gebhart/patrepeval huggingface dataset:
Mucoid conversion of Pseudomonas aeruginos by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung (1999)

The leading cause of mortality in patients with cystic fibrosis (CF) is respiratoy failure due in large part to chronic lung infection with Pseudomonas aeruginosa strains that undergo mucoid conversion, display a biofilm mode of growth in vivo and resist the infiltration of polymorphonuclear leukocytes (PMNs), which release free oxygen radicals such as H2O2. The mucoid phenotype among the strains infecting CF patients indicates overproduction of a linear polysaccharide called alginate. To mimic the inflammatory environment of the CF lung, P. aeruginosa PAO1, a typical non-mucoid strain, was grown in a biofilm. This was treated with low levels of H2O2, as if released by the PMNs, and the formation of mucoid variants was observed. These mucoid variants had mutations in mucA, which encodes an anti-σ factor; this leads to the deregulation of an alternative σ factor (σ22, AlgT or AlgU) required for expression of the alginate biosynthetic operon. All of the mucoid variants tested showed the same mutation, the mucA22 allele, a common allele seen in CF isolates. The mucoid mucA22 variants, when compared to the smooth parent strain PA01, produced 2--6-fold higher levels of alginate|ii) exhibited no detectable differences in growth rate|iii) showed an unaltered LPS profile|iv) were ~72% reduced in the amount of inducible-β-lactamase and (v) secreted little no LasA protease and only showed 44% elastase activity. A characteristic ~54 kDa protein associated with alginate overproducing strains was identified as AlgE (Alg76) by N-terminal sequence analysis. Thus, the common phenotype of the mucoid variants, which included a genetically engineered mucA22 mutant, suggested that the only mutation incurred as a result of H2O2 treatment was in mucA. When a P. aeruginosa biofilm was repeatedly expose to activated PMNs in vitro, mucoid variants were also observed, mimicking in vivo observations. Thus, PMNs and their oxygen by-products may cause P. aeruginosa to undergo the typical adaptation to the intractable mu- coid form in the CF lung. These findings indicate that gene activation in bacteria by toxic oxygen radicals, similar to that found in plants and mammalian cells, may serve as a defence mechanism for the bacteria. This suggests that mucoid conversion is a response to oxygen radical exposure and that this response is mechanism of defence by the bacteria. This is the first report to show that PMNs and their oxygen radicals can cause this phenotypic and genotypic change which is so typical of the intractable form of P. aeruginosa in the CF lung. These findings may provide a basis for the development of anti-oxidant and anti-inflammatory therapy for the early stages of infection in CF patients
LightCycler technology for the quantitation of bcr/abl fusion transcripts. (1999)

Quantifying bcr/abl fusion transcripts in chronic myelogenous leukemia is thought to serve as a powerful parameter for monitoring the kinetic nature of this clonal disease in vivo and in vitro. Recently, we demonstrated the technical advantages as well as the clinical relevance of quantitating bcr/abl fusion mRNA using the 5-nuclease assay and a real-time fluorescence reverse transcriptase-PCR (RT-PCR) detection system (ABI PRISM 7700 SDS). Meanwhile, another technique was introduced (LightCycler technology) that may be used for the same purpose. To investigate whether this method may be an appropriate alternative to the described procedure, we have established bcr/abl LightCycler RT-PCR for major and minor bcr/abl fusion transcripts. We found that, with only minor modifications, TaqMan RT-PCR and fluorescent probe design can be used to obtain comparable results in the LightCycler system. The developed method could quantitate as little as 10 bcr/abl copies per 100 ng cDNA and was as safe and reproducible as the previously described technique. Because reaction efficiency was identical within different bcr/abl major fusions, one single RT-PCR could be established that simultaneously detects b2a3, b2a2, b3a2, and b3a3 fusion RNA with equal specificity and sensitivity. Compared to results generated by the ABI PRISM 7700 SDS, absolute amounts of bcr/abl did not differ significantly, and there was a linear correlation between the respective values. We conclude that TaqMan chemistry can be used in the LightCycler and that both real-time fluorescence PCR detection systems equally fulfill the criteria for the safe and reliable quantitation of bcr/abl fusion RNA in clinical samples. This may be of help for further standardization of quantitative bcr/abl RT-PCR, which, again, is necessary for the comparison of results generated by different investigators.
Use of combinatorial peptide libraries to construct functional mimics of tumor epitopes recognized by MHC class I-restricted cytolytic T lymphocytes. (1996)

