gebhart/patrepeval huggingface dataset:
Escherichia Coli Strains with Promoter Libraries Constructed by Red/ET Recombination Pave the Way for Transcriptional Fine-Tuning (2008)

System-oriented applications of genetic engineering, such as metabolic engineering, often require the serial optimization of enzymatic reaction steps, which can be achieved by transcriptional fine-tuning. However, approaches to changing gene expression are usually limited to deletion and/or strong overexpression and rarely match the desired optimal transcript levels. A solution to this all-or-nothing approach has been the use of a synthetic promoter library (SPL) that is based on randomized sequences flanking the consensus -10 and -35 promoter regions and allows for fine-tuning of bacterial gene expression. Red/ET recombination perfectly complements SPL technology, since it enables easy modification of the Escherichia coli genome and can be accomplished with linear DNA (i.e., the SPL). To demonstrate the synergistic use of Red/ET and SPL for metabolic engineering applications, we replaced the native promoter of a genomic localized phosphoglucose isomerase (pgi)-lacZ reporter construct by an SPL. Using these technologies together, we were able to rapidly identify synthetic promoter sequences that resulted in activity range of 25% to 570% of the native pgi-promoter.
In vivoDrug-Linker Stability of an Anti-CD30 Dipeptide-Linked Auristatin Immunoconjugate (2005)

Effective antibody-drug conjugates (ADC) combine high drug-linker stability in circulation and efficient intratumoral release of drug. Conjugation of monomethyl auristatin E (MMAE) to the anti-CD30 monoclonal antibody (mAb), cAC10, produced a selective and potent ADC against CD30(+) anaplastic large cell lymphoma and Hodgkin's disease models. This ADC, cAC10-valine-citrulline-MMAE, uses a protease-sensitive dipeptide linker designed to release MMAE by lysosomal cathepsin B in target cells but maintain a stable linkage and attenuate drug potency in circulation. To evaluate ADC stability in vivo, we developed methods for measuring drug/mAb ratios at progressive times in plasma from ADC-treated mice and nonhuman primates. Anti-idiotype mAb permitted the capture and quantitation of mAb cAC10, whereas antidrug mAb and MMAE-conjugated horseradish peroxidase reporter provided quantitative detection of conjugated drug following its in vitro release by cathepsin B. These data were validated by an alternative ELISA using anti-idiotype and anti-MMAE mAbs for capture and detection, respectively. Both methods differentiated ADC with variable levels of drug loading and were subsequently applied to stability studies in severe combined immunodeficient mice and cynomolgus monkeys. Evaluation of ADC from mouse circulation showed the linker half-life to be approximately 144 hours (6.0 days), significantly greater than that reported for disulfide- or hydrazone-linked ADCs in mice or human trials. In cynomolgus monkey, the apparent linker half-life was approximately 230 hours (9.6 days), suggesting that the drug-linker will be highly stable in humans. These data represent the longest reported drug-linker half-life to date and provide the basis for the pronounced specificity and antitumor activity of cAC10-valine-citrulline-MMAE.
Limiting Laws and Counterion Condensation in Polyelectrolyte Solutions I. Colligative Properties (1969)

Formulas are derived for the osmotic coefficient, the Donnan salt-exclusion factor, and the mobile-ion activity coefficients in a polyelectrolyte solution with or without added sample salt. The formulas, which contain no adjustable parameters, are based on the (theoretical) observation by several workers that counterions will “condense” on the polyion until the charge density on the polyion is reduced below a certain critical value. The uncondensed mobile ions are treated in the Debye–Hückel approximation. In a restricted sense, the formulas are “limiting laws,” and this aspect is discussed at length. Detailed comparison with experimental data in the literature is given; agreement of the theory with experiment is usually found to be quantitative.
Biosynthesis of Phloroglucinol (2005)

Substantial concentrations of phloroglucinol were synthesized by Pseudomonas fluorescens Pf-5 expressing the plasmid-localized phlACBDE gene cluster responsible for biosynthesis of 2,4-diacetylphloroglucinol. Expression in Escherichia coli of a single gene in this cluster, P. fluorescens Pf-5 phlD, led to extracellular accumulation of phloroglucinol. Purification of PhlD to homogeneity afforded an enzyme that catalyzed the conversion of malonyl-CoA into phloroglucinol with Km = 5.6 muM and kcat = 10 min-1. Acetylase and deacetylase activities were observed with the catalyzed interconversions of phloroglucinol, 2-acetylphloroglucinol, and 2,4-diacetylphloroglucinol when phlACB was expressed in E. coli. Beyond the mechanistic implications attendant with the identification of an enzyme that catalyzes the conversion of malonyl-CoA into phloroglucinol, PhlD provides the basis for environmentally benign syntheses of phloroglucinol and resorcinol from glucose.
Vom Personenverband zur Polizey: Die Entstehung des frühneuzeitlichen Staates (2006)

