gebhart/patrepeval huggingface dataset:
Detection of IL-9 producing T cells in the PBMCs of allergic asthmatic patients (2017)

In conclusion, our results showed that Th9 cells may be the major source of IL-9 in children with allergic asthma. In these patients, IL-9 impairs IFN-γ production and synergistically promotes IL-4-induced IgE secretion.
Exploring ANT in PD (2012)

This workshop aims to explore, map and discuss the contribution of Actor Network Theory to Participatory design 's theory and practice. The links between the two are multiple and offers multiple occasions to appreciate the relevance of ANT in PD. The workshop seeks contributions especially in three areas: ANT as a descriptive tool for PD, ANT as conceptual framework for PD theory and practice, and ANT and PD education.
Distinct Stem Cells Subpopulations Isolated from Human Adipose Tissue Exhibit Different Chondrogenic and Osteogenic Differentiation Potential (2010)

Recently adipose tissue has become a research topic also for the searching for an alternative stem cells source to use in cell based therapies such as tissue engineer. In fact Adipose Stem Cells (ASCs) exhibit an important differentiation potential for several cell lineages such as chondrogenic, osteogenic, myogenic, adipogenic and endothelial cells. ASCs populations isolated using standard methodologies (i.e., based on their adherence ability) are very heterogeneous but very few studies have analysed this aspect. Consequently, several questions are still pending, as for example, on what regard the existence/ or not of distinct ASCs subpopulations. The present study is originally aimed at isolating selected ASCs subpopulations, and to analyse their behaviour towards the heterogeneous population regarding the expression of stem cell markers and also regarding their osteogenic and chondrogenic differentiation potential. Human Adipose derived Stem Cells (hASCs) subpopulations were isolated using immunomagnetic beads coated with several different antibodies (CD29, CD44, CD49d, CD73, CD90, CD 105, Stro-1 and p75) and were characterized by Real Time RT-PCR in order to assess the expression of mesenchymal stem cells markers (CD44, CD73, Stro-1, CD105 and CD90) as well as known markers of the chondrogenic (Sox 9, Collagen II) and osteogenic lineage (Osteopontin, Osteocalcin). The obtained results underline the complexity of the ASCs population demonstrating that it is composed of several subpopulations, which express different levels of ASCs markers and exhibit distinctive differentiation potentials. Furthermore, the results obtained clearly evidence of the advantages of using selected populations in cell-based therapies, such as bone and cartilage regenerative medicine approaches.
Structural basis for Hif-1α/CBP recognition in the cellular hypoxic response (2002)

The cellular response to low tissue oxygen concentrations is mediated by the hypoxia-inducible transcription factor HIF-1. Under hypoxic conditions, HIF-1 activates transcription of critical adaptive genes by recruitment of the general coactivators CBP/p300 through interactions with its alpha-subunit (Hif-1 alpha). Disruption of the Hif-1 alpha/p300 interaction has been linked to attenuation of tumor growth. To delineate the structural basis for this interaction, we have determined the solution structure of the complex between the carboxy-terminal activation domain (CAD) of Hif-1 alpha and the zinc-binding TAZ1 (CH1) motif of cyclic-AMP response element binding protein (CREB) binding protein (CBP). Despite the overall similarity of the TAZ1 structure to that of the TAZ2 (part of the CH3) domain of CBP, differences occur in the packing of helices that can account for differences in specificity. The unbound CAD is intrinsically disordered and remains relatively extended upon binding, wrapping almost entirely around the TAZ1 domain in a groove through much of its surface. Three short helices are formed upon binding, stabilized by intermolecular interactions. The Asn-803 side chain, which functions as a hypoxic switch, is located on the second of these helices and is buried in the molecular interface. The third helix of the Hif-1 alpha CAD docks in a deep hydrophobic groove in TAZ1, providing extensive intermolecular hydrophobic interactions that contribute to the stability of the complex. The structure of this complex provides new insights into the mechanism through which Hif-1 alpha recruits CBP/p300 in response to hypoxia.
Ischemic Preconditioning: From Adenosine Receptor to KATP Channel (2000)

