gebhart/patrepeval huggingface dataset:
Activation of Protein Kinase Cζ Induces Serine Phosphorylation of VAMP2 in the GLUT4 Compartment and Increases Glucose Transport in Skeletal Muscle (2001)

Insulin stimulates glucose uptake into skeletal muscle tissue mainly through the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. The precise mechanism involved in this process is presently unknown. In the cascade of events leading to insulin-induced glucose transport, insulin activates specific protein kinase C (PKC) isoforms. In this study we investigated the roles of PKC zeta in insulin-stimulated glucose uptake and GLUT4 translocation in primary cultures of rat skeletal muscle. We found that insulin initially caused PKC zeta to associate specifically with the GLUT4 compartments and that PKC zeta together with the GLUT4 compartments were then translocated to the plasma membrane as a complex. PKC zeta and GLUT4 recycled independently of one another. To further establish the importance of PKC zeta in glucose transport, we used adenovirus constructs containing wild-type or kinase-inactive, dominant-negative PKC zeta (DNPKC zeta) cDNA to overexpress this isoform in skeletal muscle myotube cultures. We found that overexpression of PKC zeta was associated with a marked increase in the activity of this isoform. The overexpressed, active PKC zeta coprecipitated with the GLUT4 compartments. Moreover, overexpression of PKC zeta caused GLUT4 translocation to the plasma membrane and increased glucose uptake in the absence of insulin. Finally, either insulin or overexpression of PKC zeta induced serine phosphorylation of the GLUT4-compartment-associated vesicle-associated membrane protein 2. Furthermore, DNPKC zeta disrupted the GLUT4 compartment integrity and abrogated insulin-induced GLUT4 translocation and glucose uptake. These results demonstrate that PKC zeta regulates insulin-stimulated GLUT4 translocation and glucose transport through the unique colocalization of this isoform with the GLUT4 compartments.
IRG1 controls host responses to restrict Mycobacterium tuberculosis infection (2019)

Abstract Mycobacterium tuberculosis ( Mtb ), the pathogen causing human tuberculosis, has evolved multiple strategies to successfully prevent clearance by immune cells and to establish dissemination and long-term survival in the host. The modulation of host immunity to maximize pathogen elimination while minimizing inflammation-mediated tissue damage may provide another tool to fight drug-resistant Mtb strains. Metabolic reprogramming of phagocytes can dramatically influence the intracellular colonization by Mtb and the key players involved in this process remain a matter of debate. Here, we demonstrate that aconitate decarboxylase 1 (Acod1; also known as immune-responsive gene 1, IRG1), which converts cis-aconitate into the metabolite itaconate, is a major player in controlling the acute phase of Mtb infection. Exposure of IRG1-deficient mice to a virulent Mtb strain (H37Rv) was lethal, while M. bovis BCG and the H37Ra attenuated Mtb strain induced neither lethality nor severe lung immunopathology. Lungs of IRG1-deficient mice infected by Mtb H37Rv displayed large areas of necrotizing granulomatous inflammation and neutrophil infiltration, accompanied by reduced levels of B and T lymphocytes and increased levels of alveolar and interstitial macrophage populations, compared to their wild type counterparts. Next, we show that IRG1, beyond its recruitment to Mtb -containing vacuoles, restricts Mtb replication and lipid droplets accumulation in phagocytes, hallmarks of a tight interplay between the bacillus and the host. Altogether, IRG1 confines the host response to create a favourable phagocytic environment for Mtb controlled intracellular replication.
Covalent Immobilization of Proteins on 3D Poly(acrylic acid) Brushes: Mechanism Study and a More Effective and Controllable Process (2013)