Die Deklaration einer "epistemischen Souveränität" (Rouse 1994, S. 103) in der Erkenntnis der Natur ist nicht zu trennen von dem Projekt der Konstitution der modernen politischen Souveränität. Die "Monopolisierung der legitimen Gewalt" in Form des frühneuzeitlichen Staates markiert einen entscheidenden Bruch mit traditionellen Herrschaftskonzepten. Im Mittelalter gab es keine politischen Institutionen im Sinne personenunabhängiger Körperschaften; die Zeitgenossen verstanden unter "Staat" vielmehr einen Herrschaftsverband, der sich durch ein Netzwerk von Abhängigkeiten und Verpflichtungen zwischen Herren und Gefolgschaft auszeichnete. Die herrschaftliche Gewalt wurde direkt von Menschen über Menschen ausgeübt, sie erstreckte sich von der Haus- und Grundwirtschaft bis hin zum Königtum und war daher weder zentralisiert noch räumlich gebunden. Entscheidende Bedeutung kam den Personenverbänden wie Stand oder Familie zu, in die man hineingeboren wurde, während das territoriale Prinzip oder die souveräne Konzentration von Herrschaftsrechten unbekannt war. Es war daher möglich, dass ein und dieselbe Person von verschiedenen Herren in unterschiedlicher Weise abhängig war; ebenso konnten in demselben Raum etwa Grand- und Gerichtsherrschaft, Dienst- und Abgabepflichten auseinander fallen.
Adequate Serum Copper Concentration Could Improve Bone Density, Postpone Bone Loss and Protect Osteoporosis in Women (2015)

Background: To determine the protective impact of efficient serum copper concentration on BMD in women and to asses its impression on bone. Methods: six hundred healthy women through a national project in Iran, IMOS, were selected via a cluster random sam-pling and enrolled the study. They were divided to pre menopausal (404/600, 67.7 % of total) and post menopausal (190/600, 32%of total) groups. BMD was measured by biphotonic absorptimetry DEXA for hip and lumbar spine. Morning serum copper concentration was determined by atomic absorption spectrometry. Results: Mean age was 40.92±14.8yr.Mean serum copper concentration = 105.85±40.15µg/dl and mean BMI = 27.13±4.81 kg/m2.Totaly 2.4 % was smoking, 5 % had regular physical activities three times a week and 17.5 % was copper deficient. Prevalence of Osteoporosis in postmenopausal women was 12.9 % in copper deficient persons vs.11.3 % in normal serum copper ones. No significant difference found according to serum copper concentration associated with BMI, age and vita-min D. Spine BMD revealed a significant correlation with serum copper content. (P = 0.001). This correlation also existed for Total hip (P&amp;lt; 0.05). Premenopausal women with serum copper level above 105 µg/dl revealed a significant difference in hip BMD compared to whom with less copper concentration.1.02 ± 0.13kg/m2 vs. 0.97 ± 0.13kg/m2 (P = 0.001). Copper had an independent role on determining hip BMD in pre menopaused women (P = 0.001). Conclusion: copper has an independent role on bone density in all healthy women. It could have an adjourning factor for bone loss as well as a protective agent for osteoporosis.
ChemInform Abstract: Synthesis and Application of Novel Glyoxylate‐Derived Chloroformates. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Oxidized low density lipoprotein stimulates aortic smooth muscle cell proliferation (1996)

