gebhart/patrepeval huggingface dataset:
A 30-Amino Acid Truncation of the Microsomal Triglyceride Transfer Protein Large Subunit Disrupts Its Interaction with Protein Disulfide-isomerase and Causes Abetalipoproteinemia (1995)

The microsomal triglyceride transfer protein (MTP) is a heterodimer composed of the multifunctional enzyme, protein disulfide-isomerase, and a unique large, 97 kDa, subunit. It is found as a soluble protein within the lumen of the endoplasmic reticulum of liver and intestine and is required for the assembly of very low density lipoproteins and chylomicrons. Mutations in MTP which result in an absence of MTP function have been shown to cause abetalipoproteinemia. Here, the gene encoding the MTP 97-kDa subunit of an abetalipoproteinemic subject, which we have previously demonstrated lacks MTP activity and protein (Wetterau, J. R., Aggerbeck, L. P., Bouma, M.-E., Eisenberg, C., Munck, A., Hermier, M., Schmitz, J., Gay, G., Rader, D. J., and Gregg, R. E. (1992) Science 258, 999-1001), was isolated and sequenced. A nonsense mutation, which predicts the truncation of the protein by 30 amino acids, was identified. To investigate if this apparently subtle change in MTP could explain the observed absence of MTP, protein disulfide-isomerase was co-expressed with either the normal or mutant MTP 97-kDa subunit in Sf9 insect cells using a baculovirus expression system. Although there were high levels of expression of both the normal and mutant forms of the MTP 97-kDa subunit, only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase. These results indicate that the carboxyl-terminal 30 amino acids of the MTP 97-kDa subunit plays an important role in its interaction with protein disulfide-isomerase.
Characterization of birefringence dispersion in polarization-maintaining fibers by use of white-light interferometry (2007)

A new method for measuring the birefringence dispersion in polarization-maintaining fibers (PMFs) with high sensitivity and accuracy is presented. The method employs white-light interferences between two orthogonally polarized modes of PMFs. The group birefringence of the fiber is calibrated first. Then the birefringence dispersion and its variation along different fiber sections are acquired by analyzing the broadening of interferograms at different fiber lengths. The main sources of error are investigated. Birefringence dispersions of two PANDA fibers at their operation wavelength are measured to be 0.011 ps/(km nm) and 0.018 ps/(km nm). A measurement repeatability of 0.001 ps/(km nm) is achieved.
Mechanistic Aspects of Formation of Chiral Ruthenium Hydride Complexes from 16‐Electron Ruthenium Amide Complexes and Formic Acid: Facile Reversible Decarboxylation and Carboxylation (2004)

Abstract The 16‐electron amide complex, Ru[( R,R )‐TsNCHPhCHPhNH](η 6 ‐ p ‐cymene) (Ts= p ‐toluenesulfonyl, Ph=C 6 H 5 ) readily reacts with formic acid to give the corresponding formate complex, which subsequently undergoes decarboxylation leading to the hydride complex with release of CO 2 . The reaction of this hydride complex with CO 2 under mild reaction conditions, a pressure of 10 atm and even at −78 °C, proceeds rapidly to give the corresponding formate complex almost quantitatively. Thus, the reversible decarboxylation and carboxylation takes place with or without the aid of a metal‐NH bifunctional effect of the Ru complexes.
Error rate performance improvement for a decorrelating CDMA receiver by introducing additional dummy pilot response (2003)

A pilot assisted CDMA system which uses extended spreading sequences with guard sequences under a quasi-synchronous condition is capable of separating the interference components included in the input of a decorrelating receiver by solving a system of linear equations. The performance of such a system, however, depends on the property of the de-correlating matrix made of the pilots responses. The regularity of the matrix often tends to degrade due to primarily the multipaths, resulting in the solutions vulnerable to AWGN. This paper proposes an effective technique to solve this problem by introducing a dummy pilot associated with a virtual user into a group of the real users to be served. The simulation indicates a remarkable improvement in the bit-error-rate performance. In addition, it proves a RAKE like function with power-sum-characteristics.
Equivalance of Time-Multiplexed and Frequency-Multiplexed Signals in Digital Communications (1972)

