gebhart/patrepeval huggingface dataset:
CD8α+ and CD8α− Subclasses of Dendritic Cells Direct the Development of Distinct T Helper Cells In Vivo (1999)

Cells of the dendritic family display some unique properties that confer to them the capacity to sensitize naive T cells in vitro and in vivo. In the mouse, two subclasses of dendritic cells (DCs) have been described that differ by their CD8alpha expression and their localization in lymphoid organs. The physiologic function of both cell populations remains obscure. Studies conducted in vitro have suggested that CD8alpha+ DCs could play a role in the regulation of immune responses, whereas conventional CD8alpha- DCs would be more stimulatory. We report here that both subclasses of DCs efficiently prime antigen-specific T cells in vivo, and direct the development of distinct T helper (Th) populations. Antigen-pulsed CD8alpha+ and CD8alpha- DCs are separated after overnight culture in recombinant granulocyte/macrophage colony-stimulating factor and injected into the footpads of syngeneic mice. Administration of CD8alpha- DCs induces a Th2-type response, whereas injection of CD8alpha+ DCs leads to Th1 differentiation. We further show that interleukin 12 plays a critical role in Th1 development by CD8alpha+ DCs. These findings suggest that the nature of the DC that presents the antigen to naive T cells may dictate the class selection of the adaptative immune response.
A novel platform to enable the high-throughput derivation and characterization of feeder-free human iPSCs (2012)

Human induced pluripotent stem cells (hiPSCs) hold enormous potential, however several obstacles impede their translation to industrial and clinical applications. Here we describe a platform to efficiently generate, characterize and maintain single cell and feeder-free (FF) cultured hiPSCs by means of a small molecule cocktail media additive. Using this strategy we have developed an effective multiplex sorting and high-throughput selection platform where individual clonal hiPSC lines are readily obtained from a pool of candidate clones, expanded and thoroughly characterized. By promoting survival and self-renewal, the selected hiPSC clones can be rapidly expanded over multiple FF, single-cell passages while maintaining their pluripotency and genomic stability as demonstrated by trilineage differentiation, karyotype and copy number variation analysis. This study provides a robust platform that increases efficiency, throughput, scale and quality of hiPSC generation and facilitates the industrial and clinical use of iPSC technology.
Semiconductor memories for IT era (2003)

Information technology (IT) emerged from the 1970s based on main-frame computers. Since then, PCs and the Internet world have drastically expanded the IT industry along with rapid growth of network and communication technology. For almost all platforms, semiconductor memories have been a key enabling technology. In the PC era, DRAM density increase has been driven by rapid expansion of applications with advanced operating systems. In the future, servers will continue driving high-density DRAM requirements, and the maximum memory size of servers will be one of the key performance parameters. 512 Mb DRAM will be widely available in 2002 and 16 Gb DRAM is expected to appear within the next 10 years. Performance of semiconductor memories will be driven by graphics applications and network systems. 1 Gb/s/pin DRAM will be popular in 2002 and 2 Gb/s/pin in 2004 for high-end graphics applications. Random-access times in the range of 5 ns for SRAM and 20 ns for DRAM range and 1 Gb/s/pin DRAM will be available in 2002, and even faster (frequency, latency) memories will be required for high-end network systems such as OC-768-based switches and routers and beyond. Mobile platforms, especially 3 G phones and PDAs, are driving low-voltage low-power memories. Standby power of DRAM and pseudo-SRAM has been reduced drastically over the last 2 years. 1.8 V DRAM will be in volume production in 2002 and 1.0 V DRAM is expected in 2005 for longer battery life and moving-picture capability of mobile applications. The small-form-factor requirement of mobile phones and consumer applications such as PDA, and DSC will expedite various multi-chip-package solutions such as SRAM+Flash, DRAM+Flash, and SRAM+DRAM+Flash. Recent digital convergence and the rapid reduction of $/MB of mass storage flash memory increased the usage of flash memory in various mobile and consumer applications. Semiconductor memory will continue to follow Moore's Law for at least the next 10 years and will be lead by mass storage flash memory technology. Memory requirement of various IT platforms will continue to increase the trend of MB/system and MB/person.
Differential effects of recombinant human leukocyte interferons on cell surface antigen expression. (1986)

