gebhart/patrepeval huggingface dataset:
Radiogenomics Monitoring in Breast Cancer Identifies Metabolism and Immune Checkpoints as Early Actionable Mechanisms of Resistance to Anti-angiogenic Treatment (2016)

Anti-VEGF antibody bevacizumab has prolonged progression-free survival in several cancer types, however acquired resistance is common. Adaption has been observed pre-clinically, but no human study has shown timing and genes involved, enabling formulation of new clinical paradigms. In a window-of-opportunity study in 35 ductal breast cancer patients for 2weeks prior to neoadjuvant chemotherapy, we monitored bevacizumab response by Dynamic Contrast-Enhanced Magnetic Resonance [DCE-MRI], transcriptomic and pathology. Initial treatment response showed significant overall decrease in DCE-MRI median K(trans), angiogenic factors such ESM1 and FLT1, and proliferation. However, it also revealed great heterogeneity, spanning from downregulation of blood vessel density and central necrosis to continued growth with new vasculature. Crucially, significantly upregulated pathways leading to resistance included glycolysis and pH adaptation, PI3K-Akt and immune checkpoint signaling, for which inhibitors exist, making a strong case to investigate such combinations. These findings support that anti-angiogenesis trials should incorporate initial enrichment of patients with high K(trans), and a range of targeted therapeutic options to meet potential early resistance pathways. Multi-arm adaptive trials are ongoing using molecular markers for targeted agents, but our results suggest this needs to be further modified by much earlier adaptation when using drugs affecting the tumor microenvironment.
Stacked-transistor mm-wave power amplifiers (2016)

A dominant theme in the evolution of integrated electronics over past decades has been Moore's law, which has led to development of silicon-based transistors with dramatically improved operating speeds and levels of integration, as well as reduced power dissipation. Although the driving motivation for the technology development has been primarily application to digital circuits, silicon-based transistors are poised, by virtue of their very high frequency response, to provide mm-wave and THz circuits with also dramatically improved performance as well as low cost. One of the tradeoffs that has been necessary in the development of scaled silicon devices, however, has been a reduction in voltage handling capability. As a result, conventional scaled silicon transistors are not very well suited to power amplifiers, which perform best with high voltage swings along with high current swings. Recent research, however, has pointed to a circuit design approach that can overcome to a considerable degree the limitations of the basic transistors: the technique of series-connection, or stackingİ of multiple devices to generate a composite structure that can handle higher voltages. The stacking technique has opened the door to higher output power as well as higher efficiency and greater bandwidth, since the resulting impedance transformations needed to generate amplifier outputs at 50 ohm levels become easier to implement with low loss and high bandwidth. This chapter describes in detail the background, design considerations and benefits of stacked Si devices in mm-wave power amplifiers. Emphasis is given to stacked CMOS devices, although bipolar transistors and HBTs can also be stacked as described in Chapter 5. A review of Si FET characteristics is first given, along with a description of the impact of voltage handling on power amplifier characteristics. Stacked FET amplifiers at low microwave frequencies, which are emerging as important contenders for cell phone handsets, is then reviewed. Key design considerations for stacking at mm-wave frequencies are then presented. The chapter also describes a number of mm-wave power amplifier example designs in detail.
Synthesis and Reactivity of some Aromatic Sulfides Substituted by an Ortho-Phosphonyl Group (1999)

Abstract As phosphorus-based members of the biologically relevant thiosalicylic acid, monoesters of ortho-sulfinylated phenylphosphonic acids such as 3 and 4 (series a, R1=Me; b, R22-C6H4C02H) are of special interest. They might act both as potential sources of new anionic bidentate ligands for the synthesis of cisplatin analogues[1] and as suitable precursors of phosphorus-containing endocyclic sulfoximides and hypervalent organo-sulfur species. We have therefore undertaken the synthesis of these compounds. The starting phenylphosphonic acid diisopropylesters 1 were formed by using a LDA-induced thiophosphate-mercaptophosphonate rearrangement[2] described earlier and converted into their dimethyl counterpans 2 by means of a trans-silylation procedure followed by alkylation. We have now performed the selective half-hydrolysis of phosphonic acid diesters 1.2 and sulfoxidation of the resulting monoesters.
Somatostatin receptor expression in vivo and response to somatostatin analog therapy with or without other antineoplastic treatments in advanced medullary thyroid carcinoma. (2004)

