gebhart/patrepeval huggingface dataset:
Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation-competent and -defective myeloid leukemic cells. (1993)

Myeloid leukemias that differ in their competence for induction of differentiation were analyzed for expression of bcl-2 and c-myc and for their sensitivity to induction of apoptosis by heat shock and cancer chemotherapy compounds. The M1 leukemia expressed a high level of bcl-2 and showed a much lower susceptibility to induction of apoptosis by heat shock, Adriamycin, 1-beta-D-arabinofuranosylcytosine, methotrexate, and cycloheximide, compared to five other leukemias which expressed a low level of bcl-2. There was no association between susceptibility to induction of apoptosis and competence for induction of differentiation. The difference in susceptibility to methotrexate, which is not regulated by the multidrug resistance (MDR) genes, and treatment with verapamil, which blocks MDR activity, have indicated that the higher resistance of the M1 leukemia to these agents was not due to MDR activity. The results indicate that the level of regulated bcl-2 expression in these myeloid leukemias was associated with cell susceptibility to induction of apoptosis by different apoptosis-inducing agents. Screening for expression of bcl-2 may thus be useful to characterize leukemias regarding susceptibility to induction of apoptosis by different agents. The level of regulated c-myc expressed in these leukemias was not associated with susceptibility to induction of apoptosis. Transfection with a deregulated mutant p53 into the M1 leukemia did not change susceptibility to apoptosis induction, but transfection with deregulated c-myc increased susceptibility to apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Phase 1 and Phase 2 Studies ofSalmonella entericaSerovar Paratyphi A O-Specific Polysaccharide-Tetanus Toxoid Conjugates in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam (2000)

Salmonella enterica serovar Paratyphi A O-specific polysaccharide (O-SP) was activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to tetanus toxoid (TT) with adipic acid dihydrazide as a linker (SPA-TT(1)) or directly (SPA-TT(2)). In mice, these two conjugates elicited high levels of immunoglobulin G (IgG) anti-lipopolysaccharide (LPS) in serum with bactericidal activity (E. Konadu, J. Shiloach, D. A. Bryla, J. B. Robbins, and S. C. Szu, Infect. Immun. 64:2709-2715, 1996). The safety and immunogenicity of the two conjugates were then evaluated sequentially in Vietnamese adults, teenagers, and 2- to 4-year-old children. None of the vaccinees experienced significant side effects, and all had preexisting LPS antibodies. At 4 weeks after injection, there were significant increases of the geometric mean IgG and IgM anti-LPS levels in the adults and teenagers: both conjugates elicited a greater than fourfold rise in the IgG anti-LPS level in serum in >/=80% of the volunteers. SPA-TT(2) elicited slightly higher, though not statistically significantly, levels of IgG anti-LPS than did SPA-TT(1) in these age groups. Accordingly, only SPA-TT(2) was evaluated in the 2- to 4-year-old children. On a random basis, one or two injections were administered 6 weeks apart to the children. No significant side effects were observed, and the levels of preexisting anti-LPS in serum were similar in children of all ages. A significant rise in the IgG anti-LPS titer was elicited by the first injection (P = 0.0001); a second injection did not elicit a booster response. Representative sera from all groups had bactericidal activity that could be adsorbed by S. enterica serovar Paratyphi A LPS.
¿Existe un curriculum postmoderno?: De las teorías curriculares de la modernidad al curriculum postmoderno (2002)

The turbulence of the curricular theories in the Modern Age, characterized by the polysemy of the term curriculum, and, recently, the disillusionment that the curricular theory is undergoing, make us think about the possibility of an emergent view of the curriculum, a post-modern curriculum. Nevertheless, it is necessary to reflect upon the risks and opportunities that the Post-modern Age offers, on the one hand, and the possibility that one metadiscourses which were the main issue in school matters in the Modern Age period, the curriculum, may become exhausted, on the other. In this paper we do not intend to defend extreme positions, we are really interested in a deeper perspective which in our opinion has to typify teachers in a changing society.
Nuclear gene silencing directs reception of long-distance mRNA silencing in Arabidopsis (2007)