Human leukocyte (alpha) interferon (IFN-alpha) is composed of a multigene family within which at least eight different species have been expressed in Escherichia coli, isolated, and shown to exert a wide range of biological activities on different human target cells. In this study we utilized eight species of IFN-alpha (A, B, C, D, F, I, J, and K) and investigated their respective capabilities to alter the proliferation of a human breast carcinoma cell line (MCF-7). The antigens studied were all constitutively expressed on the MCF-7 cell surface: the Mr 180,000 carcinoembryonic antigen; a high molecular weight (greater than 10(6] glycoprotein, termed tumor-associated glycoprotein 72; and a major HLA histocompatibility antigen. The level of expression of each antigen was measured by the binding of monoclonal antibodies B1.1, B72.3, and W6/32, respectively. A high degree of diversity was found among the various IFN-alpha species with respect to their ability to enhance antigen expression and inhibit MCF-7 cell growth. The two most potent species, IFN-alpha A and IFN-alpha B, were found to increase the expression of tumor antigens as well as the HLA determinant by 2-5-fold. In contrast, IFN-alpha D and IFN-alpha J were virtually inactive in altering antigen expression but did inhibit the growth of MCF-7 cells. The remaining IFN-alpha species, -alpha C, -alpha F, -alpha I, and -alpha K, exerted an intermediate range of activities for both antigen enhancement and inhibition of MCF-7 cell growth. The relative ability of each species of IFN-alpha to inhibit MCF-7 cell growth appeared to be independent of their effectiveness in augmenting antigen expression. IFN-alpha D and IFN-alpha J, the two species that failed to alter tumor antigen expression, did, however, seem to interact with the interferon receptor since they inhibited MCF-7 cell growth and competed with other IFN-alpha species for the increase in carcinoembryonic antigen, tumor-associated glycoprotein 72, or HLA expression. A comparison of the concentrations of each IFN-alpha necessary to enhance antigen expression revealed that the surface HLA determinant was approximately 10-fold more sensitive to enhancement than was the tumor antigen, carcinoembryonic antigen. The individual members of the IFN-alpha family thus differ extensively in their ability to alter the level of antigen expression on the surface of MCF-7 breast carcinoma cells.(ABSTRACT TRUNCATED AT 400 WORDS)
NMR structure of oxidized Escherichia coli glutaredoxin: Comparison with reduced E. coli glutaredoxin and functionally related proteins (1992)

The determination of the NMR structure of oxidized Escherichia coli glutaredoxin in aqueous solution is described, and comparisons of this structure with that of reduced E. coli glutaredoxin and the related proteins E. coli thioredoxin and T4 glutaredoxin are presented. Based on nearly complete sequence-specific 1H-NMR assignments, 804 nuclear Overhauser enhancement distance constraints and 74 dihedral angle constraints were obtained as the input for the structure calculations, for which the distance geometry program DIANA was used followed by simulated annealing with the program X-PLOR. The molecular architecture of oxidized glutaredoxin is made up of three helices and a four-stranded beta-sheet. The three-dimensional structures of oxidized and the recently described reduced glutaredoxin are very similar. Quantitative analysis of the exchange rates of 34 slowly exchanging amide protons from corresponding series of two-dimensional [15N,1H]-correlated spectra of oxidized and reduced glutaredoxin showed close agreement, indicating almost identical hydrogen-bonding patterns. Nonetheless, differences in local dynamics involving residues near the active site and the C-terminal alpha-helix were clearly manifested. Comparison of the structure of E. coli glutaredoxin with those of T4 glutaredoxin and E. coli thioredoxin showed that all three proteins have a similar overall polypeptide fold. An area of the protein surface at the active site containing Arg 8, Cys 11, Pro 12, Tyr 13, Ile 38, Thr 58, Val 59, Pro 60, Gly 71, Tyr 72, and Thr 73 is proposed as a possible site for interaction with other proteins, in particular ribonucleotide reductase. It was found that this area corresponds to previously proposed interaction sites in T4 glutaredoxin and E. coli thioredoxin. The solvent-accessible surface area at the active site of E. coli glutaredoxin showed a general trend to increase upon reduction. Only the sulfhydryl group of Cys 11 is exposed to the solvent, whereas that of Cys 14 is buried and solvent inaccessible.
A Moloney MLV-Rat Somatotropin Fusion Gene Produces Biologically Active Somatotropin in a Transgenic Pig (1988)

