gebhart/patrepeval huggingface dataset:
Role of Interleukin-1β in the Development of Malnutrition in Chronic Renal Failure Patients (2005)

Protein-energy malnutrition and wasting are common among patients with end-stage renal disease (ESRD) and these complications are strongly associated with poor survival in these patients. Whereas both under- and overweight predict in increased mortality risk in the general population, a high body mass index is associated with better outcome in ESRD patients. Circulating levels of pro-inflammatory cytokines are markedly elevated in uremia and also predictor of a poor clinical outcome in ESRD patients. Interleukin-1beta (IL-1beta), which is a major pro-inflammatory cytokine, may further amplify inflammation and lead to malnutrition, through inducing anorexia, and muscle wasting due to increased protein breakdown. Several clinical studies have shown that the circulating level of IL-1beta may affect nutritional status, especially body composition. Several IL-1 gene cluster polymorphisms were reported, and they may affect the prevalence of cytokine-mediated diseases. Although a number of factors are related to malnutrition and wasting in ESRD, pro-inflammatory cytokines, such as IL-1beta, may play an important role. This could in part be due to genetic factors. Further research, especially regarding the IL-1 gene cluster polymorphisms, is necessary to determine this hypothesis.
Oxford textbook of oncology (1996)

The Oxford Textbook of Oncology is a landmark reference resource for practising and trainee oncologists. It combines the experience of the world's leading cancer experts with an unsurpassed integration of basic science and clinical practice. It sets new standards for publishing in oncology, offering a ground-breaking innovative approach to the field combined with the quality, accuracy, and intellectual rigour you have come to expect from the world's most prestigious reference publisher. The Oxford Textbook of Oncology is the first major oncology text to provide a fully integrated discussion of the various treatment techniques available and the first to present oncology from an international perspective rather than from the narrow view of a single area or country. The Oxford Textbook of Oncology is the definitive oncology reference for this decade and beyond. It has been designed with one purpose: to help you improve the quality, ease, and speed of the care you provide your patients. It is an essential purchase for every medical oncologist, radiologists, surgical oncologists, pathologists, and others engaged in the care of cancer patients. This book is intended for oncologists, radiotherapists, pathologists, histologists, surgeons, and physicians in all branches of medicine.
Active Cache Emulator (2008)

This paper presents the active cache emulator (ACE), a novel field-programmable gate-array (FPGA)-based emulator that models an L3 cache actively and in real-time. ACE leverages interactions with its host system to model the target system. Unlike most existing FPGA-based cache emulators that collect only memory traces from their host system, ACE provides feedback to its host by injecting delays to time dilate the host system such that it experiences hit/miss latencies of the emulated cache. Such active emulation expands the context of performance evaluations by allowing measurements of system performance metrics (e.g., CPI, operations per second, frame rate) in addition to the typical cache-specific performance metrics (e.g., miss ratio) provided by existing emulators. ACE is designed to interface with a front-side bus (FSB) of a typical Pentium-based PC system. ACE utilizes the FSB snoop stall mechanism to inject delays into the system. At present, ACE is implemented using a Xilinx XC2V6000 FPGA running at 66 MHz, the same speed as its host's FSB. Verification of ACE includes using the cache calibrator and RightMark memory analyzer software to confirm proper detection of the emulated cache by the host system, and comparing ACE results with SimpleScalar software simulations. Finally, ACE is used to study L3 caches for compute-intensive, throughput-oriented, and real-time gaming benchmarks (SPEC-CPU2000, SPEC-JBB2000, Quake3). The study shows that analyzing only cache-specific metrics, as done by existing L3 cache studies with FPGA emulators, is insufficient. Active emulation mitigates this issue by providing a broader performance view, allowing researchers make better research conclusion.
For most large underdetermined systems of equations, the minimal 𝓁1‐norm near‐solution approximates the sparsest near‐solution (2006)

