gebhart/patrepeval huggingface dataset:
Requirement of NF-κB/Rel for the development of hair follicles and other epidermal appendices (2001)

NF-kappaB/Rel transcription factors and IkappaB kinases (IKK) are essential for inflammation and immune responses, but also for bone-morphogenesis, skin proliferation and differentiation. Determining their other functions has previously been impossible, owing to embryonic lethality of NF-kappaB/Rel or IKK-deficient animals. Using a gene targeting approach we have ubiquitously expressed an NF-kappaB super-repressor to investigate NF-kappaB functions in the adult. Mice with suppressed NF-kappaB revealed defective early morphogenesis of hair follicles, exocrine glands and teeth, identical to Eda (tabby) and Edar (downless) mutant mice. These affected epithelial appendices normally display high NF-kappaB activity, suppression of which resulted in increased apoptosis, indicating that NF-kappaB acts as a survival factor downstream of the tumor necrosis factor receptor family member EDAR. Furthermore, NF-kappaB is required for peripheral lymph node formation and macrophage function.
Epratuzumab for patients with moderate to severe flaring SLE: health-related quality of life outcomes and corticosteroid use in the randomized controlled ALLEVIATE trials and extension study SL0006 (2013)

Epratuzumab treatment produced clinically meaningful and sustained improvements in PGA, PtGA and HRQOL and reductions in corticosteroid doses.
Dye-sensitized nanocrystalline solar cells (2007)

The basic physical and chemical principles behind the dye-sensitized nanocrystalline solar cell (DSC: also known as the Grätzel cell after its inventor) are outlined in order to clarify the differences and similarities between the DSC and conventional semiconductor solar cells. The roles of the components of the DSC (wide bandgap oxide, sensitizer dye, redox electrolyte or hole conductor, counter electrode) are examined in order to show how they influence the performance of the system. The routes that can lead to loss of DSC performance are analyzed within a quantitative framework that considers electron transport and interfacial electron transfer processes, and strategies to improve cell performance are discussed. Electron transport and trapping in the mesoporous oxide are discussed, and a novel method to probe the electrochemical potential (quasi Fermi level) of electrons in the DSC is described. The article concludes with an assessment of the prospects for future development of the DSC concept.
Designing a Born-Digital Archive (2010)

Light spoke generally about the major issues facing archivists who manage born digital records and how the UCI Libraries responded when providing access to the Richard Rorty papers. She discussed the challenges, such as dealing with rapid technological change, ensure present and future accessibility of legacy files, managing privacy and copyrights, guaranteeing the authenticity and integrity of files, preventing loss and destruction, and selecting the most important material for preservation. She also discussed numerous decisions archivists make that impact the future archive, such as emulation or preservation of the original computing environment, the organization of files, the migration of materials to new formats, and human or machine-generated description of the materials. She concluded with a description of the UCI Libraries' Digital Scholarship Service, which endeavors to help faculty manage their digital research for future generations.
Impact of the 1000 Genomes Project on the Next Wave of Pharmacogenomic Discovery (2010)

The 1000 Genomes Project aims to provide detailed genetic variation data on over 1000 genomes from worldwide populations using the next-generation sequencing technologies. Some of the samples utilized for the 1000 Genomes Project are the International HapMap samples that are composed of lymphoblastoid cell lines derived from individuals of different world populations. These same samples have been used in pharmacogenomic discovery and validation. For example, a cell-based, genome-wide approach using the HapMap samples has been used to identify pharmacogenomic loci associated with chemotherapeutic-induced cytotoxicity with the goal to identify genetic markers for clinical evaluation. Although the coverage of the current HapMap data is generally high, the detailed map of human genetic variation promised by the 1000 Genomes Project will allow a more in-depth analysis of the contribution of genetic variation to drug response. Future studies utilizing this new resource may greatly enhance our understanding of the genetic basis of drug response and other complex traits (e.g., gene expression), therefore, help advance personalized medicine.
<title>New light source for PDT of skin lesions</title> (1994)