Expression of a Moloney murine leukemia virus (MLV) rat somatotropin fusion gene was examined in a transgenic pig. The fusion gene was integrated in a single site within the genome in a tandem array with approximately eight copies per cell. The integrated in a single site within the genome in a tandem array with approximately eight copies per cell. The integrated MLV-rat somatotropin fusion gene produced high levels of circulating rat somatotropin and resulted in an elevation in the circulating levels of insulin-like growth factor I. Although there was no increase in the rate of growth of the transgenic animal during the rapid growth phase, several phenotypic changes were evident. Skeletal growth was markedly increased and fat deposition was reduced throughout the animal. Blood glucose levels were elevated without ketosis. Northern blot analyses of rat somatotropin RNA revealed that expression of the fusion gene was highest in the spleen, lung, intestine, lymph nodes, and bone marrow. These results show that the MLV promoter can be used to express high levels of biologically active rat somatotropin in transgenic swine.
Useful preparations involving the reactions of nucleophiles with some trimethylammonio-derivatives of nitrogen heterocycles (1972)

Methods are described for the preparation of alkoxy-, amino-, n-propylamino-, hydrazino-, mercapto-, fluoro-, and cyano-derivatives of pyridine, pyrimidine, quinoline, quinazoline, and purine by treatment of the corresponding trimethylammonio-compound with the appropriate nucleophile.
Expression of Neutrophil Collagenase (Matrix Metalloproteinase-8) in Human Atheroma (2001)

These data point to MMP-8 as a previously unsuspected participant in collagen breakdown, an important determinant of the vulnerability of human atheroma.
Syntheses of 4-(2-naphthyl)pyridine derivatives from DDNP (2015)

The ethylidenemalononitrile side-chain in {1-[6-(dimethylamino)-2-naphthyl]ethylidene}malononitrile (DDNP) was elaborated into a substituted pyridine ring in a two-step process. In this manner formal derivatives of a molecular probe (1-{6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), which is successfully applied in positron emission tomography to diagnose Alzheimer's Disease, were prepared. Chloroimidate intermediate in reaction of a nitrile group with HCl in alcoholic solution was trapped in the form of 2-chloro-4-[6-(dimethylamino)-2-naphthyl)nicotinonitrile, thus proving its existence in the Pinner synthesis. The structure of 2-methylamino derivative was also proven by X-ray analysis.
Computer-assisted knee arthroplasty versus a conventional jig-based technique (2004)

We have compared a new technique of computer-assisted knee arthroplasty with the current conventional jig-based technique in 70 patients randomly allocated to receive either of the methods. Post-operative CT was performed according to the Perth CT Knee Arthroplasty protocol and pre- and post-operative Maquet views of the limb were taken. Intra-operative and peri-operative morbidity data were collected and blood loss measured. Post-operative CT showed a significant improvement in the alignment of the components using computer-assisted surgery in regard to femoral varus/valgus (p = 0.032), femoral rotation (p = 0.001), tibial varus/valgus (p = 0.047) tibial posterior slope (p = 0.0001), tibial rotation (p = 0.011) and femorotibial mismatch (p = 0.037). Standing alignment was also improved (p = 0.004) and blood loss was less (p = 0.0001). Computer-assisted surgery took longer with a mean increase of 13 minutes (p = 0.0001).
Systemic Exposure to Irradiated Apoptotic Cells Induces Autoantibody Production (1998)

