gebhart/patrepeval huggingface dataset:
In Vitro Coexpression and Pharmacological Rescue of Mutant Gonadotropin-Releasing Hormone Receptors Causing Hypogonadotropic Hypogonadism in Humans Expressing Compound Heterozygous Alleles (2005)

We analyzed the function of mutant GnRH receptor (GnRHR) pairs associated with compound heterozygous patients showing complete or partial forms of hypogonadotropic hypogonadism. We did this to examine potential interactions between misfolded mutants that may influence net receptor function and response to pharmacological rescue. Nine pairs of GnRHR mutants and an unreported combination (L314X((stop))/R262Q) were studied. Coexpression of each pair of mutants in COS-7 cells resulted in an active predominant effect (Q106R/L266R, A171T/Q106R, T32I/C200Y, and R262Q/A129D mutant GnRHR pairs), an additive effect (R262Q/Q106R, N10K/Q106R, and R262Q/Y284C human GnRHR pairs), or a dominant-negative effect (L314X((stop))/Q106R, Q106R+S217R/R262Q, and L314X((stop))/R262Q GnRHRs). For all combinations, addition of the pharmacoperone IN3 increased both agonist binding and effector coupling. The IN3 response was unpredictable because responses could be either similar, higher, or lower, compared with that exhibited by the less affected mutant. The clinical phenotype in patients expressing complex heterozygous alleles appears to be dictated by both the contribution from each mutant and a dominant-negative effect similar to that reported for mutants and wild-type receptor. Depending on the genotype, partial or full restoration of receptor function in response to pharmacological chaperones may be achievable goals in patients bearing inactivating mutations in the GnRHR gene.
Interaction of tankyrase and peroxiredoxin II is indispensable for the survival of colorectal cancer cells (2017)

Mammalian 2-Cys peroxiredoxin (Prx) enzymes are overexpressed in most cancer tissues, but their specific signaling role in cancer progression is poorly understood. Here we demonstrate that Prx type II (PrxII) plays a tumor-promoting role in colorectal cancer by interacting with a poly(ADP-ribose) polymerase (PARP) tankyrase. PrxII deletion in mice with inactivating mutation of adenomatous polyposis coli (APC) gene reduces intestinal adenomatous polyposis via Axin/β-catenin axis and thereby promotes survival. In human colorectal cancer cells with APC mutations, PrxII depletion consistently reduces the β-catenin levels and the expression of β-catenin target genes. Essentially, PrxII depletion hampers the PARP-dependent Axin1 degradation through tankyrase inactivation. Direct binding of PrxII to tankyrase ARC4/5 domains seems to be crucial for protecting tankyrase from oxidative inactivation. Furthermore, a chemical compound targeting PrxII inhibits the expansion of APC-mutant colorectal cancer cells in vitro and in vivo tumor xenografts. Collectively, this study reveals a redox mechanism for regulating tankyrase activity and implicates PrxII as a targetable antioxidant enzyme in APC-mutation-positive colorectal cancer.2-Cys peroxiredoxin (Prx) enzymes are highly expressed in most cancers but how they promote cancer progression is unclear. Here the authors show that in colorectal cancers with APC mutation, PrxII binds to tankyrase and prevents its oxidative inactivation, thereby preventing Axin1-dependent degradation of ²b-catenin.
A 114-pW PMOS-only, trim-free voltage reference with 0.26% within-wafer inaccuracy for nW systems (2016)

A sub-nW voltage reference is presented that uses only PMOS transistors, thereby providing inherently low process variation and enabling trim-free operation for LDOs and other applications in nW microsystems. Sixty chips from 3 different wafers in 180nm CMOS are measured, showing an untrimmed within-wafer σ/μ of 0.26% and wafer-to-wafer σ/μ of 1.9%. Measurement results also show a temperature coefficient of 48–124ppm/°C from −40°C to 85°C. Outputting a 0.986V reference voltage, the reference operates down to 1.2V and consumes 114pW at 25°C.
Continuous Motion Sensor Assessment of Parkinson’s Disease During Activities of Daily Living (P1.196) (2015)