Since coherence of laser light is not necessary for PDT of skin tumors, attempts have been made to construct incoherent lamps. A recent development is PDT 1200 (Waldmann Medizintechnik/FRG), a light source based on a 1200 watt metal halogen lamp. Emission of 580 to 740 nm radiation is achieved by using cut off filters. Power density can be varied from 30 mW/cm<sup>2</sup> to 200 mW/cm<sup>2</sup> in an area from 100 to 300 cm<sup>2</sup>. Biologic effectiveness was proved by comparison with the radiation of an argon-pumped dye laser emitting light at 630 nm. Three human cell lines were incubated with photofrin (5 (mu) g/ml and 10 (mu) g/ml) for 24 hours. After irradiation a MTT-test was performed to assess cell viability. Results clearly proved biological effectiveness of the light source PDT 1200. No significant difference in cell viability was detected using either concentration of sensitizer. Therefore, we believe that PDT 1200 is a promising new light source for photodynamic therapy of skin lesion.
Manganese‐Catalyzed Oxidative Benzylic C–H Fluorination by Fluoride Ions (2013)

An efficient protocol for the selective fluorination of benzylic C-H bonds is described. The process is catalyzed by manganese salen complexes and uses nucleophilic fluorine sources, such as triethylamine trihydrofluoride and KF. Reaction rates are sufficiently high (30 min) to allow adoption for the incorporation of (18)F fluoride sources for PET imaging applications.
Isolation and properties of Escherichia coli K-12 mutants impaired in the utilization of gamma-aminobutyrate (1979)

We have isolated mutants of Escherichia coli K-12 CS101B that have lost the ability to utilize gamma-aminobutyrate as a source of nitrogen. One class of mutants, which were not affected in the utilization of other nitrogen sources (proline, arginine, glycine), included many isolates with lesions in gamma-aminobutyrate transport or in its transamination and one mutant completely devoid of succinic semialdehyde dehydrogenase activity and exhibiting low gamma-aminobutyrate transport and transamination. gamma-Aminobutyrate-utilizing revertants of the latter recovered full transport and transamination capacities but remained dehydrogenaseless. Another class of mutants showed pleiotropic defects in nitrogen metabolism. One such mutant was lacking glutamate synthase activity. The genes specifying the synthesis of gamma-aminobutyrate permease, gabP, gamma-aminobutyrate transaminase, gabT, and succinic semialdehyde dehydrogenase, gabD, and the control gene, gabC, that coordinately regulates their expression all form a cluster on the E. coli chromosome, linked to the srl and recA loci (at 57.5 min). The mutations with pleiotropic effects on the metabolism of nitrogenous compounds are not linked to the gab cluster.
Recombinant Human Acid -Glucosidase: High Level Production in Mouse Milk, Biochemical Characteristics, Correction of Enzyme Deficiency in GSDII KO Mice (1998)

Glycogen storage disease type II (GSDII) is caused by lysosomal acid alpha-glucosidase deficiency. Patients have a rapidly fatal or slowly progressive impairment of muscle function. Enzyme replacement therapy is under investigation. For large-scale, cost-effective production of recombinant human acid alpha-glucosidase in the milk of transgenic animals, we have fused the human acid alpha-glucosidase gene to 6.3 kb of the bovine alphaS1-casein gene promoter and have tested the performance of this transgene in mice. The highest production level reached was 2 mg/ml. The major fraction of the purified recombinant enzyme has a molecular mass of 110 kDa and resembles the natural acid alpha-glucosidase precursor from human urine and the recombinant precursor secreted by CHO cells, with respect to pH optimum, Km, Vmax, N-terminal amino acid sequence and glycosylation pattern. The therapeutic potential of the recombinant enzyme produced in milk is demonstrated in vitro and in vivo. The precursor is taken up in a mannose 6-phosphate receptor-dependent manner by cultured fibroblasts, is converted to mature enzyme of 76 kDa and depletes the glycogen deposit in fibroblasts of patients. When injected intravenously, the milk enzyme corrects the acid alpha-glucosidase deficiency in heart and skeletal muscle of GSDII knockout mice.
Regulation of Id2 Gene Expression by the Insulin-like Growth Factor I Receptor Requires Signaling by Phosphatidylinositol 3-Kinase (2001)

