gebhart/patrepeval huggingface dataset:
Human 60-kDa Heat-Shock Protein: A Danger Signal to the Innate Immune System (1999)

Mammalian 60-kDa heat-shock protein (hsp60) is a key target of T cell and Ab responses in chronic inflammation or atherosclerosis. We show in this study that human hsp60 is also an Ag recognized by cells of the innate immune system, such as macrophages. Both mouse and human macrophages respond to contact with exogenous human hsp60 with rapid release of TNF-alpha; mouse macrophages in addition produce nitric oxide. The proinflammatory macrophage response is hsp60 dose dependent and similar in kinetics and extent to LPS stimulation. Human hsp60 was found to synergize with IFN-gamma in its proinflammatory activity. Finally, human hsp60 induces gene expression of the Th1-promoting cytokines IL-12 and IL-15. These findings identify autologous hsp60 as a danger signal for the innate immune system, with important implications for a role of local hsp60 expression/release in chronic Th1-dependent tissue inflammation.
Kinetics of cellular proliferation after arterial injury. III. Endothelial and smooth muscle growth in chronically denuded vessels. (1986)

The healing of injured rat carotid chronically denuded of endothelium was studied at late times after balloon injury. One year after injury the endothelial layer was not fully regenerated and had ceased proliferating. The denuded areas of these vessels were covered with luminal smooth muscle cells which strongly resembled endothelium but did not stain with factor VIII.R.Ag antibody. These cells were actively proliferating and formed a surface which was weakly thrombogenic. Indium-111 platelet studies showed that over 24 hours there was a slight but significant adherence of platelets to the denuded surface. Luminal smooth muscle cell proliferation was matched by cell loss and did not produce further intimal thickening or an increase in total cell number. These results demonstrate that damaged conduit arteries can exist in a stable state without endothelium and do not develop thrombosis even after prolonged periods of time.
SNP Typing on the NanoChip Electronic Microarray (2004)

We describe a single nucleotide polymorphism (SNP) typing protocol developed for the NanoChip electronic microarray. The NanoChip array consists of 100 electrodes covered by a thin hydrogel layer containing streptavidin. An electric currency can be applied to one, several, or all electrodes at the same time according to a loading protocol generated by the user. Biotinylated deoxyribonucleic acid (DNA) is directed to the pad(s) via the electronic field(s) and bound to streptavidin in the hydrogel layer. Subsequently, fluorescently labeled reporter oligos and a stabilizer oligo are hybridized to the bound DNA. Base stacking between the short reporter and the longer stabilizer oligo stabilizes the binding of a matching reporter, whereas the binding of a reporter carrying a mismatch in the SNP position will be relatively weak. Thermal stringency is applied to the NanoChip array according to a reader protocol generated by the user and the fluorescent label on the matching reporter is detected.
Enhanced detection of cytomegalovirus in confluent MRC-5 cells treated with dexamethasone and dimethyl sulfoxide (1988)

Optimum growth conditions for human cytomegalovirus (HCMV) include the use of subconfluent, actively growing cultures of human embryonic fibroblasts. Many clinical virology laboratories, however, use tissue culture cells from commercial sources. These cells are usually confluent, static cultures that tend to be less sensitive to viral infection. To determine whether dimethyl sulfoxide (DMSO) or dexamethasone (DEX), which are known enhancers of HCMV, facilitates the detection of the virus in confluent cells, we tested both HCMV AD169 and a number of clinical specimens suspected to contain HCMV on MRC-5 cells in both shell vials and conventional tube cultures. We found that, in the shell vial test, treatment of the cultures with either DMSO or DEX before and after inoculation increased the number of cells staining positive by three- to sixfold compared with untreated controls. Best results were obtained by pretreating the cultures with DEX alone and by treating the cultures with a combination of DEX and 1% DMSO postinfection. In the conventional MRC-5 culture tubes, treatment with the reagents resulted in the more rapid appearance of cytopathic effect and a more extensive infection of the cell sheet. The experimental findings indicate that the enhancing effect of DEX is attributable mainly to the increased production of a cellular mRNA during the period preceding viral infection.
RELATION OF INTRANASAL DISEASE IN THE PRODUCTION OF BRONCHIAL ASTHMA (1925)