OBJECTIVE: To use motion sensors to capture tremor, mobility, and dyskinesia in patients with Parkinson’s disease (PD) and motor fluctuations during activities of daily living. BACKGROUND: Tremor, bradykinesia, mobility, and dyskinesia have been measured previously using body worn motion sensors. However, quantification during unconstrained activities poses a unique challenge since dyskinesias can be difficult to distinguish from voluntary movement. DESIGN/METHODS: Eight subjects with PD and a history of levodopa-induced dyskinesias were instrumented with six degree-of-freedom motion sensors on the wrist and ankle. Data were recorded as subjects completed a series of activities of daily living (ADL) at stations set up in a simulated home environment for approximately two hours. Subjects first performed the activities in the OFF medication state and then took their usual prescribed dose of medication and continued to rotate through the ADL stations. Data recording sessions were videotaped for subsequent blinded clinical scoring. Time and frequency domain algorithms based on previous data were applied to generate severity scores for tremor and dyskinesia every 12 seconds. Moving average filters were applied to identify transitions in medication state. Dyskinetic periods were those for which dyskinesia score exceeded an empirically-determined threshold. RESULTS: Algorithm scores for tremor and dyskinesia showed a high level of agreement with annotations based on visual inspection of the video recordings and changed in concert with medication state. Tremor and dyskinesia scores were predictive of the presence or absence of tremor and dyskinesia, with average sensitivity and specificity greater than 90[percnt]. CONCLUSIONS: A system with two motion sensors can provide accurate measures of overall tremor and dyskinesia as patients complete complex movements associated with typical activities. Such a system could provide valuable insight on motor fluctuations in the context of daily life and aid in the development and evaluation of new therapies. Study Supported by: NIH/NIA 5R44AG044293-04
Synthesis and structure-activity studies of alkyl-substituted .gamma.-butyrolactones and .gamma.-thiobutyrolactones: ligands for the picrotoxin receptor (1991)

A series of gamma-butyrolactones and gamma-thiobutyrolactones possessing a variety of alkyl groups and alkyl-substitution patterns was prepared and evaluated for anticonvulsant and convulsant activity. Behavioral studies performed on these compounds suggest that maximal anticonvulsant activity (against maximal electroshock and pentylenetetrazol) results when three or four carbon atoms are present at the alpha-position. For convulsant potency, a similar dependence on the size of the alkyl chain at the beta-position was observed. Additional gamma-dimethyl groups were found to increase the convulsant potency of a beta-substituted compound and to cause an alpha-substituted anticonvulsant to become a convulsant. In general, sulfur for oxygen heteroatom substitution in the alpha-substituted lactones resulted in improved anticonvulsant potency and spectrum of activity. Binding of these compounds to the picrotoxin site of the GABA receptor complex was demonstrated with a [35S]-tert-butylbicyclophosphorothionate radioligand binding assay. Measurements of brain concentrations for selected compounds supports a hypothesis that correlates binding to the picrotoxin site with the pharmacological effects of these compounds.
Maternal Immunization with Pneumococcal Surface Protein A Protects against Pneumococcal Infections among Derived Offspring (2011)

Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood.
Pareto-Optimization Framework for Automated Network-on-Chip Design (2018)

With the advent of multi-core processors, network-on-chip design has been key in addressing network performances, such as bandwidth, power consumption, and communication delays when dealing with on-chip communication between the increasing number of processor cores. As the numbers of cores increase, network design becomes more complex. Therefore, there is a critical need in soliciting computer aid in determining network configurations that afford optimal performance given resources and design constraints. We propose a Pareto-optimization framework that explores the space of possible network configurations to determine optimal network latencies, power consumption, and the corresponding link allocations. For a given number of routers, average network latency and power consumption as example performance objectives can be displayed in form of Pareto-optimal fronts, thus not only offering a design tool, but also enabling trade-off studies.
Supersonic Free-Jet Combustion in a Ramjet Burner (2010)

