gebhart/patrepeval huggingface dataset:
Cell Biology of the Glomerular Podocyte (2003)

Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.
Rho GTPases: Promising Cellular Targets for Novel Anticancer Drugs (2006)

Ras-homologous (Rho) GTPases play a pivotal role in the regulation of numerous cellular functions associated with malignant transformation and metastasis. Rho GTPases are localized at membranes and become activated upon stimulation of cell surface receptors. In their GTP-bound (=active) state, Rho proteins bind to effector proteins, thereby triggering specific cellular responses. Members of the Rho family of small GTPases are key regulators of actin reorganization, cell motility, cell-cell and cell-extracellular matrix (ECM) adhesion as well as of cell cycle progression, gene expression and apoptosis. Each of these functions is of importance for the development and progression of cancer. Furthermore, Rho guanine exchange factors (GEFs) are often oncogenic and the expression level of Rho GTPases frequently increases with malignancy. Rho proteins also affect cellular susceptibility to DNA damaging agents, including antineoplastic drugs and ionizing radiation (IR). Thus, modulation of Rho driven mechanisms may influence the therapeutic efficiency and/or the side effects of conventional antineoplastic therapy. Because of their pleiotropic functions, Rho proteins appear to be promising targets for the development of novel anticancer drugs. Experimental approaches to inhibit Rho (and Ras) have focused on the attenuation of their C-terminal isoprenylation. This is because C-terminal lipid modification is required for correct intracellular localization and function of Rho/Ras. Inhibitors of farnesyltransferase (FTI), geranylgeranyltransferase (GGTI) as well as of HMG-CoA-reductase (i. e. statins) have been investigated with respect to their usefulness in tumor therapy. The studies showed that these compounds affect tumor progression and furthermore have impact on the frequency of cell death induced by tumor therapeutics. A possible drawback of inhibitors of isoprenylation is their poor selectivity for individual Rho GTPases. Therefore, specific inhibitors of individual Rho functions (notably RhoA-, RhoB-, Rac1- or Cdc42-related functions) are predicted to be of great therapeutic benefit. Indeed, compounds developed as specific inhibitors of the RhoA-effector molecule Rho-kinase (ROK) have been demonstrated to exert anti-metastatic activity in vivo.
Increased serum clearance of oligomannose species present on a human IgG1 molecule (2012)

The role of Fc glycans on clearance of IgG molecule has been examined by various groups in experiments where specific glycans have been enriched or the entire spectrum of glycans was studied after administration in pre-clinical or clinical pharmacokinetic (PK) studies. The overall conclusions from these studies are inconsistent, which may result from differences in antibody structure or experimental design. In the present study a well-characterized recombinant monoclonal IgG1 molecule (mAb-1) was analyzed from serum samples obtained from a human PK study. mAb-1 was recovered from serum using its ligand cross-linked to Sepharose beads. The overall purity and recovery of all isoforms were carefully evaluated using a variety of methods. Glycans were then enzymatically cleaved, labeled using 2-aminobenzamide and analyzed by normal phase high performance liquid chromatography. The assays for recovering mAb-1 from serum and subsequent glycan analysis were rigorously qualified at a lower limit of quantitation of 15 μg/mL, thus permitting analysis to day 14 of the clinical PK study. Eight glycans were monitored and classified into two groups: (1) the oligomannose type structures (M5, M6 and M7) and (2) fucosylated biantennary oligosaccharides (FBO) structures (NGA2F, NA1F, NA2F, NA1F-GlcNAc and NGA2F-GlcNAc). We observed that the oligomannose species were cleared at a much faster rate (40%) than FBOs and conclude that high mannose species should be carefully monitored and controlled as they may affect PK of the therapeutic; they should thus be considered an important quality attribute. These observations were only possible through the application of rigorous analytical methods that we believe will need to be employed when comparing innovator and biosimilar molecules.
The interactive whiteboard: a literature survey (2005)

