gebhart/patrepeval huggingface dataset:
Multiplex Co-Amplification of 24 Retinoblastoma Gene Exons after Pre-Amplification by Long-Distance PCR (1996)

Polymerase chain reaction (PCR) amplification has become themethod of choice for preparing the DNA template in mutationanalysis from complex mixtures of DNA or RNA molecules. Thisstrategy is optimal for small genes or genes with mutational hotspots.However, PCR-based mutation detection is neither labour nor costeffective when large or multiple genes, with many target fragments,are involved. In addition, such an approach is limited by samplequantity. A typical example is the identification of all possiblemutations, scattered along the length of disease genes. The problemis compounded by the necessity of processing large numbers ofsamples.It has been known for some time that multiple target sequencesin complex (higher animal) genomes can be amplified simulta-neously, i.e., by multiplex PCR. In multiplex PCR, different DNAfragments are co-amplified under identical conditions, in the samereaction. When the aim is simply to amplify many fragmentssimultaneously, it is possible to overcome limiting primer kineticsand fragment competition to design optimal conditions for amultiplex system. However, when other constraints are alsopertinent, the design of a set of conditions that allows multiplexingof a large number of gene fragments is not trivial (1). The firstextensive multiplex reactions of nine fragments for the dystrophingene were described by Chamberlain et al . ( 2) and Beggs et al . ( 3).These are exceptions: most multiplex systems do not involve morethan about five amplicons. The obvious reason for this is that witheach primer set added, the permissive reaction conditions allowingeach fragment to reach its annealing temperature while evadingspurious amplification products become increasingly less flexible.Ultimately, this lack of flexibility is due to the complexity of thegenomic sequence environment which allows ample opportunityfor non-specific priming (1).When primers must be selected according to specific criteria,such as in mutation analysis, special constraints greatly lower theflexibility in experimental design of the multiplex system. A goodexample is denaturing gradient gel electrophoresis (DGGE) inwhich primers must be designed to encompass fragments withoptimal melting behaviour. In such experiments, one of theprimers is usually coupled to a GC-rich ‘clamp’ sequence ( 4). Inan optimal situation, this will generate a two-domain structurewith the GC-clamp as the higher melting domain, a configurationwhich will allow the detection of all possible mutations in thetarget sequence (5). It will often turn out that primers positioned
Development and Validation of a New Adenosine-Independent Index of Stenosis Severity From Coronary Wave–Intensity Analysis (2011)

Intracoronary resistance is naturally constant and minimized during the wave-free period. The instantaneous wave-free ratio calculated over this period produces a drug-free index of stenosis severity comparable to FFR. (Vasodilator Free Measure of Fractional Flow Reserve [ADVISE]; NCT01118481).
Muscle Changes in Venous Insufficiency (1984)

The diagnosis of venous insufficiency and hypertension was established in 53 patients using standard diagnostic methods including ascending and descending venography, venous pressure measurements, and photoplethysmography. Autogenous vein valve transplant, which is gaining acceptance as a treatment for this condition, was employed in this group of patients to relieve venous valvular insufficiency. Biopsy specimens of the gastrocnemius muscle were obtained before surgery in all 53 patients and studied pathologically. Three types of morphologic injury were encountered, suggesting that disuse, denervation, and ischemia may each be partially responsible for damage in skeletal muscle subjected to venous insufficiency and hypertension. Skeletal muscle injury probably explains the preoperative elevations of serum creatine kinase levels in many of our patients and may account for the failure of venous pressures to return to normal levels following surgery.
Paclitaxel, cisplatin, and 5-fluorouracil for patients with advanced or recurrent squamous cell carcinoma of the head and neck (1999)

The dose and schedule for the combination of paclitaxel, 5-FU, and cisplatin as determined in this study are feasible, with encouraging outcomes and activity in patients with recurrent or metastatic SCCHN. The results of this trial warrant larger-scale evaluation to determine the role of this combination in the management of patients with this disease.
Transfection of Folate-Polylysine DNA Complexes: Evidence for Lysosomal Delivery (1995)

