gebhart/patrepeval huggingface dataset:
Site-Specific Transglutaminase-Mediated Conjugation of Interferon α-2b at Glutamine or Lysine Residues (2016)

Interferon α (IFN α) subtypes are important protein drugs that have been used to treat infectious diseases and cancers. Here, we studied the reactivity of IFN α-2b to microbial transglutaminase (TGase) with the aim of obtaining a site-specific conjugation of this protein drug. Interestingly, TGase allowed the production of two monoderivatized isomers of IFN with high yields. Characterization by mass spectrometry of the two conjugates indicated that they are exclusively modified at the level of Gln101 if the protein is reacted in the presence of an amino-containing ligand (i.e., dansylcadaverine) or at the level of Lys164 if a glutamine-containing molecule is used (i.e., carbobenzoxy-l-glutaminyl-glycine, ZQG). We explained the extraordinary specificity of the TGase-mediated reaction on the basis of the conformational features of IFN. Indeed, among the 10 Lys and 12 Gln residues of the protein, only Gln101 and Lys164 are located in highly flexible protein regions. The TGase-mediated derivatization of IFN was then applied to the production of IFN derivatives conjugated to a 20 kDa polyethylene glycol (PEG), using PEG-NH<sub>2</sub> for Gln101 derivatization and PEG modified with ZQG for Lys164 derivatization. The two mono-PEGylated isomers of IFN were obtained in good yields, purified, and characterized in terms of protein conformation, antiviral activity, and pharmacokinetics. Both conjugates maintained a native-like secondary structure, as indicated by far-UV circular dichroism spectra. Importantly, they disclosed good in vitro antiviral activity retention (about only 1.6- to 1.8-fold lower than that of IFN) and half-lives longer (about 5-fold) than that of IFN after intravenous administration to rats. Overall, these results provide evidence that TGase can be used for the development of site-specific derivatives of IFN α-2b possessing interesting antiviral and pharmacokinetic properties.
Sprint training reduces urinary purine loss following intense exercise in humans (2006)

The influence of sprint training on endogenous urinary purine loss was examined in 7 active male subjects (age, 23.1 +/- 1.8 y; body mass, 76.1 +/- 3.1 kg; VO2 peak, 56.3 +/- 4.0 mL.kg-1.min-1). Each subject performed a 30 s sprint performance test (PT), before and after 7 d of sprint training. Training consisted of 15 sprints, each lasting 10 s, on an air-braked cycle ergometer performed twice each day. A rest period of 50 s separated each sprint during training. Sprint training resulted in a 20% higher muscle ATP immediately after PT, a lower IMP (57% and 89%, immediately after and 10 min after PT, respectively), and inosine accumulation (53% and 56%, immediately after and 10 min after the PT, respectively). Sprint training also attenuated the exercise-induced increases in plasma inosine, hypoxanthine (Hx), and uric acid during the first 120 min of recovery and reduced the total urinary excretion of purines (inosine + Hx + uric acid) in the 24 h recovery period following intense exercise. These results show that intermittent sprint training reduces the total urinary purine excretion after a 30 s sprint bout.
Fluid Dynamics During Hemodialysis in Relationship to Sodium Gradient Between Dialysate and Plasma (2007)

Fluid shifts during hemodialysis involve changes in both extracellular and intracellular volumes. This study aimed to determine the effect of intradialytic sodium gradients (GNa), that is, the difference between dialysate and serum sodium concentration, on dynamics of extracellular and intracellular volumes in a group of maintenance hemodialysis patients. Extracellular volume change (deltaECV) between predialysis and postdialysis periods was determined by whole-body bioimpedance spectroscopy; intracellular volume change (deltaICV) was indirectly derived as the difference between deltaECV and the change in body weight, corrected for intradialytically given fluids. A total of 200 bioimpedance measurements were performed in 32 dialysis patients. Extracellular and intracellular volume changes were -2.6 +/- 0.9 L (range: -4.7 to -0.5 L) and -0.2 +/- 0.7 L (range: -2.5 to +1.5 L), respectively. There was a significant correlation between deltaICV and GNa; deltaICV = -0.12 * GNa + 0.26 (p < 0.001). In contrast, GNa was not correlated with deltaECV. We conclude that the sodium gradient between dialysate and plasma has a significant effect on the ICV during dialysis. Hemodialysis with GNa = 0 mmol/L should be sought to prevent ICV shrinking or swelling and to prevent excessive thirst, consequently high interdialytic weight gains, and ultrafiltration rates.
Kinetic Rate Law Issues in the Morphological Relaxation of Rippled Crystal Surfaces (2006)

