE. None of the results from either experiment, in which the number of strides needed to reach the target or the predictability of gait did not change from normal, supported the hypothesis that motor output requirements are necessary in forming a mental representation of the target position that can be used to walk to the target with eyes closed. Whichever locomotor technique was used to walk the estimated distance in these cases, the representation was able to be used independently. When walking mechanics were altered by externally imposed constraints, however, the success at reaching the estimated target position was reduced. These latter results are consistent with those obtained using up, down, and level walking and support the premise that mental representations used in blind walking are linked to the locomotor mechanics afforded by environmental conditions.
Pre‑treatment neutrophil‑to‑lymphocyte ratio predicts survival in patients with laryngeal cancer (2017)

An increased neutrophil-to-lymphocyte ratio (NLR) is associated with poorer prognostic outcomes in numerous types of cancer. However, a small number of studies have demonstrated the prognostic role of NLR in patients with laryngeal cancer. The present study evaluated the association between NLR and survival outcomes in patients with laryngeal squamous cancer. All patients were scheduled for follow-up visits. The levels of cytokines from tumor tissues were analyzed by ELISA. A classification and regression tree (CART) was used to determine the optimal cutoff values of NLR. The clinical features and NLR were determined using Kaplan-Meier analysis and Cox regression to analyze the survival outcomes and associated risks. Of the total 654 patients, 70 patients (70/654; 10.7%) failed to receive follow-up. Blood and biochemical parameters, including NLR, platelet-to-lymphocyte ratio and albumin-to-globulin ratio were associated with clinical characteristics of the patients, with the exception of histologic grade. Only one node with NLR at 3.18 divided patients into different categories, according to CART analysis. Survival analysis demonstrated that NLR at cutoff values subdivided patients into different survival outcomes (P<0.001). Subsequent to adjustments for age and other clinical features, NLR was identified to be an independent prognostic factor for overall survival and progression-free survival (P<0.05). Increased levels of cytokines, including IL-6 and IL-8, in tumor tissues were associated with NLR values. In summary, pre-treatment NLR was associated with the prognostic outcomes for patients with laryngeal cancer, and may assist to establish prognostic factors for these patients.