gebhart/patrepeval huggingface dataset:
In vivorepopulating hematopoietic stem cells are present in the murine yolk sac at day 9.0 postcoitus (1997)

The murine yolk sac, being the first site of embryonic blood cell production, has long been theorized to contain the migrating hematopoietic stem cells (HSC) that seed the liver and initiate hematopoiesis on day 10.0 postcoitus (pc). However, it remains controversial whether yolk sac cells isolated before day 11.0 pc possess any long-term repopulating HSC activity upon transplantation into adult recipient mice. We hypothesized that failure to demonstrate engraftment of day <11.0 yolk sac cells in adult hosts may result from an inability of yolk sac cells to home to the active adult hematopoietic sites (spleen and bone marrow). In the present studies, we transplanted yolk sac cells into conditioned newborn mice in whom the liver, as well as the spleen and bone marrow, concomitantly function as a site of blood cell formation. We report that yolk sac cells isolated from day 9.0 pc embryos provide long-term multilineage reconstitution for at least 11 months in primary conditioned newborn mice and for at least 6 months in secondary recipients. Donor yolk sac HSC progeny repopulated mature peripheral blood, thymus, spleen, and bone marrow lymphoid, myeloid, and erythroid compartments. Thus, day 9.0 pc yolk sac HSC can contribute to definitive multilineage hematopoiesis in transplanted recipients. Determination of HSC activity in the day 9.0 pc murine yolk sac suggests that yolk sac HSC are available to seed the liver on day 10.0 pc when definitive hematopoiesis is initiated.
Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of normal size. (1994)

We compared the effect of lipid composition and particle size of triglyceride-rich low density lipoprotein (LDL) upon apoprotein B conformation and binding to the LDL receptor. Three groups of triglyceride-rich LDL were studied: (a) LDL isolated from chronic hypertriglyceridemic individuals (HTG-LDL); (b) normal LDL made triglyceride-rich by in vitro incubation with triglyceride emulsion and the neutral lipid transfer protein (R-LDL); and (c) LDL from normolipidemic individuals made acutely hypertriglyceridemic by intravenous infusion of 10% Intralipid (IV-LDL). HTG-LDL was small and dense, whereas R-LDL and IV-LDL had normal size. HTG-LDL, but not R-LDL or IV-LDL, exhibited decreased binding to the LDL receptor on human skin fibroblasts in studies at 4 degrees C and reduced degradation at 37 degrees C. Apoprotein B conformation was assessed by circular dichroism and by analyzing the immunoreactivity of different monoclonal antibodies. HTG-LDL but not R-LDL or IV-LDL showed a change in the CD spectra and a consistent decrease in the immunoreactivity of monoclonal antibody 3F5 (2.5-fold) which recognizes an epitope adjacent to the receptor binding domain of apoprotein B. These findings suggest that in triglyceride-rich LDL, the relative content of neutral lipid in the core of LDL in the absence of changes in the size of the particle does not significantly affect apoprotein B conformation or its affinity for the LDL receptor.
Interference by Human Antibodies with Tumor Marker Assays (1995)

Many cancer patients respond to the in vivo application of murine monoclonal antibodies with the formation of various human antibodies which can interfere with tumor marker assays. While interferences by nonspecific human anti-mouse antibodies can be eliminated by addition of nonspecific mouse IgG, special problems can occur when the antibody applied in vivo also is employed in the in vitro assay. In ovarian cancer patients treated with the anti-CA-125 antibody OC125 and with the anti-TAG-72 antibody B72.3, respectively, we measured erroneous values for the tumor associated antigens CA-125 and TAG-72 due to human antiidiotypic or antiantiidiotypic antibodies. These interferences can only be prevented by using reagent antibodies different from the antibody applied in vivo. However, because it is difficult to eliminate interferences completely, tumor marker values determined in patients treated with monoclonal antibodies should be interpreted with care.
NUCLEAR AND MITOCHONDRIAL COMPARTMENTATION OF OXIDATIVE STRESS AND REDOX SIGNALING (2005)

New methods to measure thiol oxidation show that redox compartmentation functions as a mechanism for specificity in redox signaling and oxidative stress. Redox Western analysis and redox-sensitive green fluorescent proteins provide means to quantify thiol/disulfide redox changes in specific subcellular compartments. Analyses using these techniques show that the relative redox states from most reducing to most oxidizing are mitochondria > nuclei > cytoplasm > endoplasmic reticulum > extracellular space. Mitochondrial thiols are an important target of oxidant-induced apoptosis and necrosis and are especially vulnerable to oxidation because of the relatively alkaline pH. Maintenance of a relatively reduced nuclear redox state is critical for transcription factor binding in transcriptional activation in response to oxidative stress. The new methods are applicable to a broad range of experimental systems and their use will provide improved understanding of the pharmacologic and toxicologic actions of drugs and toxicants.
Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy (2016)