The Id proteins play an important role in proliferation, differentiation, and tumor development. We report here that Id gene expression can be regulated by the insulin-like growth factor I receptor (IGF-IR), a receptor that also participates in the regulation of cellular proliferation and differentiation. Specifically, we found that the IGF-IR activated by its ligand was a strong inducer of Id2 gene expression in 32D murine hemopoietic cells. This activation was not simply the result of cellular proliferation, as Id2 gene expression was higher in 32D cells stimulated by IGF-I than in cells exponentially growing in interleukin-3. The up-regulation of Id2 gene expression was largely dependent on the presence of insulin receptor substrate-1, a major substrate of the IGF-IR and a potent activator of the phosphatidylinositol 3-kinase (PI3K) pathway. The role of PI3K activity in the up-regulation of Id2 gene expression by the IGF-IR was confirmed by different methods and in different cell types. In 32D cells, the up-regulation of Id2 gene expression by the PI3K pathway correlated with interleukin-3 independence and inhibition of differentiation.
Conformationally Constrained DNA Mimics: Synthesis of a Novel Cyclopropyl-Amide Linked Dimer (1996)

Synthesis of a new conformationally constrained dimeric building-block containing a cyclopropyl-amide functionality is described. Potential application of this dimer for antisense oligonucleotides is discussed.
Total parenteral nutrition in sick preterm infants: effects of cysteine supplementation with nitrogen intakes of 240 and 400 mg/kg/day. (1984)

The effects of supplementing total parenteral nutrition (TPN) solutions with cysteine were assessed at two different levels of nitrogen intake by determining nitrogen retention, sulfate excretion, and sulfur-containing amino acid concentrations. Ten infants received 72 mg/kg/day of cysteine-HCl in a TPN solution for a period of 6 days. Five of these infants received 251 +/- 48 (mean +/- SD) mg/kg/day of nitrogen, and five received 403 +/- 45 mg/kg/day of nitrogen. Two other groups of five infants each received unsupplemented TPN at nitrogen intakes of 235 +/- 48 and 412 +/- 54 mg/kg/day, respectively. Fluid and nonprotein caloric intakes were similar for all four groups. Cysteine supplementation increased plasma and urine free cyst(e)ine concentrations and enhanced total sulfur retention, but did not enhance nitrogen retention. [Cyst(e)ine refers to the mixture in any proportion of the sulfhydryl (cysteine) and the disulfide (cystine) forms of this compound.] Nitrogen retention, sulfate excretion, cyst(e)ine excretion, and plasma taurine concentrations increased as the result of the increase in nitrogen intake.
Tasimelteon, a melatonin agonist for the treatment of insomnia and circadian rhythm sleep disorders. (2009)

Tasimelteon, developed by Vanda Pharmaceuticals Inc under license from Bristol-Myers Squibb Co, is a melatonin receptor agonist. Because of the high density of melatonin receptors in the circadian pacemaker, the suprachiasmatic nucleus, melatonergic actions can phase-shift circadian rhythms and promote sleep. Tasimelteon was effective in reducing sleep onset latency (in phase II and III clinical trials) and in resetting the circadian melatonin rhythm (in phase II trials), which indicated its potential suitability as treatment for jet lag, shift work and circadian rhythm sleep disorders. Statistically significant improvements in sleep maintenance have also been observed with the drug. Tasimelteon has been claimed to be useful in the treatment of depression, and preclinical evidence in this respect is to be confirmed in a phase II clinical trial, which was ready to be initiated at the time of publication. It is plausible that the drug may be effective in the treatment of depressive disorders, at least those that are related to circadian dysfunction, and that it may attenuate sleep problems in depressed patients of different subtypes. A general suitability in mitigating other symptoms of major depressive disorder cannot be deduced from the actions of tasimelteon via the melatonin receptors MT1 and MT2. The drug is well tolerated, does not induce impairment of next-day functioning or dependence, and seems to be safe in short-term treatment; however, toxicological data would be required for assessing its long-term safety.
Coiled-coils in type III secretion systems: structural flexibility, disorder and biological implications (2009)

