gebhart/patrepeval huggingface dataset:
Finding new components of the target of rapamycin (TOR) signaling network through chemical genetics and proteome chips (2004)

The TOR (target of rapamycin) proteins play important roles in nutrient signaling in eukaryotic cells. Rapamycin treatment induces a state reminiscent of the nutrient starvation response, often resulting in growth inhibition. Using a chemical genetic modifier screen, we identified two classes of small molecules, small-molecule inhibitors of rapamycin (SMIRs) and small-molecule enhancers of rapamycin (SMERs), that suppress and augment, respectively, rapamycin's effect in the yeast Saccharomyces cerevisiae. Probing proteome chips with biotinylated SMIRs revealed putative intracellular target proteins, including Tep1p, a homolog of the mammalian PTEN (phosphatase and tensin homologue deleted on chromosome 10) tumor suppressor, and Ybr077cp (Nir1p), a protein of previously unknown function that we show to be a component of the TOR signaling network. Both SMIR target proteins are associated with PI(3,4)P2, suggesting a mechanism of regulation of the TOR pathway involving phosphatidylinositides. Our results illustrate the combined use of chemical genetics and proteomics in biological discovery and map a path for creating useful therapeutics for treating human diseases involving the TOR pathway, such as diabetes and cancer.
Catalytic SN2′‐ and Enantioselective Allylic Substitution with a Diborylmethane Reagent and Application in Synthesis (2016)

A catalytic method for the site- and enantioselective addition of commercially available di-B(pin)-methane to allylic phosphates is introduced (pin=pinacolato). Transformations may be facilitated by an NHC-Cu complex (NHC=N-heterocyclic carbene) and products obtained in 63-95 % yield, 88:12 to >98:2 S(N)2'/S(N)2 selectivity, and 85:15-99:1 enantiomeric ratio. The utility of the approach, entailing the involvement of different catalytic cross-coupling processes, is highlighted by its application to the formal synthesis of the cytotoxic natural product rhopaloic acid A.
Femtosecond impulsive stimulated Raman scattering studies of LiTaO3 (1993)

Abstract Impulsive stimulated Raman scattering (ISRS) experiments on LiTaO3 were conducted over a wide range of scattering wavevectors. The results permit explanation of the anomalously high and wavevector-dependent damping rates of the low-frequency phonon-polariton mode in terms of coupling of the polariton to a weakly Raman-active low-frequency relaxational mode and to two heavily damped vibrational modes. ISRS experiments at low temperatures were made possible through the use of multiple-pulse ISRS experiments where photorefractive damage precluded experiments with single excitation pulses.
PDCD4 Is an Androgen-Repressed Tumor Suppressor that Regulates Prostate Cancer Growth and Castration Resistance (2018)

Androgen receptor (AR) transcriptional activity contributes to prostate cancer development and castration resistance. The growth and survival pathways driven by AR remain incompletely defined. Here, we found PDCD4 to be a new target of AR signaling and a potent regulator of prostate cancer cell growth, survival, and castration resistance. The 3' untranslated region of PDCD4 is directly targeted by the androgen-induced miRNA, miR-21. Androgen treatment suppressed PDCD4 expression in a dose responsive and miR-21-dependent manner. Correspondingly, AR inhibition dose-responsively induced PDCD4 expression. Using data from prostate cancer tissue samples in The Cancer Genome Atlas (TCGA), we found a significant and inverse correlation between miR-21 and PDCD4 mRNA and protein levels. Higher Gleason grade tumors exhibited significantly higher levels of miR-21 and significantly lower levels of PDCD4 mRNA and protein. PDCD4 knockdown enhanced androgen-dependent cell proliferation and cell-cycle progression, inhibited apoptosis, and was sufficient to drive androgen-independent growth. On the other hand, PDCD4 overexpression inhibited miR-21-mediated growth and androgen independence. The stable knockdown of PDCD4 in androgen-dependent prostate cancer cells enhanced subcutaneous tumor take rate <i>in vivo</i>, accelerated tumor growth, and was sufficient for castration-resistant tumor growth. IMPLICATIONS: This study provides the first evidence that PDCD4 is an androgen-suppressed protein capable of regulating prostate cancer cell proliferation, apoptosis, and castration resistance. These results uncover miR-21 and PDCD4-regulated pathways as potential new targets for castration-resistant prostate cancer.
Scattering interactions between a cylinder and a strip (1992)

