gebhart/patrepeval huggingface dataset:
Murine Model of Pulmonary Anthrax: Kinetics of Dissemination, Histopathology, and Mouse Strain Susceptibility (2004)

Bioweapons are most often designed for delivery to the lung, although this route is not the usual portal of entry for many of the pathogens in the natural environment. Vaccines and therapeutics that are efficacious for natural routes of infection may not be effective against the pulmonary route. Pulmonary models are needed to investigate the importance of specific bacterial genes in virulence, to identify components of the host immune system that are important in providing innate and acquired protection, and for testing diagnostic and therapeutic strategies. This report describes the characteristics of host and Bacillus anthracis interactions in a murine pulmonary-infection model. The infective dose varied depending on the route and method of inoculation. The germination process in the lung began within 1 h of inoculation into the lung, although growth within the lung was limited. B. anthracis was found in the lung-associated lymph nodes approximately 5 h after infection. Minimal pneumonitis was associated with the lung infection, but significant systemic pathology was noted after dissemination. Infected mice typically succumbed to infection approximately 3 to 4 days after inoculation. The 50% lethal doses differed among inbred strains of mice, but within a given mouse strain, neither the age nor the sex of the mice influenced susceptibility to B. anthracis.
Theoretical investigation of the SAW properties of ferroelectric film composite structures (1998)

The characteristics of surface acoustic waves (SAW) propagating on a three-layered structure consisting of a perovskite-type ferroelectric film, a buffer layer and a semiconductor substrate have been studied theoretically. Large coupling coefficients (K(2)) can be obtained when the interdigital transducer (IDT) is on top of the perovskite-type ferroelectric film, with (type 4) and without (type 3) the floating-plane electrode at the perovskite-type ferroelectric film-buffer layer interface. In the above cases, the peak values of K (2) Of the Pb(Zr,Ti)O(3) (PZT) films (3.2%-3.8%) are higher than those of the BaTiO(3) (BT) and PbTiO(3) (PT) films. In the IDT configuration of type 4, there exists a minor peak of the coupling coefficients for the PZT and BT films, but not for the PT films when the normalized thickness (hK) of the perovskite-type ferroelectric film is about 0.3. The minor peak values of the coupling coefficients (0.62%-0.93%) for different layered structures (PZT/STO/Si, PZT/MgO/Si, and PZT/MgO/GaAs) all decrease when we increase hK value from 0 to 0.25. The results could be useful in the integration of ferroelectric devices, semiconductor devices, and SAW devices on the same substrate.
The measurement of opsonic and phagocytic function by Luminol-dependent chemiluminescence. (1980)

Luminol-dependent chemiluminescence produced by peripheral blood phagocytic cells was measured using a light detecting instrument, the Luminometer 1250 (LKB Wallac). Although less sensitive than liquid scintillation counters, the Luminometer can measure chemiluminescence effectively and detect experimentally induced and clinical variations using small numbers of cells. It is small, inexpensive, simple to use and allows temperature within the reaction vial to be controlled accurately. Light emission can be recorded either graphically or by an intergrated digital printout. Luminol-dependent chemiluminescence is influenced by the presence of contaminating red blood cells and by composition of the medium, particularly presence of phenol red. HEPES buffer and foetal calf serum. Whereas clinical comparisons of opsonic activity are easily performed, comparisons of cellular activity require a high and uniform standard of cell preparation, characterization and maintenance.
Measurement of polysaccharides and proteins in biofilm extracellular polymers (1998)

The structure of biofilm extracellular polymers (ECPs) was studied by measuring their polysaccharide and protein spatial distributions along biofilm depth. Biofilm was collected from two aerobic heterotrophic biofilm reactors, which were seeded with Sphingomonas sp. and Sphingomonas sp. plus mixed liquor, respectively, and operated under toxic organic (in this case, azo dye) degrading conditions. Complete mixing conditions in the two reactors were verified by measuring water content, and polysaccharide and protein quantities from three vertical sampling positions over time. Experimental results showed that: (1) the biofilm water content of either reactor did not change with sample position or biofilm age, with an average biofilm water content in both reactors of 97%; (2) polysaccharides and proteins in the ECPs did not change with sample position; (3) the profiles of polysaccharides and proteins along the biofilm depth showed a stratified biofilm structure, with their ratio (proteins/polysaccharides) being relatively stable over the depth. Oxygen and substrate transport and interactions among species were considered to be the main reasons for producing such a non-uniform biofilm structure; and (4) Sphingomonas sp. could not compete well with microorganisms derived from the mixed liquor of a wastewater treatment plant aeration basin.
Promoter methylation regulates Helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells. (2001)

