gebhart/patrepeval huggingface dataset:
Mammalian target of rapamycin regulates neutrophil extracellular trap formation via induction of hypoxia-inducible factor 1 α (2012)

Neutrophils are highly specialized innate immune effector cells that evolved for antimicrobial host defense. In response to inflammatory stimuli and pathogens, they form neutrophil extracellular traps (NETs), which capture and kill extracellular microbes. Deficient NET formation predisposes humans to severe infection, but, paradoxically, dysregulated NET formation contributes to inflammatory vascular injury and tissue damage. The molecular pathways and signaling mechanisms that control NET formation remain largely uncharacterized. Using primary human neutrophils and genetically manipulated myeloid leukocytes differentiated to surrogate neutrophils, we found that mammalian target of rapamycin (mTOR) regulates NET formation by posttranscriptional control of expression of hypoxia-inducible factor 1 α (HIF-1α), a critical modulator of antimicrobial defenses. Next-generation RNA sequencing, assays of mRNA and protein expression, and analysis of NET deployment by live cell imaging and quantitative histone release showed that mTOR controls NET formation and translation of HIF-1α mRNA in response to lipopolysaccharide. Pharmacologic and genetic knockdown of HIF-1α expression and activity inhibited NET deployment, and inhibition of mTOR and HIF-1α inhibited NET-mediated extracellular bacterial killing. Our studies define a pathway to NET formation involving 2 master regulators of immune cell function and identify potential points of molecular intervention in strategies to modify NETs in disease.
ChemInform Abstract: THE REACTION OF STABLE SULFUR YLIDES DIMETHYLSULFONIUM DIACETYLMETHYLIDE AND DIMETHYLSULFONIUM ACETYLCARBOMETHOXYMETHYLIDE WITH AROMATIC AMINE N‐OXIDES (1974)

Abstract Aus dem Sulfoniummethylid (I) erhält man mit Chinolin‐1‐oxid (II) in Gegenwart von Benzoylchlorid das Addukt (IV), mit (V) entsteht ein Indolizin (VI).
ChemInform Abstract: (1,5)‐SIGMATROPIC ESTER SHIFT IN THE PENTAKIS(METHOXYCARBONYL)CYCLOPENTADIENE SYSTEM (1976)

Abstract Die Diene (I) werden nach der Methode von Le Goff und Cookson dargestellt, wobei die Verwendung von Methylenchlorid (20°C) statt siedenden Methanols als Lösungsmittel zu besseren Ausbeuten führt.
Clinical and serologic study of sjögren's syndrome in patients with progressive systemic sclerosis (1983)

Fifty-eight patients with progressive systemic sclerosis (PSS) were evaluated clinically and by biopsy of the minor salivary glands of the lips for the presence of Sjögren's syndrome. Clinical findings included dry eyes in 38%, dry mouth in 32%, parotid enlargement in 4%, and an abnormal Schirmer's test in 34%. Histologic changes in lip biopsies included lymphocytic infiltrates characteristic of Sjögren's syndrome in 17 individuals (29%). In 19 (33%) there was periglandular and intraglandular fibrosis (PSS-fibrosis) without significant inflammation, an alteration characteristic of PSS per se. In the remaining 22 patients (38%) with PSS, no abnormality was found. Of those with PSS and Sjögren's syndrome, 53% had serum antibodies to SS-A and/or SS-B, while only 1 patient with a normal biopsy had either of these antibodies. Anti-SS-A and anti-SS-B were not detected in patients with glandular fibrosis alone. The mortality rate of the PSS-fibrosis group was higher due to a variety of severe internal manifestations related to PSS. Antibodies to SS-A and SS-B are useful serologic markers of the presence of Sjögren's syndrome in patients with PSS.
Fast voltammetry of metals at carbon-fiber microelectrodes: rapid determination of solution formation constants (2016)

