gebhart/patrepeval huggingface dataset:
Hypermethylation of apoptotic genes as independent prognostic factor in neuroblastoma disease (2010)

Neuroblastoma (NB) is an embryonal tumour of neuroectodermal cells, and its prognosis is based on patient age at diagnosis, tumour stage and MYCN amplification, but it can also be classified according to their degree of methylation. Considering that epigenetic aberrations could influence patient survival, we studied the methylation status of a series of 17 genes functionally involved in different cellular pathways in patients with NB and their impact on survival. We studied 82 primary NB tumours and we used methylation-specific-PCR to perform the epigenetic analysis. We evaluated the putative association among the evidence of hypermethylation with the most important NB prognostic factors, as well as to determine the relationship among methylation, clinical classification and survival. CASP8 hypermethylation showed association with relapse susceptibility and, TMS1 and APAF1 hypermethylation are associated with bad prognosis and showed high influence on NB overall survival. Hypermethylation of apoptotic genes has been identified as a good candidate of prognostic factor. We propose the simultaneous analysis of hypermethylation of APAF1, TMS1 and CASP8 apoptotic genes on primary NB tumour as a good prognostic factor of disease progression.
Small molecule developmental screens reveal the logic and timing of vertebrate development (2000)

Much has been learned about vertebrate development by random mutagenesis followed by phenotypic screening and by targeted gene disruption followed by phenotypic analysis in model organisms. Because the timing of many developmental events is critical, it would be useful to have temporal control over modulation of gene function, a luxury frequently not possible with genetic mutants. Here, we demonstrate that small molecules capable of conditional gene product modulation can be identified through developmental screens in zebrafish. We have identified several small molecules that specifically modulate various aspects of vertebrate ontogeny, including development of the central nervous system, the cardiovascular system, the neural crest, and the ear. Several of the small molecules identified allowed us to dissect the logic of melanocyte and otolith development and to identify critical periods for these events. Small molecules identified in this way offer potential to dissect further these and other developmental processes and to identify novel genes involved in vertebrate development.
Functional cell surface expression by a recombinant single‐chain class I major histocompatibility complex molecule with a cis‐active β2‐microglobulin domain (1994)

As a preliminary step towards the use of cell surface single-chain class I major histocompatibility complex (MHC) molecules as T cell immunogens, we have engineered a recombinant gene encoding a full-length cell surface single-chain version of the H-2Dd class I MHC molecule (SC beta Ddm) which has beta 2-microglobulin (beta 2m) covalently linked to the amino terminus of a full-length H-2Dd heavy chain via a peptide spacer. The single-chain protein is correctly folded and stably expressed on the surface of transfected L cells. It can present an antigenic peptide to an H-2Dd-restricted antigen-specific T cell hybridoma. When expressed in peptide-transport-deficient cells, SC beta Ddm can be stabilized and pulsed for antigen presentation by incubation with extracellular peptide at 27 degrees or 37 degrees C, allowing the preparation of cells with single-chain molecules that are loaded with a single chosen antigenic peptide. SC beta Ddm can be stably expressed in beta 2m-negative cells, showing that the single-chain molecule uses its own beta 2m domain to achieve correct folding and surface expression. Furthermore, the beta 2m domain of SC beta Ddm, unlike transfected free beta 2m, does not rescue surface expression of endogenous class I MHC in the beta 2m-negative cells. This strict cis activity of the beta 2m domain of SC beta Ddm makes possible the investigation of class I MHC function in cells, and potentially in animals, that express but a single type of class I MHC molecule.
The utilization of fluorescence to identify the components of lipofuscin by imaging mass spectrometry (2014)

