gebhart/patrepeval huggingface dataset:
A 1-deoxy-d-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-d-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis (1998)

Several eubacteria including Esherichia coli use an alternative nonmevalonate pathway for the biosynthesis of isopentenyl diphosphate instead of the ubiquitous mevalonate pathway. In the alternative pathway, 2-C-methyl-D-erythritol or its 4-phosphate, which is proposed to be formed from 1-deoxy-D-xylulose 5-phosphate via intramolecular rearrangement followed by reduction process, is one of the biosynthetic precursors of isopentenyl diphosphate. To clone the gene(s) responsible for synthesis of 2-C-methyl-D-erythritol 4-phosphate, we prepared and selected E. coli mutants with an obligatory requirement for 2-C-methylerythritol for growth and survival. All the DNA fragments that complemented the defect in synthesizing 2-C-methyl-D-erythritol 4-phosphate of these mutants contained the yaeM gene, which is located at 4.2 min on the chromosomal map of E. coli. The gene product showed significant homologies to hypothetical proteins with unknown functions present in Haemophilus influenzae, Synechocystis sp. PCC6803, Mycobacterium tuberculosis, Helicobacter pyroli, and Bacillus subtilis. The purified recombinant yaeM gene product was overexpressed in E. coli and found to catalyze the formation of 2-C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate in the presence of NADPH. Replacement of NADPH with NADH decreased the reaction rate to about 1% of the original rate. The enzyme required Mn2+, Co2+, or Mg2+ as well. These data clearly show that the yaeM gene encodes an enzyme, designated 1-deoxy-D-xylulose 5-phosphate reductoisomerase, that synthesizes 2-C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate, in a single step by intramolecular rearrangement and reduction and that this gene is responsible for terpenoid biosynthesis in E. coli.
Biophysical aspects of blood flow in the microvasculature (1996)

The main function of the microvasculature is transport of materials. Water and solutes are carried by blood through the microvessels and exchanged, through vessel walls, with the surrounding tissues. This transport function is highly dependent on the architecture of the microvasculature and on the biophysical behavior of blood flowing through it. For example, the hydrodynamic resistance of a microvascular network, which determines the overall blood flow for a given perfusion pressure, depends on the number, size and arrangement of microvessels, the passive and active mechanisms governing their diameters, and on the apparent viscosity of blood flowing in them. Suspended elements in blood, especially red blood cells, strongly influence the apparent viscosity, which varies with several factors, including vessel diameter, hematocrit and blood flow velocity. The distribution of blood flows and red cell fluxes within a network, which influences the spatial pattern of mass transport, is determined by the mechanics of red cell motion in individual diverging bifurcations. Here, our current understanding of the biophysical processes governing blood flow in the microvasculature is reviewed, and some directions for future research are indicated.
Caveolin-1 is incorporated into mature respiratory syncytial virus particles during virus assembly on the surface of virus-infected cells (2002)

We have employed immunofluorescence microscopy and transmission electron microscopy to examine the assembly and maturation of respiratory syncytial virus (RSV) in the Vero cell line C1008. RSV matures at the apical cell surface in a filamentous form that extends from the plasma membrane. We observed that inclusion bodies containing viral ribonucleoprotein (RNP) cores predominantly appeared immediately below the plasma membrane, from where RSV filaments form during maturation at the cell surface. A comparison of mock-infected and RSV-infected cells by confocal microscopy revealed a significant change in the pattern of caveolin-1 (cav-1) fluorescence staining. Analysis by immuno-electron microscopy showed that RSV filaments formed in close proximity to cav-1 clusters at the cell surface membrane. In addition, immuno-electron microscopy showed that cav-1 was closely associated with early budding RSV. Further analysis by confocal microscopy showed that cav-1 was subsequently incorporated into the envelope of RSV filaments maturing on the host cell membrane, but was not associated with other virus structures such as the viral RNPs. Although cav-1 was incorporated into the mature virus, it was localized in clusters rather than being uniformly distributed along the length of the viral filaments. Furthermore, when RSV particles in the tissue culture medium from infected cells were examined by immuno-negative staining, the presence of cav-1 on the viral envelope was clearly demonstrated. Collectively, these findings show that cav-1 is incorporated into the envelope of mature RSV particles during egress.
Evidence for a stem cell hierarchy in the adult human breast (2007)

