gebhart/patrepeval huggingface dataset:
FURTHER 6-DEOXYTETRACYCLINE STUDIES: EFFECT OF AROMATIC SUBSTITUENTS ON BIOLOGICAL ACTIVITY (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFURTHER 6-DEOXYTETRACYCLINE STUDIES: EFFECT OF AROMATIC SUBSTITUENTS ON BIOLOGICAL ACTIVITYJohn J. Beereboom, Joseph J. Ursprung, Hans H. Rennhard, and Charles R. StephensCite this: J. Am. Chem. Soc. 1960, 82, 4, 1003–1004Publication Date (Print):February 1, 1960Publication History Published online1 May 2002Published inissue 1 February 1960https://doi.org/10.1021/ja01489a064RIGHTS & PERMISSIONSArticle Views140Altmetric-Citations23LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (257 KB) Get e-Alertsclose Get e-Alerts
Carbohydrate-Specific Receptors of the Liver (1982)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Sequencing and characterization of the sdaC gene and identification of the sdaCB operon in Escherichia coli K12 (1994)

We describe here the regulatory and coding region, and DNA sequence, for a newly recognized gene, sdaC, which codes for a hydrophobic protein with several predicted membrane-spanning domains. sdaC and sdaB form a single operon, with 57 bp between the end of sdaC and the start of sdaB. Expression of the sdaCB operon is regulated mainly by catabolite repression, but is also slightly sensitive to regulation by leucine-responsive regulatory protein. Cells carrying sdaC on a multicopy plasmid have increased L-serine transport capacity, insensitive to threonine, suggesting that sdaC might code for a recently described highly specific serine transporter [Kayahara, T., Thelen, P., Ogawa, W., Inaba, K., Tsuda, M., Goldberg, E. B. & Tsuchiya, T. (1992) J. Bacteriol. 174, 7482-7485].
Improvements in focused ion beam micromachining of interconnect materials (2002)

Focused ion beam micromachining (FIBM) of integrated circuits continues to be an important tool for design debug, editing, and verification; for metrology; and for process control. FIBM of copper interconnects has presented challenges not faced when micromachining aluminum interconnects and the introduction of low-k dielectrics present additional challenges. A new approach to chemically assisted FIBM of thin film Cu, SiO2, and SiLK low-k material using polar precursor molecules has been investigated. Polar alcohols were used to reduce the sputter rate of SiO2 and SiLK while having a minimal effect on the Cu sputter rate. A new FIBM process based on the reduction of the FIB Ga+ energy from the typical 25 to 15 keV is also introduced. The new low energy FIBM process was shown to increase the sputter rate of polycrystalline Cu with strong (111) crystallographic texture by a factor of 2.5. This increase in the sputter rate of Cu combined with a slight reduction of the sputter rate of SiO2 and SiLK results in a Cu/SiO2 selectivity of greater than 7 and a Cu/SiLK selectivity of approximately 3. These are the largest selectivity values reported until now for both systems. The Onderdelinden theory of single-crystal sputtering was used to explain this seemingly anomalous increase of the Cu sputter rate with the reduction of the FIB Ga+ energy.
Dendritic cells and HNSCC: A potential treatment option? (Review) (2005)

Patient survival in head and neck squamous cell cancer (HNSCC) has not changed significantly in many years, despite progress in surgical, radiotherapy and chemotherapy techniques. Immunotherapy, a rapidly progressing alternative cancer treatment, aims to prompt or assist the body's immune system to combat the disease itself. A number of strategies exist including the use of dendritic cells, natural antigen presenting cells capable of stimulating an anti-tumor immune response. Encouraging work has been performed using these cells as vaccines against a number of tumors especially melanoma. Work with head and neck cancer is also encouraging, but less advanced. Dendritic cell presence in head and neck squamous cell cancers is associated with an improved prognosis, however due to immunosuppression, the exact mechanism of which remains poorly understood, these cells do not function efficiently. This prevents the stimulation of an effective anti-tumor immune response by the patient and allows tumor growth to continue. This review summarises the current level of understanding of dendritic cells and their relationship with HNSCC. It briefly summarises work with dendritic cells and other cancers where relevant to HNSCC; dendritic cells and head and neck cancer; the possible causes of dendritic cell impairment; the techniques used to restore their function and the methods used to prime the dendritic cells prior to their use as vaccines for the stimulation of an anti-tumor response.
Fine-Tuning of Galactoglucan Biosynthesis in Sinorhizobium meliloti by Differential WggR (ExpG)-, PhoB-, and MucR-Dependent Regulation of Two Promoters (2008)