SummaryA comparison study of surface relaxation below roughening using two simplified rate laws for adatom motion has been made. Both rate laws, termed i-kinetics and Δi-kinetics, show kinetic pathways to equilibrium whose scaling behavior is consistent with theory. For i-kinetics, pinch-off is always observed to be the operative mechanism in surface relaxation (over the temperature and wavelength range accessible to simulation), and is consistent with the observed λ4 scaling behavior. The temperature dependence of the amplitude decay is also consistent with pinch-off, but very different from the temperature scaling expected classically (and uniformly used in experiment). For Δi-kinetics, pinch-off is observed to be operative at higher temperatures and short times, leading to λα>4 scaling behavior, again consistent with theory. However, at low temperatures and large wavelengths, the surface is observed to spontaneously island, leading to λ3 scaling behavior at long times, consistent with the relaxation of surfaces with bidirectional modulations.
Identification and activation of autocrine renin-angiotensin system in adult ventricular myocytes (1995)

To date, the demonstration that the molecular components of the renin-angiotensin system (RAS) are present in adult ventricular myocytes is lacking. In addition, whether the RAS is upregulated under conditions of overload and myocyte hypertrophy in vivo remains to be determined. By employing an in vivo model of ischemic cardiomyopathy in rats, we document that adult myocytes express genes for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) receptors. Moreover, renin, ACE, and ANG II receptor mRNAs increased in stressed myocytes undergoing cellular hypertrophy. At the protein level, the percentage of myocytes containing renin, ANG I, and ANG II was significantly increased in the overloaded heart. The number of binding sites for ANG II per myocyte also markedly increased under this setting. These results provide direct evidence of the existence of a myocyte RAS, which may be activated in pathological states of the heart to support myocyte growth and contractile function.
Genomic architecture of Autism Spectrum Disorder from comprehensive whole-genome sequence annotation (2022)

Abstract Fully understanding the genetic factors involved in Autism Spectrum Disorder (ASD) requires whole-genome sequencing (WGS), which theoretically allows the detection of all types of genetic variants. With the aim of generating an unprecedented resource for resolving the genomic architecture underlying ASD, we analyzed genome sequences and phenotypic data from 5,100 individuals with ASD and 6,212 additional parents and siblings (total n=11,312) in the Autism Speaks MSSNG Project, as well as additional individuals from other WGS cohorts. WGS data and autism phenotyping were based on high-quality short-read sequencing (&gt;30x coverage) and clinically accepted diagnostic measures for ASD, respectively. For initial discovery of ASD-associated genes, we used exonic sequence-level variants from MSSNG as well as whole-exome sequencing-based ASD data from SPARK and the Autism Sequencing Consortium (&gt;18,000 trios plus additional cases and controls), identifying 135 ASD-associated protein-coding genes with false discovery rate &lt;10%. Combined with ASD-associated genes curated from the literature, this list was used to guide the interpretation of all other variant types in WGS data from MSSNG and the Simons Simplex Collection (SSC; n=9,205). We identified ASD-associated rare variants in 789/5,100 individuals with ASD from MSSNG (15%) and 421/2,419 from SSC (17%). Considering the genomic architecture, 57% of ASD-associated rare variants were nuclear sequence-level variants, 41% were nuclear structural variants (SVs) (mainly copy number variants, but also including inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Several of the ASD-associated SVs would have been difficult to detect without WGS, including an inversion disrupting SCN2A and a nuclear mitochondrial insertion impacting SYNGAP1 . Polygenic risk scores did not differ between children with ASD in multiplex families versus simplex, and rare, damaging recessive events were significantly depleted in multiplex families, collectively suggesting that rare, dominant variation plays a predominant role in multiplex ASD. Our study provides a guidebook for exploring genotype-phenotype correlations in the 15-20% of ASD families who carry ASD-associated rare variants, as well as an entry point to the larger and more diverse studies that will be required to dissect the etiology in the &gt;80% of the ASD population that remains idiopathic. All data resulting from this study are available to the medical genomics research community in an open but protected manner.
Growing IVY: Building the Immersive Visual environment at York (2001)