We have investigated the effects of oxidized low density lipoproteins (Ox-LDL) on aortic smooth muscle cell (SMC) proliferation and the biosynthesis of glycosphingolipids. We found that Ox-LDL exerted a concentration, time, and temperature dependent alteration of cell proliferation and the biosynthesis of lactosylceramide. At low concentrations (5-10 micrograms/ml medium) Ox-LDL stimulated cell proliferation measured by an increase in the incorporation of [3H]-thymidine in cells and the synthesis of lactosylceramide, but not glucosylceramide synthesis. Oxidized LDL exerted a threefold increase in the incorporation of [3H]-galactose and [3H]-serine in lactosylceramide. The activity of lactosylceramide synthetase; UDP-galactose glucosylceramide beta 1 --> 4 galactosyltransferase (GalT-2), but not glucosylceramide synthetase (GlcT-1) was stimulated by Ox-LDL. On the other hand, LDL suppressed the activity of GalT-2 in these cells. When cells were preincubated with antibody against Ox-LDL or GalT-2 it compromised the Ox-LDL mediated stimulated in cell proliferation and GalT-2 activity. Similarly, D-PDMP an inhibitor of GalT-2 compromised the Ox-LDL mediated effects in cells. In contrast, L-PDMP further stimulated the Ox-LDL mediated cell proliferation and GalT-2 activity. However, preincubation of cells with preimmune rabbit serum IgG failed to abrogate Ox-LDL mediated stimulation in cell proliferation and GalT-2 activity. In sum, we found that Ox-LDL stimulated aortic smooth muscle cell proliferation in culture. This effect resulted from Ox-LDL mediated activation of GalT-2 that produced lactosylceramide. Lactosylceramide in turn, contributed to cell proliferation. Such correlations are supportive of the notion that GalT-2 action mediates the signal transduction of Ox-LDL contributing to cell proliferation.
Convulsive seizure detection using a wrist‐worn electrodermal activity and accelerometry biosensor (2012)

The special requirements for a seizure detector suitable for everyday use in terms of cost, comfort, and social acceptance call for alternatives to electroencephalography (EEG)-based methods. Therefore, we developed an algorithm for automatic detection of generalized tonic-clonic (GTC) seizures based on sympathetically mediated electrodermal activity (EDA) and accelerometry measured using a novel wrist-worn biosensor. The problem of GTC seizure detection was posed as a supervised learning task in which the goal was to classify 10-s epochs as a seizure or nonseizure event based on 19 extracted features from EDA and accelerometry recordings using a Support Vector Machine. Performance was evaluated using a double cross-validation method. The new seizure detection algorithm was tested on >4,213 h of recordings from 80 patients and detected 15 (94%) of 16 of the GTC seizures from seven patients with 130 false alarms (0.74 per 24 h). This algorithm can potentially provide a convulsive seizure alarm system for caregivers and objective quantification of seizure frequency.
A plant gene with homology to d‐myo‐inositol‐3‐phosphate synthase is rapidly and spatially up‐regulated during an abscisic‐acid‐induced morphogenic response in Spirodela polyrrhiza (1993)

The induction of turions (dormant vegetative buds) by the plant growth regulator abscisic acid (ABA) in the aquatic angiosperm Spirodela polyrrhiza is one of the few examples of a plant hormone triggering a morphogenic response. In order to aid our understanding of the molecular basis of this phenomenon a cDNA library has been prepared from ABA-induced S. polyrrhiza and by differential screening a number of early ABA-up-regulated genes have been isolated. This paper reports the characterization of one such cDNA (tur1) from S. polyrrhiza which codes for a protein highly homologous to yeast D-myo-inositol-3-phosphate synthase (EC.5.5.1.4), the catalyst for the first committed step in inositol biosynthesis. This is the first reported cloning of a plant gene involved in inositol production. It is shown by Northern analysis and in situ hybridization that ABA induces a rapid preferential up-regulation of this gene and that this is localized to the stolon tissue. The stolon connects the developing turion to the node of the mother frond (the meristematic region involved in the production of turions which arise as a morphogenic response to this hormone). This increase in tur1 transcript level is accompanied by a rise in the activity of D-myo-inositol-3-phosphate synthase. The possible role of inositol in ABA-induced events during turion formation is discussed.
CD45 in memory and disease. (2002)

CD45 (the leukocyte common antigen) is known to function as a tyrosine phosphatase in leukocyte signaling. Biochemical studies indicate that CD45 is involved in the regulation both of T cell receptor-associated kinases and Janus kinases that transmit signals from cytokine receptors. However, the function of the different isoforms of CD45 generated by complex alternative splicing, and indeed the role of the whole extracellular domain of the molecule, remain mysterious. Analysis of CD45 knock-outs and of transgenic mice expressing single CD45 isoforms, as well as the disease associations of human polymorphisms, is providing new insights into CD45 function. Accumulating data from these genetic and biochemical studies promises to elucidate the role of high and low molecular weight isoforms of CD45 in the function of naïve and memory T lymphocytes.
The Heat Shock Response: Systems Biology of Proteotoxic Stress in Aging and Disease (2011)

