gebhart/patrepeval huggingface dataset:
The association of aluminum Alzheimer's disease, and neurofibrillary tangles. (1987)

Alzheimer's disease is a progressive neurodegenerative disease characterized by the development of large numbers of neurofibrillary tangles in certain neuronal populations. Aluminum salts inoculated into experimental animals produce neurofilamentous lesions which are similar, but not identical, to the neurofibrillary tangle of Alzheimer's disease. Although a few reports suggest evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate. Using scanning electron microscopy with x-ray spectrometry, we have identified accumulations of aluminum in neurofibrillary tangle-bearing neurons of Alzheimer's disease. Similar accumulations have been identified in the neurofibrillary tangle-bearing neurons found in the brains of indigenous natives of Guam who suffer from parkinsonism with dementia and from amyotrophic lateral sclerosis. This ongoing research still cannot ascribe a causal role of aluminum in the pathogenesis of the neurofibrillary tangle; however, it does suggest that environmental factors may play an important part in the formation of this abnormality.
Changing the Mindset in Life Sciences Toward Translation: A Consensus (2014)

Participants at the recent Translate! 2014 meeting in Berlin, Germany, reached a consensus on the rate-limiting factor for advancing translational medicine.
Text Style Transfer: A Review and Experiment Evaluation. (2020)

The stylistic properties of text have intrigued computational linguistics researchers in recent years. Specifically, researchers have investigated the Text Style Transfer (TST) task, which aims to change the stylistic properties of the text while retaining its style independent content. Over the last few years, many novel TST algorithms have been developed, while the industry has leveraged these algorithms to enable exciting TST applications. The field of TST research has burgeoned because of this symbiosis. This article aims to provide a comprehensive review of recent research efforts on text style transfer. More concretely, we create a taxonomy to organize the TST models and provide a comprehensive summary of the state of the art. We review the existing evaluation methodologies for TST tasks and conduct a large-scale reproducibility study where we experimentally benchmark 19 state-of-the-art TST algorithms on two publicly available datasets. Finally, we expand on current trends and provide new perspectives on the new and exciting developments in the TST field.
AdVersarial: Perceptual Ad Blocking meets Adversarial Machine Learning (2018)

Perceptual ad-blocking is a novel approach that detects online advertisements based on their visual content. Compared to traditional filter lists, the use of perceptual signals is believed to be less prone to an arms race with web publishers and ad networks. We demonstrate that this may not be the case. We describe attacks on multiple perceptual ad-blocking techniques, and unveil a new arms race that likely disfavors ad-blockers. Unexpectedly, perceptual ad-blocking can also introduce new vulnerabilities that let an attacker bypass web security boundaries and mount DDoS attacks. We first analyze the design space of perceptual ad-blockers and present a unified architecture that incorporates prior academic and commercial work. We then explore a variety of attacks on the ad-blocker's detection pipeline, that enable publishers or ad networks to evade or detect ad-blocking, and at times even abuse its high privilege level to bypass web security boundaries. On one hand, we show that perceptual ad-blocking must visually classify rendered web content to escape an arms race centered on obfuscation of page markup. On the other, we present a concrete set of attacks on visual ad-blockers by constructing adversarial examples in a real web page context. For seven ad-detectors, we create perturbed ads, ad-disclosure logos, and native web content that misleads perceptual ad-blocking with 100% success rates. In one of our attacks, we demonstrate how a malicious user can upload adversarial content, such as a perturbed image in a Facebook post, that fools the ad-blocker into removing another users' non-ad content. Moving beyond the Web and visual domain, we also build adversarial examples for AdblockRadio, an open source radio client that uses machine learning to detects ads in raw audio streams.
Synthesis and antinociceptive activity of dezocine degradation products. (1987)

Three degradation products of dezocine were synthesized and tested for possible antinociceptive activity. 13-Amino-5,6,7,8,9,10-hexahydro-5-methyl-5,11-methanobenzocyclodecen+ ++-3-ol demonstrated antinociceptive properties comparable to morphine.
A 15-MHz high peak power KLM Ti:Al/sub 2/O/sub 3/ laser using multiple-pass long cavity (1998)

