gebhart/patrepeval huggingface dataset:
New‐generation recombinant factor concentrates: bridge to gene therapy (2001)

Despite our best efforts to deceive the immune system, outwit pathogens, and improve upon the design of nature, there continues to be a need to improve the margin of safety of treatment for those with bleeding disorders. The current approach includes: (1) recombinant factor concentrates free of added proteins; (2) 'designer' factor molecules that enhance function and reduce immunogenicity; and (3) modulation of the immune system to suppress immune response in those who develop inhibitors. The hope is that through advances in our understanding of the coagulation and immune systems, treatment of haemophilia in the new millennium will be safer and less immunogenic. Currently available recombinant clotting factor concentrates include those produced: (1) with pasteurized human serum albumin in the cell culture medium as a stabilizer; (2) with bovine serum proteins in the cell culture medium; and (3) free of plasma derivatives. To the extent that current recombinant clotting factor concentrates contain even trace amounts of human or animal protein, there is continuing potential for transmission of nonenveloped viruses, including hepatitis A and parvovirus, and the theoretical potential for transmission of relatively unknown agents, such as prions (Creutzfeldt-Jakob disease or its variant). Second-generation recombinant factor concentrates that do not use human albumin as a stabilizer are currently in clinical trials, and third-generation recombinant factor concentrates currently in development take advantage of new strategies to achieve a 'protein-free' cell culture, purification, and final formulation. It is likely that improvement in safety and reduction in immunogenicity will require modification not only of antigenic structure but also of the immune response to coagulation proteins.
Post-ovulatory ageing of the human oocyte and embryo failure (1998)

We carried out a prospective study of 221 healthy women who were attempting pregnancy. During the study, women collected daily urine samples and kept daily records of intercourse. Ovulation and early pregnancy losses were later identified by immunoassays of urinary human chorionic gonadotrophin and steroid metabolites. We have used these data to examine whether the risk of early pregnancy loss was higher with post-ovulatory ageing of the oocyte. 192 pregnancies were ranked by the probability that the oocyte might have aged before fertilization. There was a statistically significant increase in the risk of early loss as the likelihood of oocyte ageing increased (P < 0.05). No similar risk was observed for clinical miscarriages. Post-ovulatory ageing of the oocyte prior to fertilization may cause early pregnancy failure in humans as it does in several other mammalian species.
Effect of PCR template concentration on the composition and distribution of total community 16S rDNA clone libraries (1997)

Total DNA from sediment samples was isolated by a direct lysis technique. Purified DNA was used as template either undiluted or diluted 1:10 prior to polymerase chain reaction (PCR) amplification of 16S rRNA genes. Full-length inserts were analysed for restriction fragment length polymorphisms (RFLP) with the enzyme Cfo1, and the resulting distribution and abundance of RFLP patterns compared between the undiluted and diluted PCR reactions. Results indicate that for low PCR template concentrations, in the range from a few picograms to tens of picograms DNA, proportional representation of specific RFLP types was not reproducible upon template dilution, confirming that PCR amplification of 16S rDNA cannot be used directly to infer microbial abundance. In particular, only 15-24% of the RFLP types recovered from a sample were present in both the undiluted and diluted extracts. We propose that very low template concentrations in the PCR generate random fluctuations in priming efficiency, which led to the contrast in RFLP types observed in the libraries from the undiluted and diluted extracts.
The Protein Kinase/Endoribonuclease IRE1α That Signals the Unfolded Protein Response Has a Luminal N-terminal Ligand-independent Dimerization Domain (2002)

In response to accumulation of unfolded proteins in the endoplasmic reticulum (ER), cells activate an intracellular signal transduction pathway called the unfolded protein response (UPR). IRE and PERK are the two type-I ER transmembrane protein kinase receptors that signal the UPR. The N-terminal luminal domains (NLDs) of IRE1 and PERK sense ER stress conditions by a common mechanism and transmit the signal to regulate the cytoplasmic domains of these receptors. To provide an experimental system amenable to detailed biochemical and structural analysis to elucidate the mechanism of ER-transmembrane signaling mechanism mediated by the NLD, we overexpressed the soluble luminal domain of human IRE1alpha in COS-1 cells by transient DNA transfection. Here we report the expression, purification, and characterization of the soluble NLD. The biological function of the NLD was confirmed by its ability to associate with itself and to interact with both the membrane-bound full-length IRE1alpha receptor and the ER chaperone BiP. Functional and spectral studies suggested that the highly conserved N-linked glycosylation site is not required for proper protein folding and self-association. Interestingly, we demonstrated that the NLD forms stable dimers linked by intermolecular disulfide bridges. Our data support that the luminal domain represents a novel ligand-independent dimerization domain.
Evaluation of polycrystalline silicon membranes on fused silica for x-ray lithography masks (1989)

