gebhart/patrepeval huggingface dataset:
Chemotherapy-induced uridine diphosphate release promotes breast cancer metastasis through P2Y6 activation (2016)

Although purinergic signaling is important in regulation of immune responses, the therapeutic potential of it in the tumor microenvironment is little defined. In this study, we demonstrate that UDP/P2Y6 signaling facilitates breast cancer metastasis both in vitro and in vivo. We found that P2Y6 is not only aberrantly expressed and mutated in most tumor types, but also highly correlated with poor prognosis in breast cancer patients. Furthermore, the migration and invasion of breast cancer cells was obviously increased by UDP and blocked by P2Y6 specific inhibitor MRS2578 and P2Y6 shRNA. Similar results was also found in breast cancer cell metastasis mouse model. Interestingly, the endogenous agonist UDP was released significantly by doxorubicin treated cells. In addition, the expression and enzyme activity of MMP-9 were both promoted by UDP and inhibited by MRS2578 or P2Y6 shRNA. Furthermore, UDP-induced cell invasion was blocked by an MMP-9 inhibitor. Mechanistically, the MAPKs and NF-κB signaling pathways, known to be involved in regulation of MMP-9 expression, were both activated by UDP. Taken together, our study reveals a relationship between extracellular danger signals and breast cancer metastasis, which suggests the potential therapeutic significance of UDP/P2Y6 signaling in cancer therapy.
A BLOOD PUMP POWERED AND CONTROLLED BY A FLUID AMPLIFICATION SYSTEM (1962)

Division of Clinical Surgery, Walter Reed Army Institute of Research, WRAMC and Diamond Ordnance Fuze Laboratories, Washington 12, D.C.
Boundary Layers Refractory/Glass Melt and Glass Defects (2008)

In this paper the formation of boundary layers and their behaviour regarding corrosion and glass defect potential of different refractory/glass melt combinations will be discussed. The reaction between refractories and glass melts is determined by the diffusion of the different ions from the glass melt into the refractory material and vice versa. The connected solution reactions lead to the formation of a saturation boundary layer, which influences the corrosion behaviour and the glass defect potential. The behaviour of the boundary layers of various refractory/glass melt types are partly complete different. On the one side there are refractory/glass melt combinations which form a relative thick reaction layer, on the other side there are refractory/glass melt combinations with very thin boundary layers. Thick reaction layers affect in the most cases like a protection layer with a good corrosion resistance, but there can be a relative high glass defect potential at operation changes. Thin reaction layers have for the most cases a low glass defect potential, but partly a higher corrosion rate.
An active noise control algorithm with gain and power constraints on the adaptive filter (2013)

This article develops a new adaptive filter algorithm intended for use in active noise control systems where it is required to place gain or power constraints on the filter output to prevent overdriving the transducer, or to maintain a specified system power budget. When the frequency-domain version of the least-mean-square algorithm is used for the adaptive filter, this limiting can be done directly in the frequency domain, allowing the adaptive filter response to be reduced in frequency regions of constraint violation, with minimal effect at other frequencies. We present the development of a new adaptive filter algorithm that uses a penalty function formulation to place multiple constraints on the filter directly in the frequency domain. The new algorithm performs better than existing ones in terms of improved convergence rate and frequency-selective limiting.
WireGuard: Next Generation Kernel Network Tunnel (2017)

Author(s): Jason A. Donenfeld Download: Paper (PDF) Date: 27 Feb 2017 Document Type: Reports Additional Documents: Slides Video Associated Event: NDSS Symposium 2017 Abstract: WireGuard is a secure network tunnel, operating at layer 3, implemented as a kernel virtual network interface for Linux, which aims to replace both IPsec for most use cases, as well as popular user … Continued
ABO blood group determines plasma von Willebrand factor levels: a biologic function after all? (2006)