Polymeric brushes have emerged as a novel 3D material platform that provides great amounts of binding sites for biomolecules. This paper investigates the covalent immobilization mechanism of protein by spherical poly(acrylic acid) brushes (SPAABs) in the widely adopted N-hydroxysuccinimide/N-(3-dimethyl-aminopropyl)-N'-ethylcarbodiimide hydrochloride (NHS/EDC) process. It was discovered that electrostatic interaction plays a crucial role in the covalent immobilization of protein. Due to the existence of 3D architecture and "Donnan effect", SPAABs exhibit quite different immobilization kinetics in comparison with conventional 2D materials. Under conditions favorable to electrostatic interaction, the effect of "electrostatic interaction induced covalent binding" was observed as a result of competitive immobilization by physical adsorption and chemical binding. On the basis of the mechanism study, a new "chemical conjugation after electrostatic entrapment" (CCEE) method was developed which set the chemical and physical immobilization process apart. A more effective and well-defined covalent immobilization was achieved. And the binding capacity can be tuned in a wide range (0-4.2 mg protein/mg SPAABs) with a high level of control.
Completely Nonmagnetic Alloy for Instrumentation in Magnetic Fields (1958)

A high-purity copper-nickel alloy is described which has zero magnetic moment at room temperature and less than a tenth the moment of pure copper at all temperatures down to 2°K. The alloy has been used with considerable advantage in sample holders for magnetic force measurements, and other uses are anticipated. A method of preparing the alloy is discussed which requires limited metallurgical equipment.
[Bacterial and archaeal S-layers as object of bionanotechnology]. (2005)

Many species of Bacteria and Archaea posses a regularly structured surface layers (S-layers) as outermost cell envelope component. S-layers composed of a single protein or glycoprotein species. The individual subunits of S-layers interact with each other and with the supporting bacterial envelope component through non-covalent forces. Pores in the crystalline protein network are with mean diameter of 2-6 nm, the thickness of S-layer is 5-10 nm. The isolated S-layer subunits reassemble into two-dimensional crystalline arrays in solution, on solid supports, on planar lipid films. These unique features of S-layers have led to a broad spectrum applications. This review focuses on the structural properties S-layers and S-proteins and their applications with accent to using this structures in nanobiotechnology.
Application of Free Energy Perturbation for the Design of BACE1 Inhibitors (2016)

Novel spiroaminodihydropyrroles probing for optimized interactions at the P3 pocket of β-secretase 1 (BACE1) were designed with the use of free energy perturbation (FEP) calculations. The resulting molecules showed pIC50 potencies in enzymatic BACE1 inhibition assays ranging from approximately 5 to 7. Good correlation was observed between the predicted activity from the FEP calculations and experimental activity. Simulations run with a default 5 ns approach delivered a mean unsigned error (MUE) between prediction and experiment of 0.58 and 0.91 kcal/mol for retrospective and prospective applications, respectively. With longer simulations of 10 and 20 ns, the MUE was in both cases 0.57 kcal/mol for the retrospective application, and 0.69 and 0.59 kcal/mol for the prospective application. Other considerations that impact the quality of the calculations are discussed. This work provides an example of the value of FEP as a computational tool for drug discovery.
Electroencephalogram associations to cognitive performance in clinically active nurses (2016)

Cognitive impairment is traditionally identified via cognitive screening tools that have limited ability in detecting early or transitional stages of impairment. The dynamic nature of physiological variables such as the electroencephalogram (EEG) may provide alternate means for detecting these transitions. However, previous research examining EEG and cognitive performance is largely confined to samples with diagnosed cognitive impairments, and research examining non-impaired, and occupation specific samples, is limited. The present study aimed to investigate the associations between frontal pole and central EEG and cognitive performance in a sample of male and female nurses, and to determine the significance of these associations. Fifty seven nurses participated in the study, in which two lead bipolar EEG was recorded at positions Fp1 (frontal polar), Fp2, C3 (central) and C4 during a baseline and an active phase involving the common neuropsychological Stroop test. Participants' cognitive performance was assessed using the mini-mental state exam (MMSE) and Cognistat screening tools. Significant correlations between EEG beta activity and the outcome of MMSE and Cognistat were revealed, where an increased beta activity was associated to an increased global cognitive performance. Additionally, domain specific cognitive performance was also significantly associated to various EEG variables. The study identified potential EEG biomarkers for global and domain specific cognitive performance, and provides initial groundwork for the development of future EEG based biomarkers for detection of cognitive pathologies.
Platelet findings in 22q11.2 Deletion Syndrome correlate with disease manifestations but do not correlate with GP1b surface expression (2022)

