gebhart/patrepeval huggingface dataset:
Discovery and optimization of piperazine-1-thiourea-based human phosphoglycerate dehydrogenase inhibitors (2018)

Abstract Proliferating cells, including cancer cells, obtain serine both exogenously and via the metabolism of glucose. By catalyzing the first, rate-limiting step in the synthesis of serine from glucose, phosphoglycerate dehydrogenase (PHGDH) controls flux through the biosynthetic pathway for this important amino acid and represents a putative target in oncology. To discover inhibitors of PHGDH, a coupled biochemical assay was developed and optimized to enable high-throughput screening for inhibitors of human PHGDH. Feedback inhibition was minimized by coupling PHGDH activity to two downstream enzymes (PSAT1 and PSPH), providing a significant improvement in enzymatic turnover. Further coupling of NADH to a diaphorase/resazurin system enabled a red-shifted detection readout, minimizing interference due to compound autofluorescence. With this protocol, over 400,000 small molecules were screened for PHGDH inhibition, and following hit validation and triage work, a piperazine-1-thiourea was identified. Following rounds of medicinal chemistry and SAR exploration, two probes (NCT-502 and NCT-503) were identified. These molecules demonstrated improved target activity and encouraging ADME properties, enabling both in vitro and in vivo assessment of the biological importance of PHGDH, and its role in the fate of serine in PHGDH-dependent cancer cells.
Modified valley fill high power factor electronic ballast for compact fluorescent lamps (2002)

A simple, lost cost, high power factor ballast, referred to as the modified valley fill circuit, for compact fluorescent lamps is introduced. This circuit peak charges the valley fill (electrolytic) capacitor from an auxiliary winding on the high frequency ballasting inductor to a fraction of the peak line voltage, where the input power factor is optimized at 0.95. A simple lamp current feedback scheme is employed to keep the lamp current crest factor near 1.7. The overall efficiency is in the range of 87-89%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A Modified Asymmetrical Pulse-Width-Modulated Resonant DC/DC Converter Topology (2004)

A modified asymmetrical pulse-width-modulated resonant dc/dc converter employing an auxiliary circuit will be proposed in this paper. The auxiliary circuit consists of a network of two capacitors and an inductor. The aim of this network is to produce zero-voltage-switching (ZVS) over a wide input voltage range, while reducing the voltage stress on the resonant component. A detailed analysis and performance characteristics are presented. Experimental results for a 5 V, 35 W converter show an efficiency of 83% at a constant operating frequency of 500 kHz. Using metal oxide semiconductor field effect transistors (MOSFETs) as synchronous rectifiers can further reduce power losses and improve the efficiency to be greater than 90%.
A μL-scale micromachined microbial fuel cell having high power density (2011)

We report a MEMS (Micro-Electro-Mechanical Systems)-based microbial fuel cell (MFC) that produces a high power density. The MFC features 4.5-μL anode/cathode chambers defined by 20-μm-thick photo-definable polydimethylsiloxane (PDMS) films. The MFC uses a Geobacter-enriched mixed bacterial culture, anode-respiring bacteria (ARB) that produces a conductive biofilm matrix. The MEMS MFC generated a maximum current density of 16,000 μA cm(-3) (33 μA cm(-2)) and power density of 2300 μW cm(-3) (4.7 μW cm(-2)), both of which are substantially greater than achieved by previous MEMS MFCs. The coulombic efficiency of the MEMS MFC was at least 31%, by far the highest value among reported MEMS MFCs. The performance improvements came from using highly efficient ARB, minimizing the impact of oxygen intrusion to the anode chamber, having a large specific surface area that led to low internal resistance.
60 GHz planar doped barrier subharmonic mixer (1983)

A 60 GHz planar doped barrier (PDB) subharmonically pumped mixer using 10 μm mesa diodes has been designed and fabricated using a new cross-guide mounting configuration. RF performance data using a 30 GHz local oscillator and a signal frequency of 59.5 GHz are discussed.
Alpha-particle Gas Pressure Gauge (1995)

Described are preliminary results obtained on a novel gas pressure gauge that operates between 0.1 and 1000 mb. This gauge uses a 1- micron Ci alpha particle source to ionize the gas in a small chamber with an electric field imposed between anode and cathode electrodes that drives positive ions to the cathode where they are collected electronically. This gauge could make Martian pressure measurements.
Towards Performance Related Decision Support for Model Driven Engineering of Enterprise SOA Applications (2008)