Identification of cytolytic T lymphocyte (CTL) epitopes presented by major histocompatibility complex (MHC) class I molecules on tumor cells is critical for the design of active immunotherapy. We describe the use of combinatorial peptide libraries with defined amino acids in two MHC anchor positions to search for epitopes that are recognized by H-2Db- and Kb-restricted CTL specific for the mouse lymphoma EL4. An iterative strategy was used for screening libraries in which 16 amino acids were divided into 3 groups and 3 subgroups: alpha (AL, VT, FY); beta (GS, P, DE); gamma (KR, H, NQ). The proportions of each group and subgroup at individual peptide positions were changed in the library synthesis, and the effect of these changes on CTL activity was measured in a sensitive RMA-S cell assay. A single H-2Db epitope mimic was deduced from the original library that contained > 2 x 10(8) potential peptides and was at least 9 logs more potent than the original library. Immunization of syngeneic mice with this peptide elicited CTL that lysed EL4 cells as well as RMA-S cells pulsed with peptides isolated from Db molecules of EL4 cells, indicating functional similarity between the mimicking peptide and the naturally processed CTL epitope. Furthermore, adoptive transfer of such a CTL line had a therapeutic effect in mice with EL4 established as an ascites tumor. Two H-2Kb-restricted epitope mimics of the same tumor were also identified. Our method represents a novel approach for the construction of MHC class I-restricted targets that can serve as immunogens for active immunotherapy of cancer.
Alkaline phosphatase staining of pig and sheep epiblast cells in culture (1993)

To define better the characteristics of pig and sheep epiblast cells in culture, the cells were tested for the presence of alkaline phosphatase (AP), a biochemical marker characteristic of mouse embryonic stem cells. Pig and sheep epiblast cells were positive for AP staining both at isolation from the blastocyst and after primary in vitro culture. The innermost portion of the attendant endoderm surrounding the epiblast was also positive for AP staining during primary culture. AP staining was lost upon differentiation or senescence of the epiblast cells. Also, all differentiated epiblast-derived cell cultures were negative for AP staining, with the exception of neuron-like cultures. Epiblast-like cells were cultured from day 10 (pig) and day 13 (sheep) embryonic discs, and these cells were also AP positive until they differentiated. Trophectoderm-endoderm-like cells from embryonic discs were AP negative or weakly positive. AP is a convenient marker for undifferentiated pig and sheep epiblast cells in culture when used in conjunction with cell morphology analysis.
Folding at the rhythm of the rare codon beat (2008)

The persistent difficulties in the production of protein at high levels in heterologous systems, as well as the inability to understand pathologies associated with protein aggregation, highlight our limited knowledge on the mechanisms of protein folding in vivo. Attempts to improve yield and quality of recombinant proteins are diverse, frequently involving optimization of the cell growth temperature, the use of synonymous codons and/or the co-expression of tRNAs, chaperones and folding catalysts among others. Although protein secondary structure can be determined largely by the amino acid sequence, protein folding within the cell is affected by a range of factors beyond amino acid sequence. The folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins and ligands, the ribosome, translocation through a pore membrane, redox conditions, among others. The translation rate as well as the translation machinery itself can dramatically affect protein folding, and thus the structure and function of the protein product. This review addresses current efforts to better understand how the use of synonymous codons in the mRNA and the availability of tRNAs can modulate translation kinetics, affecting the folding, the structure and the biological activity of proteins.
The Functions and Inhibition of the Membrane Glycoproteins of Paramyxoviruses and Myxoviruses and the Role of the Measles Virus M Protein in Subacute Sclerosing Panencephalitis (1981)

