gebhart/patrepeval huggingface dataset:
Metabolic regulation of rice α‐amylase and sucrose synthase genes in planta (1992)

Isolated rice embryos were used to investigate the regulatory effects of endosperm extracts and pure sugars on the expression of alpha-amylase gene RAmy3D and a sucrose synthase gene homologous to the maize isozyme Ss2. The high-level expression of RAmy3D in the scutella of isolated embryos could be inhibited by a variety of sugars as well as endosperm extracts from germinated rice grains. Glucose, at a concentration of 250 mM, was most effective in repressing RAmy3D mRNA accumulation. Furthermore, this repression was reversible. Interestingly, RAmy3D repression was always accompanied by the induction of sucrose synthase gene expression. These results support a model in which the expression of alpha-amylase and sucrose synthase genes in the rice scutellum are counter-regulated by the influx of sugars from the endosperm.
Structure Determination of Aquomet Porcine Hemoglobin at 2.8 Å Resolution (1994)

Considerable attention is currently focused on hemoglobins from lower mammals, such as the pig, for potential use in cell-free blood substitute preparations safe for use in humans. As the first step in the elucidation of structure-function relationships in porcine hemoglobin, we have determined the three-dimensional structure of aquomet porcine hemoglobin at 2.8 A resolution. Overall, the porcine hemoglobin tetramer is structurally similar to that of human oxyhemoglobin, and the r.m.s. deviation of all backbone atoms (minus five residues at the amino and carboxyl termini of each subunit) is 0.8 A. This similarity is not unexpected given that human and porcine hemoglobins exhibit 85% sequence identity. However, regions of subtle structural differences are implicated in subtle functional differences between the two proteins, such as the 20 to 25% inhibition of the alkaline Bohr effect and the accompanying reduction in oxygen-linked chloride binding observed for porcine hemoglobin. The structural similarity of these two mammalian hemoglobins also rationalizes the novel hybridization behavior of pig and human subunits in transgenic pigs expressing both porcine and human hemoglobins in porcine erythrocytes.
Aberrant Promoter CpG Islands Methylation of Tumor Suppressor Genes in Cholangiocarcinoma (2008)

Aberrant DNA methylation of 5'-CpG islands located within gene promoters has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. To ascertain the mechanism of gene promoter hypermethylation in cholangiocarcinoma (CC), we investigated promoter methylation status of the candidate genes ID4, DLC-1, and SFRP1 in 41 CCs, 19 adjacent nontumor tissues, and 15 normal liver tissues using methylation-specific PCR (MSP). The frequencies of DNA methylation were: 57.5% (23 of 40) for ID4, 14.3% (5 of 35) for DLC-1, and 63.4% (26 of 41) for SFRP1, respectively. In contrast, a low frequency of methylation was detected in nontumor tissues. In addition, hypermethylated status of these genes was detected in three kinds of CC cell lines. Moreover, the downregulated expression of these genes in these cells was restored by treatment with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor. Taken together, these results suggest that aberrant DNA methylation may contribute to the tumorigenesis of cholangiocarcinoma.
Femtosecond laser-induced two-photon polymerization of inorganic–organic hybrid materials for applications in photonics (2003)

Investigations of two-photon polymerization of inorganic-organic hybrid materials initiated by femtosecond Ti:sapphire laser pulses are performed. First applications of this technique for the fabrication of three-dimensional microstructures and photonic crystals in inorganic-organic hybrid polymers with a structure size down to 200 nm and a periodicity of 450 nm are discussed.
Engineered Soluble Monomeric IgG1 CH3 Domain (2013)