In plants, silencing of mRNA can be transmitted from cell to cell and also over longer distances from roots to shoots. To investigate the long-distance mechanism, WT and mutant shoots were grafted onto roots silenced for an mRNA. We show that three genes involved in a chromatin silencing pathway, NRPD1a encoding RNA polymerase IVa, RNA-dependent RNA polymerase 2 ( RDR2 ), and DICER-like 3 ( DCL3 ), are required for reception of long-distance mRNA silencing in the shoot. A mutant representing a fourth gene in the pathway, argonaute4 ( ago4 ), was also partially compromised in the reception of silencing. This pathway produces 24-nt siRNAs and resulted in decapped RNA, a known substrate for amplification of dsRNA by RDR6. Activation of silencing in grafted shoots depended on RDR6, but no 24-nt siRNAs were detected in mutant rdr6 shoots, indicating that RDR6 also plays a role in initial signal perception. After amplification of decapped transcripts, DCL4 and DCL2 act hierarchically as they do in antiviral resistance to produce 21- and 22-nt siRNAs, respectively, and these guide mRNA degradation. Several dcl genotypes were also tested for their capacity to transmit the mobile silencing signal from the rootstock. dcl1–8 and a dcl2 dcl3 dcl4 triple mutant are compromised in micro-RNA and siRNA biogenesis, respectively, but were unaffected in signal transmission.
gamma/delta T cell-deficient mice have impaired mucosal immunoglobulin A responses. (1996)

Mucosal tissues of mice are enriched in T cells that express the gamma/delta T cell receptor. Since the function of these cells remains unclear, we have compared mucosal immune responses in gamma/delta T cell receptor-deficient (TCRdelta-/-) mice versus control mice of the same genetic background. The frequency of intestinal immunoglobulin (Ig) A plasma cells as well as IgA levels in serum, bile, saliva, and fecal samples were markedly reduced in TCRdelta-/- mice. The TCRdelta-/- mice produced much lower levels of IgA antibodies when immunized orally with a vaccine of tetanus toxoid plus cholera toxin as adjuvant. Conversely, the antigen-specific IgM and IgG antibody responses were comparable to orally immunized control mice. Direct assessment of the cells forming antibodies against the tetanus toxoid and cholera toxin antigens indicated that significantly lower numbers of IgA antibody-producing cells were present in the intestinal lamina propria and Peyer's patches of TCRdelta-/- mice compared with the orally immunized control mice. The selective reduction of IgA responses to ingested antigens in the absence of gamma/delta T cells suggests a specialized role for gamma/delta cells in mucosal immunity.
Detection of single base-pair mismatches in DNA by chemical modification followed by electrophoresis in 15% polyacrylamide gel. (1986)

We have developed a method for distinguishing fragments of DNA that contain single-base mismatches from their perfectly paired homologues. Single-stranded regions within a duplex fragment are accessible to 1-cyclohexyl-3-(2-[4-(4-methyl)morpholinyl]ethyl)carbodiimide, which reacts with unpaired guanidylate and thymidylate residues in DNA. Intact linear duplex DNA molecules do not react with carbodiimide, whereas DNA molecules containing single-base mismatches react quantitatively. After carbodiimide reaction, the DNA molecules are electrophoresed in high-percentage polyacrylamide gels so that modified and unmodified fragments can be resolved. Application of this technique should make it possible to locate and purify DNA fragments that exhibit sequence differences from those that do not; these might be used to signal phenotypic variation as well as to diagnose inherited disease.
Neurostimulation approaches to primary headache disorders (2009)

These findings will help to further elucidate the clinical potential of neurostimulation in chronic headache.
Surface area of the small intestine in man. (1967)

COMMENT This paper sets out the principles for measuring the surface area of small intestine and demonstrates that it decreases sharply from proximal to distal intestine.
Hemophilia A due to mutations that create new N-glycosylation sites. (1992)

