gebhart/patrepeval huggingface dataset:
Formation of Periodically-Ordered Calcium Phosphate Nanostructures by Block Copolymer-Directed Self-Assembly (2016)

Structuring ionic solids at the nanoscale with block copolymers (BCPs) is notoriously difficult due to solvent incompatibilities and strong driving forces for crystallization of the inorganic material. Here, we demonstrate that elucidating pathway complexity in the BCP-directed self-assembly of an ionic solid, amorphous calcium phosphate (ACP), is a key component in obtaining nanostructured, bulk composite materials in which the nanostructure is the result of thermodynamically controlled BCP self-assembly, i.e., exhibiting sequences of bulk morphologies as known from typical equilibrium BCP phase diagrams. Specifically, we identify three critical pathway “decision points” for the evaporation-induced self-assembly of composites from ultrasmall, organosilicate-modified amorphous calcium phosphate nanoparticles (osm-ACP-NPs) and poly(isoprene)-block-poly(2-(dimethylamino)ethyl methacrylate) (PI-b-PDMAEMA) block copolymers. Using this strategy enabled us to obtain composites with hexagonal, cubic network, and lamellar BCP morphologies, in addition to mesoporous, cellular materials and macrophase separated materials. The osm-ACP-NPs are synthesized via a two-step sol–gel process in which (3-glycidyloxypropyl)trimethoxysilane (GLYMO) quenches the reaction, limits the particle size, and functionalizes the NP surface. Dynamic light scattering evidences a transition from BCP unimers to micellar aggregates with increasing amounts of sol solution, which is reflected by a corresponding switch from BCP-type morphologies to micellar/cellular morphologies of the nanocomposites. Nanostructured organic–inorganic composites with a continuous osm-ACP-NP matrix phase have indentation moduli (measured by nanoindentation) that are an order of magnitude larger than unstructured composites with similar compositions. Insights provided by this study have relevance to understanding the effects of pathway complexity in the assembly of organic–inorganic composites and may enable access to a broad range of hybrid nanostructures with potential applications in areas including dental repair and hard tissue engineering.
Mutant Oncopeptide Immunization Induces CTL Specifically Lysing Tumor Cells Endogenously Expressing the Corresponding Intact Mutant p53 (1995)

The p53 nuclear oncoprotein frequently contains somatically acquired missense mutations and is often overexpressed in cancer cells. It is now known that nuclear and cytosolic proteins are processed into peptides and these can be transported into the endoplasmic reticulum and presented on the cell surface with class I MHC. We have previously shown that after treatment with interferon gamma (IFN-gamma), BALB/c 3T3 fibroblasts transfected with mutant p53 (135 C to Y) can be specifically lysed by mutant peptide-induced CTL. Here we show that P815 mastocytomas are effectively lysed by peptide stimulated CTL without treatment of IFN-gamma in vitro.
FASS IS A BETTER PREDICTOR OF POOR OUTCOME IN LOWER LIMB BLAST INJURY THAN AIS: IMPLICATIONS FOR BLAST RESEARCH (2013)

The defining weapon of the conflicts in Iraq and Afghanistan has been the Improvised Explosive Device (IEDs). When detonated under a vehicle, they result in significant axial loading to the lower limbs, resulting in devastating injuries. Due to the absence of clinical blast data, automotive injury data using the Abbreviated Injury Score (AIS) has been extrapolated to define current NATO injury thresholds for Anti-vehicle (AV) mine tests. We hypothesized that AIS, being a marker of fatality rather than disability would be a worse predictor of poor clinical outcome compared to the lower limb specific Foot and Ankle Severity Score (FASS). Using a prospectively collected trauma database, we identified UK Service Personnel sustaining lower leg injuries from under-vehicle explosions from Jan 2006–Dec 2008. A full review of all medical documentation was performed to determine patient demographics and the severity of lower leg injury, as assessed by AIS and FASS. Clinical endpoints were defined as (i) need for amputation or (ii) poor clinical outcome. Statistical models were developed in order to explore the relationship between the scoring systems and clinical endpoints. 63 UK casualties (89 limbs) were identified with a lower limb injury following under-vehicle explosion. The mean age of the casualty was 26.0 yrs. At 33.6 months follow-up, 29.1% (26/89) required an amputation and a further 74.6% (41/89) having a poor clinical outcome (amputation or ongoing clinical problems). Only 9(14%) casualties were deemed medically fit to return to full military duty. ROC analysis revealed that both AIS=2 and FASS=4 could predict the risk of amputation, with FASS = 4 demonstrating greater specificity (43% vs 20%) and greater positive predictive value (72% vs 32%). In predicting poor clinical outcome, FASS was significantly superior to AIS (p Foot and ankle injuries following AV mine blast are associated with significant morbidity. Our study clearly demonstrates that AIS is not a predictor of long-term clinical outcome and that FASS would be a better quantitative measure of lower limb injury severity. There is a requirement to reassess the current injury criteria used to evaluate the potential of mitigation technologies to help reduce long-term disability in military personnel. Our study highlights the critical importance of utilising contemporary battlefield injury data in order to ensure that the evaluation of mitigation measures is appropriate to the injury profile and their long-term effects.
A novel equivalent power network impedance approach for assessing the time reference in asynchronous measurements (2017)