Summary form only given. Mode-locked operation at 15 MHz has been demonstrated using a novel and long-cavity laser with a multi-pass long cavity (MPC). We successfully obtained 0.5 MW peak power and 20 fs nearly transform-limited pulse from Kerr lens mode locked (KLM) Ti:Al/sub 2/O/sub 3/ laser. This unprecedented low repetition rate laser suggests new approaches for achieving MW-level peak powers from laser cavities.
Efficacy and tolerability of the thymidylate synthase (TS) inhibitor, BGC 945 is mediated through its selective uptake via the α-folate receptor (α-FR) in IGROV-1 human tumor xenografts (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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BGC 945 is a tumor-targeted folate-based TS inhibitor in preclinical development (Gibbs et al, Cancer Res., 2005). Targeting is achieved by its unique selectivity for α-FR-mediated rather than reduced-folate carrier (RFC)-mediated uptake into cells. In contrast to the ubiquitous expression of the RFC in normal and malignant tissues, α-FR expression is over-expressed in many epithelial tumors but in most normal tissues is confined to the apical membrane surface inaccessible to circulating drugs. The sensitivity of human tumor cell lines to BGC 945 is dependent on α-FR expression levels and the GI50 can be as low as 3nM in highly overexpressing human tumor cells such as KB. Studies using pharmacodynamic (PD) markers of TS inhibition have demonstrated tumor selectivity of BGC 945 in mice bearing KB xenografts at doses ranging from 5-100mg/kg. This level of activity is explained by the slow clearance of BGC 945 from tumor (t1/2β=28h). The frequency and level of α-FR overexpression is particularly high in human ovarian tumors (~90% of cases) and we have therefore studied the effect of BGC 945 in IGROV-1 ovarian carcinoma xenografts. Expression levels are ~25% of those seen in KB cells (~23pmol folic acid (FA) binding sites/107 cells). α-FR-mediated TS and growth inhibition was demonstrated in vitro at BGC 945 concentrations as low as 30nM. Plasma and tumor deoxyuridine (dUrd) levels are PD endpoints of TS inhibition in proliferating normal tissues and tumor respectively. BGC 945 at 100mg/kg induced a 5-20-fold increase in tumor dUrd at 4-72h without increases in the plasma, consistent with tumor targeting. 200mg/kg BGC 945 induced only a small, transient increase in plasma dUrd at 4h consistent with some non-FR mediated TS inhibition when plasma drug levels were high. This dose is therefore predicted not to cause cytotoxicity to normal proliferating tissues and therefore was chosen for evaluating IGROV-1 antitumor activity. Mice have ~100-fold higher plasma thymidine levels than humans, which attenuates the activity of TS inhibitors. Chronic daily dosing of TS inhibitors can however give some antitumor activity in mice. Athymic mice bearing IGROV-1 xenografts were dosed once daily for 14 days, and growth delay was evaluated using the median time for the tumor volume to increase 4-fold ( 6 and 11.5 days in controls and treated animals respectively; p=0.01). No weight loss was observed. These data suggest that, in spite of the challenges associated with evaluation of TS inhibitors in mice, BGC 945 induces significant antitumor activity at a dose that induces no obvious toxicity, and demonstrates that both the efficacy and tolerability of BGC 945 is mediated through its selectivity for TS and the α-FR. This work is funded by Cancer Research UK and BTG International.
Optimization of plastisol processes by dynamic mechanical analysis (2007)

Abstract Dynamic mechanical analysis (DMA) can be a particularly useful tool for studying PVC plastisol manufacturing processes. DMA temperature sweeps are uniquely able to characterize plastisol gelation and fusion behavior under low shear stress conditions that are similar to conditions found in many commercial plastisol processing operations. Dynamic mechanical analysis is also well‐suited for studying plastisol melt viscosities at low shear rates such as might be encountered in a flexible PVC foaming process or rotomolding process. Likewise, DMA rate sweeps or strain sweeps can give insights into self‐association and flow properties in a plastisol which ordinary viscometers cannot provide. J. VINYL ADDIT. TECHNOL., 13:151–154, 2007. © 2007 Society of Plastics Engineers
Monolithic integration of vertical-cavity surface-emitting lasers with in-plane waveguides (2005)

