gebhart/patrepeval huggingface dataset:
A specific substrate from rabbit cerebellum for guanosine-3‘:5‘-monophosphate-dependent protein kinase. III. Amino acid sequences at the two phosphorylation sites. (1981)

G-substrate is a protein present in cerebellum which is a major endogenous substrate for cyclic GMP-dependent protein kinase, and one of the few known proteins phosphorylated more effectively by cyclic GMP-dependent protein kinase than by cyclic AMP-dependent protein kinase. G-substrate has been shown to be phosphorylated on two threonine residues, and the amino acid sequences surrounding these sites, which correspond to about 30% of the primary structure, are: Leu-Asn-Val-Glu-Ser-Asp-Gln-Lys-Lys-Pro-Arg-Arg-Lys-Asp-Thr(P)-Pro-Ala-Leu-His- Ile-Pro-Pro-Phe-Ile-Ser-Gly-Val-Ile-Ser-Gln-Asn SITE 1 Leu-His-Asn-Thr-Asp-Leu-Glu-Gln-Gln-Lys-Pro-Arg-Arg-Lys-Asp-Thr(P)-Pro-Ala-Leu- His-Thr-Ser-Pro-Phe-Gln-Ser-Gly-Val-Arg SITE 2 The amino acid sequences surrounding the phosphorylated residues show 18 identities over a sequence of 26 residues, and suggest that G-substrate contains an internal gene duplication. Site-1 appears to be located 17 residues from the COOH terminus of the protein. Site 1 and site 2 are phosphorylated at similar rates by cyclic GMP-dependent protein kinase. In contrast, cyclic AMP-dependent protein kinase phosphorylates site 1 4-fold more rapidly than site 2. A decapeptide sequence surrounding the phosphothreonine residues in G-substrate shows 5 identities with that surrounding the phosphothreonine residue in protein phosphatase inhibitor 1. Inhibitor 1, a specific substrate for cyclic AMP-dependent protein kinase, also resembles G-substrate in its physical properties. The possible function of G-substrate and the molecular specificities of cyclic AMP-dependent protein kinase and cyclic GMP-dependent protein kinase are discussed in the light of these results.
Sensorless Tilt Compensation for a Three-Axis Optical Pickup Using a Sliding-Mode Controller Equipped With a Sliding-Mode Observer (2008)

A sliding-mode controller equipped with a sliding-mode observer is synthesized and applied to a novel three-axis four-wire optical pickup for the purpose of sensorless tilt compensation. The three-axis pickup owns the capability to move the lens holder in three directions of focusing, tracking and tilting, which is required particularly for higher data-density optical disks and precision measuring instruments to annihilate nonzero lens tiltings. To achieve the sensorless compensation, Lagrange's equations are first employed to derive equations of motion for the lens holder. A sliding-mode controller is then designed to perform dynamic decoupling and forge control efforts toward the goals of precision tracking, focusing, and zero tilting. Along with the controller, a sliding-mode observer is designed to perform the online tilt estimation of the lens holder. This estimated tilt allows the previously designed sliding-mode controller to be implemented in most existing commercial pickups without additional photodiodes to detect the tilting motion of the lens holder. A full-order high-gain observer is next forged to estimate the moving velocities of the lens holder in order to provide low-noised feedback velocity signals for the designed sliding-mode controller. Simulations are carried out to choose appropriate controller and observer gains. Finally, experiments are conducted to validate the effectiveness of the controller for annihilating lens tilting and the capability of the tilt observer for performing sensorless tilt compensation.
Near-Infrared Characterization of Breast Tumors In Vivo using Spectrally-Constrained Reconstruction (2005)

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six cases were malignant (infiltrating ductal carcinomas) and showed higher hemoglobin (34-86% increase), a reduction in oxygen saturation, an increase in water content as well as scatter changes relative to surrounding normal tissue. Three of six cases were benign, two of which were diagnosed with fibrocystic disease and showed a dominant contrast in water, consistent with fluid filled cysts. Scatter amplitude was the main source of contrast in the volunteer with the benign condition fibrosis, which typically contains denser collagen tissue. The changes monitored correspond to physiological changes associated with angiogenesis, hypoxia and cell proliferation anticipated in cancers. These changes represent potential diagnostic indicators, which can be assessed to characterize breast tumors.
Battery Management for Maximum Performance in Plug-In Electric and Hybrid Vehicles (2007)