The monostatic scattering from an infinitely long, perfectly conducting cylinder and strip has been analyzed using the uniform geometrical theory of diffraction (UTD) including higher-order terms. This topic is of great interest in the study of target detection and identification in foliage. The importance of the different interactions between the tree and the target is investigated. Theoretical results are verified in the principal plane by comparison with a method of moments solution and experimental measurements. The resulting solution for the scattered fields is accurate and fast to compute. ISAR images are presented to illustrate the multiple interactions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Characterization of Electron Beams in Multiple Welders Using the Enhanced Modified Faraday Cup (2006)

Using the Enhanced Modified Faraday Cup (EMFC), the differences in the beams produced by two electron beam (EB) welders are characterized at different focus settings and work distances. For example, EMFC measurements show that sharply focused beams display different shapes and peak power densities which vary by nearly 20% for the same welding parameters on these two welders. Increases in work distance on each machine were shown to result in decreases in both the peak power density and the resulting weld size and shape. Because of the differences in machine performance, additional differences arise when comparing the welds produced by each machine. These different weld dimensions are attributed to differences in the beam shape and a 70 mm difference in the theoretical beam crossover location in the upper column of the two welders. The crossover location, which can not be physically measured, is determined using the EMFC by analyzing the beam distribution parameters of sharply focused beams over a range of work distances and can be used to explain the variation in the peak power densities of the two machines. Once the machines are characterized using this quantitative tool, changes in either the beam focus or work distance can be made to attain similar beams from different welders, thus providing a baseline for developing modern weld transfer procedures.
Reliability study of a 128Mb phase change memory chip implemented with doped Ga-Sb-Ge with extraordinary thermal stability (2016)

Doped Ga-Sb-Ge showed good thermal stability and fast switching speed. In this work, we present the results of a comprehensive reliability study for the relationship between cycling endurance and thermal stability on a 128Mb chip using modified doped Ga-Sb-Ge material. The chip exhibited good cycling endurance > 100K cycles, and there was no fail bits after soldering test. Furthermore, the chip showed no issue for 100K cycles after 260°C baking for 1000 seconds. In terms of the data retention, it was estimated that the PCM could retain data for 10 years at 215°C after 1K pre-cycles, 210°C after 10K pre-cycles, and 205°C after 100K pre-cycles. The PCM is suitable for applications requiring high thermal stability and cycling endurance.
M4Ag44(p-MBA)30Molecular Nanoparticles (2015)

M4Ag44(p-MBA)30 molecular nanoparticles, where M is an alkali metal, have recently been shown to have exceptional stability, which confers unique traits to this molecule. In particular, the synthesis is straightforward, produces a truly single-sized molecular product, and has a quantitative yield. Here we describe in detail the results of experimental and theoretical studies on the synthesis, structure, stability, and electronic and optical properties of M4Ag44(p-MBA)30, including ESI-MS, NMR, optical absorption, IR, TGA, and other measurements as well as DFT and TDDFT calculations. This work deepens our understanding of this important Ag molecule, which should facilitate its use in a wide range of fundamental studies and applications.
Influence of IGBT current rating on the thermal cycling lifetime of a power electronic active rectifier in a direct wave energy converter (2013)

Direct Wave Energy Converters offer high reliability potential, which is a key factor in offshore environments, yet their electrical power produced is strongly pulsating. The thermal cycling of their power electronic switches (considered here to be Insulated Gate Bipolar Transistors, IGBT) may reduce the lifetime of the power electronic converter. This study proposes a generic design method for choosing both the IGBT current rating and the heatsink thermal resistance in order to satisfy a reliability constraint. A parametric electro-thermal model has thus been developed to determine the junction temperature time series. Moreover, a rainflow cycle counting method is introduced for the reliability analysis and lifetime prediction using two aging models, one for wire bonds, the other for the solder joint of the chip.
Initial distribution of tritium in recoil-injected Type 304 stainless steel (1995)

Tritium contamination of stainless steel poses radiological problems at facilities that produce or process tritium on a large scale. Decommissioning tasks at these facilities are complicated by the potential of increased radiation dose to personnel either by direct skin contact with the tritiated surfaces or by inhalation of tritium gases released from the contaminated materials. A study of the migration of tritium in type 304 stainless steel was undertaken. One of the tritium impregnation methods utilized was recoil injection.
Assessment of Mutational Load in Biopsy Tissue Provides Additional Information About Genomic Instability to Histological Classifications of Barrett's Esophagus (2014)