Single crystalline Si films, heavily doped with boron for etch selectivity and often counterdoped with Ge to reduce stresses, are now commonly used as membranes in x-ray masks. We have investigated preparation and properties of much simpler membrane structures, consisting of undoped polycrystalline Si films deposited either on oxidized Si wafers or on fused silica substrates. The latter case is particularly simple since concentrated HF that is used for etching the fused silica substrate, does not attack Si. Therefore, after coating both sides of a fused silica substrate with polycrystalline Si, a window is opened in Si on one side by simple lithography, and the wafer is immersed in HF to complete the process. Stress of the membranes can be tuned by adjusting deposition conditions, annealing temperature, and choice of high temperature glass instead of silica for the substrate. Data from three polycrystalline membranes indicate a higher fracture strength and a larger effective elastic modulus than in equivalent single crystalline Si structures. However, optical transparency is lower because of light scattering by grain boundaries.
Monitoring oral anticoagulant therapy – INR values for the Owren prothrombin time (2004)

Oral anticoagulant therapy, the principal therapeutic inter-vention for preventing venous thromboembolism is monitored by the prothrombin time test using either the procedure of the Quick PT or the Owren PT. The latter is frequently called Thrombotestt after its commercial name. The prothrombin time is the most widely performed clotting test with nearly twice the number of PT’s performed as its nearest rival, the activated partial thromboplastin time (aPTT). Worldwide, the number of PT measurements in 2000 was esti-mated to be 800 million.
Lead-selective bulk optodes based on neutral ionophores with subnanomolar detection limits (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLead-selective bulk optodes based on neutral ionophores with subnanomolar detection limitsMarkus. Lerchi, Eric. Bakker, Bruno. Rusterholz, and Wilhelm. SimonCite this: Anal. Chem. 1992, 64, 14, 1534–1540Publication Date (Print):July 15, 1992Publication History Published online1 May 2002Published inissue 15 July 1992https://pubs.acs.org/doi/10.1021/ac00038a007https://doi.org/10.1021/ac00038a007research-articleACS PublicationsRequest reuse permissionsArticle Views778Altmetric-Citations185LEARN 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 Get e-Alerts
Estimating the Combustibility of Various Coals by TG-DTA (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEstimating the Combustibility of Various Coals by TG-DTAYong Chen, Shigeikatsu Mori, and Wei-Ping PanCite this: Energy Fuels 1995, 9, 1, 71–74Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://doi.org/10.1021/ef00049a011Request reuse permissionsArticle Views591Altmetric-Citations43LEARN 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 (404 KB) Get e-Alertsclose Get e-Alerts
Radioiodination techniques for small organic molecules (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRadioiodination techniques for small organic moleculesRobert H. Seevers and Raymond E. CounsellCite this: Chem. Rev. 1982, 82, 6, 575–590Publication Date (Print):December 1, 1982Publication History Published online1 May 2002Published inissue 1 December 1982https://doi.org/10.1021/cr00052a002RIGHTS & PERMISSIONSArticle Views1981Altmetric-Citations246LEARN 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 (2 MB) Get e-Alerts Get e-Alerts
The Use of Pupillometry in Joint and Connective Tissue Diseases (2002)