Cellular pathways that contribute to adult human mammary gland architecture and lineages have not been previously described. In this study, we identify a candidate stem cell niche in ducts and zones containing progenitor cells in lobules. Putative stem cells residing in ducts were essentially quiescent, whereas the progenitor cells in the lobules were more likely to be actively dividing. Cells from ducts and lobules collected under the microscope were functionally characterized by colony formation on tissue culture plastic, mammosphere formation in suspension culture, and morphogenesis in laminin-rich extracellular matrix gels. Staining for the lineage markers keratins K14 and K19 further revealed multipotent cells in the stem cell zone and three lineage-restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites in situ confirmed this pattern. The proposal that the four cell types are indeed constituents of an as of yet undescribed stem cell hierarchy was assessed in long-term cultures in which senescence was bypassed. These findings identify an adult human breast ductal stem cell activity and its earliest descendants.
Two-Mode Reed–Solomon Decoder Using A Simplified Step-by-Step Algorithm (2015)

Reed-Solomon (RS) codes are a type of forward error correction (FEC) coding that is highly efficient at combating burst errors in received messages. This efficiency has led to its widespread application in error correction in the head tag, often in combination with other channel coders for the construction of robust FEC coding. This brief outlines the design and implementation of a two-mode RS decoder using a simplified step-by-step (SS) algorithm for (255, 239) and (204, 188) RS codes. Calculation of the syndrome determinant in the RS decoder is achieved through Gaussian elimination using a 1-D systolic array with hardware architecture of low complexity, ideally suited for the higherdimensional matrices used in SS algorithms. The proposed twomode RS decoder is easily modified with regard to the delay-line buffer size, the delta accumulation and summation module, and the control unit. A two-mode RS decoder with approximately 32 K gates was fabricated using 180-nm complementary metal- oxide-semiconductor technology. Evaluation results confirm that the proposed device consumes only 57 mW at 166 MHz.
Principles of geographical information systems (1998)

1. Geographical Information: Society, Science, and Systems 2. Data models and axioms: Formal abstractions of reality 3. Geographical Data in the Computer 4. Data input, verification, storage and output 5. Creating continuous surfaces from point data 6. Optimal interpolation using geostatistics 7. The analysis of discrete entities in space 8. Spatial analysis using continuous fields 9. Errors and quality control 10. Error propagation in numerical modelling 11. Fuzzy sets and fuzzy geographical objects 12. Current issues and trends in GIS APPENDIX 1 GLOSSARY OF TERMS APPENDIX 2 A SELECTION OF WORLD WIDE WEB GEOGRAPHY AND GIS SERVERS APPENDIX 3 EXAMPLE DATA SETS
2006: the state of biologics. (2006)

In a room filled with managed care medical and pharmacy directors, the refrain was loud and clear: How are we going to pay for biologics?

Payers can’t afford them all, and employers do not yet fully grasp what the increased use of biologic therapies means for them. Self-insured plans can’t handle biologics, and municipal health plans are having a hard time providing ordinary drug benefits.

A tidal wave of specialty drugs, as one speaker called it, will hit in another four years — 60 percent of specialty drug spending will be for 4 percent of the population — pushing per-member, per-month costs ever higher.

These stark realities and more were raised at CBI’s third annual Specialty Pharmaceuticals, Biotech Therapies, and Injectables Forum, held in Washington, Jan. 23 and 24. Though biologics have been on payers’ radar screens for some time, far more questions were asked than answers given.