Abstract There has been an increasing awareness of the need to understand the match between technology and pedagogy in the development of interactive learning supported by the interactive whiteboard in schools in the United Kingdom. There is evidence that teachers are seeking some understanding of the research background and to this end a team from Keele University has been working on three aspects of interactive whiteboard use – the management of change as the technology is introduced, the learning processes as teachers become more fluent with the hardware and software, and the development of interactivity as a feature of enhanced pedagogy. There is comparatively little background or research literature available but the team have sought this out and offer an analysis of findings from a broad sweep of sources. These confirm that enhanced interactivity requires an understanding of the way in which both teachers and pupils gain from the use of the technology and demonstrate that there is a progression at all levels in learning to use the equipment and associated software to educational advantage.
Promotion of cell adhesion by single-stranded and triple-helical peptide models of basement membrane collagen alpha 1(IV)531-543. Evidence for conformationally dependent and conformationally independent type IV collagen cell adhesion sites. (1994)

Several regions within the triple-helical domain of type IV collagen function as cellular recognition sites. We have demonstrated previously that melanoma cell activities promoted by the alpha 1(IV)1263-1277 sequence are enhanced by triple helicity (Fields, C. G., Mickelson, D. J., Drake, S.L., McCarthy, J.B., and Fields, G.B. (1993) J. Biol. Chem. 268, 14153-14160), whereas Eble et al. reached similar conclusions for alpha 1 beta 1 integrin-mediated fibrosarcoma cell adhesion to [alpha 1(IV)]2 alpha 2(IV)434-472 (Eble, J. A., Golbik, R., Mann, K., and Kühn, K. (1993) EMBO J. 12, 4795-4802). In the present study, we have examined the cell adhesion activities of a third region in type IV collagen. A single-stranded peptide (SSP) incorporating the alpha 1(IV)531-543 sequence promoted the adhesion of melanoma, ovarian carcinoma, and Jurkat cells in a dose-dependent manner, with 40% cell adhesion observed at [SSP] = 1.8, 11.5, and 42.2 microM, respectively. Nearly identical results were obtained for cell adhesion to an all-D-enantiomer of the SSP, suggesting that the cell surface receptor(s) for this site do not discriminate based on chirality. The alpha 1(IV)531-543 sequence maintained its cell adhesion promoting activity when incorporated into a homotrimeric triple-helical polypeptide, although relative levels of adhesion were either slightly enhanced or slightly diminished compared with the SSP. Triple-helical conformation was thus not critical for cellular recognition of the alpha 1(IV)531-543 sequence. Single-site substitution experiments of the SSP showed no overall correlation between the biological effects of substitutions and SSP conformation. The SSP, D-SSP, triple-helical polypeptide, and SSP substitution results suggest that cell recognition of the alpha 1(IV)531-543 sequence is generally independent of substrate conformation. The present and prior studies indicate that "conformationally dependent" and "conformationally independent" cellular recognition sites exist within the triple-helical domain of type IV collagen.
Analysis of Cerebral Amyloid Angiopathy in a Transgenic Mouse Model of Alzheimer Disease Using In Vivo Multiphoton Microscopy (2001)

Transgenic mice overexpressing the human amyloid precursor protein (APPV717F) develop cerebral amyloid angiopathy (CAA) as they age. We have examined the effect of CAA on blood vessels in vivo using multiphoton laser scanning microscopy. We are able to simultaneously detect, in an alive but anesthetized animal, fluorescent angiography of microvessels as well as the presence of amyloid angiopathy in 3-dimensional volumes near the surface of the brain. Analysis revealed dilation of the portions of vessels that were associated with amyloid deposition, even when that amyloid deposition was quite mild. In addition, analysis of the 3-dimensional reconstruction of the relationship between the vasculature and CAA suggest that CAA is initiated close to branch points of vessels. Taken together, these data suggest that CAA has a substantial effect on the physiology of the microvasculature in vivo.
Activity of alemtuzumab in patients with CD52‐positive acute leukemia (2006)

Single-agent alemtuzumab was found to have limited activity in recurrent or refractory acute leukemia. An evaluation in patients with a better prognosis, in combination with other agents or as part of consolidation therapy, is warranted.
Single chain spectroscopy of conformational dependence of conjugated polymer photophysics (2000)