The long-term treatment of metastatic medullary thyroid carcinoma (MTC) with somatostatin (SST) analogs was evaluated in 22 patients with persistant or relapsed disease and with in vivo positive SST receptor (SSTR) tumors. After surgical intervention all patients but one, initially or at a later time, had persistenly (15) or after relapse (7) elevated serum calcitonin (CT, 252-69482 pg/ml) and carcinoembryonic antigen (CEA, 8-1130 ng/ml) concentrations; also, all of them showed positive uptake in 111In-pentetreotide scanning. Daily doses of 0.4-1.0 mg octreotide subcutaneously, or monthly doses of 20-30 mg long-acting octreotide (LAR) intramuscularly for 3-21 months were administered. Systemic chemotherapy (Ch) with or without external radiotherapy (eRT) was given to 13 patients simultaneously. A beneficial effect on pre-existing diarrhea was observed in 8 patients (subjective partial remmission, sPR 36.4%); 10 other patients showed stable disease, while in 4 a worsening of pre-existing diarrhea was observed. CT and CEA concentrations decreased more than 25% in 4 out of 22 patients (18%) and 11 patients showed a decrease of less than 25% (biological SD). No objective response in tumour growth was demonstrated. Patients (10 survivors in group B) treated with Ch+eRT plus Octerotide showed higher sR (92.5%), lower mortality (23.1%), longer mean time to death (130 months) and longer mean total survival (mts) time (145 months) in comparison to group A patients who had 66.7% sR, 33.3% mortality, only 88.5 months mean time to death and 101 months mts-time. Long-term octreotide and octreotide-LAR treatment offers a subjective and biological partial remission in one third and in one fourth of the MTC patients respectively, but it does not improve the natural course of the tumor. It remains to be answered if these drugs, combined with other antineoplastic therapies, have a synergistic effect relating to treatment response and to patient survival and mortality.
Pharmacology of the Ca2+‐dependent K+ channel in corn protoplasts (1990)

We investigated the sensitivity of the Ca2(+)-dependent K+ current, IK(Ca), present in corn protoplasts, to different K+ channel blockers. IK(Ca) was inhibited by external Cs+ (10 mM), Ba2+ (10 mM), and quinine (0.5 mM): reagents which block many types of outward-rectifying K+ channels. In contrast 4-aminopyridine (5 mM), an inhibitor of delayed rectifier or inactivating K+ currents, had no effect. Neither of the peptide toxins, apamin or charybdotoxin, specific for Ca2(+)-dependent K+ channels in animal cells, inhibited currents when used in the nanomolar concentration range. However, higher levels of charybdotoxin (10 microM) caused marked reduction of IK(Ca).
The Relationship between Eye Movements and Spatial Attention (1986)

Most previous studies of the attentional consequences of making saccadic eye movements have used peripheral stimuli to elicit eye movements. It is argued that in the light of evidence showing automatic “capture” of attention by peripheral stimuli, these experiments do not distinguish between attentional effects due to peripheral stimuli and those due to eye movements. In the present study, spatial attention was manipulated by varying the probability that peripheral probe stimuli would appear in different positions, while saccades were directed by a central arrow, enabling the effects of attention and eye movements to be separated. The results showed that the time to react to a peripheral stimulus could be shortened both by advance knowledge of its likely position and, separately, by preparing to make a saccade to that position. When the saccade was directed away from the most likely position of the probe, the targets for attention and eye movements were on opposite sides of the display. In this condition, the effects of preparing to make a saccade proved to be stronger than the effects of attentional allocation until well after the saccade had finished, suggesting that making a saccade necessarily involves the allocation of attention to the target position. The effects of probe stimuli on saccade latencies were also examined: probe stimuli that appeared before the saccade shortened saccade latencies if they appeared at the saccade target, and lengthened saccade latencies if they appeared on the opposite side of fixation. These facilitatory and inhibitory effects were shown to occur at different stages of saccade preparation and suggest that attention plays an important role in the generation of voluntary eye movements. The results of this study indicate that while it is possible to make attention movements without making corresponding eye movements, it is not possible to make an eye movement (in the absence of peripheral stimulation) without making a corresponding shift in the focus of attention.
Further evidence for a peripheral sympathicolytic action of the antihypertensive cicletanine in rats. (1995)

