gebhart/patrepeval huggingface dataset:
Multipotential Nestin-Positive Stem Cells Isolated From Adult Pancreatic Islets Differentiate Ex Vivo Into Pancreatic Endocrine, Exocrine, and Hepatic Phenotypes (2001)

The endocrine cells of the rat pancreatic islets of Langerhans, including insulin-producing beta-cells, turn over every 40-50 days by processes of apoptosis and the proliferation and differentiation of new islet cells (neogenesis) from progenitor epithelial cells located in the pancreatic ducts. However, the administration to rats of islet trophic factors such as glucose or glucagon-like peptide 1 for 48 h results in a doubling of islet cell mass, suggesting that islet progenitor cells may reside within the islets themselves. Here we show that rat and human pancreatic islets contain a heretofore unrecognized distinct population of cells that express the neural stem cell-specific marker nestin. Nestin-positive cells within pancreatic islets express neither the hormones insulin, glucagon, somatostatin, or pancreatic polypeptide nor the markers of vascular endothelium or neurons, such as collagen IV and galanin. Focal regions of nestin-positive cells are also identified in large, small, and centrolobular ducts of the rat pancreas. Nestin-positive cells in the islets and in pancreatic ducts are distinct from ductal epithelium because they do not express the ductal marker cytokeratin 19 (CK19). After their isolation, these nestin-positive cells have an unusually extended proliferative capacity when cultured in vitro (approximately 8 months), can be cloned repeatedly, and appear to be multipotential. Upon confluence, they are able to differentiate into cells that express liver and exocrine pancreas markers, such as alpha-fetoprotein and pancreatic amylase, and display a ductal/endocrine phenotype with expression of CK19, neural-specific cell adhesion molecule, insulin, glucagon, and the pancreas/duodenum specific homeodomain transcription factor, IDX-1. We propose that these nestin-positive islet-derived progenitor (NIP) cells are a distinct population of cells that reside within pancreatic islets and may participate in the neogenesis of islet endocrine cells. The NIP cells that also reside in the pancreatic ducts may be contributors to the established location of islet progenitor cells. The identification of NIP cells within the pancreatic islets themselves suggest possibilities for treatment of diabetes, whereby NIP cells isolated from pancreas biopsies could be expanded ex vivo and transplanted into the donor/recipient.
Involvement of the Histone Deacetylase SIRT1 in Chicken Ovalbumin Upstream Promoter Transcription Factor (COUP-TF)-interacting Protein 2-mediated Transcriptional Repression (2003)

Chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting proteins 1 and 2 (CTIP1 and CTIP2) enhance transcriptional repression mediated by COUP-TF II and have been implicated in hematopoietic cell development and malignancies. CTIP1 and CTIP2 are also sequence-specific DNA-binding proteins that repress transcription through direct, COUP-TF-in-dependent binding to a GC-rich response element. CTIP1- and CTIP2-mediated transcriptional repression is insensitive to trichostatin A, an inhibitor of known class I and II histone deacetylases. However, chromatin immunoprecipitation assays revealed that expression of CTIP2 in mammalian cells resulted in deacetylation of histones H3 and/or H4 that were associated with the promoter region of a reporter gene. CTIP2-mediated transcriptional repression, as well as deacetylation of promoter-associated histones H3/H4 in CTIP2-transfected cells, was reversed by nicotinamide, an inhibitor of class III histone deacetylases such as the mammalian homologs of yeast Silent Information Regulator 2 (Sir2). The human homolog of yeast Sir2, SIRT1, was found to interact directly with CTIP2 and was recruited to the promoter template in a CTIP2-dependent manner. Moreover, SIRT1 enhanced the deacetylation of template-associated histones H3/H4 in CTIP2-transfected cells, and stimulated CTIP2-dependent transcriptional repression. Finally, endogenous SIRT1 and CTIP2 co-purified from Jurkat cell nuclear extracts in the context of a large (1-2 mDa) complex. These findings implicate SIRT1 as a histone H3/H4 deacetylase in mammalian cells and in transcriptional repression mediated by CTIP2.
The effect of H2O2 upon thioredoxin-enriched lens epithelial cells. (1988)

