gebhart/patrepeval huggingface dataset:
Phototriggered Local Anesthesia (2015)

We report a phototriggerable formulation enabling in vivo repeated and on-demand anesthesia with minimal toxicity. Gold nanorods (GNRs) that can convert near-infrared (NIR) light into heat were attached to liposomes (Lip-GNRs), enabling light-triggered phase transition of their lipid bilayers with a consequent release of payload. Lip-GNRs containing the site 1 sodium channel blocker tetrodotoxin and the α2-adrenergic agonist dexmedetomidine (Lip-GNR-TD) were injected subcutaneously in the rat footpad. Irradiation with an 808 nm continuous wave NIR laser produced on-demand and repeated infiltration anesthesia in the rat footpad in proportion to the irradiance, with minimal toxicity. The ability to achieve on-demand and repeated local anesthesia could be very beneficial in the management of pain.
Comparison of Enabling Wafer Bonding Techniques for TSV Integration (2010)

In this study are compared the technical merits and demerits of three bonding methods suitable for manufacturing 3D-ICs. Patterned metal thermo-compression bonding facilitates fine-pitch, high-density TSV stacking with lower electrical resistance and higher mechanical strength. Direct Cu-Cu bonding is preferred over transient liquid phase bonding with Sn or Sn alloys, but reliable Cu-Cu bonds result only from high process temperature and long process time. Both bonding temperature and post-bond annealing temperature have the most significant influence on Cu-Cu bond properties. The pre-bonding of silicon oxide bonds occurs at room temperature and thus does not induce any run-out errors in wafer alignment, resulting in higher post-bond alignment accuracy. Subsequent heating to high temperatures is necessary to achieve covalent bonds, but modifying the surface chemistry by plasma activation allows the formation of strong chemical bonds at significantly lower annealing temperatures (200–400°C). Adhesive bonding has such advantages as low bonding temperature and process time compared to metal bonding, the tolerance to wafer topography and surface conditions, and the ability to join any wafer materials. However, the material reflow imposes some challenges for maintaining the alignment accuracy and another major concern is the reliability of polymer adhesives during the post-bond processes.
Multi-junction cells with monolithic bypass diodes (2003)

Bypass diodes are attached electrically parallel (but with opposite polarity) to solar cells such that when the cells are reverse biased, the bypass diodes are forward biased, passing current and preventing the cells from going into reverse breakdown. For III-V single and multi-junction space cells, discrete silicon bypass diodes have typically been used. In this paper, we present a monolithic bypass diode, grown on top of the III-V solar cell. The bypass diode is of opposite polarity to the cell, but electrically parallel to the cell. The advantage of the monolithic diode over the discrete diode is the reduction in interconnects and handling required during the interconnecting of cells into strings. We present performance, reliability, and space qualification results for the monolithic bypass diode. Of particular importance are the diode reverse bias leakage current and the forward bias turn-on voltage. Large area (/spl sim/30 cm/sup 2/) cell/monolithic diodes with efficiencies of 28% have been made.
Oral Treatment for Jaundice Using Immobilized Bilirubin Oxidase (1992)

Jaundice is characterized by an excessive accumulation of bilirubin in the blood and tissues. A novel approach to reduce plasma levels of bilirubin by blocking its enterohepatic circulation was investigated. The treatment consisted of oral administration of immobilized bilirubin oxidase, which could oxidize bilirubin in the intestine to less toxic and more water-soluble products. In vivo administration of 0.1 to 2.0 mg/day of immobilized enzyme over a four-day period to chronically jaundiced Gunn rats effectively lowered plasma bilirubin levels, but only when the molar ratio of total serum bilirubin to rat serum albumin (B/RSA) was larger than 0.35. Plasma bilirubin concentration decreased in that group from an initial value of 11.3 to 6.3 mg/dl (-40%, n = 5) after eight days. This decrease was statistically significant (p < 0.05 by Student's t test). However, administration of bilirubin oxidase to rats with a B/RSA ratio less than 0.35 (n = 10) resulted in no statistically significant change in plasma bilirubin concentration.
Stereoselective Addition of 1,3‐Diketones to β‐Nitroacrylates Catalyzed by Chiral Metal‐Free Bifunctional Catalysts (2014)

