gebhart/patrepeval huggingface dataset:
Solid-Phase Synthesis of Nucleoside Analogues (2003)

The synthesis of a 25 000 member library of nucleoside analogues as discrete compounds in milligram quantities is described. The use of the Nanokan technology developed by IRORI (Discovery Partners International) together with macroporous solid support allowed us to develop a highly reliable and practical synthetic route for the high-throughput derivatization of both the pyrimidine and purine nucleoside scaffold. A 2',3'-acetal linkage of the scaffolds to the solid support proved to be stable enough for the chemical transformations employed, yet labile enough for mild cleavage conditions to yield final products in high purity. The publication represents an example for combining synthetic organic chemistry on advanced scaffolds with the latest technologies of combinatorial chemistry in order to provide both industrial and academic institutions with compounds in high number and quality, thereby accelerating the search for novel biological targets and drug development.
A Prototype Optical Tracking System: Investigation and Development (2009)

Tracking of an object in six degrees-of-freedom (DOF) produces a position and orientation estimate of the object as it moves in 3D space. This thesis investigates the design and implementation of a prototype optical 6 DOF tracking system. Although optical scanners potentially have issues regarding occlusion they have advantages over electromagnetic scanners in that they can be used without distortion near ferromagnetic materials and can have large working volumes. This thesis focuses on the design of a small camera module named the ‘Black Spot’ that forms part of the overall tracking system. This module is capable of tracking the locations of up to 27 LED markers at 60 frames/s as the module moves in space. These markers provide fixed reference points that are utilised by the tracking system. A number of these modules will, in future revisions of the system, be clustered closely together forming a tracking hub. In this research this hub has been partially implemented in software on a PC. This software implements a ‘pose estimation’ algorithm that iteratively refines the location and position of the camera modules. Results from testing three Black Spot modules indicates that the locations of the LED markers can be determined very precisely using a centroid calculation. Standard deviations of better than 0.01 pixels have been recorded using these modules. The pose estimation algorithm has been tested revealing the need for a better minimisation algorithm. It is recommended that a bundle adjustment algorithm is used in the future to refine the world model used by the hub. The calibration of the system is a task for future research.
Specificity of transcriptional regulation by the zinc finger transcription factors Sp1, Sp3, and Egr‐1 (2004)

The transcription factors Sp1, Sp3, and Egr-1 bind with their zinc finger DNA-binding domains to GC-rich sequences in the regulatory regions of their target genes. The similarity of the DNA-binding sites of Sp1, Sp3, and Egr-1 has triggered the hypothesis that they compete for the same DNA-binding site. We have investigated the specificity of transcriptional regulation by Sp1, Sp3, and Egr-1 using dominant-negative mutants that block the DNA-binding site of Sp1, Sp3, or Egr-1, respectively. The results show that constitutive transcription of Sp1 regulated reporter genes, containing Sp1 sites derived from the aldolase C and p21WAF1/Cip1 genes, or the long terminal repeat of HIV-1, was impaired by dominant-negative mutants of Sp1 and Sp3, but not by a dominant-negative Egr-1. Transcription mediated by Egr-1 was induced by transfection of expression vectors encoding wild-type or mutated Egr-1 or by stimulation of the extracellular signal-regulated protein kinase pathway via an inducible B-Raf-estrogen receptor fusion protein. In all cases transcription of Egr-1-regulated reporter genes, containing Egr-1 binding sites derived from the Egr-1 or the synapsin I gene was impaired by a dominant-negative Egr-1, but not by dominant-negative Sp1 or Sp3 mutants. These results show that there are genuine Sp1/Sp3 or Egr-1 controlled genes showing no cross-regulation of Sp1/Sp3 and Egr-1 through the same DNA-binding site. This does not exclude the existence of composite Sp1/Sp3/Egr-1 binding sites, where competition for a common DNA-binding site occurs.
Natural and recombinant bovine interferon tau regulate basal and oxytocin-induced secretion of prostaglandins F2 alpha and E2 by epithelial cells and stromal cells in the endometrium (1994)