For many years, an association between ABO histo-blood group and risk of thrombosis has been recognized. Blood group non-O (A, B, and AB) individuals have consistently been found to demonstrate increased incidence of both arterial and venous thrombotic disease, compared to group O individuals. This increased risk is attributable to the fact that ABO blood group influences plasma levels of a coagulation glycoprotein named von Willebrand factor (VWF). VWF levels are 25 percent higher in non-O compared to group O individuals. The mechanism by which ABO group determines plasma VWF levels has not been determined. ABO(H) carbohydrate antigenic determinants, however, are expressed on the N-linked glycan chains of circulating plasma VWF. This review will focus on the carbohydrate structures of VWF and recent studies suggesting that subtle variations in these structures (particularly differences in ABO blood group antigen expression) may have clinically significant effects on VWF proteolysis and clearance.
Control, Regulation and Command System of Hydronic Radiant Floors Heating by Wireless and Energy Harvesting Sensors and Actuators (2013)

This paper presents the development of an innovative control, regulation and command system for hydronic radiant floors, more flexible and efficient that guarantees a better thermal comfort to the user and simultaneously improves the energy efficiency of this type of heating system. The majority of the actual control of hydronic radiant floors is done by thermostats that measure the air temperature and control the actuators (pumps and valves) in order to maintain the room at the specified temperature. These systems requires the frequent adjustment of thermostats set-point in order to obtain thermal comfort as it depends on other factors than just the air temperature, such as, the air humidity, external environmental conditions, radiant temperature, among others. This paper presents a control, regulation and command solution that requires minimum user intervention, as the user only has to choose the desirable thermal comfort level. The control algorithm is based on the calculation of PMV (Predicted Mean Vote) index as defined on Thermal Comfort Standard ISO 7730. Another advantage of the proposed system is related to the wireless and energy harvesting sensors and actuators that provide much more flexibility to the system.
In vitro sorption of albumin, immunoglobulin G, and lysozyme to enamel and cementum from human teeth (1984)

Sorption of three 125I-labeled human proteins (albumin, immunoglobulin G, and lysozyme) to enamel and cementum was investigated. All three proteins sorped most when suspended in 0.0005 M solution of phosphate or calcium chloride where the least competition between solute ions and label occurred. The addition of human serum to labeled proteins caused a decrease in their sorption which could be partially reversed by increasing the concentration of label. Kinetic experiments demonstrated that sorption was dependent on protein concentration and incubation time and that most of the sorption occurred within the first minute of the reaction. In conclusion, the binding of the three labeled proteins was affected by the charge of the solute ions and was dependent on ion concentration and reaction time. Sorption correlated for the most part with the pK values of the proteins and thus lysozyme, the most basic protein, sorped more than immunoglobulin G, which sorped more than albumin. In all cases, cementum bound more basic protein than did enamel. Increased levels of albumin sorption to enamel occurred when the protein was suspended in the CaCl2 solution rather than in phosphate. In addition, based on Scatchard analysis, approximately twice as many potential protein binding sites were found for cementum versus enamel.
Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia (2002)

Many postsynaptic density proteins carrying postsynaptic density-95/discs large/zone occludens-1 (PDZ) domain(s) interact with glutamate receptors to control receptor dynamics and synaptic plasticity. Here we examined the expression of PDZ proteins, synapse-associated protein (SAP) 97, postsynaptic density (PSD)-95, chapsyn-110, GRIP1 and SAP102, in post-mortem brains of schizophrenic patients and control subjects, and evaluated their contribution to schizophrenic pathology. Among these PDZ proteins, SAP97 exhibited the most marked change: SAP97 protein levels were decreased to less than half that of the control levels specifically in the prefrontal cortex of schizophrenic patients. In parallel, its binding partner, GluR1, similarly decreased in the same brain region. The correlation between SAP97 and GluR1 levels in control subjects was, however, altered in schizophrenic patients. SAP102 levels were also significantly reduced in the hippocampus of schizophrenic patients, but this reduction was correlated with sample storage time and post-mortem interval. There were no changes in the levels of the other PDZ proteins in any of the regions examined. In addition, neuroleptic treatment failed to mimic the SAP97 change. These findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients.
Nucleotide sequence of messenger RNA encoding VHDJH and VKJK of a highly conserved idiotype-defined primary response anti-hapten antibody (1992)

