gebhart/patrepeval huggingface dataset:
Cystathionine β‐synthase (CBS) Deficiency: Genetics (2010)

Abstract Cystathionine β‐synthase (CBS) is an enzyme that catalyses condensation of homocysteine and serine to cystathionine. CBS deficiency, an autosomal recessive trait with estimated population frequency of around 1:10 000–1:20 000, resembles in the most severe forms Marfan syndrome with thromboembolism and neurological impairment, whereas milder forms may manifest with only thromboembolism or may remain asymptomatic. Laboratory findings include grossly elevated plasma total homocysteine and in part of patients also elevated blood methionine; the latter feature is utilised in neonatal screening. CBS binds three cofactors: pyridoxal 5′‐phosphate, an allosteric activator S ‐adenosylmethionine and haem with as yet unresolved function. In the CBS gene, more than 150 different mutations have been described to date, almost 90% of them are missense variants. Although some of the mutations affect ribonucleic acid processing and its stability, the majority of mutations lead to enzyme misfolding and misassembly, which may be in part rescued by chemical or molecular chaperones. Key Concepts: Cystathionine β‐synthase catalyses the first step in homocysteine trans ‐sulfuration. Cystathionine β‐synthase is a modular enzyme composed of a haem‐binding N ‐terminal domain, the catalytically active core and the C ‐terminal autoinhibitory domain. More than 150 different pathogenic mutations have been described in the CBS gene, almost 90% of all mutant CBS alleles carry missense mutations. Misfolding and misassembly of mutant CBS subunits is a common pathogenic mechanism leading to CBS deficiency. Mutation topology predicts in part the behaviour of mutant CBS enzymes, solvent accessible mutations have less severe effect than those buried in the enzyme globule. Deficient CBS activity leads to gross elevation of plasma total homocysteine and often to elevated blood methionine levels. Phenotypic consequences of mutations in the CBS gene include thromboembolism and vascular occlusion, which is accompanied in some patients by lens dislocation, marfanoid features and varying degree of neurological involvement. Population frequency of clinically ascertained patients with CBS deficiency is one to two orders of magnitude lower than the frequency calculated from the prevalence of heterozygotes for pathogenic mutations; this observation indicates an ascertainment bias or lack of symptoms in many CBS‐deficient individuals. Murine models of CBS deficiency recapitulate in part the pathophysiology and organ involvement observed in human patients.
The DP-Receptor Agonist SQ27986 Raises but Does Not Lower Intraocular Pressure in Ocular Normotensive Monkeys (1992)

rostaglandin (PG) D2 and the DP-receptor selective analog BW245C have been shown to lower intraocular pressure (IOP) in rabbits, monkeys, and man. In these experiments, the effects of the DP-receptor selective agonist SQ27986 on IOP, pupil diameter, and refractive error in ocular normotensive cynomolgus monkeys were tested. Single or repeated (three days of twice-daily) unilateral doses of SQ27986 produced a 2–6 mm Hg rise in IOP 15–120 min after administration, which was not followed by ocular hypotension. The SQ27986 had no effect on pupil diameter, refraction, or anterior segment biomicroscopic appearance. Although other DP-receptor agonists can lower IOP slightly in normotensive eyes and more substantially in hypertensive eyes by decreasing aqueous formation, the inability of SQ27986 to reduce IOP in our ocular normotensive monkeys suggests that DP-receptor stimulation does not increase uveoscleral outflow or play a major role in IOP reduction by other relatively nonselective prostaglandins such as PGF2α.
Pharmacokinetics and pharmacodynamics of mepindolol sulphate. (1980)

Five clinically healthy, male volunteers were each given an intravenous dose of 1.19 mg of 2-methyl-14C-mepindolol sulphate, followed one week later by an oral dose of 20 mg. In addition, the effect of mepindolol sulphate was studied in 3 male test subjects after repeated oral administration for 8 days with a daily dose of 2 x 2.5 mg using the heart rate behaviour model during submaximum ergometer exercise. Synchronously with pharmacodynamics, pharmacokinetic data were also obtained after multiple dosing.
AAV8 Gene Therapy Rescues the Newborn Phenotype of a Mouse Model of Crigler–Najjar (2018)