During apoptotic cell death, cell surface ligands initiate phagocytosis of the dying cell. Clearance of these apoptotic cells is thought to occur without an immune response. Since a number of autoantigens are located at the cell surface or within apoptotic blebs, we examined whether exposure of mice to syngeneic apoptotic cells by the intravenous route could induce autoantibody production. Normal mice injected with syngeneic apoptotic thymocytes developed antinuclear autoantibodies and anticardiolipin and anti-ssDNA antibodies. The autoantibody levels were generally lower than those observed in MRL/Faslpr mice and were transient. Surprisingly, six out of six immunized mice demonstrated immunoglobulin G deposition in the glomeruli several months after immunization. These findings indicate that systemic exposure to apoptotic cells can induce an immune response in normal mice, and may help to explain antigen selection and initiation of the immune response in diseases characterized by increased rates of apoptosis such as AIDS and, possibly, systemic lupus erythematosus.
Micro‐chemical surface investigation of brittle carthaginian and roman silver artefacts (2012)

Brittle Carthaginian and Roman silver artefacts, such as bracelets, coins, small jewels and cups, were found in extremely brittle condition during archaeological excavations in different Italian archaeological sites. Some of these silver objects are accidentally easily broken with little applied force and with only small deformation. In order to identify the origin of brittleness, fresh fractured surfaces have been investigated by means of the combined use of surface and micro analytical techniques such as X‐ray photoelectron spectroscopy, scanning electron microscopy (SEM) and field‐emission SEM (FESEM) equipped with an energy dispersive X‐ray spectrometer, optical microscopy and X‐ray diffraction. The overall experimental findings show that the main external brittleness agents are chloride ions that come from the soil of the excavation sites and attack the silver artefacts along the grain boundaries forming a thin layer or islands of silver chloride. Copyright © 2012 John Wiley &amp; Sons, Ltd.
The pattern of joining (JH) gene usage in the human IgH chain is established predominantly at the B precursor cell stage (1992)

Preferential utilization of JH and D genes has been demonstrated in the rearranged IgH chain in human peripheral B cells. We report here that the same hierarchy of JH gene usage is observed in leukemic cells arrested in the B precursor stage of differentiation. Specifically, JH4 and JH6 accounted for 42.9% and 35.7%, respectively, of the JH gene usage in the leukemias compared with an expected frequency of 16.7% assuming unbiased gene usage. Within the D gene families, the DN1 gene appears to be overutilized in both populations, representing about 15% of the total gene usage compared with an expected frequency of 3.2%. Because 21 of the 36 leukemias contained only nonproductive IgH rearrangements, the preferential gene usage could not have arisen from pre-B cells that have undergone clonal selection after a productive rearrangement but before surface Ig expression. Nonproductive rearrangements exhibited the biased gene usage seen for productive rearrangements. These findings suggest that a recombination bias favoring certain segments may be the actual mechanism responsible for the apparent preferential utilization of JH and D genes.
Using Sybil for interactive comparative genomics of microbes on the web (2011)

The S.pneumoniae resource is online at http://strepneumo-sybil.igs.umaryland.edu. The software, database and website are available for download as a portable virtual machine and from http://sourceforge.net/projects/sybil.
Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. (1997)

To understand the genetic basis and clonal evolution underlying metastatic progression of human breast cancer in vivo, we analyzed the genetic composition of 29 primary breast carcinomas and their paired asynchronous metastases by comparative genomic hybridization and fluorescence in situ hybridization. The mean number of genetic changes by comparative genomic hybridization was 8.7 +/- 5.3 in primary tumors and 9.0 +/- 5.7 in their metastases. Although most of the genetic changes occurred equally often in the two groups, gains of the Xq12-q22 region were enriched in the metastases. According to a statistical analysis of shared genetic changes and breakpoints in paired specimens, 20 of the metastases (69%) showed a high degree of clonal relationship with the corresponding primary tumor, whereas the genetic composition of 9 metastases (31%) differed almost completely from that of the paired primary tumors. In both groups, however, chromosome X inactivation patterns suggested that the metastatic lesions originated from the same clone as the primary tumor. Fluorescence in situ hybridization analysis with probes specific to metastatic clones usually failed to find such cells in the primary tumor sample. In conclusion, detailed characterization of the in vivo progression pathways of metastatic breast cancer indicates that a linear progression model is unlikely to account for the progression of primary tumors to metastases. An early stem line clone apparently evolves independently in the primary tumor and its metastasis, eventually leading to multiple, genetically almost completely different, clones in the various tumor locations in a given patient. The resulting heterogeneity of metastatic breast cancer may underlie its poor responsiveness to therapy and explain why biomarkers of prognosis or therapy responsiveness measured exclusively from primary tumors give a restricted view of the biological properties of metastatic breast cancer.
Refolding of therapeutic proteins produced inEscherichia coli as inclusion bodies (1999)

