gebhart/patrepeval huggingface dataset:
Differential transcriptional activation by the N-terminal region of BRCA1 splice variants BRCA1a and BRCA1b. (1998)

The breast and ovarian cancer susceptibility gene BRCA1, is a nuclear phosphoprotein which functions as a tumor suppressor in human breast cancer cells. BRCA1 protein contains an amino-terminal zinc finger motif and a carboxy-terminal acidic region. Recently, the carboxy-terminal region of BRCA1 and the amino-terminal region of BRCA2 proteins were shown to function as transactivation domains when fused to GAL4 DNA binding domain. We have recently isolated and characterized two new naturally occurring variants of BRCA1 (BRCA1a/p110 and BRCA1b/p100) which are phosphoproteins containing phosphotyrosine that associate with E2F transcriptional factors, cyclins and cyclin dependent kinases indicating a role for BRCA1 proteins in cell-cycle regulation. Here we show for the first time that the amino-terminal region of BRCA1a (BNT) but not BRCA1b can also function as a transcriptional activator when fused to GAL4 DNA binding domain. Thus, BRCA1/1a proteins contain two autonomous transcriptional activation domains, one at the amino-terminal region (BNT) and the other at the carboxy-terminal region (BCT). BRCA1b retains only the BCT domain since it has lost part of the potential BNT domain as a result of alternative splicing. Our results also suggest the presence of an inhibitory domain at the carboxy terminal region of BRCA1 and BRCA1a proteins (BID). Thus, BRCA1b protein may function as a dominant negative variant that could regulate the transcriptional activity of BRCA1/BRCA1a proteins and hence may serve as a marker for identifying individuals with greater potential for developing breast cancer. It may be possible that loss of transcriptional activation or protein-protein interactions in patients with mutations in the amino terminal zinc finger domain could deprive the cell of an important mechanism for regulating cell proliferation leading to the development of breast cancer.
Novel Two-Dimensional Modeling Approach for Aircraft Icing (2004)

A new modeling approach to tackle the challenging problem of in-flight icing prediction is formulated and verified. With use of this new approach, termed morphogenetic modeling, the shape, structural details, and density of aircraft ice accretions are predicted by emulating the behavior of individual fluid elements. A two-dimensional, morphogenetic model is used to predict the ice accretion forming on a cylinder over a range of in-flight conditions. The model predicts rime, glaze, and simultaneous glaze and rime accretions. A partial verification of the model has been successfully accomplished. Although there are some discrepancies between experimental and predicted accretion shapes, especially for large and wet accretions, the overall agreement is good. In particular, the prediction of the stagnation line growth rate agrees well with experimental data. The results of our exploratory research are encouraging and suggest that morphogenetic modeling has the potential to advance the simulation of in-flight icing. Practical implementation of this approach will require coupling the model to an external flowfield solver, as well as to heat transfer and droplet impingement solvers. Further verification and extension to three dimensions are planned.
Advanced Neutron Spectrometer (2013)

Energetic neutron measurements remain a challenge for space science investigations and radiation monitoring for human exploration beyond LEO. We are investigating a new composite scintillator design that uses Li6 glass scintillator embedded in a PVT block. A comparison between Li6 and Boron 10 loaded scintillators are being studied to assess the advantages and shortcomings of these two techniques. We present the details of the new Li6 design and results from the comparison of the B10 and Li6 techniques during exposures in a mixed radiation field produced by high energy protons interacting in a target material.
A fair message exchange framework for distributed multi-player games (2003)

This paper presents a framework for message delivery in real-time multi-player distributed interactive games that use the client-server model. Based on this framework, we propose message delivery algorithms that remove the unfair advantage that players with smaller message delays from the game server receive over players with large message delays from the server. The framework is very general in the sense that it does not require assumptions of synchronized clocks at the players and servers; neither does it require a mechanism to compute the one-way delay from the players to the server accurately. It also avoids the need for bucket synchronization that leads to messages being delayed by a fixed amount of time at the server. The framework is based on a proxy architecture that is independent of game applications.
Abstract 2749: A novel small molecule inhibitor targets the DNA double strand break repair protein Ku70/80 (2016)