As the conference went on, other concerns bubbled to the surface. For physicians, there’s a realization that it’s not how you manage specialty drugs, it’s how you manage your practice. Hospital outpatient services for infusibles and injectables and how to manage them makes for another changing and contentious scene. Average sales price and specialty distribution issues have to be reckoned with now that Medicare Part D is front and center. And, like it or not, the costs involved beg the question of whether American health care is moving closer to a single-payer system. If so, where does that leave payers?

And don’t count on cost relief from follow-on products soon, despite the recent approval in Europe of a copycat human growth hormone, and with interferon alpha and beta, erythropoietin, and colony-stimulating factor not far behind.

Evidence-based medicine can help decision makers begin to answer some of these questions. Data gathered by the Cochrane Collaboration and Database of Abstracts of Reviews of Effects (DARE), for example, can be used in the absence of long-term outcomes data for many emerging biologic therapies.

The one area that may have the biggest effect on health benefits— and that will mandate realignment of that system — is genomics testing, determining even before birth what and when diseases will hit an individual. Would you tell a 25-year-old woman that by the time she reaches 55 she is likely to develop AML? Should she worry for 30 years or seek treatment to avoid its manifestation? No easy questions, no easy answers.

Finally, to make our heads spin, nanotechnology is looming. Wow!

One more thing is clear, based on the discussions and the questions people asked: Biotechnology Healthcare is ahead of the curve in showcasing these issues — as our current issue attests — as part of our mission to guide readers in making informed decisions. We intend to keep it that way.
Molecular genetics of the 1q23.3 schizophrenia susceptibility locus (2008)

Family based linkage studies have confirmed that part of chromosome lq23.3 contains a susceptibility gene for schizophrenia. This region was investigated by tests of allelic and haplotypic association in order to fine map a specific gene in the lq23.3 region. Previously published studies claimed that the genes RGS4 and CAPON on lq23.3 were associated with schizophrenia. For this research thesis multiple markers were genotyped at the RGS4 and CAPON loci in a London based case control sample, no evidence for association was found. Therefore further fine mapping was carried out in the region between the RGS4 and CAPON genes. Allelic and haplotypic associations with schizophrenia were found with three microsatellite and four SNP markers within the serine threonine kinase (UHMK1) gene. A replication study using an Aberdeen based case control sample also found statistically significant evidence of allelic and haplotypic association between TJHMK1 and schizophrenia. Re-sequencing of the UHMK1 gene was carried out in those individuals who had inherited alleles and haplotypes associated with schizophrenia. Three genetic variants were found. Genotyping of the whole case control sample showed that these changes were not associated with schizophrenia. The previously reported associations between schizophrenia and RGS4 as well as CAPON could possibly be explained by linkage disequilibrium between UHMK1 and both CAPON and RGS4. Alternatively there could be two or even three susceptibility genes within the 700 Kb region. At present no potential aetiological base pair changes have been detected in any of the three genes. UHMK1 is known to be highly expressed in regions of the brain implicated in schizophrenia and was found to be significantly down regulated in mice treated with the antipsychotic drug Clozapine. Further confirmation of the involvement of this gene in schizophrenia is needed followed by further efforts to detect genetic variation in or next to the gene which has an effect on expression and function of UHMK1.
The anti-tetanus immune response of neonatal mice is augmented by retinoic acid combined with polyriboinosinic:polyribocytidylic acid (2005)