The effects of bovine interferon tau (IFN tau) and oxytocin on secretion of the prostaglandins PGF2 alpha and PGE2 by epithelial and stromal cells in the endometrium were assessed in two experiments. Endometrial tissues were collected from cyclic cows at Day 15 after oestrus for subsequent isolation of epithelial cells (4 cows) and stromal cells (4 cows). In both experiments, confluent cells were treated with 0, 2, 10 or 50 ng mL-1 natural bovine IFN tau (nbIFN tau) or 0, 0.4, 2, 10, 50 and 250 ng mL-1 recombinant bIFN tau (rbIFN tau). Culture medium was sampled at 24 h. Oxytocin (2.0 x 10(-7) M) or placebo was then added to wells and the medium was sampled 30 and 90 min later. Epithelial cells secreted more PGF2 alpha than stromal cells whereas stromal cells predominantly secreted PGE2. Oxytocin stimulated secretion of PGF2 alpha and PGE2 (P < 0.01) from epithelial cells, but both basal secretion and oxytocin-induced secretion of PGF2 alpha and PGE2 decreased with increasing dose of either nbIFN tau or rbIFN tau (P < 0.01). At comparable doses, rbIFN tau inhibited PGF2 alpha and PGE2 secretion more strongly than did nbIFN tau (either in the absence or the presence of oxytocin). The minimal effective dose of rbIFN tau was 0.4 ng mL-1 and 50% inhibition was obtained with 1 ng mL-1 (0.043 nM). Neither nbIFN tau nor rbIFN tau nor oxytocin altered PGF2 alpha or PGE2 secretion by stromal cells. The results indicate differential prostaglandin responses by the two major endometrial cell types (epithelium and stroma) to regulatory agents such as bIFN tau and oxytocin in cattle. Suppression of prostaglandin secretion by bIFN tau in epithelial cells of endometrial tissue is supportive of an antiluteolytic effect of bIFN tau.
Delineation of Selective Influences Shaping the Mutated Expressed Human Ig Heavy Chain Repertoire (1998)

After Ag exposure, somatic hypermutation and subsequent selection play significant roles in shaping the peripheral B cell repertoire. However, the disparate impact of each process has not been completely delineated. To address this, the mutational patterns of a large panel of productive V(H)DJ(H) rearrangements of individual human B cells were analyzed and compared with those of a previously reported panel of nonproductive V(H)DJ(H) rearrangements. The productive V(H) rearrangements exhibited a significantly lower mutational frequency and a significantly smaller number of replacement mutations than the nonproductively rearranged genes, suggesting that structural constraints of the Ig molecule and selective influences both impacted the repertoire, militating against replacement mutations. Positive selection favored a mean of four to six replacements in complementarity-determining region 1 (CDR1) and CDR2, and less than two replacements in the framework regions (FRs). In contrast, the negative impact of replacement mutations generated an increased number of silent mutations within both the CDRs and FRs of the productive repertoire accompanied by a net increase in the ratio of replacement to silent mutations in the CDRs compared with that in the FRs. Moreover, there was a negative influence on the distribution of amino acid changes resulting from mutations of highly mutable codons, such as AGY, TAY, GTA, and GCT, preferentially leading to conservative changes in the expressed Ig repertoire. The results are consistent with the conclusion that the expressed repertoire is limited, compared with the potential generated by the mutational machinery, by the dual requirements of avoiding autoreactivity and satisfying structural constraints of an intact Ig molecule.
Computational Analysis of the Polymorphic Membrane Protein Superfamily of Chlamydia trachomatis and Chlamydia pneumoniae (1999)

Whole sequence genome analysis is invaluable in providing complete profiles of related proteins and gene families. The genome sequences of the obligate intracellular bacteria Chlamydia trachomatis and Chlamydia pneumoniae both encode proteins with similarity to several 90-kDa Chlamydia psittaci proteins. These proteins are members of a large superfamily, C. trachomatis with 9 members and C. pneumoniae with 21 members. All polymorphic membrane protein (Pmp) are heterogeneous, both in amino acid sequence and in predicted size. Most proteins have apparent signal peptide leader sequences and hence are predicted to be localized to the outer membrane. The unifying features of all proteins are the conserved amino acid motifs GGAI and FXXN repeated in the N-terminal half of each protein. In both genomes, the pmp genes are clustered at various locations on the chromosome. Phylogenetic analysis suggests six related families, each with at least one C. trachomatis and one C. pneumoniae orthologue. One of these families has seen prolific expansion in C. pneumoniae, resulting in 13 protein paralogues. The maintenance of orthologues from each species suggests specific functions for the proteins in chlamydial biology.
Maximization battery lifetime and improving efficiency (2012)

