gebhart/patrepeval huggingface dataset:
A Requirement for ZAK Kinase Activity in Canonical TGF-β Signaling (2016)

The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7), is a MAPK-kinase kinase (MKKK). Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK) pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β)-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity. Remarkably, we demonstrate that siRNA mediated depletion of ZAK strongly inhibited TGF-β dependent SMAD2/3 activation and subsequent promoter activation (SMAD binding element driven luciferase expression; SBE4-Luc). A ZAK specific inhibitor (DHP-2), dose-dependently activated the bioluminescent TGFBR-kinase activity reporter (BTR), blocked TGF-β induced SMAD2/3 phosphorylation and SBE4-Luc activation and cancer cell-invasion. In aggregate, these findings identify a novel role for the ZAK kinase in canonical TGF-β signaling and an invasive cancer cell phenotype thus providing a novel target for TGF-β inhibition.
P2‐354: Detection of amyloid plaques in Alzheimer's transgenic mice using contrast‐enhanced magentic resonance microimaging (2010)

Amyloid plaques are a pathological hallmark of Alzheimer's disease (AD). The visualization of amyloid plaquesis important to monitor AD progression and to evaluate efficacy of therapeutic interventions. Our group has developed several contrast-enhancing agents to detect amyloid plaques in vivo in AD transgenic mice using magnetic resonance microimaging (μMRI). However, each of our past studies involved intra-carotid injection of ligands in order to gain sufficient blood-brain-barrier penetration. This is highly invasive and not feasible for human studies. Therefore, a safer and less invasive method of ligand administration is required. In present study, we use ultrsamll superparamagnetic iron oxide (USPIO) nanoparticles to detect amyloid deposition for in vivo μMRI by femoral injection. μMRI was performed on APPK670N/M671L/PS1M146L transgenic AD mice and wild-type mice prior to and following intrafemoral injection with USPIO coupled to Aβ1-42 in 15% mannitol solution. A 3D gradient echo T2∗-weighted sequence was used for imaging (TE = 4 ms; TR = 80 ms; flip angle = 20°), providing a 100 μm isotropic resolution with imaging times of 2h 20min. After in vivo μMRI, mice were anesthetized with sodium pentobarbital and perfused transaortically with PBS followed by 4% paraformaldehyde, and their brains were extracted for ex vivo MRI and histological analysis. Amyloid plaques were detected in AD transgenic mice after intrafemoral injection of USPIO-Aβ1-42 along with mannitol. The distribution of plaques detected by MRI was in excellent agreement with those seen in matched histological sections. In addition, the quantitative measurement of T2∗ values showed contrast injected APP/PS1mice have significantly reduced T2∗ values compared to wild-type mice. This reduction correlated with the amyloid burden determined histologically in APP/PS1 mice. Our results demonstrate that it is feasible to perform intrafemoral injection for amyloid plaque detection in AD transgenic mice using USPIO-Aβ1-42 contrast ligands. USPIO has already been used in humans for CNS imaging in conditions such as multiple sclerosis and stroke. Hence if we are able to better develop this technology, this has potential to be used diagnostically in patients.
Compressed 3D ultrasound imaging with 2D arrays (2014)

Contemporary sonography is performed by digitally beamforming signals sampled by several transducer elements placed upon an array. High-resolution digital beamforming introduces the demand for a sampling rate significantly higher than the signal's Nyquist rate, which greatly increases the volume of data that must be processed. In 3D ultrasound imaging, 2D transducer arrays rather than 1D arrays are used, and more scan-lines are needed for volumetric imaging. This implies that the amount of sampled data is vastly increased with respect to 2D imaging. In this work we show that a considerable reduction both in sampling rate and processing time can be achieved by applying the ideas of Xampling and frequency domain beamforming, leading to a sub-Nyquist sampling rate. We extend previous work on frequency domain beamforming for 2D ultrasound imaging to the geometry imposed by 3D tissues and a grid of transducer elements. This method uses only a portion of the bandwidth of the ultrasound signals to reconstruct the image. We demonstrate our results by imaging a phantom comprised of fishing wires, and show that by performing 3D beamforming in the frequency domain, a sub-Nyquist sampling rate and a low processing rate are obtained, while keeping adequate image quality.
Linkage of hereditary haemorrhagic telangiectasia to chromosome 9q34 and evidence for locus heterogeneity. (1994)