Most of the therapeutic antibodies approved for clinical use are full-size IgG1 molecules. The interaction of the IgG1 Fc with the neonatal Fc receptor (FcRn) plays a critical role in maintaining their long half-life. We have hypothesized that isolated Fc domains could be engineered to functionally mimic full-size IgG1 (nanoantibodies) but with decreased (10-fold) size. Here, we report for the first time the successful generation of a soluble, monomeric CH3 domain (mCH3). In contrast to the wild-type dimeric CH3, the mCH3 exhibited pH-dependent binding to FcRn similar to that of Fc. The binding free energy of mCH3 to FcRn was higher than that of isolated CH2 but lower than that of Fc. Therefore, CH3 may contribute a larger portion of the free energy of binding to FcRn than CH2. A fusion protein of mCH3 with an engineered antibody domain (m36.4) also bound to FcRn in a pH-dependent fashion and exhibited significantly higher neutralizing activity against HIV-1 than m36.4-Fc fusion proteins. The m36.4-mCH3 fusion protein was monomeric, stable, soluble, and expressed at a high level in Escherichia coli. We also found that engineering an additional disulfide bond in mCH3 remarkably increased its thermal stability, whereas the FcRn binding was not affected. These data suggest that mCH3 could not only help in the exploration of the dual mechanisms of the CH3 contribution to Fc functions (dimerization and FcRn interactions) but could also be used for the development of candidate therapeutics with optimized half-life, enhanced tissue penetration, access to sterically restricted binding sites, and increased therapeutic efficacy.
Persistence of survivin specific T cells for seven years in a melanoma patient During domplete remission (2006)

Monitoring and evaluation of biological responses induced by immunotherapy may provide important information with regards to efficacy, side effects, and potential improvements of treatment. Herein, we describe results from monitoring of T cell reactivity against survivin derived peptides, in a melanoma patient in complete remission following IL-2 based immunotherapy. The patient remains in complete remission five years after completion of therapy. Long-time persistence of anti-tumor responses is rarely monitored, however, in the present patient longitudinal examination of anti-survivin reactivity exceeded seven years. Throughout, survivin reactivity was monitored both by INFgamma-ELISPOT as well as by flow cytometry using HLA-multimers. Survivin specific T cell reactivity was found at all time points examined over the 7-year period. Moreover, using these two methods, similar precursor frequencies was found indicating that the majority of the survivin specific T cells posses functional capabilities. Our data demonstrate that anti-survivin T cells may persist in the periphery for extended periods in the absence of clinical manifestation of disease as well as autoimmunity.
The chicken β-globin insulator element conveys chromatin boundary activity but not imprinting at the mouseIgf2/H19domain (2002)

Imprinting of the mouse insulin-like growth factor 2 (Igf2) and H19 genes is regulated by an imprinting control region (ICR). The hypomethylated maternal copy functions as a chromatin insulator through the binding of CTCF and prevents Igf2 activation in cis, while hypermethylation of the paternal copy inactivates insulator function and leads to inactivation of H19 in cis. The specificity of the ICR sequence for mediating imprinting and chromatin insulation was investigated by substituting it for two copies of the chicken beta-globin insulator element, (Ch beta GI)(2), in mice. This introduced sequence resembles the ICR in size, and in containing CTCF-binding sites and CpGs, but otherwise lacks homology. On maternal inheritance, the (Ch beta GI)(2) was hypomethylated and displayed full chromatin insulator activity. Monoallelic expression of Igf2 and H19 was retained and mice were of normal size. These results suggest that the ICR sequence, aside from CTCF-binding sites, is not uniquely specialized for chromatin insulation at the Igf2/H19 region. On paternal inheritance, the (Ch beta GI)(2) was also hypomethylated and displayed strong insulator activity--fetuses possessed very low levels of Igf2 RNA and were greatly reduced in size, being as small as Igf2-null mutants. Furthermore, the paternal H19 allele was active. These results suggest that differential ICR methylation in the female and male germ lines is not acquired through differential binding of CTCF. Rather, it is likely to be acquired through a separate or downstream process.
Interleukin 7 receptor ligation stimulates tyrosine phosphorylation, inositol phospholipid turnover, and clonal proliferation of human B-cell precursors. (1991)

Functional interleukin 7 (IL-7) receptors are expressed on the surface of multiphenotypic, biphenotypic, and immature B-lineage human lymphoid precursor cells with germ-line immunoglobulin heavy-chain genes but not on more mature B-lineage lymphoid cells with rearranged and/or expressed immunoglobulin heavy-chain genes. Thus, IL-7 may have an important regulatory role during the earliest stages of human B-cell ontogeny. The engagement of the surface IL-7 receptors on immature B-cell precursor cells with recombinant human IL-7 (rhIL-7) results in enhanced tyrosine phosphorylation of multiple phosphoproteins, stimulates inositol phospholipid turnover and DNA synthesis, and promotes their clonal proliferation. These effects are (i) specific for rhIL-7, since rhIL-3, rhIL-4, rhIL-5, rhIL-6, and recombinant human granulocyte colony-stimulating factor do not elicit similar activities on IL-7 receptor-positive human pro-B cells; and (ii) mediated by IL-7 receptors, since they are not observed in IL-7 receptor-negative B-lineage lymphoid cell populations. rhIL-7-induced tyrosine phosphorylation on the 35-, 53-, 55-, 62-, 69-, 76-, 94-, 150-, 170-, and 190-kDa substrates as well as rhIL-7-induced stimulation of inositol phospholipid turnover are abrogated by the tyrosine kinase inhibitor genistein. These results demonstrate that the IL-7 receptor on immature human B-cell precursor populations is intimately linked to a functional tyrosine kinase pathway and tyrosine phosphorylation is an important and perhaps mandatory step in the generation of the IL-7 receptor-linked transmembrane signal.
Energy efficient sensor node implementations (2010)

