gebhart/patrepeval huggingface dataset:
Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53 (2015)

The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1α (DD1α), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1α appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1α-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1α thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.
Semiconducting Nanowire Field-Effect Transistor Biomolecular Sensors (2008)

Recent studies have demonstrated the ability of semiconducting nanowire (NW) field-effect transistors (FETs) to serve as highly sensitive label-free sensors for biochemicals, including small molecules, proteins, and nucleic acids. The nanoscale confinement of the channel current in concert with the large-surface area-to-volume ratio enables charged molecules bound to the surface to effectively gate the device. Functionalization of the NW surface with specific receptors therefore enables direct electronic detection of particular molecules of interest. The original work in the field relied on NWs grown by the chemical vapor deposition method, which require hybrid bottom-up fabrication processes for device realization. The lack of reproducibility with these techniques and the associated inability to leverage the central advantage of complementary MOSFETs, namely, very large scale integration, have recently led a number of groups to create NW sensors using only traditional top-down fabrication techniques. In this paper, we focus primarily on these most recent studies and discuss necessary future studies as dictated by experimental and theoretical considerations.
Intraoperative lymphatic mapping and selective cervical lymphadenectomy for early-stage melanomas of the head and neck. (1993)

Intraoperative lymphatic mapping and SLND is a minimally invasive and highly accurate screening technique for determining which patients with CS-I head and neck melanomas have subclinical node metastases and therefore might benefit from cervical LND.
Too much vacuum‐assisted closure (2003)

There has been an explosion in the use of the vacuum-assisted closure device since 1997. Selectively and judiciously used, it is a valuable tool. However, we are concerned by the expanding list of 'indications' for its use. Prolonged applications, frequently several weeks, at the expense of early surgical reconstruction, might compromise the outcome in selected cases. We report four cases that illustrate this problem and stress the importance of timely surgical reconstruction utilizing the range of reconstructive techniques available as well as vacuum-assisted closure dressing.
An interlocked dimeric parallel-stranded DNA quadruplex: A potent inhibitor of HIV-1 integrase (2005)

We report on the NMR-based solution structure of the 93del d(GGGGTGGGAGGAGGGT) aptamer, a potent nanomolar inhibitor of HIV-1 integrase. This guanine-rich DNA sequence adopts an unusually stable dimeric quadruplex architecture in K+ solution. Within each 16-nt monomer subunit, which contains one A.(G.G.G.G) pentad sandwiched between two G.G.G.G tetrads, all G-stretches are parallel, and all guanines are anti with the exception of G1, which is syn. Dimer formation is achieved through mutual pairing of G1 of one monomer, with G2, G6, and G13 of the other monomer, to complete G.G.G.G tetrad formation. There are three single-nucleotide double-chain-reversal loops within each monomer fold, such that the first (T5) and third (A12) loops bridge three G-tetrad layers, whereas the second (A9) loop bridges two G-tetrad layers and participates in A.(G.G.G.G) pentad formation. Results of NMR and of integrase inhibition assays on loop-modified sequences allowed us to propose a strategy toward the potential design of improved HIV-1 integrase inhibitors. Finally, we propose a model, based on molecular docking approaches, for positioning the 93del dimeric DNA quadruplex within a basic channel/canyon formed between subunits of a dimer of dimers of HIV-1 integrase.
Smoldering Multiple Myeloma (1980)

MULTIPLE myeloma is characterized by an increase of abnormal plasma cells in the bone marrow and monoclonal protein in the serum, often with osteolytic bone lesions. Its course is progressive: anemia, weakness, fatigue, fractures, bone pain, hypercalcemia, renal insufficiency, recurrent infections, bleeding, and deterioration lead to death. However, we have seen six patients with illnesses that met the criteria for the diagnosis of multiple myeloma1 but have not had a progressive course. Although no chemotherapy was given, their condition has remained stable for five or more years. We designate these cases as "smoldering multiple myeloma." We wish to call attention . . .
10×10 cm/sup 2/ screen printed back contact cell with a selective emitter (2002)