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with unknown pathophysiology that is characterised by arteriovenous lesions and recurrent haemorrhage in virtually every organ. Linkage of HHT to markers on chromosome 9q has recently been reported. In this study we report confirmation of this localisation in three unrelated families of Dutch origin. A fourth unrelated HHT family, in which considerably fewer pulmonary arteriovenous malformations (PAVM) were present, yielded evidence for non-linkage to this region. We conclude that HHT is a genetically heterogeneous disorder and our results indicate that the presence of PAVM may be more common in patients with a chromosome 9 linked form of HHT than in patients with the non-linked form.
Long-term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom macroglobulinemia. (2012)

8043 Background: The mammalian target of rapamycin (mTOR) signal pathway controls cell proliferation and survival. The trial's goal was to determine the anti-tumor activity and safety of single-agent everolimus (TORC1 inhibitor) in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM). Methods: Eligible patients had measurable disease (IgM monoclonal protein &gt;1000 mg/dL with &gt;10% marrow involvement or nodal masses &gt;2 cm), a platelet count ≥75,000 x 10 6 /L, a neutrophil count ≥1,000 x 10 6 /L. Patients received everolimus 10 mg PO daily. Tumor response was assessed after cycles 2 and 6 and then every 3 cycles until progression. Results: 60 pts were treated. The median age was 64 years (range, 43-85). The median number of prior therapies was 3 (range, 1-11). All but two patients (97%) had received prior rituximab based therapy and 64% of patients had received prior alkylator based therapies. The overall response rate (complete response CR+ partial response PR+ minimal response MR) was 73% (95% CI: 60-84%), with a PR of 50% and 23% MR. The median time to progression (TTP), progression-free survival (PFS), and overall survival (OS) for the entire study population is 28 months (mos), (95% CI: 18-not reached (NR)), 22 mos (95% CI: 12 0-NR), and 55 mos (95% CI: 55-NR), respectively. The estimated PFS at 12 and 24 months is 62% (95%CI: 51-75%), and 48% (95%CI: 37-63%), respectively. The 30 patients who achieved a PR responded after a median of 2 months (range, 1-26) of treatment. The median duration of response (DR) for these patients has not yet been reached and 19 of these patients remain in response after a median follow up of 31 months (range, 3-54). All but two patients had a decrease in their serum IgM. Grade 3 or higher related toxicities were observed in 67% of patients. The most common were hematological toxicities with cytopenias. Pulmonary toxicity occurred in 5% of patients. Dose reductions due to toxicity occurred in 63% of patients. Conclusions: Everolimus has high single-agent activity with an overall response rate of 73% and manageable toxicity in patients with relapsed WM, and offers a potential new therapeutic strategy for this patient population.
Age-dependent motor dysfunction due to neuron-specific disruption of stress-activated protein kinase MKK7 (2017)

c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and controls various physiological processes including apoptosis. A specific upstream activator of JNKs is the mitogen-activated protein kinase kinase 7 (MKK7). It has been reported that MKK7-JNK signaling plays an important regulatory role in neural development, however, post-developmental functions in the nervous system have not been elucidated. In this study, we generated neuron-specific Mkk7 knockout mice (MKK7 cKO), which impaired constitutive activation of JNK in the nervous system. MKK7 cKO mice displayed impaired circadian behavioral rhythms and decreased locomotor activity. MKK7 cKO mice at 8 months showed motor dysfunctions such as weakness of hind-limb and gait abnormality in an age-dependent manner. Axonal degeneration in the spinal cord and muscle atrophy were also observed, along with accumulation of the axonal transport proteins JNK-interacting protein 1 and amyloid beta precursor protein in the brains and spinal cords of MKK7 cKO mice. Thus, the MKK7-JNK signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system.
AOSN MURI: Communication Software for the Utility Acoustic Modem (1997)