In this paper, we discuss a low power embedded sensor node architecture we are developing for distributed sensor network systems deployed in a natural environment. In particular, we examine the sensor node for energy efficient processing-at-the-sensor. We analyze the following modes of operation; event detection, data acquisition, and data processing using low power, high performance embedded technology such as specialized embedded DSP processors and low power FPGAs at the sensing node. We use compute intensive sensor node applications: an acoustic vehicle classifier (frequency domain analysis) and a video license plate identification application (learning algorithm). We report performance and energy for these applications and discuss the system architecture design trade offs.
Donor pretreatment in cadaver renal transplantation. (1977)

Excellent cadaver allograft survival has been achieved with kidneys from cadaver donors pretreated with high intravenously given dosages of cyclophosphamide and intravenous injections of methylprednisolone. To test the efficacy of this method of pretreating the donor, allograft survival in 21 patients, group A, receiving kidneys from cadaver donors pretreated with 4 grams of cyclophosphamide and 4 to 6 grams of methylprednisolone given intravenously was compared with two other groups of cadaver allograft recipients, 39 patients, 23 group B patients receiving untreated kidneys harvested at the Mayo Clinic and 16 group C patients receiving untreated kidneys harvested elsewhere. Two year actuarial allograft survivors were 16 of 21 in group A, 13 of 23 in group B and seven of 16 in group C. We believe that cadaver donor pretreatment improves allograft survival significantly.
Pathogenetic Factors in Rheumatoid Synovitis (1988)

The role of cells and cytokmes in the pathology of rheumatoid synovitis is reviewed
Simulations of shock waves and cavitation bubbles produced in water by picosecond and nanosecond laser pulses (1998)

We compare numerical simulations of bubble dynamics in water with experiments performed at the Medizineisches Laserzentrum Lubeck. Spatial and temporal features of the laser beam were modeled. Plasma growth was predicted using a moving breakdown model. We compare the measured and calculated positions of the shock front and the bubble wall as a function of time after optical breakdown in water. Nd:YAG laser pulses of 30-ps 1-mJ and 6-ns 10-mJ were simulated. We have extended previous work in which picosecond deposition was modeled at temporally instantaneous and spatially uniform.
Performance and Fecal Flora of Calves Fed a Bacillus subtilis Concentrate (1991)

Eighty-four Holstein calves were assigned at 2 d of age to one of three treatments: 1) control with no additives; 2) 10 g of a mixed microbial concentrate containing Lactobacillus acidophilus, Lactobacillus lactis, and Bacillus subtilis; or 3) 10 g of a B. subtilis concentrate. The microbial concentrates were mixed with milk replacer during the a.m. feeding. The milk replacer was offered twice daily at 5% BW per feeding; the reconstituted replacer contained 12.5% DM. Volume of replacer fed was based on initial weight of calf and held constant until weaning. Water and starter ration were offered for ad libitum intake throughout the trial. Calves were weaned abruptly at 30 d of age and received only water and starter from d 31 to 44. General health and performance of all calves were good. Although differences in weight gain and feed efficiency were not significant, the B. subtilis concentrate tended to have a positive effect on feed efficiency during wk 1 to 4 and on immediate postweaning gain. A higher fecal bacilli count at 6 wk in calves fed the microbial concentrates may be related to their tendency for improved gain during d 31 to 44, the immediate postweaning period.
Forced Expression of Id-1 in the Adult Mouse Small Intestinal Epithelium Is Associated with Development of Adenomas (1998)