The F glycoprotein of paramyxoviruses is responsible for cell fusion and hemolysis and for virus penetration via fusion of viral and cell membranes. These functions are activated by specific proteolytic cleavage of an inactive precursor (F0) into two disulfide-linked polypeptides (F1 and F2). The susceptibility of the F0 protein to cleavage by a host protease is a major determinant of virus host range and virulence. Synthetic oligopeptides that mimic the N-terminal region of the F1 polypeptide are specific inhibitors of paramyxoviruses, and oligopeptides that mimic the N-terminus of the HA2 polypeptide of influenza virus, also generated by cleavage, specifically inhibit that virus. Antibodies to F protein prevent the spread of paramyxovirus infection via membrane fusion, but antibodies to HN protein do not, although they neutralize released virus. These results and previous findings that formalin-treated virus does not induce antibodies to F protein provide an explanation for atypical measles. The HN protein has both receptor-binding and neuraminidase activities, and Cl- inhibition of neuraminidase may modulate these antagonistic activities. Studies in patients with subacute sclerosing panencephalitis (SSPE) suggest that there is a host restriction of synthesis of the M protein of measles virus in brain cells which is involved in the abortive, persistent infection that causes SSPE.
Familial colorectal cancer (2015)

Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up.
Implanted amniotic membrane as an autograft and as an allograft. (1975)

Detailed studies on autograft and allograft amniotic membranes implanted in the subcutaneous tissues to form tunnels are described. Autograft amniotic membranes appear to become permanent structures whereas allografts of this material, though accepted by the host for a longer time than most allografts, were eventually rejected. Serial histological studies were performed.
SiN Capacitors and ESD (2006)

We present Human Body Model (HBM) electrostatic discharge (ESD) test results for the three types of capacitors used in the TriQuint Texas high density interconnect process. We show a linear dependence of ESD failure voltage with respect to capacitor area (capacitance). We also show doubling of the HBM failure voltage when using two capacitors in series compared to a single capacitor of the same type with the same total capacitance. Surprisingly high HBM failure voltages were observed for large 500 A SiN capacitors. Transient simulations were performed to relate the observed HBM failure voltages to the intrinsic dielectric breakdown voltages of the three types of capacitors. By incorporating a dielectric current leakage due to Frenkel-Poole emission from traps into the simulations, we were able to obtain an excellent agreement with the HBM test results.
Structure/Properties Relationship for Bis(phenoxyamine)Zr(IV)-Based Olefin Polymerization Catalysts: A Simple DFT Model To Predict Catalytic Activity (2012)

The productivity of a number of bis(phenoxyamine)Zr(IV)-based catalysts (bis(phenoxyamine) = N,N′-bis(3-R1-5-R2-2-O-C6H2CH2)-N,N′-(R3)2-(NCH2CH2N)) in ethene and propene polymerization was evaluated for different R1/R2/R3 combinations. In previous studies on this class we demonstrated that the cations that form upon precatalyst activation (e.g., by methylalumoxane) adopt a “dormant” mer-mer geometry, and an endothermic isomerization to the active fac-fac geometry is the necessary first step of the catalytic cycle. Herewith we report a clear correlation between catalyst activity and the DFT-calculated energy difference ΔEi between the active and dormant state. The correlation only holds when the calculations are run on ion pairs, which is less obvious than it may appear because the anion in these systems is not at the catalyst front. This finding provides a comparatively simple and fast method to predict the activity of new catalysts of the same class.
Metabolic engineering and flux analysis of Escherichia coli (2009)

