gebhart/patrepeval huggingface dataset:
P4‐067: TOMM40 “523” PolyT Allele Frequencies in Different Ethnic Groups (2010)

The TOMM40 rs10524523 (“523”) polyT polymorphism, in linkage disequilibrium with APOE alleles, predicts age of Alzheimer's disease (AD) onset distributions for >85% of the Caucasian population. For Japanese, Han Chinese, and Korean populations, the mean age of AD onset is approximately 6-8 years older and the age-related prevalence is lower than for Caucasians. We hypothesized that the distribution of “523” would be skewed to shorter polyT lengths since shorter polyT lengths are associated with older age at onset in Caucasians. We determined the “523” genotypes for three Far Eastern [FE] population samples [30 Japanese, 30 Han Chinese, 30 Korean], and 42 West African [Ghana] subjects. We measured the polyT length by PCR followed by Sanger sequencing. The frequency of APOE4 was lower in the FE groups relative to Caucasians, and the polyT allele lengths linked to APOE4 were similar in the two groups [21-30 T residues]. Similar to Caucasians, there were two distinct length distributions of “523” polyT tracts, short [S] and very long [VL], in linkage with APOE3. However, the length distributions of the S and VL “523” alleles were shifted to shorter lengths in the FE populations. For Caucasians, the short “523” alleles were rarely less than 14 T residues long whereas short alleles of 11-13 T residues were common in the FE groups and the frequency of alleles of 15-16 residues was markedly reduced in these populations. The FE VL forms were generally 27-32 residues long in the FE groups while the length of the Caucasians VL alleles peaked at 33-37 residues. In a series of subjects from Ghana, we documented an enrichment of short [lower risk] “523” alleles compared to Caucasians, but the allele length distribution was similar to Caucasians. The distributions of inherited“523” polyT lengths varies in populations with different evolutionary histories, and the relatively shorter allele lengths appear to be consistent with the older age of AD onset in FE populations compared to Caucasians. West Africa distributions are also different from Caucasian and FE groups. These data may contribute to our knowledge of age-dependent disease risk in different world populations.
Evolving role of tissue factor and its pathway inhibitor (2002)

Tissue factor, a membrane-bound procoagulant glycoprotein, is the initiator of the extrinsic clotting cascade, which is the predominant coagulation pathway in vivo. The traditional view localizes tissue factor to extravascular sites, where it remains sequestered from circulating factor VII until vascular integrity is disrupted or until tissue factor expression is induced in endothelial cells or monocytes. This perspective has been challenged since the discovery of tissue factor antigen in plasma, on circulating microparticles, and on leukocytes in whole blood. Recently, the apparent role of tissue factor has expanded with the demonstration that this molecule also functions as a signaling receptor. Recombinant tissue factor pathway inhibitor, an analogue of the physiologic inhibitor of tissue factor, is a potent inhibitor of thrombus formation in experimental models. In summary, the tissue factor pathway initiates thrombosis in vivo. In addition to its classic tissue-bound distribution, recently discovered blood-borne tissue factor may have an important procoagulant function. Despite showing promise in early human studies, a recently completed phase 3 trial of recombinant tissue factor pathway inhibitor in severe sepsis failed to show a reduction in the primary end point of 28-day all-cause mortality. Tissue factor pathway inhibitor, however, remains a plausible therapeutic agent in other conditions of increased thrombogenicity, such as acute coronary syndromes, and further studies to examine this potential are warranted.
Enoxaparin-induced alopecia in patients with cerebral venous thrombosis (2006)

From the review of literature, there is no report of alopecia caused by urokinase. Using the Naranjo ADR Probability Scale, a score of 6 suggests that enoxaparin was the probable cause of alopecia in our three patients. This report introduces evidence of alopecia as a probable side effect of enoxaparin, but stresses the efficacy and safety of LMWH. As this is not a life-threatening disorder, we hope to increase the awareness of pharmacists and clinicians to this relatively rare but important side effect.
Radio-Wave Heating of Iron Oxide Nanoparticles Can Regulate Plasma Glucose in Mice (2012)

Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca(2+)-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells.
Autonomous, teleoperated, and shared control of robot systems (2002)

This paper illustrates how different modes of operation such as bilateral teleoperation, autonomous control, and shared control can be described and implemented using combinations of modules in the SMART robot control architecture. Telerobotics modes are characterized by different "grids" of SMART icons, where each icon represents a portion of run-time code that implements a passive control law. By placing strict requirements on the module's input-output behavior and using scattering theory to develop a passive sampling technique, a flexible, expansible telerobot architecture is achieved. An automatic code generation tool for generating SMART systems is also described.
Molecular cytogenetics in human cancer diagnosis (1992)

This report summarizes the application of fluorescence in situ hybridization for detection and diagnosis of human cancers and for detection of residual cancer cells. This approach allows individual interphase cancer cells to be stained so that aberrations such as aneusomies, translocations, deletions, and gene amplification can be seen in the light microscope. This is accomplished using probes for repeated sequences found at the chromosome centromeres, whole chromosome probes, and/or probes for specific aberrant sequences. Cancer 1992; 69:1536-1542.
Regulation of IgG antibody responses by epitope density and CD21-mediated costimulation (2002)

Epitope density and organization have been shown to be important factors for B cell activation in many animal model systems. However, it has been difficult to separate the role of antigen organization from the role of local antigen concentrations because highly organized antigens are usually particulate whereas non-organized antigens are more soluble. Hence, highly organized and non-organized antigens may interact with different cell types and in different locations within lymphoid organs. In order to assess the role of antigen organization in regulating B cell responses, we immunized mice with highly repetitive virus-like particles, which exhibit different epitope densities covalently attached to them. Therefore, the same particulate structure was used to present identical epitopes that differed in their degree of organization. Induction of epitope-specific IgM titers, reflecting early B cell activation, were unaffected by the degree of epitope density. Furthermore, the absence of Th cells or CD21/CD35 did not reduce the IgM response. In contrast, the degree of organization was a critical factor influencing the magnitude of the epitope-specific IgG response. Moreover, the threshold for IgG responses was shifted in the absence of CD21/CD35, resulting in the requirement for higher epitope densities to allow efficient IgG responses. Thus, IgG but not IgM responses are regulated by epitope density and B cell costimulatory thresholds.
Electronic and electromagnetic properties of nanotubes (1998)

A nanotube is phenomenologically modeled as a chain of atoms wrapped helically on a right circular cylinder. The semiclassical Hamiltonian of an electron is derived, using the Wannier approach for the Schr\"odinger equation, when the nanotube is exposed to both constant (dc) and high-frequency (ac) electromagnetic fields. The Boltzmann kinetic equation is then solved in the framework of momentum-independent relaxation time approximation. An analytical expression for electric current in a nanotube is derived. The interaction of nonlinearity and chirality is analyzed, chiefly as the dependence of a current chiral angle on the amplitude of the ac electric field. The derived expressions for the electronic transport also help in stating anisotropic impedance boundary conditions on the nanotube surface. Surface wave propagation in a carbon nanotube (CN) is examined. The idea of using CN's as nanowaveguides in the infrared frequency range is established. Convective instability is shown to occur under special conditions in a CN exposed to an axial dc electric field.
Age-Related Macular Degeneration (2008)

Age-related macular degeneration is the leading cause of irreversible blindness in people 50 years of age or older in the developed world. This article reviews the clinical and histopathological features of age-related macular degeneration and its genetics and epidemiology and discusses current management options and research advances.
Topography of Helices 5–7 in Membrane-inserted Diphtheria Toxin T Domain (2002)

