gebhart/patrepeval huggingface dataset:
Systematic characterization of short intronic splicing-regulatory elements (2021)

ABSTRACT Intronic splicing enhancers and silencers (ISEs and ISSs) are two groups of splicing-regulatory elements (SREs) that play critical roles in determining splice-site selection, particularly for alternatively spliced introns or exons. SREs are often short motifs; their mutation or dysregulation of their cognate proteins frequently causes aberrant splicing and results in disease. To date, however, knowledge about SRE sequences and how they regulate splicing remains limited. Here, using an SMN2 minigene, we generated a complete pentamer-sequence library that comprises all possible combinations of 5 nucleotides in intron 7, at a fixed site downstream of the 5′ splice site. We systematically analyzed the effects of all 1023 mutant pentamers on exon 7 splicing, in comparison to the wild-type minigene, in HEK293 cells. Our data show that the majority of pentamers significantly affect exon 7 splicing: 584 of them are stimulatory and 230 are inhibitory. To identify actual SREs, we utilized a motif set enrichment analysis (MSEA), from which we identified groups of stimulatory and inhibitory SRE motifs. We experimentally validated several strong SREs in SMN1 / 2 and MAPT minigene settings. Our results provide a valuable resource for understanding how short RNA sequences regulate splicing. Many novel SREs can be explored further to elucidate their mechanism of action.
Right Ventricular Failure in a Young Man After Chest Trauma (1982)

A 39-year-old man was examined for progressive fatigue nine months after suffering blunt chest trauma. Jugular venous distention with a C-V wave, a right ventricular lift, and a tricuspid insufficiency murmur were noted. A chest roentgenogram showed cardiomegaly and an ECG demonstrated a right bundle-branch block. The M-mode echocardiogram of the right ventricle (left panel) and of the tricuspid valve (right panel) is shown in Fig 1. What is your diagnosis? Cross-sectional echocardiogram, cardiac catheterization, and subsequent surgical repair confirmed the diagnosis. The M-mode echocardiogram of the right ventricle is taken at the level of the tricuspid valve. There is mild right ventricular enlargement with paradoxic septal movement compatible with right ventricular volume overload (Fig 1, left panel). Diastolic fluttering of the tricuspid septal leaflet (Fig 1, downward arrow, right panel) is consistent with increased transvalvular flow. Wide excursion and diastolic notching of the anterior tricuspid leaflet (Fig 1,
Novel methylated DNA markers in plasma detect distant recurrence of colorectal cancer. (2020)

4088 Background: Methylated DNA markers (MDMs) are broadly informative for early detection of colorectal cancer (CRC) but have not been extensively studied for post-treatment surveillance and disease monitoring. We aimed to assess the feasibility of novel CRC-associated MDMs for detection of distant recurrent CRC (rCRC) in plasma. Methods: A panel of 13 MDMs previously identified to be discriminant for primary CRC was selected. In a cross-sectional analysis of plasma samples, MDMs were assayed blindly (by target enrichment long-probe quantitative amplified signal assay) from 160 age/sex-balanced patients (60 healthy controls, 60 with resected CRC and no evidence of disease (NED), and 40 rCRC after primary tumor resection). Plasma-derived carcinoembryonic antigen (CEA) was measured on all patients. Random forest modeling was used to derive a prediction algorithm of MDMs (with and without CEA) for the endpoint of rCRC relative to healthy controls. The accuracy of the algorithm was summarized as sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CI) in the test set. Results: Median patient age was 55 (interquartile range: 49-64) years. As shown in the Table below, a single MDM with the highest AUC was significantly better than CEA ( p= 0.02). On cross validation, CEA provided no additional improvement to the performance of the panel of 13 MDMs ( p= 0.2). The cross-validated panel of MDMs detected rCRC liver metastases with 96% (79-100%) sensitivity, lung metastases with 78% (40-97%) sensitivity, and peritoneal/nodal metastases with 57% (18-90%) sensitivity. Lesions with Response Evaluation Criteria in Solid Tumors sum &gt; 4 cm were detected with 94% (73-100%) sensitivity and ≤4 cm with 78% (52-94%) sensitivity. Conclusions: Novel MDMs in plasma detect rCRC with promising accuracy. The clinical utility of MDMs for non-invasive post-treatment surveillance and treatment monitoring in CRC warrants further evaluation in longitudinal studies with sufficient follow-up to exclude sub-clinical recurrence in those with NED. [Table: see text]
The human cytomegalovirus UL116 glycoprotein is a chaperone to control gH-based complexes levels on virions (2020)