In comparing different techniques for multiplexing <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N</tex> binary data signals into a single channel, time-division multiplexing (TDM) is known to have a theoretic efficiency of 100 percent (neglecting sync power) and thus seems to outperform frequencydivision multiplexing systems (FDM). By considering more general FDM systems, we will show that both TDM and FDM are equivalent and have an efficiency of 100 percent. The difference between the systems is in the multiplexing and demultiplexing subsystems, but not in the performance or in the generated waveforms.
Cellular retinoic acid bioavailability in various pathologies and its therapeutic implication (2017)

Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling molecule in various cell types. We found that RA depletion caused by expression of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that the biological effect of RA on target cells is primarily determined by "cellular RA bioavailability", which is defined as the RA level in an individual cell, rather than by the serum concentration of RA. Consistently, stellate cells store approximately 80% of vitamin A in the body, and the state of cellular RA bioavailability regulates their function. Based on the similarities between stellate cells and astrocytes, we demonstrated that retinal astrocytes regulate tight junction-based endothelial integrity in a paracrine manner. Since diabetic retinopathy is characterized by increased vascular permeability in its early pathogenesis, RA normalized retinal astrocytes that are compromised in diabetes, resulting in suppression of vascular leakiness. RA also attenuated the loss of the epithelial barrier in murine experimental colitis. The concept of "cellular RA bioavailability" in various diseases will be directed at understanding various pathologies caused by RA insufficiency, implying the potential feasibility of a therapeutic strategy targeting the stellate cell system.
The <i>Saccharomyces cerevisiae</i> Hyperrecombination Mutant <i>hpr1</i> Δ Is Synthetically Lethal with Two Conditional Alleles of the Acetyl Coenzyme A Carboxylase Gene and Causes a Defect in Nuclear Export of Polyadenylated RNA (1999)

In a screen for mutants that display synthetic lethal interaction with hpr1Delta, a hyperrecombination mutant of Saccharomyces cerevisiae, we have isolated a novel cold-sensitive allele of the acetyl coenzyme A (CoA) carboxylase gene, acc1(cs), encoding the rate-limiting enzyme of fatty acid synthesis. The synthetic lethal phenotype of the acc1(cs) hpr1Delta double mutant was only partially complemented by exogenous fatty acids. hpr1Delta was also synthetically lethal with a previously isolated, temperature-sensitive allele of ACC1, mtr7 (mRNA transport), indicating that the lethality of the acc1(cs) hpr1Delta double mutant was not allele specific. The basis for the interaction between conditional acc1 alleles and hpr1Delta was investigated in more detail. In the hpr1Delta mutant background, acetyl-CoA carboxylase enzyme activity was reduced about 15-fold and steady-state levels of biotinylated Acc1p and ACC1 mRNA were reduced 2-fold. The reduced Acc1p activity in hpr1Delta cells, however, did not result in an altered lipid or fatty acid composition of the mutant membranes but rendered cells hypersensitive to soraphen A, an inhibitor of Acc1p. Similar to mtr7, hpr1Delta and acc1(cs) mutant cells displayed a defect in nuclear export of polyadenylated RNA. Oversized transcripts were detected in hpr1Delta, and rRNA processing was disturbed, but pre-mRNA splicing appeared wild type. Surprisingly, the transport defect of hpr1Delta and acc1(cs) mutant cells was accompanied by an altered ring-shaped structure of the nucleolus. These observations suggest that the basis for the synthetic lethal interaction between hpr1Delta and acc1 may lie in a functional overlap of the two mutations in nuclear poly(A)+ RNA production and export that results in an altered structure of the nucleolus.
Integrated Si Lens Antenna with Planar Log Spiral Feed for THz Band (2014)

A hybrid antenna is used to design a mixer in the heterodyne receiver for THz range application to increase the system efficiency. Design of a high precision THz range antenna for a constant far-field beam pattern is always a challenging task to the design engineers. A design procedure of THz band antenna by using CST Microwave Studio has been presented. The antenna has been designed and optimized to achieve constant far field beam as well as fixed polarization. Beam patterns, maximum directivity, on band directivity flatness, polarization, Φ = 0° and Φ = 90° beam symmetries have been studied for 5mm hemispherical lenses over WR-1.5 band (500GHz to 750GHz). Experimental results show a better matching accuracy within the design considerations.
Disheveled regulates precoupling of heterotrimeric G proteins to Frizzled 6 (2014)

