gebhart/patrepeval huggingface dataset:
Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients with EGFR inhibitor-resistant non-small cell lung cancer. (2014)

The first generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Unfortunately, disease progression generally occurs after 9 to 14 months of targeted therapy. The substitution of threonine with methionine at amino acid position 790 (T790M), as the second mutation in EGFR, is the most common resistance mechanism and is detected in tumor cells from more than 50-60% of patients after disease progression. However, current targeted therapeutic strategies for patients with acquired resistance are limited. This has led to the development of "third generation" EGFR-TKIs that are designed to target T790M and EGFR-TKI sensitizing mutations more selectively than wild-type. AZD9291, as a mono-anilino-pyrimidine compound, is a novel, irreversible EGFR-TKI, has proved to be more effective against both EGFR-TKI sensitizing and resistance T790M mutations in preclinical models. This phase I clinical study showed that AZD9291 has robust efficacy and is well tolerated in EGFR mutant NSCLC patients with acquired resistance to EGFR-TKIs.
Laser Doppler Perfusion Imaging of Eyelid Skin (1996)

We report an initial laser Doppler perfusion study of the eyelids and compare the results with those of other cutaneous regions. Eleven healthy subjects with no prior medical or surgical history, or eyelid malposition underwent laser Doppler perfusion scanning of six skin locations: right forearm, right middle fingertip, right upper eyelid, right lower eyelid, left upper eyelid, and left lower eyelid. Cutaneous perfusion in the four eyelid locations and right middle fingertip were statistically similar to each other but significantly higher than that in the right forearm (p = 0.002). Also, mean perfusion in pretarsal skin was > 50% than that in preseptal skin (p = 0.002). In addition, in an eyelid with histopathologically documented basal cell carcinoma, cutaneous perfusion was significantly higher than the mean of the normal eyelids (p = 0.002). Eyelids are perfused at the same high rate as are other regions of the head, and significantly higher than low flow regions, such as the extremities. Future application of this laser Doppler perfusion scanning include assessing burn depth, postoperative monitoring of periorbital tissue transfer, distinguishing benign and malignant adnexal skin lesions, and establishing the pathologic margins of lid tumors.
Compliance, elastic modulus, and burst pressure of small-intestine submucosa (SIS), small-diameter vascular grafts (1999)

Small-intestine submucosa (SIS) is cell-free collagen, 100 mu thick, derived from the small intestine. It has been used as a vascular graft and has the highly desirable property of remodeling itself to become host tissue. To date there has been limited reporting on its preimplantation mechanical properties as a vascular graft. In this study, compliance, elastic modulus, and burst pressure have been measured on 5- and 8-mm SIS grafts. The compliance (percent of diameter increase for a pressure rise from 80 to 120 mmHg) was 4.6% av (range 2.9 to 8.6%) for the 5-mm grafts. For the 8-mm graft, the increase in diameter for the same pressure rise was 8.7% av (range 7.2 to 9.5%). The modulus of elasticity (E) increased exponentially with increasing pressure according to E = E(o)e(alphaP), where Eo is the zero-pressure modulus and alpha is the exponent that describes the rate of increase in E with pressure; the units for E, Eo, and P are g/cm2. The mean value for Eo was 4106 (g/cm2 range 1348-5601). The mean value for alpha was 0.0059 (range 0.0028-0.0125). At 100 mmHg, the mean value for E was 8.91 x 10(3) g/cm2 (range 1.02-8.80 x 10(3)). The mean burst pressure for 5.5-mm grafts was 3517 mm Hg (range 2069-4654). In terms of preimplant compliance, the small-diameter SIS graft is about (1/2) as compliant as the dog carotid artery, about four times more compliant than a typical vein graft, and more than an order of magnitude more compliant than synthetic vascular grafts.
Microtubule-dependent Organization of Vaccinia Virus Core–derivd Early mRNAs into Distinct Cytoplasmic Structures (2001)