Cyclooxygenase (COX)-2, the inducible form of the rate-limiting enzyme for prostaglandin synthesis, is up-regulated in gastrointestinal cancers and is a key mediator of epithelial cell growth. Helicobacter pylori is causally linked to gastric cancer. In H. pylori gastritis, COX-2 expression localizes to the subepithelial region, with variable levels in the epithelium. In contrast, in gastric cancer, COX-2 strongly predominates in the epithelium, suggesting that the transition to consistent epithelial COX-2 overexpression may be a critical molecular event in gastric carcinogenesis. Because aberrant promoter methylation inhibits expression of a variety of genes in gastrointestinal cancers, we sought to determine whether methylation of the COX-2 promoter could regulate the response to H. pylori in gastric epithelial cells. We assessed COX-2 expression and promoter methylation status in six gastric epithelial cell lines. In all four of the cell lines that exhibited basal expression of COX-2 and a significant increase in expression in response to H. pylori, the COX-2 promoter was unmethylated, whereas in the two cell lines that did not express COX-2, the COX-2 promoter was methylated. Treatment of COX-2-methylated cells with the demethylating agent 5-azacytidine had a modest effect on COX-2 expression, but when 5-azacytidine-treated cells were subsequently stimulated with H. pylori, there was a significant, 5-10-fold enhancement of both COX-2 mRNA and protein expression and release of the COX-2 product, prostaglandin E2. In contrast, in COX-2-expressing cell lines that were unmethylated at the COX-2 promoter, 5-azacytidine had no effect on H. pylori-stimulated COX-2 expression. These findings suggest that loss of COX-2 methylation may facilitate COX-2 expression and promote gastric carcinogenesis associated with H. pylori infection.
Comparative Data Mining for Microarrays: A Case Study Based on Multiple Myeloma (2002)

Supervised machine learning and data mining tools have become popular for the analysis of gene expression microarray data. They have the potential to uncover new therapeutic targets for diseases, to predict how patients will respond to specific treatments, and to uncover regulatory relationships among genes in normal and disease situations. Comparative experiments are needed to identify the advantages of the leading supervised learning algorithms for microarray data, as well as to give direction in methodological decisions. This paper compares support vector machines, Bayesian networks, decision trees, boosted decision trees, and voting (ensembles of decision stumps) on a new microarray data set for cancer with over 100 samples. The paper provides evidence for several important lessons for mining microarray data, including: (1) Bayes nets and ensembles perform at least as well as other approaches but arguably provide more direct insight; (2) the common practice of throwing out low or negative average differences, or those accompanied by an absent call, is a mistake; (3) looking for consistent differences in expression may be more important than large differences.
Cytotoxicity of a Factor Isolated From Human Spleen 2 (1973)

Journal Article Cytotoxicity of a Factor Isolated From Human Spleen Get access Carmen B. Lozzio, Carmen B. Lozzio The University of Tennessee Memorial Research Center and Hospital, Knoxville, Tennessee 37920 Search for other works by this author on: Oxford Academic PubMed Google Scholar Bismarck B. Lozzio Bismarck B. Lozzio The University of Tennessee Memorial Research Center and Hospital, Knoxville, Tennessee 37920 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 535–538, https://doi.org/10.1093/jnci/50.2.535 Published: 01 February 1973 Article history Received: 14 July 1972 Accepted: 13 October 1972 Published: 01 February 1973
Current Developments in Actively Personalized Cancer Vaccination with a Focus on RNA as the Drug Format (2015)