The advances in molecular biology, genome sequencing and mathematical tools have led to growing interest in metabolic engineering, the goal of which is to redirect metabolic fluxes for industrial and medical purposes. Escherichia coli was chosen as the model system for several reasons: the ease of genetic manipulation, the wealth of genetic information, its capacity for rapid growth, and the availability of inexpensive and standardized cultivation protocols. The effects of precise perturbation in the central metabolic pathway of E. coli with an emphasis on the competition at the pyruvate node was investigated using recombinant DNA technology to create the changes and metabolic flux analysis to quantify the results.\nFirst, the effects of competition at the pyruvate node was studied by two modifications of central metabolism, the heterologous expression of the Bacillus subtilis acetolactate synthase (ALS) and the removal of the major acetate production pathway. This study was primarily a continuation of the application of metabolic engineering strategies to increase recombinant protein production through acetate reduction. The next study involved the effect of an additional mutation at the nuo gene encoding an NADH dehydrogenase recently mapped near the genes (ack4-pta ) controlling the acetate production pathway. In the earlier studies involving strains deficient in ackA-pta gene, lactate instead of acetate or ethanol was the major fermentation product. A natural extension of this project was to examine the effects of deficiency and overexpression of the lactate dehydrogenase (LDH) enzyme responsible for lactate production pathway. Next, the role of intermediate pool levels, specifically pyruvate, on redistribution of carbon flux and partitioning at the pyruvate node was examined. Sensitivity or flux control coefficients were calculated to gain further insight into dynamics of the overall reaction network. Finally, the effects of different enzyme properties on metabolic patterns were explored through the integration and expression of ALS from Klebsiella pneumoniae and a comparison with the B. subtilis ALS.
δ Opioid Affinity and Selectivity of 4-Hydroxy-3-methoxyindolomorphinan Analogues Related to Naltrindole (1999)

To investigate the effect of the introduction of a 4-phenolic substituent on the delta opioid affinity and selectivity of the indolomorphinans, a range of 4-phenolic analogues of naltrindole were prepared and evaluated in in vitro assays. Although the majority of the ligands displayed poor affinity for all three opioid receptors (mu, kappa, delta), 17-cyclopropylmethyl-6, 7-didehydro-4-hydroxy-3-methoxy-6,7:2',3'-indolomorphinan (13) was an exception, displaying excellent delta binding selectivity (delta Ki = 7 nM, mu/delta = 1900, mu/kappa = 1130). GTP-gamma-S functional assays showed 13 to be a selective delta antagonist, albeit with lower potency than naltrindole. Although the reason for the unique profile of 13 could not be determined, these results validate our approach of introducing groups into the indolomorphinans that are known to reduce mu activity, to obtain increased delta selectivity.
Ultralow-Voltage Spin-Transfer Switching in Perpendicularly Magnetized Magnetic Tunnel Junctions with Synthetic Antiferromagnetic Reference Layer (2013)

We developed top-free-type perpendicularly magnetized magnetic tunnel junctions (p-MTJs) with a synthetic antiferromagnetic (SAF) bottom reference layer consisting of [Co/Pt] superlattice and Ru spacer layers. We successfully demonstrated practical properties such as a low resistance–area (RA) product (<3 Ω µm2), ultralow writing voltage (<200 mV) for spin-transfer-torque (STT) switching, and high annealing stability (up to 350 °C) in the same p-MTJ cells. Moreover, the p-MTJs showed clear bi-stable states even at zero external magnetic fields, thanks to the low stray field from the SAF structure. The results are promising for both high integration and ultralow-voltage operation of STT magnetoresistive random access memory (MRAM).
Reliability of the peptide nucleic acid‐locked nucleic acid polymerase chain reaction clamp‐based test for epidermal growth factor receptor mutations integrated into the clinical practice for non‐small cell lung cancers (2006)

