gebhart/patrepeval huggingface dataset:
TCF7L2 transcription factor and Type 2 Diabetes: we WNT to know (2013)

Most studies on TCF7L2 SNP variants in the pathogenesis of type 2 diabetes (T2D) focus on a role of the Wnt signaling transcription factor Tcf7l2 in beta cells. Diabetes is characterized by loss or dysfunction of beta cells. A major goal of diabetes therapy is to promote the formation of new beta cells. Here, we provide evidence for a role of TCF7L2 in beta cell proliferation and regeneration. First, the results that the zebrafish Tcf7l2 gene is expressed in intestinal endocrine cells but also in pancreas suggest a possible effects on beta cell growth, differentiation or regeneration from the precursor/stem cells. We observe a phenotypic defect in Tcf7l2 mutant larvae with transgenic backgrounds fli1:eGFP/ins:dsRED, when analyzed at 3 weeks post-fertilization. Confocal microscopy of transgenic ins:dsRED/Tcf7l2 mutants demonstrate a reduction in the number of beta cells, and the analysis of transgenic fli1:eGFP/ins:dsRED/Tcf7l2 mutants show morphological changes with a reduction in the number and diameter of pancreatic islet capillaries observed under confocal microscope and measured quantitatively. Furthermore, Tcf7l2 mutants show a loss of proliferation in endothelial and beta cells, when examined with an H2B-RFP fusion protein. We show that the Tcf7l2 mutant is a suitable model for the study of T2D in zebrafish, in applications such as: a) measurement of blood glucose level, a commonly used method for assessing beta cell function; b) regeneration of tail fin and beta cells. The extensive evaluation of Tcf7l2 function and Wnt signaling effects in beta cells have resulted in contradictory findings. Indeed, the transgenic biosensor generated by Moro et al. shows a Wnt signaling activity in a wide range of tissues but not in beta cells. Our results show no alteration in the number of beta cells in transgenic embryos ins:dsRED when treated with BIO (an activator of Wnt signaling) and Xav (an inhibitor of Wnt signaling) compared to untreated control. Here, we describe the generation, validation and applications of a transgenic reporter line for Wnt/β-catenin signaling in beta cells, and show that it is a reliable and sensitive Wnt biosensor for in vivo studies in the pancreas. The responsiveness of the reporter to Wnt signaling and the resulting increased number of beta cells was tested by treating embryos with BIO and XAV and observing the reporter activity, which is respectively increased or decreased compared to untreated controls. In conclusion, these data highlight the Tcf7l2 mutant as a novel model organism to analyze diabetic complications. Therefore, the model presented here will allow exploring molecular mechanisms by which Tcf7l2, as a component of the Wnt signaling pathway, exerts its physiological functions in diabetic pathology.
Identification of a Key Residue Mediating Bone Morphogenetic Protein (BMP)-6 Resistance to Noggin Inhibition Allows for Engineered BMPs with Superior Agonist Activity (2010)

Bone morphogenetic proteins (BMPs) are used clinically to induce new bone formation in spinal fusions and long bone non-union fractures. However, large amounts of BMPs are needed to achieve these effects. BMPs were found to increase the expression of antagonists, which potentially limit their therapeutic efficacy. However, the relative susceptibility of osteoinductive BMPs to different antagonists is not well characterized. Here we show that BMP-6 is more resistant to noggin inhibition and more potent in promoting osteoblast differentiation in vitro and inducing bone regeneration in vivo when compared with its closely related BMP-7 paralog. Noggin was found to play a critical role as a negative feedback regulator of BMP-7 but not BMP-6-induced biological responses. Using BMP-6/7 chimeras, we identified lysine 60 as a key residue conferring noggin resistance within the BMP-6 protein. A remarkable correlation was found between the presence of a lysine at this position and noggin resistance among a panel of osteoinductive BMPs. Introduction of a lysine residue at the corresponding positions of BMP-2 and BMP-7 allowed for molecular engineering of recombinant BMPs with increased resistance to noggin antagonism.
Supplementary Data 1 from <i>LOXL1</i> and <i>LOXL4</i> Are Epigenetically Silenced and Can Inhibit Ras/Extracellular Signal-Regulated Kinase Signaling Pathway in Human Bladder Cancer (2023)