Thioredoxin, a dithiol polypeptide, has been examined as a potential contributor to the recovery of lens epithelial cells from oxidative insult. It is reported that Escherichia coli thioredoxin can (a) effectively reduce lens-soluble protein disulfide bonds generated by H2O2, (b) restore to its initial activity H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase, (c) act as an effective source of reducing potential for lens methionine sulfoxide peptide reductase, and (d) act as a free radical quencher based on studies with a stable free radical system generated by ascorbic acid and 2,6-dimethoxy-p-benzoquinone. Thioredoxin is much more effective than dithiothreitol in restoring glyceraldehyde-3-phosphate dehydrogenase activity and as a cofactor for methionine sulfoxide peptide reductase. Upon incubation with epithelial cells, thioredoxin can be observed in the cell using rocket immunoelectrophoresis. These cells recover from H2O2 insult more rapidly than control cell preparations based upon 1) analyses of plasma membrane-related activities: leucine and 86Rb uptake and 2) analyses of parameters primarily related to the internal cell metabolism: ATP concentration and glyceraldehyde-3-phosphate dehydrogenase activity. Analysis of thioredoxin in cell preparations indicates that only about 9% is in the reduced state implying a low effective concentration of the polypeptide. The experiments suggest that low levels of thioredoxin may significantly increase the ability of lens epithelial cells to recover from exposure to H2O2.
Differential diagnosis of monoclonal gammopathy of undetermined significance (2012)

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder occurring in 4.2% of adults &gt; 50 years of age, which can progress into symptomatic diseases either through proliferation of the plasma cell clone, giving rise to multiple myeloma and other lymphoplasmacellular neoplasms, or through organ damage caused by the monoclonal protein, as seen in light-chain amyloidosis and related conditions. Differential diagnosis of asymptomatic and symptomatic monoclonal gammopathies is the determinant for starting therapy. The criteria for determining end-organ damage should include markers of organ injury caused by the monoclonal protein. Patient assessment and optimal follow-up are now performed using risk stratification models that should also take into account the risk of developing AL amyloidosis. Patients with low-risk MGUS (approximately 40% of all MGUS patients) need limited assessment and very infrequent follow-up. The ongoing development of novel molecular biomarkers and advanced imaging techniques will improve the identification of high-risk patients who may benefit from early therapeutic intervention through innovative clinical trials.
The origin of white luminescence from silicon oxycarbide thin films (2014)

Silicon oxycarbide (SiCxOy) is a promising material for achieving strong room-temperature white luminescence. The present work investigated the mechanisms for light emission in the visible/ultraviolet range (1.5–4.0 eV) from chemical vapor deposited amorphous SiCxOythin films, using a combination of optical characterizations and electron paramagnetic resonance(EPR) measurements. Photoluminescence(PL) and EPR studies of samples, with and without post-deposition passivation in an oxygen and forming gas (H2 5 at. % and N2 95 at. %) ambient, ruled out typical structural defects in oxides, e.g., Si-related neutral oxygen vacancies or non-bridging oxygen hole centers, as the dominant mechanism for white luminescence from SiCxOy. The observed intense white luminescence (red, green, and blue emission) is believed to arise from the generation of photo-carriers by optical absorption through C-Si-O related electronic transitions,and the recombination of such carriers between bands and/or at band tail states. This assertion is based on the realization that the PL intensity dramatically increased at an excitation energy coinciding with the E04 band gaps of the material, as well as by the observed correlation between the Si-O-C bond density and the PLintensity. An additional mechanism for the existence of a blue component of the white emission is also discussed.
Sepsis: definitions and diagnosis. (1998)