Abstract Purpose: Non-Homologous End-Joining (NHEJ) is the primary pathway for the repair of DNA double strand breaks (DSBs) in human and mammalian cells. NHEJ is frequently upregulated in diverse solid malignancies and is a determining factor in the process of carcinogenesis. In addition, upregulation of the NHEJ pathway can reduce the efficiency of anti-cancer therapies including radiation or chemotherapy. Inhibition of NHEJ by siRNA reduces the growth of NHEJ-upregulated tumors and alleviates radiation-refractory disease. The Ku70/80 heterodimer is the central scaffolding protein of the NHEJ pathway, which recruits and activates all other key NHEJ factors. Therefore, Ku70/80 protein is a logical target for disruption of the NHEJ process. Experimental Procedures: We report the identification of a prospective binding pocket in the Ku70/80 crystal structure, located in close proximity to the DNA-binding domain and the Ku70/80 heterodimer interface. Based on this pocket, an idealized virtual ligand (‘protomol’) was created and utilized to screen ‘in silico’ an extensive database of small molecule compounds for potential ligands. Nine of the highest ranking hits were chosen for biological evaluation. Results: We identified one compound (designated ‘Compound L’), which proved capable of disrupting the in vitro binding of Ku70/80 to a DNA substrate in a dose-dependent manner with an IC50 of 3.5 μM. In addition, Compound L showed dose-dependent inhibition of DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKCS) activity, which requires Ku70/80 as a co-factor with an IC50 of 2.5 μM. Finally, we showed that Compound L synergistically sensitizes a glioblastoma cell line to ionizing radiation, with a marked sensitization at ∼20-25 μM. This latter observation clearly demonstrates the ability of Compound L to disrupt NHEJ-mediated repair of radiation-induced DSBs. Conclusions: Compound L is an active inhibitor of the Ku70/80 heterodimer. To the best of our knowledge, no such compound has been reported in the peer-reviewed literature. The structure of Compound L will be utilized as a scaffold for a ‘structure-activity relationship’ (SAR) based hit-to-lead drug development aimed at designing a novel class of anti-cancer agents targeting the Ku70/80 heterodimer. We predict Ku70/80 inhibitors would have applicability as single-modality drugs, following a synthetic lethality approach, or as sensitizing agents for concurrent radiation or chemotherapy in a variety of solid malignancies. Support: P30 CA023074. Citation Format: Daruka Mahadevan, Alfred C. Gallegos, Lauren N. Dominick, Laurence S. Cooke, Trace N. Bartels, Josef Vagner, Terry O. Matsunaga, Eric Weterings. A novel small molecule inhibitor targets the DNA double strand break repair protein Ku70/80. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2749.
Endocardial detection of repolarization alternans (2003)

Repolarization alternans (RPA) is prognostic of sudden cardiac death and is thought to be mechanistically linked to the initiation of ventricular tachyarrhythmias. Thus, implantable cardiac device detection of RPA may be therapeutically valuable. Because alternans detection is currently limited to surface electrocardiograms, we investigated whether RPA could be measured using a single right-ventricular endocardial lead in humans. Such a location was chosen because it is consistent with the requirements for long-term implantable-device implementation. During diagnostic electrophysiological testing, 28 patients (23 male, 5 female; 61 +/- 15 years) were evaluated for surface T-wave alternans (TWA; the current "gold standard" for RPA detection) and endocardial RPA during 5 min of 550-ms right-atrial pacing. Power spectral analysis indicated that 11/28 patients had both surface TWA and endocardial RPA, 9/28 patients had neither, and 8/28 patients had discordant results (71% concordance; p = 0.02). Importantly, unlike surface TWA, endocardial RPA was detectable on a beat-to-beat basis. Given the putative mechanistic link between RPA and ventricular arrhythmias, beat-to-beat endocardial RPA detection might be of diagnostic or therapeutic utility.
Integrated Optics Implementation Of A Fiber Optic Rotation Sensor: Analysis And Development (1987)

