gebhart/patrepeval huggingface dataset:
Spatial transcriptomics analysis of neoadjuvant cabozantinib and nivolumab in advanced hepatocellular carcinoma identifies independent mechanisms of resistance and recurrence (2023)

Novel immunotherapy combination therapies have improved outcomes for patients with hepatocellular carcinoma (HCC), but responses are limited to a subset of patients and recurrence can also occur. Little is known about the inter- and intra-tumor heterogeneity in cellular signaling networks within the HCC tumor microenvironment (TME) that underlie responses to modern systemic therapy. We applied spatial transcriptomics (ST) profiling to characterize the tumor microenvironment in HCC resection specimens from a clinical trial of neoadjuvant cabozantinib, a multi-tyrosine kinase inhibitor that primarily blocks VEGF, and nivolumab, a PD-1 inhibitor in which 5 out of 15 patients were found to have a pathologic response. ST profiling demonstrated that the TME of responding tumors was enriched for immune cells and cancer associated fibroblasts (CAF) with pro-inflammatory signaling relative to the non-responders. The enriched cancer-immune interactions in responding tumors are characterized by activation of the PAX5 module, a known regulator of B cell maturation, which colocalized with spots with increased B cell markers expression suggesting strong activity of these cells. Cancer-CAF interactions were also enriched in the responding tumors and were associated with extracellular matrix (ECM) remodeling as there was high activation of FOS and JUN in CAFs adjacent to tumor. The ECM remodeling is consistent with proliferative fibrosis in association with immune-mediated tumor regression. Among the patients with major pathologic response, a single patient experienced early HCC recurrence. ST analysis of this clinical outlier demonstrated marked tumor heterogeneity, with a distinctive immune-poor tumor region that resembles the non-responding TME across patients and was characterized by cancer-CAF interactions and expression of cancer stem cell markers, potentially mediating early tumor immune escape and recurrence in this patient. These data show that responses to modern systemic therapy in HCC are associated with distinctive molecular and cellular landscapes and provide new targets to enhance and prolong responses to systemic therapy in HCC.
Enabling energy efficiency in via-patterned gate array devices (2004)

In an attempt to enable the cost-effective production of low-and mid-volume application-specific chips, researchers have proposed a number of so-called structured ASIC architectures. These architectures represent a departure from traditional standard-cell-based ASIC designs in favor of techniques which present more physical and structural regularity. If structured ASICs are to become a viable alternative to standard cells, they must deliver performance and energy efficiency which is competitive with standard-cell-based design techniques. This paper focuses on one family of structured ASICs known as via-patterned gate arrays, or VPGAs. In this paper, we present circuit structures and power optimization algorithms which can be applied to VPGA chips in an effort to reduce their operational power dissipation.
A PEROXO-Tag Enables Rapid Isolation of Peroxisomes from Human Cells (2020)

Peroxisomes are metabolic organelles that perform a diverse array of critical functions in human physiology. Traditional isolation methods for peroxisomes can take more than 1 h to complete and can be laborious to implement. To address this, we have now extended our prior work on rapid organellar isolation to peroxisomes via the development of a peroxisomally localized 3XHA epitope tag ("PEROXO-Tag") and associated immunoprecipitation ("PEROXO-IP") workflow. Our PEROXO-IP workflow has excellent reproducibility, is easy to implement, and achieves highly rapid (~10 min post homogenization) and specific isolation of human peroxisomes, which we characterize here via proteomic profiling. By offering speed, specificity, reproducibility, and ease of use, the PEROXO-IP workflow should facilitate studies on the biology of peroxisomes.
Carbocationic Polymerization in the Presence of Sterically Hindered Bases. X. Summary and Quantitative Kinetic Confirmation of the Mechanism (1982)