Neonates are highly susceptible to infectious diseases and, in general, respond poorly to conventional vaccines due to immaturity of the immune system. In the present study, we hypothesized that the anti-tetanus toxoid (TT) vaccine response of neonatal mice could be enhanced by retinoic acid (RA), a bioactive retinoid, and polyriboinosinic:polyribocytidylic acid (PIC), an inducer of IFN. Early-life treatments with RA and/or PIC were well tolerated and stimulated both primary anti-TT IgG production in infancy and the memory response in adulthood. TT-specific lymphocyte proliferation and type 1/type 2 cytokine production were also significantly augmented. In addition, RA and PIC modulated the maturation and/or differentiation of neonatal B cells, natural killer (NK)/NKT cells, and antigen-presenting cells. Although RA alone increased the neonatal anti-TT antibody response, it selectively increased anti-TT IgG1 and IL-5, resulting in a skewed type 2 response. PIC, a potent adjuvant in adult mice, elevated neonatal anti-TT IgG as well as all IgG isotypes (IgG1, IgG2a, and IgG2b) and induced TT-specific IFN-gamma, an important type 1 cytokine; however, PIC alone failed to benefit the memory response. The combination of RA plus PIC was more potent than either agent alone in elevating primary and secondary anti-TT IgG responses as well as IgG isotypes. Moreover, RA plus PIC increased TT-specific IFN-gamma and IL-5, suggesting the combination effectively promoted both type 1 and type 2 responses in neonatal mice. Thus, RA combined with PIC, a nutritional-immunological intervention, seems promising as an adjuvant for early-life vaccination.
A new environment-sensitive fluorescent amino acid for Fmoc-based solid phase peptide synthesis (2004)

A new 4-(N,N-dimethylamino) phthalimide-based environment-sensitive fluorescent building block for solid phase peptide synthesis, has been synthesized and incorporated into peptides. Peptides incorporating this residue show great potential for biological applications in sensing protein/protein interactions.
Latent autoimmune diabetes of adults: From oral hypoglycemic agents to early insulin (2012)

Approximately 10% of phenotypic type 2 diabetics have islet autoantibodies and are referred to as having latent autoimmune diabetes of adults (LADA), and they land on early sulfonylurea failure and require insulin. Diagnosing LADA has treatment implications because of high risk of progression to insulin dependency. But often there is delay in insulin therapy, as there are no recommendations for islet antibody testing in adult-onset diabetes currently. LADA clinical risk score can identify adults at high risk who may benefit from antibody testing. The optimal treatment of LADA is not established. Early insulin therapy helps to achieve good metabolic control and better long-term outcomes by preserving β-cells and endogenous C-peptide secretion. Sulfonylureas are better avoided as they exhaust β-cells; glitazones and exenatide have favorable outcomes, whereas metformin needs to be used with caution. Understanding LADA will also bring new windows in managing type 1 diabetes. Information acquisition was done by reviewing the medical literature published since 1987, with particular attention to the natural history, genetic factors, and treatment of LADA.
Affinity‐Based Reverse Micellar Extraction and Separation (ARMES): A Facile Technique for the Purification of Peroxidase from Soybean Hulls (1993)

A new technique for the purification of proteins has been developed which combines the high selectivity of affinity interaction with the scalability and ease of operation of liquid-liquid extraction. The approach is called affinity-based reverse micellar extraction and separation (ARMES). The salient features of ARMES include the following: (1) intraphasic interaction between the ligand and ligate which provides for high ligand utilization; (2) no chemical modification of the ligand is needed; and (3) ease of operation and inherent scalability due to the use of liquid-liquid extraction. This technique has been used to purify the peroxidase from soybean hulls using the lectin concanavalin A (con A) as a sugar-binding affinity ligand. A purification factor of 30 is achieved to provide a nearly pure peroxidase solution (as determined by HPLC and SDS-PAGE) with nearly complete regeneration of the con A ligand. We propose that ARMES will be useful in the facile purification of complex biomolecules such as glycoform protein variants using lectins as affinity ligands and proteins of therapeutic importance using antibodies as affinity ligands.
Capillary Electrophoresis for the Analysis of Biopolymers (2000)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTCapillary Electrophoresis for the Analysis of BiopolymersSergey N. Krylov and Norman J. DovichiView Author Information Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2 Cite this: Anal. Chem. 2000, 72, 12, 111–128Publication Date (Web):May 9, 2000Publication History Published online9 May 2000Published inissue 1 June 2000https://pubs.acs.org/doi/10.1021/a1000014chttps://doi.org/10.1021/a1000014creview-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views1268Altmetric-Citations104LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Capillary electrophoresis,Electrophoresis,Fluorescence,Genetics,Peptides and proteins Get e-Alerts
Sequence analysis of the haemagglutinin (HA) of influenza A (H1N1) viruses present in clinical material and comparison with the HA of laboratory-derived virus (1991)