ABSTRACT Human cytomegalovirus (HCMV) relies in large part upon the viral membrane fusion glycoprotein B (gB) and two alternative gH/gL complexes, gH/gL/gO (Trimer) and the gH/gL/UL128/UL130/UL131A (Pentamer) to enter into cells. The relative amounts of the Trimer and Pentamer vary among HCMV strains and contribute to differences in cell tropism. Although the viral ER resident protein UL148 has been shown to interact with gH to facilitate gO incorporation, the mechanisms that favor the assembly and maturation of one complex over another remain poorly understood. HCMV virions also contain an alternative non-disulfide bound heterodimer comprised of gH and UL116 whose function remains unknown. Here, we show that disruption of HCMV gene UL116 causes infectivity defects of ~10-fold relative to wild-type virus and leads to reduced expression of both gH/gL complexes in virions. Furthermore, gH that is not covalently bound to other viral glycoproteins, which are readily detected in wild-type HCMV virions, become undetectable in the absence of UL116 suggesting that the gH/UL116 complex is abundant in virions. We find evidence that UL116 and UL148 interact during infection indicating that the two proteins might cooperate to regulate the abundance of HCMV gH complexes. Altogether, these results are consistent with a role of UL116 as a chaperone for gH during the assembly and maturation of gH complexes in infected cells.
Histopathologic and clinical comparison of recurrent and non-recurrent urethral stricture disease treated by reconstructive surgery (2021)

Our study supports reporting cellularity of the fibrous plaque as a potential predictor of outcome in patients undergoing reconstructive urethroplasty. Patients with paucicellular fibrosis are at increased risk of recurrence.
Open-World Dialog: Challenges, Directions, and a Prototype (2009)

We present an investigation of open-world dialog, centering on systems that can perform conversational dialog in an open-world context, where multiple people with different needs, goals, and long-term plans may enter, interact, and leave an environment. We outline and discuss a set of chal-lenges and core competencies required for supporting the kind of fluid multiparty interaction that people expect when conversing and collaborating with other people. Then, we focus as a concrete example on the challenges faced by re-ceptionists who field requests at the entries to corporate buildings. We review the subtleties and difficulties of creat-ing an automated receptionist that can work with people on solving their needs with the ease and etiquette expected from a human receptionist. Finally, we review details of the construction and operation of a working prototype. 1.
Bringing efficient advanced queries to distributed hash tables (2004)

Interest in distributed storage is fueled by demand for reliability and resilience combined with ubiquitous availability. Peer-to-peer (P2P) storage networks are known for their decentralized control, self-organization, and adaptation. Advanced searching for documents and resources remains an open problem. The flooding approach favored by some P2P networks is inefficient in resource usage, but more scalable and resource-efficient solutions based on distributed hash tables (DHT) lack in query expressiveness and flexibility. In this paper, we address this issue and introduce new efficient, scalable, and completely distributed methods that strive to keep resource consumption by queries and index information as low as possible. We describe how to improve the handling of multiple subqueries combined through Boolean set operators. The need for these operators is intensified by applications to go beyond simple exact keyword matches. We discuss, optimize, and analyze appropriate extensions to support range and prefix matching in DHT.
The Synthetic Gestagen Levonorgestrel Disrupts Sexual Development in Xenopus laevis by Affecting Gene Expression of Pituitary Gonadotropins and Gonadal Steroidogenic Enzymes (2011)

International audience
Synthesis of photoresists for 157-nm microlithography using CO 2 (2004)