Abstract The findings presented in the preceding articles of this special issue have been organized, analyzed, and summarized. Commonalities among the various polymerization systems investigated in detail have been identified and phenomena of general validity were found. Increased insight into the mechanism of initiation and chain transfer processes led to the development of a comprehensive kinetic model which was used to describe the assembled data. Excellent quantitative agreement between experimental and calculated data indicates the validity of the mechanistic/kinetic model developed from chemical principles in regard to fast-initiated nonstationary carbocationic polymerizations in the absence and presence of proton traps.
Identification of dominant recombination mechanisms in narrow-bandgap InAs/InAsSb type-II superlattices and InAsSb alloys (2013)

Minority carrier lifetimes in doped and undoped mid-wave infrared InAs/InAsSb type-II superlattices (T2SLs) and InAsSb alloys were measured from 77–300 K. The lifetimes were analyzed using Shockley-Read-Hall (SRH), radiative, and Auger recombination, allowing the contributions of the various recombination mechanisms to be distinguished and the dominant mechanisms identified. For the T2SLs, SRH recombination is the dominant mechanism. Defect levels with energies of 130 meV and 70 meV are determined for the undoped and doped T2SLs, respectively. The alloy lifetimes are limited by radiative and Auger recombination through the entire temperature range, with SRH not making a significant contribution.
Versatile Peptide C-Terminal Functionalization via a Computationally Engineered Peptide Amidase (2016)

The properties of synthetic peptides, including potency, stability, and bioavailability, are strongly influenced by modification of the peptide chain termini. Unfortunately, generally applicable methods for selective and mild C-terminal peptide functionalization are lacking. In this work, we explored the peptide amidase from Stenotrophomonas maltophilia as a versatile catalyst for diverse carboxy-terminal peptide modification reactions. Because the scope of application of the enzyme is hampered by its mediocre stability, we used computational protein engineering supported by energy calculations and molecular dynamics simulations to discover a number of stabilizing mutations. Twelve mutations were combined to yield a highly thermostable (ΔTm = 23 °C) and solvent-compatible enzyme. Protein crystallography and molecular dynamics simulations revealed the biophysical effects of mutations contributing to the enhanced robustness. The resulting enzyme catalyzed the selective C-terminal modification of synthetic peptides with small nucleophiles such as ammonia, methylamine, and hydroxylamine in various organic (co)solvents. The use of a nonaqueous environment allowed modification of peptide free acids with >85% product yield under thermodynamic control. On the basis of the crystal structure, further mutagenesis gave a biocatalyst that favors introduction of larger functional groups. Thus, the use of computational and rational protein design provided a tool for diverse enzymatic peptide modification.
Translating the Simulation of Procedural Drilling Techniques for Interactive Neurosurgical Training (2013)

Abstract BACKGROUND: Through previous efforts we have developed a fully virtual environment to provide procedural training of otologic surgical technique. The virtual environment is based on high-resolution volumetric data of the regional anatomy. These volumetric data help drive an interactive multisensory, ie, visual (stereo), aural (stereo), and tactile, simulation environment. Subsequently, we have extended our efforts to support the training of neurosurgical procedural technique as part of the Congress of Neurological Surgeons simulation initiative. OBJECTIVE: To deliberately study the integration of simulation technologies into the neurosurgical curriculum and to determine their efficacy in teaching minimally invasive cranial and skull base approaches. METHODS: We discuss issues of biofidelity and our methods to provide objective, quantitative and automated assessment for the residents. RESULTS: We conclude with a discussion of our experiences by reporting preliminary formative pilot studies and proposed approaches to take the simulation to the next level through additional validation studies. CONCLUSION: We have presented our efforts to translate an otologic simulation environment for use in the neurosurgical curriculum. We have demonstrated the initial proof of principles and define the steps to integrate and validate the system as an adjuvant to the neurosurgical curriculum.
Early Drug Discovery and Development of Novel Cancer Therapeutics Targeting DNA Polymerase Eta (POLH) (2021)