In studying the molecular defects responsible for cross-reacting material-positive hemophilia A, we have identified two patients in whom the nonfunctional factor VIII-like protein has abnormal, slower-moving heavy or light chains on SDS/PAGE. Both patients have severe hemophilia A (less than 1% of normal factor VIII activity) with a normal plasma level of factor VIII antigen. The molecular defects were identified by denaturing gradient gel electrophoresis screening of PCR-amplified products of the factor VIII-coding DNA sequence followed by nucleotide sequencing of the abnormal PCR products. In patient ARC-21, a methionine-to-threonine substitution at position 1772 in the factor VIII light chain creates a potential new N-glycosylation site at asparagine-1770. In patient ARC-22, an isoleucine-to-threonine substitution at position 566 creates a potential new N-glycosylation site at asparagine-564 in the A2 domain of the factor VIII heavy chain. The mobility of these chains on SDS/PAGE was normal after N-Glycanase digestion and procoagulant activity was generated--to a maximum of 23% and 45% of control normal plasma. Abnormal N-glycosylation, blocking factor VIII procoagulant activity, represents a newly recognized mechanism for the pathogenesis of severe hemophilia A.
Human monoclonal single chain antibodies (HuScFv) that bind to the polymerase proteins of influenza A virus. (2008)

Current anti-influenza drugs target the viral neuraminidase or inhibit the function of the ion channel M2 protein. Not only is the supply of these drugs unlikely to meet the demand during a large influenza epidemic/ pandemic, but also has an emergence of drug resistant influenza virus variants been documented. Thus a new effective drug or antiviral alternative is required. The influenza virus RNA polymerase complex consists of nucleoproteins (NP) that bind to three polymerase subunits: two basic polymerases, PB1 and PB2, and an acidic polymerase (PA). These proteins play a pivotal role in the virus life cycle; thus they are potential targets for the development of new anti-influenza agents. In this study, we produced human monoclonal antibodies that bound to the influenza A polymerase proteins by using a human antibody phage display library. Complementary DNA was prepared from the total RNA of a highly pathogenic avian influenza (HPAI) virus: A/duck/Thailand/144/2005(H5N1). The cDNA synthesized from the total virus RNA was used as template for the amplification of the gene segments encoding the N-terminal halves of the PB1, PB2 and PA polymerase proteins which encompassed the biologically active portions of the respective proteins. The cDNA amplicons were individually cloned into appropriate vectors and the recombinant vectors were introduced into Escherichia coli bacteria. Transformed E. coli clones were selected, and induced to express the recombinant proteins. Individually purified proteins were used as antigens in bio-panning to select the phage clones displaying specific human monoclonal single chain variable fragments (HuScFv) from a human antibody phage display library constructed from Thai blood donors in our laboratory. The purified HuScFv that bound specifically to the recombinant polymerase proteins were prepared. The inhibitory effects on the biological functions of the respective polymerase proteins should be tested. We envisage the use of the HuScFv in their cell penetrating version (transbodies) as an alternative influenza therapeutic to current anti-virus drugs.
Differentially expressed genes in androgen-dependent and -independent prostate carcinomas. (1997)

Differential gene expression between androgen-dependent (LNCaP-FGC) and androgen-independent (LNCaP-LNO) prostate cancer cells has been investigated using RNA arbitrarily primed and differential display PCR of mRNA. Four differentially expressed cDNA transcripts were identified, of which differential expression was confirmed by Northern blot analysis. Sequence analysis revealed two unknown (JC19 and GC79) and two known genes [B-cell translocation gene 1 and UDP-glucuronosyltransferase 2B15 (UGT2B15)]. JC19, GC79, and B-cell translocation gene 1 were more highly expressed in LNCaP-FGC cells compared with LNCaP-LNO cells, whereas UGT2B15 was only expressed in LNCaP-LNO cells. Androgens and 1,25-dihydroxyvitamin D3 were able to down-regulate UGT2B15 mRNA in LNCaP-LNO cells. For GC79 mRNA, down-regulation was only observed with androgens in LNCaP-FGC cells. Expression of JC19 mRNA was studied using a panel of human prostate cancer xenografts. In androgen-dependent xenografts, expression of JC19 mRNA was much higher compared with androgen-independent xenografts, in which significant expression was hardly detectable. The mRNA expression pattern in the xenografts is in good agreement with that observed in the cell culture system. In conclusion, the differential display technique used in the present study allows analysis of gene expression in vitro and in vivo and can be used for the identification of important genes involved in androgen-independent prostate cancer development.
Differential Expression of Alternatively Spliced Forms of MAP4: A Repertoire of Structurally Different Microtubule-Binding Domains (1995)