Depending on the phosphate concentration encountered in the environment Sinorhizobium meliloti 2011 synthesizes two different exopolysaccharides (EPS). Galactoglucan (EPS II) is produced under phosphate starvation but also in the presence of extra copies of the transcriptional regulator WggR (ExpG) or as a consequence of a mutation in mucR. The galactoglucan biosynthesis gene cluster contains the operons wga (expA), wge (expE), wgd (expD), and wggR (expG). Two promoters, differentially controlled by WggR, PhoB, and MucR, were identified upstream of each of these operons. The proximal promoters of the wga, wge, and wgd transcription units were constitutively active when separated from the upstream regulatory sequences. Promoter activity studies and the positions of predicted PhoB and WggR binding sites suggested that the proximal promoters are cooperatively induced by PhoB and WggR. MucR was shown to strongly inhibit the distal promoters and bound to the DNA in the vicinity of the distal transcription start sites. An additional inhibitory effect on the distal promoter of the structural galactoglucan biosynthesis genes was identified as a new feature of WggR in a mucR mutant. A regulatory model of the fine-tuning of galactoglucan production is proposed.
RNA Gain-of-Function in Spinocerebellar Ataxia Type 8 (2009)

Microsatellite expansions cause a number of dominantly-inherited neurological diseases. Expansions in coding-regions cause protein gain-of-function effects, while non-coding expansions produce toxic RNAs that alter RNA splicing activities of MBNL and CELF proteins. Bi-directional expression of the spinocerebellar ataxia type 8 (SCA8) CTG CAG expansion produces CUG expansion RNAs (CUG(exp)) from the ATXN8OS gene and a nearly pure polyglutamine expansion protein encoded by ATXN8 CAG(exp) transcripts expressed in the opposite direction. Here, we present three lines of evidence that RNA gain-of-function plays a significant role in SCA8: 1) CUG(exp) transcripts accumulate as ribonuclear inclusions that co-localize with MBNL1 in selected neurons in the brain; 2) loss of Mbnl1 enhances motor deficits in SCA8 mice; 3) SCA8 CUG(exp) transcripts trigger splicing changes and increased expression of the CUGBP1-MBNL1 regulated CNS target, GABA-A transporter 4 (GAT4/Gabt4). In vivo optical imaging studies in SCA8 mice confirm that Gabt4 upregulation is associated with the predicted loss of GABAergic inhibition within the granular cell layer. These data demonstrate that CUG(exp) transcripts dysregulate MBNL/CELF regulated pathways in the brain and provide mechanistic insight into the CNS effects of other CUG(exp) disorders. Moreover, our demonstration that relatively short CUG(exp) transcripts cause RNA gain-of-function effects and the growing number of antisense transcripts recently reported in mammalian genomes suggest unrecognized toxic RNAs contribute to the pathophysiology of polyglutamine CAG CTG disorders.
Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly(I:C) leads to myeloid cell maturation and activates NK cells (2011)

