gebhart/patrepeval huggingface dataset:
Basal repression of BRCA1 by multiple E2Fs and pocket proteins at adjacent E2F sites (2006)

The BRCA1 gene is rarely mutated in sporadic tumors, although numerous studies suggest that the expression of this critical tumor suppressor gene is frequently downregulated in tumors derived from a wide range of tissues. However, little is known regarding the mechanisms by which BRCA1 is transcriptionally regulated in human cells in vivo. We have shown recently that the tumor microenvironmental stress of hypoxia induces an E2F-dependent repression of BRCA1 in cancer cells. Here, we report that multiple E2Fs and associated factors bind the BRCA1 promoter at two adjacent E2F sites in the proximal promoter region of the gene, as detected by quantitative chromatin immunoprecipitation (ChIP) analysis. Intriguingly, our data suggest that E2F1 and E2F4 bind the BRCA1 proximal promoter simultaneously at the two E2F sites, although E2F4 appears to be the predominant E2F bound in log-phase cells. In contrast to previous studies, we have also detected promoter occupancy by the pocket proteins p130 and p107, but not Rb, our data indicate that E2F4 and p130/p107 complexes basally repress the BRCA1 promoter. We find that binding by these factors requires both intact E2F sites, which suggests a novel interaction between adjacent promoter elements. Taken together, these findings provide an enhanced molecular portrait of BRCA1 transcriptional regulation by E2Fs and pocket proteins, they enhance our understanding of regulation by repressive E2F complexes at target genes in vivo. Furthermore, the identification of E2F4 and p130/p107 complexes as basal repressors of BRCA1 expression may facilitate the development of strategies based on disruption of these interactions to rescue BRCA1 expression in human tumors.
Quasi-cw 3-W diffraction-limited diode-to-diode optical amplifier (1992)

Recently, broad-area (600 × 1000 μm2) amplifiers have demonstrated up to 12-W peak power diffraction-limited emission when injected with a 0.5-W tunable Ti:sapphire master laser,1 From a practical point of view, semiconductor amplifier systems should be based on a low power single-mode diode laser to minimize size and maximize efficiency. In this paper we show >3.2 W of diffraction-limited emission from a double-pass amplifier injected with a diode laser emitting 60 mW.
Preclinical Assessment of CAR T-Cell Therapy Targeting the Tumor Antigen 5T4 in Ovarian Cancer (2017)

Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome both quantitative and qualitative shortfalls of the host immune system relating to the detection and subsequent destruction of tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step in the ability to utilize CAR T cells for the treatment of cancer. The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer. Matched blood and tumor samples were collected from 12 patients with ovarian cancer; all tumors were positive for 5T4 expression by immunohistochemistry. Patient T cells were effectively transduced with 2 different anti-5T4 CAR constructs which differed in their affinity for the target antigen. Co-culture of CAR T cells with matched autologous tumor disaggregates resulted in antigen-specific secretion of IFN-gamma. Furthermore, assessment of the efficacy of anti-5T4 CAR T cells in a mouse model resulted in therapeutic benefit against established ovarian tumors. These results demonstrate proof of principle that 5T4 is an attractive target for immune intervention in ovarian cancer and that patient T cells engineered to express a 5T4-specific CAR can recognize and respond physiologically to autologous tumor cells.
A Systematic Review and Meta-Analysis of Diagnostic Performance of MRI for Evaluation of Acute Appendicitis (2016)

MRI has a high accuracy for the diagnosis of acute appendicitis, for a wide range of patients, and may be acceptable for use as a first-line diagnostic test.
A mutation in the insulin receptor that impairs proreceptor processing but not insulin binding. (1994)

