gebhart/patrepeval huggingface dataset:
Author response: Diabetes regulates fructose absorption through thioredoxin-interacting protein (2016)

Fructose is a type of sugar that is found naturally in fruits, and it is closely related to glucose. The amount of fructose in our diet has increased dramatically in the last few decades. Growing evidence suggests that excessive amounts of fructose contribute to several metabolic diseases, including fatty liver disease and diabetes. Fructose is absorbed in the small intestine via transport proteins called GLUT2 and GLUT5 and then travels to the liver where it can stimulate the cells to make fats. However, it is not clear how fructose uptake is regulated in the small intestine. Glucose is taken into cells by a transport protein that is closely related to GLUT2 and GLUT5. Another protein called thioredoxin-interacting protein (Txnip) interacts with the glucose transporter and regulates glucose uptake. Here, Dotimas et al. investigated whether Txnip also regulates the activities of GLUT2 and GLUT5 to control how cells absorb fructose. Initial experiments in cells showed that Txnip binds to both GLUT2 and GLUT5 and increases the amount of fructose taken up by both mouse and human cells. Cells from mutant mice that do not produce Txnip absorbed less fructose than normal cells did. Furthermore, the mutant mice had lower levels of fructose in the blood and less severe metabolic disease after consuming fructose regularly for six months. Mice with diabetes absorbed more fructose through the small intestine than normal mice, and the loss of Txnip from these mice abolished this effect. Together the findings of Dotimas et al. suggest that Txnip plays an important role in regulating fructose absorption and indicate that, at least in some circumstances, diabetes may lead to more fructose being absorbed in the small intestine. The next steps following on from this work are to understand the molecular details of how Txnip regulates fructose uptake and to determine if other forms of diabetes also show increased fructose uptake.
Binding of NIR-conPK and NIR-6T to Astrocytomas and Microglial Cells: Evidence for a Protein Related to TSPO (2009)

PK 11195 and DAA1106 bind with high-affinity to the translocator protein (TSPO, formerly known as the peripheral benzodiazepine receptor). TSPO expression in glial cells increases in response to cytokines and pathological stimuli. Accordingly, [(11)C]-PK 11195 and [(11)C]-DAA1106 are recognized molecular imaging (MI) agents capable of monitoring changes in TSPO expression occurring in vivo and in response to various neuropathologies.Here we tested the pharmacological characteristics and TSPO-monitoring potential of two novel MI agents: NIR-conPK and NIR-6T. NIR-conPK is an analogue of PK 11195 conjugated to the near-infrared (NIR) emitting fluorophore: IRDye 800CW. NIR-6T is a DAA1106 analogue also conjugated to IRDye 800CW.We found that NIR-6T competed for [(3)H]-PK 11195 binding in astrocytoma cell homogenates with nanomolar affinity, but did not exhibit specific binding in intact astrocytoma cells in culture, indicating that NIR-6T is unlikely to constitute a useful MI agent for monitoring TSPO expression in intact cells. Conversely, we found that NIR-conPK did not compete for [(3)H]-PK 11195 binding in astrocytoma cell homogenate, but exhibited specific binding in intact astrocytoma cells in culture with nanomolar affinity, suggesting that NIR-conPK binds to a protein distinct, but related to, TSPO. Accordingly, treating intact astrocytoma cells and microglia in culture with cytokines led to significant changes in the amount of NIR-conPK specific binding without corresponding change in TSPO expression. Remarkably, the cytokine-induced changes in the protein targeted by NIR-conPK in intact microglia were selective, since IFN-gamma (but not TNFalpha and TGFbeta) increased the amount of NIR-conPK specific binding in these cells.Together these results suggest that NIR-conPK binds to a protein that is related to TSPO, and expressed by astrocytomas and microglia. Our results also suggest that the expression of this protein is increased by specific cytokines, and thus allows for the monitoring of a particular subtype of microglia activation.
Peroxiredoxin-4 and Dopamine D5 Receptor Interact to Reduce Oxidative Stress and Inflammation in the Kidney (2022)

