gebhart/patrepeval huggingface dataset:
Tetrahydrobiopterin as an Alternative Treatment for Mild Phenylketonuria (2002)

Tetrahydrobiopterin responsiveness is common in patients with mild hyperphenylalaninemia phenotypes. Responsiveness cannot consistently be predicted on the basis of genotype, particularly in compound heterozygotes.
Oocyte activation after intracytoplasmic injection of mature and immature sperm cells (1998)

The inactivation of metaphase-promoting factor (MPF), leading to reactivation of the oocyte cell cycle after fertilization, is one of the most important results of oocyte activation in the case of intracytoplasmic injection of mature or immature sperm cells. Oocyte activation is a cell signalling event that is likely to imply receptors at the oocyte plasma membrane and a signal transduction pathway involving calcium and protein phosphorylation/dephosphorylation. The typical calcium signal during oocyte activation in mammals takes the form of calcium oscillations. Intracytoplasmic sperm injection (ICSI) is associated with a slightly different pattern of calcium oscillations in comparison with normal fertilization. Available data suggest that sperm cytosolic factor(s) play a role of oscillator, modulating the properties of the oocyte's intracellular calcium stores, whereas the role of trigger, normally realized by spermoocyte interactions at the level of their respective cell surfaces, can be supplemented in the conditions of ICSI by an artificial calcium influx generated by the procedure itself. Delayed onset and an abnormal form of the oocyte activation-promoting calcium signal are the two known molecular abnormalities of human oocyte activation; they can lead to fertilization failure and are also suspected to be at the origin of various embryo abnormalities. The impact of oocyte activation abnormalities on future development increases when oocytes are fertilized with immature sperm cells (spermatids) because the chromatin of these cells is less protected than sperm chromatin against a rapid action of the oocyte's MPF. If oocyte stimulation by the sperm calcium oscillation-promoting activity, which first appears at the round spermatid stage of human spermatogenesis, is insufficient to cause a rapid inactivation of MPF, premature condensation of spermatid chromatids may lead to aneuploidy.
Advances in Measuring the Effect of Individual Predictors of Cardiovascular Risk: The Role of Reclassification Measures (2009)

Models for risk prediction are widely used in clinical practice to stratify risk and assign treatment strategies. The contribution of new biomarkers has largely been based on the area under the receiver-operating characteristic curve, but this measure can be insensitive to important changes in absolute risk. Methods based on risk stratification have recently been proposed to compare predictive models. Such methods include the reclassification calibration statistic, the net reclassification improvement, and the integrated discrimination improvement. This article demonstrates the use of reclassification measures and illustrates their performance for well-known cardiovascular risk predictors in a cohort of women. These measures are targeted at evaluating the potential of new models and markers to change risk strata and alter treatment decisions.
Stability Study Of Cs Extraction Solvent (2003)

Researchers at the Savannah River Site (SRS) and Oak Ridge National Laboratory (ORNL) examined the performance and stability to irradiation of an improved calix[4]arene-based paraffin extraction solvent consisting of a calix[4]arene chelator, 1-(2,2,3,3-tetrafluoropropoxy)-3-(4-sec-butylphenoxy)-2-propanol (Cs-7SB modifier) and trioctylamine (TOA) for the removal of cesium from high-level waste. As a result of testing performed in 1998, modifications to the solvent system were made to improve chemical stability. The robustness to irradiation of the current calix[4]arene-based solvent system was examined by exposing agitated solvent in contact with aqueous phases representing the composition on the stages of extraction (alkaline waste simulant), scrub (0.05-M nitric acid), and strip (0.001-M nitric acid) to a dose up to 50 Mrad by a 60Co gamma source. The solvent was also agitated for 101 days with high-level liquid waste from the Savannah River Site (SRS) tanks. After irradiation, the concentration of the components in the solvent system and the identification of degradation products were determined primarily using gas chromatography (GC) and high-performance liquid chromatography (HPLC). The expected yearly dose the solvent will receive is 100 krad/year. An approximately 10% concentration drop in trioctylamine was observed at a 2-Mrad dose of gamma radiation, an estimate 20-year radiation dose. At gamma-radiation doses as high as 16 Mrad, or an estimated 160-year-radiation dose, there was not a significant loss of the calix[4]arene chelator (less than 10%), and there was only a minor loss (less than 2%) of Cs-7SB modifier that yields the degradation product 4-sec-butylphenol. Additional testing indicated that this phenol is readily removed by a caustic wash. Distribution coefficients for Cs between the phases (DCs) were also determined using inductively coupled plasma mass spectroscopy (ICP-MS) and gamma-counting methods. Relative to unirradiated solvent, extraction, scrubbing, and stripping performance were not significantly affected by external gamma-radiation doses as high as 8 Mrad, an estimated 80-year dose. These findings indicate that the solvent is stable and retains its expected extraction, scrubbing, and stripping properties after exposure to relatively high-gamma-radiation doses (up to 8 Mrad).
Induction of intercellular adhesion molecule 1 and class II histocompatibility antigens in colorectal tumour cells expressing activated ras oncogene (1995)

