gebhart/patrepeval huggingface dataset:
Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns (2018)

Digital microfluidics (DMF) is an emerging technology with the appropriate metrics for application to newborn and high-risk screening for inherited metabolic disease and other conditions that benefit from early treatment. Areas covered: This review traces the development of electrowetting-based DMF technology toward the fulfillment of its promise to provide an inexpensive platform to conduct enzymatic assays and targeted biomarker assays at the bedside. The high-throughput DMF platform, referred to as SEEKER®, was recently authorized by the United States Food and Drug Administration to screen newborns for four lysosomal storage disorders (LSDs) and is deployed in newborn screening programs in the United States. The development of reagents and methods for LSD screening and results from screening centers are reviewed. Preliminary results from a more compact DMF device, to perform disease-specific test panels from small volumes of blood, are also reviewed. Literature for this review was sourced using principal author and subject searches in PubMed. Expert commentary: Newborn screening is a vital and highly successful public health program. DMF technology adds value to the current testing platforms that will benefit apparently healthy newborns with underlying genetic disorders and infants at-risk for conditions that present with symptoms in the newborn period.
Platelet-Derived Growth Factor-Dependent Activation of Phosphatidylinositol 3-Kinase Is Regulated by Receptor Binding of SH2-Domain-Containing Proteins Which Influence Ras Activity (1996)

Upon binding of platelet-derived growth factor (PDGF), the PDGF beta receptor (PDGFR) undergoes autophosphorylation on distinct tyrosine residues and binds several SH2-domain-containing signal relay enzymes, including phosphatidylinositol 3-kinase (PI3K), phospholipase C gamma (PLC gamma), the GTPase-activating protein of Ras (RasGAP), and the tyrosine phosphatase SHP-2. In this study, we have investigated whether PDGF-dependent PI3K activation is affected by the other proteins that associate with the PDGFR. We constructed and characterized a series of PDGFR mutants which contain binding sites for PI3K as well as one additional protein, either RasGAP, SHP-2, or PLC gamma. While all of the receptors had wild-type levels of PDGF-stimulated tyrosine kinase activity and associated with comparable amounts of PI3K activity, their abilities to trigger accumulation of PI3K products in vivo differed dramatically. The wild-type receptor, as well as receptors that recruited PI3K or PI3K and SHP-2, were all capable of fully activating PI3K. In contrast, receptors that associated with PI3K and RasGAP or PI3K and PLC gamma displayed a greatly reduced ability to stimulate production of PI3K products. When this series of receptors was tested for their ability to activate Ras, we observed a strong positive correlation between Ras activation and PI3K activation. Further investigation of the relationship between Ras and PI3K indicated that Ras was upstream of PI3K. Thus, activation of PI3K requires not only binding of PI3K to the tyrosine-phosphorylated PDGFR but accumulation of GTP-bound Ras as well. Furthermore, PLC gamma and RasGAP negatively modulate PDGF-dependent PI3K activation. Finally, PDGF-stimulated signal relay can be regulated by altering the ratio of SH2-domain-containing enzymes that are recruited to the PDGFR.
Protein aggregation inEscherichia coli: role of proteases (2002)

Protein aggregation is involved in several human diseases, and presumed to be an important process in protein quality control. In bacteria, aggregation of proteins occurs during stress conditions, such as heat shock. We studied the protein aggregates of Escherichia coli during heat shock. Our results demonstrate that the concentration and diversity of proteins in the aggregates depend on the availability of proteases. Aggregates obtained from mutants in the Lon (La) protease contain three times more protein than wild-type aggregates and show the broadest protein diversity. The results support the assumption that protein aggregates are formed from partially unfolded proteins that were not refolded by chaperones or degraded by proteases.
The oncolytic peptide LTX-315 kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization (2015)