Supplementary Data 1 from &lt;i&gt;LOXL1&lt;/i&gt; and &lt;i&gt;LOXL4&lt;/i&gt; Are Epigenetically Silenced and Can Inhibit Ras/Extracellular Signal-Regulated Kinase Signaling Pathway in Human Bladder Cancer
Development and First Application of Bistable Expandable Sand Screen (2003)

Abstract Sand control in an open hole typically results in risky completions, especially in weak or unconsolidated formations. Stand-alone screen completions present the risk of wellbore collapse and screen erosion, while gravel packing involves time-consuming and complicated pumping operations. Although expandable sand screens have recently become available to provide the best of both worlds, fast installation and wellbore support, design constraints limit their application. Wellbore conformance, expansion loads, and connection integrity have been critical issues with these types of screens. Where successful applications have been found, improved production with lowered drawdown have been typical. Extensive research and finite element analysis have led to the development of bistable expansion cells. These cells have minimal plastic deformation during expansion and exhibit a hysteresis -like behavior. The specific cut pattern can open with relatively low expansion force, and then resist higher-level collapse loads. Due to the low plastic strain levels, bistable cells are compatible with any common oilfield material, achieving expansion ratios as high as 1.6 times the original screen diameter. This paper will cover the design, development, and testing of an expandable sand screen using bistable cell technology. In addition, the design and development of the proprietary expandable connection will be presented. The testing presented covers a wide range of structural integrity, expansion, sand retention, mudflow, and geomechanical tests performed on the screen, base pipe, and connection. In late 2002, the first bistable expandable sand screen was deployed in a 4,400-ft water injection well in west Texas. The compliant expansion tool deployed the screen in one trip at speeds exceeding 1,800 feet per hour with set-down loads of less than 20,000 pounds.
Optical Quality and Depth-of-field of Eyes Implanted With Spherical and Aspheric Intraocular Lenses (2005)

Our study shows a good degree of compensation of the corneal spherical aberration in eyes implanted with aspheric IOLs, as opposed to eyes implanted with spherical IOLs. Other sources of optical degradation, both with aspheric and spherical IOLs, are non-symmetric preoperative corneal aberrations, incision-induced aberrations, and third order internal aberrations. Although best corrected optical quality is significantly better with aspheric IOLs, tolerance to defocus tended to be lower.
The reversible macrocyclization of Tyrocidine A aldehyde: a hemiaminal reminiscent of the tetrahedral intermediate of macrolactamization (2009)

In spite of the important role of peptide macrocyclizations for the generation of conformationally constrained biological ligands, our knowledge of factors that determine the inclination of a substrate to cyclize is low. Therefore, methods that give access to the thermodynamic characterization of these processes are desirable. In this work, we present the isosteric substitution of the amide ligation site of a cyclopeptide by an imine. Applied to the decapeptide antibiotic Tyrocidine A (TycA), the reversible cyclization of the linear aldehyde TycA-CHO resulted in the unexpectedly stable hemiaminal Psi[CH(OH)NH]-TycA, which is equivalent to the tetrahedral intermediate of macrolactamization, and which is observed for the first time in a peptidic structure. On the basis of NMR spectroscopy and molecular modeling, we discuss the observed high stereoselectivity of hemiaminal formation, as well as its reluctance to be dehydrated to the imine. As required for thermodynamic analysis, it is possible to establish a pH- and temperature-dependent cyclization equilibrium, which allows determination of the entropy loss of the peptide chain, and quantification of the extent of preorientation of the cyclization precursor.
Target-tracking deliveries on an Elekta linac: a feasibility study (2009)