Adeno-associated viral (AAV) vectors can target the liver, making them an attractive platform for gene therapy approaches that require the correction of hepatocytes. Crigler-Najjar syndrome is an autosomal recessive disorder of bilirubin metabolism that occurs when the liver's uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) enzyme activity is partially or completely absent. This syndrome is characterized by elevated bilirubin levels in the blood. An AAV8 vector was developed expressing a codon-optimized human version of UGT1A1 from a liver-specific promoter. High doses of the vector rescued neonatal lethality in newborn UGT1 knockout (KO) mice, which serve as a model of Crigler-Najjar syndrome, and significantly increased survival from 5 to 270 days. Newborn UGT1 KO mice treated with AAV had serum total bilirubin levels that were 5.7 times higher than the levels seen in heterozygous and wild-type mice, likely due to dilution of vector genome copies (GC) in the liver resulting from a proliferation of hepatocytes during growth of the animal. The elevation in serum total bilirubin levels in adult UGT1 KO mice depended on the AAV8 vector dose. At doses <10<sup>11</sup> GC/mouse, total bilirubin levels returned to those seen in phototherapy-rescued UGT1 KO mice. Mice injected with vector at 10<sup>11</sup> or 3 × 10<sup>11</sup> GC/mouse had sustained reduced total bilirubin levels throughout the duration of the study. When an AAV8 vector was re-administered in mice with elevated total bilirubin levels, serum total bilirubin levels decreased to wild-type levels (0.1-0.3 mg/dL) in mice that received a vector dose of 3 × 10<sup>12</sup> GC/kg. Therefore, a low-level and likely transient decrease in serum total bilirubin during the first days of life is necessary for rescuing the lethal phenotype present in the neonatal UGT1 KO mouse. Furthermore, it was possible to ablate the elevated total bilirubin levels in adult mice by re-administering an AAV8 vector.
Immune aging in multiple sclerosis is characterized by abnormal CD4 T cell activation and increased frequencies of cytotoxic CD4 T cells with advancing age (2022)

Stated in Acknowledgements section of manuscript.
Towards Self‐Regulated Bioprocessing: A Compact Benchtop Bioreactor System for Monitored and Controlled 3D Cell and Tissue Culture (2019)

Bioreactors are crucial tools for the manufacturing of living cell-based tissue engineered products. However, to reach the market successfully, higher degrees of automation, as well as a decreased footprint still need to be reached. In this study, the use of a benchtop bioreactor for in vitro perfusion culture of scaffold-based tissue engineering constructs is assessed. A low-footprint benchtop bioreactor system is designed, comprising a single-use fluidic components and a bioreactor housing. The bioreactor is operated using an in-house developed program and the culture environment is monitored by specifically designed sensor ports. A gas-exchange module is incorporated allowing for heat and mass transfers. Titanium-based scaffolds are seeded with human periosteum-derived cells and cultured up to 3 weeks. The benchtop bioreactor constructs are compared to benchmark perfusion systems. Live/Dead stainings, DNA quantifications, glucose consumption, and lactate production assays confirm that the constructs cultured in the benchtop bioreactor grew similarly to the benchmark systems. Manual regulation of the system set points enabled efficient alteration of the culture environment in terms of temperature, pH, and dissolved oxygen. This study provides the necessary basis for the development of low-footprint, automated, benchtop perfusion bioreactors and enables the implementation of active environment control.
Three-Dimensional Classification of Thoracic Scoliotic Curves (2008)

Two distinct subgroups within the surgical cases (major curves) of Lenke type-1 curves were found thus suggesting that thoracic curves are not always hypokyphotic. The ISOData cluster analysis technique helped to capture inherent 3D structural curve complexities that were not evident in a 2D radiographic plane. The daVinci representation is a new clinically relevant means to report 3D spinal deformities.
Consensus Guidelines for Therapeutic Drug Monitoring of Rapamycin: Report of the Consensus Panel (1995)

Yatscoff, Randall W.; Boeckx, Roger; Holt, David W.; Kahan, Barry D.; LeGatt, Donald F.; Sehgal, Suren; Soldin, Steven J.; Napoli, Kimberly; Stiller, Calvin Author Information
High-Concentration Aqueous Dispersions of Graphene Using Nonionic, Biocompatible Block Copolymers (2011)