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy.
REACTIVITY OF THE GERMANIUM SURFACE: Chemical Passivation and Functionalization (2006)

With the rapidly changing materials needs of modern microelectronics, germanium provides an opportunity for future-generation devices. Controlling germanium interfaces will be essential for this purpose. We review germanium surface reactivity, beginning with a description of the most commonly used surfaces, Ge(100) and Ge(111). An analysis of oxide formation shows why the poor oxide properties have hindered practical use of germanium to date. This is followed by an examination of alternate means of surface passivation, with particular attention given to sulfide, chloride, and hydride termination. Specific tailoring of the interface properties is possible through organic functionalization. The few solution functionalization methods that have been studied are reviewed. Vacuum functionalization has been studied to a much greater extent, with dative bonding and cycloaddition reactions emerging as principle reaction mechanisms. These are reviewed through molecular reaction studies that demonstrate the versatility of the germanium surface.
Way Memoization to Reduce Fetch Energy in Instruction Caches (2001)

Instruction caches consume a large fraction of the total power in modern low-power microprocessors. In particular, set-associative caches, which are preferred because of lower miss rates, require greater access energy on hits than direct-mapped caches; this is because of the need to locate instructions in one of several ways. Way prediction has been proposed to reduce power dissipation in conventional set-associative caches; however, its application to CAMtagged caches, which are commonly used in low-power designs, is problematic and has not been quantitatively examined. We propose way memoization as an alternative to way prediction. As in way prediction schemes, way memoization stores way information (links) within the instruction cache, but in addition maintains a valid bit per link that when set guarantees that the way link is valid. In contrast, way prediction schemes must always read one tag to verify that the prediction is correct. Way memoization requires a link invalidation mechanism to maintain the coherence of link information. We investigate several invalidation schemes and show that simple conservative global invalidation schemes perform similarly to exact invalidation schemes but with much lower implementation cost. Based on HSPICE simulations of complete cache layouts in a 0.25 �m CMOSprocess, and processor simulations running SPECint95 and MediaBench benchmarks, we show that way memoization reduces the energy of a highly-optimized 16 KB 64-way CAM-tag low-power instruction cache by 21%, an additional 13 % savings compared to a way-predicting cache. 1
Self‐Condensation of Activated Malonic Acid Half Esters: A Model for the Decarboxylative Claisen Condensation in Polyketide Biosynthesis. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
From single-user architectural design to PAC* (1997)

This article nqmts our tiection on softsvam amhiteetm modelling for multi-usersystems (or groupware).Fi~w introduce t.k notion of software architecture and make explieit the design steps that most sofl-wam designm in HCI tend to blend in a fizzy way. Building on general concepts and pmetiee fmm main stream soikm engineering, we then present a comparative analysis of the most signifhnt architecture models developed for singleand multi-user systems. We close with the pmentation d PAC*, a new arehitectuml fmmwodc for modelling and designing the sdsvare amhitectm of multi-user systems. PAC* is a motivated combination of existing anAiteetuml models seleeted for the complementarily of their "good properties". These include operational heuristics such as rules for deriving agents in accordance to the task model or criteria for reasoning about replication as well as properties such as support for style heterogeneity, portability, and reusability.
The solubility and recrystallization of 1,3,5-triamino-2,4,6-trinitrobenzene in a 3-ethyl-1-methylimidazolium acetate–DMSO co-solvent system (2008)

Ionic liquids have previously been shown to dissolve strong inter- and intramolecular hydrogen-bonded solids, including natural fibers. Much of this solubility is attributed to the anions in ionic liquids, which can disrupt hydrogen bonding. We have studied the solubility and recrystallization of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), a very strong inter- and intramolecular hydrogen-bonded solid, in various ionic liquid solvent systems. We discovered that acetate-based ionic liquids were the best solvents for dissolving TATB, while other anions, such as Cl−, HSO4− and NO3− showed moderate improvements in the solubility compared to conventional organic solvents. Ionic liquid–DMSO co-solvent systems were also investigated for dissolving and recrystallizing TATB.
Macroporous chitin affinity membranes for lysozyme separation (1998)