Here we report the identification of a new mutation in the alpha-chain of the insulin receptor, changing Trp412 into Ser using DNA from consanguineous parents who gave birth to a child with leprechaunism. The mutant receptor was expressed stably in CHO and transiently in COS-1 cells. It was found that the Ser412 mutant is not cleaved into alpha- and beta-subunits and remains as a 210-kDa proreceptor at an intracellular site. This property of the mutant receptor is in line with the observed decreased insulin binding to the parental fibroblasts. Cross-linking experiments show that the Ser412 proreceptor is able to bind insulin with an affinity comparable to that of the wild-type alpha-chain. Despite its capacity to bind insulin, the mutant receptor is not autophosphorylated. We postulate that the patient was homozygous for the Trp412-->Ser mutation and that the mutation was responsible for the leprechaun phenotype. This is the first description of a transport-defective receptor with the mutation outside the tetrabasic processing site and a functional insulin binding domain. The ability of the Ser412 mutant to bind insulin in cross-linking experiments suggests that the impaired transport of the proreceptor to the cell surface is the primary cause for the binding defect to intact cells.
ChemInform Abstract: Mechanistic Investigation on the Remote Pummerer Reaction of 1,5‐Dithiacyclooctane 1‐Oxide with Acetic Anhydride via Intermediate Formation of Disulfide Dication. (1990)

Abstract The Pummerer reaction of (I) leading to the acetates (V) and (VI) is shown to proceed via a rapid oxygen scrambling in (I) and the tight ion pair (IV).
Caries risk assessment: methods available to clinicians for caries detection (2005)

It is hypothesized that occlusal lesions are initiated on the fissure walls and can therefore be obscured by sound superficial tissue. Additionally, there is evidence that one effect of regular use of fluorides is greater opacity of enamel, which may obscure underlying lesions in dentin, the so-called 'hidden lesions'. Dental radiographs are inadequate for detecting decay in the occlusal surfaces until the lesion is well advanced through the enamel and into the dentin. The clinician relies on visual observation of texture and discoloration, clinical judgment based upon experience, and on tactile sense by probing with an explorer. An objective detection method to complement the traditional visual assessment is used by the clinician for arriving at clinical decisions on the management of the carious lesion: whether invasive therapy or a more conservative, noninvasive approach. Objective and reliable longitudinal monitoring of the lesion's response to preventive measures allow the selection of an appropriate therapy before the lesion progresses to the stage where invasive treatment is required. This paper discusses the problem of the lack of appropriate clinical methods for the detection and quantification of carious lesions. A few commercially available methods are described (the quantitative light-induced fluorescence method, the DIAGNOdent device, and electrical caries monitor) and some new techniques mentioned.
O direito constitucional e sua interface histórica (2019)

O presente estudo objetiva analisar o salutar papel da Historia para o Direito, mormente para o Direito Constitucional, com um breve escorco historico-constitucional, analise sobre a evolucao humana e as teorias constitucionais. A elaboracao do estudo se perfectibilizou atraves de pesquisa bibliografica, bem como de apontamentos de minha visao pessoal a respeito do tema. A Historia do Direito e a ciencia vital que dirige o Direito, alem de permitir a comparacao de sistemas juridicos, auxiliando os governantes a trilhar um melhor caminho no Direito. De modo que nao e possivel estudar o Direito sem o conhecimento da Historia que o originou e o formou, pois com a constante evolucao do Estado, de suas estruturas politicas e governamentais, vai sendo adequado permanentemente de uma forma ou outra o Direito aplicado, trazendo uma nova ideia a respeito das teorias da Constituicao. Ao passo que, as teorias somente poderiam ser aplicadas em estado de absoluta normalidade e paz incontestavel, o que quase nunca se efetivou na historia humana. Seja nas democracias, seja nas ditaduras, o desconhecimento da Historia enseja a repeticao de erros pelos que detem o poder, posto que nao ha Historia sem Direito e nao ha Direito sem Historia.
A Performance Study of Alternative Object Faulting and Pointer Swizzling Strategies (1992)

This paper presents a portable, efficient method for accessing memory resident persistent objects in virtual memory in the context of the E programming language. Under the approach, objects are copied from the buffer pool of the underlying object manager into virtual memory on demand, as they are accessed by an E program. The cumulative effects of updates to a persistent object are then propagated back to the object manager via a single write operation at the end of each transaction. The method incorporates a comprehensive pointer swizzling mechanism to enhance performance. Swizzling is done a pointer-at-a-time and software checks are used to detect the use of swizzled pointers. The paper also presents the results of a performance study comparing the method presented here with several alternative software architectures including ObjectStore V1.2, a commercially available OODBMS. The results highlight the tradeoffs between providing software vs. memory-mapped support for pointer swizzli...
Regulation of the Neutrophil Respiratory Burst Oxidase (1998)

