gebhart/patrepeval huggingface dataset:
The Journal of Clinical Oncology: The Initial Years (2007)

While my positive experience as associate editor of Blood under Paul Marks had provided some sense of the job at hand, I was a bit hesitant faced with the time commitment and its potential impact on my busy lab and clinical practice. Now, looking back with
Expression of Microtubule‐Associated Proteins During the Early Stages of Neurite Extension by Brain Neurons Cultured in a Defined Medium (1986)

Immunoblotting analysis was used to identify the microtubule-associated proteins (MAPs) present in cultures of mouse brain neurons. Polyclonal antibodies were raised against the two main adult brain MAPs, i.e., MAP2 (300 kDa) and tau (60-70 kDa). Whatever the stage of the culture, which was performed in a defined medium (3 or 6 days), the anti-MAP2 serum detected several high-molecular-weight components (including MAP2) and an entity with 62-65 kDa. Anti-tau revealed essentially a major peak of 48 kDa (young tau) but also slightly cross-reacted with the 62-65 kDa entity. During the culture period (0-6 days) the cells developed progressively a dense neuritic network; the concentration of the different MAPs increased in parallel but at different rates depending on the different species. The increase in concentration of the high-molecular-weight components occurred before that of 48-kDa tau. This suggests that high-molecular-weight MAPs and 48-kDa tau might be involved respectively in the initiation and elongation of neurites. In contrast, and since the main developmental changes in tau composition seen in vivo did not occur during the time course of the culture, this transition might be related to later events of neuronal differentiation.
Flash‐Induced Stretchable Cu Conductor via Multiscale‐Interfacial Couplings (2018)

Herein, a novel stretchable Cu conductor with excellent conductivity and stretchability is reported via the flash-induced multiscale tuning of Cu and an elastomer interface. Microscale randomly wrinkled Cu (amplitude of ≈5 µm and wavelength of ≈45 µm) is formed on a polymer substrate through a single pulse of a millisecond flash light, enabling the elongation of Cu to exceed 20% regardless of the stretching direction. The nanoscale interlocked interface between the Cu nanoparticles (NPs) and the elastomer increases the adhesion force of Cu, which contributes to a significant improvement of the Cu stability and stretchability under harsh yielding stress. Simultaneously, the flash-induced photoreduction of CuO NPs and subsequent Cu NP welding lead to outstanding conductivity (≈37 kS cm<sup>-1</sup>) of the buckled elastic electrode. The 3D structure of randomly wrinkled Cu is modeled by finite element analysis simulations to show that the flash-activated stretchable Cu conductors can endure strain over 20% in all directions. Finally, the wrinkled Cu is utilized for wireless near-field communication on the skin of human wrist.
Probing color coherence effects in pp collisions at $$\sqrt{s}=7\,\text {TeV} $$ s = 7 TeV (2014)

A study of color coherence effects in pp collisions at a center-of-mass energy of 7[Formula: see text] is presented. The data used in the analysis were collected in 2010 with the CMS detector at the LHC and correspond to an integrated luminosity of 36 pb[Formula: see text]. Events are selected that contain at least three jets and where the two jets with the largest transverse momentum exhibit a back-to-back topology. The measured angular correlation between the second- and third-leading jet is shown to be sensitive to color coherence effects, and is compared to the predictions of Monte Carlo models with various implementations of color coherence. None of the models describe the data satisfactorily.
Vorinostat Induced Cellular Stress Disrupts the Balance Between p38 MAPK and Erk Pathways Leading to Apoptosis in WM Cells. (2009)