We are utilizing the folate receptor for the intracellular delivery of DNA. In this study, a folate-poly-L-lysine (FPLL) conjugate was synthesized and equilibrated with plasmid DNA encoding the firefly luciferase gene. The FPLL-DNA complexes were added to KB cells treated with chloroquine. Luciferase activity of cells incubated with FPLL-DNA was 6-fold higher than of cells exposed to poly-L-lysine (PLL)-DNA. The addition of free folic acid competitively inhibited the enhancement of gene expression. Removal of chloroquine from the media significantly inhibited transfection efficiency of FPLL-DNA complexes. We conclude that FPLL-DNA complexes are delivered into KB cells via folate receptor-mediated endocytosis and likely follow a lysosomal pathway into the cytoplasm.
Antenna Biphenols: Development of Extended Wavelength Chiroptical Reporters (2016)

Molecular hosts capable of chiroptical sensing of complexed guest molecules offer an attractive alternative to conventional methods for the analysis of the absolute configuration and enantiopurity. Sensors based on the Pfeiffer effect rely on complexation-driven asymmetric transformation of the first kind and can produce a chiroptical signal against an otherwise null background. To be most effective, the wavelength of the induced chiroptical sensor readout should be free and clear of interfering signals coming from the sample under investigation. In this study, we report the introduction of stereodynamic zinc complexes of antenna biphenols, a new class of sensors bearing antenna-like appendages that can extend the wavelength of the chiroptical signal while also improving enantioselective guest recognition.
Enzymatic synthesis of milligram quantities of ribozymes in small volumes. (1994)

Milligram quantities of ribozymes (Rzs) can be synthesized in vitro in reaction volumes of 1 mL or less using AmpliScribe T7 RNA polymerase kits to transcribe either linear plasmids or oligodeoxynucleotide templates. Model hammerhead Rzs were synthesized that specifically cleave RNA-encoding chloramphenicol acetyl transferase sequences. Methods are presented for the transcription of Rzs of virtually any length and sequence composition at a fraction of the cost of chemical synthesis.
Quantitative Relationships Between Structure, Aggregation Properties and Antimicrobial Activity of Quaternary Ammonium Bolaamphiphiles (1995)

QSAR analysis employing Kubinyi's bilinear model was applied to examine the relationship between the structure (characterized by the lengths of the terminal hydrocarbon chain, m , and of the hydrocarbon spacer chain, y ), lipophilicity (characterized by the chromatographic parameter R m and aggregation properties expressed through the critical micellar concentration c K ), and antimicrobial activity (characterized by the minimum inhibition concentration, MIC) of quaternary ammonium bolaamphiphiles. The log c K = f ( m ) dependence was found to be linear whereas the log (1/MIC) = f ( m ), log (1/MIC) = f ( y ), log (1/MIC) = f (log c K ) and log (1/MIC) = f ( R m ) dependences were nonlinear. The effect of the hydrophobic terminal chains ( m ) and of the hydrophobic spacer chain ( y ) on the aggregation properties and on the biological activity of the substances was studied.
Colour confocal reflection microscopy using red, green and blue lasers (1992)

SUMMARY To obtain colour reflected confocal images we have incorporated three lasers (HeNe: 633 nm; NdYAG: 532 nm; HeCd: 442 nm) and three photomultiplier detectors into our on‐axis scanning system then adjusted the registration of the simultaneous output signals to produce full‐colour images on a video monitor. Colour confocal images were produced from multi‐stained fixed tissue as well as from natural pigments in fresh plant material. Rayleigh scattering properties of immunogold‐labelled specimens were studied to show how variations in colour response can be utilized to identify subwavelength gold particles. Colour stereo pairs were produced to illustrate the accuracy with which the three‐laser microscope system can record depth information without incurring problems due to chromatic aberration effects.
Impaired Collateral Vessel Development Associated With Reduced Expression of Vascular Endothelial Growth Factor in ApoE −/− Mice (1999)