The ability to couple light from a vertical-cavity surface-emitting laser into a planar, on-chip waveguide creates new opportunities for achieving higher levels of integration and functionality. Here we propose to use a strong grating etched into a waveguide defined into the top layer of the epitaxially grown structure, so that epitaxial regrowth is not required. By introducing a defect mode into the cavity we were able to achieve a 40% coupling efficiency even though light is coupled through a ninety degrees bend. We also show that polarization control of the vertical-cavity surface-emitting laser is enhanced by coupling to the defect mode. Calculations were performed using the finite-difference time-domain method.
Enhanced cell culture performance using inducible anti‐apoptotic genes E1B‐19K and Aven in the production of a monoclonal antibody with Chinese hamster ovary cells (2006)

Mammalian cells are used for the production of numerous biologics including monoclonal antibodies. Unfortunately, mammalian cells can lose viability at later stages in the cell culture process. In this study, the effects of expressing the anti-apoptosis genes, E1B-19K and Aven, separately and in combination on cell growth, survival, and monoclonal antibody (MAb) production were investigated for a commercial Chinese Hamster Ovary (CHO) mammalian cell line. CHO cells were observed to undergo apoptosis following a model insult, glucose deprivation, and at later stages of batch cell culture. The CHO cell line was then genetically modified to express the anti-apoptotic proteins E1B-19K and/or Aven using an ecdysone-inducible expression system. Stable transfected pools induced to express Aven or E1B-19K alone were found to survive 1-2 days longer than the parent cell line following glucose deprivation while the expression of both genes in concert increased cell survival by 3 days. In spinner flask batch studies, a clonal isolate engineered to express both anti-apoptosis genes exhibited a longer operating lifetime and higher final MAb titer as a result of higher viable cell densities and viabilities. Interestingly, survival was increased in the absence of an inducer, most likely as a result of leaky expression of the anti-apoptosis genes confirmed in subsequent PCR studies. In fed-batch bioreactors, the expression of both anti-apoptosis genes resulted in higher growth rates and cell densities in the exponential phase and significantly higher viable cell densities, viabilities, and extended survival during the post-exponential phase. As a result, the integral of viable cells (IVC) was between 40 and 100% higher for cell lines engineered to express both Aven and E1B-19K in concert, and the operational lifetime of the fed-batch bioreactors was increased from 2 to 5 days. The maximum titers of MAb were also increased by 40-55% for bioreactors containing cells expressing Aven and E1B-19K. These increases in volumetric productivity arose primarily from enhancements in viable cell density over the course of the fed-batch culture period since the specific productivities for the cells expressing anti-apoptosis genes were comparable or slightly lower than the parental hosts. These results demonstrate that expression of anti-apoptosis genes can enhance culture performance and increase MAb titers for mammalian CHO cell cultures especially under conditions such as extended fed-batch bioreactor operation.
Practical Early Development Synthesis of Nav1.7 Inhibitor GDC-0310 (2020)

The concise early development route to the Nav1.7 inhibitor GDC-0310 is described. The active pharmaceutical ingredient (API) contains one stereocenter, which was obtained with high enantiomeric excess (&gt;99:1) by using an SN2 displacement approach to connect two intermediates: a chiral benzyl alcohol and a piperidine. The synthesis of the piperidine building block proceeded via a regioselective SNAr reaction on 1-chloro-2,4-difluorobenzene by N-Boc-4-piperidinemethanol, followed by installation of the methyl ester group by electrophilic aromatic bromination and a palladium-catalyzed alkoxycarbonylation. A subsequent Suzuki–Miyaura cross-coupling reaction was then telescoped directly into cleavage of the Boc group to provide the advanced piperidine intermediate. The key feature of the synthesis is the highly selective SN2 displacement of the chiral mesylate of (R)-1-(3,5-dichlorophenyl)ethan-1-ol with the piperidine intermediate, followed by a chiral purity upgrade via the corresponding (1S)-(+)-camphorsulfonic acid salt. After standard hydrolysis of the methyl ester and CDI mediated amidation to couple the resulting acid with methanesulfonamide, enantiomerically pure GDC-0310 was obtained in high overall yield (37%) on a 6.5 kilogram scale.
Using ultrathin double-layer gas-permeable capping metal to form sensitive low-power gas sensors (2020)