Vaccinia virus (vv) early transcription can be reconstituted in vitro from purified virions; in this assay mRNAs are made inside the viral core and subsequently extruded. Although the in vitro process has been extensively characterized, relatively little is known about vv early transcription in vivo. In the present study the fate of vv early mRNAs in infected HeLa cells was followed by BrUTP transfection and confocal and electron microscopy. The extruded vv early mRNAs were found to be organized into unique granular cytoplasmic structures that reached a size up to 1 microm. By EM these structures appeared as amorphous electron-dense cytoplasmic aggregates that were surrounded by ribosomes. Confocal images showed that the RNA structures were located some distance away from intracellular cores and that both structures appeared to be aligned on microtubules (MTs), implying that MT tracks connected mRNAs and cores. Accordingly, intact MTs were found to be required for the typical punctate organization of viral mRNAs. Biochemical evidence supported the notion that vv mRNAs were MT associated and that MT depletion severely affected viral (but not cellular) mRNA synthesis and stability. By confocal microscopy the viral mRNA structures appeared to be surrounded by molecules of the translation machinery, showing that they were active in protein synthesis. Finally, our data suggest a role for a MT and RNA-binding viral protein of 25 kDa (gene L4R), in mRNA targeting away from intracellular cores to their sites of cytoplasmic accumulation.
Continuous Production Mode as a Viable Process-Engineering Tool for Efficient Poly(hydroxyalkanoate) (PHA) Bio-Production (2014)

Poly(hydroxyalkanoates) (PHAs) constitute promising biomaterials for substituting plastics of fossil origin. Until now, all commercial processes for PHA production were based on discontinuous fed-batch cultivation of prokaryotes. Such processes embody several shortcomings: unpredictable product quality, restricted possibility for supply of toxic carbon substrates, and, most of all, low volumetric productivity. Continuous PHA biosynthesis as a remedy was already investigated on laboratory scale for production of highly crystalline PHA homopolyesters as well as for elastomeric and even functional PHA copolyesters. Apart from enhanced productivity, chemostat processes are a feasible method to elucidate kinetics of cell growth and PHA formation under constant environmental conditions. In order to adapt the process engineering to the microbial kinetic characteristics for growth and PHA accumulation, continuous single- and multistage approaches are reported.
Hearing Loss and Cochlear Pathology in Monkeys After Noise Exposure (1976)

Old World monkeys were exposed to octave-band noise from 0.5 to 8 kHz at 120 dB SPL, 8 hours daily for 20 days. Restricted permanent threshold shifts and localized loss of outer hair cells were produced, which were reasonably well correlated with the exposure frequencies. There was also a loss of both inner and outer hair cells at the extreme basal end of Corti's organ, regardless of the exposure frequency. Implications for human inner ear pathology are discussed.
Crystal structure of highly glycosylated human leukocyte elastase in complex with an S2′ site binding inhibitor (2018)

Glycosylated human leukocyte elastase (HLE) was crystallized and structurally analysed in complex with a 1,3-thiazolidine-2,4-dione derivative that had been identified as an HLE inhibitor in preliminary studies. In contrast to previously described HLE structures with small-molecule inhibitors, in this structure the inhibitor does not bind to the S1 and S2 substrate-recognition sites; rather, this is the first HLE structure with a synthetic inhibitor in which the S2' site is blocked that normally binds the second side chain at the C-terminal side of the scissile peptide bond in a substrate protein. The inhibitor also induces the formation of crystalline HLE dimers that block access to the active sites and that are also predicted to be stable in solution. Neither such HLE dimers nor the corresponding crystal packing have been observed in previous HLE crystal structures. This novel crystalline environment contributes to the observation that comparatively large parts of the N-glycan chains of HLE are defined by electron density. The final HLE structure contains the largest structurally defined carbohydrate trees among currently available HLE structures.
Functional Characterization of Flagellin Glycosylation in Campylobacter jejuni 81-176 (2009)