Back contact cells promise a cost reduction for the interconnection of cells to modules. The emitter wrap through concept allows in addition to combine low cost material, surface texture, a selective emitter (alkaline etch for Cz-Si respectively mechanical texturing for mc-Si) together with screen printed contacts as done in this work. The connecting holes are drilled by a laser. Emitter and base region at the cell rear are separated by a screen printable diffusion barrier. Computer simulations assisted the optimisation of the grid design especially in estimating the influence of the busbar regions to the series resistance. An efficiency of 15.8% was reached on Cz-silicon, which is the highest efficiency reported so far for a low-cost (i.e., no photolithographical steps) back contact cell. The authors obtained J/sub sc/ of 37.9 mA/cm/sup 2/ and V/sub oc/ of 600 mV. The internal quantum efficiency was found to be distinctly increased due to the selective emitter on the front.
Intestinal epithelial organoids fuse to form self-organizing tubes in floating collagen gels (2017)

Multiple recent examples highlight how stem cells can self-organize <i>in vitro</i> to establish organoids that closely resemble their <i>in vivo</i> counterparts. Single Lgr5<sup>+</sup> mouse intestinal stem cells can be cultured under defined conditions forming ever-expanding epithelial organoids that retain cell polarization, cell type diversity and anatomical organization of the <i>in vivo</i> epithelium. Although exhibiting a remarkable level of self-organization, the so called 'mini-guts' have a closed cystic structure of microscopic size. Here, we describe a simple protocol to generate macroscopic intestinal tubes from small cystic organoids. Embedding proliferating organoids within a contracting floating collagen gel allows them to align and fuse to generate macroscopic hollow structures ('tubes') that are lined with a simple epithelium containing all major cell types (including functional stem cells) of the small intestine. Cells lining the central contiguous lumen closely resemble the epithelial cells on luminal villi <i>in vivo</i>, whereas buds that protrude from the main tube into the surrounding matrix closely resemble crypts. Thus, the remarkable self-organizing properties of Lgr5<sup>+</sup> stem cells extend beyond the level of the microscopic cystic organoid to the next, macroscopic, level of tube formation.
A peptide containing the leucine zipper domain specifically inhibits CREB binding and transcription. (1993)

Formation of dimers via leucine zippers is an absolute requirement for several transcription factors to express their activity. Using circular dichroism spectroscopy, it was found that synthetic peptides which mimic the leucine zippers from CREB, Jun and Myc are alpha-helices in solution. The CREB leucine zipper peptide specifically inhibited the binding of wild type CREB protein and transcription from the CRE containing c-fos promoter in vitro. This inhibition is most likely caused by competition of the peptide to form complex with CREB monomers through leucine zippers.
MRI relaxometry: methods and applications (2006)

Aspects of magnetic resonance relaxation measurements in human tissues are discussed. The influence of pulse sequences and parameters are compared and analyzed for different tissues. By controlling the acquisition parameters and data fitting the relaxation rate can be useful in several clinical situations. The influence of repetition and echo time, predicted in sequences of signal acquisition, on measurement of transversal relaxation time (T2) was evaluate using simulated MRI signal.
Analysis of Recently Identified Prostate Cancer Susceptibility Loci in a Population-based Study: Associations with Family History and Clinical Features (2009)

Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however, the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features.
Targeted cytotoxic analogue of somatostatin AN-238 inhibits growth of androgen-independent Dunning R-3327-AT-1 prostate cancer in rats at nontoxic doses. (1998)