Abstract Organocatalytic stereoselective additions of different nucleophiles to β‐nitroacrylates have been investigated. A thiourea‐based cinchona‐derived bifunctional catalyst promotes the addition of 1,3‐diketones to differently substituted nitroacrylates in modest to fair yields and up to 93 % enantioselectivity. The 1,3 dicarbonyl functionality of the addition products was then used to synthesize enantiomerically enriched 3,4,5‐trialkyl substituted pyrazoles via reaction with hydrazine. The stereoselective addition of N‐ methylindole to nitroacrylate was also preliminarily studied; the Friedel–Crafts alkylation was successfully organocatalyzed in the presence of an acid additive in very good yields and up to 53 % enantioselectivity.
Use of a Chiral Praseodymium Shift Reagent in Predicting the Complete Stereostructure of Glisoprenin A (2004)

[structure: see text] The complete stereostructure of glisoprenin A has been predicted via analysis of the 13C NMR behaviors in the presence of (R)- and (S)-Pr(tfc)3.
Effects of crystal imperfections in multiple quantum well PIN optoelectronic devices and a method of restoring failed device characteristics (2002)

GaAs/AlGaAs and strained InGaAs/AlGaAs multiple quantum well (MQW) optical modulators grown by molecular beam epitaxy (MBE) on GaAs substrates have a wide range of applications in fiber-optic communication systems. One of the challenges in producing reliable devices is the requirement of having large areas of complex MQW structures for optical processing, while maintaining the necessary PIN electrical characteristics. We report the first direct link between crystalline material imperfections and reverse bias behavior in MQW PIN devices. A method of eliminating the crystalline defects and restoring the device characteristics is demonstrated.
Spontaneous Diabetes in Hemizygous Human Amylin Transgenic Mice That Developed Neither Islet Amyloid nor Peripheral Insulin Resistance (2008)

Overexpression of fibrillogenic human amylin in these human amylin transgenic mice caused beta-cell degeneration and diabetes through mechanisms independent from both peripheral insulin resistance and islet amyloid. These findings are consistent with beta-cell death evoked by misfolded but soluble cytotoxic species, such as those formed by human amylin in vitro.
Potential basis for regulation of th( fibrinogen genes: Homology in the (genomic DNA sequences/signal peptides/transcription regulation/co: (2016)

The three chains of fibrinogen are encoded by three separate genes whose transcription is coordinately regulated. The breakdown of fibrinogen during the acute- phase reaction leads to a simultaneous increase in a-, fi-, and y-fibrinogen mRNA in the liver. In a search for the basis of this coordinate increase in transcription, we have determined the sequences of the regions surrounding the points of tran- scriptional initiation of the three rat fibrinogen genes, 1490 nucleotides upstream and 730 nucleotides downstream. Two unique regions of homology have been found. One region con- sists of 15 nucleotides that have a common 6-nucleotide core lying between -116 and -160; the other is -100 nucleotides long and is in the -165 to -472 region. In this region, the 3i- and y-fibrinogen genes are -65% homologous. a-Fibrinogen has somewhat less homology with both ft- and y-fibrinogen. In addition, the ,j-fibrinogen gene has 22 nucleotides at position -480 that are homologous to sequences that have been noted to occur in glucocorticosteroid-regulated genes in a similar po- sition. We feel that these areas of conserved sequences play a role in the regulation of the transcription of fibrinogen. The fibrinogen chains are synthesized as precursor peptides, and the amino-terminal portion, the so-called signal peptide, is re- moved during the translocation of the peptide chain across the endoplasmic reticulum. We have determined those sequences that encode the signal peptides. Homology in the amino acid sequence between the rat and human signal peptides varies between 52% for a-fibrinogen and 66% for fi-fibrinogen. This homology implies that there has been strong selective pressure on this portion of these genes.
Idiotype as a tumor-specific marker in childhood B cell acute lymphoblastic leukemia (1988)