The paper presents a novel mathematical approach for assessing the phase angle displacement of voltages at nods of a power network with respect to a node taken as reference. It is accomplished without the use of a global time-reference signal, like those provided by GPS technology or through wired connections. This study origins from the growing interest of Distribution System Operators (DSOs) to deploy Distributed Synchronized Measurement Systems (DSMS) in their power networks (like, in particular, the Phasor Measurement Units) for enhancing the stability and reliability of the networks. There are circumstances where bringing a time reference signal to remote PMUs is a difficult task. The paper provides an alternative solution to evaluate phasors in Distribution lines with no need of a global time reference.
UBQLN2/P62 cellular recycling pathways in amyotrophic lateral sclerosis and frontotemporal dementia (2011)

Recent findings highlight a pathologic and functional convergence in amyotrophic lateral sclerosis (ALS) and amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD) at the level of protein recycling and disposal. Genes linked to rare cases of familial ALS and ALS-FTD, like UBQLN2, OPTN, SQSTM1/p62, and VCP, may converge onto a unifying pathogenic pathway and thereby provide novel therapeutic targets common to a spectrum of etiologically diverse forms of ALS and ALS-FTD. Interactions between these genes need to be further explored to understand their common molecular pathways. Future efforts should be directed toward generation and characterization of in vivo models to dissect the pathogenic mechanisms of ALS and ALS-FTD and the role of protein degradation pathways, both centrally, at the cell body, and peripherally, at the level of the synapse. Such efforts will rapidly accelerate the discovery of new drugs that regulate accumulation of pathogenic proteins and their downstream consequences in ALS and ALS-FTD and, possibly, other neurodegenerative diseases as well.
Refined Measurement and Signal Analysis Techniques in Vacuum and Plasma-Filled High Power Microwave Sources (2000)

Abstract : This report describes the acquisition and utilization of instrumentation in the support of high power microwave (HPM) research. Recent advances in understanding the output of intense beam-driven relativistic requires both highly temporally resolved measurement capabilities, coupled with signal processing techniques such as time-frequency analysis. In particular, better understanding of nonlinear effects such as mode-hopping due to the cross-excitation instability, required the ability to resolve frequency shifts during the generation of HPM radiation. The instrumentation acquired under this FY'99 DURIP grant led to the careful diagnosis of this instability.
A closer look at intravascular hemolysis (IVH) following intravenous anti-D for immune thrombocytopenic purpura (ITP) (2007)

To the editor:

Gaines has recently highlighted the risks of intravascular hemolysis (IVH) associated with intravenous infusion of anti-D in patients with ITP.[1][1] Collectively, we have seen uncomplicated IVH detected by routine clinical monitoring in 10 otherwise healthy patients with ITP among
A Superconducting Phase Shifter and Traveling Wave Kinetic Inductance Parametric Amplifier for W-Band Astronomy (2017)

The W-Band ($75-110\; \mathrm{GHz}$) sky contains a plethora of information about star formation, galaxy evolution and the cosmic microwave background. We have designed and fabricated a dual-purpose superconducting circuit to facilitate the next generation of astronomical observations in this regime by providing proof-of-concept for both a millimeter-wave low-loss phase shifter, which can operate as an on-chip Fourier transform spectrometer (FTS) and a traveling wave kinetic inductance parametric amplifier (TKIP). Superconducting transmission lines have a propagation speed that depends on the inductance in the line which is a combination of geometric inductance and kinetic inductance in the superconductor. The kinetic inductance has a non-linear component with a characteristic current, $I_*$, and can be modulated by applying a DC current, changing the propagation speed and effective path length. Our test circuit is designed to measure the path length difference or phase shift, $Δϕ$, between two symmetric transmission lines when one line is biased with a DC current. To provide a measurement of $Δϕ$, a key parameter for optimizing a high gain W-Band TKIP, and modulate signal path length in FTS operation, our $3.6 \times 2.5\; \mathrm{cm}$ chip employs a pair of $503\; \mathrm{mm}$ long NbTiN inverted microstrip lines coupled to circular waveguide ports through radial probes. For a line of width $3\; \mathrm{μm}$ and film thickness $20\; \mathrm{nm}$, we predict $Δϕ\approx1767\; \mathrm{rad}$ at $90\; \mathrm{GHz}$ when biased at close to $I_*$. We have fabricated a prototype with $200\; \mathrm{nm}$ thick Nb film and the same line length and width. The predicted phase shift for our prototype is $Δϕ\approx30\; \mathrm{rad}$ at $90\; \mathrm{GHz}$ when biased at close to $I_*$ for Nb.
Biochemical and biological studies on dopastin, an inhibitor of dopamine .BETA.-hydroxylase. (1974)