Many wearable and portable devices, like personal communicators, cellular phones, laptops, are equipped with two or more battery packs to increase user flexibility in selecting the optimal form-factor/weight versus required lifetime trade off. For instance, the Compaq IPAQ PDA is equipped with an add-on module that contains PCMCIA expansion and an auxiliary battery pack. Portable and wearable computers can be powered by different combinations of two or more battery packs to give the user the possibility of choosing an optimal compromise between lifetime and weight/size. Recent work on battery-driven power management has demonstrated that sequential discharge is suboptimal in multibattery systems and lifetime can be maximized by distributing (steering) the current load on the available batteries, thereby discharging them in a partially concurrent fashion. Based on these observations, we formulate multibattery lifetime maximization as a continuous, constrained optimization problem, which can be efficiently solved by nonlinear optimizers. We show that significant lifetime extensions can be obtained with respect to standard sequential discharge (up to 160 percent), as well to previously proposed battery scheduling algorithms (up to 12 percent). From the manufacturing standpoint, numerous issues must be faced when multiple batteries have to be accommodated into the case of a portable electronic appliance. They range from the selection of battery capacities and shapes to the design of the power supply circuitry (including the switching regulator that interfaces the various batteries to the current load). One degree of freedom that, so far, has not been fully exploited, is the policy to be used for discharging the available batteries. The main contribution of this paper is the development of a new class battery lifetime maximization policies and an approach for optimally tuning the policies for a given battery system.
Cerebral Blood Volume Measurements and Proton MR Spectroscopy in Grading of Oligodendroglial Tumors (2006)

Relative cerebral blood volume measurement and MRS are helpful in differentiating low-grade from anaplastic oligodendroglial tumors.
Effect of electronic strain on photoacoustic generation in silicon (1985)

The photogeneration of excess free carriers gives rise to a mechanical strain in semiconductors. An experiment has been performed to investigate the contribution of this electronic strain to photoacoustic generation, and it is found that electronic strain is an important mechanism in the photogeneration of acoustic waves in silicon. A theory is developed to predict the contribution of the electronic strain to the photoacoustic generation and is found to agree well with experiment.
Immunity in Experimental Salmonellosis II. Basis for the Avirulence and Protective Capacity of gal E Mutants of Salmonella typhimurium (1971)

Salmonella typhimurium strains which are deficient in uridine diphosphate (UDP)-galactose-4-epimerase ( gal E mutants) owe their outstanding protective capacity when used as live vaccine to the fact that when galactose is supplied exogenously, such as occurs in vivo, smooth cell wall lipopolysaccharides are synthesized. The mutants lose most of their protective capacity when this phenotypic curing is prevented by a second mutation of the kind found in strains LT 2 M 1 A (deficient in galactokinase) or E 32 (deficient in UDP-galactose-lipopolysaccharide transferase). Despite such phenotypic reversion, the gal E mutants are rendered avirulent as a result of galactose-induced bacteriolysis. Secondary mutants have been isolated which differ from each other with respect to the extent of galactose-induced lysis. The differences in galactose sensitivity are attributable to different activities of the other Leoloir pathway enzymes, namely, galactokinase and galactose-1-phosphate-uridyl transferase. The influence of these enzymes on lipopolysaccharide composition and galactose sensitivity and thus on virulence and immunogenicity of gal E mutants has been studied.
Arabidopsis ARR1 and ARR2 response regulators operate as transcriptional activators (2000)

The genes coding for the response regulators ARR1 and ARR2 have previously been identified by in silico screening of an expression sequence tag database and subsequent cloning from both Arabidopsis cDNA and genomic libraries. Their structures, in which the N-terminal signal receiver domain is followed by the output domain, are characteristic of typical bacterial response regulators of the two-component regulatory systems that control responses to a variety of environmental stimuli. Here we present evidence that these response regulators actually work as transcription factors. ARR1 and ARR2 were localized in the nuclei of plant cells regardless of the presence or absence of their signal receiver domain. Their middle segments, which faintly resemble the mammalian oncogene product Myb, were capable of binding double-stranded DNA in a sequence-specific manner in vitro. Their C-terminal halves functioned as transactivation domains in plant cells when combined with the DNA-binding domain of yeast GAL4. They thus possess all the essential components of a transcriptional activator. Both ARR1 and ARR2 promoted expression of a reporter gene in plant cells through their own target sequence. Truncation of their N-terminal signal receiver domain led to an increase in transactivation. An as yet unidentified phospho-relay signal may modulate the capability for transactivation and/or DNA binding through the signal receiver domain.
Study of CMOS-compatible Copper Etching for Organic Coating (2009)

