gebhart/patrepeval huggingface dataset:
A comparison of the effects of single-base and triple-base changes in the integrase arm-type binding sites on the site-specific recombination of bacteriophage lambda (1990)

Triple-base changes were made in each of the five Integrase (Int) arm-type binding sites of bacteriophage lambda. These triple changes, called ten mutants, were compared with single-base changes (hen mutants) for their effects on integrative and excisive recombination. The presence of ten or hen mutations in the P1, P'2, or P'3 sites inhibited integration, but the ten P'3 mutant was 10-fold more defective than the analogous hen mutant. The results with these mutants suggest that the P1, P'2, P'3, and possibly the P'1 sites are required for integration. In wild-type E. coli, the ten P'1 mutant reduced the frequency of excision 5-fold, whereas the hen P'1 mutant had no effect. The presence of ten mutations in the P2, P'1, or P'2 sites inhibited lambda excision in an E. coli strain deficient in the production of FIS, while hen mutations in the P2 and P'2 sites had little or no effect. The results with the ten mutants suggest that the P2, P'1, and P'2 sites are required for excision. The differences in the severity of the effects between the ten and hen mutations may be due to the inability of cooperative interactions among Int, IHF, Xis, and FIS to overcome the disruption of Int binding to sites with triple-base changes compared to sites with single-base changes.
Complement levels in normal and inflamed aqueous humor. (1983)

C2, C6, and C7 were measured by hemolytic assay and Factor B and IgG were measured by radial immunodiffusion in samples of normal and inflamed aqueous humor. Normal aqueous humor was found to contain functional C2, C6, and C7, but the small ratios of aqueous humor to serum measurements suggested that there was relatively little of these complement components in normal aqueous humor when compared to serum. The mean values of C2, C6, C7, and Factor B in aqueous humor and the median ratios of aqueous humor to serum measurements for each complement component were higher in patients with inflamed aqueous humor than in patients with normal aqueous humor. A comparison of the ratios of IgG to each complement component in normal and inflamed aqueous humor suggested that levels of IgG and complement increased proportionately in inflamed aqueous humor. Factor B, a component of the alternative pathway, was not detected in normal aqueous humor but measured in five of six samples of aqueous humor from eyes with anterior chamber inflammation.
Analysis of protein-protein interaction surfaces using a combination of efficient lysine acetylation and nanoLC-MALDI-MS/MS applied to the E9:Im9 bacteriotoxin—immunity protein complex (2006)

To understand how proteins perform their function, knowledge about their structure and dynamics is essential. Here we use a combination of an efficient chemical lysine acetylation reaction and nanoLC-MALDI tandem mass spectrometry to probe the accessibility of every lysine residue in a protein complex. To demonstrate the applicability of this approach, we studied the interaction between the DNase domain of Colicin E9 (E9) and its immunity protein Im9. Free E9 and E9 in complex with Im9 were rapidly acetylated, followed by proteolytic digestion and analysis by LC-MALDI-TOF/TOF MS/MS. Acetylated peptides could be filtered out of the complex peptide mixtures using selective ion chromatograms of the specific immonium marker ions. Additionally, isobaric acetylated peptides, acetylated at different sites, could be separated by their LC retention times. The combination of LC and MALDI-TOF/TOF MS/MS provided information about the amount of acetylation on each individual lysine even for peptides containing several lysine residues. In general, our data agree well with those derived from the crystal structure of E9 and the E9:Im9 complex. Interestingly, next to in the binding interface expected lysines, K89 and K97, two from the crystal structure data unexpected lysines, K81 and K76, were observed to become less exposed upon Im9 binding. Moreover, K55 and K63, positioned in the predicted DNA binding region, were also found to be less accessible upon Im9 binding. These findings may illustrate some of the described differences in the solution-phase structure of the E9:Im9 complex compared with the crystal structure.
Ultrastructural findings in horses with chronic obstructive pulmonary disease (COPD) II: pathomorphological changes of the terminal airways and the alveolar region (1990)

Extensive light and electron microscope studies (transmission and scanning electron microscopy) of the bronchioles and alveolar region, in 28 horses suffering chronic obstructive pulmonary disease (COPD) and eight control horses, revealed good correlation between clinical severity and morphological changes. In the bronchiolar epithelium the non-ciliated bronchiolar epithelial (Clara) cells, in particular, showed ultrastructural alterations and, even in the mild stages of disease, these presented degenerative changes and lack of differentiation. Together with loss of granulation in the Clara cells and metaplasia of the goblet cells, cells were seen with unusual intracytoplasmic lamellar inclusion, the number of which increased sharply with clinical severity. The focal changes in the alveolar region were necrosis of type I epithelial cells, alveolar fibrosis of varying degrees with type II epithelial transformation and emphysema or hyperinflation, with an increase in Kohn's pores. Some horse also showed morphological signs of interference with the surfactant system, in the form of marked cysts with lamellar structure. The alveolar changes were mostly in the peribronchiolar region and were, therefore, interpreted as reactive processes. No conclusions as to the aetiology of equine COPD can be derived from these morphological investigations.
The Streptomycin-Sulfadiazine-Tetracycline Antimicrobial Resistance Element of Calf-Adapted Escherichia coli Is Widely Distributed among Isolates from Washington State Cattle (2007)