Receptors for somatostatin (SST) that are found on prostate cancers might be used for targeting of chemotherapeutic agents. Thus, doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to SST analogue RC-121 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2) to form targeted cytotoxic SST analogue AN-238. In this study, we evaluated the effects of AN-238 on the growth of SST receptor (SSTR)-positive androgen-independent Dunning R-3327-AT-1 prostate cancers in Copenhagen rats. The dose range and tumor growth-inhibitory effects of AN-238 and AN-201 were investigated in preliminary experiments. Administration of cytotoxic radical AN-201 at single i.v. doses of 110, 125, and 150 nmol/kg resulted in 0, 77.7, and 100% mortality, respectively, within 6-10 days. Four weeks after the injection of 110 nmol/kg AN-201, mean tumor volume was reduced by 35.1 % (P < 0.05), as compared with controls. In contrast, a single i.v. injection of analogue AN-238 at a dose of 300 nmol/kg was nontoxic and remarkably potent in inhibiting the growth of Dunning AT-1 tumors, resulting in a 85.9% (P < 0.01) reduction in tumor volume after 4 weeks. Treatment with AN-238 extended the survival time of tumor-bearing rats from 52.0+/-3.75 to 91.8+/-3.70 days, corresponding to a 76.5% (P < 0.01) increase. In a comprehensive experiment, we compared the effects of radical AN-201 at 115 nmol/kg, analogue AN-238 at 115 and 300 nmol/kg, carrier SST analogue RC-121 at 300 nmol/kg, and a mixture of AN-201 and RC-121 at doses of 300 nmol/kg administered i.v. Administration of AN-201 at 115 nmol/kg led to 90.0% mortality in 12 days, but animals treated with 115 nmol/kg of AN-238 showed no signs of toxicity, their tumor volume was reduced by 40.0% (P < 0.05), and their tumor weight was reduced by 42.8% (P < 0.01) after 4 weeks, as compared with controls. The dose of 300 nmol/kg of AN-238 was also nontoxic and diminished tumor volume by 80.9% (P < 0.01) and tumor weight by 82.0% (P < 0.01). No reduction in tumor growth or toxic effects was observed with carrier RC-121, but after the injection of unconjugated mixture of AN-201 and RC-121 at doses of 300 nmol/kg, all rats died within 4 days. Specific high-affinity receptors for SST were found on Dunning R-3327-AT-1 tumor membranes by radioligand binding assay and were identified by reverse transcription-PCR as SSTR2. Our study indicates that cytotoxic SST analogue AN-238 can be targeted to SSTRs on tumors and produces a powerful inhibition of the growth of Dunning-AT-1 rat prostate cancer at doses that are nontoxic, whereas its cytotoxic component, 2-pyrrolinodoxorubicin, is toxic and ineffective.
Reverse genetics of negative-stranded RNA viruses: A global perspective (2005)

The advent of reverse genetics technology has revolutionized the field of RNA viruses. It is now possible to manipulate even negative-stranded RNA viruses at will, and evaluate the effects of these changes on the biology and pathogenesis of these viruses. The fundamental insights gleaned from the reverse genetics-based studies over the last several years have provided a new momentum for the development of designed therapies for the control and prevention of these viral pathogens. The recombinant viruses have been exploited also as vectors for devising targeted therapies for non-viral diseases such as malignancies, and in gene therapy for inherited disorders. This review provides a brief summary of the stumbling blocks and the successes in the development of the technology for the negative-stranded RNA viruses. The many and varied applications of the recombinant vectors are also outlined.
Nonadditive Genetic Effects and Inbreeding Depression for Somatic Cell Counts of Holstein Cattle (1995)