Battery energy and power density are limiting factors in the design of electric and hybrid vehicle systems, particularly in the context of wide-range cycling needed for plug- in systems. Many commercial hybrid designs are controlled around specific operating conditions for long battery life. In this paper, battery management aspects for long operating life are discussed. Electrical considerations in valve-regulated lead-acid batteries, nickel-metal-hydride batteries, and lithium-ion batteries are described. Emphasis is provided on charge balancing requirements and state-of-charge operating ranges. The role of ultracapacitors for power buffering is addressed briefly. It is shown that lithium-ion cells offer considerable promise because of their high input-output energy efficiency and possibility of relatively wide operating range. Charge balancing is known to be a vital aspect, and balancing requirements are quantified for sample systems.
2-Iminopyrrolidines as Potent and Selective Inhibitors of Human Inducible Nitric Oxide Synthase (1998)

A series of substituted 2-iminopyrrolidines has been prepared and shown to be potent and selective inhibitors of the human inducible nitric oxide synthase (hiNOS) isoform versus the human endothelial nitric oxide synthase (heNOS) and the human neuronal nitric oxide synthase (hnNOS). Simple substitutions at the 3-, 4-, or 5-position afforded more potent analogues than the parent 2-iminopyrrolidine 1. The effect of ring substitutions on both potency and selectivity for the different NOS isoforms is described. Substitution at the 4- and 5-positions of the 2-iminopyrrolidine yielded both potent and selective inhibitors of hiNOS. In particular, (+)-cis-4-methyl-5-pentylpyrrolidin-2-imine, monohydrochloride (20), displayed potent inhibition of hiNOS (IC50 = 0.25 microM) and selectivities of 897 (heNOS IC50/hiNOS IC50) and 13 (hnNOS IC50/hiNOS IC50). Example 20 was shown to be an efficacious inhibitor of NO production in the mouse endotoxin assay. Furthermore, 20 displayed in vivo selectivity, versus heNOS isoform, by not elevating blood pressure at multiples of the effective dose in the mouse.
Disruption of stem cell niche–confined R-spondin 3 expression leads to impaired hematopoiesis (2022)

Self-renewal and differentiation of stem and progenitor cells are tightly regulated to ensure tissue homeostasis. This regulation is enabled both remotely by systemic circulating cues, such as cytokines and hormones, and locally by various niche-confined factors. R-spondin 3 (RSPO3) is one of the most potent enhancers of Wnt signaling, and its expression is usually restricted to the stem cell niche where it provides localized enhancement of Wnt signaling to regulate stem cell expansion and differentiation. Disruption of this niche-confined expression can disturb proper tissue organization and lead to cancers. Here, we investigate the consequences of disrupting the niche-restricted expression of RSPO3 in various tissues, including the hematopoietic system. We show that normal Rspo3 expression is confined to the perivascular niche in the bone marrow. Induction of increased systemic levels of circulating RSPO3 outside of the niche results in prominent loss of early B-cell progenitors and anemia but surprisingly has no effect on hematopoietic stem cells. Using molecular, pharmacologic, and genetic approaches, we show that these RSPO3-induced hematopoietic phenotypes are Wnt and RSPO3 dependent and mediated through noncanonical Wnt signaling. Our study highlights a distinct role for a Wnt/RSPO3 signaling axis in the regulation of hematopoiesis, as well as possible challenges related to therapeutic use of RSPOs for regenerative medicine.
GATA3 germline variant is associated with CRLF2 expression and predicts outcome in pediatric B‐cell precursor acute lymphoblastic leukemia (2019)