When we move about within our environment, we are presented with a range of cues to our motion. Virtual reality systems attempt to simulate these various sensory cues. IVY – the Immersive Visual environment at York – is a virtual environment being constructed at York University to investigate aspects of human perception and to examine the relative importance of various visual and non-visual cues to the generation of an effective virtual environment. This paper describes the movation behind the design of IVY, and describes the design of the essential hardware and software components. Key words: Immersive displays 1.
On a path toward structures with reconfigurable circulatory systems (2007)

In order to provide structures with new and better characteristics, researchers often look to biological systems for inspiration. One trait that many biological system have that conventional structures do not is a circulatory system, which can be used for many purposes, one of which is the transport of structural material. This paper explores the benefits of transporting structural material for the purpose of changing the structure's static and dynamic characteristics. Several scenarios are explored, including the transport of non-load-bearing mass (mass transport) to load-bearing mass (termed stiffness transport). It is argued that stiffness transport, while more complex than simply moving mass within a structure, affords the same features as mass transport, along with several unconventional and particularly useful abilities.
The Natural Aspect of Mobile Interfaces: Becoming Borg, Designing Body Worn Technolgy (2009)

Presented on January 14, 2009 from 6:00 – 7:00 pm in the Architecture Auditorium/East Architecture Building.
Stan psychoemocjonalny rodziców i dzieci chorujących na nowotwory układu krwiotwórczego w trakcie steroidoterapii (2013)

Abstract Introduction Dexamethasone and prednisone are basic components of treatment protocols for children with hematologic malignancies. The steroid therapy might cause temporary changes in psycho-emotional and somatic state of patients which might potentially cause anxiety among them and their parents. Aim The first aim of the study was to compare effects of treatment with prednisone and dexamethasone on psycho-emotional state of children and the second aim was to assess the level of anxiety of parents and their children during steroid therapy. Material and methods The study was performed in years 2009–2011 in oncohematological departments in Zabrze, Poznan and Szczecin. The study group consisted of 39 patients and 79 of their parents. The parents completed a questionnaire for the assessment of impact of steroid therapy on psycho-emotional and somatic state of their children. Additionally, children under 9 years old and their parents completed State Trait Anxiety Inventory for the assessment of impact of steroid therapy on their level of anxiety. The control group comprised 30 patients who did not receive steroids and 50 of their parents. Results and conclusions The most common symptoms associated by parents of children with steroid treatment were: increase in appetite, mood swings, irritability. Analysis of various symptoms depending on the area of child's functioning confirmed the highest impact of steroids on somatic state of the patients. Dexamethasone had stronger influence on somatic and cognitive functioning of children than prednisone. Steroid therapy does affect anxiety level only among parents but not in children. Psychoeducation procedure about steroid therapy effects was designed for parents and sick children based on the results of the study. The knowledge that extreme psychoemotional states are natural reaction for this treatment should improve an adaptation to illness for children as well as their parents.
A Bis(tridentate)cobalt Polypyridine Complex as Mediator in Dye‐Sensitized Solar Cells (2015)