Owing to high rates of tumor relapse, ovarian cancer remains a fatal disease for which new therapeutic approaches are urgently needed. Accumulating evidence indicates that immune stimulation may delay or even prevent disease recurrence in ovarian cancer. In order to elicit proinflammatory signals that induce or amplify antitumor immune reactivity, we mimicked viral infection in ascites-derived ovarian cancer cells. By transfection or electroporation we targeted the synthetic double-stranded RNA poly(I:C) intracellularly in order to activate melanoma differentiation-associated gene-5 (MDA-5), a sensor of viral RNA in the cytosol of somatic cells. Cancer cells reacted with enhanced expression of HLA-class I, release of CXCL10, IL-6, and type I IFN as well as tumor cell apoptosis. Monocytes and monocyte-derived DCs (MoDCs) engulfed MDA-5-activated cancer cells, and subsequently upregulated HLA-class I/II and costimulatory molecules, and secreted CXCL10 and IFN-α. Further, this proinflammatory milieu promoted cytolytic activity and IFN-γ secretion of NK cells. Thus, our data suggest that the engagement of MDA-5 in a whole tumor cell vaccine is a promising approach for the immunotherapy of ovarian cancer.
Immunization of mice against Plasmodium vinckei with a combination of attenuated Salmonella typhimurium and malarial antigen (1990)

Infection with the blood stage of the malaria parasite Plasmodium vinckei is uniformly lethal in mice. We found that immunization of BALB/c mice with a combination of killed P. vinckei antigens and an attenuated (aroA) Salmonella typhimurium strain induces high levels of protection against challenge with live P. vinckei. This is especially significant because, in our previous studies, immunization of mice with killed P. vinckei antigens and adjuvants such as Bordetella pertussis, complete Freund adjuvant, and saponin failed to induce protective immunity. Immunization with attenuated S. typhimurium alone did not provide any nonspecific immunity. In vivo depletion of CD4+ T cells in the mice immunized with attenuated S. typhimurium and P. vinckei antigens caused the loss of their immunity. Expression of this immunity required the presence of a spleen. These results support our previous hypothesis that a blood stage malaria vaccine may need both induction of CD4+ T cells specific for the parasite and modification of the spleen with a vaccine vehicle. Therefore, attenuated Salmonella strains such as the one used in this study, when expressing recombinant malarial antigens, might fulfill this requirement.
B-Cell Activation by Helper T-Cell Membranes (1994)

Resting B cells can be stimulated to proliferate and differentiate to antibody-producing cells by the combination of cell contact and soluble signals provided by activated primed helper T (Th) cells. The ability of purified plasma membranes from activated Th cell clones and recombinant lymphokines to reconstitute B cell proliferation and differentiation has allowed an increased understanding of B cell activation and characterization of the molecules involved. B cell-Th cell contact appears sufficient for delivering the proliferative signal to B cells in the absence of lymphokines. A receptor ligand pair that plays a critical role in delivery of the contact signal is CD40 on the B cell surface and the ligand for CD40 on activated Th cells. Lymphokines alone do not drive resting B cell differentiation, however, when these soluble signals are delivered during the time of B cell DNA replication, they effect B cell differentiation and isotype switching. Delivery of the CD40-dependent contact signal to resting B cells appears to require a high degree of CD40 crosslinking on the B cell surface. Providing contact signals to naive B cells with recombinant molecules in membrane fractions may allow the generation of methodology to support the production of novel antibodies in vitro.
Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria (2003)

Betaine plasma concentrations change rapidly after ingestion. Elimination half-life increased during continuous dosing over 5 days. Betaine is mainly eliminated by metabolism. More pharmacokinetic and pharmacodynamic studies in hyperhomocysteinaemic patients are needed to refine the current treatment with betaine.
Concepts for the Future: In Conjunction with the HydroVision '94 Conference (1994)

None supplied. From introduction: A mission of the HydroVision '94 conference, August 17-19, 1994, is to share ideas for meeting challenges and ensuring the future of hydro as a socially and environmentally sound source of sustainable energy. This book, Concepts for the Future, contains 24 written reports submitted in conjunction with HydroVision '94 that share information about recent successful hydro activities that could be models for the future. The reports are divided into seven categories: Operations &amp; Maintenance; Regulation &amp; Legislation; Rehabilitation &amp; Retrofitting; Water Resources; Worldwide Hydro; General Topics; New Technology for Hydro; and General Topics: Pumped Storage.
Multi-site data collection and evaluation in spoken language understanding (1993)