Abstract Prior studies have demonstrated that patients with chromosome 22q11.2 deletion syndrome (22q11.2DS) have lower platelet counts (PC) compared to non-deleted populations. They also have an increased mean platelet volume. The mechanism for this has been postulated to be haploinsufficiency of the GPIBB gene. We examined platelet parameters, deletion size and factors known to influence counts, including status of thyroid hormone and CHD, in a population of 825 patients with 22q11.2DS. We also measured surface expression of GPIB-IX complex by flow cytometry. The major determinant of PC was deletion status of GP1BB , regardless of surface expression or other factors. Patients with nested distal chromosome 22q11.2 deletions (those with GP1BB present) had higher PCs than those with proximal deletions where GP1BB is deleted. Patients with 22q11.2DS also demonstrated an accelerated PC decrease with age, occurring in childhood. These data demonstrate that genes within the proximal deletion segment drive PC differences in 22q11.2DS and suggest that PC reference ranges may need to be adjusted for age and deletion size in 22q11.2DS populations. Bleeding did not correlate with either platelet count or GP1b expression. Further studies into drivers of expression of GP1b and associations with severe thrombocytopenia and immune thrombocytopenia are needed to inform clinical care.
Regularized maximum likelihood for intrinsic dimension estimation (2010)

We propose a new method for estimating the intrinsic dimension of a dataset by applying the principle of regularized maximum likelihood to the distances between close neighbors. We propose a regularization scheme which is motivated by divergence minimization principles. We derive the estimator by a Poisson process approximation, argue about its convergence properties and apply it to a number of simulated and real datasets. We also show it has the best overall performance compared with two other intrinsic dimension estimators. 1
CHF Symptoms May Not Be Related to Pump Function (1995)

The exertional dyspnea and fatigue of heart failure are usually attributed to circulatory dysfunction and treated as such. Several recent studies suggest exercise intolerance in heart failure may not be due solely to circulatory factors.

In this study 52 ambulatory patients with heart failure of at least six months duration and on digoxin, diuretics, and an ACE inhibitor were evaluated for a relation between their symptoms and …
Psychotic states in childrenEditorsMargaretRustin ,MariaRhode ,AlexDubinsky ,DubinskyHelene Psychotic states in childrenDuckworth1997,293 pages,£12.95. 0 7156 277590715627759 (1998)

The Tavistock Clinic has been a cornerstone for psychoanalytic therapy work with children. Its approach, highlighted in this book, is founded on commitment to the relief of suffering and classical psychotherapeutic techniques in helping children develop their potential. Case studies give the book its strength.
Energy-aware wireless networking with directional antennas: the case of session-based broadcasting and multicasting (2002)

We consider ad hoc wireless networks that use directional antennas and have limited energy resources. To explore quantitatively the advantage offered by the use of directional antennas over the case of omnidirectional antennas, we consider the case of connection-oriented multicast traffic. Building upon our prior work on multicasting algorithms, we introduce two protocols that exploit the use of directional antennas and evaluate their performance, We observe significant improvement with respect to the omnidirectional case, in terms of both energy efficiency and network lifetime. Additionally, we show that further substantial increase in the network's lifetime can be achieved by incorporating a simple measure of a node's residual energy into the node's cost function.
Characterization and Metrology of Gold and Copper Electroplated Stylus Ion Traps (2016)

Electrochemical fabrication offers unique advantages for nano/microfabrication of 2D and 3D structures. Precise control of deposition molds and thicknesses allows significant challenges to be solved through electrodeposition that are beyond the capabilities of standard silicon methods and conventional machining techniques. One unique application is the study of trapped ions enabling enhanced measurement techniques and reduction of anomalous motional heating 1 . The main goal is to correlate the physical features with electric field noise, which can be sensitively measured with the ions. Previous two layer ion taps were created using electroformed gold into high aspect ratio molds, here we further investigate effects of chemistry make-up, applied current density, and pulse plating of gold and copper electrochemical deposition. The effects will then be characterized using scanning electron microscopy, profilometry, energy dispersive spectroscopy, x-ray diffraction, and electron backscatter diffraction to characterize feature height, feature dimensions, surface roughness, stoichiometry, crystal structure, and crystallite size. 1 C. L. Arrington, K. S. McKay, E. D. Baca, J. J. Coleman, Y. Colombe, P. Finnegan, D. A. Hite, A. E. Hollowell, R. Jordens, J. D. Jost, D. Leibfried, A. M. Rowen, U. Warring, M. Weides, A. C. Wilson, D. J. Wineland, and D. P. Pappas, 'Micro-Fabricated Stylus Ion Trap', Review of Scientific Instruments, 84 (2013). Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-AC04-94AL85000. SAND2015-10657A
Gravitational waves by gamma-ray bursts and the Virgo detector: the case of GRB 050915a (2007)