The major flagellin of Campylobacter jejuni strain 81-176, FlaA, has been shown to be glycosylated at 19 serine or threonine sites, and this glycosylation is required for flagellar filament formation. Some enzymatic components of the glycosylation machinery of C. jejuni 81-176 are localized to the poles of the cell in an FlhF-independent manner. Flagellin glycosylation could be detected in flagellar mutants at multiple levels of the regulatory hierarchy, indicating that glycosylation occurs independently of the flagellar regulon. Mutants were constructed in which each of the 19 serine or threonines that are glycosylated in FlaA was converted to an alanine. Eleven of the 19 mutants displayed no observable phenotype, but the remaining 8 mutants had two distinct phenotypes. Five mutants (mutations S417A, S436A, S440A, S457A, and T481A) were fully motile but defective in autoagglutination (AAG). Three other mutants (mutations S425A, S454A, and S460A) were reduced in motility and synthesized truncated flagellar filaments. The data implicate certain glycans in mediating filament-filament interactions resulting in AAG and other glycans appear to be critical for structural subunit-subunit interactions within the filament.
Creating multiple-crossover DNA libraries independent of sequence identity (2001)

We have developed, experimentally implemented, and modeled in silico a methodology named SCRATCHY that enables the combinatorial engineering of target proteins, independent of sequence identity. The approach combines two methods for recombining genes: incremental truncation for the creation of hybrid enzymes and DNA shuffling. First, incremental truncation for the creation of hybrid enzymes is used to create a comprehensive set of fusions between fragments of genes in a DNA homology-independent fashion. This artificial family is then subjected to a DNA-shuffling step to augment the number of crossovers. SCRATCHY libraries were created from the glycinamide-ribonucleotide formyltransferase (GART) genes from Escherichia coli (purN) and human (hGART). The developed modeling framework eSCRATCHY provides insight into the effect of sequence identity and fragmentation length on crossover statistics and draws contrast with DNA shuffling. Sequence analysis of the naive shuffled library identified members with up to three crossovers, and modeling predictions are in good agreement with the experimental findings. Subsequent in vivo selection in an auxotrophic E. coli host yielded functional hybrid enzymes containing multiple crossovers.
Alpha-amylase from the hyperthermophilic archaebacterium Pyrococcus furiosus. Cloning and sequencing of the gene and expression in Escherichia coli. (1993)

A gene encoding a highly thermostable alpha-amylase from the hyperthermophilic archaebacterium Pyrococcus furiosus was cloned and expressed in Escherichia coli. The nucleotide sequence of the gene predicts a 649-amino acid protein with a calculated molecular mass of 76.3 kDa, which corresponds well with the value obtained from purified enzyme using denaturing polyacrylamide gel electrophoresis. The NH2 terminus of the deduced amino acid sequence corresponds precisely to that obtained from the purified enzyme, excluding the NH2-terminal methionine. The amylase expressed in E. coli exhibits temperature-dependent activation characteristic of of the original enzyme from P. furiosus, but has a higher apparent molecular weight which is attributed to the improper formation of the native quaternary structure. No homology was found with previously characterized promotor or termination sequences. The deduced amino acid sequence displayed strong homology to the alpha-amylase A of Dictyoglomus thermophilum, an obligately anaerobic, extremely thermophilic bacterium. Evolutionary implications of this homology are discussed.
Synthesis and Biological Evaluation of Boronated Folates for BNCT (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Noninvasive prenatal testing. (2014)

Results are available from 12 weeks gestation, giving a high level of reassurance for Down syndrome early in pregnancy. There are concerns, however, that the test is being offered without proper counselling and that women may not have a 12-week ultrasound to exclude significant structural abnormalities, therefore decreasing the early detection of severe abnormalities. In addition, the test is expensive and therefore prohibitive for many women and their families.
Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder (2008)

Structural neuroimaging studies have consistently identified regional abnormalities in subjects with mood disorders. Future studies should strive to definitively establish the influence of age and medication.
Bacterial Inclusion Bodies Contain Amyloid-Like Structure (2008)