Developments in sequencing technologies have not only led to a rapid generation of genomic and transcriptional data from cancer patients, but also revealed the vast diversity of cancer-specific changes in patient tumors. Among these, mutation changes in the protein sequence can result in novel epitopes recognized by the immune system and, therefore, can be employed in the development of personalized vaccines. Thanks to its easy design and scalable GMP production, vaccines based on mRNAs coding for mutated epitopes have emerged as a reliable strategy for the exploitation of the potential of patient-specific genomic data. In this review, we provide an overview of recent developments in actively personalized vaccinations, with a special focus on the promise of mRNA vaccines.
Inhibition of Human Chk1 Causes Increased Initiation of DNA Replication, Phosphorylation of ATR Targets, and DNA Breakage (2005)

Human checkpoint kinase 1 (Chk1) is an essential kinase required to preserve genome stability. Here, we show that Chk1 inhibition by two distinct drugs, UCN-01 and CEP-3891, or by Chk1 small interfering RNA (siRNA) leads to phosphorylation of ATR targets. Chk1-inhibition triggered rapid, pan-nuclear phosphorylation of histone H2AX, p53, Smc1, replication protein A, and Chk1 itself in human S-phase cells. These phosphorylations were inhibited by ATR siRNA and caffeine, but they occurred independently of ATM. Chk1 inhibition also caused an increased initiation of DNA replication, which was accompanied by increased amounts of nonextractable RPA protein, formation of single-stranded DNA, and induction of DNA strand breaks. Moreover, these responses were prevented by siRNA-mediated downregulation of Cdk2 or the replication initiation protein Cdc45, or by addition of the CDK inhibitor roscovitine. We propose that Chk1 is required during normal S phase to avoid aberrantly increased initiation of DNA replication, thereby protecting against DNA breakage. These results may help explain why Chk1 is an essential kinase and should be taken into account when drugs to inhibit this kinase are considered for use in cancer treatment.
Supercritical Carbon Dioxide Extraction of Solvent from Micromachined Structures (1997)

We have demonstrated that supercritical carbon dioxide extraction can be used for solvent removal to successfully release compliant surface micromachined structures on silicon wafers developed at Sandia National Laboratories. Structures that have been successfully extracted and released include single gear microengines, bridge and cantilever beams, pressure transducers, and experimental comb drive actuators. Since the supercritical fluid has negligible surface tension, it has virtually unabated access to solvent residing in capillary-like spaces as narrow as 1-3 μm under the micromachined features. While conventional drying techniques have been plagued with the collapse and sticking of micromachined structures due to surface tension effects, supercritical carbon dioxide has been shown to reproducibly dry components and test structures, including bridge and cantilever beams approaching 1000 μm in length, without collapsing. The equipment and the extraction process are described, and photographs of supercritically dried test structures and components are presented.
Construction and Screening of a 2‐Aminoimidazole Library Identifies a Small Molecule Capable of Inhibiting and Dispersing Bacterial Biofilms across Order, Class, and Phylum (2008)

A team of three: 2-Aminoimidazole, triazole, and tether units together resulted in conjugates (see picture, n=4–6 for the most active compounds) that are capable of inhibiting and dispersing bacteria biofilms without inducing bacterial death. Such biofilms have been implicated in a plethora of medical problems, including infection of implanted medical devices and the mortality of cystic fibrosis patients. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z800862_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Prophylactic cancer vaccination by targeting functional non-self (2011)

Despite the monumental success of childhood prophylactic vaccination, there is no similar program designed to provide protection as we age against adult onset diseases like breast cancer. Instead, the predominant focus of current cancer vaccine strategy is to vaccinate after the tumors become established. This strategy has at best provided incremental improvement in overall survival. We propose the development of an adult vaccination program modeled on the childhood program that provides protection against diseases we confront as we enter our middle age. Since most cases of adult cancers are not associated with definitive etiopathogenic viruses, we propose extending our selection of vaccine targets to tissue-specific self proteins that are over-expressed in developing tumors but are no longer expressed in normal tissues ('retired or former self'), are expressed in normal tissues under readily avoidable conditions ('conditional self'), or are incapable of targeting any clinically significant autoimmune complications ('irrelevant self'). By extending prophylactic vaccination to such "functional non-self" targets, prophylactic vaccination against adult onset diseases like breast cancer may occur safely in the absence of any autoimmune inflammatory complications and may potentially reduce disease incidence in a manner that mimics the impact of childhood vaccination on diseases like measles and polio.
An apoA-I mimetic peptide containing a proline residue has greater in vivo HDL binding and anti-inflammatory ability than the 4F peptide (2009)