Abstract We consider inexact linear equations y ≈ Φ x where y is a given vector in ℝ n , Φ is a given n × m matrix, and we wish to find x 0,ϵ as sparse as possible while obeying ‖ y − Φ x 0,ϵ ‖ 2 ≤ ϵ. In general, this requires combinatorial optimization and so is considered intractable. On the other hand, the 𝓁 1 ‐minimization problem is convex and is considered tractable. We show that for most Φ, if the optimally sparse approximation x 0,ϵ is sufficiently sparse, then the solution x 1,ϵ of the 𝓁 1 ‐minimization problem is a good approximation to x 0,ϵ . We suppose that the columns of Φ are normalized to the unit 𝓁 2 ‐norm, and we place uniform measure on such Φ. We study the underdetermined case where m ∼ τ n and τ &gt; 1, and prove the existence of ρ = ρ(τ) &gt; 0 and C = C (ρ, τ) so that for large n and for all Φ's except a negligible fraction, the following approximate sparse solution property of Φ holds: for every y having an approximation ‖ y − Φ x 0 ‖ 2 ≤ ϵ by a coefficient vector x 0 ∈ ℝ m with fewer than ρ · n nonzeros , This has two implications. First, for most Φ, whenever the combinatorial optimization result x 0,ϵ would be very sparse, x 1,ϵ is a good approximation to x 0,ϵ . Second, suppose we are given noisy data obeying y = Φ x 0 + z where the unknown x 0 is known to be sparse and the noise ‖ z ‖ 2 ≤ ϵ. For most Φ, noise‐tolerant 𝓁 1 ‐minimization will stably recover x 0 from y in the presence of noise z . We also study the barely determined case m = n and reach parallel conclusions by slightly different arguments. Proof techniques include the use of almost‐spherical sections in Banach space theory and concentration of measure for eigenvalues of random matrices. © 2006 Wiley Periodicals, Inc.
Production of hydroxy fatty acids in the seeds of Arabidopsis thaliana (2000)

Seed-specific expression in Arabidopsis thaliana of oleate hydroxylase enzymes from castor bean and Lesquerella fendleri resulted in the accumulation of hydroxy fatty acids in the seed oil. By using various Arabidopsis mutant lines it was shown that the endoplasmic reticulum (ER) n-3 desaturase (FAD3) and the FAE1 condensing enzyme are involved in the synthesis of polyunsaturated and very-long-chain hydroxy fatty acids, respectively. In Arabidopsis plants with an active ER Delta12-oleate desaturase the presence of hydroxy fatty acids corresponded to an increase in the levels of 18:1 and a decrease in 18:2 levels. Expression in yeast indicates that the castor hydroxylase also has a low level of desaturase activity.
A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018)

Translation of the CRISPR-Cas9 system to human therapeutics holds high promise. However, specificity remains a concern especially when modifying stem cell populations. We show that existing rationally engineered Cas9 high-fidelity variants have reduced on-target activity when using the therapeutically relevant ribonucleoprotein (RNP) delivery method. Therefore, we devised an unbiased bacterial screen to isolate variants that retain activity in the RNP format. Introduction of a single point mutation, p.R691A, in Cas9 (high-fidelity (HiFi) Cas9) retained the high on-target activity of Cas9 while reducing off-target editing. HiFi Cas9 induces robust AAV6-mediated gene targeting at five therapeutically relevant loci (HBB, IL2RG, CCR5, HEXB, and TRAC) in human CD34<sup>+</sup> hematopoietic stem and progenitor cells (HSPCs) as well as primary T cells. We also show that HiFi Cas9 mediates high-level correction of the sickle cell disease (SCD)-causing p.E6V mutation in HSPCs derived from patients with SCD. We anticipate that HiFi Cas9 will have wide utility for both basic science and therapeutic genome-editing applications.
The early endosome: a busy sorting station for proteins at the crossroads. (2010)