Frizzleds (FZDs) are classified as G-protein-coupling receptors, but how signals are initiated and specified through heterotrimeric G proteins is unknown. FZD6 regulates convergent extension movements, and its C-terminal Arg511Cys mutation causes nail dysplasia in humans. We investigated the functional relationship between FZD6, Disheveled (DVL), and heterotrimeric G proteins. Live cell imaging combined with fluorescence recovery after photobleaching (FRAP) revealed that inactive human FZD6 precouples to Gαi1 and Gαq but not to GαoA,Gαs, and Gα12 proteins. G-protein coupling is measured as a 10-20% reduction in the mobile fraction of fluorescently tagged G proteins on chemical receptor surface cross-linking. The FZD6 Arg511Cys mutation is incapable of G-protein precoupling, even though it still binds DVL. Using both FRAP and Förster resonance energy transfer (FRET) technology, we showed that the FZD6-Gαi1 and FZD-Gαq complexes dissociate on WNT-5A stimulation. Most important, G-protein precoupling of FZD6 and WNT-5A-induced signaling to extracellular signal-regulated kinase1/2 were impaired by DVL knockdown or overexpression, arguing for a strict dependence of FZD6-G-protein coupling on DVL levels and identifying DVL as a master regulator of FZD/G-protein signaling. In summary, we propose a mechanistic connection between DVL and G proteins integrating WNT, FZD, G-protein, and DVL function.
Micro patterns in Java code (2005)

Micro patterns are similar to design patterns, except that micro patterns are stand at a lower, closer to the implementation, level of abstraction. Micro patterns are also unique in that they are mechanically recognizable, since each such pattern can be expressed as a formal condition on the structure of a class.This paper presents a catalog of 27 micro-patterns defined on Java classes and interfaces. The catalog captures a wide spectrum of common programming practices, including a particular and (intentionally restricted) use of inheritance, immutability, data management and wrapping, restricted creation, and emulation of procedural-, modular-, and even functional- programming paradigms with object oriented constructs. Together, the patterns present a set of prototypes after which a large portion of all Java classes and interfaces are modeled. We provide empirical indication that this portion is as high as 75%.A statistical analysis of occurrences of micro patterns in a large software corpus, spanning some 70,000 Java classes drawn from a rich set of application domains, shows, with high confidence level that the use of these patterns is not random. These results indicate consciousness and discernible design decisions, which are sustained in the software evolution. With high confidence level, we can also show that the use of these patterns is tied to the specification, or the purpose, that the software realizes.The traceability, abundance and the statistical significance of micro pattern occurrence raise the hope of using the classification of software into these patterns for a more founded appreciation of its design and code quality.
Two Heme-Dependent Terminal Oxidases Power Staphylococcus aureus Organ-Specific Colonization of the Vertebrate Host (2013)

Staphylococcus aureus poses a significant threat to public health as antibiotic-resistant isolates of this pathogen continue to emerge. Our understanding of the energy-generating processes that allow S. aureus to proliferate within the host is incomplete. Host-derived heme is the preferred source of nutrient iron during infection; however, S. aureus can synthesize heme de novo and use it to facilitate aerobic respiration. We demonstrate that S. aureus heme biosynthesis powers a branched aerobic respiratory chain composed of two terminal oxidases. The importance of having two terminal oxidases is demonstrated by the finding that each plays an essential role in colonizing distinct organs during systemic infection. Additionally, this process can be targeted by small-molecule heme analogues called noniron protoporphyrins. This study serves to demonstrate that heme biosynthesis supports two terminal oxidases that are required for aerobic respiration and are also essential for S. aureus pathogenesis.
Dynamic feature-adaptive subdivision. (2015)

Feature-adaptive subdivision (FAS) is one of the state-of-the art real-time rendering methods for subdivision surfaces on modern GPUs. It enables efficient and accurate rendering of subdivision surfaces in many interactive applications, such as video games or authoring tools. In this paper, we present dynamic feature-adaptive subdivision (DFAS), which improves upon FAS by enabling an independent subdivision depth for every irregularity. Our subdivision kernels fill a dynamic patch buffer on-the-fly with the appropriate number of patches corresponding to the chosen level-of-detail scheme. By reducing the number of generated and processed patches, DFAS significantly improves upon the performance of static FAS.
Biological Control of Invading Species (2000)

We agree with Donald R. Strong and Robert W. Pemberton ( Science 's Compass, Policy Forum, “Ecology: Biological control of invading species—risk and reform,” 16 June, p. [1969][1]) ([1][2]) that invasive species pose major problems to managed and natural ecosystems in the United States. The
Autocatalytic activation of human legumain at aspartic acid residues (1998)

Human legumain was characterized following overexpression in a murine cell line as the C-terminal Ig-fusion protein. Upon acid treatment, the prolegumain autoproteolyzed distal to two aspartic acid residues to yield a highly active form. The ability of mature legumain to cleave after aspartic acid residues was confirmed with a small peptide substrate. Substitution of alanine for the putative catalytic cysteine, or for either of two strictly conserved histidine residues, partly or wholly eliminated autoactivation but not the ability of wild-type legumain to correctly process the variants to the properly sized proteins.
Determination of Lead with a Copper-Based Electrochemical Sensor (2017)

This work demonstrates determination of lead (Pb) in surface water samples using a low-cost copper (Cu)-based electrochemical sensor. Heavy metals require careful monitoring due to their toxicity, yet current methods are too complex or bulky for point-of-care (POC) use. Electrochemistry offers a convenient alternative for metal determination, but the traditional electrodes, such as carbon or gold/platinum, are costly and difficult to microfabricate. Our copper-based sensor features a low-cost electrode material-copper-that offers simple fabrication and competitive performance in electrochemical detection. For anodic stripping voltammetry (ASV) of Pb, our sensor shows 21 nM (4.4 ppb) limit of detection, resistance to interfering metals such as cadmium (Cd) and zinc (Zn), and stable response in natural water samples with minimum sample pretreatment. These results suggest this electrochemical sensor is suitable for environmental and potentially biological applications, where accurate and rapid, yet inexpensive, on-site monitoring is necessary.
Metal Gate Technology for Advanced CMOS Devices (2006)

The development and implementation of a metal gate technology (alloy, compound, or silicide) into metal-oxide-semiconductor field effect transistors (MOSFETs) is necessary to extend the life of planar CMOS devices and enable further downscaling. This thesis examines possible metal gate materials for improving the performance of the gate stack and discusses process integration as well as improved electrical and physical measurement methodologies, tested on capacitor structures and transistors. By using reactive PVD and gradually increasing the N2/Ar flow ratio, it was found that the work function (on SiO2) of the TiNx and ZrNx metal systems could be modulated ~0.7 eV from low near nMOS work functions to high pMOS work functions. After high-temperature anneals corresponding to junction activation, both metals systems reached mid-gap work function values. The mechanisms behind the work function changes are explained with XPS data and discussed in terms of metal gradients and Fermi level pinning due to extrinsic interface states. A modified scheme for improved Fowler-Nordheim tunnelling is also shown, using degenerately doped silicon substrates. In that case, the work functions of ALD/PVD TaN were accurately determined on both SiO2 and HfO2 and benchmarked against IPE (Internal Photoemission) results. KFM (Kelvin Force Microscopy) was also used to physically measure the work functions of PVD TiN and Mo deposited on SiO2; the results agreed well with C-V and I-V data. Finally, an appealing combination of novel materials is demonstrated with ALD TiN/Al2O3/HfAlOx/Al2O3/strained-SiGe surface channel pMOS devices. The drive current and transconductance were measured to be 30% higher than the Si reference, clearly demonstrating increased mobility and the absence of polydepletion. Finally, using similarly processed transistors with Al2O3 dielectric instead, low-temperature water vapour annealing was shown to improve the device characteristics by reducing the negative charge within the ALD Al2O3.
Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis† (2008)

These findings indicate that dietary cholesterol, possibly in the form of modified plasma lipoproteins, is an important risk factor for the progression to hepatic inflammation in diet-induced NASH.
A High-Intensity Plasma-Sputter Heavy Negative Ion Source (1989)

