gebhart/patrepeval huggingface dataset:
Repeated B motifs in the human immunodeficiency virus type I long terminal repeat enhancer region do not exhibit cooperative factor binding. (1988)

The enhancer element of the human immunodeficiency virus type I (HIV-I) long terminal repeat (LTR) contains two copies of nearly identical sequences AGGGACTTTCC (3G sequence) and GGGGACTTTCC (4G sequence) that are important in transcriptional regulation. A single copy of the 4G sequence is found in the NF-kappa B site of the immunoglobulin kappa-chain enhancer. Only the 4G motif in the HIV enhancer is bound by cellular proteins in extracts prepared from unstimulated HeLa cells, whereas the 3G and 4G motifs are bound by factors in extracts prepared from HeLa cells treated with phorbol esters [phorbol 12-myristate 13-acetate (PMA)] and lymphoid cells. To determine if this change in binding to the HIV enhancer was due to phosphorylation of a cellular protein, partially purified PMA-treated HeLa nuclear extracts were digested with calf intestinal phosphatase. Phosphatase digestion of nuclear extracts from PMA-treated HeLa cells markedly decreased factor binding to the HIV enhancer. Accordingly, phosphorylation of the DNA binding protein itself, or an inhibitor protein present in the partially purified extract, must mediate binding to the recognition sequence. Binding studies confirmed that each of the enhancer sequences was capable of binding factors independent of the activity of the other site and that the HIV enhancer was occupied by only one factor at any one time. Chloramphenicol acetyltransferase assays using mutants in either one or both HIV enhancer repeats revealed that each site was capable of functioning as a tat-inducible enhancer element in PMA-treated HeLa cells. These results suggest that the 3G and 4G motifs in the HIV enhancer function independently and that duplication in the HIV enhancer augments activity by a mechanism distinct from cooperative binding of NF-kappa B.
Constraint-based geolocation of internet hosts (2004)

Geolocation of Internet hosts enables a diverse and interesting new class of location-aware applications. Previous measurement-based approaches use reference hosts, called landmarks, with a well-known geographic location to provide the location estimation of a target host. This leads to a discrete space of answers, limiting the number of possible location estimates to the number of adopted landmarks. In contrast, we propose Constraint-Based Geolocation (CBG), which infers the geographic location of Internet hosts using multilateration with distance constraints, thus establishing a continuous space of answers instead of a discrete one. CBG accurately transforms delay measurements to geographic distance constraints, and then uses multilateration to infer the geolocation of the target host. Our experimental results show that CBG outperforms the previous measurement-based geolocation techniques. Moreover, in contrast to previous approaches, our method is able to assign a confidence region to each given location estimate. This allows a location-aware application to assess whether the location estimate is sufficiently accurate for its needs.
Arterial and Aortic Valve Calcification Abolished by Elastolytic Cathepsin S Deficiency in Chronic Renal Disease (2009)

The present study provides direct in vivo evidence that catS-induced elastolysis accelerates arterial and aortic valve calcification in CRD, providing new insight into the pathophysiology of cardiovascular calcification.
Association and Dissociation Kinetics of Anti-Hen Egg Lysozyme Monoclonal Antibodies HyHEL-5 and HyHEL-10 (1998)

The immunoglobulin G1 (IgG1) kappa antibodies HyHEL-5 and HyHEL-10 interact with nonoverlapping epitopes on hen egg lysozyme (HEL); the HyHEL-5/HEL interface has two energetically and structurally important salt links, whereas the HyHEL-10/HEL interface involves predominantly hydrogen bonds and van der Waals interactions. The kinetics of association and dissociation of antibodies HyHEL-5 and HyHEL-10 with HEL under a variety of conditions were investigated in this study. The association of each antibody with HEL follows second-order kinetics. The association process is significantly diffusion-limited, as indicated by the viscosity dependence of the interaction of both antibodies with HEL, although detailed energetics suggest that the association process may be more complex. The association rate constant for the HyHEL-5/HEL system is within a factor of 2 of the modified Smoluchowski estimate for proteins of this size, whereas HyHEL-10 interacts with HEL with an association rate an order of magnitude lower. The association reactions are insensitive to ionic strength, showing only a twofold decrease in the association rate constant when the ionic strength was increased from 27 mM to 500 mM. Interestingly, the association rate constant for the interaction of HyHEL-5 with HEL varies with pH in the range 6.0-10.0, whereas HyHEL-10/HEL association is not affected by pH in the same range. The dissociation of the HyHEL-5/HEL and HyHEL-10/HEL complexes follow first-order kinetics with half-lives at 25 degrees C of approximately 3,150 s and approximately 21,660 s, respectively.
The Role of CNI-1493 in the Function of Primary Microglia with Respect to Amyloid-β (2011)