Abstract Abstract 3740 Poster Board III-676 Despite advances, Waldenstrom's Macroglobulinemia (WM) remains incurable, and novel agents are urgently needed. Histone deacetylase (HDACs) are involved in transcription regulation and signal transduction of cells through a genome wide alteration in histone modification and other proteins, leading to significant increase in cellular stress in tumor cells. We therefore examined the activity of Vorinostat, a histone deacetylase inhibitor (HDAC-I), and dissected its pro-apoptotic molecular pathways in WM cells. Vorinostat exhibited dose dependent killing of both primary, bone marrow derived WM cells, as well as BCWM.1 WM cells with an LD50 of 3.5 to 5uM using Annexin V and PI staining. Vorinostat induced apoptosis in WM cells through activation of specific caspases at different time points. Caspase 3, 6, 8, and 9 were activated after 24 hours of Vorinostat. Even though caspase 7 is downstream of caspase 3, we observed that caspase 7 was activated earlier, starting at 6 hours. We therefore hypothesized that the regulators of caspase 7 may be affected by Vorinostat at an earlier time point. Further investigation confirmed that there was significant down-regulation of inhibitor of apoptosis (IAP) family members, including c-IAP1, c-IAP2, XIAP and Livin after 12 hours of treatment with Vorinostat, and may elude to greater sensitivity for IAPs in modulating Caspase 7 versus Caspase 3 in WM cells. We also studied the stress pathways including Erk, JNK and P38 pathways in Vorinostat treated WM cells. Activated p38, phospho-p38, was upregulated starting at 12 hours, while phopho-Erk abruptly decreased following 24 hours of treatment with Vorinostat. There was minimal change in the activity of JNK pathway following Vorinostat treatment. The activation of the p38 pathway coincided with a reduction in c-IAP1, c-IAP2, XIAP and Livin following treatment of WM cells with Vorinostat for 12 hours. Taken together, these studies support that stress induced apoptosis in WM cells is mediated through disruption in the balanced activity between the Erk and p38 MAPK pathways. Vorinostat induced cellular stress results in the activation of p38 MAPK pathway and a reduction of the IAP family members, leading to early activation of caspase 7. While the inhibition of Erk pathway by Vorinostat results in delayed activation of caspase 3, 6, 8, and 9 at 24 hours, the collective signaling strength of p38 activation as well as inhibition of Erk likely determines the apoptotic fate WM cells upon Vorinostat treatment. Disclosures: No relevant conflicts of interest to declare.
Data for: ON A MEASUREMENT APPROACH TO SUPPORT EVALUATION OF THERMAL SCATTERING LAW DATA (2019)

The manuscript shows measured data and related discussion.
Manifestation of Interactions of Nano-Silica in Silicone Rubber Investigated by Low-Frequency Dielectric Spectroscopy and Mechanical Tests (2019)

Silicone rubber composites filled with nano-silica are currently widely used as high voltage insulating materials in power transmission and substation systems. We present a systematic study on the dielectric and mechanical performance of silicone rubber filled with surface modified and unmodified fumed nano-silica. The results indicate that the different interfaces between the silicone rubber and the two types of nano-silica introduce changes in their dielectric response when electrically stressed by a sinusoidal excitation in the frequency range of 10<sup>-4</sup>-1 Hz. The responses of pure silicone rubber and the composite filled with modified silica can be characterized by a paralleled combination of Maxwell-Wagner-Sillars interface polarization and DC conduction. In contrast, the silicone rubber composite with the unmodified nano-silica exhibits a quasi-DC (Q-DC) transport process. The mechanical properties of the composites (represented by their stress-strain characteristics) reveal an improvement in the mechanical strength with increasing filler content. Moreover, the strain level of the composite with a modified filler is improved.
The effect of LUT and cluster size on deep-submicron FPGA performance and density (2004)

In this paper, we revisit the field-programmable gate-array (FPGA) architectural issue of the effect of logic block functionality on FPGA performance and density. In particular, in the context of lookup table, cluster-based island-style FPGAs (Betz et al. 1997) we look at the effect of lookup table (LUT) size and cluster size (number of LUTs per cluster) on the speed and logic density of an FPGA. We use a fully timing-driven experimental flow (Betz et al. 1997), (Marquardt, 1999) in which a set of benchmark circuits are synthesized into different cluster-based (Betz and Rose, 1997, 1998) and (Marquardt, 1999) logic block architectures, which contain groups of LUTs and flip-flops. Across all architectures with LUT sizes in the range of 2 to 7 inputs, and cluster size from 1 to 10 LUTs, we have experimentally determined the relationship between the number of inputs required for a cluster as a function of the LUT size (K) and cluster size (N). Second, contrary to previous results, we have shown that clustering small LUTs (sizes 2 and 3) produces better area results than what was presented in the past. However, our results also show that the performance of FPGAs with these small LUT sizes is significantly worse (by almost a factor of 2) than larger LUTs. Hence, as measured by area-delay product, or by performance, these would be a bad choice. Also, we have discovered that LUT sizes of 5 and 6 produce much better area results than were previously believed. Finally, our results show that a LUT size of 4 to 6 and cluster size of between 3-10 provides the best area-delay product for an FPGA.
5-C-Branched Deoxynojirimycin: Strategy for Designing a 1-Deoxynojirimycin-Based Pharmacological Chaperone with a Nanomolar Affinity for Pompe Disease (2022)