In the framework of the expected association between gamma-ray bursts and gravitational wave signals, we present the preliminary results of an analysis aimed to search for bursts of gravitational waves associated with the long GRB 050915a. GRB 050915a was detected by the Swift satellite in 2005, when the Virgo detector was engaged in one of its science runs, namely the C7 run, during which the best sensitivity attained in 2005 was exhibited. This offered the opportunity for the first coincident analysis between a gamma-ray burst and the Virgo gravitational wave detector. Here we give an overview of this ongoing analysis, which at the end will play the role of a prototype, crucial in defining a methodology for gamma-ray burst triggered searches with Virgo. The final results of our analysis will also allow us to evaluate up to which level Virgo will be able to constrain the amplitude of the gravitational wave signal from a typical long gamma-ray burst.
Use of germ-line polymorphisms in genes involved in the IGF pathway to predict efficacy of cetuximab independent of K-ras in mCRC patients (IMCL-0144). (2010)

3562 Background: Insulin-like growth factor (IGF) signaling pathway is an important growth-regulatory pathway involved in the CRC progression. Previous studies showed that activation of the IGF1-Receptor (IGF1R) may result in resistance to anti-EGFR targeted treatment. We tested whether germ-line variations in the IGF1, and IGF1-R genes are associated with clinical outcome in mCRC patients treated with cetuximab. Methods: Tissue samples of 130 patients enrolled in a phase II clinical trial of cetuximab monotherapy were analyzed. gDNA was extracted from dissected FFPE tumor tissue and K-Ras mutation status and six potentially functional polymorphisms were analyzed using direct DNA-sequencing and PCR-RFLP. Results: In univariate and multivariate analysis five IGF pathway SNPs were significantly associated with PFS or OS (Table). Response rate was significantly increased with 50% for IGF1rs2946834 (AA) and 24% for IGF1rs6214 (CC) (univariate p=0.0025 and p=0.042, respectively) in K-Ras wild-type patients. In recursive partitioning we were able to identify subgroups of patients with PFS of 1.1 to 4.0 months (HR: 4.97–Reference) and with OS of 2.0 to 10.1 months (HR: 6.29–Reference). Conclusions: Our data suggest that IGF pathway SNPs may be potential molecular markers to predict efficacy of EGFR inhibitors. Prospective larger studies are warranted to validate our findings. N PFS OS Median, mo (95% CI) P* uni-variate P† multi-variate Median, mo (95% CI) P* uni-variate P† multi-variate IGF1rs6214 0.038 0.008 0.044 0.01 TT 16 1.1 (1.1, 1.3) 2.3 (2.0, 6.4) CC/CT 106 1.3 (1.3, 2.0) 6.5 (4.8, 8.2) IGF1rs2946834 <.0001 0.001 0.15 0.17 GG 58 1.5 (1.3, 2.6) 6.6 (3.7, 8.6) AG 45 1.2 (1.2, 1.3) 4.4 (2.7, 7.0) AA 18 2.6 (1.3, 5.4) 8.9 (4.1, 11.5) IGF1 rs7136446 0.034 0.38 0.026 0.034 CC 30 1.3 (1.2, 3.9) 6.5 (4.1, 10.5) CT 36 1.2 (1.2, 1.4) 3.4 (2.3, 6.4) TT 51 1.5 (1.3, 2.6) 7.5 (5.3, 10.7) IGF1Rrs2272037 0.79 0.66 0.039 0.28 TT 34 1.3 (1.2, 2.4) 8.7 (4.9, 14.0) CT/CC 79 1.3 (1.2, 2.3) 6.3 (3.7, 7.9) IGF1Rrs2016347 0.080 0.27 0.038 0.033 TT 46 2.3 (1.3, 3.0) 8.2 (6.3, 10.7) GT/GG 66 1.3 (1.2, 1.4) 4.2 (3.4, 7.5) * Log-rank test. † Adjusted for race, ECOG, K-Ras, Rash, EGFR +497G>A, COX-2 +8473T>C, EGF+61A>G. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems, Merck Bristol-Myers Squibb, ImClone Systems Bristol-Myers Squibb
Wildhaber—Novikov circular arc gears: geometry and kinematics (1986)