Amyloid-β (Aβ) oligomer toxicity is a crucial factor in the development of Alzheimer's disease. Therefore, the aim of therapeutic research is to target the modification of secretase activity, increase Aβ degradation, reduce Aβ formation, and modulate Aβ-induced neuroinflammation. Recently, the p38 MAP kinase inhibitor CNI-1493 has been shown to reduce plaque load and has led to an improvement in memory performance in a transgenic mouse model. We examined the role of CNI-1493 in the microglial inflammatory response to Aβ using both a microglia cell line as well as primary microglia isolated from mesocortices. MTT assays were performed to quantify cell viability. FACS analysis was used to measure phagocytosis. We used ELISA to analyse cytokine concentrations in response to CNI-1493 treatment. Western-blot/Dot-blot techniques were used to show the interaction of CNI-1493 with Aβ-oligomers as well as to measure apoptosis in microglia cells. RT-PCR was used to analyze secretase expression, and secretase function was determined using fluorimetric assays. CNI-1493 is able to prevent oligomer formation as well as apoptosis in microglia. A significant reduction was found in the Aβ-induced release of IL-6 and TNF-α in the presence of CNI-1493. Phagocytosis is an essential Aβ removal mechanism and was enhanced by CNI-1493 in primary microglia. CNI-1493 also influenced the α-secretase product C83 with an increase in the treated cells, while a simultaneous reduction in Aβ secretion was also observed. We hypothesize that CNI-1493 not only reduces neuroinflammation and consequent neurodegeneration, but also leads to a shift in AβPP-processing towards the non-amyloidogenic pathway. Therefore, CNI-1493 is a promising candidate for the treatment of AD.
Why speech recognizers make errors ? a robustness view (2004)

The performance of large vocabulary speech recognizers often varies depending on the input speech and the quality of the trained models. The particular attributes that cause recognition errors are a research area that has not been well studied. This paper addresses this issue from a robustness perspective using a large amount of field data collected from natural language dialog services. In particular, we present a method for tracking time-varying or nonstationary extraneous events, such as music, background noise, etc. We show that this measure is a better predictor of recognition errors than a standard measure of stationary signal-to-noise ratio (SNR). Combining the two measures provides a data selection algorithm for detecting problematic speech.
Increase of brain tryptophan and stimulation of serotonin synthesis by salicylate (1973)

I ndirect evidence indicates that the rate‐limiting step in the synthesis of brain 5‐HT is the concentration of tryptophan in brain and not, as previously considered (G reen and S awyer , 1966), tryptophan hydroxylase. In fact this enzyme has a K m for its substrate much higher than the concentration of tryptophan normally present in the mammalian brain (J equier , L ovenberg and S joerdsma , 1967; J equier , R obinson , L ovesberg and S joerdsma , 1969; M cgeer , P eters and M cgeer , 1968). Tryptophan is the only amino acid circulating in plasma which is highly bound to serum proteins (M cmenamy and O ncley , 1958). We have previously shown that the free fraction of serum tryptophan controls the concentration of brain tryptophan and, therefore, 5‐HT synthesis as well (T agliamonte , B iggio and G essa , 1971d; G essa , B iggio and T agliamonte , 1972). Salicylate has been shown to displace tryptophan from its protein binding in plasma and to raise the free tryptophan concentration (M carthur and D awkins , 1969; S mith and L akatos , 1971). These considerations prompted us to study the effect of salicylate on tryptophan concentrations and 5‐HT metabolism in brain.
CCK‐B/gastrin receptors in human colorectal cancer (2001)