A new dual-mode ramjet combustor concept intended for operation over a wide flight Mach number range is described. Subsonic combustion mode is similar to that of a traditional ram combustor which allows operation at higher efficiency, and to lower flight Mach numbers than current dual-mode scramjets. High speed mode is characterized by supersonic combustion in a free-jet that traverses the subsonic combustion chamber to a variable nozzle. The maximum flight Mach number of this scheme is governed largely by the same physics as its classical counterpart. Although a variable combustor exit aperture is required, the need for fuel staging to accommodate the combustion process is eliminated. Local heating from shock-boundary-layer interactions on combustor walls is also eliminated. Given the parallel nature of the present scheme, overall flowpath length is less than that of present dual-mode configurations. Cycle analysis was done to define the flowpath geometry for computational fluid dynamics (CFD) analysis, and then to determine performance based on the CFD results. CFD results for Mach 5, 8, and 12 flight conditions indicate stable supersonic free-jet formation and nozzle reattachment, thereby establishing the basic feasibility of the concept. These results also reveal the structure of, and interactions between the free-jet and recirculating combustion chamber flows. Performance based on these CFD results is slightly less than that of the constant-pressure-combustion cycle analysis primarily due to these interactions. These differences are quantified and discussed. Additional CFD results at the Mach 8 flight condition show the effects of nozzle throat area variation on combustion chamber pressure, flow structure, and performance. Calculations with constant temperature walls were also done to evaluate heat flux and overall heat loads. Aspects of the concept that warrant further study are outlined. These include diffuser design, ramjet operation, mode transition, loss mechanisms, and the effects of secondary flow for wall cooling and combustion chamber pressurization. Also recommended is an examination of system-level aspects such as weight, thermal management and rocket integration as well as alternate geometries and variable geometry schemes.
Enantioselective Synthesis of Acyclic α‐Quaternary Carboxylic Acid Derivatives through Iridium‐Catalyzed Allylic Alkylation (2017)

The first highly enantioselective iridium-catalyzed allylic alkylation that provides access to products bearing an allylic all-carbon quaternary stereogenic center has been developed. The reaction utilizes a masked acyl cyanide (MAC) reagent, which enables the one-pot preparation of α-quaternary carboxylic acids, esters, and amides with a high degree of enantioselectivity. The utility of these products is further explored through a series of diverse product transformations.
Recovery of recyclable materials from shredder residue (1994)

Each year, about 11 million tons of metals (ferrous and nonferrous) are recovered in the US from about 10 million discarded automobiles. The recovered metals account for about 75% of the total weight of the discarded vehicles. The balance of the material or shredder residue, which amounts to about 3 million tons annually, is currently landfilled. The residue contains a diversity of potentially recyclable materials, including polyurethane foams, iron oxides, and certain thermoplastics. This paper discusses a process under development at Argonne National Laboratory to separate and recover the recyclable materials from this waste stream. The process consists essentially of two-stages. First, a physical separation is used to recover the foams and the metal oxides, followed by a chemical process to extract certain thermoplastics. Status of the technology is discussed and process economics reviewed.
2PFC CMOS image sensors: better image quality at lower cost (2009)

A modification to the standard Bayer CFA and photodiode structure for CMOS image sensors is proposed, which we call 2PFCTM, meaning "Two Pixel, Full Color". The blue and red filters of the Bayer pattern are replaced by magenta filters. Under each magenta filter are two stacked, pinned photodiodes; the diode nearest the surface absorbs mostly blue light and the deeper diode absorbs mostly red light. The magenta filter absorbs green light, improving color separation between the resulting blue and red diodes. The dopant implant defining the bottom of the red-absorbing region can be made the same as the green diodes, simplifying the fabrication. Since the spatial resolution for the red, green, and blue channels are identical, color aliasing is greatly reduced. Luminance resolution can also be improved, the thinner diodes lead to higher well capacity with resulting better dynamic range, and fabrication costs can be similar to or less than standard Bayer CMOS imagers. Also, the geometry of the layout lends itself naturally to frequency-based demosaicing.
Ultrahigh tunnel magnetoresistance using an artificial superlattice barrier with copper and aluminum oxide (2015)