Superoxide generation by the neutrophil respiratory burst oxidase (NADPH oxidase) can be reconstituted in a cell-free system using flavocytochrome b558 and the cytosolic proteins p47(phox), p67(phox), and Rac. p47(phox) functions as an adaptor protein; it increases the affinity of p67(phox) and Rac in the NADPH oxidase complex, but is not essential when high concentrations of these proteins are used (Freeman, J. L., and Lambeth, J. D. (1996) J. Biol. Chem. 271, 22578-22582), implying that p67(phox) and/or Rac directly regulates enzyme activity. Herein, we describe an activation domain in p67(phox) that is essential for NADPH oxidase activity. A series of C-terminal truncation mutants of p67(phox) showed that residues 211 to the C terminus (residue 526) are not needed for cell-free activity. However, shorter truncations were inactive, pointing to an activation domain within the region spanning residues 199-210. p67(phox) mutated at single amino acid residues within this region showed diminished activity, and p67(phox) V204A was completely inactive. The effects of mutations on activity were independent of p47(phox), and mutations did not affect the binding of p67(phox) to Rac. In the presence of wild-type p67(phox), the V204A mutant was a potent inhibitor of superoxide generation, and inhibition was partially reversed by high concentrations of p67(phox), but not by p47(phox) or Rac. The V204A mutant competed with native p67(phox) for translocation to neutrophil plasma membrane, indicating that p67(phox) V204A assembles to form an inactive complex. The data imply a direct activation of flavocytochrome b558 by an activation domain in p67(phox).
Optimal trade-off filters for noise robustness, sharpness of the correlation peak, and Horner efficiency (1991)

Filters that have optimal trade-offs among the criteria of noise robustness, sharpness of the correlation peak, and Horner efficiency are presented, and an explicit mathematical expression is provided. Owing to their optimality, these filters provide a figure of merit and then permit a rigorous characterization of filter performances for optical pattern recognition.
Measuring Traffic on the Wireless Medium: Experience and Pitfalls (2002)

A number of measurement studies have examined traffic characteristics in wireless networks.Most of these measurements [1], [6], [7] have been conducted from the wired portion of the network.In this paper we argue that such measurements are not sufficient to expose either the characteristics of the wireless medium or how such characteristics impact traffic patterns.While it is easier to make consistent measurements in the wired part of a network, such measurements can not observe the significant vagaries present in the wireless medium itself.As a consequence constructing an efficient and accurate measurement system from a wireless vantage point is important but usually quite difficult.In our work we have explored the various issues in implementing such a system to monitor traffic in an 802.11 based wireless network.We identify different challenges in making such measurements and provide detailed experimental evidence in their supports.Our work shows that the wireless measurement allows us to infer much richer information about the medium characteristics than is possible with a measurements made on the wired part of the network.We apply our measurement technique to study the end-to-end wireless network delay.We show that wireless monitoring can effectively identify the causes of end-to-end delays.
The Use of Hidden Markov Model in Natural ARABIC Language Processing: a survey (2017)

Hidden Markov Model is an empirical tool that can be used in many applications related to natural language processing. In this paper a comparative study was conducted between different applications in natural Arabic language processing that uses Hidden Markov Model such as morphological analysis, part of speech tagging, text classification, and name entity recognition. Comparative results showed that HMM can be used in different layers of natural language processing, but mainly in pre-processing phase such as: part of speech tagging, morphological analysis and syntactic structure; however in high level applications text classification their use is limited to certain number of researches.
Timing, Duration, and Transitions of the Last Interglacial Asian Monsoon (2004)