Structural alterations of CCK-B/gastrin receptors may account for increased growth-promoting effects of amidated gastrins in colorectal cancer.
Winning WNT: Race to Wnt signaling inhibitors (2011)

More than a quarter of a century ago, a mammalian homolog of Drosophila wingless, int-1 (Wnt1), was identified as an oncogenic viral integration site in mouse breast cancer (1). A decade later, deregulation of canonical Wnt/β-catenin signaling through mutations in adenomatous polyposis coli (APC) was recognized to be an initiating event in colon carcinogenesis (2). Since that time, Wnt/β-catenin–activating mutations and/or epigenetic alterations have been found in a variety of human malignancies, including that of liver, skin, prostate, and breast (3–5). Thus, this signaling cascade holds excellent potential as a therapeutic target for treating myriad human cancers (6). Despite academic pursuit and industrial investment, clinically applicable inhibitors of the pathway remain elusive, calling for continuous effort and novel approaches. In PNAS, Gonsalves et al. (7) report a unique suppressor screen that combines high-throughput chemical library screening with RNAi technology to identify small molecules that specifically inhibit the β-catenin–responsive transcription (CRT) in the nucleus.
Mechanics in Neuronal Development and Repair (2013)

Biological cells are well known to respond to a multitude of chemical signals. In the nervous system, chemical signaling has been shown to be crucially involved in development, normal functioning, and disorders of neurons and glial cells. However, there are an increasing number of studies showing that these cells also respond to mechanical cues. Here, we summarize current knowledge about the mechanical properties of nervous tissue and its building blocks, review recent progress in methodology and understanding of cellular mechanosensitivity in the nervous system, and provide an outlook on the implications of neuromechanics for future developments in biomedical engineering to aid overcoming some of the most devastating and currently incurable CNS pathologies such as spinal cord injuries and multiple sclerosis.
Phasercrystallographic software (2007)

Phaser is a program for phasing macromolecular crystal structures by both molecular replacement and experimental phasing methods. The novel phasing algorithms implemented in Phaser have been developed using maximum likelihood and multivariate statistics. For molecular replacement, the new algorithms have proved to be significantly better than traditional methods in discriminating correct solutions from noise, and for single-wavelength anomalous dispersion experimental phasing, the new algorithms, which account for correlations between F(+) and F(-), give better phases (lower mean phase error with respect to the phases given by the refined structure) than those that use mean F and anomalous differences DeltaF. One of the design concepts of Phaser was that it be capable of a high degree of automation. To this end, Phaser (written in C++) can be called directly from Python, although it can also be called using traditional CCP4 keyword-style input. Phaser is a platform for future development of improved phasing methods and their release, including source code, to the crystallographic community.
Fabrication and characterization of multiscale electrospun scaffolds for cartilage regeneration (2013)

Recently, scaffolds for tissue regeneration purposes have been observed to utilize nanoscale features in an effort to reap the cellular benefits of scaffold features resembling extracellular matrix (ECM) components. However, one complication surrounding electrospun nanofibers is limited cellular infiltration. One method to ameliorate this negative effect is by incorporating nanofibers into microfibrous scaffolds. This study shows that it is feasible to fabricate electrospun scaffolds containing two differently scaled fibers interspersed evenly throughout the entire construct as well as scaffolds containing fibers composed of two discrete materials, specifically fibrin and poly(ε-caprolactone). In order to accomplish this, multiscale fibrous scaffolds of different compositions were generated using a dual extrusion electrospinning setup with a rotating mandrel. These scaffolds were then characterized for fiber diameter, porosity and pore size and seeded with human mesenchymal stem cells to assess the influence of scaffold architecture and composition on cellular responses as determined by cellularity, histology and glycosaminoglycan (GAG) content. Analysis revealed that nanofibers within a microfiber mesh function to maintain scaffold cellularity under serum-free conditions as well as aid the deposition of GAGs. This supports the hypothesis that scaffolds with constituents more closely resembling native ECM components may be beneficial for cartilage regeneration.
Intelligent PV Module for Grid-Connected PV Systems (2006)