All organisms sense and respond to environmental and physiological stress by inducing cell stress responses that protect core biosynthetic processes such as DNA repair, protein folding, and clearance of damaged proteins. Of these, the heat shock response (HSR) protects the proteome against acute exposure to elevated temperatures, oxidants, and heavy metals, for example, and to the chronic expression of metastable, aggregation-prone proteins associated with aging and diseases of protein conformation. Induction of the HSR leads to the rapid and robust expression of molecular chaperones and other cell-protective pathways to protect nascent chain synthesis and folding, to prevent misfolding and aggregation, and to promote recovery from stress-induced damage. This review examines the properties of the stress-responsive transcription factor, HSF-1, in the regulation of the HSR, our current understanding of the stress-sensing mechanisms that recognize and distinguish between acute stress such as heat shock and chronic proteostasis imbalance as occurs in neurodegenerative diseases, and the cell nonautonomous control of the HSR by neuronal signaling in metazoans. This complex, systems-wide interdependence ensures cellular health span and organismal life span.
Delay diversity code for frequencyselective channels (2001)

Code construction criteria for frequency selective multiple input multiple output (MIMO) channels with single carrier modulation are derived. It is shown that the standard delay diversity code fails to exploit full diversity order in presence of delay spread. A generalised delay-diversity code which exploits full diversity is proposed.
Recombinant human growth hormone (GH)-binding protein enhances the growth-promoting activity of human GH in the rat. (1996)

To address the role of the GH-binding protein (GHBP) in GH physiology, two forms of recombinant human GHBP (rhGHBP) were given alone or in combination with rhGH to hypophysectomized rats or GH-deficient dwarf rats. Hypophysectomized rats were given daily sc injections of excipient, hGH, rhGHBP, or rhGH plus rhGHBP (produced in Escherichia coli) for 7 days. Injections of rhGH induced dose-related body weight gain and bone growth that were increased by the coadministration of rhGHBP with rhGH; rhGHBP alone had no effect. Serum insulin-like growth factor increased 24 h later when rhGH was given together with rhGHBP (P < 0.01), but not when rhGH was given alone. E. coli-derived rhGHBP also enhanced the bioactivity of coadministered rhGH in the GH-deficient dwarf rat. In contrast, the glycosylated rhGHBP, made in human A293 cells, inhibited the growth-promoting activity of coadministered rhGH. The opposite effects of these two forms of rhGHBP could be explained by clearance studies that showed radiolabeled rhGH bound to A293 cell-derived rhGHBP to be cleared more rapidly from the blood than free rhGH. Natural rabbit GHBP and E. coli-derived rhGHBP both prolonged the presence of rhGH in blood. It is proposed that by slowing the clearance of GH, GHBP increased the bioactivity of GH. In summary, codelivery of rhGHBP and rhGH caused a dose-dependent enhancement of the activity of rhGH in two rat models of GH deficiency. This suggests that endogenous circulating GHBP may increase the activity of blood-borne GH in a similar manner.
Rational Design, Synthesis and Structure—Activity Relationships of a Cyclic Succinate Series of TNF‐α Converting Enzyme Inhibitors. Part 1. Lead Identification. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Cloning of human acetyl-CoA carboxylase-beta and its unique features. (1996)

Acetyl-CoA carboxylase, which has a molecular mass of 265 kDa (ACC-alpha), catalyzes the rate-limiting step in the biosynthesis of long-chain fatty acids. In this study we report the complete amino acid sequence and unique features of an isoform of ACC with a molecular mass of 275 kDa (ACC-beta), which is primarily expressed in heart and skeletal muscles. In these tissues, ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. ACC-beta contains an amino acid sequence at the N terminus which is about 200 amino acids long and may be uniquely related to the role of ACC-beta in controlling carnitine palmitoyltransferase I activity and fatty acid oxidation by mitochondria. If we exclude this unique sequence at the N terminus the two forms of ACC show about 75% amino acid identity. All of the known functional domains of ACC are found in the homologous regions. Human ACC-beta cDNA has an open reading frame of 7,343 bases, encoding a protein of 2,458 amino acids, with a calculated molecular mass of 276,638 Da. The mRNA size of human ACC-beta is approximately 10 kb and is primarily expressed in heart and skeletal muscle tissues, whereas ACC-alpha mRNA is detected in all tissues tested. A fragment of ACC-beta cDNA was expressed in Escherichia coli and antibodies against the peptide were generated to establish that the cDNA sequence that we cloned is that for ACC-beta.
pH-Activated Nanoparticles for Controlled Topical Delivery of Farnesol To Disrupt Oral Biofilm Virulence (2015)