The germline variant at rs3824662 in GATA3 is a risk locus for Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), the biological subtype of B-cell precursor (BCP)-ALL defined by a distinct gene expression profile and the presence of specific somatic aberrations including rearrangements of CRLF2. In this study, we investigated whether rs3824662 in GATA3 associates with CRLF2 expression in leukemic cells and predicts prognosis in pediatric BCP-ALL patients treated according to the ALL Intercontinental Berlin-Frankfurt-Münster (IC BFM) 2009 (n = 645) and the ALL IC BFM 2002 (n = 216) protocols. High expression of CRLF2 was observed at both protein and mRNA levels (fourfold higher in AA than in CA + CC) among GATA3 AA variant carriers, independent of the presence of P2RY8-CRLF2 fusion. Additionally, the AA variant at rs3824662 was a significant factor affecting minimal residual disease level at the end of induction phase and overall survival regardless of the risk group and the protocol. The germline variant at rs3824662 in GATA3 is a prognostic factor which associates with CRLF2 expression in leukemic cells supporting the hypothesis that GATA3 may have a regulatory effect on the CRLF2 pathway in pediatric BCP-ALL.
Surgical Management of Metastatic Renal Carcinoma of the Spine (1991)

A total of 33 patients with renal cell carcinoma metastatic to the spine underwent spinal decompression over a 5-year period; 20 were operated on for neurologic dysfunction, and the remainder for pain alone. Surgery was performed anteriorly in 21, posteriorly in 9, and combined in 3 cases. The surgical approach was determined by the preoperative anatomic localization of the tumor. Of these patients 88% had fusions with instrumentation and polymethylmethacrylate; 88% of patients had partial or complete relief of pain; and 64% of bedridden patients subsequently were able to walk. Neurologic function improved in 60% of patients with a neurologic deficit; however, only 36% of incontinent patients regained bladder control. Survival averaged 8.0 +/- 1.5 months. Survival correlated with the degree of neurologic dysfunction and the presence of other known metastases. Recurrent cord compression developed in 49% of patients, usually at the same level; 9 of these 16 patients had repeat decompression, with similar operative results as the primary procedure in terms of pain and neurologic function. Blood loss was variable but often significant. Preoperative embolization appeared to be beneficial. Precise tumor localization preoperatively directing the surgical approach and better patient selection would likely improve results and decrease morbidity. Good palliation appeared to be achieved in regards to both pain relief and improved neurologic function.
Autoradiographic studies of cerebellar histogenesis in the premetamorphic bullfrog tadpole: II. Formation of the interauricular granular band (1988)

This study examines the origin of cells in the interauricular granular band (iagb) in the cerebellum of the frog tadpole during early stages of development by means of histological and autoradiographic methods. Premetamorphic bullfrog tadpoles were exposed to multiple doses of 3H-thymidine (10 microCi/g body weight per exposure) at developmental stages ranging from 1 week to 1 year and were killed at either 6 or 12 months of age. The autoradiographic data were examined to determine the time when cells of the iagb were generated. Our findings show that initial generation of iagb cells begins at week 3 and that a peak in the formation of postmitotic neurons is reached at the age of 10 weeks. This is followed by other peaks of cell generation at the ages of 16 weeks, 10 months, and 11.5 months. The generation cycles of iagb cells are interrupted by periods of quiescence when label cannot be detected in any of the cells. These quiescent periods occur at the ages of 20-26 weeks, 7 months, and 12 months. These findings indicate that cells of the iagb are generated in a cyclical manner over the entire 1-year period which was studied. Comparison of our present data on iagb cell formation with the generation of cells in the EGL shows that the production of these two groups of cells is overlapping, but cells of the iagb begin and cease production before those of the EGL. On the basis of our findings we propose that the cells of the iagb and the EGL belong in separate cell groups which are generated by distinct subpopulations of germinal cells in the neuroepithelial cap.
Ultra-precision machining technique for optical free-surface and its application (2004)

2003-2004 > Academic research: refereed > Publication in refereed journal
Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration (2018)