Most issues carried out about building integrated photovoltaic (PV) system performance show average losses of about 20%-25% in electricity production. The causes are varied, e.g., mismatching losses, partial shadows, variations in current-voltage (I-V) characteristics of PV modules due to manufacturing processes, differences in the orientations and inclinations of solar surfaces, and temperature effects. These losses can be decreased by means of suitable electronics. This paper presents the intelligent PV module concept, a low-cost high-efficiency dc-dc converter with maximum power point tracking (MPPT) functions, control, and power line communications (PLC). In addition, this paper analyses the alternatives for the architecture of grid-connected PV systems: centralized, string, and modular topologies. The proposed system, i.e., the intelligent PV module, fits within this last group. Its principles of operation, as well as the topology of boost dc-dc converter, are analyzed. Besides, a comparison of MPPT methods is performed, which shows the best results for the incremental conductance method. Regarding communications, PLC in every PV module and its feasibility for grid-connected PV plants are considered and analyzed in this paper. After developing an intelligent PV module (with dc-dc converter) prototype, its optimal performance has been experimentally confirmed by means of the PV system test platform. This paper describes this powerful tool especially designed to evaluate all kinds of PV systems
The Notch1 receptor is cleaved constitutively by a furin-like convertase (1998)

The Notch receptor, which is involved in numerous cell fate decisions in invertebrates and vertebrates, is synthesized as a 300-kDa precursor molecule (p300). We show here that proteolytic processing of p300 is an essential step in the formation of the biologically active receptor because only the cleaved fragments are present at the cell surface. Our results confirm and extend recent reports indicating that the Notch receptor exists at the plasma membrane as a heterodimeric molecule, but disagree as to the nature of the protease that is responsible for the cleavage that takes place in the extracellular region. We report here that constitutive processing of murine Notch1 involves a furin-like convertase. We show that the calcium ionophore A23187 and the alpha1-antitrypsin variant, alpha 1-PDX, a known inhibitor of furin-like convertases, inhibit p300 processing. When expressed in the furin-deficient Lovo cell line, p300 is not processed. In vitro digestion of a recombinant Notch-derived substrate with purified furin allowed mapping of the processing site to the carboxyl side of the sequence RQRR (amino acids 1651-1654). Mutation of these four amino acids (and of two secondary dibasic furin sites located nearby) completely abolished processing of the Notch1 receptor.
Prognostic value of E-cadherin, beta-catenin, MMPs (7 and 9), and TIMPs (1 and 2) in patients with colorectal carcinoma (2006)

The expression of E-cadherin and TIMP-2 could be relevant in determining the prognosis of CRC patients and providing a more accurate mechanism for their classification.
HIV entry inhibitors: mechanisms of action and resistance pathways (2006)

Entry inhibitors represent a new generation of antivirals for the treatment of HIV infection. Several compounds which block the attachment of HIV gp120 to either the CD4 T cell receptor or the CCR5/CXCR4 co-receptors are currently in clinical development. Most of these compounds have different molecular structures and specific mechanisms of action. These agents are eagerly awaited by a growing number of patients carrying viruses resistant viruses to many of the current available reverse transcriptase and protease inhibitors. For enfuvirtide, the first and, so far, only entry inhibitor approved for clinical use, the main mechanism of resistance is the selection of changes within a 10 amino acid segment encompassing residues 36-45 within the HR1 region of gp41. For other entry inhibitors, multiple changes in different gp120 domains (V1, V2, V3, C2 and C4) have been associated with loss of susceptibility to these agents, although in most cases with limited cross-resistance.
Hafnia-plugged microcavities for thermal stability of selective emitters (2013)