The site and mechanism of action of the antihypertensive agent cicletanine have been studied. In the pithed rat model, intravenous (i.v.) cicletanine was able to reduce the elevated blood pressure induced by continuous infusion of the alpha 1-adrenergic agonist, methoxamine, in a dose-related manner. In strip preparation of the aorta from deoxycorticosterone (DOCA)-salt-treated rats, cicletanine was found to prevent the contraction induced by 1 microM noradrenaline. When subeffective doses of phentolamine (0.25 mg/kg p.o.) plus cicletanine (3 mg/kg p.o.) were given together, a clear-cut antihypertensive effect was observed in DOCA-salt rats. Moreover, subchronic administration of cicletanine (30 mg/kg p.o.), during the one month period of DOCA-salt administration to produce high blood pressure readings, was able to prevent cardiac noradrenaline depletion. These data suggest that the antihypertensive effect of cicletanine, which is clinically well tolerated, may be due to a multifactorial mechanism of its action, through which it might alter a number of physiological mediators while exercising a slight potency on each of them.
Optimal design of five phase permanent magnet assisted synchronous reluctance motor for integrated starter generator application (2015)

This paper presents the design of optimal five-phase permanent magnet assisted synchronous reluctance motor (PMa-SynRM) for integrated starter generator (ISG) application. PMa-SynRM is the hybrid structure of interior permanent magnet (IPM) motor and synchronous reluctance motor (SynRM). In this study, an optimized 15kW five-phase PMa-SynRM has been proposed as a better substitute for three-phase IPM motor for ISG operation in Honda Civic Hybrid car. A new reverse engineering technique (RET) has been applied to model the Honda IPM ISG. In order to develop a better PMa-SynRM ISG, the model developed using RET has been used as reference. Thorough analytical and finite element analysis have been performed to obtain the optimal PMa-SynRM design which has better performance characteristics compared to the Honda IPM ISG. Lumped parameter modeling (LPM) has been utilized with differential evolution (DE) optimizer to extract the best optimal design for the five-phase PMa-SynRM ISG. For the same power and volume, five-phase PMa-SynRM design has shown better performance characteristics in terms of cogging torque and torque developed.
MASS TRANSFER IN A MULTISTAGE VIBRATING DISK COLUMN WITH COCURRENT GAS-LIQUID FLOW (1974)

Mass transfer characteristics of a cocurrent multistage vibrating disk column are studied by the absorption of pure carbon dioxide into water. Axial mixing in the liquid phase is taken into account by using a back-flow model. Disk vibration definitely enhances the mass transfer rate at low gas velocity and high liquid velocity. On the other hand, at high gas velocity and low liquid velocity, disk vibration does not noticeably improve the mass transfer characteristics, and even worsens them in some cases. The increase in absorption rate by disk vibration can be well estimated by information on the gas holdup characteristics, the mass transfer characteristics without vibration, the gas bubble size data and the axial mixing characteristics in the liquid phase.
SPME-GC/MS Method for the Determination of Herbicides in Drinking Waters (2009)

A SPME-GC/MS method for the determination of herbicides acetochlor, butachlor and metolachlor in drinking waters was developed. SPME conditions, including SPME fibre types, extraction and desorption time, ion strength, agitation speed and pH have been evaluated and optimized. The extract was analyzed by GC-MS under select ion monitoring (SIM) mode. The herbicide residues were quantified by external standard method. The detection limits and relative standard deviations for acetochlor, butachlor and metolachlor were 2.8ng L-1, 3.2 ng L-1, 7.4 ng L -1, and 5.6 %, 4.1 %, 7.9 %, respectively. The average recoveries ranged from 81%to 102%. The three target herbicides were not detected in all the samples we analyzed. The method is easy to operation, and with good precision, it is therefore well suited for the routine analysis of herbicides in drinking waters.
Targeting the site encoded by SERPINA1*E342K for treating alpha‐1 antitrypsin deficiency‐associated liver diseases (2019)