Nasal accessory sinus disease is a very common finding in patients suffering with bronchial asthma. Because of this occurrence, many thoughtful investigators have suggested that there is an etiologic relation between disease in the paranasal sinuses and this baffling malady. There are four conceivable ways by which the symptom complex called asthma may be produced through nasal disease. Mucopurulent material may drip into the pharynx from an infected sinus and the infection gradually involve the mucous membrane of the trachea and bronchi. Mucopurulent material may be retained in a sinus and the toxic products be absorbed through the blood stream or lymphatics or both and produce allergic phenomena that may manifest themselves in asthma. The nose may be obstructed by polypi and enlarged turbinates, and the patient is compelled to breathe constantly through the mouth, and the effect of cold and dry inspired air, combined with the presence of infected
Human herpesvirus 6 is closely related to human cytomegalovirus (1990)

A sequence of 21,858 base pairs from the genome of human herpesvirus 6 (HHV-6) strain U1102 is presented. The sequence has a mean composition of 41% G + C, and the observed frequency of CpG dinucleotides is close to that predicted from this mononucleotide composition. The sequence contains 17 complete open reading frames (ORFs) and part of another at the 5' end of the sequence. The predicted protein products of two of these ORFs have no recognizable homologs in the genomes of other sequenced human herpesviruses (i.e., Epstein-Barr virus [EBV], human cytomegalovirus [HCMV], herpes simplex virus [HSV], and varicella-zoster virus [VZV]). However, the products of nine other ORFs are clearly homologous to a set of genes that is conserved in all other sequenced herpesviruses, including homologs of the alkaline exonuclease, the phosphotransferase, the spliced ORF, and the major capsid protein genes. Measurements of similarity between these homologous sequences showed that HHV-6 is clearly most closely related to HCMV. The degree of relatedness between HHV-6 and HCMV was commensurate with that observed in comparisons between HSV and VZV or EBV and herpesvirus saimiri and significantly greater than its relatedness to EBV, HSV, or VZV. In addition, the gene for the major capsid protein and its 5' neighbor are reoriented with respect to the spliced ORFs in the genomes of both HHV-6 and HCMV relative to the organization observed in EBV, HSV, and VZV. Three ORFs in HHV-6 have recognizable homologs only in the genome of HCMV. Despite differences in gross composition and size, we conclude that the genomes of HHV-6 and HCMV are closely related.
Conformational dynamics of insulin in solution. Circular dichroic studies (1980)

Conformational changes of bovine insulin in solution with concentration and pH detected by circular dichroic (CD) studies are reported. The change in the CD spectrum of insulin in the higher concentration range (from 100 microM down to 2 microM) is relatively small, but in the lower concentration range (from 2 microM down to 60 nM) the CD spectrum changes substantially with concentration. A detailed analysis of the data indicates that the hormone has two major conformational states: conformation I, a form which predominates in extremely dilute solutions and corresponds to the monomeric state, and conformation II, a form present in the crystalline state and also, with but minor changes, in all associated states in solution. The apparent conformation of insulin at various concentrations is computed by using a nonlinear least-squares iterative computer program. The mean residue ellipticities at 223 and 208 nm are extrapolated by using [theta] lambda VS. fmonomer plots to calculate the conformations of monomeric and dimeric insulin. These calculations indicate that conformation I of insulin has 21% less helix content than conformation II, the latter conformation being very similar to that found in the crystalline state. It is also evident from these calculations that the conformational transition is of the helix--coil type. Studies pertaining to the dependence of the CD spectrum of insulin on pH are also reported, and a comparison is made with earlier sedimentation coefficient studies. An analysis of the data indicates that changes in the sedimentation coefficient correspond quite closely to changes of CD spectra with pH. This paper is the first report known to us pertaining to conformational studies of insulin in the monomeric state; it presents evidence for conformational transitions of the protein hormone induced by concentration and pH. Since insulin is biologically active mainly in the monomeric state, a knowledge of its conformation in this state should be an important tool in deciphering the molecular basis of insulin action.
ObliviAd: Provably Secure and Practical Online Behavioral Advertising (2012)