Thorium-230 ages and oxygen isotope ratios of stalagmites from Dongge Cave, China, characterize the Asian Monsoon and low-latitude precipitation over the past 160,000 years. Numerous abrupt changes in 18O/16O values result from changes in tropical and subtropical precipitation driven by insolation and millennial-scale circulation shifts. The Last Interglacial Monsoon lasted 9.7 +/- 1.1 thousand years, beginning with an abrupt (less than 200 years) drop in 18O/16O values 129.3 +/- 0.9 thousand years ago and ending with an abrupt (less than 300 years) rise in 18O/16O values 119.6 +/- 0.6 thousand years ago. The start coincides with insolation rise and measures of full interglacial conditions, indicating that insolation triggered the final rise to full interglacial conditions.
Webwrap and the Law of Contracts (1999)

Abstract The Internet provides a prime location to anyone who wishes to conduct business. An individual with a product or service to sell can operate out of his garage and do business on the Internet. Even the smallest businesses can establish a presence and conduct transactions anywhere in the world and at a fraction of the cost of traditional marketing methods.
An Approach for Characterization and Lumping of Plus Fractions of Heavy Oil (2010)

Summary Heavy-oil fluids contain large concentrations of high-molecular-weight components, including a large content of the plus fractions, such as C7+. Different approaches have been developed to characterize the petroleum plus fractions to improve prediction of the pseudocomponents properties by equations of state (EOSs). A method is developed in this work to split the plus fraction into single carbon numbers (SCN), generating the mole fraction and the respective molecular weight. The developed method is based on the relationships between three-parameter gamma (TPG) distribution, experimental mole fraction, molecular weight, and SCN data obtained from the literature and industrial contacts. TPG is used to fit the trend of the compositional analysis. The characterized mole distribution as a function of SCNs is generated by integrating the TPG between the limiting molecular weights (LMw). The limiting molecular weights are determined simultaneously during the integration process by fitting the characterized and experimental mole fractions. The developed method is easy to use. In addition, the approach is not dependent on the assumption that only normal carbon numbers exist in the composition resulting on fixed molecular weights for each single carbon number. There are several correlations generated to predict physicochemical properties as a function of SCNs. Those correlations have been originally developed to work with light oil. Our approach is combined with some of the correlations and is tested for heavy-oil samples to identify the ranges in which they can be applied. Two lumping schemes are used to group the SCNs into pseudocomponents. The properties for each pseudo-component in this work are used to predict pressure/volume/temperature (PVT) data, constant volume depletion, using the Peng-Robinson EOS (PR-EOS), and the PVTP™ commercial simulator.
Beam Tracking for UAV Mounted SatCom on-the-Move With Massive Antenna Array (2018)

Unmanned aerial vehicle (UAV)-satellite communication has drawn dramatic attention for its potential to build the integrated space-air-ground network and the seamless wide-area coverage. A key challenge to UAV-satellite communication is its unstable beam pointing due to the UAV navigation, which is a typical SatCom on-the-move scenario. In this paper, we propose a blind beam tracking approach for Ka-band UAV-satellite communication system, where UAV is equipped with a hybrid large-scale antenna array. The effects of UAV navigation are firstly released through the mechanical adjustment, which could approximately point the beam towards the target satellite through beam stabilization and dynamic isolation. Specially, the attitude information for mechanical adjustment can be realtimely derived from data fusion of low-cost sensors. Then, the precision of beam pointing is blindly refined through electrically adjusting the weight of the massive antennas, where an array structure based simultaneous perturbation algorithm is designed. Simulation results are provided to demonstrate the superiority of the proposed method over the existing ones.
Antioxidant Effects of Plant Extracts on Free Radicals and Lipid Peroxidation (2003)

Reactive oxygen species damage biomolecules such as lipids, proteins, sugars and DNA, which can not only lead to various diseases but also oxidative damage resulting aging. In order to search for antioxidants from plants, the antioxidant effects of the MeOH extracts from 182 plants were evaluated. The results showed that thirteen plant extracts exhibited antioxidant activity (>80%) in DPPH radical assay, seven plant extracts demonstrated antioxidant activity (>40%) in the hydroxy1 radical assay and eighteen plant extracts were active (>80%) in the lipid peroxidation assay. In particular, the extracts of Distylium racemosum (Hamamelidaceae), Astilbe korena (Saxifragaceae), Astilbe chinensis and Euphorbia supina (Euphorbiaceae) were identified as potent principles of antioxidant activity in all the assay systems.
Angiotensin II Induces Skeletal Muscle Wasting through Enhanced Protein Degradation and Down-Regulates Autocrine Insulin-Like Growth Factor I* (2001)