LTX-315 has been developed as an amphipathic cationic peptide that kills cancer cells. Here, we investigated the putative involvement of mitochondria in the cytotoxic action of LTX-315. Subcellular fractionation of LTX-315-treated cells, followed by mass spectrometric quantification, revealed that the agent was enriched in mitochondria. LTX-315 caused an immediate arrest of mitochondrial respiration without any major uncoupling effect. Accordingly, LTX-315 disrupted the mitochondrial network, dissipated the mitochondrial inner transmembrane potential, and caused the release of mitochondrial intermembrane proteins into the cytosol. LTX-315 was relatively inefficient in stimulating mitophagy. Cells lacking the two pro-apoptotic multidomain proteins from the BCL-2 family, BAX and BAK, were less susceptible to LTX-315-mediated killing. Moreover, cells engineered to lose their mitochondria (by transfection with Parkin combined with treatment with a protonophore causing mitophagy) were relatively resistant against LTX-315, underscoring the importance of this organelle for LTX-315-mediated cytotoxicity. Altogether, these results support the notion that LTX-315 kills cancer cells by virtue of its capacity to permeabilize mitochondrial membranes.
Ring-opening polymerization of cyclooctyne (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRing-opening polymerization of cyclooctyneS. A. Krouse, R. R. Schrock, and R. E. CohenCite this: Macromolecules 1987, 20, 4, 903–904Publication Date (Print):April 1, 1987Publication History Published online1 May 2002Published inissue 1 April 1987https://pubs.acs.org/doi/10.1021/ma00170a033https://doi.org/10.1021/ma00170a033research-articleACS PublicationsRequest reuse permissionsArticle Views396Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Refolding and purification of recombinant L-asparaginase from inclusion bodies of E. coli into active tetrameric protein (2014)

A tetrameric protein of therapeutic importance, Escherichia coli L-asparaginase-II was expressed in Escherichia coli as inclusion bodies (IBs). Asparaginase IBs were solubilized using low concentration of urea and refolded into active tetrameric protein using pulsatile dilution method. Refolded asparaginase was purified in two steps by ion-exchange and gel filtration chromatographic techniques. The recovery of bioactive asparaginase from IBs was around 50%. The melting temperature (Tm) of the purified asparaginase was found to be 64°C. The specific activity of refolded, purified asparaginase was found to be comparable to the commercial asparaginase (190 IU/mg). Enzymatic activity of the refolded asparaginase was high even at four molar urea solutions, where the IB aggregates are completely solubilized. From the comparison of chemical denaturation data and activity at different concentrations of guanidine hydrochloride, it was observed that dissociation of monomeric units precedes the complete loss of helical secondary structures. Protection of the existing native-like protein structure during solubilization of IB aggregates with 4 M urea improved the propensity of monomer units to form oligomeric structure. Our mild solubilization technique retaining native-like structures, improved recovery of asparaginase in bioactive tetrameric form.
Development and Testing of a Concrete Median Barrier for Flood-Prone Areas (2021)

Concrete median barriers are designed to mitigate serious cross-median crashes by preventing penetration of errant vehicles into oncoming traffic. When implemented in flood-prone areas, however, solid concrete median barriers can act as a dam to floodwaters, as recently seen in the U.S. in Texas during Hurricane Harvey, or in Louisiana and Pennsylvania following severe storms. This raises the height of the floodwaters and increases the severity of flooding on highways and surrounding roads and communities. To reduce flooding, new median barrier options with openings were investigated. Finite element simulations were used to aid investigation and evaluation of the designs, and laboratory testing was performed to evaluate the hydraulic efficiency of barrier designs in a variety of simulated flood conditions. A concrete single-slope profile median barrier with a large scupper was selected for crash testing following Manual for Assessing Safety Hardware (MASH) Test Level 4 (TL-4) impact conditions and evaluation criteria. The median barrier design was deemed MASH compliant and is ready for implementation in areas susceptible to flooding, with the goal of reducing flooding severity, decreasing associated risk to motorists, and reducing the level of flood damage to both highways and surrounding areas.
Conformational Changes and Charge Transfer in Biomolecules Resolved Using Dynamic Enhanced Raman Correlation Spectroscopy (2019)