Metal speciation controls the behavior of aqueous metal ions. Fundamental thermodynamic parameters, such as the formation constant (K<sub>f</sub>) of metal-ligand equilibria, provide useful speciation information. Although this information can be determined by spectroscopic techniques with high accuracy, it comes at the expense of time and cost. In this work, we studied Cu<sup>2+</sup> complexation with different ligands using an ultra-fast method, fast scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFMs). We observed a correlation between the FSCV response and the previously reported Cu<sup>2+</sup>-ligand equilibrium constants. This relationship allowed us to model a predictive relationship between K<sub>f</sub> and 16 model ligands. We hence present an essential proof of principle study that highlights FSCV's capability to prove speciation information in real time.
Identification, evolution, and expression partitioning of miRNAs in allopolyploid<i>Brassica napus</i> (2015)

The recently published genome of Brassica napus offers for the first time the opportunity to gain insights into the genomic organization and the evolution of miRNAs in oilseed rape. In this study, 12 small RNA libraries from two B. napus cultivars (Tapidor and Ningyou7) and their four double-haploid lines were sequenced, employing the newly sequenced B. napus genome, together with genomes of its progenitors Brassica rapa and Brassica oleracea. A total of 645 miRNAs including 280 conserved and 365 novel miRNAs were identified. Comparative analysis revealed a high level of genomic conservation of MIRNAs (75.9%) between the subgenomes of B. napus and its two progenitors' genomes, and MIRNA lost/gain events (133) occurred in B. napus after its speciation. Furthermore, significant partitioning of miRNA expressions between the two subgenomes in B. napus was detected. The data of degradome sequencing, miRNA-mediated cleavage, and expression analyses support specific interactions between miRNAs and their targets in the modulation of diverse physiological processes in roots and leaves, as well as in biosynthesis of, for example, glucosinolates and lipids in oilseed rape. These data provide a first genome-wide view on the origin, evolution, and genomic organization of B. napus MIRNAs.
Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects (2017)

Prostate carcinoma and benign prostate hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS) are among the most prevalent and clinically relevant diseases in men. BPH is characterized by an enlargement of prostate tissue associated with increased tone of smooth muscle cells (SMCs) which surround the single glands composing the prostate. Secretions of the glands leave the prostate through local excretory ducts during the emission phase of ejaculation. Pharmacological treatment of BPH suggests different local drug targets based on reduction of prostate smooth muscle tone as the main effect and disturbed ejaculation as a common side effect. This highlights the need for detailed investigation of single prostate glands and ducts. We combined structural and functional imaging techniques-notably, clear lipid-exchanged, acrylamide-hybridized rigid imaging/immunostaining/ in situ hybridization-compatible tissue-hydrogel (CLARITY) and time-lapse imaging-and defined glands and ducts as distinct SMC compartments in human and rat prostate tissue. The single glands of the prostate (comprising the secretory part) are characterized by spontaneous contractions mediated by the surrounding SMCs, whereas the ducts (excretory part) are quiescent. In both SMC compartments, phosphodiesterase (PDE)-5 is expressed. PDE5 inhibitors have recently emerged as alternative treatment options for BPH. We directly visualized that the PDE5 inhibitors sildenafil and tadalafil act by reducing spontaneous contractility of the glands, thereby reducing the muscle tone of the organ. In contrast, the ductal (excretory) system and thus the prostate's contribution to ejaculation is unaffected by PDE5 inhibitors. Our differentiated imaging approach reveals new details about prostate function and local drug actions and thus may support clinical management of BPH.-Kügler, R., Mietens, A., Seidensticker, M., Tasch, S., Wagenlehner, F. M., Kaschtanow, A., Tjahjono, Y., Tomczyk, C. U., Beyer, D., Risbridger, G. P., Exintaris, B., Ellem, S. J., Middendorff, R. Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.
Impact of a multidisciplinary day program on disease and healthcare costs in children and adolescents with severe asthma: A two‐year follow‐up study (2001)