Abstract An exact analysis of the geometry and kinematics of the Wildhaber—Novikov (W. -N.) system of high-conformity gears is described. The techniques of gear analysis developed by Dyson (1969) are used to obtain the shape of the gap between the gear teeth in contact at zero load. Exact expressions for the entrainment and sliding velocities at the point of contact are also obtained. The theory therefore provides the basic geometrical and kinematic data required for the precise analysis of contact stresses and elastohydrodynamic lubrication. The analysis has been applied to a pair of real gears, and contours of the zero-load gap between the teeth are shown for a range of centre distances and corresponding pressure angles. Values of entrainment and sliding velocities are also obtained for these gears. Regions of potential interference between W. —N. gear teeth are demonstrated and the analysis may be used to show how they can be avoided in practice.
Large-scale solvothermal synthesis of fluorescent carbon nanoparticles (2014)

The large-scale production of high-quality carbon nanomaterials is highly desirable for a variety of applications. We demonstrate a novel synthetic route to the production of fluorescent carbon nanoparticles (CNPs) in large quantities via a single-step reaction. The simple heating of a mixture of benzaldehyde, ethanol and graphite oxide (GO) with residual sulfuric acid in an autoclave produced 7 g of CNPs with a quantum yield of 20%. The CNPs can be dispersed in various organic solvents; hence, they are easily incorporated into polymer composites in forms such as nanofibers and thin films. Additionally, we observed that the GO present during the CNP synthesis was reduced. The reduced GO (RGO) was sufficiently conductive (σ ≈ 282 S m(-1)) such that it could be used as an electrode material in a supercapacitor; in addition, it can provide excellent capacitive behavior and high-rate capability. This work will contribute greatly to the development of efficient synthetic routes to diverse carbon nanomaterials, including CNPs and RGO, that are suitable for a wide range of applications.
Physical limits to magnetogenetics (2016)

This is an analysis of how magnetic fields affect biological molecules and cells. It was prompted by a series of prominent reports regarding magnetism in biological systems. The first claims to have identified a protein complex that acts like a compass needle to guide magnetic orientation in animals (Qin et al., 2016). Two other articles report magnetic control of membrane conductance by attaching ferritin to an ion channel protein and then tugging the ferritin or heating it with a magnetic field (Stanley et al., 2015; Wheeler et al., 2016). Here I argue that these claims conflict with basic laws of physics. The discrepancies are large: from 5 to 10 log units. If the reported phenomena do in fact occur, they must have causes entirely different from the ones proposed by the authors. The paramagnetic nature of protein complexes is found to seriously limit their utility for engineering magnetically sensitive cells.
Computationally efficient QRD-based wide-band beamforming (2002)

Taking advantage of the time-shift properties inherent in the data makes it possible to reduce the computational load of a least-squares wideband beamforming algorithm from O(N/sup 2/p/sup 2/) to O(Np/sup 2/), assuming a p-channel beamformer with an N-tap filter in each channel. It is shown how the theory behind the recent work on QR decomposition (QRD)-based lattice filter algorithms can be applied to the wideband beamforming problem, and the computationally efficient QRD-based algorithm that results is described. The resulting architecture is essentially the same as the lattice of triangular arrays that has been derived, separately, by B. Yang and J.F. Bohme (1989) and by F. Ling (1989). The connection between these different approaches is reviewed. Also described is a simplified derivation of the QRD-based lattice algorithm that is applicable to both the adaptive filtering and the wideband beamforming problems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>