We used the polymerase chain reaction to amplify the HA1 coding region of influenza A (H1N1) viruses present in clinical material from recent cases of influenza in the U.K. Previously, we have demonstrated that isolation of human influenza viruses in embryonated hens' eggs selects variants which have amino acid substitutions in their haemagglutinin (HA) clustering around the receptor-binding site. Such egg-selected variants are often antigenically distinct from each other and from corresponding viruses isolated on mammalian cells. Since in general the virus used for vaccine production is an egg-adapted virus, it is important to determine the extent to which these variants are present in the natural virus which causes disease in man. To achieve this, amplified products from clinical material were cloned and many individual clones sequenced. Our results indicate that the HA of the naturally occurring virus is relatively homogeneous and represented by virus isolated in the laboratory on MDCK cells, whereas the variants isolated in eggs are present only at low levels in clinical material.
The role of the opioid system in alcohol dependence (2013)

The role of the brain opioid system in alcohol dependence has been the subject of much research for over 25 years. This review explores the evidence: firstly describing the opioid receptors in terms of their individual subtypes, neuroanatomy, neurophysiology and ligands; secondly, summarising emerging data from specific neurochemical, behavioural and neuroimaging studies, explaining the characteristics of addiction with a focus on alcohol dependence and connecting the opioid system with alcohol dependence; and finally reviewing the known literature regarding opioid antagonists in clinical use for alcohol dependence. Further interrogation of how modulation of the opioid system, via use of MOP (mu), DOP (delta) and KOP (kappa) agents, restores the balance of a dysregulated system in alcohol dependence should increase our insight into this disease process and therefore guide better methods for understanding and treating alcohol dependence in the future.
Identification of a vitamin D-responsive element in the 5'-flanking region of the rat 25-hydroxyvitamin D3 24-hydroxylase gene. (1994)

The 5'-flanking region of the rat vitamin D3 24-hydroxylase (P450cc24) gene was examined and a vitamin D-responsive element (VDRE) responsible for the 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) enhancement was identified. Unidirectional deletion analyses of the 5'-flanking region indicated that the region [-167/-102] is involved in vitamin D responsiveness. Further functional analyses showed that the segment [-204/-129] conferred the hormone responsiveness in an orientation-independent manner when it was placed upstream to the heterologous thymidine kinase promoter or the rabbit beta-globin promoter. The segment [-204/-129] contained two direct repeat motifs homologous to other VDREs found in the osteocalcin and osteopontin genes. Synthetic oligonucleotides containing the putative VDRE were used for functional analyses and gel mobility shift assays. The proximal [-151/-137], but not the distal [-169/-155] direct repeat activated the transcription in response to 1,25-(OH)2D3 through the beta-globin promoter. Furthermore, the proximal direct repeat formed a complex with the vitamin D receptor and a nuclear accessory factor(s) from COS cells (or retinoid X receptor) in the presence of 1,25-(OH)2D3. These results indicate that a direct repeat motif, AGGTGAgt-gAGGGCG, located at -151 base pairs upstream in the antisense strand binds to a heterologous dimer consisting of the VDR occupied with 1,25-(OH)2D3 and the nuclear accessory factor and that it plays a critical role in mediating the vitamin D enhancement of the rat P450cc24 gene expression.
Vagal paraganglioma (2 case reports). (1991)

Paragangliomas are rare tumours of the head and neck and are a diagnostic challenge. Two cases of paragangliomas arising from the vagus are being reported. In the first case, an angiogram raised the possibility of intravagal tumour and exploration followed by biopsy confirmed the diagnosis. In the second case, it was a diagnostic surprise where exploration was done on a clinical suspicion of parotid swelling and on the table, the swelling was found to arise from the vagus nerve pushing the parotid gland laterally.