The ability to disperse pristine graphene at high concentrations in aqueous solutions is an enabling step for large-scale processing and emerging biomedical applications. Herein we demonstrate that nonionic, biocompatible block copolymers are able to produce graphene dispersions with concentrations exceeding 0.07 mg mL–1 via sonication and centrifugation, resulting in optical densities above 4 OD cm–1 in the visible and near-infrared regions of the electromagnetic spectrum. The dispersion efficiency of graphene using Pluronic and Tetronic block copolymers varies substantially depending on the lengths of their hydrophilic and hydrophobic domains, with the best of these copolymers sharing similar domain molecular weight ratios and comparable overall molecular weights. This study presents a new class of biocompatible dispersing agents for graphene in aqueous solution, thus suggesting a facile route to employ graphene in biomedical sensing, imaging, and therapeutic applications.
Modular Type III Porous Liquids based on Porous Organic Cage Microparticles (2021)

The dispersion of particulate porous solids in size-excluded liquids has emerged as a method to create Type III porous liquids, mostly using insoluble microporous materials such as metal-organic frameworks (MOFs) and zeolites. Here, we present the first examples of Type III porous liquids based on porous organic cages (POCs). By exploiting the solution processability of the POCs, racemic and quasiracemic cage microparticles were formed by chiral recognition. Dispersion of these porous microparticles in a range of size-excluded liquids, including oils and ionic liquids, formed stable POC-based Type III porous liquids. The flexible pairing between the solid POC particles and a carrier liquid allows the formation of a range of compositions, pore sizes, and other physicochemical properties to suit different applications and operating conditions. For example, we show that it is possible to produce porous liquids with relatively low viscosities (7-14 mpa∙s) or high thermal stability (325 °C). A 12.5 wt. % Type III porous liquid comprising racemic POC microparticles and an ionic liquid, [BPy][NTf&lt;sub&gt;2&lt;/sub&gt;], shows a CO&lt;sub&gt;2&lt;/sub&gt; working capacity (104.30 μmol/g&lt;sub&gt;L&lt;/sub&gt;) that is significantly higher than the neat ionic liquid (37.27 μmol/g&lt;sub&gt;L&lt;/sub&gt;) between 25 °C and 100 °C. This liquid is colloidally stable and can be recycled at least 10 times without loss of CO&lt;sub&gt;2&lt;/sub&gt; capacity.
PLASMA URIC ACID LEVEL AND ITS ASSOCIATION WITH DIABETES MELLITUS AND SOME BIOLOGIC PARAMETERS IN A BIRACIAL POPULATION OF FIJI (1988)

Plasma uric acid was investigated in a population survey on diabetes and cardiovascular risk factors among Melanesians and Asian Indians in Fiji in 1980. Plasma uric acid levels were elevated in men and women with impaired glucose tolerance in both ethnic groups. The lowest plasma uric acid levels were found in diabetic patients, especially in diabetic men. Even though obesity was positively associated with plasma uric acid, it did not explain the high plasma uric acid level in persons with impaired glucose tolerance. Body mass index had a significant and independent impact on plasma uric acid levels both in nondiabetic and diabetic men and women. The strongest predictor of plasma uric acid in the multiple regression analysis in our study populations was plasma creatinine: it alone explained 9% of the variation in men and 2% in women; and 24% in Melanesians and 5% in Asian Indians. Our findings suggest a strong renal involvement in the balance of plasma uric acid and may also reflect certain dietary patterns, such as a high intake of protein, fats, and certain local vegetables. Although the prevalence of hyperuricemia was high, 27% in both Melanesian men and women, 22% in Asian Indian men, and 11% in Asian Indian women, clinical gout was uncommon. Many predictor variables and their interactions were analyzed along with the reasons for the high plasma uric acid levels in persons with impaired glucose tolerance and for the low plasma uric acid levels in diabetic patients.
Thermal cycle reliability of stacked via structures with copper metallization and an organic low-k dielectric (2004)