Lipofuscin, an aging marker in the retinal pigment epithelium (RPE) associated with the development of age-related macular degeneration, is primarily characterized by its fluorescence. The most abundant component of RPE lipofuscin is N-retinylidene-N-retinylethanolamine (A2E) but its exact composition is not known due to the complexity of the RPE extract. In this study, we utilized MALDI imaging to find potential molecules responsible for lipofuscin fluorescence in RPE tissue from Abca4(-/-) , Sv129, and C57Bl6/J mice aged 2 and 6 months. To assert relationships, the individual images in the MALDI imaging datasets were correlated with lipofuscin fluorescence recorded from the same tissues following proper registration. Spatial correlation information, which is usually lost in bioanalytics, pinpointed a relatively small number of potential lipofuscin components. The comparison of four samples in each condition further limited the possibility of false positives and provided various new, age- and strain-specific targets. Validating the usefulness of the fluorescence-enhanced imaging strategy, many known adducts of A2E were identified in the short list of lipofuscin components. These results provided evidence that mass spectrometric imaging can be utilized as a tool to begin to identify the molecular substructure of clinically-relevant diagnostic information.
Comprehensive serotyping and epidemiology of human adenovirus isolated from the respiratory tract of Korean children over 17 consecutive years (1991–2007) (2010)

Among the 53 serotypes of human adenoviruses (HAdVs), identified to date, only a limited number have been associated with human respiratory infections. The epidemiology of each of the serotypes differs depending on the location and/or time of surveillance. This study was performed to elucidate the epidemiology of HAdV respiratory infections by comprehensive serotyping of the HAdVs isolated from the respiratory tract of Korean children. HAdVs isolated from respiratory specimens of Korean children over 17 consecutive years (1991-2007) were typed by the neutralization test or molecular methods, including two-sets of multiplex PCR assays, and/or sequence analysis of the hexon gene. From January 1991 through December 2007, a total of 741 isolates were obtained from nasal aspirates of children hospitalized or requiring medical treatment in the emergency room. All isolates were type-determined successfully and 13 different serotypes were identified, which included HAdV serotypes 1-8, 11, 19, 34, 37, and 41. HAdV-3 (n = 285, 37.7%) and HAdV-7 (n = 181, 23.9%) were the predominant serotypes; HAdV-8, -11, -19, -34, -37, and -41 were not usually associated with respiratory diseases. HAdV-3 was present both during outbreaks and in sporadic cases. HAdV-7 emerged in a very large outbreak, followed by smaller outbreaks. HAdV-1, -2, -4, -5, and -6 were isolated sporadically throughout the study period. In conclusion, a total of 13 different serotypes of HAdV were detected among Korean children with respiratory tract infections. HAdV-3 and HAdV-7 were the most common serotypes, and they were associated with HAdV outbreaks.
Hybrid tracking system for retinal photocoagulation prototype II. (1999)

Laser photocoagulation has been employed extensively by ophthalmologists to treat retinal diseases and disorders such as diabetic retinopathy, macular degeneration, and retinal tears. Treatment is a manual task requiring the physician to carefully place therapeutic lesions on the retina while avoiding critical vision anatomy. We have developed a hybrid tracking system using two retinal tracking modalities: a digital imaging-based subsystem and an analog tracking subsystem to stabilize the irradiating laser on the retina. We have also investigated a lesion parameter control subsystem to provide uniform therapeutic lesions.
The role of the carboxyl-terminal tail in human O6-methylguanine DNA methyltransferase substrate specificity and temperature sensitivity. (1993)