The primary humoral immune response of mice to the hapten phthalate (Xmp) is focused upon two adjacent immunodominant negatively charged carboxyl groups on a benzene ring that are in positions meta and para to the azolinkage (i.e., Xmp) to the protein carrier keyhole limpet hemocyanin. A significant fraction of the anti-Xmp antibodies raised in several different inbred mouse strains (BALB/c, DBA/2, A/HeHa; C3H, and SM/J), and many wild mouse populations express a cross-reactive Id, CRIXmp-1. This CRIXmp-1 is conspicuously absent in C57BL/6 mice. In order to obtain a better understanding of the events and parameters that influence the selection and regulation of the primary response B cell repertoire, and to explore the structural basis of Ag binding, we have determined the nucleotide sequence of the entire V region gene complexes, which encode the H and L chains of these highly conserved and dominant CRIXmp-1+ antibodies. Our data establish that the H chain gene complex consists of a single VH germ-line gene that is identical to VH Oxazolone-1, encoding the H chain of another highly conserved and dominant cross-reactive Id family associated with the primary response to Oxazolone. In CRIXmp-1+ Xmp-specific hybridomas this gene is joined to a limited set of D region sequences that express a conserved amino acid motif-GLR. At least three of the five D regions examined are coded for by DFL16.2. This VHD complex can be utilized with one of three different JH region genes (JH1, JH2, and JH4) without any significant effect upon antibody fine specificity or Id. In spite of this lack of JH fidelity all of the CRIXmp-1+ hybridomas have precisely maintained the same length in the H chain CDR3 and FRW4 by altering either the length of the D segment or the length of JH. Nucleotide sequence analysis of the VL gene complex of CRIXmp-1+ anti-Xmp antibodies indicates that the L chain V region is also encoded by a single germ-line gene. The amino acid sequence predicted from the nucleotide sequence of the VKJK from Xmp-specific CRIXmp-1+ hybridomas is identical to the sequence of the anti-arsonate antibody 1210.7, which is the prototype of another Id family (CRI) that is conserved and dominant in BALB/c mice.
A universal discoidal nanoplatform for the intracellular delivery of PNAs (2019)

Peptide nucleic acids (PNAs) have gained considerable attention due to their remarkable potential in gene editing and targeting-based strategies. However, cellular delivery of PNAs remains a challenge in developing their broader therapeutic applications. Here, we investigated a novel complex made of lipid bicelles and PNA-based carriers for the efficient delivery of PNAs. For proof of concept, PNAs targeting microRNA (miR) 210 and 155 were tested. Comprehensive evaluation of positive as well as negative charge-containing bicelles with PNA : lipid ratios of 1 : 100, 1 : 1000, and 1 : 2500 was performed. The negatively charged bicelles with a PNA : lipid molar ratio of 1 : 2500 yielded a discoidal shape with a uniform diameter of ∼30 nm and a bilayer thickness of 5 nm, while the positively charged bicellar system contained irregular vesicles after the incorporation of PNA. Small-angle X-ray scattering (SAXS) analysis was performed to provide insight into how the hydrophobic PNAs interact with bicelles. Further, flow cytometry followed by confocal microscopy analyses substantiate the superior transfection efficiency of bicelles containing dye-conjugated antimiR PNAs. Functional analysis also confirmed miR inhibition by PNA oligomers delivered by bicelles. The nanodiscoidal complex opens a new pathway to deliver PNAs, which, on their own, are a great challenge to be endocytosed into cells.
Structural integrity during remanufacture of a topologically interlocked material (2012)