The Jet Propulsion Laboratory is developing a Fiber Optic Rotation Sensor (FORS) for use on the Mariner Mark II series of planetary explorer craft and in other space applications. FORS is a closed-loop, phase-nulling device and embodies a number of interesting innovations. Chief among these are the incorporation of the device's couplers, phase modulators and polarizer on a single lithium niobate (LiNbO<sub>3</sub>) integrate optics chip and a novel means of reading out angular position and rotation rate based on optical beat detection Various aspects of the FORS design and operation are described and discussed. Particular attention is paid to analyzing errors attributable to polarizer imperfection and the so-called residual Michelson effect.
High<sub>χ</sub> block copolymers for directed self-assembly patterning without the need for topcoat or solvent annealing (2017)

High-χ block copolymers for directed self-assembly (DSA) patterning that do not need topcoat or solvent annealing have been developed. A variety of functionalities have been successfully added into the block copolymers, such as balanced surface energy between the polymer blocks, outstandingly high χ, tunable glass transition temperature (Tg), and selective crosslinking. Perpendicular orientation control, as desired for patterning, of the block copolymers can be simply achieved by thermal annealing due to the equal surface energy of the polymer blocks at the annealing temperatures, which allows avoiding solvent annealing or top-coat. The χ value can be tuned up to achieve L0 as low as 8-10 nm for lamellar-structured block copolymers and hole/pillar size as small as 5-6 nm for cylinder-structured block copolymers. The Tg of the block copolymers can be tuned to improve the kinetics of thermal annealing by enhancing the polymer chain mobility. Block-selective crosslinking facilitates the pattern transfer by mitigating pattern collapse during wet etching and improving oxygen plasma etching selectivity between the polymer blocks. This paper provides an introductory review of our high-χ block copolymer materials with various functionalities for achieving improved DSA performance.
Use of granular NbN as a superconducting bolometer (1981)

An ultrathin film of granular NbN is used as a superconducting bolometer. The bolometer has a high operating temperature (∼12 K), is very sensitive (∼5000 Ω/deg), and exhibits a fast thermal response time, which is estimated to be less than 10−10 sec.
Observer-tracking autostereoscopic 3D display systems (1997)

This paper presents an examination of the requirements for observer tracking autostereoscopic 3D display systems. The optical requirements for the imaging of autostereoscopic viewing windows in order to maintain high image quality over a large range of observer positions are described. A number of novel displays based on LCD (liquid crystal display) technology have been developed and demonstrated at Sharp Laboratories of Europe Ltd (SLE). This includes an electronically switchable illuminator for the macro-optic twin-LCD display; and a compact micro-optic twin-LCD display which maintains image quality while extending display size and viewing freedom. Work has also been in progress with flat panel displays to improve window quality using a new arrangement of LCD pixels. This has led to a new means to track such a display with no moving parts.
Gate-on-germanium source tunnel field-effect transistor enabling sub-0.5-V operation (2014)

Abstract In this paper, a novel device structure for a gate-on-germanium source (GoGeS) tunnel field-effect transistor (TFET) on a bulk silicon substrate is proposed for sub-0.5-V operation. Tunneling in line with the gate electric field, which increases the effective tunneling area and, hence, the ON-state current ( I ON ) is achieved in this device by constructing its gate on the germanium source region. To improve the subthreshold swing ( SS ), lateral carrier tunneling is eliminated by carefully designing the device structure. The use of a small gate-to-channel overlap results in reduced fringing-induced barrier lowering at the gate edge that further improves the SS and I ON of the device. The spreading of the fringing electric field is also reduced by employing a step in the silicon channel region, which again improves both SS and I ON . As a result of all these, supersteep SS and high I ON are achieved, enabling sub-0.5-V operation of the proposed GoGeS TFET.
Effectiveness and efficiency of three-dimensional shape retrieval (2005)