Macroporous chitin membranes with high, controlled porosity and good mechanical properties have been prepared using a technique developed in this laboratory based on silica particles as porogen. They were employed for the affinity separation of lysozyme. Chitin membranes (1 mm thickness) can be operated at high fluxes (>/=1.1 mL/min/cm(2)) corresponding to pressure drops >/=2 psi. Their adsorption capacity for lysozyme ( approximately 50 mg/mL membrane) is by an order of magnitude higher than that of the chitin beads employed in column separation. In a binary mixture of lysozyme and ovalbumin, the membranes showed very high selectivity towards lysozyme. The effect of some important operation parameters, such as the flow rates during loading and elution were investigated. Lysozyme of very high purity (>98%) was obtained from a mixture of lysozyme and ovalbumin, and from egg white. The results indicate that the macroporous chitin membranes can be used for the separation, purification, and recovery of lysozyme at large scale. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 610-617, 1997.
Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk. (1996)

Despite the fact that breast cancer is the most common non-cutaneous cancer and a leading cause of cancer deaths in women, accepted markers of breast cancer risk miss up to 40% of these tumors. Moreover, screening methods involving the analysis of tissue or cells are limited by the need for a surgical biopsy. Nipple aspiration is a quick, efficient, noninvasive method to obtain breast epithelial cells, the cells at risk for transformation to carcinoma. Prostate-specific antigen (PSA), a protein thought to be specific to the prostate but recently found in a subset of breast tumors, has been correlated with improved survival. The purpose of this study was to measure PSA in a group of women with increasing breast cancer risk (no risk or family history of breast cancer, precancerous mastopathy, and invasive cancer) and determine if PSA correlates with risk. Nipple aspirate fluid was obtained from the intact breast and from surgical specimens using a modified breast pump. PSA was then measured in the fluid using a highly sensitive and specific immunofluorometric procedure. PSA was found at levels ranging from 0-13,423 ng/g of total protein, and there was a significant relationship between PSA level and breast cancer risk (P = 0.001). That is, all women with no risk factors and 90% of those with a family history had high PSA levels, whereas 68% of subjects with precancerous mastopathy or invasive cancer had low PSA levels. PSA was higher in premenopausal subjects (P = 0.002). After adjusting for the effect of menopausal status, there remained a significant association between PSA and breast cancer risk. These findings suggest that PSA in nipple aspirate fluid may be a useful marker of breast cancer risk.
SUPPORT VECTOR MACHINES FOR AUTOMATIC DETECTION OF TUBERCULOSIS BACTERIA IN CONFOCAL MICROSCOPY IMAGES (2007)

This paper presents an image segmentation method based on support vector machines classifiers at a pixel level. We apply this method to quantify the amount of Mycobacterium tuberculosis in confocal microscopy images for drug-discovery within the context of high content screening (HCS). To deal with the performance constraints of HCS, we propose a model-selection algorithm that finds the best classifier's hyperparameters by optimizing both classification rate and complexity. We validate our HCS adapted approach against commonly used readout techniques
Prediction of germ‐line transformation events in chimeric Ro transgenic soybean plantlets using tissue‐specific expression patterns (1992)

Summary Chimeric soybean plants derived from electric discharge particle acceleration experiments were used to develop relationships between tissue‐specific expression patterns of a marker gene and germ‐line transformation events in R o plants. Using the GUS histochemical assay the likelihood of germ‐line transformation was correlated to the localization of enzyme activity in specific tissues of the parent plant. The expression patterns of the 35S‐GUS marker gene in specific tissue types in R o plants and correlation with transmission of the introduced gene to progeny allowed the production of a clear picture of the development of these plants and their germ‐line cells. Advances reported in this article resulted in the development of a commercial process for the genetic improvement of this important staple crop which until recently was very recalcitrant to conventional transformation methods.
Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation (1997)

The expression of activation antigens, namely CD25, CD69, CD71, and HLA-DR on T cells from 15 healthy individuals stimulated with different mitogens and specific antigens was evaluated by immunofluorescence assay and flow cytometric analysis and compared with cell proliferation as a function of [3H]thymidine incorporation. CD69 was the earliest expressed antigen on stimulated cells, while HLA-DR was the latest. Regardless of the stimulus used, lymphocytes expressing CD25 and CD71 were always more numerous than cells expressing CD69 and HLA-DR. Variations in the proportion of CD4+ and CD8+ T cells expressing each activation marker were observed with different antigenic stimuli. The expression of each activation marker showed overall agreement with the [3H]thymidine incorporation assay in discriminating between positive and negative immune response. However, no correlation was observed between the percentage of CD25-, CD69-, CD71-, and HLA-DR-positive T cells and the amount of [3H]thymidine incorporation. Moreover, low doses of mitogens and antigens as well as short time of stimulation were sufficient to induce T cells to express activation antigens but not to proliferate. Our data show that results obtained by flow cytometry and [3H]thymidine incorporation may differ qualitatively, at least under certain conditions; this suggests that the 2 assays are complementary, and when combined, may gives a clearer understanding of events leading to efficient cell-mediated immune response.
Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficient Tumor Cell Growth (2007)