The central and peripheral nervous systems are variably affected in the rheumatic diseases. Automated standardized infrared pupillometry allows the safe, noninvasive assessment of the pupillary innervation. Pupillometry has already been used in studying the autonomic nervous system (ANS) in various rheumatic diseases. In systemic lupus erythematosus, the irideal parasympathetic branch of ANS was more affected then the sympathetic branch. In Sjögren's syndrome, signs of pupillary parasympathetic denervation have been reported. In rheumatoid arthritis, pupil parasympathetic dysfunction has been shown to correlate with ocular dryness. In systemic sclerosis (SSc), both sympathetic and parasympathetic irideal impairment have been demonstrated. Beside providing autonomic innervation, sensory nerves fibers are able to control iris diameter. Exogenous ocular instillation of substance P (SP), a sensory neuropeptide, can determine an omathropine-resistant, non-cholinergic myosis, acting on specific receptors present on the iris sphincter muscle. We first studied pupillary SP-ergic responsiveness in SSc, evaluating substance P (SP)-stimulated pupillary diameters by pupillometry. A higher basal and SP-stimulated myosis was found in lSSc versus both dSSc and controls, whereas no differences existed between dSSc and controls. From the literature, the pupillary parasympathetic nervous system seems to be more affected than the sympathetic branch of ANS in the rheumatic diseases characterized by an inflammatory status. However, we found in SSc both sympathetic and parasympathetic pupil control to be equally impaired. From our experience, we conclude that pupillary nervous control is differently affected in the two subsets of SSc, and that the SP-ergic system seems to be impaired only in lSSc.
Transmit antenna diversity in Ricean fading MIMO channels with co-channel interference (2001)

Transmit antenna diversity using closed loop and open loop modes are compared in environments with line of sight propagation and spatially and temporally non-white noise. The connection between the feedback channel capacity in closed loop modes and the channel coherence time is investigated. It is shown that in LOS environments, the requirements on the feedback channel bit rate is lower. Furthermore, we derived the beamforming vector in closed loop transmit diversity with directional interference and showed how this gives an equivalent gain in SNR of about 3 dB at the receiver, even at a beamforming weight phase resolution of 90 .
Evidence that Na+/H+ exchanger isoforms NHE1 and NHE3 exist as stable dimers in membranes with a high degree of specificity for homodimers. (1994)

In this study, we have investigated whether members of the Na+/H+ exchanger (NHE) family are oligomers and whether such oligomeric structure is required for function. Fibroblasts overexpressing NHE1 were treated briefly at 0 degrees C with the cross-linker disuccinimidyl suberate, then membranes were prepared and proteins analyzed by SDS-polyacrylamide gel electrophoresis. Disuccinimidyl suberate treatment converted quantitatively the immunoreactive monomeric form of NHE1 (110 kDa) to a putative dimeric form (210 kDa). Utilization of NHE1 mutant deleted of the cytoplasmic domain (delta 515TH) demonstrates that the transmembrane domain of the antiporter is sufficient for dimerization. Moreover, coimmunoprecipitation of NHE1 and delta 515TH, coexpressed in the same cell, formally proved the existence of dimers. This dimerization was also shown to take place with the epithelial and apically expressed NHE3 isoform, suggesting that oligomerization is a common feature of these transporters. However, coexpression of NHE1 and NHE3 in the same cells did not lead to the formation of heterodimers demonstrating an isoform specificity for the subunit interaction. The domain(s) involved in the isoform-specific dimerization is (are) likely to be confined within the transmembrane segments, as deletion of the 300 amino acids of the cytoplasmic domain did not disrupt dimerization. Exploiting the dimeric properties of the receptor tyrosine kinases and the fact that dimerization triggers kinase activity, we constructed a NHE1/insulin receptor chimera to probe NHE1 dimerization in vivo. When transfected into hamster fibroblasts, this chimera containing the N-terminal transmembrane domain of NHE1 and the cytoplasmic beta-subunit domain of the insulin receptor generates a functional transporter that is autophosphorylated on tyrosine and that presents properties of a constitutively active insulin receptor. These findings support the notion that NHE1 exists in an oligomeric state in intact cells. Finally, to test whether individual subunits of NHE1 are the minimum functional unit for Na+/H+ exchange, we coexpressed a truncated form of NHE1 (delta 515) together with an inactive mutant of NHE1 (E262I). In spite of good expression of the inactive transporter and its capacity to dimerize with active NHE1, no dominant negative effect was observed on amiloride-sensitive 22Na+ flux. This observation would suggest that individual subunits of NHE1 function independently within the oligomeric state.
Regulation of CpG‐Induced Immune Activation by Suppressive Oligodeoxynucleotides (2003)

Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated "CpG motifs" stimulate an innate immune response characterized by the production of cytokines, chemokines, and polyreactive Igs that promote host survival following infectious challenge. Yet CpG-driven immune activation can have deleterious consequences, such as increasing the host's susceptibility to autoimmune disease. The immunomodulatory activity of CpG DNA can be blocked by DNA containing "suppressive" motifs. This work explores the rules governing cellular recognition of stimulatory and suppressive motifs, and the resultant modulation of the immune system. Results suggest that both CpG and suppressive ODN may find use as therapeutic agents.
A hidden Markov model for predicting transmembrane helices in protein sequences. (1998)

A novel method to model and predict the location and orientation of alpha helices in membrane-spanning proteins is presented. It is based on a hidden Markov model (HMM) with an architecture that corresponds closely to the biological system. The model is cyclic with 7 types of states for helix core, helix caps on either side, loop on the cytoplasmic side, two loops for the non-cytoplasmic side, and a globular domain state in the middle of each loop. The two loop paths on the non-cytoplasmic side are used to model short and long loops separately, which corresponds biologically to the two known different membrane insertions mechanisms. The close mapping between the biological and computational states allows us to infer which parts of the model architecture are important to capture the information that encodes the membrane topology, and to gain a better understanding of the mechanisms and constraints involved. Models were estimated both by maximum likelihood and a discriminative method, and a method for reassignment of the membrane helix boundaries were developed. In a cross validated test on single sequences, our transmembrane HMM, TMHMM, correctly predicts the entire topology for 77% of the sequences in a standard dataset of 83 proteins with known topology. The same accuracy was achieved on a larger dataset of 160 proteins. These results compare favourably with existing methods.
Studies on a Live Virus Vaccine against Infectious Laryngotracheitis of Chickens. I. Biological Properties of Attenuated Strain C7 (1983)

The biological properties of tissue-culture-modified strain C7 of infectious laryngotracheitis (ILT) virus were studied. Strain C7 formed well-defined small white pocks that were distinguishable from those formed by the original strain when it was inoculated onto the chorioallantoic membrane of embryonating chicken eggs (pock marker). Strain C7 grew in chicken kidney cell cultures and embryonating chicken eggs better than the original strain. When inoculated intratracheally into chickens, strain C7 propagated primarily in the larynx, trachea, and lung, but the virus was unrecoverable after 6 days postinoculation. No contact infection was demonstrated among chickens. These biological characteristics of strain C7 were stable through five consecutive back-passages in susceptible chickens. In chickens vaccinated ocularly at 14 days of age or older, strain C7 gave good protection against challenge with the virulent strain of ILT virus. These results indicate that strain C7 may be an adequate candidate for a live virus vaccine against ILT.
Structure of Three-Way DNA Junctions 1. Non-Planar DNA Geometry (1994)

Three-way junctions were obtained by annealing two synthetic DNA-oligomers. One of the strands contains a short palindrome sequence, leading to the formation of a hairpin with four base pairs in the stem and four bases in the loop. Another strand is complementary to the linear arms of the first hairpin-containing strand. Both strands were annealed to form a three-way branched structure with sticky ends on the linear arms. The branched molecules were ligated, and the ligation mixture was analysed on a two-dimensional gel in conditions which separated linear and circular molecules. Analysis of 2D-electrophoresis data shows that circular molecules with high mobility are formed. Formation of circular molecules is indicative of bends between linear arms. We estimate the magnitude of the angle between linear arms from the predominant size of the circular molecules formed. When the junction-to-junction distance is 20-21 bp, trimers and tetramers are formed predominately, giving an angle between linear arms as small as 60-90 degrees. Rotation of the hairpin position in the three-way junction allowed us to measure angles between other arms, yielding similar values. These results led us to conclude that the three-way DNA junction possesses a non-planar pyramidal geometry with 60-90 degrees between the arms. Computer modeling of the three-way junction with 60 degrees pyramidal geometry showed a predominantly B-form structure with local distortions at the junction points that diminish towards the ends of the helices. The size distributions of circular molecules are rather broad indicating a dynamic flexibility of three-way DNA junctions.