For patients whose asthma remains in poor control necessitating high utilization of medical services, a referral to a specialized "center of excellence" is often considered. A decade ago, we evaluated our pediatric asthma program of long-term hospitalization (median stay of 75 days) and found significant decreases in subjects' medical utilization following this intervention. In an effort to contain treatment costs, the former program was markedly altered to one of abbreviated stay with emphasis on family management of asthma. The purpose of the present study was to determine the outcome of children treated in the revised program with regard to disease severity, quality of life, and subsequent utilization of medical resources. Children with severe asthma who were admitted to the program and fulfilled study criteria were consecutively enrolled. Data was obtained concerning disease characteristics, treatment, and quality of life at admission, and at 1 and 2 years following discharge. Medical records for the year prior to program admission and for the 2 years following discharge were coded for medical care encounters. Ninety-eight children, aged 9 months to 18 years (mean age, 10.9 years), were enrolled. They participated in the program for a mean of 15.6 ( +/- 8 SD), median of 15.0, and range of 2-51 treatment days. The group showed significant improvement (P < 0.0001) from admission to 1- and 2-year follow-up in median corticosteroid use, asthma functional severity, perceived competence in asthma management, and quality of life for both caregiver and child. Medical record data showed significant improvement (P < 0.0001) at both 1- and 2-year follow-up in median number of corticosteroid bursts, emergency department visits, hospital days, and overall utilization of medical care encounters. A median total medical encounter cost/patient of $16,250 ($6,972-$25,714 interquartile range (IQR)) for the year prior to program participation was reduced to $1,902 ($505-$6,524 IQR) at 1-year and $690 ($185-$3,550 IQR) at 2- year follow-up (P < 0.0001). We conclude that multidisciplinary care in a short-term, outpatient, day treatment program can significantly contribute to improvement in asthma severity, quality of life, and reduction in healthcare costs.
Editorial (2003)

DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.
An unusual presentation of a common condition: Allergic contact dermatitis (2018)

Allergic contact dermatitis commonly affects patients with chronic venous leg ulcers and can contribute to impaired wound healing. Many allergens have been identified, and despite the use of advanced dressings, the incidence of allergy has remained high. We discuss an unusual presentation of allergic contact dermatitis in a patient with a chronic wound. The patient's history was consistent with a recurrent venous leg ulcer, but on this occasion, the wound continued to deteriorate despite optimal treatment. This prompted further investigation, which included patch testing. Although the clinical features were not suggestive of allergy, the patch test was positive for several allergens, including Atrauman<sup>®</sup> dressings, which the patient was using at the time. This case highlights the importance of regular reassessment and accurate diagnosis for the management of chronic wounds. It also demonstrates that allergic contact dermatitis can contribute to delayed wound healing without causing the classical clinical features of inflammation of the surrounding skin, and even hypoallergenic, non-adherent dressings can be sensitising.
Analysis and design of ESD protection circuits for high-frequency/RF applications (2002)

Electrostatic discharge (ESD) protection devices can have an adverse effect on the performance of high frequency and RF circuits. This work presents for the first time, an S-parameter based analysis of the performance of RF circuits with various ESD protection designs. Additionally, a design methodology for distributed ESD protection using coplanar waveguides is developed to achieve a better impedance match over a broad frequency range. By using this technique, an ESD device with a parasitic capacitance of 200 fF will attenuate the signal power by only 0.27 dB at 10 GHz.
Role of β-Dystrobrevin in Nonmuscle Dystrophin-Associated Protein Complex-Like Complexes in Kidney and Liver (2001)

beta-Dystrobrevin is a dystrophin-related and -associated protein that is highly expressed in brain, kidney, and liver. Recent studies with the kidneys of the mdx3Cv mouse, which lacks all dystrophin isoforms, suggest that beta-dystrobrevin, and not the dystrophin isoforms, may be the key component in the assembly of complexes similar to the muscle dystrophin-associated protein complexes (DPC) in nonmuscle tissues. To understand the role of beta-dystrobrevin in the function of nonmuscle tissues, we generated beta-dystrobrevin-deficient (dtnb(-/-)) mice by gene targeting. dtnb(-/-) mice are healthy, fertile, and normal in appearance. No beta-dystrobrevin was detected in these mice by Western blotting or immunocytochemistry. In addition, the levels of several beta-dystrobrevin-interacting proteins, namely Dp71 isoforms and the syntrophins, were greatly reduced from the basal membranes of kidney tubules and liver sinusoids and on Western blots of crude kidney and liver microsomes of beta-dystrobrevin-deficient mice. However, no abnormality was detected in the ultrastructure of membranes of kidney and liver cells or in the renal function of these mice. beta-Dystrobrevin may therefore be an anchor or scaffold for Dp71 and syntrophin isoforms, as well as other associating proteins at the basal membranes of kidney and liver, but is not necessary for the normal function of these mice.
Automated method for overlay sample plan optimization based on spatial variation modeling (2001)