Ischemic preconditioning is a phenomenon whereby exposure of the myocardium to a brief episode of ischemia and reperfusion markedly reduces tissue necrosis induced by a subsequent prolonged ischemia. It is hoped that elucidation of the mechanism for preconditioning will yield therapeutic strategies capable of reducing myocardial infarction. In the rabbit, the brief period of preconditioning ischemia and reperfusion releases adenosine, bradykinin, opioids, and oxygen radicals. The combined effect of the release of these substances on G proteins and the cell's phospholipases induces the translocation and activation of the epsilon isozyme of protein kinase C. Protein kinase C appears to be the first element of a complex kinase cascade that is activated during the prolonged ischemia in preconditioned hearts. Current evidence indicates that this cascade contains at least one tyrosine kinase and ultimately leads to the activation of p38 mitogen-activated protein kinase. p38 Mitogen-activated protein kinase phosphorylates mitogen-activated protein kinase-activated protein kinase 2. Mitogen-activated protein kinase-activated protein kinase 2 phosphorylates HSP27, a 27-kDa heat shock protein that controls actin filament polymerization, and, therefore, affects the integrity of the cytoskeleton. Finally, mitochondrial adenosine 5'-triphosphate-sensitive K+ channels open, and the latter may be the final mediator of protection for ischemic preconditioning. The protective pathway has many built-in redundancies, perhaps creating a safety factor. These redundancies may also explain some of the species-related differences seen in ischemic preconditioning in which one redundant pathway may predominate over another.
Prevention of Autoimmune Myocarditis Through the Induction of Antigen-Specific Peripheral Immune Tolerance (2001)

These results suggest that the induction of antigen-specific peripheral immune tolerance may be an effective approach for the treatment of myocarditides with autoimmune involvement.
The set-top box as "multi-media terminal" (1998)

The current platform for digital television services in Germany, the "d-box", based on the DVB/MPEG-2 standards provides the technical basis for the handling of services. With the integrated modem, SCART, and SCSI-2 interfaces, the d-box offers two service classes: video/audio services, and data services. This paper discusses important technical consumer and commercial aspects of providing services over satellite and cable involving both a TV and a PC connected to a "multimedia" terminal.
Automated measurement of mouse apolipoprotein B: convenient screening tool for mouse models of atherosclerosis (1997)

Although mice are commonly used for studies of atherosclerosis, investigators have had no convenient way to quantify apolipoprotein (apo) B, the major protein of atherogenic lipoproteins, in this model. We now report an automated immunoturbidimetric assay for mouse apo B with an NCCLS imprecision study CV < 5%. Added hemoglobin up to 50 g/L did not interfere with the assay, nor did one freeze-thaw cycle of serum samples. Assay linearity extends to apo B concentrations of 325 mg/L. We have used the assay to determine serum apo B concentrations under several atherogenic conditions, including the apo E "knock-out" genotype and treatment with a high-cholesterol diet. Our assay can be used to survey inbred mouse strains for variants in apo B concentrations or regulation. Moreover, the mouse can now be used as a convenient small-animal model to screen compounds that may lower apo B concentrations.
Tissue Cross‐Reactivity Studies for Monoclonal Antibodies: Predictive Value and Use for Selection of Relevant Animal Species for Toxicity Testing (2007)

This chapter contains sections titled: Introduction Antibody Types and Their Evolution Biological Effects of Antibodies Tissue Cross-Reactivity Procedures Interpretation of Tissue Cross-Reactivity Findings Biological Relevance of Human Tissue Cross-Reactivity Studies Conclusions References
Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells (2007)

We hypothesise that methylol cross-links between RNA and protein which occur during tissue processing inhibit the yield of total RNA. However, small RNA molecules appear to be less affected by this process and are recovered more easily in the extraction process. In general miRNAs demonstrated reliable expression levels in FFPE compared with snap frozen paired samples, suggesting these molecules might prove to be robust targets amenable to detection in archival material in the molecular pathology setting.
Automatic Nuclei Segmentation in H&E Stained Breast Cancer Histopathology Images (2013)