The Air Travel Information System (ATIS) domain serves as the common task for DARPA spoken language system research and development. The approaches and results possible in this rapidly growing area are structured by available corpora, annotations of that data, and evaluation methods. Coordination of this crucial infrastructure is the charter of the Multi-Site ATIS Data COllection Working group (MADCOW). We focus here on selection of training and test data, evaluation of language understanding, and the continuing search for evaluation methods that will correlate well with expected performance of the technology in applications.
Flip-chip-bonded, 8-wavelength AlGaInAs DFB laser array operable up to 70&#x00B0;C for silicon WDM interconnects (2014)

An 8-wavelength light source for silicon WDM transceiver was developed using an AlGaInAs DFB laser array integrated with tapered-SOA and precise flip-chip bonding technology. The device demonstrated high Si-waveguide-coupled output powers of >+2.3dBm/ch under 8-ch simultaneous operation at 70°C.
A convenient and adaptable microcomputer environment for DNA and protein sequence manipulation and analysis (1986)

We describe the further development of a widely used package of DNA and protein sequence analysis programs for microcomputers (1,2,3). The package now provides a screen oriented user interface, and an enhanced working environment with powerful formatting, disk access, and memory management tools. The new GenBank floppy disk database is supported transparently to the user and a similar version of the NBRF protein database is provided. The programs can use sequence file annotation to automatically annotate printouts and translate or extract specified regions from sequences by name. The sequence comparison programs can now perform a 5000 X 5000 bp analysis in 12 minutes on an IBM PC. A program to locate potential protein coding regions in nucleic acids, a digitizer interface, and other additions are also described.
Characterization of cis-regulatory elements of the vascular endothelial growth inhibitor gene promoter (2005)

VEGI (vascular endothelial growth inhibitor), a member of the tumour necrosis factor superfamily, has been reported to inhibit endothelial cell proliferation, angiogenesis and tumour growth. We identified and cloned approx. 2.2 kb of the VEGI promoter from mouse cerebral endothelial cells. The promoter contained an atypical TATA-box-binding protein sequence TAAAAAA residing at -32/-26 relative to the transcription initiation site (+1), 83 bp upstream from the ATG start codon. To investigate critical sequences in the VEGI promoter, a series of deleted and truncated segments were constructed from a 2300 bp promoter construct (-2201/+96) linked to a luciferase reporter gene. Transient transfection of cerebral microvascular cells (bEND.3) and rat C6 glioma cells demonstrated that a 1700 bp deletion from the -2201 to -501 did not significantly affect promoter activity; however, a truncated construct (-501/+96) lacking the region between -312 and -57 resulted in nearly 90% loss of promoter activity. A consensus NF-kappaB (nuclear factor kappaB) and several SP1 (specificity protein-1)-binding sequences were identified within the deleted segment. Supershift analysis revealed that NF-kappaB subunits, p50 and p65, interacted with the VEGI promoter. Exposure of cerebral endothermic cells to the pro-inflammatory cytokine, tumour necrosis factor-alpha, increased VEGI mRNA levels and DNA-binding activities, whereas an NF-kappaB inhibitor attenuated this increase. In addition, p65 overexpression enhanced, whereas p50 overexpression decreased, the luciferase activity. Furthermore, mutation of the NF-kappaB DNA binding site blocked this p65- and tumour necrosis factor-alpha-induced luciferase activity. These findings suggest that the transcription factor NF-kappaB plays an important role in the regulation of VEGI expression.
Low-Loss Integrated Photonic Switch Using Subwavelength Patterned Phase Change Material (2018)

Efficient integrated photonic switches play a critical role in both interchip optical interconnects and data center networks that need to be dynamically reconfigured. Here, we demonstrate a 1 × 2 switch using phase change material Ge–Sb–Te (GST) combined with a silicon nitride microring resonator. The switch operates by utilizing the dramatic difference in the optical refractive index and extinction coefficient between the crystalline and amorphous phases of GST. By patterning and encapsulating the GST into subwavelength structures, the device achieves a low insertion loss of less than 1 dB in both output ports and can be switched reliably both photothermally and electrothermally.
BCR pathway inhibition as therapy for chronic lymphocytic leukemia and lymphoplasmacytic lymphoma (2014)