Endocytosis marks the entry of internalized receptors into the complex network of endocytic trafficking pathways. Endocytic vesicles are rapidly targeted to a distinct membrane-bound endocytic organelle referred to as the early endosome. Despite the existence of numerous internalization routes, early endosomes (EE) serve as a focal point of the endocytic pathway. Sorting events initiated at this compartment determine the subsequent fate of internalized proteins and lipids, destining them either for recycling to the plasma membrane, degradation in lysosomes or delivery to the trans-Golgi network. Sorting of endocytic cargo to the latter compartments is accomplished through the formation of distinct microdomains within early endosomes, through the coordinate recruitment and assembly of the sorting machinery. An elaborate network of interactions between endocytic regulatory proteins ensures synchronized sorting of cargo to microdomains followed by morphological changes at the early endosomal membranes. Consequently, the cargo targeted either for recycling back to the plasma membrane, or for retrograde transport to the trans-Golgi network, localizes to newly-formed tubular membranes. With a high ratio of membrane surface to lumenal volume, these tubules effectively concentrate the recycling cargo, ensuring efficient transport out of the EE. Conversely, receptors sorted for degradation cluster at the flat clathrin lattices involved in invaginations of the limiting membrane, associating with newly formed intralumenal vesicles. In this review we will discuss the characteristics of early endosomes, their role in the regulation of endocytic transport, and their aberrant function in a variety of diseases.
Surface micromachining by sacrificial aluminium etching (1996)

Sacrificial aluminium etching enables micromechanical structures integrated with circuitry to be fabricated using standard IC processes followed by simple post-processing. In this paper, the etching characteristics of CMOS aluminium in four etch solutions are reported. The solutions are (A) a commercially available aluminium etchant, (B) Krumm etch, (C) diluted hydrochloric acid, and (D) diluted hydrochloric acid with hydrogen peroxide. The etching of narrow channels is studied as a function of time and temperature. Initially, the etching process is reaction-rate controlled and then crosses over to a diffusion-controlled regime with reduced etch rate. Underetching distances larger than are readily achieved with etchants `A', `B', and `D'. The commercially available aluminium etchant has a low initial underetch rate of at but offers best control. The initial etch rate of hydrochloric acid with hydrogen peroxide is at . However, irregular etch fronts are obtained. Reliable protection of aluminium pads against etchants `A', `B', and `D' is guaranteed by Shipley's photoresist S1828 spun at 3000 rpm and hardbaked at .
Supra-Nanosecond Dynamics of a Red-to-Blue Photon Upconversion System (2009)

Blue-green upconverted emission from 2-chloro-bis-phenylethynylanthracene (2CBPEA) sensitized by the red-absorbing platinum(II)tetraphenyltetrabenzoporphyrin (PtTPBP) has been investigated in N,N-dimethylformamide (DMF). The upconverted singlet fluorescence of 2CBPEA resulting from its sensitized triplet-triplet annihilation (TTA) is observed following selective excitation of PtTPBP at 635 +/- 5 nm. Stern-Volmer analysis of the photoluminescence quenching of PtTPBP by 2CBPEA yields a bimolecular quenching constant of 1.62 x 10(9) M(-1) s(-1), slightly below the diffusion limit in DMF at room temperature. The TTA process was confirmed by the quadratic dependence of the integrated upconverted singlet fluorescence emission profile of 2CBPEA measured as a function of 635 nm incident laser power. Time-resolved emission spectra following 630 nm nanosecond laser pulses illustrate the prompt nature of porphyrin phosphorescence quenching and the delayed nature of the upconverted singlet fluorescence from 2CBPEA. Transient absorption decays monitored at the peak of the characteristic 2CBPEA triplet-triplet excited-state absorption (490 nm) measured as a function of incident nanosecond 630 nm pump laser fluence recovered the rate constant for the sensitized TTA process, k(TT) = 5.64 +/- 0.08 x 10(9) M(-1) s(-1). To calculate this rate constant, we determined the triplet-triplet extinction coefficient of 2CBPEA (12,500 M(-1) cm(-1) at 490 nm) utilizing triplet energy transfer from donors with known excited-state extinction coefficients, namely [Ru(bpy)(3)](2+) and 2-acetonaphthone and averaged these values. The current work, to the best of our knowledge, represents the first example of red-to-blue upconversion thus demonstrating another viable sensitized TTA process, as well as providing the first measurements of k(TT) in a photon upconverting scheme. As 2CBPEA is stable under ambient conditions, this chromophore represents an almost ideal candidate for light-producing sensitized TTA in aerated polymeric materials, and we demonstrate successful translation of the present donor-acceptor/annihilator system into a low T(g) polyurethane.
Mitogenic Signals and Transforming Potential of Nyk, a Newly Identified Neural Cell Adhesion Molecule-Related Receptor Tyrosine Kinase (1995)