Norbornene-based monomers were synthesized to include fluorinated moieties and/or chemical amplification switching groups. Fluorinated homopolymers to be used as the basis of resist materials were synthesized from these monomers by addition polymerization using allylpalladium chloride dimmer. Monomers and polymers have been identified and partially characterized for important lithographic properties. A monomer containing a silsesquioxane group has been incorporated into this platform to enhance etch resistance. A monomer containing an acid-cleavable group has also been synthesized and will be incorporated into this platform.
In Vitro Adipose Tissue Engineering Using an Electrospun Nanofibrous Scaffold (2008)

Electrospun 3-dimensional nanofibrous scaffolds share morphologic similarities to collagen fibrils, and promote favorable biologic responses of seeded cells. In this study, we have fabricated a 3-dimensional nanofibrous scaffold made of poly L-lactic acid, and examined its ability to support and maintain the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro. After a 21-day incubation, oil red O staining of constructs treated with adipogenic supplements revealed positive adipose-like staining, compared with lack of staining in untreated cultures. Semi-quantitative RT-PCR analysis of human bone marrow-derived mesenchymal stem cells cultured in adipogenic medium revealed highly elevated levels of adipogenesis-associated genes (1797-fold for lipoprotein lipase, and 5.6-fold for peroxisome proliferator-activated receptor gamma). Immunofluorescence staining of cellular constructs in adipogenic culture media showed the presence of lipoprotein lipase vesicles, a characteristic feature of adipose tissue. These results suggest that the poly L-lactic acid-based nanofibrous scaffold is a promising candidate for adult stem cell-based engineering of adipose tissue.
Inbreeding in 35 Generations of Development of Cornell S Strain of Leghorns (1979)

The average coefficient of inbreeding after 35 years of development of Cornell S strain was estimated at 39% using pedigree data. Based on the number of breeders used and assuming that all breeders were one year old, the expected coefficient of inbreeding would have been 69%. The average age of breeders used in any one year varied between 1.05 and 2.36 years. It is suggested that the smaller coefficient of inbreeding was primarily the result of a decrease in the number of generations possible in the fixed time span of 35 years when the average age of breeders was greater than one year.
Statistical Properties of the Tensile Strength of B/Al Composites at Elevated Temperatures. (1994)

Tensile tests of a l0vol% boron-aluminum composite were carried out at room temperature, 150°C and 300°C, in order to investigate the validity of the finite-element-method (FEM) simulation proposed in the previous report, which evaluates the tensile strength of fiber-reinforced metals. The average strengths of the simulated result were in good agreement with those of the experimental result, although the range of the variability in strength was somewhat underestimated. The stress distributions on the fibers around a broken fiber were estimated by FEM analysis, by taking into account the matrix constitutive equation at the elevated temperatures. Then, the relation between the stress distributions and the statistical properties of strength obtained in the experiment and simulation were discussed, using the probabilistic model based on the Markov chain. It was pointed out that, consequently, the statistical properties of room temperature are maintained to some degree at elevated temperatures. Additionally, the effect of the thermal stress occurring in the composite on the tensile strength was also investigated.
Determination of Dimethyl Ether in Air by Cataluminescence-Based Gas Sensor (2013)

A rapid and sensitive cataluminescence-based gas sensor utilizing nanosized Y 2 MnO 5 as the sensing materials for determining dimethyl ether in air was proposed. The luminescence characteristics and the optimal conditions were investigated in detail. The gas sensor showed high selectivity for dimethyl ether at 620 nm and satisfying activity at 210°C under the optimized conditions. The linear range of cataluminescence intensity versus concentration of dimethyl ether was 5~120 mg/m 3 , and the detection limit (3σ) was 3 mg/m 3 . No or weak interference was observed while the foreign substances, such as formaldehyde, ammonia, ethanol, benzene, carbon monoxide and sulfur dioxide, were passing through the sensor under selected conditions. The gas sensor displayed good stability for continuously introducing dimethyl ether over 100 h, and allowed real-time monitoring of dimethyl ether in air.
Cloning and characterization of a lung-specific cDNA corresponding to the γ chain of hepatic fibrinogen (1995)