In recent years, the function of pharmacological chaperones as a "thermodynamic stabilizer" has been attracting attention in combination therapy. The coadministration of a pharmacological chaperone and recombinant human acid α-glucosidase (rhGAA) leads to improved stability and maturation by binding to the folded state of the rhGAA and thereby promotes enzyme delivery. This study provides the first example of a strategy to design a high-affinity ligand toward lysosomal acid α-glucosidase (GAA) focusing on alkyl branches on 1-deoxynojirimycin (DNJ); 5-<i>C</i>-heptyl-DNJ produced a nanomolar affinity for GAA with a <i>K</i><sub>i</sub> value of 0.0047 μM, which is 13-fold more potent than DNJ. The protein thermal shift assay revealed that 10 μM 5-<i>C</i>-heptyl-DNJ increased the midpoint of the protein denaturation temperature (<i>T</i><sub>m</sub>) to 73.6 °C from 58.6 °C in the absence of the ligand, significantly improving the thermal stability of rhGAA. Furthermore, 5-<i>C</i>-heptyl-DNJ dose dependency increased intracellular GAA activities in Pompe patient's fibroblasts with the M519V mutation. The introduction of C5 alkyl branches on DNJ provides a new molecular strategy for pharmacological chaperone therapy for Pompe disease, which may lead to the development of higher-affinity and practically useful chaperones.
Declines and Impairment in Executive Function Predict Onset of Physical Frailty (2016)

Findings inform the association of executive functioning with transitions to frailty, suggesting both impairments in and declines in executive functioning are associated with risk of frailty onset. It remains to be determined whether these associations are causal or whether shared aging related or other mechanisms are involved.
Supplementary Data from Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-Associated <i>N</i>-Acetylglucosamine Glycan Antigens (2023)

Supplementary Data from Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-Associated &lt;i&gt;N&lt;/i&gt;-Acetylglucosamine Glycan Antigens
Targeting Gain of Function and Resistance Mutations in Abl and KIT by Hybrid Compound Design (2013)

Mutations in the catalytic domain at the gatekeeper position represent the most prominent drug-resistant variants of kinases and significantly impair the efficacy of targeted cancer therapies. Understanding the mechanisms of drug resistance at the molecular and atomic levels will aid in the design and development of inhibitors that have the potential to overcome these resistance mutations. Herein, by introducing adaptive elements into the inhibitor core structure, we undertake the structure-based development of type II hybrid inhibitors to overcome gatekeeper drug-resistant mutations in cSrc-T338M, as well as clinically relevant tyrosine kinase KIT-T670I and Abl-T315I variants, as essential targets in gastrointestinal stromal tumors (GISTs) and chronic myelogenous leukemia (CML). Using protein X-ray crystallography, we confirm the anticipated binding mode in cSrc, which proved to be essential for overcoming the respective resistances. More importantly, the novel compounds effectively inhibit clinically relevant gatekeeper mutants of KIT and Abl in biochemical and cellular studies.
Inflammatory pseudotumor of the terminal ileum mimicking malignancy in a patient with Behçet's disease CT and pathological findings (1996)

Behçet's disease is an idiopathic, recurrent multisystem syndrome characterized by oral aphthous ulcers, genital ulcers, and ocular inflammation. Small bowel involvement may occur in 1% of patients with aphthous ulceration which may mimic Crohn's disease. We report a case of a patient with Behçet's disease with small bowel pathology which simulated a mass and at surgery was an inflammatory pseudotumor. Inflammatory pseudotumors can be mistaken for a malignancy as was the case in this patient.
ChemInform Abstract: Novel 1,3‐Bis(aryloxy)propanes as Leukotriene D4 Antagonists. (1986)

The synthesis and structure-activity relationships of a number of 1,3-bis(aryloxy)propanes, which are in vivo antagonists of LTD4 in the guinea pig, are described. One of these compounds, 4 (Wy-44,329), was not only approximately equipotent with the standard 1 (FPL 55712) in the LTC4 (ID50 = 0.17 and 0.23 mg/kg iv, respectively) and LTD4 (ID50 = 0.11 and 0.15 mg/kg iv, respectively) challenge models but also possessed greater potency in the ovalbumin challenge model (ID50 = 0.47 mg/kg and 4.1 mg/kg iv, respectively) and a longer duration of action. This compound was a competitive LTD4 antagonist on guinea pig ileum (pA2 = 9.4) and possessed mediator release (rat PCA, ID50 = 0.26 mg/kg iv) and 5-lipoxygenase (IC50 = 32 microM vs. 5-HETE) inhibitory activities.
Development of Activate Capture and Digital Counting (AC+DC) Assay on a Self-Powered Microfluidic Cartridge for Protein Biomarker Detection (2020)