Abstract In this work, we investigated a simple, sensitive, and low-powered ammonia (NH 3 ) gas sensor using a thin bi-layered metal capped on an organic semiconductor chemoresistor to deliver a sensitive response to NH 3 (ppb level) at room temperature. An optimized thin bi-layered Al/Ag metal (2 nm/10 nm) successfully forms a gas-permeable structure to realize ppb-regime gas sensing better than other single-layered thin Ag, Al, or Au (12 nm) metal electrodes. The performance of the simple metal-capped gas sensor is greatly dependent on the surface roughness of the thin metal electrodes, and the very rough thin bi-layered metal Al/Ag (2 nm/10 nm) allows high gas penetration. The optimized device exhibits more than 10% response to 100 ppb NH 3 at only 0.5 V. The simple, low-cost, highly sensitive, and low-powered gas sensors are promising for Internet of things applications.
The First Total Synthesis of (R)‐Convolutamydine A. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Effect of Oxidation on Single‐Fiber Pullout Interfacial Shear Stresses in a Silicon Carbide–Borosilicate Glass System (1991)

The debonding, τ d , and frictional, τ f , interfacial shear strengths between 140‐μm diameter SiC (with a 1‐μm C‐rich coating in which SiC particles are embedded) monofilaments and borosilicate glass were measured using the single‐fiber pullout method as a function of postfabrication heat treatments [5 h at temperatures between 200° and 525°C] in 4% H 2 –96% Ar and air. The debonding shear stress remained virtually unchanged after extended H 2 anneals. In air, however, τ d , was found to initially increase and then subsequently decrease with increasing postfabrication heat treatment temperature. The initial increase in τ d is due to enhanced bonding between the fiber and the borosilicate matrix as a result of the oxidation of the SiC particles embedded in the outermost carbon layer coating. At temperatures greater than about 450°C, oxidation of the C layer results in the severe degradation of the interfacial shear strengths.
Mechanical control of tissue morphogenesis during embryological development (2006)

Twenty years ago, we proposed a model of developmental control based on tensegrity architecture, in which tissue pattern formation in the embryo is controlled through mechanical interactions between cells and extracellular matrix (ECM) which place the tissue in a state of isometric tension (prestress). The model proposed that local changes in the mechanical compliance of the ECM, for example, due to regional variations in basement membrane degradation beneath growing epithelium, may result in local stretching of the ECM and associated adherent cells, much like a "run-in-a-stocking". Cell growth and function would be controlled locally though physical distortion of the associated cells, or changes in cytoskeletal tension. Importantly, experimental studies have demonstrated that cultured cells can be switched between different fates, including growth, differentiation, apoptosis, directional motility and different stem cell lineages, by modulating cell shape. Experiments in whole embryonic organ rudiments also have confirmed the tight correlation between basement membrane thinning, cell tension generation and new bud and branch formation during tissue morphogenesis and that this process can be inhibited or accelerated by dissipating or enhancing cytoskeletal tension, respectively. Taken together, this work confirms that mechanical forces generated in the cytoskeleton of individual cells and exerted on ECM scaffolds, play a critical role in the sculpting of the embryo.
Acoustic radiation force impulse imaging on an IVUS circular array (2013)

Our long-term goal is the detection and characterization of vulnerable plaque in the coronary arteries of the heart using IVUS catheters. Vulnerable plaque, characterized by a thin fibrous cap and a soft, lipid-rich, necrotic core is a pre-cursor to heart attack and stroke. Early detection of such plaques may potentially alter the course of treatment of the patient in order to prevent ischemic events. In this paper, we modified Volcano Visions 8.2 French, 9MHz catheters and Volcano Platinum 3.5 French, 20MHz catheters by short circuiting portions of the array for ARFI applications. The catheters had an effective transmit aperture size of 2mm and 1.5mm respectively. The catheters were connected to a Verasonics scanner and driven with pushing pulses of 180V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p-p</sub> to acquire ARFI data from a soft gel phantom with a Young's modulus of 2.9 kPa. The dynamic response of the tissue-mimicking material demonstrates a typical ARFI motion of 1-2 microns as the gel phantom displaces away and recovers back to its normal position. Our results demonstrate that the generation of radiation force from IVUS catheters and the development of intravascular ARFI may be feasible.
<title>Volumetric three-dimensional display using projection CRT</title> (2002)