These findings thus underscore the extent to which hyperlipidemia adversely affects native collateral development but does not preclude augmented collateral vessel growth in response to exogenous cytokines. Moreover, results obtained in the apoE-/- and athymic nude mice imply a critical role for infiltrating T cells as a source of VEGF in neovascularization of ischemic tissues.
Administration of Vaccinia Virus Complement Control Protein Shows Significant Cognitive Improvement in a Mild Injury Model (2005)

Previous studies have shown that traumatic mild brain injury in a rat model is accompanied by breakdown of the blood brain barrier and the accumulation of inflammatory cells. A therapeutic agent, vaccinia virus complement control protein (VCP), inhibits both the classic and the alternative pathways of the complement system and, in so doing, prevents cell death and inflammation. With the use of a rat mild injury model, the effects of VCP on spatial learning and memory were tested. Training in a Morris water maze consisted of a total of 16 trials over a 2-day period before rats were anesthetized and subjected to mild (1.0-1.1 atm) lateral fluid percussion injury (FPI) 3.0 mm lateral to the sagittal suture and 4.5 mm posterior to bregma. Ten microl of VCP (1.7 mg/ml) was injected into the injury site immediately after FPI. Two weeks post-FPI the rats were assessed in the Morris water maze for spatial learning and memory. Neurologic motor function tests were carried out after FPI for 14 consecutive days and again after 28 days. The Morris water maze data show that FPI plus saline-injected rats spent a significantly (P <0.05) larger amount of time in one of the incorrect quadrants than did the FPI plus VCP-injected group. Neurologic evaluations 24 hours postinjury revealed differences in sensorimotor function between groups. The results suggest that in a mild injury model, VCP influences neurologic outcome and offers some enhancement in spatial memory and learning.
Assessment of the Role of GM-CSF in the Cellular Transformation and the Development of Erosive Lesions Around Orthopaedic Implants (1996)

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor with a regulatory effect on the transformation of immature macrophages into multinucleated giant cells (MNGC) that exhibit phenotypic and functional characteristics of osteoclasts (OC). The authors analyzed the bone implant interface membranes harvested from 15 patients with failed total joint replacements for the production and tissue distribution of GM-CSF and interleukin-1 (IL-1). Immunohistology and liquid culture were employed to assess the contribution of these factors in the recruitment of macrophages and the development of bone resorbing MNGC at these sites. This process has been implicated in osteoclastic bone resorption, bone, and bone marrow necrosis adjacent to orthopaedic implants. Histologic assessment of the interface indicated the presence of granuloma and a variable number of MNGC in 11 cases. Four cases showed sites of intramembranous formation of osteoid and mineralized bone that was accompanied by normal bone marrow in two cases. Granulocyte-macrophage colony stimulating factor was expressed by a distinct subset of phagocytic macrophages in the lining layer on the implant side. interleukin-1-positive cells outnumbered those stained for GM-CSF. Stimulation of cultured cells with prosthetic metal particulate material showed marked similarity in the expression of these cytokines to cultures treated with lipopolysaccharide (LPS) or phytohemagglutinin (PHA). The induction of GM-CSF production in the lining layer where small MNGC develop indicates that these cells differentiate locally following the phagocytosis of particulate wear debris. In conclusion, GM-CSF promotes the proliferation and early stages of fusion and development of MNGC responsible for osteolysis at these sites. These results also highlight the capacity of the interface to display both osteogenic and inflammatory characteristics. Collectively, the findings suggest that the local bone marrow could participate in the development of the interface as a source of myeloid cells in addition to the capacity of marrow stroma to generate various osteogenic cells essential for the ingrowth of bone into prosthetic implants.
Acute pancreatitis: a literature review. (2009)