This paper proposes an ultrahigh tunnel magnetoresistance that is achieved by a magnetic tunnel junction with an artificial superlattice barrier that is composed of alternate layers of copper and aluminium oxide. By designing proper thickness filling factor of the superlattice barrier, ultrahigh magnetoresistance can be achieved. The tunnel magnetoresistance increases as the number of cells in the superlattice barrier increases. This ultrahigh magnetoresistance effect is attributed to the crystalline property of superlattices, similarly to the high magnetoresistance effect achieved by traditional crystalline MgO. There are more adjustable parameters, such as the lattice constant and the barrier height, in the artificial superlattice barrier than in a traditional crystalline-MgO barrier. This ultrahigh magnetoresistance effect may be used to design spintronic devices.
Oxide Mediated Solid Phase Epitaxy (OMSPE) of Silicon: A New Low Temperature Epitaxy Technique Using Intentionally Grown Native Oxide (1999)

A new low-temperature epitaxial technique is proposed, which utilizes the native oxide on the Si surface. A good quality epitaxial Si layer can be obtained using solid phase epitaxy (SPE), mediated by an intentionally grown native oxide layer on the Si substrate. Oxygen coverage of 0.25 ML was determined to be most suitable for obtaining defect-free epitaxy. The mechanism of this new epitaxial technique is presented, based on a detailed investigation of defect formation due to the oxygen at the interface.
An Efficient Hierarchical Video Coding Scheme Combining Visual Perception Characteristics (2014)

Different visual perception characteristic saliencies are the key to constitute the low-complexity video coding framework. A hierarchical video coding scheme based on human visual systems (HVS) is proposed in this paper. The proposed scheme uses a joint video coding framework consisting of visual perception analysis layer (VPAL) and video coding layer (VCL). In VPAL, effective visual perception characteristics detection algorithm is proposed to achieve visual region of interest (VROI) based on the correlation between coding information (such as motion vector, prediction mode, etc.) and visual attention. Then, the interest priority setting for VROI according to visual perception characteristics is completed. In VCL, the optional encoding method is developed utilizing the visual interested priority setting results from VPAL. As a result, the proposed scheme achieves information reuse and complementary between visual perception analysis and video coding. Experimental results show that the proposed hierarchical video coding scheme effectively alleviates the contradiction between complexity and accuracy. Compared with H.264/AVC (JM17.0), the proposed scheme reduces 80% video coding time approximately and maintains a good video image quality as well. It improves video coding performance significantly.
Isolation of erucic acid from rapeseed oil by lipase‐catalyzed hydrolysis (1995)

Abstract Three lipases were compared for their ability to hydrolyze high erucic acid rapeseed oil, with the objective of concentrating the erucic acid in a single glyceride fraction. Lipase from Pseudomonas cepacia released all fatty acids rapidly and did not result in selective distribution of erucic acid. Geotrichum candidum lipase released C20 and C22 fatty acids extremely slowly, resulting in their accumulation in the di‐ and triglyceride fractions. Less than 2% of the total erucic acid was found in the free fatty acid (FFA) fraction. Lipase from Candida rugosa released erucic acid more slowly than C20 and C18 fatty acids at 35°C but only resulted in a limited accumulation of the erucic acid in the di‐ and triglyceride fractions. However, when hydrolysis catalyzed by C. rugosa lipase was carried out below 20°C, the reaction mixture solidified and was composed solely of FFAs and diglycerides. The diglyceride fraction contained approximately 95% erucic acid while about 20% of the total erucic acid was found in the FFA fraction. It is concluded that hydrolysis at low temperature with C. rugosa lipase results in a higher purity of erucic acid in the glyceride fraction than can be obtained with G. candidum lipase, but with considerable loss of erucic acid to the FFA fraction.
A Novel Approach to Serine Protease Inhibition:  Kinetic Characterization of Inhibitors Whose Potencies and Selectivities Are Dramatically Enhanced by Zinc(II) (2000)