Nyk/Mer is a recently identified receptor tyrosine kinase with neural cell adhesion molecule-like structure (two immunoglobulin G-like domains and two fibronectin III-like domains) in its extracellular region and belongs to the Ufo/Axl family of receptors. The ligand for Nyk/Mer is presently unknown, as are the signal transduction pathways mediated by this receptor. We constructed and expressed a chimeric receptor (Fms-Nyk) composed of the extracellular domain of the human colony-stimulating factor 1 receptor (Fms) and the transmembrane and cytoplasmic domains of human Nyk/Mer in NIH 3T3 fibroblasts in order to investigate the mitogenic signaling and biochemical properties of Nyk/Mer. Colony-stimulating factor 1 stimulation of the Fms-Nyk chimeric receptor in transfected NIH 3T3 fibroblasts leads to a transformed phenotype and generates a proliferative response in the absence of other growth factors. We show that phospholipase C gamma, phosphatidylinositol 3-kinase/p70 S6 kinase, Shc, Grb2, Raf-1, and mitogen-activated protein kinase are downstream components of the Nyk/Mer signal transduction pathways. In addition, Nyk/Mer weakly activates p90rsk, while stress-activated protein kinase, Ras GTPase-activating protein (GAP), and GAP-associated p62 and p190 proteins are not activated or tyrosine phosphorylated by Nyk/Mer. An analysis comparing the Nyk/Mer signal cascade with that of the epidermal growth factor receptor indicates substrate preferences by these two receptors. Our results provide a detailed description of the Nyk/Mer signaling pathways. Given the structural similarity between the Ufo/Axl family receptors, some of the information may also be applied to other members of this receptor tyrosine kinase family.
Prediction of cost overruns using ensemble methods in data mining and text mining algorithms (2014)

In competitive bidding in the United States, the lowest bid is most often than not selected to perform the project. However, the lowest bidder tends to undervalue the costs in order to win the bid and as a result may incur significant cost increases during the construction life cycle due to change orders. For project owners to accurately estimate the actual project cost and to predict the bid that is close to the actual project, there is an urgent need for new decision aids to analyze the bidding patterns. The goal of this research has been to select the predictive features in a bid package to help minimize the cost overruns with the help of open source data mining software. The features were selected based on correlation and regression analysis by studying the p-values and r-squared values. The data set was then prepared with only the features that were affecting the output, which in our case were the cost overruns. The output is divided into 4 classes depending on the percentage of overrun. The learning algorithms used for prediction were neural networks, support vector machines, decision trees along with the ensemble methods. The empirical study of the prediction models suggest an efficiency of up to 50% in predicting whether a project will have cost overruns and what is the approximate range of percentage overrun.
Inhaled Therapies for Pulmonary Hypertension (2015)

The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies.
Structure and Activity of Recombinant Human Interferon-γ Analogs (1986)