Immunoglobulin (Ig) or idiotype (Id) is a tumor-specific target in those B cell malignancies that express this molecule on their surface. We explored the biology of B cell acute lymphoblastic leukemia (B cell ALL) using Id as a tumor marker. In this report we describe the development of anti-Id monoclonal antibodies (MAB) for two children with B cell ALL. These reagents were used retrospectively to study tumor kinetics and to detect residual disease after chemotherapy. In both cases serum Id values were strikingly high at diagnosis (1.2 mg/mL and 10.8 mg/mL), suggesting that the tumor cells were relatively mature B cells capable of significant antibody production. In both patients the serum Id levels fell with the institution of therapy and confirmed that the patients were in remission. Increasing serum Id predicted relapse four months before conventional methods in patient 1, and Id proved to be a more sensitive measure of tumor burden than Southern blot analysis of rearranged Ig genes in bone marrow samples. Surprisingly, low levels of Id were redetected in the second patient just before completing therapy and have persisted for over a year despite the absence of clinical evidence of recurrent disease. Thus, serum Id levels reflect tumor burden during initial therapy but may not necessarily predict tumor progression after a complete clinical remission.
Expression and Role of VEGF in the Adult Retinal Pigment Epithelium (2011)

PURPOSE. Despite a lack of active angiogenesis, VEGF is expressed in nearly every adult tissue, and recent evidence suggests that VEGF may serve as a survival factor for both vascular and nonvascular tissues. VEGF blockade is a widely used treatment for neovascular diseases such as wet age-related macular degeneration (AMD). Therefore, it was sought in this study to evaluate the expression and role of endogenous VEGF in RPE. METHODS. VEGF and VEGFR2 expression in the murine retina were assessed during development. Bevacizumab was used to neutralize VEGF in ARPE-19 cells, and the effects on cell survival and apical microvill were assessed by TUNEL and SEM, respectively. VEGF was systemically neutralized in vivo by adenoviral-mediated overexpression of soluble VEGFR1 (sFlt). RPE and choriocapillaris were analyzed by transmission electron microscopy (TEM). Changes in gene expression were evaluated by quantitative real-time PCR. RESULTS. VEGF expression was detected in the developing RPE as early as embryonic day (E) 9.5, whereas VEGFR2 expression by RPE began nonuniformly between postnatal (P) day 6.5 and P8.5. VEGF neutralization in vitro led to increased apoptosis and reduced microvilli density and length. Systemic VEGF neutralization led to transient degenerative changes; RPE were vacuolated and separated from photoreceptor outer segments, and choriocapillaris fenestrations were decreased. VEGF levels were elevated in RPE of Ad-sFlt1 mice at day 4 postinfection, and there was increased expression of the neurotrophic factor CD59a at day 14. CONCLUSIONS. These results indicate that VEGF plays a critical role in survival and maintenance of RPE integrity. Potential undesired off-target effects should be considered with chronic use of anti-VEGF agents.
Facile solid‐phase synthesis of C‐terminal peptide aldehydes and hydroxamates from a common Backbone Amide‐Linked (BAL) intermediate*† (2005)

C-Terminal peptide aldehydes and hydroxamates comprise two separate classes of effective inhibitors of a number of serine, aspartate, cysteine, and metalloproteases. Presented here is a method for preparation of both classes of peptide derivatives from the same resin-bound Weinreb amide precursor. Thus, 5-[(2 or 4)-formyl-3,5-dimethoxyphenoxy]butyramido-polyethylene glycol-polystyrene (BAL-PEG-PS) was treated with methoxylamine hydrochloride in the presence of sodium cyanoborohydride to provide a resin-bound methoxylamine, which was efficiently acylated by different Fmoc-amino acids upon bromo-tris-pyrrolidone-phosphonium hexafluorophosphate (PyBrOP) activation. Solid-phase chain elongation gave backbone amide-linked (BAL) peptide Weinreb amides, which were cleaved either by trifluoroacetic acid (TFA) in the presence of scavengers to provide the corresponding peptide hydroxamates, or by lithium aluminum hydride in tetrahydrofuran (THF) to provide the corresponding C-terminal peptide aldehydes. With several model sequences, peptide hydroxamates were obtained in crude yields of 68-83% and initial purities of at least 85%, whereas peptide aldehydes were obtained in crude yields of 16-53% and initial purities in the range of 30-40%. Under the LiAlH4 cleavage conditions used, those model peptides containing t-Bu-protected aspartate residues underwent partial side chain reduction to the corresponding homoserine-containing peptides. Similar results were obtained when working with high-load aminomethyl-polystyrene, suggesting that this chemistry will be generally applicable to a range of supporting materials.
Deletions at 22q11.2 in idiopathic Parkinson's disease: a combined analysis of genome-wide association data (2016)