Polymerase eta (or Pol η or POLH) is a specialized DNA polymerase that is able to bypass certain blocking lesions, such as those generated by ultraviolet radiation (UVR) or cisplatin, and is deployed to replication foci for translesion synthesis as part of the DNA damage response (DDR). Inherited defects in the gene encoding POLH (a.k.a., XPV) are associated with the rare, sun-sensitive, cancer-prone disorder, xeroderma pigmentosum, owing to the enzyme's ability to accurately bypass UVR-induced thymine dimers. In standard-of-care cancer therapies involving platinum-based clinical agents, e.g., cisplatin or oxaliplatin, POLH can bypass platinum-DNA adducts, negating benefits of the treatment and enabling drug resistance. POLH inhibition can sensitize cells to platinum-based chemotherapies, and the polymerase has also been implicated in resistance to nucleoside analogs, such as gemcitabine. POLH overexpression has been linked to the development of chemoresistance in several cancers, including lung, ovarian, and bladder. Co-inhibition of POLH and the ATR serine/threonine kinase, another DDR protein, causes synthetic lethality in a range of cancers, reinforcing that POLH is an emerging target for the development of novel oncology therapeutics. Using a fragment-based drug discovery approach in combination with an optimized crystallization screen, we have solved the first X-ray crystal structures of small novel drug-like compounds, i.e., fragments, bound to POLH, as starting points for the design of POLH inhibitors. The intrinsic molecular resolution afforded by the method can be quickly exploited in fragment growth and elaboration as well as analog scoping and scaffold hopping using medicinal and computational chemistry to advance hits to lead. An initial small round of medicinal chemistry has resulted in inhibitors with a range of functional activity in an <i>in vitro</i> biochemical assay, leading to the rapid identification of an inhibitor to advance to subsequent rounds of chemistry to generate a lead compound. Importantly, our chemical matter is different from the traditional nucleoside analog-based approaches for targeting DNA polymerases.
Supplementary Figure 4 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes (2023)

&lt;p&gt;GenoScape - example of HPV genotype profiling report and visualization. Number, characteristics and percentage of reads that map to thirteen (13) HPV types, human, bacteria and unknown genomes after profiling reads of the clinical sample TrDNA-456 by tiered read mapping.&lt;/p&gt;
Poly(diphenanthrenequinone-substituted norbornene) for Long Life and Efficient Lithium Battery Cathodes (2018)

Abstract Redox-active polymers with large charge-storage density are candidates for electrode-active materials in next-generation energy storage devices, due to their swift charge-discharge capabilities and their inherent characteristics of redox reactions that occur without significant structural changes, leading to their highly energy-efficient and durable performance. Here we report poly(diphenanthrenequinone-substituted norbornene) (PQN) as a novel class of organic electrode-active material. A Li coin cell composed of the PQN/carbon composite electrode as the cathode exhibited 2.8 V (V vs. Li/Li+) and great cycle performance maintaining a capacity higher than 100 mAh/g for more than 100 cycles at 60 C (i.e. in 1 min charging and discharging). Among many types of o-quinone-containing polymers for Li-ion batteries reported so far, the present research provides the first example of introducing phenanthrenequinone as the pendant group per repeating unit of polymers, which proved to be especially advantageous in terms of robustness and cyclability by virtue of the fused-ring structure to protect the reactive positions of the o-benzoquinone. We also report that the functional group tolerance against many types of redox-active groups, which we have established for the initiator and the propagating end of norbornene derivatives, apply for the phenanthrenequinone-substituted monomer, giving rise to a reversible redox activity.
Evolution of the Simulated Data Problem (2001)

The simulated data problem was designed via an interactive process by the Simulation Problem Organizing Committee and the selected data simulators. Based on discussions at the previous Genetic Analysis Workshop, many of the features of previous simulation problems, such as a complex disease, genome scan, and replication, were retained and in addition, a population genetics model was used to generate the simulated genes. We describe the process that was used to structure the problem and summarize the discussions about many of the scientific issues that were considered.
Low-Temperature Chemiluminescence from cis-1,4-Polybutadiene, 1,2-Polybutadiene, and trans-Polypentenamer at Temperatures near Ambient (1978)