Model driven performance engineering (MDPE) enables early performance feedback in a MDE process, in order to avoid late identification of performance problems which could cause significant additional development costs. In our past work we argued that a synchronization mechanism between development and performance analysis models is required to adequately integrate analysis results into the development process enabling performance related decision support. In this paper we present a solution for this requirement. We present a new multi-view based approach and its implementation enabling systematic performance related decision support. We currently apply our research on the model driven engineering of process orchestrations on top of SAP's enterprise service oriented architecture (Enterprise SOA).
Estimating Cell Transfer Delay and Cell Delay Variation in ATM Networks: Measurement Techniques and Results (1999)

Abstract Performance parameters of the ATM layer related to delay are the cell transfer delay (CTD) and cell delay variation (CDV). Monitoring CTD and CDV is important for the operator of an ATM network, in order to guarantee the quality of service expected by the user. This paper discusses basic properties of CTD and CDV, the latter one being defined in terms of 2‐‐point CDV and 1‐‐point CDV. It outlines fundamental measurement techniques and methods for estimating CTD and 2‐‐point CDV, which do not rely on the availability of synchronized clocks at the measurement points. Finally, measurement results obtained from the ATM network operated by Deutsche Telekom are presented.
EVOLUTION OF PEST-INDUCED DEFENSES IN<i>BRASSICA</i>PLANTS: TESTS OF THEORY (1998)

Theory on the evolution of pest-induced defenses in plants predicts (1) a negative genetic correlation between induced and constitutive (basal) levels of secondary metabolites, and (2) costs of maintaining high constitutive levels of secondary metabolites. We tested these predictions with genetically diverged populations created by artificial selection on myrosinase and glucosinolate levels in Brassica rapa. Glucosinolates and their breakdown products from the action of the enzyme myrosinase are putative defensive compounds in brassicas. Theory also suggests that effects of genetic changes in secondary metabolites may depend on resource availability, so nitrogen, a main constituent of glucosinolates and myrosinase was added in fertilizer treatments to assess costs. We used the fungal pathogen Leptosphaeria maculans and diamondback moth larvae Plutella xylostella as induction agents in comparisons of the diverged myrosinase populations. We found pleiotropic effects among constitutive myrosinase levels and pathogen-induced levels of myrosinase, glucosinolates, and resistance to diamondback moth larvae. In field experiments, genetic increases in myrosinase production were associated with significant decreases in estimated seed production, despite potential benefits from increased resistance to flea beetles Phylotreta cruciferae. No genotype-by-nitrogen interaction was found. Although costs were detected, our results indicate, in contrast to theory, mainly positive pleiotropic effects between constitutive levels of secondary metabolites and induced responses.
Molecular Weight Dependence of Equilibrium Melting Temperature and Lamellar Thickening of Isotactic Polypropylene with High Tacticity (2003)

Molecular weight (M) dependence of the equilibrium melting temperature of isotactic polypropylene (iPP) with high tacticity ([mmmm]=99.6%) was studied. Four fractionated iPPs with M n=23×103, 64×103, 94×103, and 263×103 were used. was obtained by using an improved method based on the Gibbs–Thomson plot proposed in previous papers. The effect of “melting kinetics” on melting temperature (T m) was eliminated by observing isothermal melting of spherulites. The effect of lamellar thickening on T m during T m measurement at high temperature was also eliminated by observing thick lamellae formed at high crystallization temperatures (T c=148∼166°C). With increase of M, increased significantly. The empirical equation, (°C), was obtained. The molecular weight dependence of the α2–α2′ transition was observed. The transition temperature (T α2–α2′) also increased with increase of M. The ΔT dependence of lamellar thickness was concluded to be controlled by that of lamellar thickening.
A phase 1 trial extension to assess immunologic efficacy and safety of prime-boost vaccination with VXM01, an oral T cell vaccine against VEGF-receptor 2, in patients with advanced pancreatic cancer. (2016)