The human O6-methylguanine DNA methyltransferase (MGMT) repairs O6-methylguanine (O6-MG) in DNA at a much lower rate than the Escherichia coli Ada protein, and only MGMT repairs the altered base, O6-benzylguanine (O6-BG). The diversity in DNA repair properties between MGMT and Ada may be a result of divergent amino acid sequences outside their common proline-cysteine-histidine-arginine-valine (PCHRV) acceptor site. One notable sequence difference is an MGMT 28-amino acid carboxyl-terminal tail which is highly conserved among all mammalian alkyltransferases. The role of this tail sequence in substrate specificity was assessed by expressing full-length MGMT and Ada proteins, and mutant MGMT proteins lacking either 10 or 28 amino acids from the carboxyl terminus, as GST fusion proteins in alkyltransferase-deficient E. coli cells, and comparing rates of repair of O6-MG containing DNA and O6-BG by these fusion proteins at 4 degrees C and 37 degrees C. The MGMT carboxyl-terminal tail was not required for repair of O6-MG in DNA at 37 degrees C although the deletion of this tail sequence reversibly inhibited the ability of MGMT to repair O6-MG in DNA at 4 degrees C. Therefore, the absence of this region affects the ability of the protein to repair O6-MG in DNA at lower temperatures. Furthermore, removal of the tail sequence from MGMT decreased the rate of O6-BG repair 5-fold. We conclude that the 28-amino acid carboxyl-terminal MGMT tail, while not required for activity, modulates the rate of MGMT repair at reduced temperatures and plays a role in substrate specificity.
Inhibition of erbB-2-Positive Breast Cancer Cell Growth by erbB-2 Antisense Oligonucleotides (1996)

Overexpression of erbB-2 proto-oncogene has been found in 20%-30% of human breast carcinomas and in most cases correlates with poor clinical prognosis. Using antisense oligonucleotides targeted to the 5' cap region of erbB-2RNA, we were able to inhibit erbB-2 protein expression, proliferation, and anchorage-independent growth of breast cancer cells up to 90%. These effects were sequence specific and restricted to cells expressing elevated level of erbB-2 protein. These support the feasibility of using antisense erbB-2 oligonucleotides to inhibit the progression of erbB-2-overexpressing breast cancer cells.
A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure (2001)

Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure, when added to prescribed therapy. However, the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan, an ACE inhibitor, and a beta-blocker raises concern about the potential safety of this specific combination.
Development of a Phosphorus Spray Diffusion System for Low-Cost Silicon Solar Cells (2006)

Phosphoric acid was used an n-type doping source to make an emitter for silicon solar cells. This paper reports on a cold spray method to coat phosphoric acid on the silicon wafer without any additional complicated and corrosive heating system. The key spray parameters such as belt speed, flow rate of the carrier gas, and concentration of phosphoric acid are optimized to get uniform and reproducible sheet resistance for the emitter. The diffusion process has been studied by firing silicon wafers that are spray-coated with phosphoric acid. screen printed solar cells have been fabricated using the emitter formed by the spray coating. The effects of the emitter on cell performance have been investigated and compared with those of the conventional -diffused emitter. screen printed/spray-diffused cells give impressive cell efficiencies of on float zone wafers, which is nearly equal to those of emitter cells . Compared with the emitter cell, the spray-diffused cells show slightly lower quantum efficiency at the short-wavelength response and slightly higher emitter saturation current density ( compared with ). Further optimization can eliminate this small difference in efficiency.
Photosensitivity of solution-based indium gallium zinc oxide single-walled carbon nanotubes blend thin film transistors (2009)

We studied the optical and electrical properties of solution-based indium gallium zinc oxide single-walled carbon nanotubes blend thin film transistors (SB-IGZO/SWNTs blend TFTs). When the SB-IGZO/SWNTs blend TFTs were illuminated at a wavelength of 660 nm, the off-state drain current slightly increased, while below 550 nm, it increased significantly. The SB-IGZO/SWNTs blend TFTs were incredibly sensitive, with deep-level defects at approximately 2.25 eV, near the midgap. We also presented the photosensitivity (signal-to-noise ratio) of these TFTs. Our results demonstrate that the SB-IGZO/SWNTs blend could be a good candidate for an ultraviolet photodetector.
Recent development in therapeutics for breakthrough pain (2010)