There have been many attempts to provide a uniform definition for the diagnosis of sepsis that can be used for research and clinical purposes. Several definitions are too broad and, as a result, clinicians are unable to direct appropriate therapies to patients. Disappointing immunomodulatory trials have led many researchers to the conclusion that the current diagnostic criteria of sepsis fails to identify patients who could benefit from immunomodulatory therapies. In order to restore clinical and experimental relevance, many researchers and clinicians believe that sepsis should be defined as an inflammatory response to infection with signs of remote organ dysfunction. However, because common clinical signs of systemic inflammation are neither specific nor sensitive for sepsis, other markers may be helpful. Markers of the systemic inflammatory response to infection could include cytokines such as tumour necrosis factor alpha, interleukin 1, 6 and 8 and the propeptide procalcitonin. As well as identifying patients who may benefit from pro- or anti-inflammatory therapies, these markers may gauge the extent of the inflammatory response and could be used for monitoring the immune status of the patient.
Complementary DNA cloning of a receptor for tumor necrosis factor and demonstration of a shed form of the receptor. (1990)

Tumor necrosis factor (TNF) receptor (TNFR) was isolated as a 68-kDa glycoprotein from UC/HeLa 2-5 cells developed from a parental B-cell line (UC cells) to overexpress the receptor. Tryptic digests of two separate TNFR preparations provided amino acid sequences of four different peptides. Amino-terminal analysis indicated the presence of the amino-acid sequence Val-Ala-Phe-Thr-Pro, reported to be the amino-terminal sequence of a 30-kDa urinary TNF-binding protein II. Examination of the cultured medium of UC/HeLa 2-5 cells showed an abundance of a 40-kDa TNF-binding protein, indicating that the previously cited 30-kDa TNF-binding protein II is likely to be a shed form of the TNFR. Based on the peptide sequences, oligonucleotides were synthesized, and two of these were used as primers in the polymerase chain reaction to amplify cDNA sequences from poly(A)+ RNA of UC/HeLa 2-5 cells. These PCR fragments were radiolabeled and used to screen a cDNA library made from UC/HeLa 2-5 mRNA. Further analysis identified cDNA sequences that encoded the amino acid sequences of all four TNFR peptides. RNA blot-hybridization analysis of UC/HeLa 2-5 mRNA revealed a 3.8-kilobase transcript of the same size as the mRNA in the parental UC cells. Genomic Southern blots indicated the presence of a single gene in parental cells and a second, amplified gene in TNFR-overexpressing cells, suggesting amplification of the transfected gene as a possible mechanism for the increase in TNFR numbers in UC/HeLa 2-5 cells.
Structural modifications of the potassium channel activator cromakalim: the C-3 position (1991)

The syntheses of a selection of C-3 analogues of 6-cyano-3,4-dihydro-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-2H-1-benzopyran-3-ol, the potassium channel activator cromakalim 1, are described. Particular interest has focused on the corresponding 3-ketone 2 and compounds in which the hydroxy group of 1 has been replaced by fluorine, carbon and nitrogen containing residues. The hindered neopentylic nature of the C-3 hydroxy group in 1 has a marked effect on its reactivity and has necessitated the independent synthesis of many of these analogues from simpler precursors rather than from the direct modification of compound 1 itself.
Hierarchical recognition of CpG motifs expressed by immunostimulatory oligodeoxynucleotides (2003)

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs trigger human PBMC to proliferate and secrete Ig, cytokines and chemokines. CpG ODN have entered clinical trials, and show promise as vaccine adjuvants, antiallergens, and for the treatment of infectious diseases and cancer. ODNs under consideration for human use vary in the sequence, number and location of the CpG motifs they contain. Yet little is known of the magnitude of the immune response elicited by these diverse ODNs, or the rules governing their interaction with immune cells. This work compares the proliferative, IgM, IL-6 and IP-10 response of PBMC from normal donors to a diverse panel of CpG ODNs. Results indicate that ODNs expressing 3-4 different CpG motifs are strongly stimulatory. The location of these motifs is important, with those at the 5' end exerting the greatest influence on ODN activity. These findings provide a basis for the rational design of ODNs optimized for clinical use.
SiO2nanoparticles biocompatibility and their potential for gene delivery and silencing (2011)