A target-tracking, intensity-modulated delivery on an Elekta MLCi system was assessed by film measurement with a simulated target-motion trajectory. A toroidally shaped idealized target surrounding an organ at risk necessitating multiple field segments to irradiate the target and spare the organ at risk was defined in a solid-water phantom. The phantom was programmed to move following a reproducible 2D elliptical trajectory in the beam's-eye view with a period of 10 s. Static and target-tracking treatments were planned for delivery on a standard Elekta Precise series linac with integrated MLCi system. Dose was delivered in three ways: (i) a static treatment to a static phantom, (ii) a static treatment to a moving phantom and (iii) a target-tracking treatment to a moving phantom. The dose delivered was assessed by film measurement on the central plane through the target and organ at risk. The target dose blurring was quantified by the standard deviation of the dose to the target which was evaluated as 2.8% for the static treatment to the static phantom, 7.2% for the static treatment to the moving phantom and 2.6% for the tracking treatment to the moving phantom. The mean organ-at-risk dose was 38.2%, 54.0% and 38.2% of the prescription dose for each delivery case. We have therefore shown that the linac is capable of delivering target-tracking fields with MLCs for the target trajectories tested.
Surgical Technique and Clinically Relevant Resection Cavity Dynamics Following Implantation of Cesium-131 Brachytherapy in Patients With Brain Metastases (2015)

Cs-131 patients exhibited significantly less cavity shrinkage than SRS patients during the first critical month with 88% Cs-131 dose delivery. This significant difference in shrinkage suggests that the intracavitary seeds-on-a-string technique facilitates increased cavity stability, promoting more homogenous dose delivery.
390 THE EFFECT OF CHRONIC HYPERINSULINEMIA ON CORONARY ARTERIES IN NONTRANSPLANT DOG MODEL (2005)

Manuscript Submission Guidelines: Journal if Investigative Medicine (JIM) This Journal recommends that authors follow the Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals formulated by the International Committee of Medical Journal Editors (ICMJE). Please read the guidelines below and then visit the Journal’s submission
Tachykinin receptor antagonists in irritable bowel syndrome. (2002)

Tachykinins (TKs) are abundantly expressed in the gastrointestinal (GI) tract in intrinsic excitatory motor neurons, interneurons, sensory neurons and extrinsic sensory neurons. Their role in the regulation of enteric secretomotor functions is well established, especially following pathophysiological stimuli. Recent evidence emphasizes the role of TKs in the sensitization of peripheral branches of visceral afferent neurons, implying a role in determining visceral hypersensitivity. Furthermore, the involvement of both CNS and peripheral TK receptors in autonomic reactions to stress, render these receptors an appealing target for the development of drugs aimed at the treatment of irritable bowel syndrome (IBS), a functional GI disorder. The available preclinical evidence indicates that TK receptor antagonists could normalize motor disturbance (diarrhea and constipation) and reduce the painful symptoms that characterize IBS.
Thermal Study in Solid State of Zn(II)‐Diclofenac Complex: Behavior Kinetic of the Dehydration, Transition Phase and Thermal Decomposition (2010)

Abstract The dehydration, thermal decomposition and transition phase stage of Zn(II)‐diclofenac compound were studied by simultaneous TG‐DTA and DSC techniques. The TG and DSC curves of this compound were obtained with the mass of sample of 2 and 5 mg. Additionally, DSC curves were carried out in opened and closed α‐alumina pans under static and nitrogen atmosphere. The DTA and DSC curves show that this compound possesses exothermic transition phase between 170‐180 °C, which it is irreversible (monotropic reaction). The kinetics study of this transition phase stage was evaluated by DSC under non‐isothermal conditions. The obtained data were evaluated with the isoconversional method, where the values of activation energy (E a / kJ mol −1 ) was plotted in function of the conversion degree (α). The results show that due to mass sample, different activation energies were obtained. From these curves a tendency can be seen where the plots maintain the same profile for closed lids and almost run parallel to each other.
Solar-Reflective “Cool” Walls: Benefits, Technologies, and Implementation Final Project Report (2019)