<b><i>Aims:</i></b> Reactive oxygen species are highly reactive molecules generated in different subcellular compartments. Both the dopamine D5 receptor (D<sub>5</sub>R) and endoplasmic reticulum (ER)-resident peroxiredoxin-4 (PRDX4) play protective roles against oxidative stress. This study is aimed at investigating the interaction between PRDX4 and D<sub>5</sub>R in regulating oxidative stress in the kidney. <b><i>Results:</i></b> Fenoldopam (FEN), a D<sub>1</sub>R and D<sub>5</sub>R agonist, increased PRDX4 protein expression, mainly in non-lipid rafts, in D<sub>5</sub>R-HEK 293 cells. FEN increased the co-immunoprecipitation of D<sub>5</sub>R and PRDX4 and their colocalization, particularly in the ER. The efficiency of Förster resonance energy transfer was increased with FEN treatment measured with fluorescence lifetime imaging microscopy. Silencing of <i>PRDX4</i> increased hydrogen peroxide production, impaired the inhibitory effect of FEN on hydrogen peroxide production, and increased the production of interleukin-1β, tumor necrosis factor (TNF), and caspase-12 in renal cells. Furthermore, in <i>Drd5</i><sup>-/-</sup> mice, which are in a state of oxidative stress, renal cortical PRDX4 was decreased whereas interleukin-1β, TNF, and caspase-12 were increased, relative to their normotensive wild-type <i>Drd5</i><sup>+/+</sup> littermates. <b><i>Innovation:</i></b> Our findings demonstrate a novel relationship between D<sub>5</sub>R and PRDX4 and the consequent effects of this relationship in attenuating hydrogen peroxide production in the ER and the production of proinflammatory cytokines. This study provides the potential for the development of biomarkers and new therapeutics for renal inflammatory disorders, including hypertension. <b><i>Conclusion:</i></b> PRDX4 interacts with D<sub>5</sub>R to decrease oxidative stress and inflammation in renal cells that may have the potential for translational significance. <i>Antioxid. Redox Signal</i>. 38, 1150-1166.
A phase II trial of bryostatin 1 in patients with non-Hodgkin's lymphoma (2001)

Bryostatin 1 is a naturally occurring macrocyclic lactone with promising antitumour and immunomodulatory function in preclinical and phase I clinical investigations. In this phase II study, 17 patients with progressive non-Hodgkin's lymphoma of indolent type (NHL), previously treated with chemotherapy, received a median of 6 (range 1-9) intravenous infusions of 25 microg/m(2) bryostatin 1 given once weekly over 24 hours. In 14 evaluable patients no responses were seen. Stable disease was attained in one patient for 9 months. The principal toxicities were myalgia and phlebitis. Treatment was discontinued early because of toxicity alone (phlebitis) in 2 patients, toxicity in addition to progressive disease in 3 patients (myalgia and phlebitis n = 2; thrombocytopenia n = 1) and progressive disease in 5 patients. The results fail to demonstrate efficacy of this regimen of bryostatin 1 in the treatment of NHL. In light of preclinical data that demonstrate synergy between bryostatin 1 and several cytotoxic agents and cytokines, clinical studies to investigate bryostatin 1 in combination are warranted. We also present data to demonstrate that central venous lines may be used in future studies to avoid phlebitis.
Optically Transparent Wood Substrate for Perovskite Solar Cells (2019)

Transparent wood is a candidate for use as an energy-saving building material due to its low density (ca. 1.2 g/cm<sup>3</sup>), high optical transmittance (over 85% at 1 mm thickness), low thermal conductivity (0.23 W m<sup>-1</sup> K<sup>-1</sup>), and good load-bearing performance with tough failure behavior (no shattering). High optical transmittance also makes transparent wood a candidate for optoelectronic devices. In this work, for the first time, perovskite solar cells processed at low temperature (<150 °C) were successfully assembled directly on transparent wood substrates. A power conversion efficiency up to 16.8% was obtained. The technologies demonstrated may pave the way for integration of solar cells with light transmitting wood building structures for energy-saving purposes.
Genome-Wide Copy Number Variation Analysis in Extended Families and Unrelated Individuals Characterized for Musical Aptitude and Creativity in Music (2013)