The introduction of fast digital slide scanners that provide whole slide images has led to a revival of interest in image analysis applications in pathology. Segmentation of cells and nuclei is an important first step towards automatic analysis of digitized microscopy images. We therefore developed an automated nuclei segmentation method that works with hematoxylin and eosin (H&E) stained breast cancer histopathology images, which represent regions of whole digital slides. The procedure can be divided into four main steps: 1) pre-processing with color unmixing and morphological operators, 2) marker-controlled watershed segmentation at multiple scales and with different markers, 3) post-processing for rejection of false regions and 4) merging of the results from multiple scales. The procedure was developed on a set of 21 breast cancer cases (subset A) and tested on a separate validation set of 18 cases (subset B). The evaluation was done in terms of both detection accuracy (sensitivity and positive predictive value) and segmentation accuracy (Dice coefficient). The mean estimated sensitivity for subset A was 0.875 (±0.092) and for subset B 0.853 (±0.077). The mean estimated positive predictive value was 0.904 (±0.075) and 0.886 (±0.069) for subsets A and B, respectively. For both subsets, the distribution of the Dice coefficients had a high peak around 0.9, with the vast majority of segmentations having values larger than 0.8.
A Soluble Activin Receptor IIB Fails to Prevent Muscle Atrophy in a Mouse Model of Spinal Cord Injury (2015)

Myostatin (MST) is a potent regulator of muscle growth and size. Spinal cord injury (SCI) results in marked atrophy of muscle below the level of injury. Currently, there is no effective pharmaceutical treatment available to prevent sublesional muscle atrophy post-SCI. To determine whether inhibition of MST with a soluble activin IIB receptor (RAP-031) prevents sublesional SCI-induced muscle atrophy, mice were randomly assigned to the following groups: Sham-SCI; SCI+Vehicle group (SCI-VEH); and SCI+RAP-031 (SCI-RAP-031). SCI was induced by complete transection at thoracic level 10. Animals were euthanized at 56 days post-surgery. RAP-031 reduced, but did not prevent, body weight loss post-SCI. RAP-031 increased total lean tissue mass compared to SCI-VEH (14.8%). RAP-031 increased forelimb muscle mass post-SCI by 38% and 19% for biceps and triceps, respectively (p < 0.001). There were no differences in hindlimb muscle weights between the RAP-031 and SCI-VEH groups. In the gastrocnemius, messenger RNA (mRNA) expression was elevated for interleukin (IL)-6 (8-fold), IL-1β (3-fold), and tumor necrosis factor alpha (8-fold) in the SCI-VEH, compared to the Sham group. Muscle RING finger protein 1 mRNA was 2-fold greater in the RAP-031 group, compared to Sham-SCI. RAP-031 did not influence cytokine expression. Bone mineral density of the distal femur and proximal tibia were decreased post-SCI (-26% and -28%, respectively) and were not altered by RAP-031. In conclusion, MST inhibition increased supralesional muscle mass, but did not prevent sublesional muscle or bone loss, or the inflammation in paralyzed muscle.
Improvement of protein quality in cereals (1983)

Protein quality is defined related to the uses of the grain for breadmaking, malting or feeding. Feeding quality, the subject of this review, is limited by the proportions of the limiting essential amino acids, notably lysine. This in turn is determined by the amino acid compositions of the nitrogenous fractions of the grain. The chemical characteristics and genetic control of the free amino acid, storage protein, and structural and metabolic protein fractions are described and their contributions to grain quality defined. Strategies and progress in improvement of the three fractions are examined for the major cereal crops. Some promising areas of research are outlined in which the storage protein genes are modified by genetic manipulation techniques.
Chronic Pancreatitis and the Differential Diagnosis Versus Pancreatic Cancer (2009)