Raising the albedo (solar reflectance) of a building’s walls reduces unwanted solar heat gain in the cooling season. This saves electricity and lowers peak power demand by decreasing the need for air conditioning. It can also cool the outside air, which can mitigate the urban heat island effect and also improve air quality by slowing the reactions that produce smog. This project quantified the energy savings, peak demand reduction, urban cooling, and air quality improvements attainable from solar-reflective “cool” walls in California; collaborated with industry to assess the performance of existing cool-wall technologies, and to develop innovative cool-wall solutions; and worked with state and federal government agencies, utilities, and industry to create a cool-wall infrastructure, including application guidelines, a product rating program, incentives, and building code credits. Simulations indicate that cool walls provide annual energy savings, peak demand reduction, annual emission reduction, and summer heat island mitigation benefits comparable to those yielded by cool roofs, and are helpful across California and in most of the southern half of the United States (that is, in U.S. climate zones 1—4). Natural exposure trials conducted at three sites in California and another three sites across the United States indicate that cool-wall materials tend to stay clean and reflective. Significant advances were made in novel cool-wall technologies, such as fluorescent cool pigments that expand the color palette for cool-wall products. We prepared guidelines for the climate- and building-appropriate use of cool walls, convened a stakeholder workshop, and created a working group. Ongoing efforts seek to introduce or expand cool-wall provisions in building energy standards, green building programs, and energy efficiency incentive programs, and to develop a cool-wall product rating system.
Elementally Resolved Dissolution Kinetics of a Ni-Fe-Cr-Mn-Co Multi-Principal Element Alloy in Sulfuric Acid Using AESEC-EIS (2022)

Atomic emission spectroelectrochemistry (AESEC) combined with linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) provided insights on both active and passive dissolution of Ni-Fe-Cr-Mn-Co multi-principal element alloy. Elemental dissolution rates measured by AESEC during open circuit experiment were in agreement with those extrapolated from AESEC-LSV and indicated element-specific dissolution tendencies. AESEC-EIS at open circuit potential showed nearly in-phase elemental dissolution during potential modulation which suggests direct dissolution from the alloy surface to the electrolyte. In the passive potential domain, no oscillation of the elemental dissolution rate was detected by AESEC-EIS, suggesting non-oxidative chemical dissolution of the outer layer of the passive film. In this case, dissolution at the passive film/electrolyte interface was equal to the metal oxidation rate (passive current density) at the metal/passive film interface and the passive current density was independent of potential.
Transient and Prolonged Increase in Endothelial Permeability Induced by Histamine and Thrombin (1998)

In the present study, we differentiated between short- and long-term effects of vasoactive compounds on human endothelial permeability in an in vitro model. Histamine induced a rapid and transient (<3 minutes) decrease in barrier function, as evidenced by a decreased transendothelial electrical resistance and an increased passage of 22Na ions. This increase in permeability was inhibited completely by chelation of intracellular calcium ions by BAPTA-AM and inhibition of calmodulin activity and myosin light chain (MLC) phosphorylation. The presence of serum factors prolonged the barrier dysfunction induced by histamine. Thrombin by itself induced a prolonged barrier dysfunction (>30 minutes) as evidenced by an increased passage of peroxidase and 40 kDa dextran. It was dependent only partially on calcium ions and calmodulin. The protein tyrosine kinase inhibitors genistein and herbimycin A, but not the inactive analogue daidzein, inhibited to a large extent the increase in permeability induced by thrombin. Genistein and BAPTA-AM inhibited the thrombin-induced permeability in an additive way, causing together an almost complete prevention of the thrombin-induced increase in permeability. Inhibition of protein tyrosine kinase was accompanied by a decrease in MLC phosphorylation and a reduction in the extent of F-actin fiber and focal attachment formation. Inhibition of RhoA by C3 transferase toxin reduced both the thrombin-induced barrier dysfunction and MLC phosphorylation. Genistein and C3 transferase toxin did not elevate the cellular cAMP levels. No evidence was found for a significant role of protein kinase C in the thrombin-induced increase in permeability or in the accompanying MLC phosphorylation. These data indicate that in endothelial cell monolayers that respond to histamine in a physiological way, thrombin induces a prolonged increase in permeability by "calcium sensitization," which involves protein tyrosine phosphorylation and RhoA activation.
A scalable content-addressable network (2001)