The effect of the antidiabetic drug metformin on tumor growth was investigated using the paired isogenic colon cancer cell lines HCT116 p53(+/+) and HCT116 p53(-/-). Treatment with metformin selectively suppressed the tumor growth of HCT116 p53(-/-) xenografts. Following treatment with metformin, we detected increased apoptosis in p53(-/-) tumor sections and an enhanced susceptibility of p53(-/-) cells to undergo apoptosis in vitro when subject to nutrient deprivation. Metformin is proposed to function in diabetes treatment as an indirect activator of AMP-activated protein kinase (AMPK). Treatment with AICAR, another AMPK activator, also showed a selective ability to inhibit p53(-/-) tumor growth in vivo. In the presence of either of the two drugs, HCT116 p53(+/+) cells, but not HCT116 p53(-/-) cells, activated autophagy. A similar p53-dependent induction of autophagy was observed when nontransformed mouse embryo fibroblasts were treated. Treatment with either metformin or AICAR also led to enhanced fatty acid beta-oxidation in p53(+/+) MEFs, but not in p53(-/-) MEFs. However, the magnitude of induction was significantly lower in metformin-treated cells, as metformin treatment also suppressed mitochondrial electron transport. Metformin-treated cells compensated for this suppression of oxidative phosphorylation by increasing their rate of glycolysis in a p53-dependent manner. Together, these data suggest that metformin treatment forces a metabolic conversion that p53(-/-) cells are unable to execute. Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin.
Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis. (1996)

Neuraminidases (sialidases) have an essential role in the removal of terminal sialic acid residues from sialoglycoconjugates and are distributed widely in nature. The human lysosomal enzyme occurs in complex with beta-galactosidase and protective protein/cathepsin A (PPCA), and is deficient in two genetic disorders: sialidosis, caused by a structural defect in the neuraminidase gene, and galactosialidosis, in which the loss of neuraminidase activity is secondary to a deficiency of PPCA. We identified a full-length cDNA clone in the dbEST data base, of which the predicted amino acid sequence has extensive homology to other mammalian and bacterial neuraminidases, including the F(Y)RIP domain and "Asp-boxes." In situ hybridization localized the human neuraminidase gene to chromosome band 6p21, a region known to contain the HLA locus. Transient expression of the cDNA in deficient human fibroblasts showed that the enzyme is compartmentalized in lysosomes and restored neuraminidase activity in a PPCA-dependent manner. The authenticity of the cDNA was verified by the identification of three independent mutations in the open reading frame of the mRNA from clinically distinct sialidosis patients. Coexpression of the mutant cDNAs with PPCA failed to generate neuraminidase activity, confirming the inactivating effect of the mutations. These results establish the molecular basis of sialidosis in these patients, and clearly identify the cDNA-encoded protein as lysosomal neuraminidase.
Dienes in the Diels-Alder reaction (1990)

Classifications: Dienes Dienophilic Center Diels-AlderReaction: Diene Dienophile Reactivity and FMO Theory Regioselectivity Stereoselectivity Open-Chain Dienes:1,3-Butadienes Hetereo-1,3-Butadienes References Outer-RingDienes: Reactivity, Selectivity, Synthesis Tables of Diels-AlderReactions References Inner-Outer Ring Dienes: Reactivity,Selectivity, Synthesis Tables of Diels-Alder Reactions References Across-Rings Dienes Reactivity, Selectivity,Synthesis References Inner-Ring Dienes: Carbocyclic Dienes Six-Membered Rings Seven-, Eight-, and Ten- Membered Rings Aromatic Hydrocarbons Heterocyclic Dienes BenzofusedFive-Membered Rings Six-Membered Rings.
Identification of Human Cadherin-14, a Novel Neurally Specific Type II Cadherin, by Protein Interaction Cloning (1997)

Cadherins, a family of Ca2+-dependent cell-cell adhesion molecules, mediate neural cell-cell interactions and may play important roles in neural development. By searching for molecules that interact with beta-catenin, a cytoplasmic regulator of cadherins, we have identified a new member of the cadherin family, which we named human cadherin-14. Cadherin-14 had high amino acid sequence homology with the type II subgroup of cadherins and was broadly expressed in the central nervous system. Cadherin-14 is a novel neurally specific cell-cell adhesion molecule and may regulate neural morphogenesis.
Profiling cancer testis antigens in non–small-cell lung cancer (2016)

Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.