Activate capture and digital counting (AC + DC) is a rapid, 2-step, and ultrasensitive assay for protein quantification from a single droplet through the nanoparticle-photonic crystal coupling embedded in a self-powered microfluidic cartridge.
Effects of Ag Addition on Solidification Process and Microstructure of InSn Alloy (2018)

The mechanical strength of In-48mass%Sn eutectic solder has high variation because the microstructure is formed with nonuniformity structure during solidification process. In this paper, the effect of Ag addition for solidification process of In-48mass%Sn eutectic solder was investigated to suppress the variation of the strength. It was found that not only crystallization peak but also exothermic peak around 70 – 90℃ was detected in Differential Scanning Calorimetry (DSC) analysis. This peak was the transformation peak from non-equilibrium phase to equilibrium phase. And more, in this study, it was found the exothermic peak around 70 – 90℃ disappeared due to decreasing In concentration in liquid phase by adding Ag and a variation of the mechanical strength of InSn solder was suppressed by Ag addition.
A projector-camera setup for geometry-invariant frequency demultiplexing (2009)

Consider a projector-camera setup where a sinusoidal pattern is projected onto the scene, and an image of the objects imprinted with the pattern is captured by the camera. In this configuration, the local frequency of the sinusoidal pattern as seen by the camera is a function of both the frequency of the projected sinusoid and the local geometry of objects in the scene. We observe that, by strategically placing the projector and the camera in canonical configuration and projecting sinusoidal patterns aligned with the epipolar lines, the frequency of the sinusoids seen in the image becomes invariant to the local object geometry. This property allows us to design systems composed of a camera and multiple projectors, which can be used to capture a single image of a scene illuminated by all projectors at the same time, and then demultiplex the frequencies generated by each individual projector separately. We show how imaging systems like those can be used to segment, from a single image, the shadows cast by each individual projector - an application that we call coded shadow photography. The method is useful to extend the applicability of techniques that rely on the analysis of shadows cast by multiple light sources placed at different positions, as the individual shadows captured at distinct instants of time now can be obtained from a single shot, enabling the processing of dynamic scenes.
Guided-mode-resonance coupled localized surface plasmons for dually resonance enhanced Raman scattering sensing (2017)

Raman scattering spectroscopy is a unique tool to probe vibrational, rotational, and other low-frequency modes of a molecular system and therefore could be utilized to identify chemistry and quantity of molecules. However, the ultralow efficient Raman scattering, which is only 1/10<sup>9</sup> ~ 1/10<sup>14</sup> of the excitation light due to the small Raman scattering cross-sections of molecules, have significantly hindered its development in practical sensing applications. The discovery of surface-enhanced Raman scattering (SERS) in the 1970s and the significant progress in nanofabrication technique, provide a promising solution to overcome the inherent issues of Raman spectroscopy. It is found that In the vicinity of nanoparticles and their junctions, the Raman signals of molecules can be significantly improved by an enhancement factor as high as 10<sup>10</sup>, due to the ultrahigh electric field generated by the localized surface plasmons resonance (LSPR), where the intensity of Raman scattering is proportional to the |<strong>E</strong>|<sup>4</sup>. In this work, we propose and demonstrate a new approach combining LSPR from nanocapsules with densely assembled silver nanoparticles (NC-AgNPs) and guidemode- resonance (GMR) from dielectric photonic crystal slabs (PCSs) for SERS substrates with robustly high performance.
SYNTHESIS, CHARACTERIZATION, CRYSTAL STRUCTURE, AND DFT STUDY OF 3-BROMO-N- (3-FLUOROPHENYL)BENZENESULFONAMIDE (2021)