The chemiluminescence emission at 25-60°C was measured from films of cis-1,4-polybutadiene, 1,2-polybutadiene, and trans-polypentenamer. The polymers were autoxidized previously in air 100°C, or allowed to react with singlet molecular oxygen in solution, and then cast into films. Values of β(or kd(1O2 → 3O2)/kr(1O2 + polymer → products)) were determined in benzene for cis-1,4-polybutadiene and cis-1,4-and for model compounds cis-3-hexene and cis-3-methyl-3-hexene by independent methods. The chemiluminescence emission from irradiated films of the polymers containing a dye sensitizer showed a complicated time dependence, and the results depended on the length of irradiation.
Sum Throughput Maximization in Multi-Tag Backscattering to Multiantenna Reader (2019)

Backscatter communication (BSC) is being realized as the core technology for pervasive sustainable Internet-of-Things applications. However, owing to the resource-limitations of passive tags, the efficient usage of multiple antennas at the reader is essential for both downlink excitation and uplink detection. This work targets at maximizing the achievable sum-backscattered-throughput by jointly optimizing the transceiver (TRX) design at the reader and backscattering coefficients (BC) at the tags. Since, this joint problem is nonconvex, we first present individually-optimal designs for the TRX and BC. We show that with precoder and {combiner} designs at the reader respectively targeting downlink energy beamforming and uplink Wiener filtering operations, the BC optimization at tags can be reduced to a binary power control problem. Next, the asymptotically-optimal joint-TRX-BC designs are proposed for both low and high signal-to-noise-ratio regimes. Based on these developments, an iterative low-complexity algorithm is proposed to yield an efficient jointly-suboptimal design. Thereafter, we discuss the practical utility of the proposed designs to other application settings like wireless powered communication networks and BSC with imperfect channel state information. Lastly, selected numerical results, validating the analysis and shedding novel insights, demonstrate that the proposed designs can yield significant enhancement in the sum-backscattered throughput over existing benchmarks.
Composite 3D-printed reactors for gas absorption, purification, and reaction (2023)

A composite material for gas capture, notably CO2 capture and storage. The composite material includes a mixture of a solid or liquid reactive filler and a gas-permeable polymer such that the reactive filler forms micron-scale domains in the polymer matrix.
Biotransformation of Myricetin: A Novel Metabolic Pathway to Produce Aminated Products in Mice (2019)

This result demonstrates that amination is a novel biotransformation mechanism of myricetin to produce aminated metabolites.
Fracture Toughness of Microfiber Reinforced Cement Composites (2002)

An investigation into the reinforcing behavior of microdiameter fibers in cement composites, with an emphasis on their behavior in the frontal process zone (FPZ) ahead of the crack tip, is presented. Fracture toughness tests were conducted on thin sheet cement composites reinforced with polypropylene (PP), polyvinyl alcohol (PVA), and refined cellulose (RC) fibers under air-dry conditions. Fracture toughness in the absence of microscopic damage was quantified for these composites, as was fracture toughness that included the energy absorbed in the microcracked region prior to failure crack localization. These tests revealed that the PVA and RC fibers were able to effectively postpone microcrack formation, thereby delaying the localization of the failure crack. The PP fibers were not able to provide the same level of reinforcement. An optical microscope was used to monitor the progression of damage during testing. In addition, the acoustic emission technique was used to confirm the accuracy of the fracture toughness values.
905 nm Wavelength Laser as a Means for In Situ End-point Detection of Dry Etching of Al[sub x]Ga[sub 1−x]As on GaAs (1999)

A method has been developed for in situ end‐point detection of etching of over . The results obtained with a conventional and a new infrared laser during etching have been compared. Light from a laser was strongly absorbed in both and materials and no interference was detected. In contrast, incidence of wavelength infrared laser light on the materials caused some interference with , and no interference with due to absorption. The results produced a noticeable difference of signal patterns for etching of the two materials. End‐point detection data with the laser on various compositions and different types are also reported. ©1999 The Electrochemical Society
Shotgun Proteomics (2016)