Modifying apolipoprotein (apo) A-I mimetic peptides to include a proline-punctuated alpha-helical repeat increases their anti-inflammatory properties as well as allows better mimicry of full-length apoA-I function. This study compares the following mimetics, either acetylated or biotinylated (b): 4F (18mer) and 4F-proline-4F (37mer, Pro). b4F interacts with both mouse HDL (moHDL) and LDL in vitro. b4F in vivo plasma clearance kinetics are not affected by mouse HDL level. Administration of biotinylated peptides to mice demonstrates that b4F does not associate with lipoproteins smaller than LDL in vivo, though it does associate with fractions containing free hemoglobin (Hb). In contrast, bPro specifically interacts with HDL. b4F and bPro show opposite binding responses to HDL by surface plasmon resonance. Administration of acetylated Pro to apoE(-/-) mice significantly decreases plasma serum amyloid A levels, while acetylated 4F does not have this ability. In contrast to previous reports that inferred that 4F associates with HDL in vivo, we systematically examined this potential interaction and demonstrated that b4F does not interact with HDL in vivo but rather elutes with Hb-containing plasma fractions. bPro, however, specifically binds to moHDL in vivo. In addition, the number of amphipathic alpha-helices and their linker influences the anti-inflammatory effects of apoA-I mimetic peptides in vivo.
Efficient and Recyclable Monomeric and Dendritic Ru-Based Metathesis Catalysts (2000)

Several highly active, recoverable and recyclable Ru-based metathesis catalysts are presented. The crystal structure of Ru complex 5, bearing a 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene and styrenyl ether ligand is disclosed. The heterocyclic ligand significantly enhances the catalytic activity, and the styrenyl ether allows for the easy recovery of the Ru complex. Catalyst 5 promotes ring-closing metathesis (RCM) and the efficient formation of various trisubstituted olefins at ambient temperature in high yield within 2 h; the catalyst is obtained in >95% yield after silica gel chromatography and can be used directly in subsequent reactions. Tetrasubstituted olefins can also be synthesized by RCM reactions catalyzed by 5. In addition, the synthesis and catalytic activities of two dendritic and recyclable Ru-based complexes are disclosed (32 and 33). Examples involving catalytic ring-closing, ring-opening, and cross metatheses are presented where, unlike monomer 5, dendritic 33 can be readily recovered.
Alternative extracellular and cytoplasmic domains of the integrin alpha 7 subunit are differentially expressed during development. (1993)

Examination of cDNAs for the laminin-binding alpha 7 integrin subunit identified two different sequences (designated X1 and X2) coding for the variable region between the III and IV homology repeat domains near the putative ligand-binding site. Sequencing of a mouse alpha 7 genomic clone established that the X1 and X2 regions are derived by mutually exclusive alternative mRNA splicing. Reverse transcriptase-polymerase chain reaction analysis of alpha 7 mRNA indicated that the X1 and X2 isoforms were present in equal amounts in mouse skeletal myoblasts and adult heart. However, in adult skeletal muscle, the X2 variant was exclusively expressed. Amino acid sequence homologies in the III/IV segment suggest that alpha 3 and alpha 6 are also alternatively spliced at this site. We identified alternatively spliced exons in a human alpha 6 genomic clone that encode X1- and X2-like segments. Analysis of the alpha 7 cytoplasmic domain indicated that this region was also alternatively spliced and like alpha 3 and alpha 6 could exist as the A or B form. In mouse skeletal and cardiac muscle the B form of alpha 7 was strongly expressed. However, we identified alpha 7A in neonate and adult skeletal muscle but not in cardiac tissue. High levels of alpha 7A were detected in differentiating myotubes, but in proliferating myoblasts only the alpha 7B isoform was present. These results indicate that alternative splicing of alpha 7 mRNA is differentially regulated during development and generates variant integrin chains with structurally and presumably functionally unique ligand-binding and cytoplasmic domains.
Printable, Flexible, and Stretchable Forms of Ultrananocrystalline Diamond with Applications in Thermal Management (2008)

Stretchable ultrananocrystalline diamond (UNCD) ribbons are created by transfer printing these elements onto a prestrained elastomeric substrate of poly(dimethylsiloxane) followed by release of this prestrain. Transfer printing techniques applied to thin films of UNCD such as these expand the range of potential applications of diamond to include, as an example, thermal management in plastic electronic systems.
Basic fibroblast growth factor enters the nucleolus and stimulates the transcription of ribosomal genes in ABAE cells undergoing G0----G1 transition. (1987)

The cellular action of growth factors, among them basic fibroblast growth factor (bFGF), is mediated by their interaction with a cell surface receptor, but the mechanism of transfer of mitogenic (or other) signals to the nucleus has not been identified. In this work, we show that bFGF is translocated to and accumulated in the nucleolus. Furthermore, the nucleolar localization of bFGF is correlated with a stimulation of transcription of ribosomal genes during G0----G1 transition induced by bFGF alone in adult bovine aortic endothelial cells (ABAE cells). Stimulation of ribosomal gene transcription is preceded by a significant increase of the major nonhistone nucleolar protein, nucleolin. In vitro, the growth factor has a direct effect on the enhancement of RNA polymerase I activity in isolated nuclei from quiescent sparse (G0) ABAE cells. The direct action of bFGF on the level of ribosomal gene transcription could correspond to an additional growth-signaling pathway, mediated by this growth factor.
Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome (2002)

Immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX, OMIM 304790) is a rare, recessive disorder resulting in aggressive autoimmunity and early death. Mutations in FOXP3 have been identified in 13 of 14 patients tested. Research in the mouse model, scurfy, suggests that autoimmunity may stem from a lack of working regulatory T cells. We review published reports regarding the genetics, clinical features, immunology, pathology, and treatment of IPEX. We also report three new patients who were treated with long term immunosuppression, followed by bone marrow transplantation in two. IPEX can be differentiated from other genetic immune disorders by its genetics, clinical presentation, characteristic pattern of pathology, and, except for high IgE, absence of substantial laboratory evidence of immunodeficiency. While chronic treatment with immunosuppressive drugs may provide temporary benefit for some patients, it does not cause complete remission. Remission has been observed with bone marrow transplantation despite incomplete engraftment, but the long term outcome is uncertain.
Atmospheric Reactions Influence Seasonal PAH and Nitro-PAH Concentrations in the Los Angeles Basin (2004)

Ambient measurements of polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs were carried out during August 2002 and January 2003 in Los Angeles, CA, a source site and in Riverside, CA, a downwind receptor site approximately 90 km to the east of Los Angeles. Atmospheric concentrations of PAHs and nitro-PAHs are of interest because both of these compound classes include potent mutagens and carcinogens. To augment our current understanding of atmospheric formation of nitro-PAHs, four sampling periods were employed to study the diurnal variations of these compounds. The PAH concentrations were highest in Los Angeles during January, as a result of traffic input at this source site undertightwintertime atmospheric inversions. In contrast, nitro-PAH levels were highest in Riverside during August, as a result of enhanced summertime photochemistry. Hydroxyl radical-initiated reactions produced nitro-PAHs in both seasons, while in winter little evidence for nitrate radical chemistry was seen. For the August samples, nitrate radical-initiated formation of nitro-PAHs is suggested by nitro-PAH isomer profiles not only at the downwind location as anticipated, but also atthe source site. In southern California, the contribution of atmospheric formation through gas-phase radical-initiated PAH reactions to the ambient burden of nitro-PAHs is dominant, with the semi-volatile nitro-PAHs being the most abundant and 2-nitrofluoranthene being the major particle-associated nitro-PAH.