The T domain of diphtheria toxin undergoes a low pH-induced conformational change that allows it to penetrate cell membranes. T domain hydrophobic helices 8 and 9 can adopt two conformations, one close to the membrane surface (P state) and a second in which they apparently form a transmembrane hairpin (TM state). We have now studied T domain helices 5-7, a second cluster of hydrophobic helices, using Cys-scanning mutagenesis. After fluorescently labeling a series of Cys residues, penetration into a non-polar environment, accessibility to externally added antibodies, and relative depth in the bilayer were monitored. It was found that helices 5-7 insert shallowly in the P state and deeply in the TM state. Thus, the conformational changes in helices 5-7 are both similar and somehow linked to those in helices 8 and 9. The boundaries of deeply inserting sequences were also identified. One deeply inserted segment was found to span residues 270 to 290, which overlaps helix 5, and a second spanned residues 300 to 320, which includes most of helix 6 and all of helix 7. This indicates that helices 6 and 7 form a continuous hydrophobic segment despite their separation by a Pro-containing kink. Additionally, it is found that in the TM state some residues in the hydrophilic loop between helices 5 and 6 become more highly exposed than they are in the P state. Their exposure to external solution in the TM state indicates that helices 5-7 do not form a stable transmembrane hairpin. However, helix 5 and/or helices 6 plus 7 could form transmembrane structures that are in equilibrium with non-transmembrane states, or be kinetically prevented from forming a transmembrane structure. How helices 5-7 might influence the mechanism by which the T domain aids translocation of the diphtheria toxin A chain across membranes is discussed.
Fine-tuning p53 activity through C-terminal modification significantly contributes to HSC homeostasis and mouse radiosensitivity (2011)

Cell cycle regulation in hematopoietic stem cells (HSCs) is tightly controlled during homeostasis and in response to extrinsic stress. p53, a well-known tumor suppressor and transducer of diverse stress signals, has been implicated in maintaining HSC quiescence and self-renewal. However, the mechanisms that control its activity in HSCs, and how p53 activity contributes to HSC cell cycle control, are poorly understood. Here, we use a genetically engineered mouse to show that p53 C-terminal modification is critical for controlling HSC abundance during homeostasis and HSC and progenitor proliferation after irradiation. Preventing p53 C-terminal modification renders mice exquisitely radiosensitive due to defects in HSC/progenitor proliferation, a critical determinant for restoring hematopoiesis after irradiation. We show that fine-tuning the expression levels of the cyclin-dependent kinase inhibitor p21, a p53 target gene, contributes significantly to p53-mediated effects on the hematopoietic system. These results have implications for understanding cell competition in response to stresses involved in stem cell transplantation, recovery from adverse hematologic effects of DNA-damaging cancer therapies, and development of radioprotection strategies.
Effects of eicosapentaenoic and docosahexaenoic acids on apoprotein B mRNA and secretion of very low density lipoprotein in HepG2 cells. (1989)

Oleic acid (18:1n-9, OA), docosahexaenoic acid (22:6n-3, DHA), or eicosapentaenoic acid (20:5n-3, EPA) was added to HepG2 cells at a concentration of 1 mM in a 5:1 or 2:1 molar complex with bovine serum albumin (BSA), and this was incubated for 3 hours. The incorporation of 3H-glycerol into cellular and medium triglyceride (TG), and the mass of TG were measured. The effects of these fatty acids on the secretion of very low density lipoprotein (VLDL) apolipoprotein B (apo B) were estimated from the incorporation of 3H-leucine into the medium apo B in comparison to cells incubated with fatty acid-poor albumin. The secretion of human albumin by the cells was also estimated by immunochemical precipitation of the labeled albumin. In addition, the intracellular levels of apo B messenger ribonucleic acid (mRNA) were measured by the dot-blot hybridization technique. Relative to control cells incubated with BSA, OA (complexed to BSA at a 5:1 molar ratio) stimulated TG synthesis and secretion sevenfold. Compared to OA, EPA was 24% less effective for both processes, whereas DHA inhibited only the secretion of TG (-43%). The secretion of VLDL apo B was not affected by OA, but was decreased 31% by EPA and 54% by DHA. When the molar ratio of fatty acid complexed to albumin was changed to 2:1, similar results were obtained with respect to TG production. The levels of apo B mRNA relative to actin mRNA were not significantly altered by any of the fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)
Technique for the selective heating of corneal stroma (1980)