Acute pancreatitis (AP) is an inflammatory disease characterized by steady, acute abdominal pain of varying severity, often radiating from the epigastrium to the back. Its presentation ranges from a self-limiting mild disorder to a more severe and fulminant disease. Severe acute pancreatitis accounts for 30% of all deaths related to pancreatitis. The incidence of AP is increasing progressively with a corresponding increase in the incidence of its risk factors. Alcohol abuse and gallstone migration are the established risk factors for development of AP. In recent years, genetic factors and obesity have also been identified as risk factors responsible for the development of AP. The pathophysiology of AP involves acute inflammation of the acinar cells. Excessive acinar cell injury leads to a condition called systemic inflammatory response syndrome (SIRS). Protracted SIRS is responsible for most of the life-threatening complications associated with AP. Most common AP-related complications include pulmonary, renal, cardiovascular, and central nervous system dysfunction. Thus prompt and accurate diagnosis of AP is of paramount importance. The medical management of AP includes controlling pain, providing adequate nutritional support, and monitoring complications. Endoscopic retrograde cholangiopancreatography and surgery have also shown to reduce the mortality and morbidity associated with AP. Drugs such as resveratrol and rosiglitazone are being investigated as potential candidates for the treatment of AP.
Alkylierende Polymere: freigesetzte Carbenium-Ionen als vielseitige reaktive Intermediate in der Polymer-unterstützten Synthese in Lösung (2001)

Als festphasengebundene Diazoalkan-Analoga für die milde und saubere Veresterung von Carbonsäuren [Gl. (1)] sowie von komplexen Gemischen konnten die hier vorgestellten alkylierenden Polymere verwendet werden. Sie wurden als Polymer-unterstützte 3-Alkyl-1-aryltriazene hergestellt und setzen bei saurer Aktivierung Carbenium-Ionen frei.
Intragenic recombination and a chimeric outer membrane protein in the relapsing fever agent Borrelia hermsii (1993)

The spirochete Borrelia hermsii, a relapsing fever agent, evades the host's immune response through multiphasic antigenic variation. Antigen switching results from sequential expression of genes for serotype-specific outer membrane proteins known as variable major proteins (Vmp's); of the 25 serotypes that have been identified for the HS1 strain, serotypes 7 and 21 have been studied in greatest detail. In the present study, an atypical variant was predominant in the relapse from a serotype 21 infection in mice; relapse cells were bound by monoclonal antibodies specific for Vmp21 as well as antibodies specific for Vmp7. In Western blots (immunoblots), the variant had a single Vmp that was reactive with monoclonal antibodies representing both serotypes. The gene encoding this Vmp, vmp7/21, was cloned and characterized by restriction mapping and sequence analysis to determine the likely recombination event. Whereas the 5' end of vmp7/21 was identical to that of vmp21, its 3' end and flanking sequences were identical to the 3' end of vmp7. Unlike other vmp genes examined thus far, the vmp7/21 gene existed only in an expressed form; a silent, storage form of the gene was not detected. We conclude that the vmp7/21 gene was created by an intragenic recombination between the formerly expressed vmp21 gene and a silent vmp7 gene. This finding suggests that the lack of cross-reactivity between variants, which is usually observed, results from immunoselection against variants possessing chimeric Vmp's rather than from a switching mechanism that excludes partial gene replacements.
Multicyclic Study on the Simultaneous Carbonation and Sulfation of High-Reactivity CaO (2004)

Micron-sized CaO, obtained by calcination of mesoporous CaCO3, attained 36 wt % CO2 sorption capacity after 100 cycles of carbonation and calcination reactions at 700 °C. The extent of simultaneous carbonation (XCO2) and sulfation (XSO2) of CaO at 700 °C was obtained under simulated flue gas conditions (10% CO2, 3000 ppm of SO2, 4% O2 in N2). CaO reacts with SO2 to form thermally stable CaSO4, which leads to a reduction in the CO2 capture capacity of CaO. Whereas XSO2 increases monotonically with the residence time, XCO2 goes through a maximum and eventually drops as a result of direct sulfation of CaCO3. The maximum value attained by XCO2 was 50% in 10 min in the first cycle. The highest XCO2/XSO2 ratio of 5 is attained at a residence time of 5 min. XSO2 is higher under simultaneous carbonation and sulfation conditions compared to sulfation of CaO or direct sulfation of CaCO3.
Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors. (1987)