This document contains recommendations for terminology in mass spectrometry. Development of standard terms dates back to 1974 when the IUPAC Commission on Analytical Nomenclature issued recommendations on mass spectrometry terms and definitions. In 1978, the IUPAC Commission on Molecular Structure and Spectroscopy updated and extended the recommendations and made further recommendations regarding symbols, acronyms, and abbreviations. The IUPAC Physical Chemistry Division Commission on Molecular Structure and Spectroscopy’s Subcommittee on Mass Spectroscopy revised the recommended terms in 1991 and appended terms relating to vacuum technology. Some additional terms related to tandem mass spectrometry were added in 1993 and accelerator mass spectrometry in 1994. Owing to the rapid expansion of the field in the intervening years, particularly in mass spectrometry of biomolecules, a further revision of the recommendations has become necessary. This document contains a comprehensive revision of mass spectrometry terminology that represents the current consensus of the mass spectrometry community.
Solid-state dynamic nuclear polarization at 263 GHz: spectrometer design and experimental results (2010)

Dynamic Nuclear Polarization (DNP) experiments transfer polarization from electron spins to nuclear spins with microwave irradiation of the electron spins for enhanced sensitivity in nuclear magnetic resonance (NMR) spectroscopy. Design and testing of a spectrometer for magic angle spinning (MAS) DNP experiments at 263 GHz microwave frequency, 400 MHz (1)H frequency is described. Microwaves are generated by a novel continuous-wave gyrotron, transmitted to the NMR probe via a transmission line, and irradiated on a 3.2 mm rotor for MAS DNP experiments. DNP signal enhancements of up to 80 have been measured at 95 K on urea and proline in water-glycerol with the biradical polarizing agent TOTAPOL. We characterize the experimental parameters affecting the DNP efficiency: the magnetic field dependence, temperature dependence and polarization build-up times, microwave power dependence, sample heating effects, and spinning frequency dependence of the DNP signal enhancement. Stable system operation, including DNP performance, is also demonstrated over a 36 h period.
Reduced phase error through optimized control of a superconducting qubit (2010)

Minimizing phase and other errors in experimental quantum gates allows higher fidelity quantum processing. To quantify and correct for phase errors, in particular, we have developed an experimental metrology---amplified phase error (APE) pulses---that amplifies and helps identify phase errors in general multilevel qubit architectures. In order to correct for both phase and amplitude errors specific to virtual transitions and leakage outside of the qubit manifold, we implement ``half derivative,'' an experimental simplification of derivative reduction by adiabatic gate (DRAG) control theory. The phase errors are lowered by about a factor of five using this method to $~{1.6}^{\ifmmode^\circ\else\textdegree\fi{}}$ per gate, and can be tuned to zero. Leakage outside the qubit manifold, to the qubit $|2\ensuremath{\rangle}$ state, is also reduced to $~{10}^{\ensuremath{-}4}$ for $20%$ faster gates.
DUV laser light sources (Abstract Only) (1999)

High power laser sources of deep UV radiation play an important role in numerous applications such as microlithography, micromachining and material modification. Usefulness of deep UV lasers for each specific application arises from their unique characteristics, most importantly wavelength, temporal and spatial coherence and intensity distribution of the beam. Recent progress in the areas of DUV optical materials, laser resonators and electronics made possible dramatic improvements in power levels, brightness and intensity uniformity at these extremely short wavelengths, combined with long term stability and reliability. We report on recent advances in development of high power excimer lasers at the wavelengths of 248 nm, 1 93 nm and 1 57 nm for applications requiring high spectral brightness, such as microlithography, and high spatial and temporal coherence, such as writing of fiber Bragg gratings. We also present new data on high power all-solid-state laser sources of 266 nm, 213 nm and tunable UV radiation which are becoming a real alternative to excimer lasers in some DUV applications. We discuss impact of the long-term degradation of optical elements on the performance, reliability and running costs of recently developed DUV lasers