Asthma is a phenotypically heterogeneous disease. In severe asthma, airway inflammation can be predominantly eosinophilic, neutrophilic, or mixed. Only a limited number of drug candidates are in development to address this unmet clinical need. Live biotherapeutics derived from the gut microbiota are a promising new therapeutic area. MRx0004 is a commensal Bifidobacterium breve strain isolated from the microbiota of a healthy human. The strain was tested prophylactically and therapeutically by oral gavage in a house dust mite mouse model of severe asthma. A strong reduction of neutrophil and eosinophil infiltration was observed in lung bronchoalveolar lavage fluid following MRx0004 treatment. Peribronchiolar and perivascular immunopathology was also reduced. MRx0004 increased lung CD4<sup>+</sup>CD44<sup>+</sup> cells and CD4<sup>+</sup>FoxP3<sup>+</sup> cells and decreased activated CD11b<sup>+</sup> dendritic cells. Cytokine analysis of lung tissue revealed reductions of pro-inflammatory cytokines and chemokines involved in neutrophil migration. In comparison, anti-IL-17 antibody treatment effectively reduced neutrophilic infiltration and increased CD4<sup>+</sup>FoxP3<sup>+</sup> cells, but it induced lung eosinophilia and did not decrease histopathology scores. We have demonstrated that MRx0004, a microbiota-derived bacterial strain, can reduce both neutrophilic and eosinophilic infiltration in a mouse model of severe asthma. This novel therapeutic is a promising next-generation drug for management of severe asthma.
Glucose-induced Toxicity in Insulin-producing Pituitary Cells That Coexpress GLUT2 and Glucokinase (2001)

We have shown that intermediate lobe (IL) pituitary cells can be engineered to produce sufficient amounts of insulin (ins) to cure diabetes in nonobese diabetic mice but, unlike transplanted islets, ILins cells evade immune attack. To confer glucose-sensing capabilities into these cells, they were further modified with recombinant adenoviruses to express high levels of GLUT2 and the beta-cell isoform of glucokinase (GK). Although expression of GLUT2 alone had negligible effects on glucose usage and lactate production, expression of GK alone resulted in approximately 2-fold increase in glycolytic flux within the physiological (3-20 mm) glucose range. GLUT2/GK coexpression further increased glycolytic flux at 20 mm glucose but disproportionately increased flux at 3 mm glucose. Despite enhanced glycolytic fluxes, GLUT2/GK-coexpressing cells showed glucose dose-dependent accumulation of hexose phosphates, depletion of intracellular ATP, and severe apoptotic cell death. These studies demonstrate that glucose-sensing properties can be introduced into non-islet cells by the single expression of GK and that glucose responsiveness can be augmented by the coexpression of GLUT2. However, in the metabolic engineering of surrogate beta cells, it is critical that the levels of the components be closely optimized to ensure their physiological function and to avoid the deleterious consequences of glucose-induced toxicity.
52.2: Long Life UHP Lamps for Consumer Applications (2005)

Abstract UHP‐lamp based rear projection systems capture the market for large screens. This requires new generations of reliable lamps with very long lifetimes at powers higher than 100W. Sophisticated modelling of plasma, burner and high temperature chemistry allows to extend the traditional limits.
A variable-transmittance apodizing filter at 157 nm (2005)

A variable-transmittance apodizing filter has been designed and demonstrated at 157 nm. The Gaussian transmission function is created by flowing oxygen gas, which is absorptive below 185 nm, between the two spherical surfaces of meniscus lenses. By varying the oxygen partial pressure, the degree of apodization can be controlled.
P3463The association between vasospasm and serum concentrations of aldehyde dehydrogenase 2 in patients with variant angina (2017)

Cardiovascular risk factors in general population / Vascular biology and the microcirculation 727 by their HDL-C levels. Cox proportional hazard models stratified by cohorts were used to estimate hazard ratios (HRs) after adjusting for age, sex, non-HDL-C, hypertension, diabetes, smoking and alcohol drinking. Results: During follow-up, we observed 289 deaths due to CHD and 265 deaths due to ischemic stroke. The relationship between HDL-C and CHD was U-shaped. The lowest HRs were observed in 3rd and 4th groups (HDL-C: 40-59, 60-79 mg/dl), of which HRs were 1.0 (reference) and 0.87 (95% confidence interval: 95% CI: 0.62-1.21), respectively. Increased CHD mortality were observed both in 1st to 2nd groups (-29, 30-39 mg/dl) and 6th group (90 mg/dl and greater), of which HRs were 1.32 (95% CI: 0.73-2.43), 1.21 (1.21, 95% CI: 0.89-1.64) and 2.45 (95% CI: 1.13-5.32), respectively. Similar results were observed in ischemic stroke, of which HR in 6th group was 2.30 (95% CI: 1.06-4.98). More narrow confidence intervals were observed when CHD and ischemic stroke were combined as one composite outcome. Sex-specific analysis also showed similar results. Conclusions: Serum HDL-C levels showed U-shaped associations with atherosclerotic diseases. Similar to clinical trials by cholesterol ester transfer protein (CETP) inhibitors, unexpected increased risks were observed in very high HDL-C group in this pooled analysis of long-term cohort studies of Japanese general populations.
Integrated circuits using embedded III-V-on-Ge MHEMTs in multi-layer thin-film technology (2003)