Single molecule confocal fluorescence microscopy was used to perform photoluminescence spectroscopy on single, isolated molecules of the conjugated polymer poly[2-methoxy, 5-(2'-ethyl-hexyloxy)-p-phenylene-vinylene] (MEH-PPV). We show that the fluorescence from single chains of this electroluminescent polymer depends strongly on chain conformation. The time evolution of the spectra, emission intensity, and polarization all provide direct evidence that memory of the chain conformation in solution is retained after solvent evaporation. Chains cast from toluene solution are highly folded and show memory of the excitation polarization. Exciton funneling to highly aggregated low energy regions causes the chain to mimic the photophysical behavior of a single chromophore. Chains cast from chloroform, however, behave as multichromophore systems, and no sudden discrete spectral or intensity jumps are observed. These also exhibit different spectroscopy from the folded chromophores.
Center for RF-Measurement Technology (2008)

In February 2006 the Centre for RF Measurement Technology was established at the University of Gavle (HIG). The long term objectives of the centre are to establish world leading research in the are ...
Coordination Chemistry of the Carboxylate Type Siderophore Rhizoferrin:  The Iron(III) Complex and Its Metal Analogs (1996)

Rhizoferrin is a member of a new class of siderophores (microbial iron transport compounds) based on carboxylate and hydroxy donor groups rather than the commonly encountered hydroxamates and catecholates. We have studied the coordination chemistry of rhizoferrin (Rf), as a representative of this group, with Fe(3+), Rh(3+), Cr(3+), Al(3+), Ga(3+), VO(2+), and Cu(2+). The metal complexes have been studied by UV-vis, CD, NMR, and EPR spectroscopies and mass spectrometry. The formation constants for the iron complex have also been measured and yield a log K(LFe) of 25.3. The Rh and Cr rhizoferrin complexes are unusual in that they appear to adopt a chirality about the metal center that is the opposite of the native iron analog. Several of the alternative metal ion complexes are found to have biological activity toward Morganella morganii in a plate type assay.
Phase I/IIa Study of Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease. (2016)

Chronic graft versus host disease (cGVHD) remains a major problem for long survivors after allogeneic hematopoietic stem cell transplantation (HSCT). Currently, corticosteroid therapy is effective for cGVHD as the first line therapy. However, prolonged therapy with corticosteroids causes various severe adverse events. To develop the new therapeutic strategy of cGVHD, we have launched a multicenter phase I/IIa clinical trial of low dose subcutaneous interleukin-2 (IL-2) for treatment of steroid refractory cGVHD, which is constituted of 2 sequential phases (induction phase and maitanance phase). This study will provide the new therapeutic option for patients with refractory cGVHD after allogeneic HSCT.
Cromolyn sodium delays disease onset and is neuroprotective in the SOD1G93A Mouse Model of amyotrophic lateral sclerosis (2019)

Accumulating evidence suggests that neuroinflammatory processes are implicated in the initiation and progression of amyotrophic lateral sclerosis (ALS). Previous reports have demonstrated an increase in microgliosis and astrogliosis in the lumbar spinal cord of SOD1<sup>G93A</sup> transgenic mice before the onset of symptoms, a neuroinflammatory response which correlated with disease progression. Importantly, early stage homeostatic microglia enhanced motor neuron survival, while pro-inflammatory microglia were toxic to motor neurons in the SOD1<sup>G93A</sup> mice. Recent studies from our group have demonstrated that cromolyn sodium, an FDA approved compound, exerts neuroprotective effects in mouse models of Alzheimer's disease by altering microglial cell activation. Here, we tested the neuroprotective and anti-inflammatory effects of cromolyn sodium in the SOD1<sup>G93A</sup> mouse model of ALS. Our results indicate that cromolyn sodium treatment significantly delayed the onset of neurological symptoms, and improved deficits in PaGE performance in both male and female mice, however, there was only an effect on survival in female mice. Furthermore, there was a significant increase in motor neuron survival in the lumbar spinal cord as well as a significant decrease in the denervation of the neuromuscular junction of the tibialis anterior muscle in cromolyn treated transgenic SOD1<sup>G93A</sup> mice. Lastly, cromolyn treatment decreased the expression of pro-inflammatory cytokines/chemokines in the lumbar spinal cord and plasma and decreased mast cell degranulation in the tibialis anterior muscle of transgenic SOD1<sup>G93A</sup> mice. Together, these findings suggest that cromolyn sodium provides neuroprotection in the SOD1<sup>G93A</sup> mice by decreasing the inflammatory response.
Optimization of Protein Expression in Mammalian Cells (2018)