Protein aggregation is a process in which identical proteins self-associate into imperfectly ordered macroscopic entities. Such aggregates are generally classified as amorphous, lacking any long-range order, or highly ordered fibrils. Protein fibrils can be composed of native globular molecules, such as the hemoglobin molecules in sickle-cell fibrils, or can be reorganized &beta;-sheet&ndash;rich aggregates, termed amyloid-like fibrils. Amyloid fibrils are associated with several pathological conditions in humans, including Alzheimer disease and diabetes type II.
Synthesis of 6-, 7- and 8-carbon sugar analogues of potent anti-influenza 2,3-didehydro-2,3-dideoxy-N-acetylneuraminic acid derivatives (1995)

Analogues of the potent anti-influenza A and B compound, 4-guanidino-Neu5Ac2en, are described in which the stereochemically demanding C-6-glycerol side-chain is truncated. Syntheses of the one- and two-carbon side-chain analogues, of both 4-guanidino- and 4-amino-Neu5Ac2en, are presented, as well as the syntheses of analogues lacking any side-chain. Whilst complete removal of the C-6 side-chain abolishes activity, a stepwise increase in inhibition of influenza neuraminidase and influenza A and B in cell culture with increasing C-6 chain length is observed. The one-carbon, hydroxymethyl derivative retains significant activity to represent a suitable lead in the search for neuraminidase inhibitors of reduced stereochemical demand and synthetic complexity.
A gene signature of 8 genes could identify the risk of recurrence and progression in Dukes' B colon cancer patients (2007)

The benefit of postoperative adjuvant chemotherapy in patients with Dukes' B colorectal cancer is still uncertain and its routine use is not recommended. The five-year relapse rate is approximately 25-40% and the identification of patients at high risk of recurrence would represent an important strategy for the use of adjuvant chemotherapy. We retrospectively analyzed gene expression profiles in frozen tumor specimens from patients with Dukes' B colorectal cancer by using high density oligonucleotide microarrays. Our results show a subset of 48 genes differentially expressed with an associated probability <0.001 in the t-test. Another statistical procedure based on the Fisher criterion resulted in 11 genes able to separate both groups. We selected the 8 genes present in both subsets. The differential expression of five genes (CHD2, RPS5, ZNF148, BRI3 and MGC23401) in colon cancer progression was confirmed by real-time PCR in an independent set of patients of Dukes' B and C stages.
Trends in infection morbidity in a pediatric oncology ward, 1986-1995 (1999)

Rapid recovery of the WBC was associated with an excellent prognosis whereas persisting neutropenia was found to be a negative factor associated with fatal outcomes. The fatality rate of all febrile episodes (2.3%) remained the same throughout the study period despite the availability and wider use of recombinant hematopoietic growth factors since 1991.
Development of GnRH Antagonists for Prostate Cancer: New Approaches to Treatment (2000)

Prostate cancer has become the most common cancer among American men and is second only to lung cancer as a cause of male cancer-related death. Several treatment options exist for different stages of prostate cancer including observation, prostatectomy, radiation therapy, chemotherapy, and hormone therapy. Hormone therapy has evolved from the use of estrogens to gonadotropin-releasing hormone (GnRH) agonists and recently, investigational GnRH antagonists. GnRH receptor agonists such as leuprolide, bruserelin and goserelin have been used for the treatment of prostate cancer. These agonists eventually cause the inhibition of lutenizing hormone production, which in turn causes a suppression of testosterone and dihydrotestosterone, on which continued growth of prostate cancer cells depend. Several comparative studies of leuprorelin administered as daily injections or monthly depot injections have been reported. Disease progression was prevented in more than 72% of men administered daily leuprorelin, and in 82% to 89% of those receiving monthly depots. Another synthetic GnRH analog, goserelin, has been studied in a similar population of men with daily injections producing partial responses in 60% to 80% of men with previously untreated prostate cancer. Abarelix, a peptide antagonist of GnRH receptor, is also being studied for the treatment of prostate cancer. The discovery and development of GnRH antagonists may provide an important advance for patients with prostate cancer. Clearly the studies described herein, as well as many others, outline an exciting era of research to define the optimal use of hormonal therapy in prostate cancer.
Ultraviolet-induced fluorescence: shedding new light on dental biofilms and dental caries (2007)