UK Medical Research Council, UK Wellcome Trust, Parkinson's UK, Patrick Berthoud Trust, National Institutes of Health, "Investissements d'Avenir" ANR-10-IAIHU-06, Dutch Parkinson Foundation (Parkinson Vereniging), Neuroscience Campus Amsterdam, National Institute for Health Research, National Institute on Aging, National Institutes of Health.
ChemInform Abstract: The Gif System as a Tool in Medicinal Chemistry: The Oxidation of Sch 57726 Under GoAggIII Conditions. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Nanocomposite hyaluronic acid-based hydrogel for the treatment of esophageal fistulas (2021)

Fistulas are abnormal connections between two body parts that can impair the quality of life. The use of biological glues represents the least invasive procedure to fill the fistula; however, it is limited by the need of multiple injections, the persistence of infection and the failure in the treatment of high-output fistulas. We describe herein the use of an injectable nanocomposite hydrogel that is able to form <i>in situ</i> a tissue-mimicking matrix as an innovative material for the treatment of esophageal fistulas. Injectable hydrogels that have the dual advantage of being implantable with a minimally invasive approach and of adapting their shape to the target cavity, while the introduction of mesoporous silica nanoparticles opens the possibility of drug/biomolecules delivery. The hydrogel is based on hyaluronic acid (HA), the crosslinking process occurs at physiological conditions leading to a hydrogel made of >96% by water and with a large-pore micro-architecture. The kinetic profile of the hydrogel formation is studied as a function of HA molecular weight and concentration with the aim of designing a material that is easily injectable with an endoscopic needle, is formed in a time compatible with the surgical procedure and has final mechanical properties suitable for cell proliferation. The <i>in vivo</i> experiments (porcine model) on esophageal-cutaneous fistulas, showed improved healing in the animals treated with the hydrogel compared with the control group.
Modelling of nitric acid and U(VI) Co-extraction in annular centrifugal contactors (2000)

British Nuclear Fuels Limited (BNFL) is currently developing novel flow sheets for an advanced PUREX process using centrifugal contactors. This technology provides two major advantages. Firstly, centrifugal contactors can process high throughputs of liquid, while being an equipment of small size, compared to pulsed columns for example. Secondly, during the reprocessing of actinides with diluted tributyl phosphate (TBP) solutions, centrifugal contactors also minimize solvent hydrolysis and radiolysis because of the very short contact times involved.
Genotoxic impact of long-term cigarette and waterpipe smoking on DNA damage and oxidative stress in healthy subjects (2018)

Although a plethora of studies have examined tobacco smoke-cancer disease association, the involvement of cellular genetic toxicity remains unclear. Therefore, the present study provides molecular evidence for a pathway involved in the DNA damage induced by long-term cigarette and waterpipe smoke in human subjects. The study population consisted of 45 subjects who were divided into three groups; healthy nonsmokers group, cigarette smokers group, and waterpipe smokers group. A questionnaire and consent form was distributed and signed by all participants. Total RNA was extracted from the blood using PAXgene Blood RNA Kit and mRNA expression levels of target genes were quantified by RT-PCR. Our results showed that 80% of the participants smoke 20-39 cigarettes/day, whereas 12% smoke more than 40 cigarettes/day. With regard to waterpipe smoke, the majority (46%) smoke more than 5 times/week. Both cigarette and waterpipe smokers showed increased the plasma levels 8-hydroxy-2'-deoxyguanosine (8-OHdG), of DNA damage marker. In addition, the mRNA expression levels of DNA repair genes (OGG1 and XRCC1) were significantly inhibited in both cigarette and waterpipe smokers groups by 30% and 60%, respectively. This was associated with a marked decrease (50%) in the expression of detoxifying genes (NQO1 and GSTA1) with an increase in CYP1A1 mRNA expression, a cancer-activating gene. Both cigarette and waterpipe smokers increased in the plasma concentrations of several toxic heavy metals such as Cd (130%), Pb (47%), and Ni (30%). In conclusion: the present findings clearly explore the genotoxic effect of cigarette and waterpipe smoking on human DNA.
Introduction to Dynamic Stochastic Computing (2020)