ABSTRACT Association of specific antimicrobial resistance patterns with unrelated selective traits has long been implicated in the maintenance of antimicrobial resistance in a population. Previously we demonstrated that Escherichia coli strains with a specific resistance pattern (resistant to s treptomycin, su lfadiazine, and t etracycline [SSuT]) have a selective advantage in dairy calf intestinal environments and in the presence of a milk supplement commonly fed to the calves. In the present study we identified the sequence of the genetic element that confers the SSuT phenotype and show that this element is present in a genetically diverse group of E. coli isolates, as assessed by macrorestriction digestion and pulsed-field gel electrophoresis. This element was also found in E. coli isolates from 18 different cattle farms in Washington State. Using in vitro competition experiments we further demonstrated that SSuT strains from 17 of 18 farms were able to outcompete pansusceptible strains. In a separate set of experiments, we were able to transfer the antimicrobial resistance phenotype by electroporation to a laboratory strain of E. coli (DH10B), making that new strain more competitive during in vitro competition with the parental DH10B strain. These data indicate that a relatively large genetic element conferring the SSuT phenotype is widely distributed in E. coli from cattle in Washington State. Furthermore, our results indicate that this element is responsible for maintenance of these traits owing to linkage to genetic traits that confer a selective advantage in the intestinal lumens of dairy calves.
[Channelopathy of voltage-gated sodium channel]. (1999)

This review will give a brief introduction on "Channelopathy" of voltage-gated sodium channel involved with inherited diseases including skeletal muscle diseases (such as HyperPP and PC) and cardiac diseases (such as LQT3 and IVF), voltage-gated sodium channel mutations and the electrophysiological characteristics of the sodium channel mutations.
Intracerebroventricular cholinergic drug administration in Alzheimer's disease: preliminary results of a double-blind study. (1987)

In June 1983, we began evaluating intracerebroventricular (ICV) cholinergic drug infusion in patients with biopsy-documented Alzheimer's disease (AD). An initial trial in four patients showed this treatment approach to be feasible, but objective improvement in cognitive or social function was not documented (Harbaugh et al., 1984; Harbaugh, 1986). A double-blind, placebo-controlled crossover study involving a larger number of patients has since been done. The results of this study, presented here, document a statistically significant improvement in some cognitive test results during periods of drug infusion. However, the clinical applicability of this treatment approach is still questionable. A collaborative, double-blind study evaluating activities of daily living and cognitive test results during drug and placebo infusion is presently underway and should better define the safety and efficacy of this treatment approach for patients with AD.
Structure-activity relationships for substituted 9-oxo-9,10-dihydroacridine-4-acetic acids: analogues of the colon tumour active agent xanthenone-4-acetic acid. (1992)

A series of 9-oxo-9,10-dihydroacridine-4-acetic acids (acridone-4-acetic acids) were prepared by Jourdan-Ullmann condensation of 2-halobenzoic acids with 2-aminophenylacetic acids, followed by H2SO4-induced cyclodehydration of the resulting 2-[2-(carboxymethyl)phenylamino]benzoic acids. These were evaluated for their ability to induce haemorrhagic necrosis in transplanted colon 38 tumours in mice, using a short-term histology assay. The results broadly paralleled those seen previously for xanthenone-4-acetic acids, with 1-, 2- and 7-substitution being dystherapeutic, and substitution at the 5- and 6-positions by lipophilic groups increasing activity. While some analogues were as active as xanthenone-4-acetic acids in the histology assay and gave significant growth delays against colon 38 tumours in vivo, as a class the 9-oxo-9,10-dihydroacridine-4-acetic acids were generally less potent than the xanthenone-4-acetic acids.
[Comparison of reactive oxygen species production in neat semen and washed spermatozoa]. (2009)

Measurement of ROS in neat semen is simpler, faster and better reflecting the actual level of oxidative stress than the same measurement in spermatozoa suspension. The implementation of this method can complement the algorithm of diagnostics and treatment of male infertility and be helpful in selection of patients for antioxidant or antibiotic treatment.
Substrate Recognition of Collagen-specific Molecular Chaperone HSP47 (1999)