Music perception and practice represent complex cognitive functions of the human brain. Recently, evidence for the molecular genetic background of music related phenotypes has been obtained. In order to further elucidate the molecular background of musical phenotypes we analyzed genome wide copy number variations (CNVs) in five extended pedigrees and in 172 unrelated subjects characterized for musical aptitude and creative functions in music. Musical aptitude was defined by combination of the scores of three music tests (COMB scores): auditory structuring ability, Seashores test for pitch and for time. Data on creativity in music (herein composing, improvising and/or arranging music) was surveyed using a web-based questionnaire.Several CNVRs containing genes that affect neurodevelopment, learning and memory were detected. A deletion at 5q31.1 covering the protocadherin-α gene cluster (Pcdha 1-9) was found co-segregating with low music test scores (COMB) in both sample sets. Pcdha is involved in neural migration, differentiation and synaptogenesis. Creativity in music was found to co-segregate with a duplication covering glucose mutarotase gene (GALM) at 2p22. GALM has influence on serotonin release and membrane trafficking of the human serotonin transporter. Interestingly, genes related to serotonergic systems have been shown to associate not only with psychiatric disorders but also with creativity and music perception. Both, Pcdha and GALM, are related to the serotonergic systems influencing cognitive and motor functions, important for music perception and practice. Finally, a 1.3 Mb duplication was identified in a subject with low COMB scores in the region previously linked with absolute pitch (AP) at 8q24. No differences in the CNV burden was detected among the high/low music test scores or creative/non-creative groups. In summary, CNVs and genes found in this study are related to cognitive functions. Our result suggests new candidate genes for music perception related traits and supports the previous results from AP study.
Prospects of Neurotrophic Factors for Parkinson's Disease: Comparison of Protein and Gene Therapy (2015)

Neurotrophic factors (NTFs) hold great potential as therapeutic agents in the treatment of neurodegenerative conditions, including Parkinson's disease (PD), in which the progressive loss of dopamine neurons in the substantia nigra pars compacta causes severe motor symptoms. There is extensive evidence that in preclinical animal models of PD NTFs are both neuroprotective and neurorestorative. In particular, glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), cerebral dopamine neurotrophic factor, and mesencephalic astrocyte-derived neurotrophic factor have shown great potential to restore dopamine neurocircuitry. Although some previous clinical trials have demonstrated limited efficacy of GDNF and NRTN, there are several concerns raised with these studies. Moreover, open-label studies with GDNF as well as a study with NRTN showed clinical improvement, particularly in patients with early-stage PD. Indeed, as previous clinical trials with NTFs were associated with several technical problems, there is a great need for further investigations. In this review we discuss the emerging and existing possibilities to use NTFs as neurorestorative agents and the ways to improve their efficacy, and compare gene therapy and recombinant protein therapy approaches for restoring the dopamine circuitry in PD.
Particle dynamics predicts shear rheology of soft particle glasses (2020)

Soft particle glasses are amorphous materials made of soft and deformable particles that are jammed above close-packing. They behave like weak solids at rest, but they yield and flow under external mechanical constraints. Although soft particle glasses are widely used in applications, little is known about how the particle softness and microscopic dynamics determine the macroscopic rheology. Here, we use three-dimensional particle dynamic simulations to analyze the dynamical properties of soft particle glasses at different scales. We demonstrate how the dynamics is determined by the persistence time and the magnitude of the fluctuating elastic forces that develop at contact in the flow. The shear-induced diffusion coefficient, the local structural relaxation times, the shear stress, and the normal stress differences are interconnected through simple relationships that allow the prediction of the macroscopic rheology from the microscopic dynamics.
Ultra-flat dispersion in an integrated waveguide with five and six zero-dispersion wavelengths for mid-infrared photonics (2019)

We propose a new type of dispersion flattening technology, which can generate an ultra-flat group velocity dispersion profile with five and six zero-dispersion wavelengths (ZDWs). The dispersion value varies from −0.15 to 0.35 ps/(nm·km) from 4 to 8 μm, which to the best of our knowledge is the flattest one reported so far, and the dispersion flatness is improved by more than an order of magnitude. We explain the principle of producing six ZDWs. Mode distribution in this waveguide is made stable over a wide bandwidth. General guidelines to systematically control the dispersion value, sign, and slope are provided, and one can achieve the desired dispersion by properly adjusting the structural parameters. Fabrication tolerance of this waveguide is also examined.
Coaxial tip piezoresistive scanning probes with sub-nanometer vertical displacement resolution (2010)