Stochastic computing (SC) is an old but reviving computing paradigm for its simple data path that can perform various arithmetic operations. It allows for low power implementation, which would otherwise be complex using the conventional positional binary coding. In SC, a number is encoded by a random bit stream of '0's and '1's with an equal weight for every bit. However, a long bit stream is usually required to achieve a high accuracy. This requirement inevitably incurs a long latency and high energy consumption in an SC system. In this article, we present a new type of stochastic computing that uses dynamically variable bit streams, which is, therefore, referred to as dynamic stochastic computing (DSC). In DSC, a random bit is used to encode a single value from a digital signal. A sequence of such random bits is referred to as a dynamic stochastic sequence. Using a stochastic integrator, DSC is well suited for implementing accumulation-based iterative algorithms such as numerical integration and gradient descent. The underlying mathematical models are formulated for functional analysis and error estimation. A DSC system features a higher energy efficiency than conventional computing using a fixed-point representation with a power consumption as low as conventional SC. It is potentially useful in a broad spectrum of applications including signal processing, numerical integration and machine learning.
Evaluation of osseointegration using image analysis and visualization of 2D and 3D image data (2011)

Computerized image analysis, the discipline of using computers to automatically extract information from digital images, is a powerful tool for automating time consuming analysis tasks. In this thesis, image analysis and visualization methods are developed to facilitate the evaluation of osseointegration, i.e., the biological integration of a load-carrying implant in living bone.\n\n\nAdequate osseointegration is essential in patients who are in need of implant treatment. New implant types, with variations in bulk material and surface structural parameters, are continuously being developed. The main goal is to improve and speed up the osseointegration and thereby enhance patient well-being. The level of osseointegration can be evaluated by quantifying the bone tissue in proximity to the implant in e.g., light microscopy images of thin cross sections of bone implant samples extracted from humans or animals. This operator dependent quantitative analysis is cumbersome, time consuming and subjective. Furthermore, the thin sections represent only a small region of the whole sample.\n\n\nIn this thesis work, computerized image analysis methods are developed to automate the quantification step. An image segmentation method is proposed for classifying the pixels of the images as bone tissue, non-bone tissue or implant. Subsequently, bone area and bone implant contact length in regions of interest are quantified. To achieve an accurate classification, the segmentation is based on both intensity and spatial information of the pixels. The automated method speeds up and facilitates the evaluation of osseointegration in the research laboratories. \n\n\nAnother aim of this thesis is extending the 2D analysis to 3D and presenting methods for visualization of the 3D image volumes. To get a complete picture, information from the whole sample should be considered, rather than thin sections only. As a first step, 3D imaging of the implant samples is evaluated. 3D analysis methods, which follow the helix shaped implant thread and collects quantified features along the path, are presented. Additionally, methods for finding the position of the 2D section in the corresponding 3D image volume, i.e., image registration, are presented, enabling a direct comparison of the data from the two modalities. These novel and unique 3D quantification and visualization methods support the biomaterial researchers with improved tools for gaining a wider insight into the osseointegration process, with the ultimate goal of improved quality of life for the patients.
Fem‐Based Analysis Techniques for Electrical Machine Design (2017)

The Newton-Raphson technique for the solution of nonlinear problems in finite element analysis (FEA) has been widely accepted due to its quadratic convergence characteristics. This chapter introduces an indirect approach with parameter coupling. It also introduces an efficient method, referred to as alternating flux linkage (AF) model, to speed up the transient process for reaching fast AC steady state, almost suitable for all AC machines. Transient electromagnetic field simulation allows analysis of dynamic behaviors with nonlinear materials, permanent magnets, and induced eddy currents under various excitations. The basic procedure of transient simulation includes the spatial and temporal discretization of the physical equations. The finite element method (FEM) is widely used in engineering practice because using the irregular grids it can represent complicated geometry. The chapter explores some advanced algorithms to create look-uptable based ROMs, and some efficient techniques to reduce computational time at specified density of the sampling points.
Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation (2019)

ClinicalTrials.gov, NCT01277757 . Registered 13 January 2011.