Prior to secretion, procollagen molecules are correctly folded to triple helices in the endoplasmic reticulum (ER). HSP47 specifically associates with procollagen in the ER during its folding and/or modification processes and is thought to function as a collagen-specific molecular chaperone (Nagata, K. (1996) Trends Biochem. Sci. 21, 23-26). However, structural requirements for substrate recognition and regulation of the binding have not yet been elucidated. Here, we show that a typical collagen model sequence, (Pro-Pro-Gly)(n), possesses sufficient structural information required for recognition by HSP47. A structure-activity relationship study using synthetic analogs of (Pro-Pro-Gly)(n) has revealed the requirements in both chain length and primary structure for the interaction. The substrate recognition of HSP47 has also been shown to be similar but distinct from that of prolyl 4-hydroxylase, an ER resident enzyme. Further, it has shown that the interaction of HSP47 with the substrate peptides is abolished by prolyl 4-hydroxylation of the second Pro residues in Pro-Pro-Gly triplets and that the fully prolyl 4-hydroxylated peptide, (Pro-Hyp-Gly)(n), does not interact with HSP47. We thus have proposed a model in which HSP47 dissociates from procollagen during the process of prolyl 4-hydroxylation in the ER.
[Fetal placental antigens in the serum of tumor patients]. (1975)

With the anti-placente rabbit serum three different placente antigens could be demonstrated in the serum of pregnant women and new borns, in ascites hydropic new borns and in liquor ammin. These fetal antigens could be also demonstrated in the serum of women with malignant and benign tumors. There was no identity with alpha1-fetal protein or C-reactive protein. It is discussed either the tumor cells synthesize fetal proteins directly or they produce substances which stimulate the organism for production of these antigens.
Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System (2017)

The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient's genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.
Image transformation for object tracking in high-resolution video (2008)

We propose a new method for warping high-resolution images to efficiently track objects on the ground plane in real time. Recently, the emergence of high resolution video cameras (> 5 megapixels) has enabled surveillance over a much larger area using only a single camera. However, real-time processing of high resolution video for automatic detection and tracking of multiple targets is a challenge. When the surveillance camera covers greater depth of ground regions, due to perspective effect, the image size of a target varies significantly depending on the distance between the camera and the target. In this study, we propose a framework to transform high resolution images into warped images using a plane homography to make the target size uniform regardless of the position. The method not only reduces the number of pixels to be processed for speed-up, but also improves the tracking performance. We provide experimental results on object tracking in high-resolution maritime videos to demonstrate the validity of our method.
Etk/Bmx Transactivates Vascular Endothelial Growth Factor 2 and Recruits Phosphatidylinositol 3-Kinase to Mediate the Tumor Necrosis Factor-induced Angiogenic Pathway (2003)

Tumor necrosis factor (TNF), via its receptor 2 (TNFR2), induces Etk (or Bmx) activation and Etk-dependent endothelial cell (EC) migration and tube formation. Because TNF receptor 2 lacks an intrinsic kinase activity, we examined the kinase(s) mediating TNF-induced Etk activation. TNF induces a coordinated phosphorylation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and Etk, which is blocked by VEGFR2-specific inhibitors. In response to TNF, Etk and VEGFR2 form a complex resulting in a reciprocal activation between the two kinases. Subsequently, the downstream phosphatidylinositol 3-kinase (PI3K)-Akt signaling (but not signaling through phospholipase C-gamma) was initiated and directly led to TNF-induced EC migration, which was significantly inhibited by VEGFR2-, PI3K-, or Akt-specific inhibitors. Phosphorylation of VEGFR2 at Tyr-801 and Tyr-1175, the critical sites for VEGF-induced PI3K-Akt signaling, was not involved in TNF-mediated Akt activation. However, TNF induces phosphorylation of Etk at Tyr-566, directly mediating the recruitment of the p85 subunit of PI3K. Furthermore, TNF- but not VEGF-induced activation of VEGFR2, Akt, and EC migration are blunted in EC genetically deficient with Etk. Taken together, our data demonstrated that TNF induces transactivation between Etk and VEGFR2, and Etk directly activates PI3K-Akt angiogenic signaling independent of VEGF-induced VEGFR2-PI3K-Akt signaling pathway.
Global, local, and stochastic background modeling for target detection in mixed pixels (2010)

As hyperspectral sensors and exploitation methods have evolved, the accuracy of conventional background models has become a limiting factor for high confidence and low false alarm detection of mixed pixel targets. Many common target detection algorithms, such as the Adaptive Coherence/Cosine Estimator, implicitly use a global background model that assumes the background can be modeled by a single, multivariate Gaussian random variable with additive independent and identically distributed Gaussian noise. In order to improve the accuracy of the Gaussianity assumptions, a local background model, which models the background as multiple, disjoint Gaussian clusters, has also been widely considered. This paper introduces an improved variant of the local background model, as well as a novel stochastic background model that is free from distributional assumptions and accounts for the spectral variability of the background on a pixel-by-pixel basis. The performance of the global, local, and stochastic background models is evaluated on a controlled data set and the tradeoffs associated with each method are discussed.
Cyano esters and malononitriles. V. Cyano(fluorenyl)acetic esters, hydroxy nitriles and benzimidazolylacetonitriles (1977)