Dopastin produced by a pseudomonas is a potent inhibitor of dopamine β-hydroxylase. Kinetic studies with the purified enzyme indicated that inhibition by dopastin was of the uncompetitive type to the substrate and of the competitive to the cofactor, ascorbic acid. The nitrosohydroxylamino group of dopastin was found to be essential in inhibition of dopamine β-hydroxylase. Both racemic and natural dopastins showed the same activity. Dopastin showed significant hypotensive effect to spontaneously hypertensive rats and phytotoxicity to barley germination.
Substrate specificity of 2-deoxy-D-ribose 5-phosphate aldolase (DERA) assessed by different protein engineering and machine learning methods (2020)

In this work, deoxyribose-5-phosphate aldolase (Ec DERA, EC 4.1.2.4) from Escherichia coli was chosen as the protein engineering target for improving the substrate preference towards smaller, non-phosphorylated aldehyde donor substrates, in particular towards acetaldehyde. The initial broad set of mutations was directed to 24 amino acid positions in the active site or in the close vicinity, based on the 3D complex structure of the E. coli DERA wild-type aldolase. The specific activity of the DERA variants containing one to three amino acid mutations was characterised using three different substrates. A novel machine learning (ML) model utilising Gaussian processes and feature learning was applied for the 3rd mutagenesis round to predict new beneficial mutant combinations. This led to the most clear-cut (two- to threefold) improvement in acetaldehyde (C2) addition capability with the concomitant abolishment of the activity towards the natural donor molecule glyceraldehyde-3-phosphate (C3P) as well as the non-phosphorylated equivalent (C3). The Ec DERA variants were also tested on aldol reaction utilising formaldehyde (C1) as the donor. Ec DERA wild-type was shown to be able to carry out this reaction, and furthermore, some of the improved variants on acetaldehyde addition reaction turned out to have also improved activity on formaldehyde. KEY POINTS: • DERA aldolases are promiscuous enzymes. • Synthetic utility of DERA aldolase was improved by protein engineering approaches. • Machine learning methods aid the protein engineering of DERA.
Genomic analysis, immunomodulation and deep phenotyping of patients with nodding syndrome (2022)

The aetiology of nodding syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with nodding syndrome, investigate potential contributors to disease aetiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for nodding syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had nodding syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. CSF was non-inflammatory and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus-specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal aetiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention.
EB1 Targets to Kinetochores with Attached, Polymerizing Microtubules (2020)

Microtubule polymerization dynamics at kinetochores is coupled to chromosome movements, but its regulation there is poorly understood. The plus end tracking protein EB1 is required both for regulating microtubule dynamics and for maintaining a euploid genome. To address the role of EB1 in aneuploidy, we visualized its targeting in mitotic PtK1 cells. Fluorescent EB1, which localized to polymerizing ends of astral and spindle microtubules, was used to track their polymerization. EB1 also associated with a subset of attached kinetochores in late prometaphase and metaphase, and rarely in anaphase. Localization occurred in a narrow crescent, concave toward the centromere, consistent with targeting to the microtubule plus end–kinetochore interface. EB1 did not localize to kinetochores lacking attached kinetochore microtubules in prophase or early prometaphase, or upon nocodazole treatment. By time lapse, EB1 specifically targeted to kinetochores moving antipoleward, coupled to microtubule plus end polymerization, and not during plus end depolymerization. It localized independently of spindle bipolarity, the spindle checkpoint, and dynein/dynactin function. EB1 is the first protein whose targeting reflects kinetochore directionality, unlike other plus end tracking proteins that show enhanced kinetochore binding in the absence of microtubules. Our results suggest EB1 may modulate kinetochore microtubule polymerization and/or attachment.
ChemInform Abstract: Pyridopyrimidine Analogues as Novel Adenosine Kinase Inhibitors. (2001)

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.
A Spectroscopic Investigation Of The Naphthalene In Biphenyl And The Biphenyl Crystal Systems. (1974)

PhD
Screen for Agents That Induce Autolysis in Bacillus subtilis (2012)