Recombinant proteins, such as monoclonal antibodies, are produced in mammalian cell lines to introduce proper protein folding and post-translational modifications, which are essential for full biological activity. In both the industrial and academic environments, the use of recombinant proteins varies widely and, with it, the method of production. The amount of an antibody needed for a toxicity study is far greater than that needed by a research lab performing cellular assays, and the amount of effort put into the development of the protein will vary accordingly. There is no universal strategy for mammalian expression systems, and scientists often struggle to develop a suitable process from the myriad of choices at each step. Here, we elaborate on the various obstacles encountered when planning high-yield experiments to produce the recombinant proteins of interest. © 2018 by John Wiley & Sons, Inc.
Localization of multiple acoustic sources with small arrays using a coherence test (2008)

Direction finding of more sources than sensors is appealing in situations with small sensor arrays. Potential applications include surveillance, teleconferencing, and auditory scene analysis for hearing aids. A new technique for time-frequency-sparse sources, such as speech and vehicle sounds, uses a coherence test to identify low-rank time-frequency bins. These low-rank bins are processed in one of two ways: (1) narrowband spatial spectrum estimation at each bin followed by summation of directional spectra across time and frequency or (2) clustering low-rank covariance matrices, averaging covariance matrices within clusters, and narrowband spatial spectrum estimation of each cluster. Experimental results with omnidirectional microphones and colocated directional microphones demonstrate the algorithm's ability to localize 3-5 simultaneous speech sources over 4 s with 2-3 microphones to less than 1 degree of error, and the ability to localize simultaneously two moving military vehicles and small arms gunfire.
Mesenchymal stem cell infusion therapy in a carbon tetrachloride‐induced liver fibrosis model affects matrix metalloproteinase expression (2010)

In order to investigate the effects of bone marrow-derived MSCs (mesenchymal stem cells) in reversing liver fibrosis and to determine their possible mechanism of action, mouse MSCs were infused into the tail vein of a CCl(4) injection mouse chronic model. MSCs caused a decrease in liver fibrosis histopathologically, 4 weeks after transplantation. The reduction in liver collagen was confirmed by quantitative analysis. Moreover, lipid peroxidation in the CCl(4)/MSC group decreased significantly. Quantitative RT (reverse transcription)-PCR analysis showed administration of MSCs has a significant antifibrotic effect as evidenced by the decrease in expression of liver collagen and increase in MMP13 (matrix metalloproteinase 13) in the CCl(4)/MSC group when compared with the CCl(4) group, 4 weeks after transplantation. The expression of alphaSMA (smooth muscle actin) and TIMP1 was also down-regulated in the CCl(4)/MSC group. Additionally, the expression of MMP9 was significantly up-regulated in the CCl(4)-treated group; however, there was no significant change after MSC injection. Few engrafted cells in the recipient liver and were able to differentiate into albumin-positive cells. In conclusion, MSCs can enhance recovery of a CCl(4)-injured mouse liver through their influence in reducing collagen deposition by possibly affecting expression of MMPs.
Xenopus Heat Shock Factor 1 Is a Nuclear Protein before Heat Stress (1997)