Having the lowest photon energy of the three ultra-violet wavebands, UVA has little effect onmicrobial pathogens and virtually no effect onhuman tissue with short-term exposures.UVA is the important band in terms of diagnosticapplications in dentistry. The ability of UVA tomake biological materials fluoresce is well knownin medicine and dentistry as well as in industry. Forexample, UVA sources have application for identi-fying materials such as dyes, inks, minerals,chemical and various biological materials (such asblood, when used in forensic science). Light in thevisible violet and UVA wave bands can also initiatechemical reactions which contribute to the photo-polymerization of some dental compositematerials, as well as adhesives, coatings, and resinsused in fields other than dentistry.
An in vitro model of the leukocyte interactions associated with granuloma formation in Mycobacterium tuberculosis infection (2007)

The principal defense of the human host against a Mycobacterium tuberculosis infection is the formation of granulomas, organized collections of activated macrophages, including epithelioid and multinucleated giant cells, surrounded by lymphocytes. This granuloma can sequester and contain the bacteria preventing active disease, and if the granuloma is maintained, these bacteria may remain latent for a person's lifetime. Secretion of a variety of chemoattractant cytokines following phagocytosis of the bacilli by the macrophage is critical not only to the formation of the granuloma but also to its maintenance. To investigate this process of early granuloma formation, we developed an in vitro model composed entirely of human cells. Combining blood lymphocytes and autologous macrophages from healthy purified protein derivative skin test-negative individuals and mycobacteria resulted in the formation of small, rounded aggregate structures. Microscopic examination found macrophage-specific CD68(+) epithelioid macrophages and small round CD3(+) lymphocytes that in complex resembled small granulomas seen in clinical pathology specimens. Acid-fast staining bacteria were observed between and possibly within the cells composing the granulomas. Supernatants from the infected cells collected at 24 and 48 h and 5 and 9 days after infection were analyzed by a multiplexed cytokine bead-based assay using the Luminex 100 and were found to contain interleukin (IL)-6, IL-8, interferon-gamma and tumor necrosis factor-alpha, cytokines known to be involved in human granuloma formation, in quantities from two-fold to 7000-fold higher than supernatants from uninfected control cells. In addition, chemotaxis assays demonstrated that the same supernatants attracted significantly more human peripheral blood mononuclear cells than those of uninfected cells (P<0.001). This model may provide insight into the earliest stages of granuloma formation in those newly infected.
Memory-efficient 3D multi-resolution image enhancement and processing to increase throughput (2008)

Advanced signal processing such as multi-resolution decomposition and three-dimensional processing and data sets are gradually becoming a integral part of medical imaging. With the growing number of signal dimensions, the bandwidth requirements increase exponentially. Because memory bandwidth is a scarce parameter, this paper focusses on bandwidth optimization at the processor-chip level within multiprocessor systems. We introduce a practical model including formulas for the computing, memory and cache read/write procedures to optimize the mapping of data into the memory and cache for different configurations. A substantial performance improvement is realized by a new memory-communication model that incorporates the data-dependencies of the image-processing functions. More specifically, bandwidth optimization and minimization is achieved by implementing two measures: (1) breaking down the algorithm such that the processing gets a locality that fits with the cache size of the processor, and (2) a technique known from based on addressing and organizing the data prior to processing in such a way that memory traffic is minimized. For the experiments, we have concentrated particularly on image enhancement and noise reduction build around image pyramids for 3D X-ray data sets. First experimental results show a bandwidth reduction in the order of 80% and a throughput increase of 60% compared to straightforward implementations.
Bayesian Radial Basis Functions of Variable Dimension (1998)

A Bayesian framework for the analysis of radial basis functions (RBF) is proposed that accommodates uncertainty in the dimension of the model. A distribution is defined over the space of all RBF models of a given basis function, and posterior densities are computed using reversible jump Markov chain Monte Carlo samplers (Green, 1995). This alleviates the need to select the architecture during the modeling process. The resulting networks are shown to adjust their size to the complexity of the data.