We isolated overlapping cDNA clones corresponding to the major MET protooncogene transcript. The cDNA nucleotide sequence contained an open reading frame of 1408 amino acids with features characteristic of the tyrosine kinase family of growth factor receptors. These features include a putative 24-amino acid signal peptide and a candidate, hybrophobic, membrane-spanning segment of 23 amino acids, which defines an extracellular domain of 926 amino acids that could serve as a ligand-binding domain. A putative intracellular domain 435 amino acids long shows high homology with the SRC family of tyrosine kinases and within the kinase domain is most homologous with the human insulin receptor (44%) and v-abl (41%). Despite these similarities, however, we found no apparent sequence homology to other growth factor receptors in the putative ligand-binding domain. We conclude from these results that the MET protooncogene is a cell-surface receptor for an as-yet-unknown ligand.
Alcohol acetyltransferases and the significance of ester synthesis in yeast (2000)

This paper reviews our current knowledge of yeast alcohol acyltransferases. Much of this information has been gathered over the past 10 years through the application of powerful yeast molecular biology techniques. Evidence from gene disruption and expression analysis of members of the alcohol acyltransferase (ATF) gene family indicates that different ester synthases are involved in the synthesis of esters during alcoholic fermentation. The natural physiological rationale behind these enzyme activities remains unclear. However, it is believed that these enzymes may be involved in very different functions, including cellular fatty acid homeostasis and detoxification mechanisms. Insights into the regulation of yeast ester synthesis by oxygen and unsaturated fatty acids have contributed to our understanding of the general mechanisms of gene regulation. In particular, control mechanisms that underpin the oxygen-mediated regulation of ATF1 gene transcription appear to be closely linked to those involved in the regulation of fatty acid metabolism. Data pertaining to the regulation of ATF1 gene transcription have been integrated into a working model for future research.
Cutting Edge: Down-Regulation of MICA on Human Tumors by Proteolytic Shedding (2002)

The immunoreceptor NKG2D stimulates tumor immunity through activation of CD8 T cells and NK cells. Its ligand MICA has been shown to be broadly expressed on human tumors of epithelial origin. MICA expression correlates with an enrichment of Vdelta1 T cells in tumor tissue. We report that human tumor cells spontaneously release a soluble form of MICA encompassing the three extracellular domains, which is present at high levels in sera of patients with gastrointestinal malignancies, but not in healthy donors. Release of MICA from tumor cells is blocked by inhibition of metalloproteinases, concomitantly causing accumulation of MICA on the cell surface. Shedding of MICA by tumor cells may modulate NKG2D-mediated tumor immune surveillance. In addition, determination of soluble MICA levels may be implemented as an immunological diagnostic marker in patients with epithelial malignancies.
Managing retinal vein occlusion (2012)

#### Summary points

Retinal vein occlusion—obstruction of the retinal venous system by thrombus formation, external compression, or disease of the vein wall1—is the second most common retinal vascular disease after diabetic retinopathy.2 Pooled data from population studies in the United States, Europe, Asia, and Australia suggest that about 16 million adults are affected by this condition.3 Not all cases need treatment. In the past, the visual prognosis for most patients was poor because treatment comprised lowering the pressure in the eye, if raised, and laser treatment to try to control associated complications. However, two new treatments have recently been licensed in the US and the European Union, one of which has been approved by the National Institute for Health and Clinical Excellence (NICE) for use in England and Wales. Consequently, the outlook for patients with retinal vein occlusion is likely to improve. We review the diagnosis and management of retinal vein occlusion and examine the evidence for the effectiveness of the newly licensed drugs.

#### Sources and selection criteria

We searched PubMed for articles on retinal vein occlusion that had been published in 2010 and 2011 and looked for published evidence that had been presented in major ophthalmology meetings up to 1 October 2011, focusing mainly on well designed randomised …