Aims-To determine whether there is a correlation between activation of the ras oncogene and the induction of MHC class II antigens and intercellular adhesion molecule 1 (ICAM-1) by interferon-gamma (IFN-gamma).Methods-Expression of class II antigens, ICAM-1 and intracellular ras oncoprotein (p21) in established colorectal cell lines and short term cultures of primary colorectal tumour cells was determined by flow cytometry and mutation in the ras gene by sequencing of amplified segments of the gene.Results-The cell lines showed a variation in their modulation of MHC class II antigens and ICAM-1, ranging from no induction to a 98-fold increase in class II antigen expression in the HT29 cell line. Previous work indicated that most tumours could not be induced to express class II antigens. Four of the five least inducible lines either contained mutant ras or highly expressed the oncoprotein. The four highly inducible cell lines all contained non-mutant ras. Of the 21 tumours studied in primary culture, 10 were inducible, one of which contained mutant ras. Of the remaining non-inducible tumours, four were mutant.Conclusions-Correlations between ras activation and failure to respond to IFN-gamma could not be shown to be significant. Therefore, ras activation, and concomitant subversion of intracellular signalling pathways, is probably not the major determinant in failure to activate class II antigens and ICAM-1.
Demethylation and epigenetic modification with 5-azacytidine reduces IDH1 mutant glioma growth in combination with temozolomide (2018)

5-Aza provided a survival benefit as a single agent but worked best in combination with TMZ in 2 different IDH1 R132H mutant glioma models.
Molecular diversity of heparan sulfate (2001)

Heparan sulfate proteoglycansHeparan sulfate (HS) appeared early in metazoan evolution.As such, many of the structural motifs (variably sulfated disaccharide subunits) that characterize HS (and heparin) were established early on and have been preserved in modern organisms.Thus, many of the biological functions associated with HS either occurred early in evolution or have depended on the subsequent evolution of the protein ligands that bind to the polysaccharide.Today, we know of literally hundreds of heparin-binding proteins, and many interactions have profound consequences in vertebrate and invertebrate physiology.This Perspective aims to provide an overview of HS structure, function, and biosynthesis and to set the stage for discussing the relationship between structure and function of these fascinating molecules and how altered HS biosynthesis and catabolism can lead to human disorders.
HIGH EFFICIENCY FLOWBACK TECHNOLOGY USED IN LOW-PERMEABILITY TIGHT RESERVOIRS (2010)

The flowback mechanism of fracturing fluid was studied in low-permeability tight reservoir,and the factors of influence fracturing fluid flowback were also analyzed,which included water-lock damage of fracturing fluid,kickoff pressure and flowback pressure difference besides the basic geological features.On this basis of these factors,a high efficiency flowback technique was proposed in low-permeability tight reservoirs,and it was applied successfully in tight gas reservoir of West Sichuan.It could shorten flowback time enormously,enhance flowback rate and flowback efficiency of fracturing fluid,decrease reservoir damage,and ensure fracturing effect
Ranpirnase (Frog RNase) Targeted with a Humanized, Internalizing, Anti–Trop-2 Antibody Has Potent Cytotoxicity against Diverse Epithelial Cancer Cells (2010)

Ranpirnase (Rap), an amphibian RNase, has been extensively studied both preclinically and clinically as an antitumor agent. Rap can be administered repeatedly to patients without any untoward immune response, with reversible renal toxicity reported to be dose limiting. To enhance its potency and targeted tumor therapy, we describe the generation of a novel IgG-based immunotoxin, designated 2L-Rap(Q)-hRS7, comprising Rap(Q), a mutant Rap with the putative N-glycosylation site removed, and hRS7, an internalizing, humanized antibody against Trop-2, a cell surface glycoprotein overexpressed in variety of epithelial cancers. The immunotoxin was generated recombinantly by fusing Rap(Q) to each of the two hRS7 light (L) chains at the NH(2) terminus, produced in stably transfected myeloma cells, purified by Protein A, and evaluated by a panel of in vitro studies. The results, including size-exclusion high-performance liquid chromatography, SDS-PAGE, flow cytometry, RNase activity, internalization, cell viability, and colony formation, showed its purity, molecular integrity, comparable affinity to hRS7 for binding to several Trop-2-expressing cell lines of different cancer types, and potency to inhibit growth of these cell lines at nanomolar concentrations. In addition, 2L-Rap(Q)-hRS7 suppressed tumor growth in a prophylactic model of nude mice bearing Calu-3 human non-small cell lung cancer xenografts, with an increase in the median survival time from 55 to 96 days (P < 0.01). These results warrant further development of 2L-Rap(Q)-hRS7 as a potential therapeutic for various Trop-2-expressing cancers, such as cervical, breast, colon, pancreatic, ovarian, and prostate cancers.
Targeted Gene Delivery to Vascular Tissue In Vivo by Tropism-Modified Adeno-Associated Virus Vectors (2004)

AAV tropism can be genetically engineered by use of phage display-derived peptides to generate vectors that are selective for the vasculature.
Novel multimode coupler switch (1998)

We propose a new type of multimode waveguide (MMW) where the switching operation is controlled by decreasing the refractive indexes of certain regions of the waveguide. They are simpler in structure than those based on a phase shifter, and need fewer controllers in every switching operation—a feature very attractive for larger matrices. © 1998 John Wiley & Sons, Inc. Microwave Opt Technol Lett 17: 1–7, 1998.
Efficient design method for multi-pump flat-gain fiber Raman amplifiers (2002)

There is much current interest in fiber Raman amplifiers pumped at multiple wavelengths (MW-FRA), which can combine the low-noise advantage of distributed Raman amplification with the possibility of ultra-wide (80 nm and above) gain bandwidths.
Effect of Sterics and Degree of Cross-Linking on the Mechanical Properties of Dynamic Poly(alkylurea–urethane) Networks (2017)

Dynamic covalent networks are polymer networks that contain a dynamic covalent bond which allows them to be reprocessable, remoldable, and recyclable as well as exhibit crack healing or stress-relaxation properties. A key component of these materials is the nature of the dynamic covalent bond, which in addition to chemical composition and architecture can be used to dramatically alter the physical properties of these networks. The aim of this study is to understand the impact of steric hindrance of N-alkyl substituents and network connectivity in poly(alkylurea–urethane) dynamic network films. In these materials, the dynamic bond is the hindered alkyl urea moiety, whose dynamic behavior is dictated by the sterics of the alkyl substituent. Networks were prepared by the noncatalyzed curing reaction of aminoethanol compounds of varying substituents with a trifunctional isocyanate cross-linker and varying amounts of a monofunctional capping agent. Thermomechanical properties and FTIR studies show the impact of hindered urea bond sterics on the reaction conversion, network connectivity, and therefore the relaxation of the dynamic networks. Stress relaxation analysis show the vitrimer-like behavior of these dynamic networks only when the degree of cross-linking is maintained by high reaction conversion (high equilibrium constant of the dynamic bond). These results give some insights into the design and properties of dynamic covalent networks and how the nature of dynamic bonds can be used to impact their properties.
Diversity of Heteropolysaccharide-Producing Lactic Acid Bacterium Strains and Their Biopolymers (2006)

Thirty-one lactic acid bacterial strains from different species were evaluated for exopolysaccharide (EPS) production in milk. Thermophilic strains produced more EPS than mesophilic ones, but EPS yields were generally low. Ropiness or capsular polysaccharide formation was strain dependent. Six strains produced high-molecular-mass EPS. Polymers were classified into nine groups on the basis of their monomer composition. EPS from Enterococcus strains were isolated and characterized.
Death on the Cooper: King's Secret? (2007)

The Burke and Wills disaster is one of the iconic stories of Australian history, incorporating exploration, misadventure, death and the lone survivor. An inquiry into the fate of the expedition relied on the public testimony of the sole survivor, John King, and this has long been accepted as a factual account of Burke's passing, but, later, other versions came to light that have either been missed or not seriously considered by historians. This purpose of this paper is to give these alternative versions the serious consideration they deserve.
Transgenic mouse model of malignant skin melanoma. (1993)

Tyr-SV40E transgenic mice are specifically susceptible to melanoma due to expression of the oncogene in pigment cells. Mice of the more susceptible lines die young of early-onset eye melanomas, when skin melanomas are still infrequent and benign. To surmount this obstacle, skin from donors of two high-susceptibility lines was grafted to Tyr-SV40E hosts of a low-susceptibility line of the same inbred strain, thereby enabling the skin to outlive the donors and continue to grow in immunocompetent but tolerant hosts. Unexpectedly, donor pigment cells in all the grafts soon selectively proliferated close to areas of greatest wound healing, forming a dense black tracery, especially at the outer rim of the grafts. These lesions slowly grew radially within the grafts, producing irregular greyish patches. Local vertical thickenings then appeared and developed into small melanomas, which soon ulcerated through the epidermis. The tumors rapidly enlarged and became deeply invasive. Discrete black nevi also arose, with many becoming larger and distinctly blue, but those not near areas of pronounced wound healing did not progress to malignancy. In this first series, malignant melanoma resulted in all the grafts from the more susceptible of two donor lines and in some grafts from the other line. Distant metastases occurred in some cases from each line. Most tumors were hypomelanotic and heterogeneous, with lobes or areas differing in melanization. The results strongly suggest that growth factors and cytokines--known to be produced in wound repair--are triggering the growth and malignant conversion of these genetically susceptible melanocytes and that in the graft situation we are merely witnessing a caricature--a usefully exaggerated manifestation of the true events underlying the genesis of melanomas. The striking resemblance to the human malignancy, the genetic uniformity and different susceptibilities of the transgenic lines, and the experimental possibilities in the grafted mice all make them an excellent model of the disease.
Therapeutic Effect of Anti–TNF-α Antibodies in an Experimental Model of Anti-Neutrophil Cytoplasm Antibody–Associated Systemic Vasculitis (2005)

The therapeutic options for anti-neutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis (AASV) remain limited and hampered by adverse effects. One potential novel therapeutic avenue involves inhibition of TNF-alpha, with encouraging uncontrolled data in humans with one agent (infliximab) but disappointing controlled data from another (etanercept). For investigating the potential role of TNF-alpha as a therapeutic target in AASV, the effect of an anti-rat TNF-alpha mAb (CNTO 1081) in a rat model of AASV was investigated. For testing the effect of TNF-alpha blockade in this model, starting on day 28 after immunization (a point when glomerulonephritis is established), animals were randomized to treatment with CNTO 1081 or control mouse IgG. Treatment with CNTO 1081 significantly reduced albuminuria (mean 1.1 +/- 0.3 mg/24 h CNTO 1081 versus 8.0 +/- 1.9 controls; P < 0.05) and crescent formation (0% CNTO 1081 versus 60% controls; P < 0.05). Lung hemorrhage was also reduced (CNTO 1081: median score 0, range 0 to 2; controls: 2, range 1 to 3; P < 0.05). When analyzed by intravital microscopy, there was a 43% inhibition of leukocyte transmigration in mesenteric venules in response to topical CXCL1 (a neutrophil chemoattractant) in the CNTO 1081 group compared with controls (P < 0.001). Anti-myeloperoxidase antibody titers were similar in both groups throughout the study. In conclusion, these findings indicate that TNF-alpha plays an important role in the pathogenesis of experimental autoimmune vasculitis and suggest that blockade of this cytokine with an mAb is effective in treating established vasculitis. The therapeutic action of anti-TNF-alpha reagents may be mediated, in part, by suppression of the enhanced leukocyte-endothelial interactions in this disorder.
The Role of Animal Models in Evaluating Reasonable Safety and Efficacy for Human Trials of Cell-Based Interventions for Neurologic Conditions (2008)