Chronic lymphocytic leukemia (CLL) and lymphoplasmacytic lymphoma (LPL) are malignancies of mature B cells. In LPL, mutations of the adaptor protein MYD88 (L265P) in the Toll-like receptor pathway have been recognized recently as being a hallmark of the disease and indicate a dependence of the tumor on this pathway. In CLL, functional studies have implicated BCR activation in the tissue microenvironment as a pivotal pathway in the pathogenesis. Bruton's tyrosine kinase (BTK) and the PI3Kδ isoform are essential for BCR signaling and also seem to be required for signal transduction in LPL cells, even if the role of BCR signaling in this disease remains less well defined. Ibrutinib, a covalent inhibitor of BTK approved by the Food and Drug Administration as a second-line treatment for CLL, and idelalisib, a selective inhibitor of PI3Kδ, achieve excellent clinical responses in both diseases irrespective of classic markers indicating high-risk disease. Several additional inhibitors targeting BTK and PI3Kδ, as well as the spleen tyrosine kinase, have entered clinical trials. This review discusses the biologic basis for kinase inhibitors as targeted therapy for CLL and LPL and summarizes the clinical experience with these agents.
Extracellular production of L -ascorbic acid by Chlorella protothecoides , Prototheca species, and mutants of P. moriformis during aerobic culturing at low pH (2002)

Nine strains of Chlorella protothecoides and 43 strains representing the five species of Prototheca were screened in flask culture for their ability to synthesize L-ascorbic acid (AA). Ascorbic acid was detected in all strains, ranging from 4.8 to 0.38 mg AA g x (-1) of dry cells. Organisms selected for further study grew well and maintained their AA productivity above a pH of 3.5. They can produce AA using a variety of carbon and nitrogen sources. Aerobic fermentation of selected strains resulted in extracellular accumulation of AA up to 76 mg x l(-1). By classical mutagenesis and selection methods, we created mutants of Prototheca moriformis ATCC 75669 that produced greater quantities of AA than the wild-type strain (78.4 vs 21.9 mg AA g x (-1) of cells). A process based on extracellular production could greatly reduce the cost of AA manufacture by eliminating the need for extraction of the AA from the cells.
Controllable Reversibility of ansp2tosp3Transition of a Single Wall Nanotube under the Manipulation of an AFM Tip: A Nanoscale Electromechanical Switch? (2000)

A simulation of the deflection of a single wall nanotube under the manipulation of an atomic force microscope tip revealed the key feature characterizing the deformation at relatively small bending angles to be a reversible transition from sp(2) to sp(3) bonding configurations in the bending region, leading to a 2 orders of magnitude reduction in conductance consistent with our most recent experimental observation. A local analysis elucidating the underlying physics of the findings is also discussed.
p400 Is Required for E1A to Promote Apoptosis (2005)

The adenovirus E1A oncoprotein promotes proliferation and transformation by binding cellular proteins, including members of the retinoblastoma protein family, the p300/CREB-binding protein transcriptional coactivators, and the p400-TRRAP chromatin-remodeling complex. E1A also promotes apoptosis, in part, by engaging the ARF-p53 tumor suppressor pathway. We show that E1A induces ARF and p53 and promotes apoptosis in normal fibroblasts by physically associating with the retinoblastoma protein and a p400-TRRAP complex and that its interaction with p300 is largely dispensable for these effects. We further show that E1A increases p400 expression and, conversely, that suppression of p400 using stable RNA interference reduces the levels of ARF, p53, and apoptosis in E1A-expressing cells. Therefore, whereas E1A inactivates the retinoblastoma protein, it requires p400 to efficiently promote cell death. These results identify p400 as a regulator of the ARF-p53 pathway and a component of the cellular machinery that couples proliferation to cell death.
Allogeneic tumor cell vaccines (2013)

The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies.