gebhart/patrepeval huggingface dataset:
Expression of cathepsin E in pancreas: A possible tumor marker for pancreas, a preliminary report (1996)

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non-lysosomal proteinase found in the highest concentration in the superficial epithelial cells of the stomach. The aims of our study were to examine the expression of CTSE in the pancreas, to establish an assay system of CTSE and to evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma, 3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were examined. Surgically resected pancreatic tissues were subjected to immunohistochemistry for CTSE. Pancreatic juice was collected from the patients and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive staining for CTSE was observed in pancreatic ductal adenocarcinoma by immunohistochemistry. CTSE was also expressed in mucin-producing adenoma, intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the pancreatic juice was present in 8 of 11 patients with pancreatic ductal adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis. The detection frequency of CTSE in the pancreatic juice was significantly higher in the patients with pancreatic ductal adenocarcinoma than in the patients with chronic pancreatitis. Our findings suggest that the expression of CTSE is associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE in the pancreatic juice seems to be a useful marker for a definitive diagnosis and that CTSE may be expressed at a relatively early stage of multistep carcinogenesis in pancreatic lesions.
Polycondensed heterocycles. II. A new preparative route to 11‐Oxo‐5H,11H‐pyrrolo[2,1‐c][1,4]benzothiazepine (1986)

Abstract 6‐Methylthio‐10‐oxo‐5 H ,10 H ‐pyrrolo[1,2‐ b ]isoquinoline 11 was isolated in an attempted synthesis of 11‐oxo‐5 H ,11 H ‐pyrrolo[2,1‐ c ][1,4]benzothiazepine 1 from 1‐(2‐methylthiobenzyl)pyrrole‐2‐carboxylic acid chloride 9 , obtained using as starting material o ‐methylthiobenzyl bromide 3 and passing through 1‐(2‐methylthiobenzyl)pyrrole‐2‐carbonitrile 5 , by cyclization with aluminum chloride. However the successful demethylation with sodium in dimethylacetamide of 1‐(2‐methylthiobenzyl)pyrrole‐2‐carboxyamide 12 , formed by hydrolysis of nitrile 5 , allowed us to prepare by another way the corresponding thiol 13 and consequently the 1‐(2‐mercaptobenzyl)pyrrole‐2‐carboxylic acid 14 , which when subjected to intramolecular ring closure by CDI in place of DCC gave 1 in higher yield, 69% instead of 43%. Finally, the direct cyanation of 1‐(2‐ethoxycarbonylthiobenzyl)pyrrole 16 , prepared utilizing the 1‐(2‐mercaptobenzyl)pyrrole 15 obtained by demethylation of the corresponding thioanisol 4 which was carried out as above, afforded the unexpected 1‐(2‐ethylthio‐benzyl)pyrrole‐2‐carbonitrile 17 .
A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer (2014)

Bladder cancer is one of the most common cancers and, together with prostate carcinoma, accounts for the majority of the malignancies of the genitourinary tract. Since prognosis ameliorates with early detection, it will be beneficial to have a repertoire of diagnostic markers that could complement the current diagnosis protocols. Recently, cell-secreted extracellular vesicles have received great interest as a source of low invasive disease biomarkers because they are found in many body fluids, including urine. The current work describes a pilot study to generate an array-based catalogue of mRNA associated to urinary vesicles, and also a comparison with samples obtained from bladder cancer patients. After an analysis of presence/absence of transcripts in bladder cancer EVs, a list of genes was selected for further validation using PCR technique. We found four genes differentially expressed in cancer samples. LASS2 and GALNT1 were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non-cancer urinary vesicles. Previous studies have pointed to the involvement of those genes in tumour progression and metastasis.
2′-O-methyl-modified RNAs Act as TLR7 Antagonists (2007)