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.
Cell surface markers in hematologic malignancies. (1987)

Cell surface markers have identified considerably more heterogeneity within human T, B, and myeloid neoplasms than was evident by standard morphologic and histochemical techniques. Using markers specific for the lineage and state of differentiation, it is now possible to correlate malignant lymphoid and myeloid cells to their normal cellular counterparts. Considering the complexity of the normal hematopoietic system with regard to ontogeny, differentiation, and function, it is not surprising that these malignancies reflect this diversity. Hopefully, with increasing characterization of the normal function of cell surface molecules, as well as the subpopulations of normal cells to which these malignancies correspond, we will have a better understanding of the biologic and clinical behavior of these malignancies.
Configuring robust DNA strand displacement reactions for in situ molecular analyses (2011)

The number of distinct biomolecules that can be visualized within individual cells and tissue sections via fluorescence microscopy is limited by the spectral overlap of the fluorescent dye molecules that are coupled permanently to their targets. This issue prohibits characterization of important functional relationships between different molecular pathway components in cells. Yet, recent improved understandings of DNA strand displacement reactions now provides opportunities to create programmable labeling and detection approaches that operate through controlled transient interactions between different dynamic DNA complexes. We examined whether erasable molecular imaging probes could be created that harness this mechanism to couple and then remove fluorophore-bearing oligonucleotides to and from DNA-tagged protein markers within fixed cell samples. We show that the efficiency of marker erasing via strand displacement can be limited by non-toehold mediated stand exchange processes that lower the rates that fluorophore-bearing strands diffuse out of cells. Two probe constructions are described that avoid this problem and allow efficient fluorophore removal from their targets. With these modifications, we show one can at least double the number of proteins that can be visualized on the same cells via reiterative in situ labeling and erasing of markers on cells.
Feasibility of Using Ultra-High Field (7 T) MRI for Clinical Surgical Targeting (2012)

The advantages of ultra-high magnetic field (7 Tesla) MRI for basic science research and neuroscience applications have proven invaluable. Structural and functional MR images of the human brain acquired at 7 T exhibit rich information content with potential utility for clinical applications. However, (1) substantial increases in susceptibility artifacts, and (2) geometrical distortions at 7 T would be detrimental for stereotactic surgeries such as deep brain stimulation (DBS), which typically use 1.5 T images for surgical planning. Here, we explore whether these issues can be addressed, making feasible the use of 7 T MRI to guide surgical planning. Twelve patients with Parkinson's disease, candidates for DBS, were scanned on a standard clinical 1.5 T MRI and a 7 T MRI scanner. Qualitative and quantitative assessments of global and regional distortion were evaluated based on anatomical landmarks and transformation matrix values. Our analyses show that distances between identical landmarks on 1.5 T vs. 7 T, in the mid-brain region, were less than one voxel, indicating a successful co-registration between the 1.5 T and 7 T images under these specific imaging parameter sets. On regional analysis, the central part of the brain showed minimal distortion, while inferior and frontal areas exhibited larger distortion due to proximity to air-filled cavities. We conclude that 7 T MR images of the central brain regions have comparable distortions to that observed on a 1.5 T MRI, and that clinical applications targeting structures such as the STN, are feasible with information-rich 7 T imaging.