Ids are dominant-negative helix-loop-helix (HLH) proteins that play overlapping yet distinct roles in antagonizing basic HLH transcription factors. Although Ids affect myogenesis, neurogenesis, and B-cell development, little is known about their in vivo functions in epithelia. We have examined the effects of forced expression of Id-1 in the small intestinal epithelium of adult chimeric mice. 129/Sv embryonic stem cells, transfected with DNA containing Id-1 under the control of transcriptional regulatory elements that function in all intestinal epithelial cell lineages, were introduced into C57Bl/6 (B6) blastocysts heterozygous for the ROSA26 marker. The B6 ROSA26/+ intestinal epithelium of the resulting adult chimeras produces Escherichia coli beta-galactosidase, allowing identification of this internal control cell population. Chimeras produced from nontransfected embryonic stem cells served as additional controls. Immunohistochemical studies of the control chimeras indicated that the small intestinal epithelium supports a complex pattern of endogenous Id expression. Id-1 is restricted to the cytoplasm; levels do not decrease as descendants of multipotent intestinal stem cells differentiate. Id-2 and Id-3 are only detectable in nuclei; levels increase markedly as epithelial cells differentiate. Forced expression of Id-1 in the 129/Sv epithelium results in a decline in Id-2 and Id-3 to below the limits of immunodetection. A subset of chimeric-transgenic mice lacked growth factor- and defensin-producing Paneth cells in their 129/Sv epithelium and also developed intestinal adenomas. These changes were not present in normal control chimeras. Adenomas were composed of proliferating beta-Gal-positive and -negative epithelial cells, suggesting that they arose through cooperative interactions between 129/Sv(Id-1) and B6 ROSA26/+ cells. These chimeras provide a model for studying how perturbations in Id expression affect tumorigenesis.
A genome-wide search for schizophrenia susceptibility genes (1998)

We completed a systematic genome-wide search for evidence of loci linked to schizophrenia using a collection of 70 pedigrees containing multiple affected individuals according to three phenotype classifications: schizophrenia only (48 pedigrees; 70 sib-pairs); schizophrenia plus schizoaffective disorder (70 pedigrees; 101 sib-pairs); and a broad category consisting of schizophrenia, schizoaffective disorder, paranoid or schizotypal personality disorder, psychosis not otherwise specified (NOS), delusional disorder, and brief reactive psychosis (70 pedigrees; 111 sib-pairs). All 70 families contained at least one individual affected with chronic schizophrenia according to DSM-III-R criteria. Three hundred and thirty-eight markers spanning the genome were typed in all pedigrees for an average resolution of 10.5 cM (range, 0-31 cM) and an average heterozygosity of 74.3% per marker. The data were analyzed using multipoint nonparametric allele-sharing and traditional two-point lod score analyses using dominant and recessive, affecteds-only models. Twelve chromosomes (1, 2, 4, 5, 8, 10, 11, 12, 13, 14, 16, and 22) had at least one region with a nominal P value <0.05, and two of these chromosomes had a nominal P value <0.01 (chromosomes 13 and 16), using allele-sharing tests in GENEHUNTER. Five chromosomes (1, 2, 4, 11, and 13) had at least one marker with a lod score >2.0, allowing for heterogeneity. These regions will be saturated with additional markers and investigated in a new, larger set of families to test for replication.
Lead Optimization Studies on FimH Antagonists: Discovery of Potent and Orally Bioavailable Ortho-Substituted Biphenyl Mannosides (2012)

Herein, we describe the X-ray structure-based design and optimization of biaryl mannoside FimH inhibitors. Diverse modifications to the biaryl ring to improve druglike physical and pharmacokinetic properties of mannosides were assessed for FimH binding affinity based on their effects on hemagglutination and biofilm formation along with direct FimH binding assays. Substitution on the mannoside phenyl ring ortho to the glycosidic bond results in large potency enhancements several-fold higher than those of corresponding unsubstituted matched pairs and can be rationalized from increased hydrophobic interactions with the FimH hydrophobic ridge (Ile13) or "tyrosine gate" (Tyr137 and Tyr48) also lined by Ile52. The lead mannosides have increased metabolic stability and oral bioavailability as determined from in vitro PAMPA predictive model of cellular permeability and in vivo pharmacokinetic studies in mice, thereby representing advanced preclinical candidates with promising potential as novel therapeutics for the clinical treatment and prevention of recurring urinary tract infections.
Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells (2013)