A multicusp magnetic field plasma surface ion source, normally used for H/sup /minus//ion beam formation, has been modified for the generation of high-intensity, pulsed, heavy negative ion beams suitable for a variety of uses. To date, the source has been utilized to produce mA intensity pulsed beams of more than 24 species. A brief description of the source, and basic pulsed-mode operational data, (e.g., intensity versus cesium oven temperature, sputter probe voltage, and discharge pressure), are given. In addition, illustrative examples of intensity versus time and the mass distributions of ion beams extracted from a number of samples along with emittance data, are also presented. Preliminary results obtained during dc operation of the source under low discharge power conditions suggest that sources of this type may also be used to produce high-intensity (mA) dc beams. The results of these investigations are given, as well, and the technical issues that must be addressed for this mode of operation are discussed. 15 refs., 10 figs., 2 tabs.
On general routing problems (1976)

Abstract In two recent papers by C. S. Orloff (Networks, 4(1974)35–64, 147–162) general routing problems for one or more vehicles on a graph G = (N,A) are introduced and discussed. The single vehicle problem is to find an optimal tour on G, containing required subsets Q ⊆ N and R ⊆ A. We show that a proposed conversion of required nodes to required arcs is not allowed and that the problem remains polynomial complete if Q = θ. Furthermore, the proposed transformations from M vehicle to single vehicle problems are shown to be incorrect; correct transformations are presented as well.
In vitro and in vivo characterization of a monoclonal antibody, ATN-658, targeting the uPA system (2005)

6179 A substantial body of in vitro and in vivo data has implicated the urokinase plasminogen activator system, comprised of the serine protease urokinase (uPA), its cell surface receptor uPAR and plasminogen activator inhibitor-1 (PAI-1), in the neo-vascularization, invasion and metastasis of many solid tumors. More recent work has suggested that the interaction of uPAR with other cell surface receptors, particularly integrins, may play a significant role in these processes - independent of uPA catalytic activity. The important role of uPA-uPAR in tumor growth combined with its abundant expression within tumor, but not normal tissue makes it an attractive diagnostic and therapeutic target. We previously described the production and characterization of monoclonal antibodies specific for the D2D3 domain of uPAR. We have extensively characterized one of these antibodies, ATN-658, both in vitro and in vivo. ATN-658 bound immobilized recombinant uPAR and uPAR expressed on the surface of HeLa cells with a KD of ∼ 1 nM. Importantly, ATN-658 bound recombinant suPAR in which all non-essential glycosylation sites were mutated with a similar affinity - indicating that the antibody is specific for the protein portion of uPAR. Interestingly, although [I-125]-labeled ATN-658 bound to HeLa cells with high affinity, its binding was not competed by uPA. Similarly, binding of [I-125]-labeled scuPA to HeLa cells was unaffected by pre-incubation with unlabeled ATN-658. Unlike other antibodies we have tested, ATN-658 was not internalized upon binding to HeLa cells or MDA MB231 cells. To characterize the functional activity of the antibody, migration assays were performed. Although ATN-658 does not disrupt uPA binding to its receptor, ATN-658 inhibited uPA-induced migration of CHO cells expressing uPAR. Similarly, using a modified Boyden chamber model, ATN-658 inhibited the growth factor (HGF and IGF) induced migration of tumor cells. This data suggests that ATN-658 disrupts the interaction of uPAR with other cell surface receptors. The ability of ATN-658 to inhibit primary tumor growth was investigated in a number of in vivo models. To identify an appropriate dose and schedule for antibody treatment the circulating levels of ATN-658 were measured using a modified ELISA assay. Twice weekly treatment IP at 10 mg/kg resulted in a steady state plasma concentration of antibody of ∼0.4 μM, or 100-fold higher than the KD measured by in vitro binding assays. Using this dose and treatment schedule, ATN-658 significantly inhibited tumor growth in an A549 NSCLC early treatment model. Similarly, ATN-658 inhibited tumor growth in a staged A2780 ovarian carcinoma model. Taken together these data suggest that ATN-658, a monoclonal antibody specific for the D2D3 domain of uPAR, significantly inhibits tumor growth by a mechanism independent of uPA binding to its receptor.
HER2 Transmembrane Domain (TMD) Mutations (V659/G660) That Stabilize Homo- and Heterodimerization Are Rare Oncogenic Drivers in Lung Adenocarcinoma That Respond to Afatinib (2016)

HER2 TMD mutations represent rare but distinct targetable driver mutations in lung adenocarcinoma. CGP capable of detecting diverse HER2 alterations, including HER2 TMD mutations, should be broadly adopted to identify all patients who may benefit from HER2-targeted therapies.