Purpose Topologically interlocked materials are a class of materials in which individual unit elements interact with each other through contact only. Cracks and other defects occurring due to external loading are contained in the individual unit elements. Thus, topologically interlocked materials are damage tolerant and provide high structural integrity. The purpose of this paper is to investigate the concepts of remanufacturing in the context of a material for which the intended use is structural such that the material's structural integrity is of concern. In particular, the study is concerned with the mechanical behavior of a topologically interlocked material. Design/methodology/approach A topologically interlocked material based on tetrahedron unit elements is investigated experimentally. Manufacturing with aid of a robotically controlled end‐effector is demonstrated, and mechanical properties are determined for a plate configuration. A conceptual mechanical model for failure of topologically interlocked materials is developed and used to interpret the experimental results. Findings It is demonstrated that remanufacturing of the topologically interlocked material is possible with only a limited loss of material performance. The proposed model predicts trends in agreement with the experimental findings. Research limitations/implications While the model predictions are qualitatively in agreement with experiments, more detailed finite element models are needed to predict the material performance accurately. Experiments were conducted on a model material obtained from a 3D printer and should be verified on other solids. Practical implications The authors demonstrate that damage containment together with the absence of binders or adhesives enables reuse through remanufacturing without loss of structural integrity. Social implications Topologically interlocked materials emerge as attractive materials for sustainable engineering once their material performance are weighted with an environmental impact factor. Originality/value Remanufacturing experiments on a novel class of materials were conducted and a new model for the characterization of the structural integrity of topologically interlocked materials is proposed and successfully evaluated against experiments in at least qualitative form.
Design of complementary tilt-gate TFETs with SiGe/Si and III-V integrations feasible for ultra-low-power applications (2015)

A new concept of the structure design with an alignment between the maximum band-to-band tunneling rate and electric field has been proposed to enhance the performance of TFETs. It was found that the specific gate of TFET to form an obtuse shape can dramatically improve the on-current of TFET, with over 4 order improvement in comparison to planar ones. This complementary TFET (CTFET) was also demonstrated by SRAM as a benchmark, with SiGe/Si integrated with III-V on Si substrate. In order to increase WNM and RSNM of CTFET SRAM, a new scheme has been adopted, in which SRAM has been successfully demonstrated with operating bias down to 0.3V.
Correction to "Revision of Tunneling Field-Effect Transistor in Standard CMOS Technologies" (2007)

Previously published results by the authors, from 2004 to 2006, on the tunneling field-effect transistor (TFET) are revised in this correction. The devices that they had characterized as TFETs contain a conducting path in parallel to the intended tunneling junction. Therefore, the measured characteristics are similar to a MOSFET with a resistive source connection
Improving Pollution Control in Uranium Mining and Milling (1977)

In many respects, the environmental impact of uranium mining and milling resembles that of any hydrometallurgical processing operation. Mine water and run-off from ore and waste heaps contain heavy metals as a result of natural leaching. Liquid wastes produced during milling may be highly acidic or alkaline, and may contain a high concentration of dissolved salts including heavy metals. The finely divided tailings residue must be impounded and stabilised against erosion. Uranium processing poses two unique problems: possible leaching of radioactive elements (particularly radium) into natural waters and escape of radon gas from ore and tailings leading to airborne dispersal of its radioactive daughters. Laboratory experiments have been conducted to characterise the likely composition of wastes from the mining and milling of Australian ores and to demonstrate methods for their treatment. Neutralisation of acidic tailings-raffinate slurries to pH 8 was found to reduce most heavy metal concentrations to less than 0.5 mg R-1. Two-stage neutralisation, using limestone to pH 4.5 and then lime, is economically attractive. Treatment of mine water and process raffinates with barium chloride to co-precipitate barium and radium sulphates is effective in reducing radium-226 concentrations below 3 pg l-1. Other waste treatment processes discussed include radon adsorption on activated charcoal, chemical leaching of radium from tailings and adsorption of residual heavy metals on manganese dioxide.
Manganese(III)‐Promoted Tandem Oxidation and Cyclization of β‐Keto Ester Derivatives of Terpenoids (2011)

Abstract A new type of terpenoid cyclization directed by a β‐keto ester moiety has been developed, which proceeded by manganese(III)‐initiated oxidation of the β‐keto ester, followed by an intramolecular hetero Diels–Alder reaction with the terpenoid chain. This reaction produces polycyclic dihydropyrans in high yields and stereoselectivities under mild conditions.
Phage engineering: how advances in molecular biology and synthetic biology are being utilized to enhance the therapeutic potential of bacteriophages (2017)