In this paper, we present an automated method for selecting optimal overlay sampling plans based on a systematic evaluation of the spatial variation components of overlay errors, overlay prediction errors, sampling confidence, and yield loss due to inadequate sampling. Generalized nested ANOVA and clustering analysis are used to quantify the major components of overlay variations in terms of stepper-related systematic variances, systematic variances of residuals, and random variances at the wafer, field and site levels. Analysis programs have been developed to automatically evaluate various sampling plans with different number of fields and layouts, and identify the optimum plan for effective excursion detection and stepper/scanner control. For each sample plan, the overlay prediction error relative to full wafer sample is calculated, and its sampling confidence is estimated using robust tests. The relative yield loss risk due to inadequate sampling is quantified, and compared with the cost of sampling in determining a cost-optimal sampling plan. The methodology is applied to overlay data of CMP processed wafers. The different spatial variation characteristics of oxide and metal CMP processes are compared and proper sampling strategies are recommended. The robustness of the recommended sample plans was validated over time. The sample plan optimization program successfully detected process change while maintaining accurate and robust stepper/scanner control.
Kindling‐induced overexpression of <i>Homer 1A</i> and its functional implications for epileptogenesis (2002)

Despite an extensive research on the molecular basis of epilepsy, the essential players in the epileptogenic process leading to epilepsy are not known. Gene expression analysis is one strategy to enhance our understanding of the genes contributing to the functional neuronal changes underlying epileptogenesis. In the present study, we used the novel MPSS (massively parallel signature sequencing) method for analysis of gene expression in the rat kindling model of temporal lobe epilepsy. Kindling by repeated electrical stimulation of the amygdala resulted in the differential expression of 264 genes in the hippocampus compared to sham controls. The most strongly induced gene was Homer 1A, an immediate early gene involved in the modulation of glutamate receptor function. The overexpression of Homer 1A in the hippocampus of kindled rats was confirmed by RT-PCR. In order to evaluate the functional implications of Homer 1A overexpression for kindling, we used transgenic mice that permanently overexpress Homer 1A. Immunohistochemical characterization of these mice showed a marked Homer 1A overexpression in glutamatergic neurons of the hippocampus. Kindling of Homer 1A overexpressing mice resulted in a retardation of seizure generalization compared to wild-type controls. The data demonstrate that kindling-induced epileptogenesis leads to a striking overexpression of Homer 1A in the hippocampus, which may represent an intrinsic antiepileptogenic and anticonvulsant mechanism in the course of epileptogenesis that counteracts progression of the disease.
Nonlinear regularization using constrained edges in image reconstruction (2002)

This paper deals with edge-preserving regularization for image reconstruction. We use a non-quadratic regularization term involving a /spl phi/-function applied on the intensity gradient modulus. During the process, small gradients are smoothed while high gradients are preserved. In order to take into account the noise more specifically, we propose to use the explicit version of the regularization term involving the edge variable. We add a nonlinear constraint on this edge variable, in order to remove the noise. It allows edge enhancement while smoothing the noise, even in the case where the edge and noise generate the same high gradient modulus. We have previously proposed a model composed of two coupled partial differential equations (PDE) on the image intensity and image edges. In this paper, we show that, for a particular regularization intensity function, the two coupled PDE can be slightly modified in order to correspond to the Euler equations associated with the minimization of a global criterion. This new criterion contains a nonlinear regularization term on both the intensity and the edges. We use convergence towards Mumford and Shah (1989) functional to improve our results.
Growth and remodeling of load-bearing biological soft tissues (2016)