In this contribution, we report that conformational changes of molecules that are often buried in a wide-distributed Gaussian distribution can be discerned by analyzing the dynamics of specific Raman lines. We investigate the pertinence of the auto- and cross-correlation functions applied to the dynamics of three Raman lines of an amino acid, the tryptophan. The cross-correlation between intensity and the Raman band is an indicator of the charge transfer during the diffusion limited reaction of tryptophan and the gold surface. The Péclet number Pe can provide a valuable indicator of the convective and/or diffusive features of each Raman band. Adsorption induced conformation changes can be identified using the autocorrelation of the multiples states within the Raman band centered at 1550 cm<sup>-1</sup>.
Biochemical Investigation of Pikromycin Biosynthesis Employing Native Penta- and Hexaketide Chain Elongation Intermediates (2005)

The unique ability of the pikromycin (Pik) polyketide synthase to generate 12- and 14-membered ring macrolactones presents an opportunity to explore the fundamental processes underlying polyketide synthesis, specifically the mechanistic details of chain extension, keto group processing, acyl chain release, and macrocyclization. We have synthesized the natural pentaketide and hexaketide chain elongation intermediates as N-acetyl cysteamine (NAC) thioesters and have used them as substrates for in vitro conversions with engineered PikAIII+TE and in combination with native PikAIII (module 5) and PikAIV (module 6) multifunctional proteins. This investigation demonstrates directly the remarkable ability of these monomodules to catalyze one or two chain extension reactions, keto group processing steps, acyl-ACP release, and cyclization to generate 10-deoxymethynolide and narbonolide. The results reveal the enormous preference of Pik monomodules for their natural polyketide substrates and provide an important comparative analysis with previous studies using unnatural diketide NAC thioester substrates.
Interactions of the Amino Acid Residue at Position 31 of the c-Ha-Ras Protein with Raf-1 and RalGDS (1998)

The Ras and Rap1A proteins can bind to the Raf and RalGDS families. Ras and Rap1A have Glu and Lys, respectively, at position 31. In the present study, we analyzed the effects of mutating the Glu at position 31 of the c-Ha-Ras protein to Asp, Ala, Arg, and Lys on the interactions with Raf-1 and RalGDS. The Ras-binding domain (RBD) of Raf-1 binds the E31R and E31K Ras mutants less tightly than the wild-type, E31A, and E31D Ras proteins; the introduction of the positively charged Lys or Arg residue at position 31 specifically impairs the binding of Ras with the Raf-1 RBD. On the other hand, the ability of the oncogenic RasG12V protein to activate Raf-1 in HEK293 cells was only partially reduced by the E31R mutation but was drastically impaired by the E31K mutation. Correspondingly, RasG12V(E31K) as well as Rap1A, but not RasG12V(E31R), exhibited abnormally tight binding with the cysteine-rich domain of Raf-1. On the other hand, the E31A, E31R, and E31K mutations, but not the E31D mutation, enhanced the RalGDS RBD-binding activity of Ras, indicating that the negative charge at position 31 of Ras is particularly unfavorable to the interaction with the RalGDS RBD. RasG12V(E31K), RasG12V(E31A), and Rap1A stimulate the RalGDS action more efficiently than the wild-type Ras in the liposome reconstitution assay. All of these results clearly show that the sharp contrast between the characteristics of Ras and Rap1A, with respect to the interactions with Raf-1 and RalGDS, depends on their residues at position 31.
Axonal Degeneration Is Blocked by Nicotinamide Mononucleotide Adenylyltransferase (Nmnat) Protein Transduction into Transected Axons (2010)