Background The therapeutic potential of bacteriophages has been debated since their first isolation and characterisation in the early 20 th century. However, a lack of consistency in application and observed efficacy during their early use meant that upon the discovery of antibiotic compounds research in the field of phage therapy quickly slowed. The rise of antibiotic resistance in bacteria and improvements in our abilities to modify and manipulate DNA, especially in the context of small viral genomes, has led to a recent resurgence of interest in utilising phage as antimicrobial therapeutics. Results In this article a number of results from the literature that have aimed to address key issues regarding the utility and efficacy of phage as antimicrobial therapeutics utilising molecular biology and synthetic biology approaches will be introduced and discussed, giving a general view of the recent progress in the field. Conclusions Advances in molecular biology and synthetic biology have enabled rapid progress in the field of phage engineering, with this article highlighting a number of promising strategies developed to optimise phages for the treatment of bacterial disease. Whilst many of the same issues that have historically limited the use of phages as therapeutics still exist, these modifications, or combinations thereof, may form a basis upon which future advances can be built. A focus on rigorous in vivo testing and investment in clinical trials for promising candidate phages may be required for the field to truly mature, but there is renewed hope that the potential benefits of phage therapy may finally be realised.
High-fidelity full-waveform inversion with an initial velocity model from multiple wells interpolation (2016)

Full waveform inversion (FWI) is a promising technique for inverting a high-resolution subsurface velocity model. The success of FWI highly depends on a fairly well initial velocity model. We propose a method for building a remarkable initial velocity model that can be put into the FWI framework for inverting nearly perfect velocity structure. We use a well log interpolated velocity model as a high-fidelity initial model for the subsequent FWI. The interpolation problem is solved via a least-squares method with a structural regularization. In order to obtain the geological structure of subsurface reflectors, an initial reverse time migration (RTM) with a fairly realistic initial velocity model is used to roughly calculate the local slope of subsurface structure. The well log interpolated initial velocity model can be very close to the true velocity while having small velocity anomaly or over-smoothing caused by the imperfect velocity interpolation, which however can be compensated during the subsequent FWI iterations. Regarding the field deployment, we suggest that future drilling should be seismic-oriented, which can help fully utilize the well logs for building initial subsurface velocity model and will facilitate a wide application of the proposed methodology. Presentation Date: Wednesday, October 19, 2016 Start Time: 4:25:00 PM Location: 162/164 Presentation Type: ORAL
Pax6 Is Crucial for β-Cell Function, Insulin Biosynthesis, and Glucose-Induced Insulin Secretion (2012)

The Pax6 transcription factor is crucial for endocrine cell differentiation and function. Indeed, mutations of Pax6 are associated with a diabetic phenotype and a drastic decrease of insulin-positive cell number. Our aim was to better define the β-cell Pax6 transcriptional network and thus provide further information concerning the role of Pax6 in β-cell function. We developed a Pax6-deficient model in rat primary β-cells with specific small interfering RNA leading to a 75% knockdown of Pax6 expression. Through candidate gene approach, we confirmed that Pax6 controls the mRNA levels of the insulin 1 and 2, Pdx1, MafA, GLUT2, and PC1/3 genes in β-cells. Importantly, we identified new Pax6 target genes coding for GK, Nkx6.1, cMaf, PC2, GLP-1R and GIPR which are all involved in β-cell function. Furthermore, we demonstrated that Pax6 directly binds and activates specific elements on the promoter region of these genes. We also demonstrated that Pax6 knockdown led to decreases in insulin cell content, in insulin processing, and a specific defect of glucose-induced insulin secretion as well as a significant reduction of GLP-1 action in primary β-cells. Our results strongly suggest that Pax6 is crucial for β-cells through transcriptional control of key genes coding for proteins that are involved in insulin biosynthesis and secretion as well as glucose and incretin actions on β-cells. We provide further evidence that Pax6 represents a key element of mature β-cell function.