Abstract : The long-term goal is to create and demonstrate a reactive survey system, capable of long-term unattended deployments in harsh environments. We refer to such a system as an Autonomous Ocean Sampling Network (AOSN). An integral part of this effort is the development, design, and implementation of both hardware and software for a Utility Acoustic Modem (UAM), which permits 2-way communications between survey vehicles and researchers. The effort described in this report pertains to UAM software development.
Enhydrazine, II. Cycloacylierung von tautomeriefähigen Enhydrazinen (1982)

Abstract Die Cycloacylierung der Enhydrazine 1, 9, 12 und 20 mit (Chlorthio)ameisensäurechlorid ( 2 ), (Chlorcarbonyl)isocyanat ( 10 ), N ‐Methyliminodicarbonyldichiorid ( 13 ) und den Malonyldichloriden 18 führt zu den neuen 2‐Oxothiazol‐ 3, 1‐Aminouracil‐ 11 und 14 , 1‐Amino‐2,4(1 H ,1 H )‐pyridindion‐ 19 oder 2,4,6(1 H ,3 H ,5 H )‐Pyridintrion‐Derivaten 22. Es werden die Eigenschaften und spektroskopischen Daten angegeben.
An Overview of Compressor Abradables (2000)

Abstract Very many gap-sealing products are now available for use in the compressor section of gas turbines. This paper attempts to give an overview of these and where they are best used. Data is presented for abradability, erosion resistance and application technique. By explaining how abradables function tribologically it is hoped that selection will be simpler for designers. New products are introduced as well as the way forward described. It is shown how with time the diversity of application techniques has decreased with thermal spraying becoming the preferred technique, and that abradables are now available to run against titanium blading up to 600°C.
Biosorption of Tungsten by Escherichia coli for an Environmentally Friendly Recycling System (2013)

In this study, tungsten (W) recovery via biosorption using Escherichia coli was assessed to establish an environmentally friendly recycling system for W. The recovery fraction of soluble WVI was highly dependent on the solution pH, and E. coli cells exhibited the highest WVI uptake capacity for an initial pH of 1.08–2.56. Fourier transform infrared analysis revealed that carboxyl and phosphate functional groups on the surface of the bacteria play a crucial role in adsorption of WVI. Equilibrium and kinetic modeling of WVI biosorption showed that the equilibrium adsorption data fit the Langmuir isotherm model better than the Freundlich model. Kinetic studies revealed that WVI adsorption followed a pseudo-second-order rate model. WVI was recovered by desorption and heating, and adjustment of the pH enabled 95.8% WVI desorption from the E. coli cells. Heating at 1000 °C for 2 h under atmospheric conditions produced concentrates with relatively high concentrations of WVI (97.1% WO3).
Direct Catalytic Intermolecular α‐Allylic Alkylation of Aldehydes by Combination of Transition‐Metal and Organocatalysis (2006)

Alles in einem Topf: Die direkte katalytische Alkylierung von Aldehyden und cyclischen Ketonen mit einem α-Allylrest gelingt mit einem einfachen, neuartigen Eintopfverfahren. Diese chemo- und regioselektive Methode kombiniert Übergangsmetall- und Enaminkatalyse und liefert die alkylierten Aldehyde und cyclischen Ketone in hoher Ausbeute.
Frequency doublers with 10.2/5.2 dBm peak power at 100/202 GHz in 45nm SOI CMOS (2015)

This paper presents frequency doublers with high output power for millimeter-wave applications. The circuits are fabricated using a 45nm SOI CMOS technology. A new circuit topology, combining a push-push doubler core with a cascaded stacked amplifier, has been implemented to increase the output power. The first doubler delivers 10.2 dBm peak power at 100 GHz output, with a 3-dB bandwidth from 88 to 104 GHz and DC-RF efficiency of 4.1%, while the second doubler has 5.2 dBm peak power at 202 GHz, with a 3-dB bandwidth from 180 to 212 GHz and DC-RF efficiency of 3.3%. To the authors' knowledge, these are the highest powers reported for silicon frequency doublers in similar frequency ranges to date. The 200 GHz doubler also provides the highest on-chip power from a single-element signal generation circuit without power combining.
Effects of wavelength-dependent fluence attenuation on the noninvasive photoacoustic imaging of hemoglobin oxygen saturation in subcutaneous vasculature in vivo (2008)