Serine proteases play a role in a variety of disease states and thus are attractive targets for therapeutic intervention. We report the kinetic characterization of a class of serine protease inhibitors whose potencies and selectivities are dramatically enhanced in the presence of Zn(II). The structural basis for Zn(II)-mediated inhibition of trypsin-like proteases has recently been reported [Katz, B. A., Clark, J. M., Finer-Moore, J. S., Jenkins, T. E., Johnson, C. R., Ross, M. J., Luong, C., Moore, W. R., and Stroud, R. M. (1998) Nature 391, 608-612]. A case study of the kinetic behavior of human tryptase inhibitors is provided to illustrate the general phenomenon of Zn(II)-mediated inhibition. Tryptase, Zn(II), and the inhibitor form a ternary complex which exhibits classic tight-binding inhibition. The half-life for release of inhibitor from the tryptase-Zn(II)-inhibitor complex has been measured for a number of inhibitors. Consistent with tight-binding behavior, potent tryptase inhibitors are characterized by extremely slow rates of dissociation from the ternary complex with half-lives on the order of hours. A model of human serum, designed to reproduce physiological levels of Zn(II), has been employed to evaluate the performance of Zn(II)-potentiated tryptase inhibitors under physiological conditions. We demonstrate that Zn(II)-mediated inhibition can be achieved at physiological Zn(II) levels.
Automatic 4D Reconstruction of Patient-Specific Cardiac Mesh with 1-to-1 Vertex Correspondence from Segmented Contours Lines (2014)

We propose an automatic algorithm for the reconstruction of patient-specific cardiac mesh models with 1-to-1 vertex correspondence. In this framework, a series of 3D meshes depicting the endocardial surface of the heart at each time step is constructed, based on a set of border delineated magnetic resonance imaging (MRI) data of the whole cardiac cycle. The key contribution in this work involves a novel reconstruction technique to generate a 4D (i.e., spatial-temporal) model of the heart with 1-to-1 vertex mapping throughout the time frames. The reconstructed 3D model from the first time step is used as a base template model and then deformed to fit the segmented contours from the subsequent time steps. A method to determine a tree-based connectivity relationship is proposed to ensure robust mapping during mesh deformation. The novel feature is the ability to handle intra- and inter-frame 2D topology changes of the contours, which manifests as a series of merging and splitting of contours when the images are viewed either in a spatial or temporal sequence. Our algorithm has been tested on five acquisitions of cardiac MRI and can successfully reconstruct the full 4D heart model in around 30 minutes per subject. The generated 4D heart model conforms very well with the input segmented contours and the mesh element shape is of reasonably good quality. The work is important in the support of downstream computational simulation activities.
Optical-fibre thermometer for medical use (1984)

A new optical-fibre temperature sensor is proposed which is based on light amplitude modulation induced by a thermosensitive cladding applied on the distal end of the fibre. The experimental set-up for detecting and processing the signal is described, and the measured characteristics of the thermometer are reported.
Calibration and measurement of six-port reflectometer using a matrix approach. Part II, Description and performance (1986)

ABSTRACT: System description -- Six-port junction -- Power detectors -- Microwave generator and frequency counter -- Software -- Desk-top computer -- Calibration -- System performance -- Adaptation to other transmission systems -- Six-port network stability -- Sensitivity to power level variation -- Measurement in sweep frequency mode -- Results.