A total of 65,491 lactation means of log2-transformed SCC measures were analyzed from first lactation Holstein cows in Ontario. Effects of inbreeding on SCC were estimated by a nonadditive sire and dam model that included additive, dominance, and additive by additive genetic effects and regression of lactation somatic cell score on inbreeding coefficients of the cows. Variance components were estimated using the tildehat approximation to REML. Solutions were by iteration on data. Estimates of heritability for lactation somatic cell score in the narrow sense were .165 and in the broad sense were .203. The additive by additive component (2.5% of the total phenotypic variance) was almost twice as large as the dominance component (1.3%). The regression coefficient of lactation somatic cell score per 1% increase of inbreeding was .012. The average increase of the population mean of lactation somatic cell score caused by a 10% increase of inbreeding coefficient was estimated to be 10.5% of the original phenotypic standard deviation of 1.153. The inbreeding depression was thus relatively low, but, on average, inbred animals tended to have higher lactation somatic cell score. This study provides preliminary evidence that inbreeding is related to disease prevalence in large purebred dairy populations.
Copper-67 Radioimmunotherapy and Growth Inhibition by Anti–L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis (2007)

The results show improved pharmacokinetics and biodistributions as well as the therapeutic effect of the (67)Cu-labeled single amino acid mutant chCE7agl. Therapeutic data indicate, for the first time, the feasibility of combining anti-L1-directed growth inhibition and (67)Cu-radioimmunotherapy, thereby increasing the efficiency of antibody treatment of metastatic ovarian carcinoma.
Analysis of different endoscopic methods for resection of rectal neuroendocrine tumors: A 10‐year experience at a secondary care hospital (2018)

Rectal neuroendocrine tumors (NETs) account for one‐third of all digestive NETs and are often incidentally found during colonoscopy. They also carry the risk of metastasis. Given their subepithelial growth, complete removal, R0 resection, is a challenge for endoscopists. Inadequate endoscopic management would lead to incomplete removal and additional complications for surveillance. The aim of this study is to compare R0 resection rates among all endoscopic methods. The database of our pathology department was reviewed from January 2005 to July 2015. Diagnoses of carcinoid and NETs located at rectum were enrolled. NETs removed by endoscopy were further selected for analysis. R0 resection was defined as being free of tumor at lateral and vertical margins on pathological examination. Three methods of endoscopic management were performed for our patients; these were snare polypectomy, endoscopic submucosal resection‐ligation assisted (ESMR‐L), and endoscopic submucosal dissection (ESD). In all, 48 rectal NETs were diagnosed. Thirty‐six rectal NETs were removed by endoscopy. Pathology validated hepatic metastasis was found in a patient with18 mm tumor size and G2 mitosis. The R0 resection rates for snare polypectomy, ESMR‐L, and ESD were 33.3% (6/18), 90.9% (10/11), and 100% (7/7) respectively ( P = 0.001). Procedure time for the ESMR‐L group (5.36 min) was shorter than the ESD group (38.86 min) ( P &lt; 0.001). Percentage of patients receiving endoscopic ultrasonography before endoscopic management also revealed significant differences among the three groups (3/18, 16.7%; 6/11, 54.5%; 7/7, 100%; P = 0.001). ESD offered the highest R0 resection rate, followed by ESMR‐L and snare polypectomy. However, ESMR‐L has shorter procedure time.
Enhanced expression of basement‐membrane‐type heparan sulfate proteoglycan in tumor fibro‐myxoid stroma of intrahepatic cholangiocarcinoma (2001)

To investigate the molecular mechanism for enhanced fibrous stroma formation in intrahepatic cholangiocarcinoma (ICC), we surveyed the expression pattern of basement-membrane-type heparan sulfate proteoglycan (HSPG; also known as perlecan) at the core protein and the mRNA level in ICC as well as in other liver neoplasms and reactive hepatic diseases. Immunohistochemistry of paraffin-embedded liver sections with hyaluronidase pretreatment showed that HSPG was present in small amounts in normal liver around the bile ducts and the blood vessels within the portal area. There was no evident expression within the hepatic lobules. Intense immunoexpression of HSPG was seen in the tumor-specific fibro-myxoid stroma of ICC and metastatic liver cancer originating from the colon. However, tumor-specific stroma of hepatocellular carcinomas showed little or no expression of HSPG. At the mRNA level, signals for HSPG were found in tumor cells of cholangiocarcinoma and metastatic colonic carcinomas, and in myofibroblasts in the tumor fibro-myxoid-specific stroma. From immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analyses, a cultured human intrahepatic cholangiocarcinoma cell line (CCKS1), was found to express high levels of HSPG core protein and mRNA. These findings suggest that biliary and metastatic colon carcinoma cells as well as stromal myofibroblasts have a potential for HSPG production. In order to investigate the growth, invasion and metastatic ability of ICC, further study of the 'self-made' stromal component of ICC may provide a new approach.
Unconstrained web-based color naming experiment (2003)