Online behavioral advertising (OBA) involves the tracking of web users' online activities in order to deliver tailored advertisements. OBA has become a rapidly increasing source of revenue for a number of web services, and it is typically conducted by third-party data analytics firms such as brokers, which track user behaviors across web-sessions using mechanisms such as persistent cookies. This practice raises significant privacy concerns among users and privacy advocates alike. Therefore, the task of designing OBA systems that do not reveal user profiles to third parties has been receiving growing interest from the research community. Nevertheless, existing solutions are not ideal for privacy preserving OBA: some of them do not provide adequate privacy to users or adequate targeting information to brokers, while others require trusted third parties that are difficult to realize. In this paper, we propose ObliviAd a provably secure architecture for privacy preserving OBA. The distinguishing features of our approach are the usage of secure hardware-based private information retrieval for distributing advertisements and high-latency mixing of electronic tokens for billing advertisers without disclosing any information about client profiles to brokers. ObliviAd does not assume any trusted party and provides brokers an economical alternative that preserves the privacy of users without hampering the precision of ads selection. We present the first formal security definitions for OBA systems (namely, profile privacy, profile unlink ability, and billing correctness) and conduct a formal security analysis of ObliviAd using ProVerif, an automated cryptographic protocol verifier, establishing the aforementioned security properties against a strong adversarial model. Finally, we demonstrated the practicality of our approach with an experimental evaluation.
Diaryliodonium Salts. II. The Phenylation of Organic and Inorganic Bases1,2 (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiaryliodonium Salts. II. The Phenylation of Organic and Inorganic Bases1,2F. Marshall Beringer, Arthur Brierley, Milton Drexler, E. Melvin Gindler, and Charles C. LumpkinCite this: J. Am. Chem. Soc. 1953, 75, 11, 2708–2712Publication Date (Print):June 1, 1953Publication History Published online1 May 2002Published inissue 1 June 1953https://pubs.acs.org/doi/10.1021/ja01107a047https://doi.org/10.1021/ja01107a047research-articleACS PublicationsRequest reuse permissionsArticle Views1618Altmetric-Citations141LEARN 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
Biodegradable Polymeric Nanoparticles Show High Efficacy and Specificity at DNA Delivery to Human Glioblastoma in Vitro and in Vivo (2014)

Current glioblastoma therapies are insufficient to prevent tumor recurrence and eventual death. Here, we describe a method to treat malignant glioma by nonviral DNA delivery using biodegradable poly(β-amino ester)s (PBAEs), with a focus on the brain tumor initiating cells (BTICs), the tumor cell population believed to be responsible for the formation of new tumors and resistance to many conventional therapies. We show transfection efficacy of >60% and low biomaterial-mediated cytotoxicity in primary human BTICs in vitro even when the BTICs are grown as 3-D oncospheres. Intriguingly, we find that these polymeric nanoparticles show intrinsic specificity for nonviral transfection of primary human BTICs over primary healthy human neural progenitor cells and that this specificity is not due to differences in cellular growth rate or total cellular uptake of nanoparticles. Moreover, we demonstrate that biodegradable PBAE/DNA nanoparticles can be fabricated, lyophilized, and then stored for at least 2 years without losing efficacy, increasing the translational relevance of this technology. Using lyophilized nanoparticles, we show transgene expression by tumor cells after intratumoral injection into an orthotopic murine model of human glioblastoma. PBAE/DNA nanoparticles were more effective than naked DNA at exogenous gene expression in vivo, and tumor cells were transfected more effectively than noninvaded brain parenchyma in vivo. This work shows the potential of nonviral gene delivery tools to target human brain tumors.
The contribution of glomerular mesangial cells to progressive glomerulosclerosis. (1989)

