gebhart/patrepeval huggingface dataset:
Homologous and heterologous asynchronicity between identified α‐, β‐ and δ‐cells within intact islets of Langerhans in the mouse (1999)

1. Using laser scanning confocal microscopy to image [Ca2+]i within intact murine islets of Langerhans, we analysed the [Ca2+]i signals generated by glucose in immunocytochemically identified alpha-, beta- and delta-cells. 2. Glucagon-containing alpha-cells exhibited [Ca2+]i oscillations in the absence of glucose, which petered out when islets were exposed to high glucose concentrations. 3. Somatostatin-containing delta-cells were silent in the absence of glucose but concentrations of glucose as low as 3 mM elicited oscillations. 4. In pancreatic beta-cells, a characteristic oscillatory calcium pattern was evoked when glucose levels were raised from 3 to 11 mM and this was synchronized throughout the beta-cell population. Remarkably, [Ca2+]i oscillations in non-beta-cells were completely asynchronous, both with respect to each other and to beta-cells. 5. These results demonstrate that the islet of Langerhans behaves as a functional syncytium only in terms of beta-cells, implying a pulsatile secretion of insulin. However, the lack of a co-ordinated calcium signal in alpha- and delta-cells implies that each cell acts as an independent functional unit and the concerted activity of these units results in a smoothly graded secretion of glucagon and somatostatin. Understanding the calcium signals underlying glucagon and somatostatin secretion may be of importance in the treatment of non-insulin-dependent diabetes mellitus since both glucagon and somatostatin appear to regulate insulin release in a paracrine fashion.
Differentiation in vivo of classical non-steroidal antiinflammatory drugs from cytokine suppressive antiinflammatory drugs and other pharmacological classes using mouse tumour necrosis factor alpha production. (1993)

The stimulation of tumour necrosis factor alpha (TNF alpha) production by lipopolysaccharide (LPS) has been widely used, both in vitro and in vivo, to examine the biochemistry and pharmacology of inflammatory cytokine production. It appears that classical nonsteroidal antiinflammatory drugs (NSAIDs) (prostaglandin H synthase 1 (PGHS-1) inhibitors) do not inhibit but instead stimulate cytokine production. In the current study, the authors utilized LPS-induced TNF alpha production in the Balb/c mouse to evaluate the activity of a classical NSAID, a mixed inhibitor, and SmithKline Beecham cytokine suppressive antiinflammatory drugs (CSAID). The results corroborated the stimulation of TNF alpha production by NSAIDs (indomethacin, naproxen, ibuprofen) and indicated that the stimulation rank-ordered with the potency of inhibition of PGHS-1. Neither acetaminophen nor nabumetone was found to stimulate TNF alpha production significantly. Tenidap, a compound reported to inhibit 5-lipoxygenase, cyclooxygenase and cytokine production, also stimulated TNF alpha production while the 5-lipoxygenase inhibitor, phenidone, was inactive. The CSAID (exemplified by SK&F 86002, SK&F 105809 and SK&F 104351), strongly inhibited TNF alpha production in this model system (ED50s of 32, 48, and 34 mg/kg p.o., respectively). These results clearly differentiate CSAID from the other compounds tested and suggest that CSAID are relatively weak inhibitors of PGHS 1 while being potent inhibitors of inflammatory cytokine production.
Identification and Characterization of Small Molecule Functional Antagonists of the CCR1 Chemokine Receptor (1998)

The CC chemokines macrophage inflammatory protein-1alpha (MIP-1alpha) and RANTES (regulated on activation normal T cell expressed) have been implicated in rheumatoid arthritis and multiple sclerosis. Since their effects are mediated through the CCR1 chemokine receptor, we set up a small molecule CCR1 antagonist program to search for inhibitors. Through high capacity screening we discovered a number of 4-hydroxypiperidine compounds with CCR1 antagonist activity and report their synthesis and in vitro pharmacology here. Scatchard analysis of the competition binding data revealed that the compounds had Ki values ranging from 40 to 4000 nM. The pharmacological profile of the most potent member of this series, compound 1 (2-2-diphenyl-5-(4-chlorophenyl)piperidin-lyl)valeronitri te), was further evaluated. Compound 1 showed concentration-dependent inhibition of MIP-1alpha-induced extracellular acidification and Ca2+ mobilization demonstrating functional antagonism. When given alone, the compound did not elicit any responses, indicating the absence of intrinsic agonist activity. Compound 1 inhibited MIP-1alpha- and RANTES-induced migration in peripheral blood mononuclear cells in a dose-responsive manner. Selectivity testing against a panel of seven transmembrane domain receptors indicated that compound 1 is inactive on a number of receptors at concentrations up to 10 microM. This is the first description of CCR1 receptor antagonists that may be useful in the treatment of chronic inflammatory diseases involving MIP-1alpha, RANTES, and CCR1.
New Advances in the Application of FTIR Microscopy and Spectroscopy for the Characterization of Artistic Materials (2010)