Given that EAC is associated with accumulated genomic instability, high ML in less severe histology may identify BE disease at greater risk of progression to EAC. ML may help to better manage BE in early histological stages and when histology alone provides insufficient information.
Stochastic wire-length and delay distributions of 3-dimensional circuits (2000)

3-D technology promises higher integration density and lower interconnection complexity and delay. At present, however, not much work on circuit applications has been done due to lack of insight into 3-D circuit architecture and performance. In this paper, we investigate the interconnect distributions of 3-D circuits. We divide the 3-D interconnects into horizontal wires and vertical wires and derive their wire-length distributions, respectively. Based on the stochastic wire-length distributions, we calculate 3-D circuit interconnect delay distribution. We show that 3-D structures effectively reduce the number of long delay nets, significantly reduce the number of repeaters needed, and dramatically improve the performance. With 3-D structures, a circuit can work at a much higher clock rate (double, even triple) than with 2-D. However, we also show that the impacts of vertical wires on chip area and interconnect delay may limit the number of device layers that we can integrate.
Nanoparticle clearance is governed by Th1/Th2 immunity and strain background (2013)

Extended circulation of nanoparticles in blood is essential for most clinical applications. Nanoparticles are rapidly cleared by cells of the mononuclear phagocyte system (MPS). Approaches such as grafting polyethylene glycol onto particles (PEGylation) extend circulation times; however, these particles are still cleared, and the processes involved in this clearance remain poorly understood. Here, we present an intravital microscopy-based assay for the quantification of nanoparticle clearance, allowing us to determine the effect of mouse strain and immune system function on particle clearance. We demonstrate that mouse strains that are prone to Th1 immune responses clear nanoparticles at a slower rate than Th2-prone mice. Using depletion strategies, we show that both granulocytes and macrophages participate in the enhanced clearance observed in Th2-prone mice. Macrophages isolated from Th1 strains took up fewer particles in vitro than macrophages from Th2 strains. Treating macrophages from Th1 strains with cytokines to differentiate them into M2 macrophages increased the amount of particle uptake. Conversely, treating macrophages from Th2 strains with cytokines to differentiate them into M1 macrophages decreased their particle uptake. Moreover, these results were confirmed in human monocyte-derived macrophages, suggesting that global immune regulation has a significant impact on nanoparticle clearance in humans.
3D-tissue engineered bone marrow as predictive tool for personalized therapy in multiple myeloma (2014)

M myeloma (MM) is the second most common hematological malignancy and represents approximately 20% of deaths from hematological malignancies. Despite the success of numerous contemporary therapies to eradicate MM in vitro and in animal models, more than 90% of MM patients develop resistance to therapy and relapse. The discrepancy between drug efficacy in laboratory settings and the dissatisfactory clinical outcomes can be attributed to limitations of the classic drug development models, including the neglect of the interaction of tumor cells with other components of the bone marrow (BM) microenvironment; lack of tri-dimensional (3D) aspects of the BM niche (hypoxia and drug-gradient); and relying on a limited number of cell lines and do not reflect the enormous heterogeneity between individual patients. In our study, we produced a 3D-tissue engineered in vitro model of BM (3DTEBM) in MM, including MM cells, stromal cells, endothelial cells and extracellular matrix. All cells used for one 3DTEBM are isolated from a BM aspirate from individual MM patient. The 3D scaffold to accommodate the cells was produced by biological cross-linking of the BM supernatant of the same individual MM patient. We found that, in the 3DTEBM, MM cells proliferated more and showed significantly more drug resistance compared to classic tissue cultures. This 3DTEBM is currently investigated to predict the drug-response in MM patients, in which, we develop 3DTEBM for individual patients to test their response to therapy in vitro and correlate our findings with clinical response; to develop personalized therapeutic strategies for each individual MM patients.
Preferred solution conformation of peptides rich in the lipophilic, chiral, Cα-methylated α-amino acid (αMe)Aoc (1999)

The lipophilic, chiral, C(alpha)-methylated alpha-amino acid L-(alphaMe)Aoc (2-methyl-2-amino-octanoic acid) was prepared using a chemo-enzymatic approach. Two series of terminally protected model peptides, from dimer through to hexamer, containing L-(alphaMe)Aoc in combination with either Gly or Aib, were synthesized by solution methods and were fully characterized. A solution conformational analysis, based on FT-IR absorption, 1H-NMR and circular dichroism (CD) techniques, was performed with the aim at determining the preferred conformation of this novel amino acid and the relationship between chirality at its alpha-carbon atom and screw sense of the helix that is formed. The results obtained strongly support the view that L-(alphaMe)Aoc favours the formation of the right-handed 3(10)-helical conformation.
Rational Vaccinology: Harnessing Nanoscale Chemical Design for Cancer Immunotherapy (2022)