The past two decades reveal a growing role of continuum biomechanics in understanding homeostasis, adaptation, and disease progression in soft tissues. In this paper, we briefly review the two primary theoretical approaches for describing mechano-regulated soft tissue growth and remodeling on the continuum level as well as hybrid approaches that attempt to combine the advantages of these two approaches while avoiding their disadvantages. We also discuss emerging concepts, including that of mechanobiological stability. Moreover, to motivate and put into context the different theoretical approaches, we briefly review findings from mechanobiology that show the importance of mass turnover and the prestressing of both extant and new extracellular matrix in most cases of growth and remodeling. For illustrative purposes, these concepts and findings are discussed, in large part, within the context of two load-bearing, collagen dominated soft tissues—tendons/ligaments and blood vessels. We conclude by emphasizing further examples, needs, and opportunities in this exciting field of modeling soft tissues.
Molecular characterization of the first aromatic nutrient transporter from the sodium neurotransmitter symporter family (2006)

Nutrient amino acid transporters (NATs, subfamily of sodium neurotransmitter symporter family SNF, a.k.a. SLC6) represent a set of phylogenetically and functionally related transport proteins, which perform intracellular absorption of neutral, predominantly essential amino acids. Functions of NATs appear to be critical for the development and survival in organisms. However, mechanisms of specific and synergetic action of various NAT members in the amino acid transport network are virtually unexplored. A new transporter, agNAT8, was cloned from the malaria vector mosquito Anopheles gambiae (SS). Upon heterologous expression in Xenopus oocytes it performs high-capacity, sodium-coupled (2:1) uptake of nutrients with a strong preference for aromatic catechol-branched substrates, especially phenylalanine and its derivatives tyrosine and L-DOPA, but not catecholamines. It represents a previously unknown SNF phenotype, and also appears to be the first sodium-dependent B(0) type transporter with a narrow selectivity for essential precursors of catecholamine synthesis pathways. It is strongly and specifically transcribed in absorptive and secretory parts of the larval alimentary canal and specific populations of central and peripheral neurons of visual-, chemo- and mechano-sensory afferents. We have identified a new SNF transporter with previously unknown phenotype and showed its important role in the accumulation and redistribution of aromatic substrates. Our results strongly suggest that agNAT8 is an important, if not the major, provider of an essential catechol group in the synthesis of catecholamines for neurochemical signaling as well as ecdysozoan melanization and sclerotization pathways, which may include cuticle hardening/coloring, wound curing, oogenesis, immune responses and melanization of pathogens.
The effect of edge artifacts on quantification of Positron Emission Tomography (2010)

We examined the quantitative effect of the edge artifacts caused by using a point spread function (PSF) system model for Positron Emission Tomography (PET) image reconstruction. Two phantoms were used in this study. The first phantom was a new small PET phantom that was used to measure the quantitative effects. The cylindrical phantom had 5 hot cylinder inserts with different diameters and was scanned with different hot insert-to-background ratios. Results showed that the region of interest (ROI) mean value (equal diameters for ROIs and cylinders) of PSF-OSEM was higher than that of OSEM without PSF model due to better resolution recovery, and the total activity was preserved in all images. However the ROI maximum value of PSF-OSEM could be significantly higher than the true value, and this overshoot depends on both the cylinder size and the concentration ratio. The largest effect was observed with the 8mm diameter cylinder insert at the highest concentration ratio. The second phantom was a Hoffman brain phantom, which was used to display the effect visually without quantitative measurements.
<i>Salmonella</i> Modulates Vesicular Traffic by Altering Phosphoinositide Metabolism (2004)

Salmonella enterica, the cause of food poisoning and typhoid fever, induces actin cytoskeleton rearrangements and membrane ruffling to gain access into nonphagocytic cells, where it can replicate and avoid innate immune defenses. Here, we found that SopB, a phosphoinositide phosphatase that is delivered into host cells by a type III secretion system, was essential for the establishment of Salmonella's intracellular replicative niche. SopB mediated the formation of spacious phagosomes following bacterial entry and was responsible for maintaining high levels of phosphatidylinositol-three-phosphate [PtdIns(3)P] in the membrane of the bacteria-containing vacuoles. Absence of SopB caused a significant defect in the maturation of the Salmonella-containing vacuole and impaired bacterial intracellular growth.