Alpha1-antitrypsin (AAT) deficiency predisposes individuals to emphysema and liver diseases such as cirrhosis and hepatocellular carcinoma. The deficiency results from mutations in the SERPIN1A gene encoding AAT molecules that cause hepatotoxic retention within the endoplasmic reticulum. Since the E342K mutation is the basis for destabilization leading to lung and liver pathologies, we used the crystal structure of the mutated AAT as the basis for molecular docking selection of candidate compounds that may bind and stabilize the 342K structural pocket. We identified compounds that inhibited intracellular accumulation of AAT in hepatocytes in vitro. These data suggest that drug binding to a structural site encoded by a mutation associated with AAT deficiency has the potential for clinical utility by modulating conformational transitions.
Filamentation in air with ultrashort mid-infrared pulses (2011)

We theoretically investigate filamentation of ultrashort laser pulses in air in the mid-infrared regime under conditions in which the group-velocity dispersion (GVD) is anomalous. When a high-power, ultra-short mid-infrared laser beam centered at 3.1-μm forms a filament, a spatial solitary wave is stabilized by the plasma formation and propagates several times its diffraction length. Compared with temporal self-compression in gases due to plasma formation and pulse splitting in the normal-GVD regime, the minimum achievable pulse duration (∼70 fs) is limited by the bandwidth of the anomalous-GVD region in air. For the relatively high powers, multiple pulse splitting due to the plasma effect and shock formation is observed, which is similar to that which occurs in solids. Our simulations show that the energy reservoir also plays a critical role for longer propagation of the air filament in the anomalous-GVD regime.
Use of Ultrasonography as a Diagnostic and Therapeutic Tool in Sports Medicine (2014)

Ultrasonography has many important advantages over other imaging modalities and many important applications in sports medicine. This article presents an evidence-based discussion of the use of ultrasound technology to diagnose and treat common musculoskeletal disorders, with emphasis on the shoulder, elbow, hip, knee, and foot and ankle. Topics include basic principles, scan artifacts, the appearance of musculoskeletal structure characteristics and pathologies, and various diagnostic and therapeutic applications in sports medicine.
The mechanochemical Scholl reaction – a solvent-free and versatile graphitization tool (2018)

Herein, we report on the mechanochemical Scholl reaction of dendritic oligophenylene precursors to produce benchmark nanographenes such as hexa-peri-hexabenzocoronene (HBC), triangular shaped C60 and expanded C222 under solvent-free conditions. The solvent-free approach overcomes the bottleneck of solubility limitation in this well-known and powerful reaction. The mechanochemical approach allows tracking the reaction process by in situ pressure measurements. The quality of produced nanographenes has been confirmed by MALDI-TOF mass spectrometry and UV-Vis absorption spectroscopy. This approach paves the way towards gram scale and environmentally benign synthesis of extended nanographenes and possibly graphene nanoribbons suitable for application in carbon based electronics or energy applications.
Decoding the role of transcriptomic clocks in the human prefrontal cortex (2023)

Aging is a complex process with interindividual variability, which can be measured by aging biological clocks. Aging clocks are machine-learning algorithms guided by biological information and associated with mortality risk and a wide range of health outcomes. One of these aging clocks are transcriptomic clocks, which uses gene expression data to predict biological age; however, their functional role is unknown. Here, we profiled two transcriptomic clocks (RNAAgeCalc and knowledge-based deep neural network clock) in a large dataset of human postmortem prefrontal cortex (PFC) samples. We identified that deep-learning transcriptomic clock outperforms RNAAgeCalc to predict transcriptomic age in the human PFC. We identified associations of transcriptomic clocks with psychiatric-related traits. Further, we applied system biology algorithms to identify common gene networks among both clocks and performed pathways enrichment analyses to assess its functionality and prioritize genes involved in the aging processes. Identified gene networks showed enrichment for diseases of signal transduction by growth factor receptors and second messenger pathways. We also observed enrichment of genome-wide signals of mental and physical health outcomes and identified genes previously associated with human brain aging. Our findings suggest a link between transcriptomic aging and health disorders, including psychiatric traits. Further, it reveals functional genes within the human PFC that may play an important role in aging and health risk.
Amyloid-β Alters the DNA Methylation Status of Cell-fate Genes in an Alzheimer's Disease Model (2013)