Hash tables - which map "keys" onto "values" - are an essential building block in modern software systems. We believe a similar functionality would be equally valuable to large distributed systems. In this paper, we introduce the concept of a Content-Addressable Network (CAN) as a distributed infrastructure that provides hash table-like functionality on Internet-like scales. The CAN is scalable, fault-tolerant and completely self-organizing, and we demonstrate its scalability, robustness and low-latency properties through simulation.
Second-order time integration of the wave equation with dispersion correction procedures (2019)

Second-order time integration of the wave equation is numerically efficient with time steps close to the limit set by the stability criterion. However, dispersion errors over realistic propagation distances are unacceptable with time steps in this range. Dispersion-free results, using second-order time integration of the wave equation, can be achieved by applying a time-domain prepropagation filter to all source time functions followed by a time-domain postpropagation filter applied to the simulated wavefield at all recording positions. The time-domain implementation of the filtering process is an order of magnitude more effective, in terms of CPU time, compared to an implementation via discrete and fast Fourier transforms. Pre- and postpropagation filters are valid for any simulation time step. The two filters can be calculated once because they are independent of the simulation time step, and they can be applied with any modeling scheme that uses second-order time integration. Second-order time integration results in traveltime and amplitude errors. The amplitude errors depend on the spatial source distribution. The combined application of the two filters removes traveltime-related errors and amplitude-related errors independently of the spatial source distribution.
Stage-by-stage detection of distributed space-time block encoded relaying networks (2005)

Distributed multi-hop communication systems have been introduced recently which allow the application of multiple-input-multiple-output (MIMO) capacity enhancement techniques over spatially separated relaying mobile terminals. They were shown to yield significant capacity gains over direct communication or non-distributed single-input-single-output (SlSO) relaying networks. The contribution of This work is the derivation of throughput-maximising resource allocation strategies in terms of fractional frame duration and transmission power. It is assumed that distributed terminals cooperate at each relaying stage and that the detection of packets is performed at each relaying stage.
Comparison of Enhanced Potency Inactivated Poliovirus Vaccine (EIPV) Versus Standard Oral Poliovirus Vaccine (OPV) in Thai Infants (1994)

Enhanced potency inactivated poliovirus vaccine (EIPV), combined with diphtheria-tetanus-pertussis (DTP) vaccine, was compared with oral poliovirus vaccine (OPV) regarding immunogenicity in Thai infants, vaccinated at 2, 4 and 6 months of age. EIPV induced significantly higher seroconversion rates than OPV to all 3 poliovirus types after the second and third immunization. After 3 doses of each vaccine, at 7 months of age, all infants receiving EIPV proved seropositive for poliovirus type 1, type 2 and type 3 neutralizing antibodies, whereas of those receiving OPV, 9% remained seronegative (titre < 1:4) for type 1 (p = 0.0042) and 11% for type 3 (p = 0.0013). All participating children were given an additional dose of OPV at the age of 9 months and tested again at 12 months of age. At that point, virtually all infants had poliovirus neutralizing antibodies, but the geometric mean titres to each poliovirus type were significantly higher in the vaccinees who had received EIPV. It is concluded that the greater immunogenicity of EIPV vis-à-vis 3 doses of OPV may be biologically significant for protection against poliovirus types 1 and 3 in countries where cases of poliomyelitis occur in young children. These findings warrant considering EIPV, alone or in combination with OPV, for an immunization programme in Thailand and similar countries in the future.
A Review of: “Augmentation of Landsat MSS Data by Seasat SAR Imagery for Agricultural Inventories.” By D. R. NÜESCH. (Zürich: University of Zürich, Remote Sensing Series, Vol. 7, 1982. [Pp. 106,] Price SFr. 30.00 (paperback). (1983)

(1983). A Review of: “Augmentation of Landsat MSS Data by Seasat SAR Imagery for Agricultural Inventories.” By D. R. NUESCH. (Zurich: University of Zurich, Remote Sensing Series, Vol. 7, 1982. [Pp. 106,] Price SFr. 30.00 (paperback). International Journal of Remote Sensing: Vol. 4, No. 2, pp. 479-479.