We previously reported that the microtubule (MT)-binding domain of microtubule-associated protein 4 (MAP4) contains three 18-amino acid imperfect repeats that are homologous to the repeats found in the MT-binding domains of the neuronal MAPs, MAP2 and tau [Chapin, S. J., & Bulinski, J. C. (1991) J. Cell Sci. 98, 27-36]. Here we report the isolation of clones encoding additional isoforms of MAP4, which differ in the number of repeated elements contained within their MT-binding domains. In addition to clones encoding three repeats, we isolated clones encoding a four-repeat isoform, whose MT-binding domain bears a striking similarity to the four-repeat isoform of tau. Other MAP4 clones that we isolated encode five repeats. The additional repeat in the five-repeat isoform of MAP4 is quite unusual in its amino acid sequence; this unusual repeat was also found by Aizawa et al. [Aizawa, H., et al. (1990) J. Biol. Chem. 265, 13849-13855] among the repeats encoded by bovine MAP4 clones possessing four repeats. In humans, MAP4 was recently shown to be encoded by a single-copy gene [West, R. R., et al. (1991) J. Biol. Chem. 266, 21886-21896]; we demonstrated that the human MAP4 gene is located on human chromosome 3p21. Expression of multiple MAP4 isoforms from this gene, which appears to result from alternative RNA splicing, was investigated by RNase protection analysis of mammalian cell lines and rat tissues. The five-repeat isoform was the only form detectable in most cell lines, and it was the most abundant isoform expressed in rat lung, liver, kidney, spleen, and testis. However, in rat brain, heart, and skeletal muscle, although the five-repeat isoform was expressed at all developmental stages examined, the tau-like four-repeat isoform was also expressed, and its expression increased during development. The three-repeat isoform was expressed in heart and, to a lesser extent, in brain, skeletal muscle, and lung. Our results demonstrate that several different MAP4 isoforms are expressed in the rat in different tissues and at various developmental stages. Furthermore, our data suggest that differential expression of MAP4 isoforms possessing distinct MT-binding domains may be involved in the changes in MT dynamics or function that are known to accompany differentiation.
Lrp4, a Novel Receptor for Dickkopf 1 and Sclerostin, Is Expressed by Osteoblasts and Regulates Bone Growth and Turnover In Vivo (2009)

Lrp4 is a multifunctional member of the low density lipoprotein-receptor gene family and a modulator of extracellular cell signaling pathways in development. For example, Lrp4 binds Wise, a secreted Wnt modulator and BMP antagonist. Lrp4 shares structural elements within the extracellular ligand binding domain with Lrp5 and Lrp6, two established Wnt co-receptors with important roles in osteogenesis. Sclerostin is a potent osteocyte secreted inhibitor of bone formation that directly binds Lrp5 and Lrp6 and modulates both BMP and Wnt signaling. The anti-osteogenic effect of sclerostin is thought to be mediated mainly by inhibition of Wnt signaling through Lrp5/6 within osteoblasts. Dickkopf1 (Dkk1) is another potent soluble Wnt inhibitor that binds to Lrp5 and Lrp6, can displace Lrp5-bound sclerostin and is itself regulated by BMPs. In a recent genome-wide association study of bone mineral density a significant modifier locus was detected near the SOST gene at 17q21, which encodes sclerostin. In addition, nonsynonymous SNPs in the LRP4 gene were suggestively associated with bone mineral density. Here we show that Lrp4 is expressed in bone and cultured osteoblasts and binds Dkk1 and sclerostin in vitro. MicroCT analysis of Lrp4 deficient mutant mice revealed shortened total femur length, reduced cortical femoral perimeter, and reduced total femur bone mineral content (BMC) and bone mineral density (BMD). Lumbar spine trabecular bone volume per total volume (BV/TV) was significantly reduced in the mutants and the serum and urinary bone turnover markers alkaline phosphatase, osteocalcin and desoxypyridinoline were increased. We conclude that Lrp4 is a novel osteoblast expressed Dkk1 and sclerostin receptor with a physiological role in the regulation of bone growth and turnover, which is likely mediated through its function as an integrator of Wnt and BMP signaling pathways.
Phase I and Pharmacologic Study of SNS-032, a Potent and Selective Cdk2, 7, and 9 Inhibitor, in Patients With Advanced Chronic Lymphocytic Leukemia and Multiple Myeloma (2010)