Two-dimensional arrays of micro-cavities effectively control photon motion and selectively emit radiation tailored to the preferred bandgap of photovoltaic (PV) cells, thus enhancing the efficiency of thermophotovoltaic energy conversion. At the high operating temperatures, however, the micro- and nano-patterned structures of the selective emitters quickly lose their integrity––obliterating the tight tolerances required for precise spectral control. Even if oxidation, recrystallization, and grain growth could be avoided with single-crystal tungsten (W) selective emitters with vacuum packaging, surface diffusion, evaporation, and re-condensation are not avoidable in long-term operation at high temperatures. The concept of a planar array of plugged micro-cavities to suppress the curvature-dependent thermal degradation modes is proposed and tested. Based on scale-accelerated failure tests of silicon devices, the lifetime of W selective emitters operating at 1100 K is estimated to be at least 30 yr.
GaAs/GaAlAs diode lasers with angled pumping stripes (1978)

Operation of DH GaAs/GaAlAs stripe contact lasers with stripes oriented nonorthogonally to the cleaved end facets of the laser is described. Such lasers, with misalignment angles of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\sim2\deg</tex> , do not exhibit "kinking" behavior to power levels greater than 90 mW/facet, and do not exhibit relaxation oscillations under pulsed operation. Data showing the dependence of laser wavelength, spectral half-width, transverse mode structure, facet reflectivity, and output beam angle on both stripe angle and pump current level are also presented.
Antisense palmitoyl protein thioesterase 1 (PPT1) treatment inhibits PPT1 activity and increases cell death in LA-N-5 neuroblastoma cells (2000)

Infantile neuronal ceroid lipofuscinosis (INCL) is a childhood neurodegenerative disease caused by the selective death of cortical neurons and retinal degeneration, as the result of a palmitoyl protein thioesterase 1 (PPT1) deficiency. Recently, we showed that overexpression of PPT1 protects LA-N-5 human neuroblastoma cells against apoptotic death (Cho and Dawson [2000a] J. Neurochem. 74:1478-1488) and we now show that inhibition of PPT1 increases the susceptibility of these cells to apoptotic cell death. Transient transfection of LA-N-5 neuroblastoma cells with PPT1-FLAG resulted in a strong expression of PPT-FLAG-tagged protein as evidenced by Western blot analysis and immunofluorescence. Co-transfection of a reverse-oriented (antisense) PPT1 (AS-PPT1) decreased the expression of PPT-FLAG to almost zero, reduced PPT1 enzyme activity (as measured by an in vitro assay) and increased the susceptibility to apoptosis induced by C(2) ceramide. Similarly, inhibition of PPT1 with a synthetic inhibitor (AcG-palmitoyl diaminoproprionate-VKIKK) (DAP1) (100 microM) increased the susceptibility of the cells to apoptosis induced by either C(2)-ceramide or etoposide, a common chemotherapeutic agent used in the treatment of neuroblastoma. Cells stably overexpressing PPT1 were resistant to apoptosis induced by DAP1 suggesting that the inhibitor has a specific action and confirming that low levels of protein palmitoylation block the death pathway. Drugs that raise the level of protein palmitoylation are pro-apoptotic and PPT1 inhibition may enhance the killing efficacy of chemotherapeutic agents used to kill neuroblastoma-derived cells.
Microelectronic Circuits Revised Edition (2007)

Today's Technology. Tomorrow's Engineers. This market-leading textbook continues its standard of excellence and innovation built on the solid pedagogical foundation that instructors expect from Adel S. Sedra and Kenneth C. Smith. All material in the fifth edition of Microelectronic Circuits is thoroughly updated to reflect changes in technology-CMOS technology in particular. These technological changes have shaped the book's organization and topical coverage, making it the most current resource available for teaching tomorrow's engineers how to analyze and design electronic circuits.
Die Reaktion von Borsäuremethylester mit Ammoniak und Aminen. I (1951)

Abstract Bei der Umsetzung von Borsäuremethylester mit überschüssigem Ammoniak wurde das Anlagerungsprodukt H 3 N · B(OCH 3 ) 3 isoliert. Läßt man dagegen Ammoniak mit überschüssigem Ester reagieren, so werden Produkte erhalten, in denen eine Molekel Ammoniak mit bis zu vier Estern sich umgesetzt hat. Es wird ein allgemeines Schema für die Reaktion aufgestellt.