This paper describes an ongoing web-based approach to collecting color names or color categories. Previous studies have tended to require a large number of observations from a small number of observers. These studies have also tended to limit responses to one-word or monolexical replies. Many studies have also focused on response time or levels of intra-observer agreement in order to identify focal colors. This web-based study uses a distributed design to collect a small number of names from a large number of observers. The responses are neither limited to nor restricted from being monolexical. The focal color analysis is then based on statistical analysis of monolexcially named colors. This paper presents the methodology and infrastructure, as well as considerations for data analysis. Finally, preliminary results of the experiment are results are considered. The data from over 700 participants results in CIELAB hues and lightnesses for the basic colors that agree with previous investigations as well as those investigations agree with each other.
THE UNLABELED ANTIBODY ENZYME METHOD OF IMMUNOHISTOCHEMISTRY PREPARATION AND PROPERTIES OF SOLUBLE ANTIGEN-ANTIBODY COMPLEX (HORSERADISH PEROXIDASE-ANTIHORSERADISH PEROXIDASE) AND ITS USE IN IDENTIFICATION OF SPIROCHETES (1970)

Antigen was identified histochemically without the use of labeled antibodies by the sequential application of (a) specific rabbit antiserum, (b) sheep antiserum to rabbit immunoglobulin G, (c) specifically purified, soluble horseradish peroxidase-anti-horseradish peroxidase complex (PAP), (d) 3,3'-diaminobenzidine and hydrogen peroxide and (e) osmium tetroxide. A simple method for preparation of high yields of PAP consisted of precipitation of antibody from specific rabbit antiserum with horseradish peroxidase (PO) at equivalence, solubilization of the washed precipitate with excess PO at pH 2.3, 1°C, followed by immediate neutralization and separation of PAP from PO by half-saturation with ammonium sulfate. The ratio of PO to anti-PO in PAP was 3:2 irrespective of the source of antiserum. PAP was heterogeneous on electrophoresis, homogeneous on sedimentation, diffusion and electron microscopy and consisted of pentagons with diameters of 205 Å. s 20, w , 11.98 x 10 –13 ; d 20, w , 2.48 x 10 –7 ; molecular weight by sedimentation velocity, 429,000, and equilibrium, 413,000. Sensitivity and specificity of immunohistochemical staining of spirochetes was about 100- to 1000-fold that of immunofluorescence. The unexpected ratio of PO to anti-PO is presumed to be due to stabilization by the pentagonal shape in which three corners are suspected to be PO and two antibody fragment Fc.
Toward a new blood vessel (2002)

Strategies to treat atherosclerotic coronary artery disease include coronary artery bypass grafting (CABG), in which grafts are used to bypass atherosclerotic vessels and restore blood flow to the ischemic myocardium. The grafts used include healthy arteries or veins harvested from a separate site. Results with arterial grafts have been superior to venous grafts; promoting the practice of total arterial revascularization using only arterial grafts. Suitable arterial grafts, however, are scarce and harvest procedures add to morbidity and cost. Tissue engineering combines the principles of engineering with life sciences for the development of biological substitutes and restore, maintain or improve tissue function. Advances in this field have included the development of tissue-engineered blood vessels, with the potential to serve as arterial grafts, conduits or fistulae. This review describes the history of tissue engineering arteries, the techniques used, and progress to date. The source of cells and the future direction of this field are explored.