Development of effective therapies to control oral biofilms is challenging, as topically introduced agents must avoid rapid clearance from biofilm-tooth interfaces while targeting biofilm microenvironments. Additionally, exopolysaccharides-matrix and acidification of biofilm microenvironments are associated with cariogenic (caries-producing) biofilm virulence. Thus, nanoparticle carriers capable of binding to hydroxyapatite (HA), saliva-coated HA (sHA), and exopolysaccharides with enhanced drug release at acidic pH were developed. Nanoparticles are formed from diblock copolymers composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA), butyl methacrylate (BMA), and 2-propylacrylic acid (PAA) (p(DMAEMA)-b-p(DMAEMA-co-BMA-co-PAA)) that self-assemble into ∼21 nm cationic nanoparticles. Nanoparticles exhibit outstanding adsorption affinities (∼244 L-mmol(-1)) to negatively charged HA, sHA, and exopolysaccharide-coated sHA due to strong electrostatic interactions via multivalent tertiary amines of p(DMAEMA). Owing to hydrophobic cores, nanoparticles load farnesol, a hydrophobic antibacterial drug, at ∼22 wt %. Farnesol release is pH-dependent with t1/2 = 7 and 15 h for release at pH 4.5 and 7.2, as nanoparticles undergo core destabilization at acidic pH, characteristic of cariogenic biofilm microenvironments. Importantly, topical applications of farnesol-loaded nanoparticles disrupted Streptococcus mutans biofilms 4-fold more effectively than free farnesol. Mechanical stability of biofilms treated with drug-loaded nanoparticles was compromised, resulting in >2-fold enhancement in biofilm removal under shear stress compared to free farnesol and controls. Farnesol-loaded nanoparticles effectively attenuated biofilm virulence in vivo using a clinically relevant topical treatment regimen (2×/day) in a rodent dental caries disease model. Strikingly, treatment with farnesol-loaded nanoparticles reduced both the number and severity of carious lesions, while free farnesol had no effect. Nanoparticle carriers have great potential to enhance the efficacy of antibiofilm agents through multitargeted binding and pH-responsive drug release due to microenvironmental triggers.
Diquaternary Ammonium Compounds in Zeolite Synthesis: Cyclic and Polycyclic N-Heterocycles Connected by Methylene Chains (2009)

An additional dimension has been added to our long-standing studies in high silica zeolite synthesis via a guest/host synergism. We have created and studied the impact of making symmetric diquaternary ammonium compounds, by varying the chain length between nitrogen charge centers, and the heterocycle size and geometry containing the nitrogen. This allows the introduction of a second spatial parameter in the use of the charged organo-cation guest in the zeolite synthesis. The series of 15 diquaternary ammonium compounds (5 heterocycles synthesized onto chain lengths of C4-C6) were tested in a total of 135 zeolite syntheses reactions. Nine screening reactions were employed for each guest molecule, and the conditions built upon past successes in finding novel high silica zeolites via introduction of boron, aluminum, or germanium as substituting tetrahedral framework atoms for silicon. Eighteen different zeolite structures emerged from the studies. The use of specific chain lengths for derivatives of the pyrrolidine ring system produced novel zeolite materials SSZ-74 and 75.
Majorana fermion exchange in quasi-one-dimensional networks (2011)

Heterostructures of spin-orbit coupled materials with $s$-wave superconductors are thought to be capable of supporting zero-energy Majorana bound states. Such excitations are known to obey non-Abelian statistics in two dimensions, and are thus relevant to topological quantum computation (TQC). In a one-dimensional system, Majorana states are localized to phase boundaries. In order to bypass the constraints of one dimension, a wire network may be created, allowing the exchange of Majoranas by way of junctions in the network. Alicea et al. have proposed such a network as a platform for TQC, showing that the Majorana bound states obey non-Abelian exchange statistics even in quasi-one-dimensional systems.1 Here we show that the particular realization of non-Abelian statistics produced in a Majorana wire network is highly dependent on the local properties of individual wire junctions. For a simply connected network, the possible realizations can be characterized by the chirality of individual junctions. There is in general no requirement for junction chiralities to remain consistent across a wire network. We show how the chiralities of different junctions may be compared experimentally and discuss the implications for TQC in Majorana wire networks.