Abstract Dye‐sensitized solar cells equipped with cationic and neutral Ru II ‐based sensitizers [Ru(ddpd){tpy(COOH) 3 }] 2+ [ 1 2+ ; ddpd = N , N′ ‐dimethyl‐ N , N′ ‐di(pyridin‐2‐yl)pyridin‐2,6‐diamine, tpy(COOH) 3 = 2,2″6′,2″‐terpyridine‐4,4′,4″‐tricarboxylic acid] and [Ru(ddpd){tpy(COOH)(COO) 2 }] ( 2 ) with and without the coadsorbent chenodeoxycholic acid were constructed with I 3 – /I – or the Co III/II ‐based redox mediators [Co(bpy) 3 ] 3+/2+ ( 3 3+/2+ ; bpy = 2,2′‐bipyridine) and [Co(ddpd) 2 ] 3+/2+ ( 4 3+/2+ ) in the presence of LiClO 4 and 4‐ tert ‐butylpyridine. The best photovoltaic performance was achieved by using the 4 3+/2+ shuttle and the neutral sensitizer 2 without coadsorbent. The higher short‐circuit photocurrent density and higher electron recombination lifetimes obtained with this combination suggest slow electron recombination kinetics at the TiO 2 surface with the Co III complex 4 3+ . The slow electron transfer to 4 3+ is tentatively ascribed to the high‐lying π* orbitals of the electron‐rich ddpd ligands, which result in a weak electronic coupling. This contrasts with the faster recombination with 3 3+ , which features the low‐energy π* orbitals of the bpy ligands.
Identification of hidden Markov models for ion channel currents. I. Colored background noise (1998)

Signal processing based on hidden Markov models (HMM's) has been applied recently to the characterization of single ion channel currents as recorded with the patch clamp technique from living cells. The estimation of HMM parameters using the traditional forward-backward and Baum-Welch algorithms can be performed at signal-to-noise ratios (SNR's) that are too low for conventional analysis; however, the application of these algorithms relies on the assumption that the background noise is white. In this paper, the observed single channel current is modeled as a vector hidden Markov process. An extension of the forward-backward and Baum-Welch algorithms is described to model ion channel kinetics under conditions of colored noise like that seen in patch clamp recordings. Using simulated data, we demonstrate that the traditional algorithms result in biased estimates and that the vector HMM approach provides unbiased estimates of the parameters of the underlying hidden Markov scheme.
Enzyme–substrate complex structures of CYP154C5 shed light on its mode of highly selective steroid hydroxylation (2014)

CYP154C5 from Nocardia farcinica is a bacterial cytochrome P450 monooxygenase active on steroid molecules. The enzyme has recently been shown to exhibit exclusive regioselectivity and stereoselectivity in the conversion of various pregnans and androstans, yielding 16α-hydroxylated steroid products. This makes the enzyme an attractive candidate for industrial application in steroid hormone synthesis. Here, crystal structures of CYP154C5 in complex with four different steroid molecules were solved at resolutions of up to 1.9 Å. These are the first reported P450 structures from the CYP154 family in complex with a substrate. The active site of CYP154C5 forms a flattened hydrophobic channel with two opposing polar regions, perfectly resembling the size and polarity distribution of the steroids and thus resulting in highly specific steroid binding with Kd values in the range 10-100 nM. Key enzyme-substrate interactions were identified that accounted for the exclusive regioselectivity and stereoselectivity of the enzyme. Additionally, comparison of the four CYP154C5-steroid structures revealed distinct structural differences, explaining the observed variations in kinetic data obtained for this P450 with the steroids pregnenolone, dehydroepiandrosterone, progesterone, androstenedione, testosterone and nandrolone. This will facilitate the generation of variants with improved activity or altered selectivity in the future by means of protein engineering.
Wind Loads on Components of Multi-Layer Wall Systems with Air-Permeable Exterior Cladding (2012)