In contrast to the analogous ylidenemalononitriles, it is found that xanthen-, thioxanthen- and fluoren-9-ylidene cyanoacetates react with organomagnesium halides to give 1,4-adducts regardless of the nature of the Grignard reagent and its steric requirements. Apparently the reaction proceeds through the intermediate formation of a cyclic transition state of lower energy in the case of cyano esters than in the case of malononitriles. &amp;nbsp;&amp;nbsp;&amp;nbsp; The fluorenyl cyano esters (2b-e,g) react with o-phenylenediamine at 240° affording the benz-imidazolyl(fluorenyl)acetonitriles (10a-e), whereas, at lower temperature, the intermediate cyano anilides (11a-e) are obtained which cyclize readily to the corresponding benzimidazoles.
Hemimasticatory spasm (1992)

Hemimasticatory spasm is a rare disorder of the trigeminal nerve that produces involuntary jaw closure due to paroxysmal unilateral contraction of jaw-closing muscles. We report three patients with this disorder. Electrophysiologic studies demonstrated normal blink and masseter reflexes. The masseter inhibitory reflex was absent during periods of spasm. Needle electromyography demonstrated irregular bursts of motor unit potentials that were identical to the pattern observed in hemifacial spasm. The electrophysiologic findings suggest ectopic excitation of the trigeminal motor root or its nucleus, an abnormality that is analogous to ectopic excitation of the facial nerve in hemifacial spasm. One patient improved temporarily with surgery, one improved while on treatment with carbamazepine, and another responded favorably to botulinum toxin injection.
Combination Therapy with Anti–CTL Antigen-4 and Anti-4-1BB Antibodies Enhances Cancer Immunity and Reduces Autoimmunity (2006)

The majority of cancer antigens identified thus far have limited expression in normal tissues. It has been suggested that autoimmune disease is a necessary price for cancer immunity. This notion is supported by a recent clinical trial involving an anti-CTL antigen-4 (CTLA-4) antibody that showed significant clinical responses but severe autoimmune diseases in melanoma patients. To selectively modulate cancer immunity and autoimmunity, we used anti-CTLA-4 and anti-4-1BB antibodies to treat mice with a preexisting cancer, MC38. The combination of the two antibodies led to CD8 T-cell-mediated rejection of large established MC38 tumors and long-lasting immunity to the same tumor cells, although the same regimen was not effective for B16 melanoma. More importantly, whereas individual antibodies induced inflammation and autoimmune manifestations, combination therapy increased cancer immunity while reducing autoimmunity. The reduction of autoimmune effects correlates with an increased function of regulatory T cells. Our results suggest a novel approach to simultaneously enhance cancer immunity and reduce autoimmunity.
Low-k dielectrics characterization for damascene integration (2001)

Both CVD and SOD low-k organosilicate dielectrics (2.2<k<3.0), provided by various material suppliers, were evaluated for material properties and 1LM integration performance. Correlations between blanket wafer characterization of material properties and integration issues were evaluated to determine what key material properties might be predictors of integration performance in CMP and via poisoning. Two material analysis techniques, nanoindentation for Young's modulus and thermal extraction-gas chromatography-mass spectroscopy (TE-GC-MS) were shown to provide highly valuable information. From the evaluation by nanoindentation, low-k dielectrics with higher modulus possess the advantage of good CMP performance of interconnect structures. Blanket CMP test is also a severe CMP test to predict integration CMP results. Through nanoindentation and blanket CMP tests, CMP results can be divided into 4 categories and integration results can therefore be predicted. TE-GC-MS demonstrated a capability to identify ammonia, other potentially deleterious species, which correlated with a photoresist poisoning behavior during via-first-trench-last (VFTL) dual damascene integration. Lastly, the RC product formed from parametric test data for comb/serpentine structures, and Raphael modeling of the same structures shows the need to understand how etch/ash/clean processes affect the final integrated K value of the low-k dielectric.
Measurement of otoacoustic emissions for hearing assessment (1994)

The present report describes the development of hardware and software for the clinical application of otoacoustic emissions (OAEs). This development is driven by the need to quickly, inexpensively, and reliably detect and measure the properties of these small acoustic signals, across a range of audio frequencies, in background noise that is often greater than the evoked sound. However, before exploring the techniques used to measure OAEs, the authors briefly explain the nature of these responses and their clinical significance, which forms the motivation for the development of biomedical instrumentation for their measurement.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>