RNA molecules such as single-stranded RNA (ssRNA) and small interfering RNA (siRNA) duplexes induce Toll-like receptor (TLR)-mediated immune stimulation after intracellular delivery. We have previously shown that selective incorporation of 2'-O-methyl (2'OMe) residues into siRNA abrogates cytokine production without reduction of gene silencing activity. Here we show that 2'OMe-modified RNA acts as a potent inhibitor of RNA-mediated cytokine induction in both human and murine systems. This activity does not require the direct incorporation of 2'OMe nucleotides into the immunostimulatory RNA or that the 2'OMe nucleotide-containing RNA be annealed as a complementary strand to form a duplex. Our results indicate that 2'OMe RNA acts as a potent antagonist of immunostimulatory RNA. We further show that 2'OMe RNA is able significantly to reduce both interferon-alpha (IFN-alpha) and interleukin-6 (IL-6) induction by the small-molecule TLR7 agonist loxoribine in human peripheral blood mononuclear cells (human PBMCs), in murine Flt3L dendritic cells (Flt3L DCs), and in vivo in mice. These results indicate that 2'OMe-modified RNA may have utility as an inhibitor of TLR7 with potential applications in the treatment of inflammatory and autoimmune diseases that involve TLR7-mediated immune stimulation.
Intracellular Barriers to Non-Viral Gene Transfer (2002)

Non-viral vector mediated gene transfer, compared to viral vector mediated one, is a promising tool for the safe delivery of therapeutic DNA in genetic and acquired human diseases. Although the lack of specific immune response favor the clinical application of non-viral vectors, comprising of an expression cassette complexed to cationic liposome or cationic polymer, the limited efficacy and short duration of transgene expression impose major hurdles in the widespread application of non-viral gene therapy. The trafficking of transgene, complexed with chemical vectors, has been the subject of intensive investigations to improve our understanding of cellular and extracellular barriers impeding gene delivery. Here, we review those physical and metabolic impediments that account, at least in part, for the inefficient translocation of transgene into the nucleus of target cells. Following the internalization of the DNA-polycation complex by endocytosis, a large fraction is targeted to the lysosomal compartment by default. Since the cytosolic release of heterelogous DNA is a prerequisite for nuclear translocation, entrapment and degradation of plasmid DNA in endo-lysosomes constitute a major impediment to efficient gene transfer. Only a small fraction of internalized plasmid DNA penetrates the cytoplasm. Plasmid DNA encounters the diffusional and metabolic barriers of the cytoplasm, further decreasing the number of intact plasmid molecules reaching the nuclear pore complex (NPC), the gateway of nucleosol. Nuclear translocation of DNA requires either the disassembly of the nuclear envelope or active nuclear transport via the NPC. Comparison of viral and plasmid DNA cellular trafficking should reveal strategies that viruses have developed to overcome those cellular barriers that impede non-viral DNA delivery in gene therapy attempts.
The use of modified primers to eliminate cycle sequencing artifacts (1999)

Cycle sequencing is the workhorse of DNA sequencing projects, allowing the production of large amounts of product from relatively little template. This cycling regime, which is aimed at linear growth of the desired products, can also produce artifacts by exponential amplification of minor side-products. These artifacts can interfere with sequence determination. In an attempt to allow linear but prevent exponential growth of products, and thus eliminate artifacts, we have investigated the use of primers containing modified residues that cannot be replicated by DNA polymerase. Specifically, we have used primers containing 2'- O -methyl RNA residues or abasic residues. Oligomers consisting of six DNA residues and 20 2'- O -methyl RNA residues, with the DNA residues located at the 3'-end, primed as efficiently as DNA primers but would not support exponential amplification. Oligonucleotides containing fewer DNA residues were not used as efficiently as primers. DNA primers containing a single abasic site located six residues from the 3'-end also showed efficient priming ability without yielding exponential amplification products. Together these results demonstrate that certain types of modified primers can be used to eliminate artifacts in DNA sequencing. The technique should be particularly useful in protocols involving large numbers of cycles, such as direct sequencing of BAC and genomic DNA.
CD8+ T cells from mice vaccinated against Toxoplasma gondii are cytotoxic for parasite-infected or antigen-pulsed host cells (1991)