The reliability of a stacked via chain stressed under various thermal cycle conditions is described. The chain consists of Cu Dual Damascene metallization with SiLK (trademark of Dow Chemical) as the organic low-k dielectric. Failure analysis indicates that cracks form in the Cu vias during thermal cycle stress. Due to the presence of two failure modes, the thermal cycle statistical behavior is described by a bimodal lognormal failure distribution. The thermal cycle lifetime exhibits a strong dependence on the temperature range and a rather weak dependence, on the maximum temperature in the cycle. Evidence of a threshold temperature range below which thermal cycle fails should not occur as well as a correlation between the test structure yield and reliability are also reported.
<title>New block-matching-based color interpolation algorithm</title> (1998)

In an electronic color image capturing device using a single CCD or CMOS sensor, the color information is usually acquired into three sub-sampled color planes such as Red (R), Green (G) and Blue (B). Full resolution color is subsequently generated from this sub-sampled image using a suitable 'color interpolation' methodology. The color accuracy and appearance of the image is significantly affected by the color interpolation algorithm used to generate the full-resolution color image. In this paper, we present a new block matching based algorithm for color interpolation. The computational complexity of this algorithm is very low and hence suitable for real-time implementation in a portable image capture device e.g. a digital camera. The proposed algorithm produces the similar or better quality color images compared to most of the known color interpolation algorithms in the literature. We have presented results of comparison of the performance of the proposed algorithm with median interpolation and bilinear interpolation which are commonly used in practice.
TS-1 zeolite microengineered reactors for 1-pentene epoxidation (2002)

A zeolite-based microengineered reactor was fabricated and tested for 1-pentene epoxidation over titanium silicalite-1 (TS-1) catalyst, which has been selectively incorporated within the microreactor channel using a new synthesis procedure.
Static and dynamic mode coupling in a double-pass rod-type fiber amplifier (2018)

This Letter describes an experimental realization of a double-pass amplifier using rod-type fiber. In this device, the gain reaches 26 dB amplifying a 300 mW, 20 ps, 20 MHz seed up to 120 W, with an optical-to-optical efficiency of 50% and excellent beam quality. In addition, by design the output of the amplifier has a polarization extinction ratio of 33 dB. Besides these good performances, we report a marginal degradation of mode quality and degree of polarization followed by the so-called transverse mode instability which occurs at 120 W signal power. The first degradation is static, and by analyzing its two polarizations, we conclude it is caused by a coupling between modes due to the formation of a static thermal long-period grating, which in turn initiates the dynamic instability.
Repository-scale propagated spectral library of suspects (2020)

In untargeted metabolomics a majority of the acquired MS/MS spectra typically remains unidentified. In part, this is due to the fact that the molecular coverage of reference spectral libraries is necessarily incomplete. However, even if an exact match cannot be found in a spectral library, it is often possible to propagate annotations to structurally related molecules. We have created a "suspect" reference spectral library, consisting of putative molecule identities and a loss or addition characterized by a difference in precursor mass. By propagating library annotations to previously unidentified spectra using repository-scale molecular networking, we are able to extract 79,461 high-quality suspect spectra in a data-driven fashion from 92,063 raw files originating from 1,289 heterogeneous public datasets deposited to GNPS. This forms a rich data resource of novel, real-life, reference spectra that will be freely available for the community to use via GNPS.
Supplementary Data from Association of Tissue Abiraterone Levels and <i>SLCO</i> Genotype with Intraprostatic Steroids and Pathologic Response in Men with High-Risk Localized Prostate Cancer (2023)

&lt;p&gt;Supplementary Figures and Tables Supplementary Table S1. Baseline Patient Demographic and Clinical Characteristics Supplementary Table S2. Observed and Expected Hardy Weinberg (HW) Frequency of SLCO Genotypes Supplementary Table S3. Distribution of Men with Undetectable Tissue ABI Levels Supplementary Table S4. Characteristics of SLCO Genotypes and Potential Prostate Cancer Associations Supplementary Table S5. Association of SLCO Genotype with Tissue Abiraterone, Estimated Tumor Volume and Minimal Residual Disease (MRD) Supplementary Figure S1. Representative chromatograms showing retention time for abiraterone standard and tissue samples. Supplementary Figure S2. Serum steroid levels in samples with undetectable vs detectable prostate abiraterone levels. Supplementary Figure S3. Association of SLCO single nucleotide polymorphisms with serum or tissue steroid levels. Supplementary Figure S4. Absolute abiraterone levels measured in LNCaP cells overexpressing SLCO2B1 or SLCO1B3.&lt;/p&gt;
ChemInform Abstract: δ‐Sultone Formation Through Rh‐Catalyzed C—H Insertion. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
An (E,E)‐α‐farnesene synthase gene of soybean has a role in defence against nematodes and is involved in synthesizing insect‐induced volatiles (2016)