Fourier transform infrared (FTIR) spectroscopy is one of the most widely applied techniques for the investigation of cultural heritage materials. FTIR microscopy is well established as an essential tool in the microdestructive analysis of small samples, and the recent introduction of mapping and imaging equipment allows the collection of a large number of FTIR spectra on a surface, providing a distribution map of identified compounds. In this Account, we report recent advances in FTIR spectroscopy and microscopy in our research group. Our laboratory develops, tests, and refines new and less-studied IR spectroscopy and microscopy methods, with the goal of their adoption as routine analytical techniques in conservation laboratories. We discuss (i) the analysis of inorganic materials inactive in the mid-IR region by means of far-IR spectroscopy, (ii) the development of new methods for preparing cross sections, (iii) the characterization and spatial location of thin layers and small particles, and (iv) the evaluation of protective treatments. FTIR spectroscopy and microscopy have been mostly used in the mid-IR region of 4000-600 cm(-1). Some inorganic pigments, however, are inactive in this region, so other spectroscopic techniques have been applied, such as Raman spectroscopy. We suggest an alternative: harnessing the far-IR (600-50 cm(-1)). Our initial results show that far-IR spectroscopy is exceptionally useful with mural paintings or with corrosion products from which larger sample quantities can generally be collected. Moreover, the inorganic composition of a sample can be characterized by the presence of several compounds that are inactive in the mid-IR range (such as sulfides, oxides, and so forth). Stratigraphical analyses by FTIR microscopy can be hindered by the process of cross section preparation, which often involves an embedding organic polymer penetrating the sample's porous structure. Here, the polymer bands may completely cover the bands of organic compounds in the sample. However, a correct methodological approach can prevent such limitations. For example, it is always advisable to analyze the sample surface before preparing the cross section in order to characterize the preparation layers and the varnish layers, which are generally applied to the surface of a painting both to protect it and improve the color saturation. Furthermore, the innovative use of IR-transparent salts as embedding material for cross sections can prevent contamination of the embedding resin and improve detection of organic substances. Another key point in the use of FTIR microscopy in artwork analysis is spatial resolution. The high-energy output of a new integrated FTIR microscope enhances the ability to characterize and spatially locate small particles and thin layers. Moreover, the new configuration proves extremely useful in the evaluation of protective treatments, because larger areas may be analyzed in less time in comparison to traditional systems, allowing the collection of more statistical data.
Nickel-catalyzed Carboannulation Reaction of o-Bromobenzyl Zinc Bromide with Unsaturated Compounds (2007)

A number of indenes have been prepared in good yields by treating o-bromobenzyl zinc bromide 1 with various terminal and internal alkynes in the presence of a nickel catalyst. The nickel-catalyzed carboannulation reaction was successfully extended to the synthesis of indane derivatives by reaction of 1 with acrylates and styrene.
Accumulation of NFAT mediates IL-2 expression in memory, but not naïve, CD4 + T cells (2007)

In contrast to naïve CD4+ T cells, memory CD4+ T cells rapidly express high levels of effector cytokines in response to antigen stimulation. The molecular mechanism for this specific behavior is not well understood. The nuclear factor of activated T cells (NFAT) family of transcription factors plays an important role in the transcription of many cytokine genes. Here we show that memory CD4+ T cells rapidly induce NFAT-mediated transcription upon T cell receptor ligation whereas NFAT activation in naïve CD4+ T cells requires longer periods of stimulation. The difference in kinetics correlates with the low levels of NFATc1 and NFATc2 proteins present in naïve CD4+ T cells and their high levels in memory CD4+ T cells. Accordingly, IL-2 expression requires NFAT activation only in memory CD4+ T cells whereas it is NFAT-independent in naïve CD4+ T cells. Thus, the accumulation of NFATc1 and NFATc2 in memory CD4+ T cells represents a previously uncharacterized regulatory mechanism for the induction of early gene expression after antigen stimulation.
Dynamic local remeshing for elastoplastic simulation (2010)

We propose a finite element simulation method that addresses the full range of material behavior, from purely elastic to highly plastic, for physical domains that are substantially reshaped by plastic flow, fracture, or large elastic deformations. To mitigate artificial plasticity, we maintain a simulation mesh in both the current state and the rest shape, and store plastic offsets only to represent the non-embeddable portion of the plastic deformation. To maintain high element quality in a tetrahedral mesh undergoing gross changes, we use a dynamic meshing algorithm that attempts to replace as few tetrahedra as possible, and thereby limits the visual artifacts and artificial diffusion that would otherwise be introduced by repeatedly remeshing the domain from scratch. Our dynamic mesher also locally refines and coarsens a mesh, and even creates anisotropic tetrahedra, wherever a simulation requests it. We illustrate these features with animations of elastic and plastic behavior, extreme deformations, and fracture.
[Transformation of Populus tomentosa with anti-PLD gene]. (2002)