3091 Background: VXM01 is an orally applied tumor vaccine based on live, attenuated salmonella bacteria carrying a eukaryotic expression plasmid, which encodes VEGFR-2. A recent randomized and placebo controlled phase I trial demonstrated in advanced pancreatic cancer patients safety, immunogenicity and T cell response related transient anti-angiogenic activity of 4 priming vaccinations applied within one week. As VEGFR2 specific T cell responses gradually declined after a peak response at day 21, an extension trial was conducted to explore whether monthly boost vaccinations can be safely administered and maintain increased vaccine specific T cell levels. Methods: 18 patients with advanced pancreatic cancer received a priming regimen with VXM01 followed by 6 monthly boost vaccinations starting on day 38 and 8 patients received placebo treatment in a randomized and blinded fashion. Immunomonitoring involved IFN-gamma Elispot analysis against VEGFR2 derived long peptides and was performed on blood samples harvested on days 0, 4, 14, 21 and 38 and 10 days after boost vaccination. Results: 12 out of 18 vaccinated patients showed considerable, in some cases high, increases in VEGFR2 specific T cell response over d0 levels. In the entire vaccinated group, VEGFR2 specific T cells peaked after 3 months with an average 4-fold increase over d0 levels. At study completion after 6 months VEGFR2 specific T cells were still increased over d0 values. Drug-related adverse events preferentially associated with boosting doses of VXM01 were decreases in lymphocyte count (22% vs 0) and increases in diarrhea (22% vs 0). Median overall survival was 9.3 months in the vaccinated group and 8.4 months in the placebo group. Within the vaccinated group, patients with a T-cell response to VXM01 showed a longer median overall survival (10.3 months) than patients without (5.4 months). Conclusions: Oral prime boost vaccination with VXM01 was well tolerated and is suitable to induce and maintain for several months effector T cell responses against VEGFR-2 in advanced stage pancreatic cancer patients. Clinical trial information: EudraCT 2011-000222-29.
Regulation of Human Cystathionine β-Synthase by <i>S</i>-Adenosyl-<scp>l</scp>-methionine:  Evidence for Two Catalytically Active Conformations Involving an Autoinhibitory Domain in the C-Terminal Region (2001)

Cystathionine beta-synthase (CBS), condensing homocysteine and serine, represents a key regulatory point in the biosynthesis of cysteine via the transsulfuration pathway. Inherited deficiency of CBS causes homocystinuria. CBS is activated by S-adenosyl-L-methionine (AdoMet) by inducing a conformational change involving a noncatalytic C-terminal region spanning residues 414-551. We report the purification of two patient-derived C-terminal mutant forms of CBS, S466L and I435T, that provide new insight into the mechanism of CBS regulation and indicate a regulatory function for the "CBS domain". Both of these point mutations confer catalytically active proteins. The I435T protein is AdoMet inducible but is 10-fold less responsive than wild-type (WT) CBS to physiologically relevant concentrations of this compound. The S466L form does not respond to AdoMet but is constitutively activated to a level intermediate between those of WT CBS in the presence and absence of AdoMet. Both mutant proteins are able to bind AdoMet, indicating that their impairment is related to their ability to assume the fully activated conformation that AdoMet induces in WT CBS. We found that I435T and WT CBS can be activated by partial thermal denaturation but that the AdoMet-stimulated WT, S466L, and a truncated form of CBS lacking the C-terminal region cannot be further activated by this treatment. Tryptophan and PLP fluorescence data for these different forms of CBS indicate that activation by AdoMet, limited proteolysis, and thermal denaturation share a common mechanism involving the displacement of an autoinhibitory domain located in the C-terminal region of the protein.
Molecular Mechanisms of Photoaging in Human Skin <i>In Vivo</i> and Their Prevention by All‐Trans Retinoic Acid (1999)

Abstract— Solar UV radiation damages human skin, affecting skin tone and resiliency and leading to premature aging (photoaging), the symptoms of which include leathery texture, wrinkles, mottled pigmentation, laxity and sallowness. We propose that photoaging results largely from UV induction of matrix metalloproteinases (MMP) that degrade skin collagen. We find that pretreatment of human skin with all‐ trans retinoic acid (tRA) inhibits UV induction of MMP, suggesting that tRA can protect against UV‐induced collagen destruction and may therefore be able to lessen the effects of photoaging. The tRA prevents UV‐induced accumulation of c‐Jun protein, which is required for MMP gene expression. Activation of c‐Jun transcriptional activity requires N‐terminal phosphorylation. The majority of c‐Jun in human skin in vivo is Nterminal phosphorylated. Topically applied t RA does not inhibit N‐terminal phosphorylation by UV‐induced c‐Jun kinase activity in human skin. The tRA likely acts to reduce UV induction of c‐Jun protein by stimulating its breakdown through the ubiquitin‐proteasome pathway.
Correlation Plenoptic Imaging: An Overview (2018)