These data from in vitro studies, partially confirmed on intact glomeruli, suggest that glomerular cells are not only responsive to a number of growth-regulatory peptides but they are also important sources of several of these agents. The studies on transgenic mice confirm the potential role of the insulin-like peptides. This model also provides clear evidence that genetically directed modifications of cell behavior are important in the pathogenesis of glomerulosclerosis. The ability of glomerular cells to undergo proliferation and participate in hypertrophy of the glomerulus may be a critical determinant in the development of progressive glomerulosclerosis. That this ability is controlled by genetic differences between species and individuals seems well-established in both animal studies and clinical experience.
Porosity control in high internal phase emulsion templated polyelectrolytes via ionic crosslinking (2016)

ABSTRACT A series of novel macroporous materials based on poly( N ‐isopropylacrylamide)‐ b ‐sodium polyacrylate is synthesized via aqueous reversible addition‐fragmentation chain transfer polymerization in an oil‐in‐water high internal phase emulsion (HIPE) utilizing both covalent and ionic crosslinkers (PEG diacrylate and calcium diacrylate, respectively). Porosity is directly related to the calcium diacrylate content of the polyHIPE. Depth profiling XPS of pressed samples reveal the segregation of less polar substituents (PNIPAM, PEGDA) to the interface, whereas ionic components are located deeper within the continuous aqueous phase, primarily driven by ionic strength. This segregation of components stabilizes the internal‐continuous phase interface and results in decreased void diameter. Calcium diacrylate also forms ionic crosslinks in the polyHIPE material, resulting in increased interconnecting pore diameter due to volume contraction upon polymerization. Evidence of volume contraction is provided by the stress induced on PEG at the o/w interface by internally located calcium polyacrylate crosslinks, resulting in a decrease in XRD peak intensity. It is therefore proposed that calcium diacrylate is capable of modifying polyHIPE morphology via two separate mechanisms. Published 2016 . Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54 , 2486–2492
Characterization of inhibitors to FVIII with an ELISA in congenital and acquired haemophilia A (2002)

Different methods can be used for the detection and quantification of inhibitors or antibodies to coagulation factor VIII (FVIII). Traditionally, clotting assays have been used, in particular the Bethesda assay. These assays have, however, several shortcomings, due to the complex reaction kinetics of some inhibitors and a low sensitivity to low-titre antibodies. In addition, a universal FVIII inhibitor standard is lacking. Furthermore, clotting assays do not detect noninhibitory antibodies. Use of ELISAs has been described and FVIII from various commercially available FVIII concentrates has been used as target antigen in the assays. In the present study, we systematically explored the influence of different FVIII concentrates on the performance of an ELISA for detection of FVIII antibodies. The described ELISA was also used for further characterization of FVIII inhibitors in patients with acquired and congenital haemophilia A. We found that the source of FVIII had a substantial impact on the frequency of antibody detection. Albumin-free recombinant FVIII as target antigen gave the highest sensitivity for the assay, whereas plasma-derived concentrates containing a high level of von Willebrand factor (vWF) gave the lowest sensitivity. Presumably vWF interferes with the binding of antibodies to FVIII. We suggest that albumin-free recombinant FVIII should be used as target antigen when ELISAs are used for detection of FVIII antibodies.
Androstenediol in Canine Spermatic Vein Blood and Its Significance in Testosterone Biosynthesisin Vivo (1968)

A change in androgen content of spermatic vein blood of anesthetized dogs after luteinizing hormone (LH: NIH-LH-B3) administration was studied using gas-liquid chromatography. A definite increase in content of androstenediol as well as testosterone, androstenedione and dehydroepiandrosterone was noted. Androstenediol was identified by several chromatographic procedures and by infrared spectroanalysis. In situ and in vivo perfusion study revealed the conversion of dehydroepiandrosterone-4-11C to androstenediol-14C and testosterone-14C, and that of androstenediol-3H to testosterone-3H by the dog testis. Perfusion of androstenedione-4-14C or testosterone-4-14C via the spermatic artery produced no demonstrable androstenediol-14C in canine spermatic vein blood. These findings strongly support the view that androstenediol is one of the important intermediates in testosterone biosynthesis by dog testis. (Endocrinology83: 992, 1968)
Enhancement of a constitutively active promoter for gene therapy by a positive feed-back transcriptional activator mechanism. (1998)