The gene (gamma FBG) encoding the fibrinogen gamma chain (gamma FBG) has been shown to exhibit both tissue-specific and ubiquitous expression. To confirm the identity of the gamma FBG transcripts expressed in extrahepatic tissue, lung tissue was chosen as a model of extrahepatic gamma FBG gene expression. A ferret lung cDNA clone bank was constructed in lambda gt11 and several positive plaques were isolated using cross-species hybridization with the rat gamma FBG cDNA. Sequence data of the longest clone, designated pFLG gamma 3, was compared at the nucleotide and deduced amino acid (aa) levels with sequences of gamma FBG from other species. The results indicated that the identity of the ferret lung-specific gamma FBG cDNA to pig, rat, bovine and human gamma FBG cDNAs ranged from 78-88%; the similarity of the ferret lung-specific gamma FBG deduced aa sequence ranged from 84-88% across species. Cysteine aa involved in intra- and inter-chain disulfide-bonded secondary and tertiary structure are absolutely conserved in ferret gamma FBG. The putative cell-cell adhesion sites for both platelet alpha IIb beta 3 and intercellular adhesion molecule-1 receptor binding to ferret gamma FBG are > 90% similar to the corresponding sites in the human gamma FBG. The results of Northern hybridization indicated that the ferret lung gamma FBG mRNA was equivalent in size to the liver gamma FBG mRNA; Southern hybridization suggested that ferret gamma FBG is a single-copy gene, as is the gamma FBG of other species. Lung-specific gamma FBG expression was localized to epithelial cells of the large and small airways and chondrocytes by in situ RNA:RNA hybridization. The functional significance of gamma FBG expression in lung is not presently known. Since expression of FBG is up-regulated 2-10-fold in the liver during an inflammatory event, it is possible that lung-specific gamma FBG expression occurs predominantly during lung disease or injury.
Initial results for airframe shadowing in L- and C-band air-ground channels (2015)

• Unmanned Aircraft System (UAS) use is growing & will continue to grow rapidly • UAS integration in the National Airspace System (NAS) via a reliable & safe link: Control & Non-payload Communication (CNPC).
Photobiomodulation‐Induced Differentiation of Immortalized Adipose Stem Cells to Neuronal Cells (2020)

This study demonstrates that a combination of biological and physical inducers can advance the differentiation of adipose stem cells to neurons. We were able to establish the optimal energy for the neuronal differentiation of iASCs in vitro. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
Effects of a-Bromoergocriptine on Pituitary Hormone Secretion in Children* (1981)

The effect of bromoergocryptine (BE) on human GH (hGH), PRL, LH, FSH, TSH, and blood sugar levels was evaluated in a series of 22 normal children. Blood samples were collected in basal conditions and after 30, 60, 90, 120, 150, and 180 min of BE administration (1.25 or 0.62 mg/os). The drug induced a marked and sustained increase in hGH secretion when basal serum levels of the hormone were lower than 10.0 ng/ml (n = 15). When basal hGH serum levels were higher (n = 7), BE provoked either a later increase of serum hGH in most children (n = 5) or a persistent decrease in hGH (n = 2). On the other hand, BE markedly inhibited PRL secretion without modifying LH, FSH, or TSH. The data obtained suggest that BE can be used as a useful tool for the assessment of hGH secretion in children.
Computer-Aided Engineering of Semiconductor Integrated Circuits. (1978)

Economical procurement of small quantities of high performance custom integrated circuits for military systems is severely impeded by inadequate process, device and circuit models that handicap accurate computer-aided design at low cost. The salient objective of this program is to formulate physical models of fabrication processes, devices and circuits to allow total computer-aided design of custom large-scale integrated circuit subsystems to reduce development cycle time and cost. The basic areas under investigation are: (1) ion implantation and diffusion of dopants; (2) thermal oxidation; (3) chemical vapor deposition of silicon epitaxy; and (4) device simulation and statistical circuit modeling. This report discusses the results of the second year of the program. (Author)
Enhanced Cas12a multi-gene regulation using a CRISPR array separator (2021)