Abstract Context. —Distinguishing chronic pancreatitis from pancreatic ductal adenocarcinoma (PDAC) is a well-known challenge, at both the clinical and the morphologic level. Objective. —To focus on the histopathologic findings that are diagnostic or suggestive of PDAC. Data Sources. —Findings that are specific to PDAC are the presence of duct structures in perineural and vascular spaces and (“naked”) ducts in fatty tissue. However, these findings are only observed in specimens containing extrapancreatic tissue. The features that are suggestive of PDAC in specimens from the pancreas include haphazard distribution of ductlike structures (ie, loss of a lobular pattern), markedly irregular ductal contours, ruptured ducts, nuclear enlargement, pleomorphism and hyperchromatism, and mitotic figures. Immunohistologic markers that are helpful are carcinoembryonic antigen, MUC1, p53, and Ki-67/ MIB1. Conclusions. —There are a few features that are diagnostic and a number that are suggestive of PDAC. Therefore, a combination of several features may be required to clearly distinguish chronic pancreatitis from invasive PDAC.
Examination of Listeria monocytogenes Intracellular Gene Expression by Using the Green Fluorescent Protein of Aequorea victoria (1999)

The ActA protein of Listeria monocytogenes is an essential virulence factor and is required for intracellular bacterial motility and cell-to-cell spread. plcB, cotranscribed with actA, encodes a broad-specificity phospholipase C that contributes to lysis of host cell vacuoles and cell-to-cell spread. Construction of a transcriptional fusion between actA-plcB and the green fluorescent protein gene of Aequorea victoria has facilitated the detailed examination of patterns of actA/plcB expression within infected tissue culture cells. actA/plcB expression began approximately 30 min postinfection and was dependent upon entry of L. monocytogenes into the host cytosol. L. monocytogenes Deltahly mutants, which are unable to escape from host cell vacuoles, did not express actA/plcB at detectable levels within infected tissue culture cells; however, complementation of the hly defect allowed entry of the bacteria into the host cytoplasm and subsequent actA/plcB expression. These results emphasize the ability of L. monocytogenes to sense the different host cell compartment environments encountered during the course of infection and to regulate virulence gene expression in response.
Oral history and indigenous Australia: The national library's Mura Gadi (2002)

The National Library of Australia (NLA) holds more than 35,000 hours of sound recordings in its Oral History Collection. It produces, collects and preserves three categories of recorded interviews and other forms of oral history concerning Australians of national standing, social history which documents the experiences and encounters of everyday life and field recordings in folklore.
Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage (1986)

The addition of foetal calf serum to explant cultures of adult bovine articular cartilage is known to stimulate proteoglycan synthesis in a dose-dependent manner. We have now shown the activity in serum responsible for this effect to be heat- and acid-stable, to be associated with a high-Mr complex in normal serum but converted to a low-Mr form under acid conditions. The activity has an apparent Mr approximately 10,000 and isoelectric points similar to those reported for insulin-like growth factors (IGFs). Addition of a monoclonal antibody against insulin-like growth factor-I (IGF-I) prevented foetal calf serum from stimulating proteoglycan synthesis. Physiological concentrations of recombinant IGF-I or pharmacological levels of insulin when added to cartilage cultures mimicked the proteoglycan-stimulatory activity of serum. IGF-I appeared to act by increasing the rate of proteoglycan synthesis and did not change the nature of the proteoglycan synthesized nor the rate of proteoglycan catabolism by the tissue, suggesting that IGF-I may be important in the regulation of proteoglycan metabolism in adult articular cartilage. Furthermore, IGF-I can replace foetal calf serum in the culture medium, thereby allowing the use of a fully-defined medium which will maintain the synthesis and tissue levels of proteoglycan in adult articular cartilage explants for up to 5 days.
Synthesis and Pharmacology of Potential Cocaine Antagonists. 2. Structure−Activity Relationship Studies of Aromatic Ring-Substituted Methylphenidate Analogs (1996)