Despite the extensive use of silica nanoparticles (SiO(2)NPs) in many fields, the results about their potential toxicity are still controversial. In this work, we have performed a systematic in vitro study to assess the biological impact of SiO(2)NPs, by investigating 3 different sizes (25, 60 and 115 nm) and 2 surface charges (positive and negative) of the nanoparticles in 5 cell lines (3 in adherence and 2 in suspension). We analyzed the cellular uptake and distribution of the NPs along with their possible effects on cell viability, membrane integrity and generation of reactive oxygen species (ROS). Experimental results show that all the investigated SiO(2)NPs do not induce detectable cytotoxic effects (up to 2.5 nM concentration) in all cell lines, and that cellular uptake is mediated by an endocytic process strongly dependent on the particle size and independent of its original surface charge, due to protein corona effects. Once having assessed the biocompatibility of SiO(2)NPs, we have evaluated their potential in gene delivery, showing their ability to silence specific protein expression. The results of this work indicate that monodisperse and stable SiO(2)NPs are not toxic, revealing their promising potential in various biomedical applications.
Improved Fourier coefficients for maps using phases from partial structures with errors (1986)

Unrefined or partially refined models of macromolecules are generally incomplete and typically have large coordinate errors. It is shown that phase probability equations appropriate for a perfect partial structure lead to inaccurate estimates of phase probabilities in such cases. Therefore, it is necessary to use equations that have been derived allowing for errors in the partial structure. A method is given to estimate the parameter σA in these phase probability expressions from the observed and calculated structure factor amplitudes. From the variation of σA with resolution, one can estimate the mean coordinate error for the model. Electron density maps calculated using partial structure phases are biased towards the partial structure. When there are coordinate errors, a new expression for the non-centric Fourier coefficients [(2m|FN| - D|FcP|) exp(iαcP)] is required to suppress this model bias. Judged by correlation coefficients comparing electron density maps with the correct and the partial structure maps, the Fourier coefficients derived here are superior to others currently in use.
ChemInform Abstract: Derivatives of o‐Phenylene Phosphate. Part 34. Halogenation of o‐Methoxyphenyl Phosphinites, Phosphonites, and Phosphites. (1986)

Abstract The o‐methoxyphenyl esters (III) (preparation described for the first time), and the analogous phenyl esters (VII) react with halogenes to yield the halogenophosphonium halides (IV) or (VIII), which are stabilized by ligand exchange with the Starting material to form phosphonium 132 salts or by elimination of alkyl halide to give cyclic phosphoranes or halogeno phosphates.
Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of Tie2 signaling in vascular progenitor cells (2004)

Inhibition by all-trans retinoic acid (atRA) of the microvasculature formation in chicken chorioallantoic membrane (CAM) accompanied remarkably reduced numbers of endothelial cells (ECs) and increased numbers of mural cells (MCs) under the chorionic epithelial layer. Ro41-5253 (retinoid antagonist) exerted the opposite effect. Although atRA did not affect the differentiation of murine embryonic stem cell-derived vascular progenitor cells (VPCs) into ECs or MCs, atRA suppressed EC-MC interaction, leading to impaired branching. In both atRA-treated VPC cultures and CAM tissues underneath the chorionic epithelial layer, the expression of angiopoietin-2 (Ang-2; competitor for Ang-1) was enhanced, whereas that of Tie2 (a receptor for Angs) was reduced. Simultaneous treatment with Ang-1 partially blocked RA induction of EC-MC malinteraction and reduction in blood vessel formation. These results suggest that retinoid(s) may reduce EC-MC interaction by down-regulating Tie2 signaling as well as decreased EC numbers, which lead to impaired vascular remodeling.
Determining relaxation times for porous media: Theory, measurement, and the inverse problem (2007)

This thesis provides an introduction to and analysis of the problem of determining nuclear magnetic resonance (NMR) relaxation times of porous media by using the so-called Carr-Purcell-Meiboom-Gill (CPMG) technique. We introduce the principles of NMR, the CPMG technique and the signals produced, porous effects on the NMR relaxation times and discuss various numerical methods for the inverse problem of extracting the relaxation times from CPMG signals. The numerical methods for solving Fredholm integral equations of the first kind are sketched from a series expansion perspective. A method of using arbitrary constituent functions for improving the performance of non-negative least squares (NNLS) is developed and applied to several synthesized data sets and real experimental data sets of saturated porous glass gels. The data sets were obtained by the author of this thesis and the experimental procedure will be presented. We discuss the imperfections in the assumptions on the physical and numerical models, the numerical schemes, and the experimental results, which may lead to new research possibilities.
Multiuser space-time block coded MIMO system with downlink precoding (2004)