Axonal degeneration is an early and important component of many neurological disorders. Overexpression of nicotinamide mononucleotide adenylyltransferase (Nmnat), a component of the slow Wallerian degeneration (Wld(s)) protein, protects axons from a variety of insults. We found that transduction of Nmnat protein into severed axons via virus-like particles prevented axonal degeneration. The post-injury efficacy of Nmnat indicates that its protective effects occur locally within the axon and provides an opportunity to develop novel agents to treat axonal damage.
Admission plasma neutrophil gelatinase associated lipocalin (NGAL) predicts worsening renal function during hospitalization and post discharge outcome in patients with acute heart failure (2014)

Admission NGAL measurement appears a sensible tool for in-hospital WRF prediction as well as an early marker for adverse outcome during post discharge vulnerable phase.
Heat Transfer and Property Development in Liquid Silicone Rubber Molding (1985)

Abstract This study has used a heat transfer model to describe the cure of liquid silicone rubbers. The model shows that cure always starts from the wall and will continue during cooling. Thick parts may not be totally cured upon demolding, although the material near the wall has reached a desirable mechanical strength. Since silicone rubbers gel fast at high temperature, mold filling problems may occur for the thin and long molds, especially at high mold temperatures.
Plasma Ignition: A Timely Transportation Breakthrough (2018)

Even with highly developed public transportation, there is a need for personal transport. This is particularly true for large landmasses where the population density may not economically warrant the creation of public transit systems. This is evident in developing countries that need individualized modes of transportation prior to justifying the need for public transport.
Community Outbreak ofMycoplasma pneumoniaeInfection: School‐Based Cluster of Neurologic Disease Associated with Household Transmission of Respiratory Illness (2008)

M. pneumoniae caused a community-wide outbreak of cough illness and pneumonia and was associated with the development of life-threatening neurologic disease. Although M. pneumoniae was detected in schools, its transmission in households amplified the outbreak. Interrupting household transmission should be a priority during future outbreaks.
Serum periostin relates to type‐2 inflammation and lung function in asthma: Data from the large population‐based cohort Swedish GA(2)LEN (2017)

We confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.
Application Aware Workload Allocation for Edge Computing-Based IoT (2018)

Empowered by computing resources at the network edge, data sensed from Internet of Things (IoT) devices can be processed and stored in their nearby cloudlets to reduce the traffic load in the core network, while various IoT applications can be run in cloudlets to reduce the response time between IoT users (e.g., user equipment in mobile networks) and cloudlets. Considering the spatial and temporal dynamics of each application's workloads among cloudlets, the workload allocation among cloudlets for each IoT application affects the response time of the application's requests. While assigning IoT users' requests to their nearby cloudlets can minimize the network delay, the computing delay of a type of requests may be unbearable if the corresponding virtual machine of the application in a cloudlet is overloaded. To solve this problem, we design an application aware workload allocation scheme for edge computing-based IoT to minimize the response time of IoT application requests by deciding the destination cloudlets for each IoT user's different types of requests and the amount of computing resources allocated for each application in each cloudlet. In this scheme, both the network delay and computing delay are taken into account, i.e., IoT users' requests are more likely assigned to closer and lightly loaded cloudlets. Meanwhile, the scheme will dynamically adjust computing resources of different applications in each cloudlet based on their workloads, thus reducing the computing delay of all requests in the cloudlet. The performance of the proposed scheme has been validated by extensive simulations.
A Short Stereoselective Preparation of Dienamides from Cyclobutene Compounds. Application in the Synthesis of a New Cyclohexene Nucleoside (2000)

A short stereoselective synthesis of N-acylamino-1,3-dienes was developed starting from the cyclobutene lactam 8, which was obtained from 2-hydroxypyridine by a photochemical electrocyclic reaction. The tert-butoxycarbonyl derivative 17 was prepared to facilitate nucleophilic attacks to the carbonyl group, and the subsequent thermal ring opening provided dienes 18-21. One of these (20) was used in the synthesis of the cyclohexene nucleoside 30. A Diels-Alder reaction between diene 20 and maleic anhydride provided the endo-cycloadduct 22a. Three additional steps yielded amine 26. Construction of the uracil moiety afforded intermediate 29. Cyclization and removal of the protecting groups occurred in one step in the presence of ammonia, giving the target molecule 30. Diene 20 also underwent [4 + 2] cycloaddition with methyl acrylate to provide predominantly the endo-product 23a, regioselectively.
Simulating and Measuring Structural Intensity Fields in Plates Induced by Spatially and Temporally Random Excitation (2004)