Biosensors based on advanced CMOS processing have copper surfaces. These copper surfaces have to be functionalized with biological receptors to allow bio-sensing. The cleaning of the CMOS copper interface is therefore a critical step to allow good attachment and formation of self-assembled monolayers of thiol-molecules. Different cleaning procedures were tested and evaluated in terms of roughness (by atomic force microscopy AFM), oxide formation and contamination (by time of flight - secondary ion mass spectrometry TOF-SIMS). The quality of the deposited self-assembled monolayer was assessed by x-ray photoelectron spectroscopy (XPS) and by grazing-angle Fourier transform infrared spectroscopy (GA-FTIR). The optimal cleaning treatment for the formation of a well-ordered octadecanethiol monolayer was obtained with an etching of 5 minutes in 3.7% HCl.
The human DEK oncogene regulates DNA damage response signaling and repair (2011)

The human DEK gene is frequently overexpressed and sometimes amplified in human cancer. Consistent with oncogenic functions, Dek knockout mice are partially resistant to chemically induced papilloma formation. Additionally, DEK knockdown in vitro sensitizes cancer cells to DNA damaging agents and induces cell death via p53-dependent and -independent mechanisms. Here we report that DEK is important for DNA double-strand break repair. DEK depletion in human cancer cell lines and xenografts was sufficient to induce a DNA damage response as assessed by detection of γH2AX and FANCD2. Phosphorylation of H2AX was accompanied by contrasting activation and suppression, respectively, of the ATM and DNA-PK pathways. Similar DNA damage responses were observed in primary Dek knockout mouse embryonic fibroblasts (MEFs), along with increased levels of DNA damage and exaggerated induction of senescence in response to genotoxic stress. Importantly, Dek knockout MEFs exhibited distinct defects in non-homologous end joining (NHEJ) when compared to their wild-type counterparts. Taken together, the data demonstrate new molecular links between DEK and DNA damage response signaling pathways, and suggest that DEK contributes to DNA repair.
Genomewide studies of histone deacetylase function in yeast (2000)

The trichostatin A (TSA)-sensitive histone deacetylase (HDAC) Rpd3p exists in a complex with Sin3p and Sap30p in yeast that is recruited to target promoters by transcription factors including Ume6p. Sir2p is a TSA-resistant HDAC that mediates yeast silencing. The transcription profile of rpd3 is similar to the profiles of sin3, sap30, ume6, and TSA-treated wild-type yeast. A Ume6p-binding site was identified in the promoters of genes up-regulated in the sin3 strain. Two genes appear to participate in feedback loops that modulate HDAC activity: ZRT1 encodes a zinc transporter and is repressed by RPD3 (Rpd3p is zinc-dependent); BNA1 encodes a nicotinamide adenine dinucleotide (NAD)-biosynthesis enzyme and is repressed by SIR2 (Sir2p is NAD-dependent). Although HDACs are transcriptional repressors, deletion of RPD3 down-regulates certain genes. Many of these are down-regulated rapidly by TSA, indicating that Rpd3p may also activate transcription. Deletion of RPD3 previously has been shown to repress ("silence") reporter genes inserted near telomeres. The profiles demonstrate that 40% of endogenous genes located within 20 kb of telomeres are down-regulated by RPD3 deletion. Rpd3p appears to activate telomeric genes sensitive to histone depletion indirectly by repressing transcription of histone genes. Rpd3p also appears to activate telomeric genes repressed by the silent information regulator (SIR) proteins directly, possibly by deacetylating lysine 12 of histone H4. Finally, bioinformatic analyses indicate that the yeast HDACs RPD3, SIR2, and HDA1 play distinct roles in regulating genes involved in cell cycle progression, amino acid biosynthesis, and carbohydrate transport and utilization, respectively.
Hematopoietic Cytokines Can Instruct Lineage Choice (2009)