Recent structural studies and analyses of microbial genomes have consolidated the understanding of the structural and functional versatility of coiled-coil domains in proteins from bacterial type III secretion systems (T3SS). Such domains consist of two or more α-helices forming a bundle structure. The occurrence of coiled-coils in T3SS is considerably higher than the average predicted occurrence in prokaryotic proteomes. T3SS proteins comprising coiled-coil domains are frequently characterized by an increased structural flexibility, which may vary from localized structural disorder to the establishment of molten globule-like state. The propensity for coiled-coil formation and structural disorder are frequently essential requirements for various T3SS functions, including the establishment of protein-protein interaction networks and the polymerization of extracellular components of T3SS appendages. Possible correlations between the frequently observed N-terminal structural disorder of effectors and the T3SS secretion signal are discussed. The results for T3SS are also compared with other Gram-negative secretory systems.
Phospholipid-nucleoside conjugates. 3. Syntheses and preliminary biological evaluation of 1-.beta.-D-arabinofuranosylcytosine 5'-monophosphate-L-1,2-dipalmitin and selected 1-.beta.-D-arabinofuranosylcytosine 5'-diphosphate-L-1,2-diacylglycerols (1982)

Several new phospholipid-ara-C conjugates have been prepared and tested as prodrugs of the parent ara-C. The new derivative include ara-CMP-L-dipalmitin, ara-CDP-L-distearin, ara-CDP-L dimyristin, ara-CDP-L-diolein, and the radioactively labeled derivative ara-CDP-L-di[1-14C]palmitin. In addition, the unusually stable ara-CMP-L-dipalmitin-N-phosphoryldicyclohexylurea adduct was isolated as a crystalline solid (two diastereomers) in the reaction sequence to prepare ara-CMP-L-dipalmitin. The new prodrugs were solubilized by sonication methods and tested for their antiproliferative activity in vitro against mouse myeloma MPC-11 cells and against L1210 lymphoid leukemia. Such studies demonstrated that the antiproliferative activities of the prodrugs (as determined by ED50) were less that ara-C on a molar basis. In the mouse myeloma cell line some evidence was obtained that the antiproliferative activity was related to the chain length of the fatty acid side chains in the prodrugs. In in vivo studies against L1210 lymphoid leukemia in mice, the prodrugs were shown to be much more effective than ara-C, with the overall efficacy apparently being independent of the length of the fatty acid side chain. Some evidence was obtained in the vivo studies that the ara-CDP-L-dimyristin, which bears the shortest fatty acid side chain, was more toxic at the higher dosages than the longer chain length derivatives.
Biomimetic Catalysis of a Porous Iron-Based Metal–Metalloporphyrin Framework (2012)

A porous metal-metalloporphyrin framework, MMPF-6, based upon an iron(III)-metalated porphyrin ligand and a secondary binding unit of a zirconium oxide cluster was constructed; MMPF-6 demonstrated interesting peroxidase activity comparable to that of the heme protein myoglobin as well as exhibited solvent adaptability of retaining the peroxidase activity in an organic solvent.
Becoming Pilgrims: Engaging Theory Through Practice in the Introductory World Religions Course (2004)

Abstract. This paper explores the use of the educational pilgrimage as an active learning strategy in the introductory world religions course. As we study pilgrimages from different religious traditions throughout the semester using Victor Turner as our theoretical guide, students also plan their own campus pilgrimage, paying homage to sites that help them reach their educational goals. Using student comments and my own observations, I highlight the ways in which the educational pilgrimage both affirms and raises critical questions about Turner's theory of pilgrimage. In this way, the educational pilgrimage is an opportunity for students to enhance and clarify their understanding of theory through practice.
Structure of the human renin gene. (1984)