Alzheimer's disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. DNA was isolated from neurons treated with Aβ or vehicle, and the two samples were digested with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. The fragments were amplified and co-hybridized to a commercial promoter microarray. Data analysis revealed a subset of genomic loci that shows a significant change in DNA methylation following Aβ treatment in comparison to the control group. After mapping these loci to nearby genes, we discovered high enrichment for cell-fate genes that control apoptosis and neuronal differentiation. Finally, we incorporated three of those genes in a possible model suggesting the means by which Aβ contributes to the brain shrinkage and memory loss seen in AD.
Novel current limitation technique without current feedback for digital-controlled battery charger in UPS applications (2010)

The objective of this paper is to present a new current limitation technique without current feedback for digital-controlled battery charger in UPS applications. A control method is proposed to achieve constant current and constant voltage charging without current feedback. The basic idea is to keep constant charging current by limiting the duty of charger. As the battery voltage is increased after charge, constant voltage mode is achieved by voltage mode control. A digital-controlled charger is designed and implemented for UPS applications. A low cost MCU is used to realize the proposed control method in software. Experimental results demonstrate that the effectiveness of the design and implementation.
Single femtosecond exposure recording of an image hologram by spectral hole burning in an unstable tautomer of a phthalocyanine derivative (2000)

We demonstrate, for what we believe is the first time, recording of a femtosecond image hologram by illumination with a single pair of high-intensity femtosecond pulses in a broad inhomogeneous bandwidth spectral hole-burning material consisting of a polymer film doped with anthraceno-phthalocyanine dye molecules. High efficiency of spectral hole burning is achieved by preillumination of the sample at a low temperature to convert the dye molecules into an unstable tautomer form.
Core-shell AlGaAs nanowires for high efficiency tandem solar cell on Si (2016)

session III-V, Multijonctions, Nanofils
Toward Harvesting Vibration Energy from Multiple Directions by a Nonlinear Compressive-Mode Piezoelectric Transducer (2015)

We propose a new concept for harvesting vibration energy from multiple directions. Our approach effectively exploits the nonlinear vibration of a doubly clamped elastic rod, converting and amplifying excitations to compressive loads in piezoelectric materials. The proposed multidirectional compressive-mode piezoelectric energy harvester (MC-PEH) is capable of isotropically harnessing vibration energy from any angle in a plane. Meanwhile, the MC-PEH demonstrates a high-voltage output and a wide working bandwidth, along with the distinct softening nonlinear phenomena. Theoretical analysis and experimental testing are performed and exhibit good agreement over a range of excitation frequencies. This study enhances the practicability and adaptability of using energy harvesters in a complex environment.
Evaluating image resolution in stimulated emission depletion microscopy (2018)

Precise knowledge of the effective spatial resolution in a stimulated emission depletion (STED) microscopy experiment is essential for reliable interpretation of the imaging results. STED microscopy theoretically provides molecular resolution, but practically different factors limit its resolution. Because these factors are related to both the sample and the system, a reliable estimation of the resolution is not straightforward. Here we show a method based on the Fourier ring correlation (FRC), which estimates an absolute resolution value directly from any STED and, more in general, point-scanning microscopy image. The FRC-based resolution metric shows terrific sensitivity to the image signal-to-noise ratio, as well as to all sample and system dependent factors. We validated the method both on commercial and on custom-made microscopes. Since the FRC-based metric can be computed in real time, without any prior information of the system/sample, it can become a fundamental tool for (i) microscopy users to optimize the experimental conditions and (ii) microscopy specialists to optimize the system conditions.