Volumetric 3D display systems have been expected to be able to reproduce natural view without eye fatigue. We have developed a prototype of the volumetric 3D monochromatic display system. It consists of a flat screen rotating at the speed of 1200 rpm(rotations per minute) and a synchronized projection engine. The projection engine can project 300 image slices per one rotation of the screen, so that we can see the continuous real three-dimensional image by residual images to human eyes. For this prototype, we use a 7 inch green projection CRT that is used in projection TVs as a two-dimensional image engine. In order to rapidly scan 3D display space, vector (random) scanning rather than normal raster scanning is used. We specially designed a lenticular type screen that has such a shape as to achieve constant gain over 180 degrees horizontal viewing angle. To collimate and redirect the light rays, Fresnel lenses and projection lens system are used, and to hide mirrors from viewer's viewing zone, off-axis optics are used. To obtain a stable volumetric three-dimensional image, the projected two-dimensional images and the positions of the screen should be synchronized. We devise a new algorithm that reconstructs the contour data of image slices from real three-dimensional shape. Vibration and noise is minimized. Brightness is not a problem and high enough resolution for relatively simple images can be achieved. A new version of full color and the higher resolution is on the way.
Silicon Optical Modulator Using a Low-Loss Phase Shifter Based on a Multimode Interference Waveguide (2019)

We have developed a novel phase modulator, based on fin-type electrodes placed at self-imaging positions of a silicon multimode interference (MMI) waveguide, which allows reduced scattering losses and relaxes the fabrication tolerance. The measured propagation losses and spectral bandwidth are 0.7 dB and 33 nm, respectively, on a 987 μm-long phase shifter. Owing to the self-imaging effect in the MMI waveguide, the wave-front expansion to the electrode was counteracted, and therefore, the scattering loss caused by electrode fins was successfully mitigated. As a proof-of-concept for the MMI-based phase modulator applications, we performed optical modulation based on Mach-Zehnder interferometers (MZIs). The π shift current of the modulator was 1.5 mA.
A split horseradish peroxidase for the detection of intercellular protein-protein interactions and sensitive visualization of synapses. (2016)

Intercellular protein-protein interactions (PPIs) enable communication between cells in diverse biological processes, including cell proliferation, immune responses, infection, and synaptic transmission, but they are challenging to visualize because existing techniques have insufficient sensitivity and/or specificity. Here we report a split horseradish peroxidase (sHRP) as a sensitive and specific tool for the detection of intercellular PPIs. The two sHRP fragments, engineered through screening of 17 cut sites in HRP followed by directed evolution, reconstitute into an active form when driven together by an intercellular PPI, producing bright fluorescence or contrast for electron microscopy. Fusing the sHRP fragments to the proteins neurexin (NRX) and neuroligin (NLG), which bind each other across the synaptic cleft, enabled sensitive visualization of synapses between specific sets of neurons, including two classes of synapses in the mouse visual system. sHRP should be widely applicable to studying mechanisms of communication between a variety of cell types.
A Benzodiazepine Receptor Antagonist Decreases Sleep and Reverses the Hypnotic Actions of Flurazepam (1983)

The benzodiazepine receptor antagonist 3-hydroxymethyl-beta-carboline, which blocks several of the pharmacological actions of benzodiazepines, induces a dose-dependent increase in sleep latency in the rat. Furthermore, at a low dose that by itself does not affect sleep, 3-hydroxymethyl-beta-carboline blocks sleep induction by a large dose of flurazepam. The benzodiazepine receptor may play a role in both the physiological regulation and pharmacological induction of sleep.