Cancer immunotherapy is a powerful treatment strategy that mobilizes the immune system to fight disease. Cancer vaccination is one form of cancer immunotherapy, where spatiotemporal control of the delivery of tumor-specific antigens, adjuvants, and/or cytokines has been key to successfully activating the immune system. Nanoscale materials that take advantage of chemistry to control the nanoscale structural arrangement, composition, and release of immunostimulatory components have shown significant promise in this regard. In this Outlook, we examine how the nanoscale structure, chemistry, and composition of immunostimulatory compounds can be modulated to maximize immune response and mitigate off-target effects, focusing on spherical nucleic acids as a model system. Furthermore, we emphasize how chemistry and materials science are driving the rational design and development of next-generation cancer vaccines. Finally, we identify gaps in the field that should be addressed moving forward and outline future directions to galvanize researchers from multiple disciplines to help realize the full potential of this form of cancer immunotherapy through chemistry and rational vaccinology.
Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink (2016)

While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal-bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA's cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed.
Signal processing for interference suppression in direct-sequence CDMA systems (2002)

The major limitation on the performance and capacity of direct-sequence code division multiple access (CDMA) is the multiple-access interference due to simultaneous transmissions. The signal processing for near-far resistant multiuser detectors typically follows a bank of matched filters or correlators (sampled at the symbol rate to produce sufficient statistics for demodulation) corresponding to all simultaneous transmissions. Due to the asynchronism among the transmissions, implementation of any near-far resistant demodulator using such a front end requires an infinite memory. However, an alternative front end which consists of a chip matched filter sampled at a multiple of the chip rate, coupled with the use of a finite observation interval for the demodulation of each symbol, can be used to obtain finite memory, near-far resistant, methods for demodulation and timing acquisition for asynchronous CDMA systems. We discuss the design of interference suppression schemes based on this front end.
Volume Electrical Failure Analysis for Product-Specific Yield Enhancement (2010)

Abstract Yield on specific designs often falls far short of predicted yield, especially at new technology nodes. Product-specific yield ramp is particularly challenging because the defects are, by definition, specific to the design, and often require some degree of design knowledge to isolate the failure. Despite the wide variety of advanced electrical failure analysis (EFA) techniques available today, they are not routinely applied during yield ramp. EFA techniques typically require a significant amount of test pattern customization, fixturing modification, or design knowledge. Unless the problem is critical, there is usually not time to apply advanced EFA techniques during yield ramp, despite the potential of EFA to provide valuable defect insight. We present a volume-oriented workflow integrating a limited set of electrical failure analysis (EFA) techniques. We believe this workflow will provide significant benefit by improving defect localization and identification beyond what is available using test-based techniques.
Polyethylene crosslinking using the epoxy‐anhydride reaction I: A strategy for a curing process with high thermal sensitivity (2022)

Abstract The initiated epoxy‐anhydride reaction was examined as a crosslink motif for effecting cure in functionalized polyethylene for electrical cable insulation applications. A specific challenge for this application is that little to no crosslinking can occur during the processing steps (~140°C), but crosslinking must be rapid and complete within a few minutes during the curing process (~200°C). To achieve this, we coupled the kinetics of the formation of an initiator for the epoxy‐anhydride reaction to the crosslinking step to achieve a phenomenological temperature sensitivity or “latency” that would be difficult to access via a single simple reaction. Evaluations of different imidazolium and phosphonium salts as initiator precursors were conducted with model compounds in solution, and specific salts were chosen for polymer studies based on the ratio of the phenomenological rates measured for the model reaction at ~140°C and ~200°C. In polymer studies using epoxide‐functional poly(ethylene), high crosslinking rates were observed at ~200°C while crosslinking was minimal at ~140°C. However, inclusion of the anhydride‐functional polyethylene in the formulation led to loss of initiator latency, and significant crosslinking was observed at ~140°C. A reaction between the anhydride or an impurity and initiator precursor is postulated to produce a kinetically‐competent initiator at lower temperatures that destroys latency.