Space-time block codes (STBC) are powerful tech- niques to achieve full spatial diversity in Rayleigh fading channels with low decoding complexity. When channel state information is available to the transmitter, space-time block codes can be improved through the use of a transmit precoder chosen based in part on the current channel state. In this paper, we investigate the downlink transmission of an Alamouti space-time block coded multiuser wireless system in which complete channel knowledge is available to the base transceiver station. A novel unitary precoder is proposed that, with enough antennas, can effectively precancel co-channel interference at each mobile user thus enabling simple single user space-time block decoding. It is shown that excess transmit antennas, beyond the minimum required for precancellation, can be used to further improve the diversity performance through careful selection of the precoding matrix. Though the derivation assumes perfect channel state information, the impact of estimation error is investigated by deriving an lower bound on the signal to interference plus noise ratio. Monte Carlo simulations show that our proposed downlink precoder can effectively cancel the interference between mobiles, while still providing good diversity performance.
Two dominant-acting selectable markers for gene transfer studies in mammalian cells. (1988)

We report the development of two dominant-acting genetic markers useful for monitoring gene transfer in mammalian cells that are based on prokaryotic genes encoding key steps in the synthesis of the essential amino acids, tryptophan and histidine. Under appropriate conditions, expression of these genes obviates the nutritional requirements for their respective amino acid products. Expression of the trpB gene of Escherichia coli, which encodes the beta subunit of tryptophan synthase (EC 4.2.1.20), allows mammalian cell survival and multiplication in medium containing indole in place of tryptophan. The hisD gene of Salmonella typhimurium encodes histidinol dehydrogenase (EC 1.1.1.23), which catalyzes the two-step NAD+-dependent oxidation of L-histidinol to L-histidine. In medium lacking histidine and containing histidinol, only mammalian cells expressing the hisD product survive. The selection is a double one in that the provided precursor histidinol is itself toxic to animal cells through its inhibition of histidyl-tRNA synthetase; thus, the dehydrogenase both removes an inhibitor and forms a required end product. Alternatively, the his selection may be carried out under conditions in which the dehydrogenase serves mainly to detoxify histidinol. For either the trp or his selections the substitute nutrient (indole or histidinol) is readily available, inexpensive, stable, permeable to cells, and convertible to the end product in a step controlled by a single gene. Vectors based upon murine retrovirus and papovavirus backbones have been successfully employed for both genes, allowing selection in a range of cell types, including 3T3, CV-1, and HeLa. These dominant selective schemes should provide generally useful and inexpensive alternatives to others currently in use, such as the gpt, neo, hygro, dhfr, and tk selections.
A CMOS delay locked loop and sub-nanosecond time-to-digital converter chip (1996)

Phase-locked loops have been employed in the past to obtain sub-nanosecond time resolution in high energy physics and nuclear science applications. An alternative solution based on a delay-locked loop (DLL) is described. This solution allows for a very high level of integration yet still offers resolution in the sub-nanosecond regime. Two variations on this solution are outlined. A novel phase detector, based on the Muller C-element, is used to implement a charge pump where the injected charge approaches zero as the loop approaches lock on the leading edge of an input clock reference. This greatly reduces timing jitter. In the second variation the loop locks to both the leading and trailing clock edges. In this second implementation, software coded layout generators are used to automatically layout a highly integrated, multichannel, time-to-digital converter (TDC) targeted for one specific frequency. The two circuits, DLL and TDC, are implemented in CMOS 1.21 /spl mu/m and 0.8 /spl mu/m technologies, respectively. Test results show a timing jitter of less than 30 ps for the DLL circuit and less than 190 ps integral and differential non-linearity for the TDC circuit.