Plant terpene synthase genes (TPSs) have roles in diverse biological processes. Here, we report the functional characterization of one member of the soybean TPS gene family, which was designated GmAFS. Recombinant GmAFS produced in Escherichia coli catalysed the formation of a sesquiterpene (E,E)-α-farnesene. GmAFS is closely related to (E,E)-α-farnesene synthase gene from apple, both phylogenetically and structurally. GmAFS was further investigated for its biological role in defence against nematodes and insects. Soybean cyst nematode (SCN) is the most important pathogen of soybean. The expression of GmAFS in a SCN-resistant soybean was significantly induced by SCN infection compared with the control, whereas its expression in a SCN-susceptible soybean was not changed by SCN infection. Transgenic hairy roots overexpressing GmAFS under the control of the CaMV 35S promoter were generated in an SCN-susceptible soybean line. The transgenic lines showed significantly higher resistance to SCN, which indicates that GmAFS contributes to the resistance of soybean to SCN. In soybean leaves, the expression of GmAFS was found to be induced by Tetranychus urticae (two-spotted spider mites). Exogenous application of methyl jasmonate to soybean plants also induced the expression of GmAFS in leaves. Using headspace collection combined with gas chromatography-mass spectrometry analysis, soybean plants that were infested with T. urticae were shown to emit a mixture of volatiles with (E,E)-α-farnesene as one of the most abundant constituents. In summary, this study showed that GmAFS has defence roles in both below-ground and above-ground organs of soybean against nematodes and insects, respectively.
Should We Be Performing More Pancreas Transplants? (2015)

Pancreas transplantation can provide insulin independence, improved survival, and improved quality of life for patients with diabetes mellitus. However, there has been a steady decline in the number of pancreas transplants (either alone or with a kidney) performed in the United States over the past decade. This decline has occurred despite a steady increase in the number of diabetic patients with end stage renal disease on the kidney transplant alone waiting list. This paper will review the current status of pancreas transplantation, suggest possible explanations for the declining numbers of transplants, highlight current gaps in knowledge, and suggest possible future studies and developments aimed at increasing the application of this effective therapy.
Efficient synergistic single-cell genome assembly (2014)

Abstract As the vast majority of all microbes are unculturable, single-cell sequencing has become a significant method to gain insight into microbial physiology. Single-cell sequencing methods, currently powered by multiple displacement genome amplification (MDA), have passed important milestones such as finishing and closing the genome of a prokaryote. However, the quality and reliability of genome assemblies from single cells are still unsatisfactory due to uneven coverage depth and the absence of scattered chunks of the genome in the final collection of reads caused by MDA bias. In this work, our new algorithm Hybrid De novo Assembler (HyDA) demonstrates the power of co-assembly of multiple single-cell genomic data sets through significant improvement of the assembly quality in terms of predicted functional elements and length statistics. Co-assemblies contain significantly more base pairs and protein coding genes, cover more subsystems, and consist of longer contigs compared to individual assemblies by the same algorithm as well as state-of-the-art single-cell assemblers SPAdes and IDBA-UD. Hybrid De novo Assembler (HyDA) is also able to avoid chimeric assemblies by detecting and separating shared and exclusive pieces of sequence for input data sets. By replacing one deep single-cell sequencing experiment with a few single-cell sequencing experiments of lower depth, the co-assembly method can hedge against the risk of failure and loss of the sample, without significantly increasing sequencing cost. Application of the single-cell coassembler HyDA to the study of three uncultured members of an alkane-degrading methanogenic community validated the usefulness of the co-assembly concept.