Due to wavelength-dependent optical attenuation in the skin, the local fluence at a subcutaneous vessel varies with the optical wavelength in a spectral measurement. Hence compensation for such a spectral attenuation is necessary in quantitative measurements of the oxygen saturation of hemoglobin (sO<sub>2</sub>) in blood vessels in vivo using photoacoustic (PA)imaging. Here, by employing a simplified double-layer skin model, we find that although the absolute value of sO<sub>2</sub> in a vessel is seriously affected by the volume fraction of blood and the spatially averaged sO2 in the dermis, the difference of sO<sub>2</sub> between neighboring vessels is minimally affected. Based on in vivo experiments, we demonstrate that the difference in sO<sub>2</sub> between a typical artery and a typical vein is conserved before and after an experimentally acquired spectral compensation. This conservation holds regardless of the animal's systemic physiological state.
QUANTUM AUCTIONS USING ADIABATIC EVOLUTION: THE CORRUPT AUCTIONEER AND CIRCUIT IMPLEMENTATIONS (2008)

We examine a proposed auction algorithm using quantum states to represent bids and distributed adiabatic search to find the winner. 1 When the auctioneer follows the protocol, the final measurement giving the outcome of the auction also destroys the bid states, thereby preserving the privacy of losing bidders. We describe how a dishonest auctioneer could alter the protocol to violate this privacy guarantee, and present methods by which bidders can counter such attacks. We also suggest possible quantum circuit implementations of the auction protocol, and quantum circuits to perpetrate and to counter attacks by a dishonest auctioneer.
Effects of priming volume reduction on allogeneic red blood cell transfusions and renal outcome after heart surgery (2014)

The Inspire 6™ oxygenator allows a significant containment of hemodilution during CPB, reducing the risk of RBC transfusions and postoperative AKI.
Analysis of an offloading scheme for data centers in the framework of fog computing (2015)

In the context of fog computing, we consider a simple case when data centers are installed at the edge of the network and assume that if a request arrives at an overloaded data center, then it is forwarded to a neighboring data center with some probability. Data centers are assumed to have a large number of servers and that traffic at some of them is causing saturation. In this case the other data centers may help to cope with this saturation regime by accepting some of the rejected requests. Our aim is to qualitatively estimate the gain achieved via cooperation between neighboring data centers. After proving some convergence results, related to the scaling limits of loss systems, for the process describing the number of free servers at both data centers, we show that the performance of the system can be expressed in terms of the invariant distribution of a random walk in the quarter plane. By using and developing existing results in the technical literature, explicit formulas for the blocking rates of such a system are derived.
Stiff and Electrically Conductive Composites of Carbon Nanotube Aerogels and Polymers (2011)

Abstract not provided
Tool flank wear effects on the cutting edge shrink in ultra-precision raster fly cutting (2016)

31st Annual Meeting of the American Society for Precision Engineering, ASPE 2016, Portland, US, 23-28 October 2016
The Giant Magellan Telescope adaptive optics program (2012)

The Giant Magellan Telescope adaptive optics system will be an integral part of the telescope, providing laser guide star generation, wavefront sensing, and wavefront correction to most of the currently envisioned instruments. The system will provide three observing modes: Natural Guidestar AO (NGSAO), Laser Tomography AO (LTAO), and Ground Layer AO (GLAO). Every AO observing mode will use the telescope's segmented adaptive secondary mirror to deliver a corrected beam directly to the instruments. High-order wavefront sensing for the NGSAO and LTAO modes is provided by a set of wavefront sensors replicated for each instrument and fed by visible light reflected off the cryostat window. An infrared natural guidestar wavefront sensor with open-loop AO correction is also required to sense tip-tilt, focus, segment piston, and dynamic calibration errors in the LTAO mode. GLAO mode wavefront sensing is provided by laser guidestars over a ∼5 arcminute field of view, and natural guidestars over wider fields. A laser guidestar facility will project 120 W of 589 nm laser light in 6 beacons from the periphery of the primary mirror. An off-axis phasing camera and primary and secondary mirror metrology systems will ensure that the telescope optics remain phased. We describe the system requirements, overall architecture, and innovative solutions found to the challenges presented by high-order AO on a segmented extremely large telescope. Further details may be found in specific papers on each of the observing modes and major subsystems.
Differential Desensitization and Internalization of Three Different Bullfrog Gonadotropin-releasing Hormone Receptors (2002)