We present the design and fabrication of an improved probe for scanning gate microscopy (SGM). Like our previously reported design, the new probe integrates a coaxial tip to produce highly localized electric fields and a piezoresistor to self-sense tip deflection. However, the new design achieves a vertical displacement resolution of 3.7 Å in a 10 kHz bandwidth, enabling the study of both topography and electron organization of semiconductor nanostructures with sub-nanometer features. The design is based on a numerical optimizer for force-sensing piezoresistive cantilevers, which we have extended for SGM.
Supplementary Table 4 from Elimination of IL-10–Inducing T-Helper Epitopes from an IGFBP-2 Vaccine Ensures Potent Antitumor Activity (2023)

&lt;p&gt;PDF file - 51KB, Human protein sequence homologies for IGFBP-2 C-terminus.&lt;/p&gt;
Advanced Dynamical Models for Escalators Simulation (2008)

In this paper are described the dynamical models developed for the analysis of the solutions for new escalator designs. The current escalator design is an evolution of a very ancient one that has gone adding improvements along the time. But actually, new solutions are searching for a cheaper, safer and more reliable escalator design. For this task the models here described constitute a necessary tool in order to test series of new design ideas in a quick way. With the dynamical models is easy to obtain values of tension, reaction, velocities, etc. before building the physical escalator and therefore deduce the best solution. For a more efficient results analysis a statistical procedure has been developed that guide the improving trajectory.
Citrus fruit bitter flavors: isolation and functional characterization of the gene Cm1,2RhaT encoding a 1,2 rhamnosyltransferase, a key enzyme in the biosynthesis of the bitter flavonoids of citrus (2004)

Species of the genus Citrus accumulate large quantities of flavanones that affect fruit flavor and have been documented to benefit human health. Bitter species, such as grapefruit and pummelo, accumulate bitter flavanone-7-O-neohesperidosides responsible, in part, for their characteristic taste. Non-bitter species, such as mandarin and orange, accumulate only tasteless flavanone-7-O-rutinosides. The key flavor-determining step of citrus flavanone-glycoside biosynthesis is catalyzed by rhamnosyltransferases; 1,2 rhamnosyltransferases (1,2RhaT) catalyze biosynthesis of the bitter neohesperidosides, while 1,6 rhamnosyltransferases (1,6RhaT) catalyze biosynthesis of the tasteless rutinosides. We report on the isolation and functional characterization of the gene Cm1,2RhaT from pummelo which encodes a citrus 1,2RhaT. Functional analysis of Cm1,2RhaT recombinant enzyme was conducted by biotransformation of the substrates using transgenic plant cell culture. Flavanones and flavones, but not flavonols, were biotransformed into 7-O-neohesperidosides by the transgenic BY2 tobacco cells expressing recombinant Cm1,2RhaT. Immunoblot analysis established that 1,2RhaT protein was expressed only in the bitter citrus species and that 1,6RhaT enzyme, whose activity was previously documented in non-bitter species, was not cross-reactive. Expression of Cm1,2RhaT at the RNA level was prominent in young fruit and leaves, but low in the corresponding mature tissue, thus correlating well with the developmental pattern of accumulation of flavanone-neohesperidosides previously established. Phylogenetic analysis of the flavonoid glycosyltransferase gene family places Cm1,2RhaT on a separate gene cluster together with the only other functionally characterized flavonoid-glucoside rhamnosyltransferase gene, suggesting a common evolutionary origin for rhamnosyltransferases specializing in glycosylation of the sugar moieties of flavonoid glucosides.
Tunable narrow linewidth chip-scale mid-IR laser (2021)