SNS-032 demonstrated mechanism-based target modulation and limited clinical activity in heavily pretreated patients with CLL and MM. Further single-agent, PD-based, dose and schedule modification is warranted to maximize clinical efficacy.
Molecular biology underlying the clinical heterogeneity of prostate cancer: an update. (2009)

Prostatic adenocarcinoma is a heterogeneous group of neoplasms with a broad spectrum of pathologic and molecular characteristics and clinical behaviors. Numerous mechanisms contribute to the development of resistance to androgen ablation therapy, resulting in ligand-independent reactivation of the androgen receptor, including amplification, mutation, phosphorylation, and activation of coreceptors. Multiple translocations of members of the ETS oncogene family are present in approximately half of clinically localized prostate cancers. TMPRSS2:ERG gene rearrangement appears to be an early event in prostate cancer and is not observed in benign or hyperplastic prostatic epithelium. Duplication of TMPRSS2:ERG appears to predict a worse prognosis. The relationship between TMPRSS2:ERG gene rearrangement and other morphologic and prognostic parameters of prostate cancer is still unclear.
Acceleration of genetic gain in cattle by reduction of generation interval (2015)

Genomic selection (GS) approaches, in combination with reproductive technologies, are revolutionizing the design and implementation of breeding programs in livestock species, particularly in cattle. GS leverages genomic readouts to provide estimates of breeding value early in the life of animals. However, the capacity of these approaches for improving genetic gain in breeding programs is limited by generation interval, the average age of an animal when replacement progeny are born. Here, we present a cost-effective approach that combines GS with reproductive technologies to reduce generation interval by rapidly producing high genetic merit calves.
Ultrastructure of a cloned astrocytoma in tissue culture (1971)

The ultrastructure of a cloned astrocytoma line which produces a protein unique to the nervous system (S-100 protein) is described. The cells have features that are consistent with an origin from neoplastic astrocytes. They are characterized by a sparsity of organelles and the presence of many fine filaments in their cytoplasm. Two classes of filaments are present. One type is 90 to 100 Å in diameter filaments that frequently appear hollow, are gently curved, can be followed for long distances in thin sections, and are arranged in loose fascicles. These filaments are similar to the cytoplasmic filaments in normal and neoplastic astrocytes in vivo but are more loosely arrayed in TC-158 cells than in normal astrocytes. The other type is 70 to 75 Å filaments that are uniformly electron dense, straight, can only be followed for short distances in sections, and are arranged in compact bundles. These filaments are without counterpart in normal or neoplastic astrocytes in vivo although they are frequently seen in cultured cells from diverse origins (so-called “stress fibers”). In TC-158 cells examined with the light microscope, PTAH-stainable fibrils are present that mimic the distribution of the fine bundles of 70 to 75 Å filaments seen in the electron microscope. We suggest that the PTAH-stainable fibrils and bundles of 70 to 75 Å filaments share a common identity in TC-158 astrocytes. Although PTAH-staining fibrils in cultured astrocytes have been called “gliofibrils” in the literature, our results indicate that they are analogous to the “stress fibers” which are a nonspecific finding when present in cultured cells.
Ex Vivo Expansion of Haematopoietic Stem Cells to Improve Engraftment in Stem Cell Transplantation (2011)

The efficient use of haematopoietic stem cells (HSC) for transplantation is often limited by the relatively low numbers of HSC collected. The ex vivo expansion of HSC for clinical use is a potentially valuable and safe approach to increase HSC numbers thereby increasing engraftment and reducing the risk of morbidity from infection. Here we describe a protocol for the robust ex vivo expansion of human CD34(+) HSC isolated from umbilical cord blood. The protocol described can efficiently generate large numbers of HSC. We also describe a flow cytometry-based method using high resolution division tracking to characterise the kinetics of HSC growth and differentiation. Utilising the guidelines discussed, it is possible for investigators to use this protocol as presented or to modify it for their specific needs.
Inhibition of activator protein 1 signaling abrogates transforming growth factor β–mediated activation of fibroblasts and prevents experimental fibrosis (2011)

AP-1 is up-regulated in a TGFβ-dependent manner in SSc. The selective AP-1 inhibitor T-5224 reduced collagen synthesis selectively in SSc fibroblasts and efficiently prevented the development of experimental dermal fibrosis. Thus, AP-1 might be a promising new molecular target for the treatment of SSc.