Mice vaccinated with a live temperature sensitive mutant (TS-4) of Toxoplasma gondii develop complete resistance to subsequent challenge with a highly virulent Toxoplasma strain (RH). Because CD8+ T cells have been demonstrated to be critical to this protective immunity in vivo, the involvement of cytotoxic T lymphocytes in the killing of infected cells in vaccinated mice was investigated. After restimulation in vitro, splenic T cells from vaccinated mice of either the BALB/c or C57BL/6 strains were found to kill syngeneic bone marrow-derived macrophages infected with TS-4 tachyzoites or preincubated with soluble T. gondii Ag. Unimmunized control mice or mice vaccinated with heat-killed TS-4 tachyzoites failed to generate significant CTL activity in vitro. Moreover, the observed lytic reaction was found to be target specific, not killing uninfected or unpulsed macrophages even when included as bystanders in the assay. Target lysis did not depend on the production by the effector cells of either a cytotoxic supernatant factor or IFN-gamma. Depletion of CD8+ cells from the splenic effector cell population, however, abrogated the cytotoxic activity, whereas depletion of CD4+ cells had little effect. The MHC restriction of the Toxoplasma-specific cytolytic reaction was confirmed in studies using effector cells from BALB/c mice and targets from congenic or mutant haplotype strains. These experiments indicated that target killing is primarily restricted by genes mapping within the H-2D/Ld loci. Together, these results establish MHC-restricted cytolysis as a major parameter of CD8+ effector function against T. gondii and indicate that, in the case of this protozoan, Ag presentation to CD8+ lymphocytes can occur as a result of either processing within infected cells or exogenous uptake of parasite Ag.
AN EXPERIMENTAL STUDY ON TRAUMATIC CHANGES IN MICROVESSELS PRODUCED BY PRESSURE CLAMPING (1980)

Acute and chronic changes produced in microvessels by clamping with serial clips were investigated by macroscopic observation and by light and scanning electron microscopy. The degree of damage of the artery was well correlated with the clamping pressure. The results of the present study revealed that a pressure of 131 g or less did not produce damage to the endothelium, while a pressure of 250 g or more brought about complete fracture or disruption of the intima and necrosis of the media.
Designing Computer Systems from a Human Perspective: The Use of Narratives (1994)

From the assumption that we need techniques and tools, which support designers making descriptions of human living people during the design process, I propose that we use narratives as a form of expression. I present a model, which illustrates how the designer can work with narratives, and the model is explained referring to experiences derived from different kinds of student reports and activities carried out in the years 1990- 92.
Russian Experience in Screening, Analysis, and Clinical Application of Novel Interferon Inducers (2001)

This review describes a long-standing experience of screening for interferon (IFN) inducers in Russia. IFN inducers represent a special group of potential antiviral compounds. The main requirements for them are (1) high IFN-inducing activity, (2) absence of side effects, (3) wide spectrum of antimicrobial activity, (4) broad therapeutic security and, (5) good solubility in water and biologic liquids. IFN inducers stimulate IFN production in different cells and organs, and that determines the strategy for their application. Amixin (OOO "Lancepharm," Moscow, Russia) induces IFN-alpha/beta production mostly in T cells. Cycloferon (NTFF "Polysan," St. Petersburg, Russia) stimulates B cells and macrophages to produce almost pure IFN-alpha. Double-stranded RNA (dsRNA) and polyphenols of natural origin stimulate IFN production in different populations of immunocytes. Only polymers, such as Larifan (Riga, Latvia), Kagocel ("NIARnedicplus," Moscow, Russia), and Ragosin (N.F. Gamaleya Institute, Moscow, Russia), induce IFN synthesis in muscles, so they may be effective against rabies. Cycloferon, Larifan, and Kagocel, which induce IFN formation in lungs, may be effective against influenza and rhinoviral infections. Cycloferon and Larifan stimulate IFN production in liver and spleen and may be effective against hepatitis B. Oral compounds (Amixin, Kagocel) that stimulate IFN production in intestines may be effective against hepatitis A and enteroviral infections. Low molecular weight inducers (Amixin, Cycloferon, Kagocel) that penetrate the blood-brain barrier may be active against viral encephalitis. At present, clinical trials of IFN inducers are limited, but in the near future, IFN inducers may be used against very different infections and conditions.
Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines (2014)