Stress-induced expression of the heat shock (hs) genes in eukaryotes is mediated by a transcription factor known as heat shock factor 1 (HSF1). HSF1 is present in a latent, monomeric form in unstressed metazoan cells and upon exposure to heat or other forms of stress is converted to an "active" trimeric form, which binds the promoters of hs genes and induces their transcription. The conversion of HSF1 to its active form is hypothesized to be a multistep process involving (i) oligomerization of HSF1, plus (ii) additional changes in its physical conformation, (iii) changes in its phosphorylation state, and for some species (iv) translocation from the cytoplasm to the nucleus. Oligomerization of HSF appears to be essential for high affinity DNA binding, but it remains unclear whether the other steps occur in all organisms or what their mechanistic roles are. In this study we have examined if heat-induced cytoplasmic-nuclear translocation of HSF1 occurs in Xenopus oocytes. We observed that germinal vesicles (nuclei) that were physically dissected from unshocked Xenopus laevis oocytes contain no HSF1 binding activity. Interestingly, in vitro heat shock treatments of isolated nuclei from unshocked oocytes activated HSF1 binding, indicating that HSF1 must have been present in the unshocked nuclei prior to isolation. Induction of HSF1 binding was not observed in enucleated oocytes. Western blot analysis using an affinity-purified polyclonal antibody made against X. laevis HSF1 showed that HSF1 is present in equal amounts in unshocked and shocked oocytes and isolated nuclei. HSF1 was not detected in enucleated oocytes. These results clearly demonstrate that HSF1 is a nuclear protein in oocytes prior to exposure to stress. In Xenopus oocytes, therefore, HSF1 translocation from the cytoplasm to the nucleus is not part of the multistep process of HSF1 activation. These results also imply that the signals and/or factors involved in HSF1 activation must have their effect in the nuclear compartment.
Recent Advances in the Stabilization of Proteins Encapsulated in Injectable PLGA Delivery Systems (2002)

Injectable controlled-release systems based on biodegradable copolymers of lactic and glycolic acids (PLGAs) have become widely used for delivery of protein therapeutics and vaccine antigens. Over the last five years, great strides have been made toward overcoming the difficulty of stabilizing PLGA-encapsulated proteins. In addition to stabilizing proteins during encapsulation with anhydrous methods, two approaches have proven highly effective to stabilize proteins during 1-month release incubation under physiological conditions: protein complexation with zinc and control of PLGA microclimate pH with antacid excipients. Described here are recent advances in the stabilization of proteins encapsulated in PLGA delivery systems.
Refractive index of ZnSe at 38 μm and 106 μm, from 80 K to 300 K (1979)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text C. J. C. Thompson, A. G. DeBell, and W. L. Wolfe, "Refractive index of ZnSe at 3.8 μm and 10.6 μm, from 80 K to 300 K," Appl. Opt. 18, 2085_1-2086 (1979) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Isolation and characterization of the yeast gene encoding the MDH3 isozyme of malate dehydrogenase. (1992)

The MDH3 isozyme of Saccharomyces cerevisiae was purified from a haploid strain containing disruptions in genomic loci encoding the mitochondrial MDH1 and nonmitochondrial MDH2 isozymes. Partial amino acid sequence analysis of the purified enzyme was conducted and used to plan polymerase chain reaction techniques to clone the MDH3 gene. The isolated gene was found to encode a 343-residue polypeptide with a molecular weight of 37,200. The deduced amino acid sequence was closely related to those of MDH1 (50% residue identity) and of MDH2 (43% residue identity). The MDH3 sequence was found to contain a carboxyl-terminal SKL tripeptide, characteristic of many peroxisomal enzymes, and immunochemical analysis was used to confirm organellar localization of the MDH3 isozyme. Levels of MDH3 were determined to be elevated in cells grown with acetate as a carbon source, and under these conditions, MDH3 contributed approximately 10% of the total cellular malate dehydrogenase activity. Disruption of the chromosomal MDH3 locus produced a reduction in cellular growth rates on acetate, consistent with the presumed function of this isozyme in the glyoxylate pathway of yeast. Combined disruption of MDH1, MDH2, and MDH3 loci in a haploid strain resulted in the absence of detectable cellular malate dehydrogenase activity.