The effectiveness and efficiency of a content-based three-dimensional shape search system are investigated for supporting the re-use of engineering designs. Search effectiveness is characterized by precision and recall values from repeated search experiments. We extract four feature vectors from each three-dimensional shape and compare them for effectiveness. The performance of an R-tree-based index structure is also evaluated to characterize search efficiency. Search efficiency is evaluated by the ratio of the number of visited nodes in a search operation to the number of nodes in a database index. A multi-step refinement approach is proposed to improve search effectiveness. Based on the results of the experiments with a database of real models, the effectiveness of using multi-step refinement is predicted to be 51% higher than that of one-shot search using a single feature vector, although the difference becomes smaller when the number of retrieved shapes is larger. The R-tree index significantly improves the efficiency of our search system. Search efficiency decreases with the dimensionality of the data records and the capacity of database nodes. Based on our experiments with the synthetic database, the efficiency is predicted to be stable when the size of a database increases.
High-sensitivity nanometer-scale infrared spectroscopy using a contact mode microcantilever with an internal resonator paddle (2010)

Infrared (IR) spectroscopy is one of the most widely used techniques for identifying and characterizing materials, but is diffraction limited to a spatial resolution of no smaller than several micrometers. This paper reports IR spectroscopy with 100 nm spatial resolution, using a tunable laser whose absorption in an organic layer is measured via atomic force microscopy. Wavelength-dependent absorption in the sample results in local thermomechanical deformation, which is sensed using the sharp tip of a resonant atomic force microscope cantilever. We introduce a cantilever and system design capable of 100 nm spatial resolution and a 6 x sensitivity improvement over previous approaches.
Tat-SF1: Cofactor for Stimulation of Transcriptional Elongation by HIV-1 Tat (1996)

Tat may stimulate transcriptional elongation by recruitment of a complex containing Tat-SF1 and a kinase to the human immunodeficiency virus-type 1 (HIV-1) promoter through a Tat-TAR interaction. A complementary DNA for the cellular activity, Tat-SF1, has been isolated. This factor is required for Tat trans-activation and is a substrate of an associated cellular kinase. Cotransfection with the complementary DNA for Tat-SF1 specifically modulates Tat activation. Tat-SF1 contains two RNA recognition motifs and a highly acidic carboxyl-terminal half. It is distantly related to EWS and FUS/TLS, members of a family of putative transcription factors with RNA recognition motifs that are associated with sarcomas.
Development of Diphenethylamines as Selective Kappa Opioid Receptor Ligands and Their Pharmacological Activities (2020)

Among the opioid receptors, the kappa opioid receptor (KOR) has been gaining substantial attention as a promising molecular target for the treatment of numerous human disorders, including pain, pruritus, affective disorders (i.e., depression and anxiety), drug addiction, and neurological diseases (i.e., epilepsy). Particularly, the knowledge that activation of the KOR, opposite to the mu opioid receptor (MOR), does not produce euphoria or leads to respiratory depression or overdose, has stimulated the interest in discovering ligands targeting the KOR as novel pharmacotherapeutics. However, the KOR mediates the negative side effects of dysphoria/aversion, sedation, and psychotomimesis, with the therapeutic promise of biased agonism (i.e., selective activation of beneficial over deleterious signaling pathways) for designing safer KOR therapeutics without the liabilities of conventional KOR agonists. In this review, the development of new KOR ligands from the class of diphenethylamines is presented. Specifically, we describe the design strategies, synthesis, and pharmacological activities of differently substituted diphenethylamines, where structure-activity relationships have been extensively studied. Ligands with distinct profiles as potent and selective agonists, G protein-biased agonists, and selective antagonists, and their potential use as therapeutic agents (i.e., pain treatment) and research tools are described.
A DNA Segment Controlling Metal-Regulated Expression of the <i>Drosophila Melanogaster</i> Metallothionein Gene <i>Mtn</i> (1987)