Overexpression of cloned or synthetic genes in Escherichia coli often results in the formation of insoluble protein inclusion bodies. Within the last decade, specific methods and strategies have been developed for preparing active recombinant proteins from these inclusion bodies. Usually, the inclusion bodies can be separated easily from other cell components by centrifugation, solubilized by denaturants such as guanidine hydrochloride (Gdn-HCl) or urea, and then renatured through a refolding process such as dilution or dialysis. Recent improvements in renaturation procedures have included the inhibition of aggregation during refolding by application of low molecular weight additives and matrix-bound renaturation. These methods have made it possible to obtain high yields of biologically active proteins by taking into account process parameters such as protein concentration, redox conditions, temperature, pH, and ionic strength.
On multi-carrier code division multiple access (MC-CDMA) modem design (2002)

Standard spread-spectrum techniques encounter a severe performance loss under channels with large Doppler spread. It is shown that the novel spread-spectrum technique, called multi-carrier (MC) CDMA, is dual to direct-sequence CDMA. This enables to derive that MC-CDMA is a signalling technique which allows optimum detection under severe Doppler spread. The receiver for this is a RAKE receiver in the frequency domain.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Expression of Epiregulin and Amphiregulin and K-ras Mutation Status Predict Disease Control in Metastatic Colorectal Cancer Patients Treated With Cetuximab (2007)

Patients with tumors that have high gene expression levels of epiregulin and amphiregulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment. The identified markers could be developed further to select patients for cetuximab therapy.
New and Emerging Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis: What is New and What is to Come (2012)

The therapeutic landscape for multiple sclerosis (MS) is rapidly changing. Currently, there are eight FDA approved disease modifying therapies for MS including: IFN-β-1a (Avonex, Rebif), IFN-β-1b (Betaseron, Extavia), glatiramer acetate (Copaxone), mitoxantrone (Novantrone), natalizumab (Tysabri), and fingolimod (Gilenya). This review will highlight the experience to date and key clinical trials of the newest FDA approved agents, natalizumab and fingolimod. It will also review available efficacy and safety data on several promising therapies under active investigation including four monoclonal antibody therapies: alemtuzumab, daclizumab, ocrelizumab and ofatumumab and three oral agents: BG12, laquinimod, and teriflunomide. To conclude, we will discuss where each of these new therapies may best fit into treatment algorithms.
Oxidative Stress And Potassium Channel Function (2002)

1. Modulation of K+ channel activities by cellular oxidative stress has emerged as a significant determinant of vasomotor function in multiple disease states. 2. Evidence from in vitro and in vivo studies suggest that superoxide (O2-) and hydrogen peroxide (H2O2) enhance BKCa channel activity in rat and cat cerebral arterioles; however, activity is decreased by peroxynitrite (ONOO-) in rat cerebral arteries. The mechanisms of changes in BKCa channel properties are not fully understood and may involve oxidation of cysteine residues that are located in the cell membranes. 3. Studies further suggest that O2- increases KATP channel activity in guinea-pig cardiac myocytes, but decreases opening in cerebral vasculature. Both H2O2 and ONOO- enhance KATP channel activity in the myocardium and in coronary, renal, mesenteric and cerebral vascular beds. Alteration of KATP channels by free radicals may be due to oxidation of SH groups or changes in the cytosolic concentration of ATP. 4. It does appear that O2- produced by either reaction of xanthine and xanthine oxidase or elevated levels of glucose reduces Kv channel activity and the impairments can be partially restored by free radical scavengers, superoxide dismutase and catalase. 5. Thus, redox modulation of potassium channel activity is an important mechanism regulating cell vascular smooth muscle membrane potential.