While the past decade has seen great progress in mapping loci for common diseases, studying how these risk alleles lead to pathology remains a challenge. Age-related macular degeneration (AMD) affects 9 million older Americans, and is characterized by the loss of the retinal pigment epithelium (RPE). Although the closely linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are strongly associated with the risk of AMD, their downstream targets are unknown. Low population frequencies of risk alleles in tissue banks make it impractical to study their function in cells derived from autopsied tissue. Moreover, autopsy eyes from end-stage AMD patients, where age-related RPE atrophy and fibrosis are already present, cannot be used to determine how abnormal ARMS2/HTRA1 expression can initiate RPE pathology. Instead, induced pluripotent stem (iPS) cell-derived RPE from patients provides us with earlier stage AMD patient-specific cells and allows us to analyze the underlying mechanisms at this critical time point. An unbiased proteome screen of A2E-aged patient-specific iPS-derived RPE cell lines identified superoxide dismutase 2 (SOD2)-mediated antioxidative defense in the genetic allele's susceptibility of AMD. The AMD-associated risk haplotype (T-in/del-A) impairs the ability of the RPE to defend against aging-related oxidative stress. SOD2 defense is impaired in RPE homozygous for the risk haplotype (T-in/del-A; T-in/del-A), while the effect was less pronounced in RPE homozygous for the protective haplotype (G-Wt-G; G-Wt-G). ARMS2/HTRA1 risk alleles decrease SOD2 defense, making RPE more susceptible to oxidative damage and thereby contributing to AMD pathogenesis.
Size-dependent single-particle energy levels and interparticle Coulomb interactions in CdSe quantum dots measured by scanning tunneling spectroscopy (2006)

We report on tunneling spectroscopy measurements on colloidal CdSe quantum dots of different sizes. The size-dependent energy level structure and electron-hole Coulomb attraction in CdSe quantum dots are obtained by a combination of shell-tunneling spectroscopy and optical spectroscopy. The results are in good agreement with tight-binding calculations. The electron-electron interactions are investigated by shell-filling spectroscopy. The tunneling spectra in this regime are analyzed by solving the master equation for the electron and hole occupancy of the quantum dot.
Predictive approaches for drug combination discovery in cancer (2016)

Drug combinations have been proposed as a promising therapeutic strategy to overcome drug resistance and improve efficacy of monotherapy regimens in cancer. This strategy aims at targeting multiple components of this complex disease. Despite the increasing number of drug combinations in use, many of them were empirically found in the clinic, and the molecular mechanisms underlying these drug combinations are often unclear. These challenges call for rational, systematic approaches for drug combination discovery. Although high-throughput screening of single-agent therapeutics has been successfully implemented, it is not feasible to test all possible drug combinations, even for a reduced subset of anticancer drugs. Hence, in vitro and in vivo screening of a large number of drug combinations are not practical. Therefore, devising computational methods to efficiently explore the space of drug combinations and to discover efficacious combinations has attracted a lot of attention from the scientific community in the past few years. Nevertheless, in the absence of consensus regarding the computational approaches used to predict efficacious drug combinations, a plethora of methods, techniques and hypotheses have been developed to date, while the research field lacks an elaborate categorization of the existing computational methods and the available data sources. In this manuscript, we review and categorize the state-of-the-art computational approaches for drug combination prediction, and elaborate on the limitations of these methods and the existing challenges. We also discuss about the recent pan-cancer drug combination data sets and their importance in revising the available methods or developing more performant approaches.
Endoscopic evaluation of Crohnʼs disease activity (2010)