We previously showed that angiotensin II (ang II) infusion in the rat produces cachexia and decreases circulating insulin-like growth factor I (IGF-I). The weight loss derives from an anorexigenic response and a catabolic effect of ang II. In these experiments we assessed potential catabolic mechanisms and the involvement of the IGF-I system in these responses to ang II. Ang II infusion caused a significant decrease in body weight compared with that of pair-fed control rats. Kidney and left ventricular weights were significantly increased by ang II, whereas fat tissue was unchanged. Skeletal muscle mass was significantly decreased in the ang II-infused rats, and a reduction in lean muscle mass was a major reason for their overall loss of body weight. In skeletal muscles, ang II did not significantly decrease protein synthesis, but overall protein breakdown was accelerated; inhibiting lysosomal and calcium-activated proteases did not reduce the ang II-induced increase in muscle proteolysis. Circulating IGF-I levels were 33% lower in ang II rats vs. control rats, and this difference was reflected in lower IGF-I messenger RNA levels in the liver. Moreover, IGF-I, IGF-binding protein-3, and IGF-binding protein-5 messenger RNAs in the gastrocnemius were significantly reduced. To investigate whether the reduced circulating IGF-I accounts for the loss in muscle mass, we increased circulating IGF-I by coinfusing ang II and IGF-I, but this did not prevent muscle loss. Our data suggest that ang II causes a loss in skeletal muscle mass by enhancing protein degradation probably via its inhibitory effect on the autocrine IGF-I system.
Continuous intranigral infusion is not associated with observable behavioral deficits or marked pathology: a preclinical safety study (2016)

OBJECTIVE A better understanding of the effects of chronically delivering compounds to the substantia nigra and nearby areas is important for the development of new therapeutic approaches to treat alpha-synucleinopathies, like Parkinson's disease. Whether chronic intranigral delivery of an infusate could be achieved without causing motor dysfunction or marked pathology remains unclear. The authors evaluated the tolerability of continuously delivering an infusate directly into the rhesus monkey substantia nigra via a programmable pump coupled to a novel intraparenchymal needle-tip catheter surgically implanted using MRI-guided techniques. METHODS The MRI contrast agent gadopentetate dimeglumine (Magnevist, 5 mM) was used to noninvasively evaluate catheter patency and infusion volume associated with 2 flow rates sequentially tested in each of 3 animals: 0.1 µl/min for 14 days into the right substantia nigra and 0.1 µl/min for 7 days plus 0.2 µl/min for an additional 7 days into the left substantia nigra. Flow rate tolerability was assessed via clinical observations and a microscopic examination of the striatum and midbrain regions. RESULTS Evaluation of postsurgical MRI indicated that all 6 catheters remained patent throughout the study and that the volume of distribution achieved in the left midbrain region at a rate of up to 0.2 µl/min (2052 ± 168 mm<sup>3</sup>) was greater than that achieved in the right midbrain region at a constant rate of 0.1 µl/min (1225 ± 273 mm<sup>3</sup>) by nearly 2-fold. Both flow rates provided sufficient infusate coverage of the rhesus (and possibly the human) midbrain region. There were no indications of observable deficits in behavior. Histopathological evaluations confirmed that all catheter tips were placed in or near the pars compacta region of the substantia nigra in all animals. There was no evidence of infection at any of the 6 catheter sites. Mild to moderate microglial reactions were observed at most catheter track sites and were comparable between the 2 infusion rates. Finally, there was neither observable decrease of tyrosine hydroxylase staining in the striatum nor detectable necrosis of neurons in the pars compacta region of the substantia nigra in any of the animals. CONCLUSIONS The data from this study support the feasibility of using a pump-and-catheter system for chronic intranigral infusion and lay the foundation for using this approach to treat Parkinson's disease or other related degenerative diseases that would benefit from targeted drug delivery to the substantia nigra or to other brainstem regions.