Cloned fragments of DNA including the Drosophila melanogaster metallothionein gene Mtn and different amounts of 5' flanking sequences were introduced into flies by P-element-mediated germ line transformation. Comparison of RNA levels in different transformants revealed that metal-regulated and tissue-specific expression of Mtn requires no more than 373 base pairs upstream of the initiation site of transcription. Transformants having an additional, transcribed copy of Mtn could tolerate increased concentrations of cadmium, indicating that Mtn expression is directly related to this phenotype. In separate experiments, these D. melanogaster promoter sequences were fused to the coding sequences of the herpes simplex virus thymidine kinase (TK) gene. After transfection of this fusion into baby hamster kidney cells, increases in TK activity and accumulation of TK RNA were inducible by metals. A series of 5' and 3' deletions showed that D. melanogaster sequences from -130 to -6 were sufficient to confer metal-regulated expression to the TK gene. The function of the D. melanogaster metallothionein promoter in mammalian cells indicates that the mechanism controlling metal regulation is evolutionarily conserved.
A Spray-Based Method for the Production of Semiconductor Nanocrystals (2005)

We present a spray based-method for the formation and production of semiconductor nanocrystals that provides an attractive alternative to the commonly used epitaxial and colloidal procedures. According to this spray-based method, mainly thermospray, solutions of semiconductor salts are first sprayed into monodispersed droplets, which subsequently become solid nanocrystals by solvent evaporation. A semiconductor nanocrystal is produced from a single spray droplet upon the full vaporization of the solvent. The average diameter and size distribution of the final nanocrystals are controlled and determined by the solute concentration of the sprayed solution and by the droplet size, hence by the spray production parameters. The spray-produced nanocrystals are collected on any selected solid support. Representative results, shown in this letter, reveal the formation of CdS nanocrystals in the size range of 3 to 6 nanometers and with a size distribution of as low as five percent. A further structural analysis of these nanocrystals showed that they were formed in the zinc blend phase with a high degree of crystallinity.
A Synthetic Biology Approach to Engineer a Functional Reversal of the β-Oxidation Cycle (2012)

While we have recently constructed a functional reversal of the β-oxidation cycle as a platform for the production of fuels and chemicals by engineering global regulators and eliminating native fermentative pathways, the system-level approach used makes it difficult to determine which of the many deregulated enzymes are responsible for product synthesis. This, in turn, limits efforts to fine-tune the synthesis of specific products and prevents the transfer of the engineered pathway to other organisms. In the work reported here, we overcome the aforementioned limitations by using a synthetic biology approach to construct and functionally characterize a reversal of the β-oxidation cycle. This was achieved through the in vitro kinetic characterization of each functional unit of the core and termination pathways, followed by their in vivo assembly and functional characterization. With this approach, the four functional units of the core pathway, thiolase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydratase, and acyl-CoA dehydrogenase/trans-enoyl-CoA reductase, were purified and kinetically characterized in vitro. When these four functional units were assembled in vivo in combination with thioesterases as the termination pathway, the synthesis of a variety of 4-C carboxylic acids from a one-turn functional reversal of the β-oxidation cycle was realized. The individual expression and modular construction of these well-defined core components exerted the majority of control over product formation, with only highly selective termination pathways resulting in shifts in product formation. Further control over product synthesis was demonstrated by overexpressing a long-chain thiolase that enables the operation of multiple turns of the reversal of the β-oxidation cycle and hence the synthesis of longer-chain carboxylic acids. The well-defined and self-contained nature of each functional unit makes the engineered reversal of the β-oxidation cycle "chassis neutral" and hence transferrable to the host of choice for efficient fuel or chemical production.
Multitarget Stool RNA Test for Noninvasive Detection of Colorectal Neoplasia in a Multicenter, Prospective, and Retrospective Cohort (2021)

The RNA-FIT assay demonstrated clinically relevant detection of all grades of colorectal neoplasia, including carcinomas, AAs, and ONAs. This assay could represent a noninvasive option to screen for both CRC and precancerous adenomas.