Both validated endoscopic scores, the CDEIS and SES-CD, and their changes during CD therapy demonstrated a close correlation. For scoring of endoscopic activity in clinical routine, the SES-CD could replace the CDEIS.
Tailoring Secretion of Proteoglycan 4 (PRG4) in Tissue-Engineered Cartilage (2006)

Articular cartilage provides a low-friction surface for joint articulation, with boundary lubrication facilitated by proteoglycan 4 (PRG4), which is secreted by chondrocytes of the superficial zone. Chondrocytes from different zones are phenotypically distinct, and their phenotypes in vitro are influenced by the system in which they are cultured. We hypothesized that culturing cells from the superficial (S) zone in two-dimensional monolayer or three-dimensional alginate would affect their synthesis of PRG4, and that subsequently seeding them atop alginate-recovered cells from the middle/ deep (M) zone in various proportions would result in tissue-engineered constructs with varying levels of PRG4 secretion and matrix accumulation. During monolayer culture, S cells retained their PRG4-secreting phenotype, whereas in alginate culture the percentage of cells secreting PRG4 decreased with time. Constructs formed with increasing percentages of S cells decreased in thickness and matrix accumulation, depending on both the culture conditions before construct formation and the S-cell density. PRG4-secreting cells were localized to the S-cell seeded construct surface, with secretion rates of 0.1-4 pg/cell/day or 0.1-1 pg/cell/day for constructs formed with monolayer-recovered or alginate-recovered S cells, respectively. Tailoring secretion of PRG4 in cartilage constructs may be useful for enhancing low-friction properties at the articular surface, while maintaining other surfaces free of PRG4 for enhancing integration with surrounding tissues.
COSMETIC SURGERY For Small Breasts (1961)

Dr. Baker is clinical assistant professor in plastic surgery at the University of Miami School of Medicine in Miami, Fla., and is the author of “Open Technique in the Management of Burns,” in the September 1959 issue of the Jounal.
Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing (2015)

Bacteria are central to human health and disease, but existing tools to edit microbial consortia are limited. For example, broad-spectrum antibiotics are unable to accurately manipulate bacterial communities. Bacteriophages can provide highly specific targeting of bacteria, but assembling well-defined phage cocktails solely with natural phages can be a time-, labor- and cost-intensive process. Here, we present a synthetic-biology strategy to modulate phage host ranges by engineering phage genomes in <i>Saccharomyces cerevisiae</i>. We used this technology to redirect <i>Escherichia coli</i> phage scaffolds to target pathogenic <i>Yersinia</i> and <i>Klebsiella</i> bacteria, and conversely, <i>Klebsiella</i> phage scaffolds to target <i>E. coli</i> by modular swapping of phage tail components. The synthetic phages achieved efficient killing of their new target bacteria and were used to selectively remove bacteria from multi-species bacterial communities with cocktails based on common viral scaffolds. We envision that this approach will accelerate phage-biology studies and enable new technologies for bacterial population editing.
Multiplex PCR for differential diagnosis of emerging typhoidal pathogens directly from blood samples (2008)

Classically Salmonella enterica serovar Typhi (S. Typhi) is associated with typhoid, a major health problem in developing countries. However, in recent years S. Paratyphi A and Vi-negative variants of S. Typhi have emerged rapidly. We have developed a nested multiplex PCR targeting five different genes for differential diagnosis of typhoidal pathogens which has been optimized to be directly applicable on clinical blood samples. Of 42 multiplex PCR-positive blood samples, 26, nine, and two were Vi-positive S. Typhi, Vi-negative S. Typhi and S. Paratyphi A, respectively, and five patients were found to have mixed infection. Seventeen patients grew Salmonella from blood culture and the remaining 25 were positive in the Salmonella-specific PCR. Tests with several common pathogens confirmed the specificity of the assay. We conclude that the proposed multiplex PCR is rapid, sensitive and specific for the diagnosis of typhoidal pathogens directly from blood samples.