Gefitinib is an inhibitor of the tyrosine kinase activity of epidermal growth factor receptor (EGFR). Accumulating evidence suggests that gefitinib may provide a survival benefit to EGFR mutation-positive non-small lung cancer patients. We have established a clinical test that can detect EGFR mutations from cytological specimens or paraffin-embedded tissue specimens that are contaminated by normal cells. This test is based on the peptide nucleic acid, locked nucleic acid polymerase chain reaction clamp method that can detect G719S, G719C, L858R, L861Q and seven different exon 19 deletions in the presence of 100-1000-fold wild-type alleles. Consequently, using a small aliquot of samples isolated to establish a cancer diagnosis, the EGFR mutation status is determined soon after the diagnosis of cancer is made. We investigated the EGFR mutation status in 86 patients using a variety of cytological specimens (59 bronchoscopy specimens, 16 pleural effusion, 9 sputum, and 2 pericardial effusion) and in 46 patients who had a disease relapse and paraffin-embedded tissues were available. Forty-five patients (34%) were positive for mutation (29 exon 19 deletions, 16 L858R and 1 L861Q). The sensitivity and the specificity of this test was 97% and 100%, respectively. EGFR mutation status thereby obtained was used to determine each patient's therapeutic regimen. This test is easily integrated into the normal clinical practice for lung cancer, while allowing the medical staff to select therapeutic regimen depending on the EGFR mutation status.
Opto-Current-Clamp Actuation of Cortical Neurons Using a Strategically Designed Channelrhodopsin (2010)

The opto-current-clamp study suggests that the depolarization of a small number of neurons wakes up the motor cortical network over some critical point to the activated state.
MPIIGaze: Real-World Dataset and Deep Appearance-Based Gaze Estimation (2017)

Learning-based methods are believed to work well for unconstrained gaze estimation, i.e. gaze estimation from a monocular RGB camera without assumptions regarding user, environment, or camera. However, current gaze datasets were collected under laboratory conditions and methods were not evaluated across multiple datasets. Our work makes three contributions towards addressing these limitations. First, we present the MPIIGaze that contains 213,659 full face images and corresponding ground-truth gaze positions collected from 15 users during everyday laptop use over several months. An experience sampling approach ensured continuous gaze and head poses and realistic variation in eye appearance and illumination. To facilitate cross-dataset evaluations, 37,667 images were manually annotated with eye corners, mouth corners, and pupil centres. Second, we present an extensive evaluation of state-of-the-art gaze estimation methods on three current datasets, including MPIIGaze. We study key challenges including target gaze range, illumination conditions, and facial appearance variation. We show that image resolution and the use of both eyes affect gaze estimation performance while head pose and pupil centre information are less informative. Finally, we propose GazeNet, the first deep appearance-based gaze estimation method. GazeNet improves the state of the art by 22% percent (from a mean error of 13.9 degrees to 10.8 degrees) for the most challenging cross-dataset evaluation.
Specific identification of fibrin polymers, fibrinogen degradation products, and crosslinked fibrin degradation products in plasma and serum with a new sensitive technique (1985)

A new method is described for identifying low concentrations of circulating derivatives of fibrinogen and fibrin, even when present in heterogeneous mixtures. This technique is applicable to plasma and serum and uses electrophoresis in 2% agarose in the presence of sodium dodecyl sulfate (SDS) followed by immunological identification of separated derivatives, using radiolabeled antifibrinogen antiserum and autoradiography. Unique electrophoretic patterns distinguish plasmic derivatives of crosslinked fibrin from those of fibrinogen and also identify crosslinked fibrin polymers produced by the combined action of thrombin and factor XIII on fibrinogen. The assay is sensitive to a concentration of 0.1 micrograms/mL of fibrinogen in serum or plasma. Fibrin polymers, plasmic degradation products of fibrinogen, and plasmic degradation products of crosslinked fibrin were detected in the plasma or serum of a patient with disseminated intravascular coagulation. Plasmic derivatives of both fibrinogen and crosslinked fibrin appeared in serum in the course of fibrinolytic therapy for pulmonary embolism, whereas during acute myocardial infarction a marked increase in the proportion of fibrin polymers in plasma was found in comparison with normal controls. Thus, the procedure can distinguish between the simultaneous processes of fibrin polymer formation, fibrinogenolysis, and fibrinolysis, and is sufficiently sensitive to detect relevant quantities of derivatives in pathologic conditions.