Plenoptic imaging (PI) enables refocusing, depth-of-field (DOF) extension and 3D visualization, thanks to its ability to reconstruct the path of light rays from the lens to the image. However, in state-of-the-art plenoptic devices, these advantages come at the expenses of the image resolution, which is always well above the diffraction limit defined by the lens numerical aperture (NA). To overcome this limitation, we have proposed exploiting the spatio-temporal correlations of light, and to modify the ghost imaging scheme by endowing it with plenoptic properties. This approach, named Correlation Plenoptic Imaging (CPI), enables pushing both resolution and DOF to the fundamental limit imposed by wave-optics. In this paper, we review the methods to perform CPI both with chaotic light and with entangled photon pairs. Both simulations and a proof-of-principle experimental demonstration of CPI will be presented.
New Constrained-Geometry <i>C</i><sub>2</sub>-Symmetric Di<i>-</i>N<i>-</i>heterocyclic Carbene Ligands and Their Mono- and Dinuclear Rhodium(I) Complexes: Design, Synthesis, and Structural Analysis (2008)

A new C2-symmetric di-N-heterocyclic carbene (di-NHC) ligand is synthesized, and its coordination behavior with Rh(I) salts is examined. A comprehensive list is presented describing the synthesis of all chiral di-NHC ligands reported to date, including pertinent catalytic and structural features. The historical perspective indicates few structural archetypes have been investigated and more structural alternatives are needed. Accordingly, the synthesis of the diimidazolium salts [DEA-MI](I)2 (4) and [DEA-MBI](I)2 (8) (where DEA = 9,10-dihydro-11,12-ethanoanthracene; MI = methylimidazolium, and MBI = methylbenzimidazolium) are presented. When 8 is treated with 2 equiv of KN(SiMe3)2, the strained enetetramine [DEA-MBY] (9) is obtained and is characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The highly strained mononuclear complex [(DEA-MBY)Rh(COD)]I (10-COD) is obtained when 8 is treated with KN(SiMe3)2 followed by half an equivalent of [Rh(COD)Cl]2. A 1H NMR spectrum of 10-COD revealed an unusual downfield signal at 9.26 ppm, assigned to an aliphatic bridge proton, and provides a clue as to the relative orientation of the anthracene ligand to the metal center. Ultimately, a single-crystal X-ray diffraction experiment assisted in determining the absolute solid-state structure of 10-COD. Although an X-ray crystal structure was not obtained for the imidazole derivative [DEA-MY][Rh(COD)]I (11-COD), a similar structure is implied by the occurrence of a downfield signal for the bridge proton at 8.24 ppm. In addition, the dinuclear complexes [μ-DEA-MY][Rh(NBD)I]2 (12-NBD) and [μ-DEA-MBY][Rh(COD)Cl]2 (13-COD) are obtained. A structural comparison of the ligand precursors 2 and 7·(HCl)2 and the dinuclear species 12-NBD and 13-COD is presented.
Synthesis of Highly Uniform Nickel Multipods with Tunable Aspect Ratio by Microwave Power Control (2018)

As the importance of anisotropic nanostructures and the role of surfaces continues to rise in applications including catalysis, magneto-optics, and electromagnetic interference shielding, there is a need for efficient and economical synthesis routes for such nanostructures. The article describes the application of cycled microwave power for the rapid synthesis of highly branched pure-phase face-centered cubic crystalline nickel multipod nanostructures with >99% multipod population. By controlling the power delivery to the reaction mixture through cycling, superior control is achieved over the growth kinetics of the metallic nanostructures, allowing formation of multipods consisting of arms with different aspect ratios. The multipod structures are formed under ambient conditions in a simple reaction system composed of nickel acetylacetonate (Ni(acac)<sub>2</sub>), oleylamine (OAm), and oleic acid (OAc) in a matter of minutes by selective heating at the (111) overgrowth corners on Ni nanoseeds. The selective heating at the corners leads to accelerated autocatalytic growth along the ⟨111⟩ direction through a "lightning rod" effect. The length is proprtional to the length and number of microwave (MW)-on cycles, whereas the core size is controlled by continuous MW power delivery. The roles of heating mode (cycling versus variable power versus convective heating) during synthesis of the materials is explored, allowing a mechanism into how cycled microwave energy may allow fast multipod evolution to be proposed.
Characterization of port wine stain skin erythema and melanin content using cross‐polarized diffuse reflectance imaging (2004)