Success of gene replacement therapy depends on long-term, high level expression of the transgene. Gene therapy vectors incorporating a promoter of a constitutively active eukaryotic gene may allow long-term expression in vivo, but the expression level may be insufficient for therapeutic effects. To enhance transcription from eukaryotic promoters, a strategy with dicistronic vectors encoding the therapeutic gene of interest together with a transcription factor that binds and activates the promoter was tested. Expression vectors for the chimeric tet repressor/VP16 transcription factor (tTA) driven by the human beta-actin promoter were constructed, and tandem tet operators were inserted within the promoter. This arrangement significantly enhanced expression of G-CSF in fibroblasts to higher levels than the immediate/early CMV promoter. Stably transfected fibroblast clones produced up to 2.4 microg G-CSF per 10(6) cells x 24 h. After injection of genetically engineered cells into SCID mice, the enhanced beta-actin promoter construct resulted in marked leukocytosis, whereas the unmodified promoter had only a marginal therapeutic effect. Transcription factor-enhanced, feed-back-activated human promoters may thus achieve higher expression levels than viral control elements, and may be advantageous for gene therapy due to high constitutive activity in vivo.
Protein Sequencing (1998)

It is approaching half a century since Edman developed a chemistry for the determination of the N-terminus of a protein or peptide (1), and thts chemistry is still being used today. in the intervening decades various ancillary techniques have come (and some have gone) that have allowed the field to develop. Apart from the automation of Edman chemistry itself, the most sigmticant advances have been improvements in sample preparation and the advent of mass spectrometric techniques. in the early days the task of sequencing a protem was a signnificant one, limited to those protems that could be prepared in sufficiently large amounts. Then, the aim (other than to develop the technology) was to obtam the full sequence of the protein in question to begin to understand how protems were structured, which was done by use of Edman chemistry exclusively. Currently, the situation is different, and it is usually necessary to obtam only partial protein sequence from the protein itself From the partial sequence, suitable ohgonucleotides can be designed and used to clone the corresponding gene, which can be rapidly analyzed to yield the full sequence, For identification of a protein the partial sequence may need to be only 3–5 residues long Such short sequences, known as “sequence tags,” are currently of importance in the study of the “proteome,” the set of protems that is expressed by the genome. Studies of the proteome follow the results of genome sequencing, which are giving an explosion of information. The sequence of the genome suggests what proteins might be made, but does not prove which are actually expressed in any gtven tissue(s), how they are regulated, or what their functions e For these purposes there is a need to separate and identify mdividual proteins, then to correlate then presence and modification with function.
Cervical dysplasia: early intervention. (2003)

Cervical cancer is the second-most common cancer in young women and is one of the most common causes of cancer deaths among women, particularly in minorities and in impoverished countries. Cervical dysplasia, a premalignant lesion that can progress to cervical cancer, is caused primarily by a sexually transmitted infection with an oncogenic strain of the human papillomavirus (HPV). Not all women with the virus develop cervical dysplasia or cervical cancer. It has been postulated there are multiple host factors that contribute to progression of disease. Many of these factors, such as nutrient deficiencies, can be reversed, which will result in regression of dysplastic lesions. Studies have shown dietary intervention and nutrient supplementation to be effective in preventing cervical cancer. Additionally, local escharotic treatment combined with systemic treatment shows significant potential in reducing dysplasia. Recent advances in vaccination technology demonstrate the effectiveness of an HPV vaccine. The vaccine, however, may have many social and cost-prohibiting limitations, as well as health side effects.