Antisense Phospholipase Dgamma( PLDgamma) gene was introduced into Populus tomentosa mediated by Agrobactrium tumefaciens. The young leaves of triploid populus were used as the material and the regeneration system of high frequency has been established. We have developed the traditional transgene method by Agrobactrium trmefaciens and obtained many transgenic plants of anti-PLDgamma gene. Tests showed that the transgenic plants can grow well on the culture medium with 0.7% NaCl.
Quantitative assessment of cartilage status in osteoarthritis by quantitative magnetic resonance imaging: Technical validation for use in analysis of cartilage volume and further morphologic parameters (2004)

Quantitative MRI permits technically accurate and differential assessment of increases in eroded joint surface area and reductions in cartilage thickness in OA. The surrogate validity of these parameters requires testing in longitudinal studies. These parameters may be advantageous over determination of cartilage volume alone when diagnosing OA, exploring its progression, or testing responsiveness to new therapies.
Routes to S -nitroso-hemoglobin formation with heme redox and preferential reactivity in the β subunits (2003)

Previous studies of the interactions of NO with human hemoglobin have implied the predominance of reaction channels that alternatively eliminate NO by converting it to nitrate, or tightly complex it on the alpha subunit ferrous hemes. Both channels could effectively quench NO bioactivity. More recent work has raised the idea that NO groups can efficiently transfer from the hemes to cysteine thiols within the beta subunit (cysbeta-93) to form bioactive nitrosothiols. The regulation of NO function, through its chemical position in the hemoglobin, is supported by response to oxygen and to redox agents that modulate the molecular and electronic structure of the protein. In this article, we focus on reactions in which Fe(III) hemes could provide the oxidative requirements of this NO-group transfer chemistry. We report a detailed investigation of the reductive nitrosylation of human met-Hb, in which we demonstrate the production of S-nitroso (SNO)-Hb through a heme-Fe(III)NO intermediate. The production of SNO-Hb is strongly favored (over nitrite) when NO is gradually introduced in limited total quantities; in this situation, moreover, heme nitrosylation occurs primarily within the beta subunits of the hemoglobin tetramer. SNO-Hb can similarly be produced when Fe(II)NO hemes are subjected to mild oxidation. The reaction of deoxygenated hemoglobin with limited quantities of nitrite leads to the production of beta subunit Fe(II)NO hemes, with SNO-Hb produced on subsequent oxygenation. The common theme of these reactions is the effective coupling of heme-iron and NO redox chemistries. Collectively, they establish a connectivity between hemes and thiols in Hb, through which NO is readily dislodged from storage on the heme to form bioactive SNO-Hb.
FERMENTATION OF PEANUT MILK WITH (1978)

ABSTRACT Several extraction procedures were examined for their suitability to yield desirable peanut milks for fermentation by four strains of lactic acid bacteria. Studies revealed that a procedure in which peanuts were soaked in 1.0% sodium bicarbonate for 16‐18 hr, drained, washed with tap water, ground, steeped for 4‐5 hr in tap water, and filtered resulted in milk most desirable for fermentation. The addition of lactose (2%) to pasteurized peanut milk before fermenting with Lactobacillus bulgaricus NRRL B‐1909 and L. acidophilus NRRL B‐1910 for 3 days at 37°C resulted in a custard‐like product having 0.38‐0.53% titratable acidity at pH 4.76‐4.43, respectively. Sensory panel evaluations of blended, fermented peanut milks containing added sucrose (2%) and fruit flavorings showed that the products were acceptable and competed favorably with flavored buttermilk. Fermented peanut milk substituted for buttermilk in a corn muffin recipe resulted in products with organoleptic characteristics not significantly (P &lt; 0.05) different from those of the control. Further investigations are required to determine the optimum conditions for preparing fermented peanut milk products.
Tissue refractive index as marker of disease (2011)

The gold standard in histopathology relies on manual investigation of stained tissue biopsies. A sensitive and quantitative method for in situ tissue specimen inspection is highly desirable, as it would allow early disease diagnosis and automatic screening. Here we demonstrate that quantitative phase imaging of entire unstained biopsies has the potential to fulfill this requirement. Our data indicates that the refractive index distribution of histopathology slides, which contains information about the molecular scale organization of tissue, reveals prostate tumors and breast calcifications. These optical maps report on subtle, nanoscale morphological properties of tissues and cells that cannot be recovered by common stains, including hematoxylin and eosin. We found that cancer progression significantly alters the tissue organization, as exhibited by consistently higher refractive index variance in prostate tumors versus normal regions. Furthermore, using the quantitative phase information, we obtained the spatially resolved scattering mean free path and anisotropy factor g for entire biopsies and demonstrated their direct correlation with tumor presence. In essence, our results show that the tissue refractive index reports on the nanoscale tissue architecture and, in principle, can be used as an intrinsic marker for cancer diagnosis.
N- and C-Terminal Sequences Control Degradation of MAD3/IκBα in Response to Inducers of NF-κB Activity (1995)

The proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide. In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation. Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein. We propose that treatment of 70Z/3 cells with either phorbol myristate acetate or lipopolysaccharide induces a kinase activity which phosphorylates serines 32 and that these phosphorylations target the protein for rapid proteolytic degradation, possibly by the ubiquitin-26S proteasome pathway, thus allowing NF-kappa B to translocate to the nucleus and to activate gene expression.
Endogenous expression of a high-affinity pseudoknot RNA aptamer suppresses replication of HIV-1 (2002)

Aptamers, small oligonucleotides derived from an in vitro evolution process called SELEX, are promising therapeutic and diagnostic agents. Although very effective in vitro, only a few examples are available showing their potential in vivo. We have analyzed the effect of a well characterized pseudoknot RNA aptamer selected for tight binding to human immunodeficiency virus (HIV) type 1 reverse transcriptase on HIV replication. Transient intracellular expression of a chimeric RNA consisting of the human initiator tRNA(Met) (tRNA(Meti))/aptamer sequence in human 293T cells showed inhibition of HIV particle release by >75% when the cells were co-transfected with proviral HIV-1 DNA. Subsequent virus production of human T-lymphoid C8166 cells, infected with viral particles derived from co-transfected 293T cells, was again reduced by >75% as compared with the control. As the observed effects are additive, in this model for virus spread, the total reduction of HIV particle formation by transient intracellular expression of the pseudoknot RNA aptamer amounts to >95%. Low-dose HIV infection of human T cells stably expressing the aptamer did not show any virus replication over a period of 35 days. This is the first example of an RNA aptamer selected against a viral enzyme target to show powerful antiviral activity in HIV-1-permissive human T-lymphoid cell lines.
Hypermethylation of Cell-Free Serum DNA Indicates Worse Outcome in Patients With Bladder Cancer (2007)

The detection of hypermethylation in cell-free serum DNA provides valuable diagnostic and prognostic information that can still be improved by combining the results of 3 gene sites (APC, GSTP1 and TIG1). The presence of hypermethylated DNA in the serum of patients with bladder cancer is associated with a worse outcome. Our results suggest that measuring hypermethylation in the serum of patients with bladder cancer is a useful biomarker.
Fixation of the tongue below mandible in Pierre Robin syndrome. (1996)

For some children with a diagnosis of Robin syndrome the conservative treatment will not be sufficient due to recurrent glossoptosis and acute obturation of the airways which leads to asphyxia. The risk for children with this complication is so serious that it needs emergency surgical treatment. Its aim is an artificial ankyloglossia. However, often it fails when the stitches cut through. The technique of tongue fixation presented in this paper has proved successful.
New Therapeutic Options in Colon Cancer: Focus on Oxaliplatin (2002)

Colon cancer is the third leading cause of cancer death in the United States and the second leading cause in the Northern, Central, and Southern Americas. Appropriate treatment depends on the stage of malignancy, which is determined using the tumor-lymph node-metastases system. In stage III disease, adjuvant chemotherapy increases disease-free and long-term survival following surgery, and chemotherapy is the mainstay of treatment for advanced disease. New therapies are being evaluated, including oxaliplatin, a third-generation platinum analogue approved as first- and second-line therapy for metastatic colorectal cancer in Europe; the drug shows great promise combined with 5-fluorouracil/leucovorin or with irinotecan. The dose-limiting toxicity of oxaliplatin is neurologic, which can be acute or chronic; this can be prevented or reduced in some cases through patient education. Nurses play a critical role in education concerning prevention and management of oxaliplatin-related side effects.
Oral domperidone: double blind comparison with placebo in irritable bowel syndrome. (1983)

Symptom scores, stool data, and the transit of a standard, solid meal were measured in 25 patients with irritable bowel syndrome during baseline conditions and after four weeks treatment with placebo and domperidone in the form of a double-blind cross-over trial. All patients had previously undergone a comprehensive series of diagnostic investigations and had failed to respond to dietary supplementation with coarse wheat bran (10-30 g daily). Compared with placebo treatment, domperidone had no significant effect on gastric emptying, small bowel or whole gut transit times, stool weight, frequency, or consistency. Most symptoms improved significantly with both placebo and domperidone treatments, compared with the baseline period, but there was no significant difference between placebo and domperidone for any of the symptoms. Abdominal distension, however, was reported on more days per week during domperidone treatment (p = 0.02). The findings in this study do not support the use of domperidone in the management of irritable bowel syndrome.