Portable mid-infrared (mid-IR) spectroscopy and sensing applications require widely tunable, narrow linewidth, chip-scale, single-mode sources without sacrificing significant output power. However, no such lasers have been demonstrated beyond 3 $μ$m due to the challenge of building tunable, high quality-factor (Q) on-chip cavities. We demonstrate a tunable, single-mode mid-IR laser at 3.4 $μ$m using a high-Q silicon microring cavity with integrated heaters and a multi-mode Interband Cascade Laser (ICL). We show that the multiple longitudinal modes of an ICL collapse into a single frequency via self-injection locking with an output power of 0.4 mW and achieve an oxide-clad high confinement waveguide microresonator with a loaded Q of $2.8\times 10^5$. Using integrated microheaters, our laser exhibits a wide tuning range of 54 nm at 3.4 $μ$m with 3 dB output power variation. We further measure an upper-bound effective linewidth of 9.1 MHz from the locked laser using a scanning Fabry-Perot interferometer. Our design of a single-mode laser based on a tunable high-Q microresonator can be expanded to quantum-cascade lasers at higher wavelengths and lead to the development of compact, portable, high-performance mid-IR sensors for spectroscopic and sensing applications.
Retinal Oximetry Using Intravitreal Illumination (2006)

Retinal oximetry using intravitreal illumination has been demonstrated. As a research tool, intravitreal illumination addresses several difficulties encountered when performing retinal oximetry with transcorneal illumination.
Characteristics and Durability of Water Hydraulic Cylinders (2017)

Durability tests of two water hydraulic cylinders with different surface roughness are made. The piston diameter, rod diameter and stroke of the test cylinders are 50 mm, 28 mm, and 250 mm, respectively. Each test cylinder is operated at a velocity of 0.25 m/s under a supply pressure of about 10.5 MPa by an electro-oil hydraulic servo cylinder which is placed in alignment with the test cylinder. The variations of friction characteristic, low speed performance, leakage characteristic of each test cylinder with operating distance are measured until 300 km operation. Friction force decreases at first with increasing operating distance and then becomes an almost constant value. No negative resistance characteristic is observed at low velocities. Both test cylinders can move very smoothly at velocities lower than 0.1 mm/s without stick-slip irrespective of the magnitude of surface roughness. Leakage flow rate tends to increase with increasing operating distance and surface roughness.
Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers (2023)

&lt;p&gt;(A) In vivo primary human colorectal xenograft model HCOX4087 treated with trametinib (0.3 mg/kg QD), SHP099 (100 mg/kg QD), and a pan-RTK inhibitor, Dovitinib (100 mg/kg QD). (B-C) In vivo efficacy of selective VEGFR2 inhibitor, BFH772 (3 mg/kg QD) in MIA PaCA-2 and T3M-4 cells implanted subcutaneously. Data plotted are tumor volume means {plus minus} s.e.m (T3M-4, n=8. MIA PaCA-2, n=7) (D) Evaluation of SHP099 in firefly- luciferase labeled MIA PaCa-2 pancreatic cells implanted surgically into the mouse pancreas. Data plotted are mean bioluminescent signal (BLI) {plus minus} s.e.m (n=6). (E-F) Immunoblot of SHP2 and soft agar assay with MIA Paca-2 cells with Dox-inducible shRNA targeting SHP2 or control non-targeting shRNA after Dox treatment. (G) In vivo SHP2 expression levels evaluated by Western blot and levels of MAPK pathway suppression by DUSP6, 3 hours after the last dose of SHP099 from MIA PaCa-2 tumors in Fig. 4F (n=3).&lt;/p&gt;
Gender difference in levels of Cu/Zn superoxide dismutase (SOD1) in cerebrospinal fluid of patients with amyotrophic lateral sclerosis (2008)

Currently the best studied mechanism for amyotrophic lateral sclerosis (ALS) is the one caused by mutations in the gene for cytosolic Cu/Zn-binding superoxide dismutase (SOD1). Mutant SOD1 protein causes motor neuron degeneration due to the gain of a novel toxic function. To evaluate the relevance of SOD1 levels in cerebrospinal fluid (CSF) in ALS patients, the SOD1 concentration was immunoassayed in the CSF of 11 patients with ALS and 19 neurological controls. The mean level of SOD1 in CSF from all samples was 45.5+/-11.3 ng/ml. There was no statistically significant difference between the levels of SOD1 in CSF of ALS patients and neurological control subjects. Here we show that the SOD1 concentration in the CSF is significantly higher in male ALS patients (54.0+/-9.0 ng/ml) compared to female ALS patients (38.1+/-6.4 ng/ml) (p=0.007). This gender difference is not observed in the CSF of neurological controls. This is the first report of a potential gender difference in levels of SOD1 in CSF of ALS patients. Further investigation of larger sample groups is needed to determine whether it is relevant to gender related differences in disease incidence.