We have prepared interferon-gamma (IFN-gamma) analogs to study the structural role of particular amino acids in relation to their effects on antiviral activity. Three IFN-gamma analogs were prepared on the basis of predicted secondary structure. In two of the analogs, [Gln25]IFN-gamma and [Thr45]IFN-gamma, changes were made at residue 25 (Asn to Gln) and at residue 45 (Met to Thr), respectively. [Gln25Lys78]IFN-gamma had two changes, at residue 25 (Asn to Gln) and residue 78 (Asn to Lys). Another analog, [Cys-Tyr-Cys]IFN-gamma, incorporated Cys-Tyr-Cys at the amino terminus. Comparison of the structure and activity of these analogs with that of the natural sequence protein suggested that residues 25 and 78 are at the protein surface and play an important role in antiviral activity. The residue at position 45 was found to be important for maintaining the protein structure, as assessed by circular dichroism spectroscopy. The addition of Cys-Tyr-Cys resulted in a small perturbation of protein structure and a small decrease in antiviral activity.
Synthesis and processing of glycoproteins gD and gC of herpes simplex virus type 1 (1980)

Herpes simplex virus type 1 (HSV-1) contains five glycoproteins, designated gA, gB, gC, gD, and gE. The present studies focused on the synthesis and processing of two of these, gC and gD. By using monoprecipitin antibody to gC, we demonstrated an antigenic and structural relationship between the precursor, pgC(110), and the product, gC(130). Tryptic peptide analysis showed that pgC and gC shared methionine peptides and that these molecules had the same fingerprint pattern as that of gC(130) extracted from the purified virion. These results suggested that post-translational processing of gC involved no major changes in methionine-containing tryptic peptides or in the cleavage sites required to generate those peptides. The syntheses of gC and gD were compared. We found that the glycoproteins were synthesized starting at different times in the infectious cycle; pgD was detected by 2 h postinfection, whereas pgC was first detected at 4 to 6 h postinfection. Both precursor molecules, pgC(110) and pgD(52), are basic glycopolypeptides, and in both cases processing involved changes in molecular weight and charge. These changes were detected by two-dimensional gel electrophoresis. Both glycoproteins exhibited heterogeneity, displayed as a series of spots (6 for gD and 15 to 20 for gC) of increasing negative charge and molecular weight. Neuraminidase treatment decreased the size, number, and acidic charge of the spots, suggesting that processing was due in part, but not entirely, to addition of sialic acid to pgD and pgC.
An Efficient Route to Macromonomers via ATRP and Click Chemistry (2006)

The combination of atom transfer radical polymerization (ATRP) and click chemistry was employed to prepare well-defined ω-(meth)acryloyl macromonomers in an efficient manner. Poly(n-butyl acrylate) (PBA), polystyrene (PS), and PS-b-PBA were prepared by ATRP and subsequently derivatized to contain azido end groups. The reaction of the azido-terminated polymers with alkyne-containing acrylate and methacrylate monomers resulted in near-quantitative chain end functionalization. Macromonomers of various molecular weights [PBA: Mn = 2.2−6.4 × 103 g/mol (DPn = 16−49); PS: Mn = 3.2−5.9 × 103 g/mol (DPn = 29−55)] and architectures were prepared by this method. The end group transformations required to incorporate the polymerizable functionality were accomplished either as a stepwise series of discrete reactions or as an in situ process, wherein azidation was immediately followed by azide−alkyne coupling in situ. In both cases, the degree of end group functionalization generally exceeded 90%. To demonstrate polymerizability, examples of ω-methacryloyloxy−PBA and ω-acryloyloxy−PS macromonomers were homopolymerized by conventional radical polymerization in toluene. The macromonomers and polymacromonomers were characterized by a combination of gel permeation chromatography using refractive index, light scattering, and viscosity detection, as well as 1H NMR spectroscopy and 1H−1H NMR correlation spectroscopy (COSY). This versatile method of incorporating polymerizable end groups from commercially available reagents should be applicable to a variety of (co)polymers accessible by ATRP.