We have investigated whether the recently discovered transcription factor, zinc finger BED domain-containing protein 6 (ZBED6), is expressed in insulin-producing cells and, if so, to what extent it affects beta cell function. ZBED6 was translated from a ZC3H11A transcript in which the ZBED6-containing intron was retained. ZBED6 was present in mouse βTC-6 cells and human islets as a double nuclear band at 115/120 kDa and as a single cytoplasmic band at 95-100 kDa, which lacked N-terminal nuclear localization signals. We propose that ZBED6 supports proliferation and survival of beta cells, possibly at the expense of specialized beta cell function-i.e., insulin production-because (i) the nuclear ZBED6 were the predominant forms in rapidly proliferating βTC-6 cells, but not in human islet cells; (ii) down-regulation of ZBED6 in βTC-6 cells resulted in altered morphology, decreased proliferation, a partial S/G2 cell-cycle arrest, increased expression of beta cell-specific genes, and higher rates of apoptosis; (iii) silencing of ZBED6 in the human PANC-1 duct cell line reduced proliferation rates; and (iv) ZBED6 binding was preferentially to genes that control transcription, macromolecule biosynthesis, and apoptosis. Furthermore, it is possible that beta cells, by switching from full length to a truncated form of ZBED6, can decide the subcellular localization of ZBED6, thereby achieving differential ZBED6-mediated transcriptional regulation.
Molecular Cloning and Functional Characterization of a Novel CC Chemokine, Stimulated T Cell Chemotactic Protein (STCP-1) That Specifically Acts on Activated T Lymphocytes (1997)

A novel human chemokine STCP-1 (stimulated T cell chemotactic protein) was isolated from an activated macrophage cDNA library. The chemokine has four cysteines positioned in a manner that identifies STCP-1 as a member of the CC chemokine family. The amino acid sequence shows 34% identity with RANTES. The gene consists of 3 exons and 2 introns with the position of intron/exon boundaries similar to that of RANTES. The gene is expressed as a 3.4-kilobase transcript on lymph node, thymus, and Appendix. STCP-1 induces Ca2+ mobilization in a small percentage of primary activated T lymphocytes, but on repeated stimulation the percentage of T lymphocytes that respond to STCP-1 increases. The chemokine STCP-1 does not induce Ca2+ mobilization in monocytes, dendritic cells, neutrophils, eosinophils, lipopolysaccharide-activated B lymphocytes, and freshly isolated resting T lymphocytes. Similarly, STCP-1, while acting as a mild chemoattractant for primary activated T lymphocytes, is a potent chemoattractant for chronically activated T lymphocytes but has no chemoattractant activity for monocytes, neutrophils, eosinophils, and resting T lymphocytes. As STCP-1 acts specifically on activated T lymphocytes, it may play a role in the trafficking of activated/effector T lymphocytes to inflammatory sites and other aspects of activated T lymphocyte physiology.
Flow cytometric monitoring of cellular anthracycline accumulation in murine leukemic cells. (1986)

Cellular accumulation of daunorubicin (DNR), N-trifluoroacetyl-adriamycin-14-valerate, and THP-Adriamycin (THP-ADR) in doxorubicin sensitive and resistant murine leukemic P388 cells was studied with laser excited flow cytometry. Appearance of DNR fluorescence in P388/S cells was rapid in contrast to that of P388/R cells. A comparison of P388/S and P388/R cells incubated for 20-30 min showed that DNR fluorescence in P388/R cells was one-sixth that of P388/S cells. In contrast, the difference between fluorescence value of P388/S and P388/R cells similarly incubated with N-trifluoroacetyl-adriamycin-14-valerate or THP-ADR was less than 2-fold. Chlorpromazine, verapamil, and trifluoperazine increased the cellular accumulation and cytotoxicity of DNR and THP-ADR but had no major effect on N-trifluoroacetyl-adriamycin-14-valerate fluorescence or cytotoxicity in P388/R cells. Fluorometric and soft agar assays confirmed the data on the effect of these modulators on drug accumulation obtained by the more rapid method of laser flow cytometry.
Regulation of Vein Graft Hyperplasia by Survivin, an Inhibitor of Apoptosis Protein (2005)

SVV is a critical regulator of multiple processes, including proliferation, apoptosis, and angiogenesis, that determine the remodeling response of vein grafts following arterialization.