Abstract Background and Objectives Objective methods to assess quantitatively port wine stain (PWS) blanching in response to laser therapy are needed to improve laser therapeutic outcome. Previous studies have attempted to assess objectively PWS color based on point measurement devices. To date, these approaches have typically been limited by a number of factors such as small test area and need for contact. To address these issues, a cross‐polarized diffuse reflectance imaging system and color image analysis method has been developed to evaluate quantitatively erythema and melanin content in PWS skin. Study Design/Materials and Methods A cross‐polarized diffuse reflectance system has been constructed to acquire high resolution digital images while minimizing artifacts such as glare, shadowing, and nonuniform illumination effects that can compromise image fidelity. Furthermore, an image analysis algorithm has also been developed to analyze normal and PWS skin in terms of CIEL*a*b* color space parameters. Using the algorithm, images of color space intensity, L*, and saturation, a*, indices have been calculated to extract quantitative metrics of melanin and erythema, respectively. Results Compared to the cross‐polarized diffuse reflectance image, the a* index image enhanced the contrast in regions of high and low erythema and seems to have quasi correlation with the L* index image. In the presented PWS patient example, the relative a* index difference (Δa*) image showed less erythema in PWS skin after laser treatment when compared to pre‐treatment values. Conclusions Our cross‐polarized imaging system and color image analysis method is a simple, noncontact technique that can indirectly provide quantitative measurement of erythema and melanin content in PWS skin. Lasers Surg. Med. 34:174–181, 2004. © 2004 Wiley‐Liss, Inc.
Tunable Narrowband Photonic Filters with Whispering Gallery Mode Resonators (2005)

We discuss designs of photonic systems, based on high quality factor optical whispering gallery mode resonators fabricated with crystalline electro-optically active materials, for detection of weak narrowband signals buried in noisy background.
Dual Beam Laser: A Gaas Double-Cavity Laser with Branching Output Waveguides (1978)

A new device is reported in this paper which incorporates a branching taper within the optical cavity of a GaAs double heterostructure (DH) injection laser as shown in Fig. 1. Dual output waveguides are therefore provided at one of the mirrors. The coupled cavities resulting from this configuration tend to suppress all but one dominant longitudinal mode. By suitable variations of layer thickness and/or composition, the device operates either as a tapered power divider (TPD), branching the incident power of a single mode into the two output arms of the device, or as a tapered mode splitter (TMS), diverting different transverse modes into different arms. We have achieved power ratios of between 4:1 and 5:1 for the TPD, oscillating in a dominant longitudinal mode at λ ≈ 8850 Å. For the TMS, a transverse mode at λ ≈ 8780 Å exits from one output arm of the device, while another transverse mode at λ ≈ 8550 Å is observed from the other; the relative intensity of these two output beams can be varied by changing the injection current.
Quantitative ultrasound assessment of tumor responses to chemotherapy using a time-integrated multi-parameter approach (2014)

Radiofrequency ultrasound data were collected from 60 breast cancer patients prior to treatment and at during the onset of their several-month treatment, using a clinical ultrasound scanner operating a ~7 MHz linear array probe. ACE, SAS, spectral, and BSC parameters were computed from 2 × 2 mm RF segments within the tumor region of interest (ROI) and averaged over all segments to obtain a mean value for the ROI. The results were separated into two groups—responders and non-responders—based on the ultimate clinical/pathologic response based on residual tumor size and tumor cellularity. Using a single parameter approach, the best prediction of response was achieved using the ACE parameter (76% accuracy at week 1). In general, more favorable classifications were achieved using spectral parameter combinations (82% accuracy at week 8), compared to BSC parameter combinations (73% accuracy). Using the multi-parameter approach, the best prediction was achieved using the set [MBF, SS, SAS, ACE] and by combining week 1 QUS data with week 4 QUS data to predict the response at week 4, providing accuracy as high as 91%. The proposed QUS method may potentially provide early response information and guide cancer therapies on an individual patient basis.