The constant regeneration of the blood system during hematopoiesis requires tightly controlled lineage decisions of hematopoietic progenitor cells (HPCs). Because of technical limitations, differentiation of individual HPCs could not previously be analyzed continuously. It was therefore disputed whether cell-extrinsic cytokines can instruct HPC lineage choice or only allow survival of cells that are already lineage-restricted. Here, we used bioimaging approaches that allow the continuous long-term observation of individual differentiating mouse HPCs. We demonstrate that the physiological cytokines, macrophage colony-stimulating factor and granulocyte colony-stimulating factor, can instruct hematopoietic lineage choice.
Crystal structure and substrate specificity of the β‐ketoacyl‐acyl carrier protein synthase III (FabH) from Staphylococcus aureus (2005)

Abstract β‐Ketoacyl‐ACP synthase III (FabH), an essential enzyme for bacterial viability, catalyzes the initiation of fatty acid elongation by condensing malonyl‐ACP with acetyl‐CoA. We have determined the crystal structure of FabH from Staphylococcus aureus , a Gram‐positive human pathogen, to 2 Å resolution. Although the overall structure of S. aureus FabH is similar to that of Escherichia coli FabH, the primer binding pocket in S. aureus FabH is significantly larger than that present in E. coli FabH. The structural differences, which agree with kinetic parameters, provide explanation for the observed varying substrate specificity for E. coli and S. aureus FabH. The rank order of activity of S. aureus FabH with various acyl‐CoA primers was as follows: isobutyryl‐ &gt; hexanoyl‐ &gt; butyryl‐ &gt; isovaleryl‐ &gt;&gt; acetyl‐CoA. The availability of crystal structure may aid in designing potent, selective inhibitors of S. aureus FabH.
Identification of single-nucleotide polymorphisms in the human N-methyl-D-aspartate receptor subunit NR2D gene, GRIN2D, and association study with schizophrenia (2005)

We conclude that the GRIN2D locus is a possible genomic region contributing to schizophrenia susceptibility in the Japanese population.
Parallel Single-Cell Monitoring of Receptor-Triggered Membrane Translocation of a Calcium-Sensing Protein Module (2002)

Time courses of translocation of fluorescently conjugated proteins to the plasma membrane were simultaneously measured in thousands of individual rat basophilic leukemia cells. We found that the C2 domain---a calcium-sensing, lipid-binding protein module that is an essential regulator of protein kinase C and numerous other proteins---targeted proteins to the plasma membrane transiently if calcium was released from internal stores, and persistently in response to entry of extracellular calcium across the plasma membrane. The C2 domain translocation time courses of stimulated cells clustered into only two primary modes. Hence, the reversible recruitment of families of signaling proteins from one cellular compartment to another is a rapid bifurcation mechanism for inducing discrete states of cellular signaling networks.
Uptake of azithromycin by various cells and its intracellular activity under in vivo conditions (1996)

The concentrations of azithromycin in polymorphonuclear leukocytes (PMNLs), monocytes, erythrocytes, and plasma were measured in six healthy volunteers after the last treatment of a 3-day regimen of 500 mg once daily. Marked enrichment of azithromycin was found in PMNLs and monocytes. The drug concentrations after the last dose amounted to 114 +/- 43 (mean +/- standard deviation) mg/liter at 12 h in PMNLs and 34 +/- 17 mg/liter at 6 h in monocytes. Fourteen days thereafter, azithromycin was still detectable in the PMNLs at 53 +/- 34 mg/liter and in the monocytes at 1 +/- 2 mg/liter, although the drug was no longer detectable in plasma (< 0.02 mg/liter). Maximum drug concentrations for azithromycin in plasma (0.40 +/- 0.30 mg/liter) and erythrocytes (0.15 +/- 0.05 mg/liter) at 3 h after the last administration were much lower and occurred earlier than those observed in the phagocytic cells. The mean enrichment factors (cellular/extracellular ratios) of azithromycin in phagocytes relative to plasma came to 231 +/- 150 and 3,924 +/- 584 at 3 and 120 h, respectively, for PMNLs and 83 +/- 55 and 523 +/- 285 at 3 and 120 h for monocytes, respectively, after the last dose. The phagocytosis tests with PMNLs separated from the blood of volunteers at various times after the last treatment confirmed the enhanced intracellular activity of these cells against staphylococci.