Conventional thermokeratoplasty, which relies upon thermal conduction from the epithelium into the stroma, does not generate a desirable temperature profile through the cornea. Previous reports show that temperature levels in the epithelium and in Bowman's membrane are excessive, often resulting in damage to these structures. In addition, this study shows that when corneal thickness exceeds approximately 300 microns, the central portion of the stroma probably will not reach critical shrinkage temperature. Shrinkage only in the superficial stroma may result in minimal and transitory alterations of corneal shape. Variation in treatment results may also occur due to the difficulty in precise control of treatment duration. An alternative corneal heating technique is discussed which appears to solve these three basic problems.
Tampering identification using Empirical Frequency Response (2009)

With the widespread popularity of digital images and the presence of easy-to-use image editing software, content integrity can no longer be taken for granted, and there is a strong need for techniques that not only detect the presence of tampering but also identify its type. This paper focusses on tampering-type identification and introduces a new approach based on the empirical frequency response (EFR) to address this problem. We show that several types of tampering operations, both linear shift invariant (LSI) and non-LSI, can be characterized consistently and distinctly by their EFRs. We then extend the approach to estimate the EFR for scenarios where only the final image is available. Theoretical reasoning supported by experimental results verify the effectiveness of this method for identifying the type of a tampering operation.
Antifactor VIII Antibody Inhibiting Allogeneic but not Autologous Factor VIII in Patients With Mild Hemophilia A (1999)

Two unrelated patients with the same Arg2150His mutation in the factor VIII (FVIII) C1 domain, a residual FVIII activity of 0.09 IU/mL, and inhibitor titres of 300 and 6 Bethesda Units, respectively, were studied. Further analysis of patient LE, with the highest inhibitor titer, showed that (1) plasma or polyclonal IgG antibodies prepared from LE plasma inhibited the activity of allogeneic (wild-type) but not of self FVIII; (2) the presence of von Willebrand factor (vWF) increased by over 10-fold the inhibitory activity on wild-type FVIII; (3) the kinetics of FVIII inhibition followed a type II pattern, but in contrast to previously described type II inhibitors, LE IgG was potentiated by the presence of vWF instead of being in competition with it; (4) polyclonal LE IgG recognized the FVIII light chain in enzyme-linked immunosorbent assay and the recombinant A3-C1 domains in an immunoprecipitation assay, indicating that at least part of LE antibodies reacted with the FVIII domain encompassing the mutation site; and (5) LE IgG inhibited FVIII activity by decreasing the rate of FVIIIa release from vWF, but LE IgG recognized an epitope distinct from ESH8, a murine monoclonal antibody exhibiting the same property. We conclude that the present inhibitors are unique in that they clearly distinguish wild-type from self, mutated FVIII. The inhibition of wild-type FVIII by LE antibody is enhanced by vWF and is associated with an antibody-dependent reduced rate of FVIIIa release from vWF.
TGF-β1is a negative regulator of lymphatic regeneration during wound repair (2008)

Although clinical studies have identified scarring/fibrosis as significant risk factors for lymphedema, the mechanisms by which lymphatic repair is impaired remain unknown. Transforming growth factor -beta1 (TGF-beta1) is a critical regulator of tissue fibrosis/scarring and may therefore also play a role in the regulation of lymphatic regeneration. The purpose of this study was therefore to assess the role of TGF-beta1 on scarring/fibrosis and lymphatic regeneration in a mouse tail model. Acute lymphedema was induced in mouse tails by full-thickness skin excision and lymphatic ligation. TGF-beta1 expression and scarring were modulated by repairing the wounds with or without a topical collagen gel. Lymphatic function and histological analyses were performed at various time points. Finally, the effects of TGF-beta1 on lymphatic endothelial cells (LECs) in vitro were evaluated. As a result, the wound repair with collagen gel significantly reduced the expression of TGF-beta1, decreased scarring/fibrosis, and significantly accelerated lymphatic regeneration. The addition of recombinant TGF-beta1 to the collagen gel negated these effects. The improved lymphatic regeneration secondary to TGF-beta1 inhibition was associated with increased infiltration and proliferation of LECs and macrophages. TGF-beta1 caused a dose-dependent significant decrease in cellular proliferation and tubule formation of isolated LECs without changes in the expression of VEGF-C/D. Finally, the increased expression of TGF-beta1 during wound repair resulted in lymphatic fibrosis and the coexpression of alpha-smooth muscle actin and lymphatic vessel endothelial receptor-1 in regenerated lymphatics. In conclusion, the inhibition of TGF-beta1 expression significantly accelerates lymphatic regeneration during wound healing. An increased TGF-beta1 expression inhibits LEC proliferation and function and promotes lymphatic fibrosis. These findings imply that the clinical interventions that diminish TGF-beta1 expression may be useful in promoting more rapid lymphatic regeneration.
Beta-2 Microglobulin Removal during Continuous Ambulatory Peritoneal Dialysis (CAPD) (1989)

Beta-2 microglobulin (B2M) handling in continuous ambulatory peritoneal dialysis (CAPD) was characterized in acute and chronic clinical studies. Average clearance rate was 0.7 mL/min and mean mass transfer coefficient, KoA, was calculated to be 0.95 cm2/min; these values are in the range expected from extrapolation of published data for other large solutes. In chronic studies with both anuric and oliguric populations, CAPD was shown to be much more effective than conventional hemodialysis in removing B2M and, in fact, CAPD removal rates were equivalent to those reported for high flux dialysis therapies. However, this greater extraction was not associated with any clinically significant reduction in circulating plasma concentrations. These trends remained valid in both the anuric and oliguric subsets of the study population.
Fatty acid transporters in animal cells (1997)

The mechanism by which fatty acids transverse the plasma membrane has been a controversial subject. Kinetic studies of fatty acid uptake suggested the presence of a protein carrier system in certain cells which exhibit rapid fatty acid influx and/or efflux such as hepatocytes, adipocytes and jejunal mucosal cells. Five plasma membrane proteins have been identified and proposed as candidates for fatty acid transporters thus far. These includes: Plasma Membrane Fatty Acid Binding Protein (FABPpm), Fatty Acid Translocase (FAT), caveolin, a 56-kDa renal fatty acid binding protein and Fatty Acid Transport Protein (FATP). The first four proteins were identified by classical biochemical techniques while FATP, the one most recently reported, was identified by expression cloning strategies. Each of these proteins has distinct primary amino acid sequence and tissue-specific pattern of expression. It remains to be determined whether the proteins identified to date function as individual polypeptides or as a single component of a larger complex. This review summarizes recent advances concerning the structure, function and regulation of these putative fatty acid transporters.
[Tibial neuromodulation in the treatment of neurogenic detrusor hyperactivity in patients with Parkinson's disease]. (2006)

Twenty nine patients with neurogenic detrusor overactivity due to Parkinson's disease have undergone percutaneous tibial neuromodulation. The treatment consisted of percutaneous insertion of a 34-gauge solid stainless steel needle at a point of 5 cm cephald from the medial malleolus. The patients were treated weekly for 30 minutes. A subjective effect was assessed using a dairy and I-PSS score. Objective results were evaluated by cystometry. We observed a decrease in the average voiding frequency, number of leakage episodes after 12 sessions and 6 months of the tibial neuromodulation. An over 50% symptomatic improvement was achieved in 26 of 29 patients including 6 patients who were refractory to anticholinergic agents and 9 men with benign prostatic hyperplasia. Tibial neuromodulation is an effective treatment in patients with neurogenic detrusor overactivity due to Parkinson's disease.