Breakthrough pain is defined as transitory flares of pain. Breakthrough pain is caused by cancer, cancer complications, treatment or comorbidities. The usual onset to maximum breakthrough pain intensity time is 3 min and duration is 30 min; therefore, the assessment for response needs to be at short intervals. The rapid onset and offset of pain results in inadequate responses when oral opioids are used to manage pain flares. Several strategies have been used to manage breakthrough pain: titration of the chronic opioid, independent titration of rescue opioids and alternative routes. Buccal fentanyl has a rapid onset to analgesia and appears to be superior to oral morphine. Newer fentanyl preparations have been released to manage breakthrough pain in the opioid-tolerant individual. Other routes of administration that have a rapid onset to analgesia include intranasal hydrophilic and lipophilic opioids, inhaled opioids delivered by special delivery devices and parenteral morphine. In a small series of patients experiencing severe flares of pain with spinal opioids unrelieved by parenteral opioids, sublingual ketamine and bolus doses of intrathecal local anesthetics have been effective. Nonpharmacological approaches to managing activity-related pain include radiation therapy, surgical correction of impending fractures, kyphoplasty and radioisotopes.
Universal Oligonucleotide Microarray for Sub-Typing of Influenza A Virus (2011)

A universal microchip was developed for genotyping Influenza A viruses. It contains two sets of oligonucleotide probes allowing viruses to be classified by the subtypes of hemagglutinin (H1-H13, H15, H16) and neuraminidase (N1-N9). Additional sets of probes are used to detect H1N1 swine influenza viruses. Selection of probes was done in two steps. Initially, amino acid sequences specific to each subtype were identified, and then the most specific and representative oligonucleotide probes were selected. Overall, between 19 and 24 probes were used to identify each subtype of hemagglutinin (HA) and neuraminidase (NA). Genotyping included preparation of fluorescently labeled PCR amplicons of influenza virus cDNA and their hybridization to microarrays of specific oligonucleotide probes. Out of 40 samples tested, 36 unambiguously identified HA and NA subtypes of Influenza A virus.
Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development. (1996)

Targeted inactivation of the murine gene encoding the transcription factor LEF-1 abrogates the formation of organs that depend on epithelial-mesenchymal tissue interactions. In this study we have recombined epithelial and mesenchymal tissues from normal and LEF-1-deficient embryos at different stages of development to define the LEF-1-dependent steps in tooth and whisker organogenesis. At the initiation of organ development, formation of the epithelial primordium of the whisker but not tooth is dependent on mesenchymal Lef1 gene expression. Subsequent formation of a whisker and tooth mesenchymal papilla and completion of organogenesis require transient expression of Lef1 in the epithelium. These experiments indicate that the effect of Lef1 expression is transmitted from one tissue to the other. In addition, the finding that the expression of Lef1 can be activated by bone morphogenetic protein 4 (BMP-4) suggests a regulatory role of this transcription factor in BMP-mediated inductive tissue interactions.
Generation of mice with a 200-kb amyloid precursor protein gene deletion by Cre recombinase-mediated site-specific recombination in embryonic stem cells. (1996)

Gene disruptions and deletions of up to 20kb have been generated by homologous recombination with appropriate targeting vectors in murine embryonic stem (ES) cells. Because we could not obtain a deletion of about 200 kb in the mouse amyloid precursor protein gene by the classical technique, we employed strategies involving the insertion of loxP sites upstream and downstream of the region to be deleted by homologous recombination and elicited excision of the loxP-flanked region by introduction of a Cre expression vector into the ES cells. In the first approach, the loxP sequences were inserted in two successive steps and after each step, ES cell clones were isolated and characterized. Deletion of the loxP-flanked sequence was accomplished by introducing the cre gene in a third step. In the second approach, ES cells containing the upstream loxP cassette were electroporated simultaneously with the downstream loxP targeting vector and the Cre expression plasmid. ES cells were obtained that gave rise to chimeric mice capable of germ-line transmission of the deleted amyloid precursor protein allele.
Collagen Binding Assay for von Willebrand Factor (VWF:CBA): Detection of von Willebrands Disease (VWD), and Discrimination of VWD Subtypes, Depends on Collagen Source (2000)