As part of a program to develop medications which can block the binding of cocaine to the dopamine transporter, yet spare dopamine uptake, a series of aromatic ring-substituted methylphenidate derivatives was synthesized and tested for inhibitory potency in [3H]WIN 35,428 binding and [3H]dopamine uptake assays using rat striatal tissue. Synthesis was accomplished by alkylation of 2-bromopyridine with anions derived from various substituted phenylacetonitriles. In most cases, erythro compounds were markedly less potent than the corresponding (+/-)-threo-methylphenidate (TMP; Ritalin) derivatives. The ortho-substituted compounds were much less potent than the corresponding meta- and/or para-substituted derivatives. The most potent compound against [3H]WIN 35,428 binding, m-bromo-TMP, was 20-fold more potent than the parent compound, whereas the most potent compound against [3H]dopamine uptake, m,p-dichloro-TMP, was 32-fold more potent. Threo derivatives with m- or p-halo substituents were more potent than TMP, while electron-donating substituents caused little change or small loss of potency. All of the derivatives had Hill coefficients approaching unity, except m,p-dichloro-TMP, which had an nH of 2.0. Although the potency of the (+/-)-methylphenidate derivatives in the two assays was highly correlated (R2 = 0.986), the compounds m-chloro-,m-methyl-, and p-iodo-TMP were 4-5-fold more potent at inhibiting [3H]-WIN 35,428 binding than [3H]dopamine uptake (cocaine has a ratio of 2.3). These and other compounds may be promising candidates for further testing as potential partial agonists or antagonists of cocaine.
The response of Escherichia coli K12 upon exposure to hypochlorous acid and hydrogen peroxide (1996)

The aim of the work reported here was to investigate the growth-inhibitory activity of HOCI and hydrogen peroxide toward Escherichia coli K12 during both logarithmic and stationary phases of the growth cycle, as well as the response of E. coli K12 to these oxidants. Stationary phase cultures were exposed to sub-inhibitory oxidising stress, and the minimum inhibitory concentrations (MIC) were determined during the ensuing 24h. The effect of oxidant on logarithmically growing cultures was also determined. Stationary phase cultures of E. coli K12 responded to hydrogen peroxide stress, both the MIC and the survival following exposure to high concentrations increasing following exposure to stress. By contrast stationary phase cells did not become more tolerant of high concentrations of HOCI following HOCI stress. Logarithmically growing E. coli K12 did not display increased tolerance to either inhibitory or lethal concentrations of hydrogen peroxide or HOCI following the relevant oxidising stress.
Pharmacokinetic/pharmacodynamic (PK/PD) modeling and trial simulations to guide dose selection with CNTO 328, a chimeric anti-IL-6 monoclonal antibody (MAb), in patients with renal cell carcinoma (RCC) (2004)

2608 Background: PK/PD modeling and trial simulation were employed to guide dose selection for a Phase I/II clinical study with CNTO 328 in patients with RCC. Methods: Modeling and simulations were conducted using WinNonlin and Trial Simulator software. The PK model was developed using published data from patients with advanced multiple myeloma (van Zaanen, 1996). It was further refined following the availability of single dose PK data from the current study in RCC. The PK properties of CNTO 328 after IV infusion were best described using a two-compartment model. A PK/PD inhibitory effect of sigmoidal Emax model was developed for characterization of the relationship between serum CNTO 328 concentration and the concentration of the biomarker, C-reactive protein (CRP). Trial simulations were performed to guide the selection of a multiple dosing regimen for further clinical evaluation in RCC. Results: The PK/PD modeling and simulations predicted that 3 and 6 mg/kg of CNTO 328 administered at weeks 0, 3, 6, and 9 would suppress the CRP values to below 4 μg/mL (lower limit of quantification) for approximately 9 and 14 weeks, respectively. Conclusions: This PK/PD modeling and trial simulation approach has been used to rationally select an optimal dosing regimen for CNTO 328 to expedite the further clinical evaluation of this agent in the treatment of RCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor Centocor Centocor
Chronic Relapsing Experimental Allergic Encephalomyelitis (1979)

Clinical and neuropathological observations in chronic, relapsing experimental allergic encephalomyelitis (EAE) are reported and compared with data available for multiple sclerosis (MS). Clinical, relapsing EAE was found in 95 of 119 of the strain 13 and 22 of 57 of the Hartley guinea pigs immunized. Examination of the brains and spinal cords of the guinea pigs showed a high incidence of macroscopically visible, demyelinated plaques. The topographic distribution of lesions resembled a pattern similar to that described in MS. Microscopic features of the lesions consisted of perivenous inflammation, primary demyelination, oligodendrocyte loss, and reactive gliosis. It is concluded that, with the exception of minor differences, the clinical and pathological alterations in chronic, relapsing EAE closely resemble those found in MS.