The growing prevalence of antibiotic-resistant infections underscores the need to discover new antibiotics and to use them with maximum effectiveness. In response to these needs, we describe a screening protocol for the discovery of autolysis-inducing agents that uses two Bacillus subtilis reporter strains, SH-536 and BAU-102. To screen chemical libraries, autolysis-inducing agents were first identified with a BAU-102-based screen and then subdivided with SH-536 into two major groups: those that induce autolysis by their direct action on the cell membrane and those that induce autolysis secondary to inhibition of cell wall synthesis. SH-536 distinguishes between the two groups of autolysis-inducing agents by synthesizing and then releasing β-galactosidase (β-Gal) in late stationary phase at a time that cells have nearly stopped growing and are therefore tolerant of cell wall synthesis inhibitors. Four hits, named compound 2, compound 3, compound 5, and compound 24, obtained previously as inducers of autolysis by screening a 10,080-compound discovery library with BAU-102, were probed with SH-536 and found to release β-Gal, indicating that their mode of action was to permeabilize the B. subtilis cell membrane. The four primary hits inhibited growth in Staphylococcus aureus, Enterococcus faecium, Bacillus subtilis, and Bacillus anthracis, with MICs in the 12.5- to 25-μg/ml (20 to 60 μM) range. The four primary hits were further used to probe B. subtilis, and their action was partially characterized with respect to the dependence of induced autolysis on specific autolysins.
LAB-EXPERIMENTAL (PRE-CLINICAL) THERAPEUTICS AND PHARMACOLOGY (2012)

Ginsenoside Rg3 is a natural active ingredient that is extracted from Korean red ginseng root. It elevates the therapeutic effect of radiotherapy and chemotherapy, but previous studies found that the application of Rg3 is heavily limited by its low bioavailability and poor absorption via oral administration. To overcome these problems, Rg3-loaded PEG-PLGA-NPs (Rg3-NPs) were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method, and the physicochemical characteristics of Rg3-NPs were investigated. We treated primary glioblastoma with 50 mM Rg3-NPs for 48h. We then used gene expression arrays (Illumina) for genome-wide expression analysis and validated the results for genes of interest by means of real-time PCR. Functional annotations were then performed using the DAVID and KEGG online tools. The results showed that the Rg3-NPs are slick and uniform, the average diameter of the nanoparticles is 75-90 nm, and their entrapment efficiency is 89.7+1.7%. MTT showed that the growth of cells can be significantly inhibited by Rg3-NPs in a dose-dependent manner. FCM testing showed Rg3-NPs can be released from the conjugate nanoparticle and react with the genes in the cell nuclei, causing changes in the gene molecules. We also found that cancer cells treated with Rg3-NPs undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes BUB1, CDC20, TTK, and CENPE, as determined by microarray analysis and verified by real-time PCR. Furthermore, Rg3-NPs induced the expression of the apoptotic and antimigratory protein p53 in cell lines. The results of the present study, together with the results of earlier studies, show that Rg3-NPs target genes involved in theprogressionoftheM-phaseofthecellcycle.Itisassociatedwithseveralimportant pathways, which include apoptosis (p53). Rg3-NPs may be a potent cell-cycle regulation drug targeting the M-phase in glioblastoma cell lines.
MSP RFLP for X-linked proteolipid protein gene (PLP) identified with either rat or humanPLPcDNA clone (1987)

Journal Article MSP RFLP for X-linked proteolipid protein gene (PLP) identified with either rat or human PLP cDNA clone Get access J.-S. Wu, J.-S. Wu 1Department of Human Genetics, Yale University School of MedicineNew Haven, CT 06510 Search for other works by this author on: Oxford Academic PubMed Google Scholar J.R. Riordan, J.R. Riordan 2Research Institute, Hospital for Sick ChildrenToronto M5G 1A8 Search for other works by this author on: Oxford Academic PubMed Google Scholar H.F. Willard, H.F. Willard 2Research Institute, Hospital for Sick ChildrenToronto M5G 1A83Department of Medical Genetics, University of TorontoToronto M5G 1A8 Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Milner, R. Milner 4Division of Preclinical Neuroscience and Endocrinology, Scripps Clinic and Research FoundationLa Jolla, CA 92037. USA Search for other works by this author on: Oxford Academic PubMed Google Scholar K.K. Kidd K.K. Kidd 1Department of Human Genetics, Yale University School of MedicineNew Haven, CT 06510 Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 15, Issue 4, 25 February 1987, Page 1882, https://doi.org/10.1093/nar/15.4.1882 Published: 25 February 1987
Optical loop mirror with semiconductor laser amplifier: application as optical correlator (1993)

A nonlinear optical loop mirror is reported, employing a semiconductor laser amplifier (SLA). The input-output characteristic is distinctly nonlinear and when operating as an optical correlator an extinction ratio of 13 dB was revealed.