A large number of different collagen preparations [n = 21] have been assessed for their ability to both detect von Willebrands Disease (VWD), and discriminate different VWD subtypes. Collagen preparations were tested at a range of concentrations and included: Type I, III and IV, and various mixtures of these, as aqueous supplied preparations and/or reconstituted from bulk lyophilised stock. Tissue sources for collagens ranged from human placenta to calf skin to equine tendon. Three of the collagen preparations tested did not support von Willebrand factor (VWF) binding in an ELISA process (therefore unable to detect VWD). The ability of the remaining preparations to detect VWF was variable, as was their ability to discriminate VWD subtypes. Detection of VWF and discrimination of VWD subtypes was not mutually inclusive. Thus, some collagen preparations provided excellent detection systems for VWF, but comparatively poorer discrimination of Type 2 VWD, while others provided good to acceptable detection and discrimination. Subtype discrimination was also dependent on the collagen concentration, and some batch to batch variation was evident with some preparations (particularly Type I collagens). Overall, best discrimination was typically achieved with Type I/III collagen mixtures, or Type III collagen preparations (where effectiveness was highly dependent on concentration). Good discrimination was also achieved with a commercial Type III collagen based VWF:CBA kit method. Results of the various 'VWF:CBA assays' are also compared with those using the Ristocetin Cofactor (VWF:RCof) assay (by platelet agglutination) and that using a commercial 'VWF:RCof-alternative/activity' ELISA procedure. These latter methodologies tended to be less sensitive to VWF-discordance when compared to that detected by the majority of the VWF:CBA procedures.
Pluripotent cells in farm animals: state of the art and future perspectives (2012)

Pluripotent cells, such as embryonic stem (ES) cells, embryonic germ cells and embryonic carcinoma cells are a unique type of cell because they remain undifferentiated indefinitely in in vitro culture, show self-renewal and possess the ability to differentiate into derivatives of the three germ layers. These capabilities make them a unique in vitro model for studying development, differentiation and for targeted modification of the genome. True pluripotent ESCs have only been described in the laboratory mouse and rat. However, rodent physiology and anatomy differ substantially from that of humans, detracting from the value of the rodent model for studies of human diseases and the development of cellular therapies in regenerative medicine. Recently, progress in the isolation of pluripotent cells in farm animals has been made and new technologies for reprogramming of somatic cells into a pluripotent state have been developed. Prior to clinical application of therapeutic cells differentiated from pluripotent stem cells in human patients, their survival and the absence of tumourigenic potential must be assessed in suitable preclinical large animal models. The establishment of pluripotent cell lines in farm animals may provide new opportunities for the production of transgenic animals, would facilitate development and validation of large animal models for evaluating ESC-based therapies and would thus contribute to the improvement of human and animal health. This review summarises the recent progress in the derivation of pluripotent and reprogrammed cells from farm animals. We refer to our recent review on this area, to which this article is complementary.
Intravenous immunoglobulin therapy for severe Clostridium difficile colitis (1997)

Background —Many individuals have serum antibodies against Clostridium difficile toxins. Those with an impaired antitoxin response may be susceptible to recurrent, prolonged, or severe C difficile diarrhoea and colitis. Aims —To examine whether treatment with intravenous immunoglobulin might be effective in patients with severe pseudomembranous colitis unresponsive to standard antimicrobial therapy. Patients —Two patients with pseudomembranous colitis not responding to metronidazole and vancomycin were given normal pooled human immunoglobulin intravenously (200–300 mg/kg). Methods —Antibodies against C difficile toxins were measured in nine immunoglobulin preparations by ELISA and by cytotoxin neutralisation assay. Results —Both patients responded quickly as shown by resolution of diarrhoea, abdominal tenderness, and distension. All immunoglobulin preparations tested contained IgG against C difficile toxins A and B by ELISA and neutralised the cytotoxic activity of C difficile toxins in vitro at IgG concentrations of 0.4–1.6 mg/ml. Conclusion —Passive immunotherapy with intravenous immunoglobulin may be a useful addition to antibiotic therapy for severe, refractory C difficile colitis. IgG antitoxin is present in standard immunoglobulin preparations and C difficile toxin neutralising activity is evident at IgG concentrations which are readily achieved in the serum by intravenous immunoglobulin administration.