In this paper a demonstrator oscillator circuit integrated in a MCM-D on glass technology is presented. The active device of the oscillator is a thin-film Ge (germanium) -based MHEMT. The MHEMT is embedded in the bottom dielectric layer of the MCM-D. The combination of passive MCM-D technology and MHEMTs on Ge allows for efficient semi-monolithic integration of active devices and realisation of (optoelectronic) MCMs with embedded passive and active components.
Aromatic-Turmerone Induces Neural Stem Cell Proliferation In Vitro and In Vivo (S24.007) (2014)

OBJECTIVE:We explored the effects of Aromatic(ar-)turmerone on neural stem cells in the subventricular zone and hippocampus in rats. BACKGROUND: Ar-turmerone is one of the major bioactive compounds found in the herb Curcuma longa. Regarding its use in neurology, it was reported to inhibit microglia activation. However, its effects on neural stem cells (NSC) are unknown to date. DESIGN/METHODS:Primary fetal rat NSC were exposed to various concentrations of ar-turmerone to assess cell proliferation and differentiation potential. In vivo, naïve rats were treated with a single intracerebroventricular (i.c.v.) injection of ar-turmerone. Proliferative activity of endogenous NSC was assessed in vivo via non-invasive positron emission tomography (PET) imaging using the tracer [18F]-fluoro-L-thymidine ([18F]FLT), and ex vivo. RESULTS:Ar-turmerone dose-dependently increased the number of cultured NSC, caused by an increase in NSC proliferation (p<0.01). Those results on proliferation were supported by q-PCR data for Ki-67 mRNA. After mitogen withdrawal, ar-turmerone promoted an early neuronal differentiation. After i.c.v. injection of ar-turmerone in vivo, proliferative activity in the subventricular zone (SVZ) of adult rats was significantly increased (p<0.05). Moreover, non-invasive imaging of cell proliferation in vivo using [18F]FLT-PET supported an turmerone-induced mobilization of NSC from both the SVZ and the hippocampus (p<0.01). CONCLUSIONS:Ar-turmerone induces NSC proliferation in vitro and in vivo. Data suggest ar-tumerone being a promising drug candidate to support regeneration in neurological disorders. Study Supported by:This work was supported by the Koeln Fortune Program / Faculty of Medicine, University of Cologne, Germany (106/2012), and the EU FP7 project “NeuroFGL”.
In vitro release of vascular endothelial growth factor from gadolinium‐doped biodegradable microspheres (2004)

A drug delivery vehicle was constructed that could be visualized noninvasively with MRI. The biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) was used to fabricate microspheres containing vascular endothelial growth factor (VEGF) and the MRI contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The microspheres were characterized in terms of size, drug and contrast agent encapsulation, and degradation rate. The PLGA microspheres had a mean diameter of 48 +/- 18 microm. The gadolinium loading was 17 +/- 3 microg/mg polymer and the VEGF loading was 163 +/- 22 ng/mg polymer. Electron microscopy revealed that the Gd was dispersed throughout the microspheres and it was confirmed that the Gd loading was sufficient to visualize the microspheres under MRI. VEGF and Gd-DTPA were released from the microspheres in vitro over a period of approximately 6 weeks in three phases: a burst, followed by a slow steady-state, then a rapid steady-state. Biodegradable Gd-doped microspheres can be effectively used to deliver drugs in a sustained manner, while being monitored noninvasively with MRI.