The structure-borne power in bending waves is well understood, and has been studied by many investigators in ideal beam and plate structures. All studies to date, however, have considered only the structural intensity induced by deterministic, localized drives. Since many structures of practical interest are excited by spatially random pressure fields, such as diffuse and turbulent boundary layer pressure fluctuations, techniques for measuring and predicting the structural intensity patterns in plates excited by such fields are presented here. The structural intensity at various frequencies in a simply-supported, baffled, flat plate driven by a diffuse pressure field is simulated using analytical techniques and measured by post-processing data from a scanning laser Doppler vibrometer and reference accelerometer using finite differencing techniques. The measured and simulated fields are similar, and show intensity patterns different from those caused by deterministic point drives.
J-DFA: A Novel Approach for Robust Differential Fault Analysis (2015)

Fault attacks are among the most effective techniquesto break real implementations of cryptographic algorithms. They usually require some kind of knowledge bythe attacker on the effect of the faults on the target device, which in practice turns to be a poorly reliable informationtypically affected by uncertainty. This paper is devoted toaddress this problem by softening the a-priori knowledge on the injection technique needed by the attacker in the contextof Differential Fault Analysis (DFA). We conceive an originalsolution, named J-DFA, based on translating the stage ofdifferential cryptanalysis of DFA attacks into terms of fittingmultiple models to data corrupted by outliers. Specifically, wetailor J-Linkage algorithm [9] to the fault analysis. In order toshow the effectiveness of J-DFA and its benefits in practicalscenarios, we applied the technique under different attackconditions.
Genetic Craniofacial Disorders Affecting the Dentition (2018)

Genetic disorders that alter early events in tooth development may be limited in their phenotypes to the dentition or compromise the development of other ectodermal organs, as in syndromes. This chapter provides a concise overview of dental genetic malformations that offer early evidence of undiagnosed syndromic or systemic conditions of bone and mineral. The most common disorder with dentin malformations is autosomal dominant (AD) osteogenesis imperfecta (OI), which is caused by defects in the genes that encode type I collagen. Metabolic diseases of bone are disorders of bone remodeling that characteristically involve the entire skeleton, and are often manifest in the oral cavity, which can lead to the diagnosis of the underlying systemic disease. Hypophosphatasia (HPP) is caused by loss of function mutation of the skeletal alkaline phosphatase. The classic oral presentation of childhood hypophosphatasia is premature loss of fully-rooted deciduous teeth.
DNA-MEDIATED REF1 CONFORMATIONAL CHANGES: POSSIBLE MECHANISM FOR PROTEIN RECRUITMENT IN BASE EXCISION REPAIR (BER) PATHWAY. (2016)

Abstract not provided.
Figure S4 from Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma (2023)

&lt;p&gt;CITE-seq identifies differential modulation of PBMC subsets&lt;/p&gt;
Data-Efficient Bayesian Optimization with Constraints for Power Amplifier Design (2018)

Finding the optimal working conditions for non-linear electrical components under large signal stimuli can be challenging, mainly due to the high number of input dimensions and multiple local minima of the goal function. In this paper a Bayesian optimization method is applied in order to limit the number of evaluations by a commercial harmonic balance simulator. The method is applied to amplifier optimization utilizing Wolsfspeed CGH40010F HEMT, for which input power, bias voltages and load at fundamental harmonic frequencies are changed in order to maximize for combined efficiency, gain, and output power. The optimum is found already after 80 iterations.