The human renin gene was isolated from a Charon 4A human genomic library and characterized. The gene spans about 11.7 kilobases and consists of 10 exons and 9 introns that map at points that could be variable surface loops of the enzyme. The complete coding regions, the 5'- and 3'-flanking regions, and the exon-intron boundaries were sequenced. The active site aspartyl residues Asp-38 and Asp-226 are encoded by the third and eighth exons, respectively. The extra three amino acids (Asp-165, Ser-166, Glu-167) that are not present in mouse renin are encoded by the separate sixth exon, an exon as small as 9 nucleotides. The positions of the introns are in remarkable agreement with those in the human pepsin gene, supporting the view that the genes coding for aspartyl proteinases have arisen as the result of duplication of a common ancestral gene. As in most eukaryotic genes, the putative T-A-T-A and C-A-A-T sequences, which may play a role in the initiation of gene transcription, are found in the vicinity of -29 and -51 nucleotides of the cap site. Further upstream, at nucleotides -456 to -451, is located the hexanucleotide T-G-T-T-C-T, which has recently been suggested as a binding site for the glucocorticoid receptor. In the 3'-flanking region, there is the conserved hexanucleotide sequence A-A-T-A-A-A, thought to be necessary for polyadenylylation. Blot-hybridization analyses of the isolated gene clone and the total cellular DNA after digestion with restriction enzymes revealed that human renin is encoded by a single gene.
Cellular systems with many antennas: Large system analysis under pilot contamination (2012)

Base stations with a large number of transmit antennas have the potential to serve a large number of users simultaneously at higher rates. They also promise a lower power consumption due to coherent combining at the receiver. However, the receiver processing in the uplink relies on the channel estimates which are known to suffer from pilot interference. In this work, we perform an uplink large system analysis of multi-cell multi-antenna system when the receiver employs a matched filtering with a pilot contaminated estimate. We find the asymptotic Signal to Interference plus Noise Ratio (SINR) as the number of antennas and number of users per base station grow large while maintaining a fixed ratio. To do this, we make use of the similarity of the uplink received signal in a multi-antenna system to the representation of the received signal in CDMA systems. The asymptotic SINR expression explicitly captures the effect of pilot contamination and that of interference averaging. This also explains the SINR performance of receiver processing schemes at different regimes such as instances when the number of antennas are comparable to number of users as well as when antennas exceed greatly the number of users. Finally, we also propose that the adaptive MMSE symbol detection scheme, which does not require the explicit channel knowledge, can be employed for cellular systems with large number of antennas.
Frequency of off-targeting in genome edited pigs produced via direct injection of the CRISPR/Cas9 system into developing embryos (2019)

The prevalence of off-targeting is low via direct injection of CRISPR/Cas9 system into developing embryos, but the events cannot be accurately predicted. Off-targeting frequency of each CRISPR/Cas9 system should be deliberately assessed prior to its application in clinics.
Three-Dimensional Imaging of Intact Isolated Islets of Langerhans With Confocal Microscopy (1989)

We present a new technique for analyzing the three-dimensional structure of intact isolated islets of Langerhans. Adult rat and human islets were stained with whole-mount immunofluorescence techniques and optically sectioned with a confocal microscope. This has several advantages over traditional methods: 1) the technical difficulties in serial sectioning and handling the large numbers of sections are avoided, 2) optical sectioning by confocal microscopy gives improved resolution and strongly suppresses light from out-of-focus structures, and 3) entire islets can be rapidly imaged for the presence of positive staining. This new technique should facilitate the study of the three-dimensional structure of islets of Langerhans.
Lineage commitment in the progeny of murine hematopoietic preprogenitor cells: Influence of thrombopoietin and interleukin 5 (1998)

Normal mouse marrow cells were stimulated by stem cell factor (SCF) to form dispersed or multicentric blast colonies containing progenitor cells committed to various hematopoietic lineages. Combination of the eosinophil-specific regulator interleukin 5 with SCF increased the frequency of colonies containing eosinophil-committed progenitor cells with multicentric but not dispersed blast colonies. Combination of thrombopoietin with SCF increased the frequency of colonies containing megakaryocyte-committed progenitor cells with both types of blast colony. Neither interleukin 5 nor thrombopoietin significantly altered the number or total cell content of blast colonies or progenitor cell numbers in blast colonies from those stimulated by SCF alone. No correlation was observed between total progenitor cell content and the presence or absence of either eosinophil or megakaryocyte progenitors in either type of blast colony. The data argue against a random process as being responsible for the formation of particular committed progenitor cells or the possibility that lineage-specific regulators merely enhance survival of such committed progenitor cells formed in developing blast colonies.