We previously demonstrated the presence of three distinct types of the gonadotropin-releasing hormone receptor (GnRHR) in a bullfrog (denoted bfGnRHR-1, bfGnRHR-2, and bfGnRHR-3). The bfGnRHRs exhibited differential tissue distribution and ligand selectivity. In the present study, we demonstrated the desensitization and internalization kinetics of these receptors in both transiently-transfected HEK293 cells and retrovirus-mediated stable cells. The time-course accumulation of the inositol phosphate in response to GnRH revealed that bfGnRHR-1 and -2 were rapidly desensitized, whereas bfGnRHR-3 was slowly desensitized. A comparison of the internalization kinetics revealed the most rapid rate and highest extent of internalization of bfGnRHR-2 among the three receptors. Interestingly, the mechanisms that underlie the receptor internalization appear to differ from each other. Internalization of bfGnRHR-1 was dependent on both dynamin and beta-arrestin, whereas those of bfGnRHR-2 and -3 were dependent on dynamin, but not on arrestin. These results, therefore, suggest that differential regulatory mechanisms for desensitization and internalization of the GnRHR are involved in diverse cellular and physiological responses to GnRH stimulation.
A new type of local defects in very thin silicon dioxide films on arsenic-implanted p-type silicon (2002)

Local oxide defects in thin silicon dioxide films thermally grown on arsenic-implanted n/sup +/ layer on a p-type Si substrate as well as on a plain p-type substrate were studied with the EBIC/TCM (Electron Beam Induced Current/Tunneling Current Microscopy) technique. We have captured the EBIC micrographs and the EBIC linescans for the defects. A new type of local oxide defect was observed with the property that the TOEBIC (True Oxide EBIC) contrast and the TCM contrast are of the same polarity. This is not the same as the more usual type of oxide defects, which have opposite TOEBIC and TCM contrast. The more usual type of local oxide defects can be found in silicon dioxide films thermally grown on p-type Si substrate with or without the n/sup +/ implanted layer. However, the new type of local oxide defects can be found only in thin silicon dioxide films thermally grown on arsenic-implanted n/sup +/ layer on a p-type Si substrate. A tentative explanation was proposed to explain our experimental observations.
Pharmacokinetic/Pharmacodynamic Properties of Phosphorothioate 2-O-(2-Methoxyethyl)- Modified Antisense Oligonucleotides in Animals and Man (2007)

Accumulation and Clearance ................................................................................314 11.3 Pharmacokinetics/Pharmacodynamics in Man ...................................................................316
Neutral DNA–avidin nanoparticles as ultrasensitive reporters in immuno-PCR (2020)

We have developed an immuno-PCR based diagnostic platform which couples detection antibodies to self-assembled, ultra-detectable DNA-avidin nanoparticles stabilized with poly(ethylene glycol) to link DNA amplification to target protein concentration. Electrostatic neutralization and cloaking of the PCR-amplifiable DNA labels by avidin and PEG coating reduces non-specific "stickiness" and enhances assay sensitivity. We further optimized the detectability of the nanoparticles by incorporating four repeats of a unique synthetic DNA PCR target into each nanoparticle. Using human chorionic gonadotropin hormone (hCG) as a model analyte, this platform was able to quantitate the target hCG protein in femtomolar concentrations using only standard laboratory equipment.
Staffing optimization in complex service delivery systems (2011)

Enterprises and service providers are increasingly challenged with improving the quality of service delivery while containing the cost. However, it is often difficult to effectively manage the conflicting needs associated with dynamic customer workload, strict service level constraints, and service personnel with diverse skill sets. In this paper we propose an optimization model to provide recommended staffing levels in a complex service delivery system. The optimization model minimizes the total staffing related variable cost while considering the contractual service level constraints, the skills required to respond to different types of service requests, and the shift schedules that the service agents must follow. We describe how model-based decision making can be conducted using a combination of optimization and discrete event simulation techniques. We demonstrate the applicability of the proposed approach in a large IT services delivery environment.