Abstract The type V-A Cas12a protein can process its CRISPR array, a feature useful for multiplexed gene editing and regulation. However, CRISPR arrays often exhibit unpredictable performance due to interference between multiple crRNAs. Here, we report that Cas12a array performance is hypersensitive to the GC content of crRNA spacers, as high-GC spacers can impair activity of the downstream crRNA. We analyzed naturally occurring CRISPR arrays and observed that repeats always contain an AT-rich fragment that separates crRNAs; we term this fragment a CRISPR separator. Inspired by this observation, we designed short, AT-rich synthetic separators ( synSeparators ) that successfully removed the disruptive effects between crRNAs. We demonstrate enhanced simultaneous activation of seven endogenous genes in human cells using an array containing the synSeparator. These results elucidate a previously unknown feature of natural CRISPR arrays and demonstrate how nature-inspired engineering solutions can improve multi-gene control in mammalian cells.
Negative Field Reliability of ONO Gate Dielectric on 4H-SiC (2008)

It was experimentally shown that an ONO gate dielectric carefully formed on 4H-SiC has extremely high reliability even under a negative electric field at least up to a junction temperature of 300°C, making it promising for power MOS and CMOS applications. Medium charge to failure of –30 C/cm2 was achieved for fully processed polycrystalline Si gate MONOS capacitors with an equivalent SiO2 thickness of teq = 44 nm and a 200-μm diameter. The medium time to failure of these capacitors projected for –3 MV/cm exceeds 86 and 6.3 thousand years at room temperature and 300°C, respectively. A parasitic memory action did not appear even when Eox of -6.6 MV/cm was applied for 5000 seconds.
Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice (2007)

Dietary antioxidants and selenium compounds were shown to have a therapeutic effect against hepatocellular carcinoma in several mouse models. We tested the effects of tannic acid and selenomethionine on hepatocellular carcinoma development in Mdr2 knockout (Mdr2-KO) mice. Mdr2-KO and age-matched Mdr2 heterozygous control mice were fed with tannic acid or selenomethionine during the first 3 months of life. Then, several mice from each group were sacrificed, and liver tissue samples were removed for analysis. The remaining mice were fed a regular diet until the age of 16 months, at which time the number and size of liver tumors were determined. Liver tissue samples of 3-month-old mice were subjected to gene expression profiling analysis using cDNA macroarrays containing probes for 240 genes that regulate responses to oxidative stress and inflammation or lipid metabolism. Both tannic acid and selenomethionine had partial chemopreventive effect on development of hepatocellular carcinoma in Mdr2-KO mice: they reduced the incidence of large tumor nodules (diameter >1 cm) at age 16 months. Both agents inhibited gene expression and reversed up-regulation of many genes that control inflammation or response to oxidative stress in Mdr2-KO livers at age 3 months. This inhibitory effect on gene expression correlated with the ability of agents to reduce incidence of large tumors: selenomethionine was more active than tannic acid in both aspects. Understanding the molecular mechanism of chemoprevention effect could improve our therapeutic modalities while using these agents.
The synchronous oscillator in frequency generation: an overview (2004)

The Synchronous Oscillator (SO) as a frequency generation device is presented, and the impact of the technology on the circuit behavior is discussed. Several prototypes, either in bipolar, CMOS or SiGe BiCMOS technologies are presented and discussed.
Optimization of Naphthyridones into Selective TATA-Binding Protein Associated Factor 1 (TAF1) Bromodomain Inhibitors (2021)

Bromodomain containing proteins and the acetyl-lysine binding bromodomains contained therein are increasingly attractive targets for the development of novel epigenetic therapeutics. To help validate this target class and unravel the complex associated biology, there has been a concerted effort to develop selective small molecule bromodomain inhibitors. Herein we describe the structure-based efforts and multiple challenges encountered in optimizing a naphthyridone template into selective TAF1(2) bromodomain inhibitors which, while unsuitable as chemical probes themselves, show promise for the future development of small molecules to interrogate TAF1(2) biology. Key to this work was the introduction and modulation of the basicity of a pendant amine which had a substantial impact on not only bromodomain selectivity but also cellular target engagement.