Post-hurricane damage assessments have documented the failure of wall components and connections including the loss of various types of siding materials. In addition, recent U.S. model building/energy code changes are expected to lead to increased use of continuous insulation, particularly foam sheathing attached to the exterior surface of light-frame wall framing, to achieve advanced energy code compliance. A particular need for multi-layer wall systems is the understanding of wind loads on the various layers so that designers and product manufacturers can ensure acceptable building envelope performance of energy efficient wall systems in high-wind events, such as hurricanes. To address the knowledge gaps and practical concerns related to multi-layer wall systems with air-permeable exterior cladding, the Foam Sheathing Committee (FSC) of the American Chemistry Council (ACC), the Vinyl Siding Institute (VSI), the National Association Home Builders Research Center (NAHB RC), State Farm Mutual Automobile Insurance Company, Insurance Institute for Business & Home Safety (IBHS), and others have initiated research into wind loads on layers of multi-layer wall systems. Results presented in this paper include determination of wind pressure loading on layers of exterior wall assemblies that include vinyl siding, continuous insulation (rigid foam sheathing) on the exterior side of the wall assembly or Oriented Strand Board (OSB) exterior sheathing, insulation in the wall cavity and gypsum board interior sheathing. This paper presents results obtained from full-scale wind tunnel tests and compares them with results obtained using dynamic pressure chamber tests. The full-scale wind tunnel tests indicate that porous exterior siding experiences higher wind loads and that the interior gypsum wall board experiences lower loads than previously measured in dynamic pressure chamber tests. Results of the different test methods are compared and implications are discussed.
Preparation of Electroconductive and Transparent Thin Films of AgSbO<sub>3</sub> (1995)

Sintered ceramics and RF-sputter deposited thin films of AgSbO3 with defect pyrochlore structure were prepared and their electrical conductivities and optical properties were measured. Sintered ceramics of AgSbO3 showed n-type electric conduction with a conductivity of -2×10-1Ω-1·cm-1 and the cut off wavelength of -400 nm for optical transmittance at room temperature. Polycrystalline thin films obtained by post-annealing at 675°C in O2 gas flow also showed n-type conduction with a conductivity of -100Ω-1·cm-1 at room temperature. The optical transmission spectrum of the film with the thickness of -200 nm showed the optical transmittance of -80% at a wavelength of 400 nm. The carrier concentration and the Hall mobility of the polycrystalline film were -3×1018cm-3 and -8cm2·V-1·s-1, respectively.
Virtual Reality Promises New Design Capabilities (1994)

Abstract Virtual reality has received much attention in the past few years in relation to entertainment and simulation. Although there is much hype surrounding virtual reality, the underlying technologies and concepts could have a significant impact on computer-based design engineering tools. This paper explores the possible applications of virtual reality to the engineering design process. The objective of the described research is to explore opportunities to create tools, environments, and systems which will increase the designer’s productivity through the application of virtual reality (VR) technologies and concepts. Background on design, CAD and VR is presented to give a context for later proposals. Previous research in the application of VR to CAD is reviewed. Specific VR capabilities are presented to show their possible application in mechanical design and CAD systems specifically. The potential applications of VR are explored in a structured manner with examples for each category. The paper concludes with recommendations on further research and development directions.
Impact of Growth Hormone on Regulation of Adipose Tissue (2017)

Increasing prevalence of obesity and obesity-related conditions worldwide has necessitated a more thorough understanding of adipose tissue (AT) and expanded the scope of research in this field. AT is now understood to be far more complex and dynamic than previously thought, which has also fueled research to reevaluate how hormones, such as growth hormone (GH), alter the tissue. In this review, we will introduce properties of AT important for understanding how GH alters the tissue, such as anatomical location of depots and adipokine output. We will provide an overview of GH structure and function and define several human conditions and cognate mouse lines with extremes in GH action that have helped shape our understanding of GH and AT. A detailed discussion of the GH/AT relationship will be included that addresses adipokine production, immune cell populations, lipid metabolism, senescence, differentiation, and fibrosis, as well as brown AT and beiging of white AT. A brief overview of how GH levels are altered in an obese state, and the efficacy of GH as a therapeutic option to manage obesity will be given. As we will reveal, the effects of GH on AT are numerous, dynamic and depot-dependent. © 2017 American Physiological Society. Compr Physiol 7:819-840, 2017.