Sulfonamides are used as antibacterial drugs for decades. 3-bromo-N-(3-fluorophenyl) benzenesulfonamide is synthesized by the amidation reaction. The structure of the title compound is confirmed by FTIR, 1H and 13C NMR, and MS spectroscopies. At the same time, the single crystal of the compound is analyzed by X-ray diffraction and the conformational analysis is performed. Density functional theory (DFT) is used to further calculate the molecular structure, and the results are consistent with the X-ray diffraction results. In addition, DFT is also used to calculate and analyze the electrostatic potential and the frontier molecular orbital of the molecule, which provides some references for the analysis of the physical and chemical properties of the molecule. In addition, vibrational frequencies are analyzed, revealing some physicochemical properties of the title compound.
Pharmacological and genetic activation of cAMP synthesis disrupts cholesterol utilization in Mycobacterium tuberculosis (2021)

Abstract There is a growing appreciation for the idea that bacterial utilization of host-derived lipids, including cholesterol, supports Mycobacterium tuberculosis (Mtb) pathogenesis. This has generated interest in identifying novel antibiotics that can disrupt cholesterol utilization by Mtb in vivo . Here we identify a novel small molecule agonist (V-59) of the Mtb adenylyl cyclase Rv1625c, which stimulates 3’, 5’-cyclic adenosine monophosphate (cAMP) synthesis and inhibits cholesterol utilization by Mtb. Similarly, using a complementary genetic approach that induces bacterial cAMP synthesis independent of Rv1625c, we demonstrate that inducing cAMP synthesis is sufficient to inhibit cholesterol utilization in Mtb. Although the physiological roles of individual adenylyl cyclase enzymes in Mtb are largely unknown, here we demonstrate that the transmembrane region of Rv1625c is required for cholesterol metabolism. Finally, in this work the pharmacokinetic properties of Rv1625c agonists are optimized, producing an orally-available Rv1625c agonist that impairs Mtb pathogenesis in infected mice. Collectively, this work demonstrates a novel role for Rv1625c and cAMP signaling in controlling cholesterol metabolism in Mtb and establishes that cAMP signaling can be pharmacologically manipulated for the development of new antibiotic strategies. Author Summary The recalcitrance of Mycobacterium tuberculosis (Mtb) to conventional antibiotics has created a need to identify novel pharmacological mechanisms to inhibit Mtb pathogenesis. There is a growing understanding of the metabolic adaptations Mtb adopts during infection to support its survival and pathogenesis. This has generated interest in identifying small molecule compounds that effectively inhibit these in vivo metabolic adaptations, while overcoming challenges like poor pharmacokinetic properties or redundancy in target pathways. The Mtb cholesterol utilization pathway has repeatedly been speculated to be a desirable antibiotic target, but compounds that successfully inhibit this complex pathway and are suitable for use in vivo are lacking. Here, we establish that stimulating cAMP synthesis in Mtb is a mechanism that is sufficient to block cholesterol utilization by the bacterium, preventing the release of key metabolic intermediates that are derived from breakdown of the cholesterol molecule. For the first time, we identify small molecule agonists of the Mtb adenylyl cyclase Rv1625c that have promising pharmacological properties and are suitable for use during in vivo studies. These Rv1625c agonists increase cAMP synthesis, inhibit cholesterol utilization by Mtb, and disrupt Mtb pathogenesis in mouse models of chronic infection.
Microwave Cavity Spectroscopy (2001)

Abstract : The influence of vibrational and collision energy on ion-molecule reactions was investigated by measuring the cross sections for reactions of NH3(+) created with varying degrees of excitation in the umbrella bending and symmetric stretching modes. Under these conditions, the three major product channels for the NH3(+)/CD3NH2(+) system are CD3NH2(+), CD2=NH2(+) and CD3NH3(+). Two minor product channels correspond to NH3D(+) and NH4(+). This reaction is found to be mode selective based on the reactivity of two isoenergetic vibrational states having differing concerted atom motions. The reaction of state selected ammonia ions with CD4 produces two major products, deuterium abstraction (NH3D(+)) and collision induced dissociation (NH2D(+)). The reaction was found not to be mod selective. In the NH3(+)/THF system, four products were identified: hydrogen abstraction (NH4(+)), charge transfer (C4H8O(+)), proton transfer (C4H9O(+)) and an endothermic product corresponding to charge transfer with loss of H (C4H7O(=)). The branching ratios show a dependence on ammonia ion vibrational state In separate experiments, it was demonstrated that the new class of quantum cascade lasers that produce tunable infrared coherent radiation are well suited to cavity ring-down detection of ammonia. A detection limit of less than one part per billion was achieved.