gebhart/patrepeval huggingface dataset:
Assessing Methods and Obstacles in Chemical Space Exploration (2020)

Benchmarking the performance of generative methods for drug design is complex and multifaceted. In this report, we propose a separation of concerns for de novo drug design, categorizing the task into three main categories: generation, discrimination, and exploration. We demonstrate that changes to any of these three concerns impacts benchmark performance for drug design tasks. In this report we present Deriver, an open-source Python package that acts as a modular framework for molecule generation, with a focus on integrating multiple generative methods. Using Deriver, we demonstrate that changing parameters related to each of these three concerns impacts chemical space traversal significantly, and that the freedom to independently adjust each is critical to real-world applications having conflicting priorities. We find that combining multiple generative methods can improve optimization of molecular properties, and lower the chance of becoming trapped in local minima. Additionally, filtering molecules for drug-likeness (based on physicochemical properties and SMARTS pattern matching) before they are scored can hinder exploration, but can improve the quality of the final molecules. Finally, we demonstrate that any given task has an exploration algorithm best suited to it, though in practice linear probabilistic sampling generally results in the best outcomes, when compared to Monte Carlo sampling or greedy sampling. We intend that Deriver, which is being made freely available, will be helpful to others interested in collaboratively improving existing methods in de novo drug design centered around inheritance of molecular structure, modularity, extensibility, and separation of concerns.
Low-current field-assisted assembly of copper nanoparticles for current collectors (2015)

Current collectors are essential features of batteries and many other electronic devices being responsible for efficient charge transport to active electrode materials. Three-dimensional (3D), high surface area current collectors considerably improve the performance of cathodes and anodes in batteries, but their technological implementation is impeded by the complexity of their preparation, which needs to be simple, fast, and energy efficient. Here we demonstrate that field-stimulated assembly of ∼3 nm copper nanoparticles (NPs) enables the preparation of porous Cu NP films. The use of NP dispersions enables 30× reduction of the deposition current for making functional 3D coatings. In addition to high surface area, lattice-to-lattice connectivity in the self-assembly of NPs in 3D structures enables fast charge transport. The mesoscale dimensions of out-of-plane features and the spacing between them in Cu films made by field-stimulated self-assembly of NPs provides promising morphology for current collection in lithium ion batteries (LIBs). Half-cell electrochemical models based on self-assembled films show improved specific capacity, total capacity, and cycling performance compared to traditional flat and other 3D current collectors. While integration of active electrode material into the 3D topography of the current collector needs to be improved, this study indicates that self-assembled NP films represent a viable manufacturing approach for 3D electrodes.
The Economic Significance of Orthopaedic Infections (2015)

Musculoskeletal infections are a leading cause of patient morbidity and rising healthcare expenditures. The incidence of musculoskeletal infections, including soft-tissue infections, periprosthetic joint infection, and osteomyelitis, is increasing. Cases involving both drug-resistant bacterial strains and periprosthetic joint infection in total hip and total knee arthroplasty are particularly costly and represent a growing economic burden for the American healthcare system. With the institution of the Affordable Care Act, there has been an increasing drive in the United States toward rewarding healthcare organizations for their quality of care, bundling episodes of care, and capitating approaches to managing populations. In current reimbursement models, complications following the index event, including infection, are not typically reimbursed, placing the burden of caring for infections on the physician, hospital, or accountable care organization. Without the ability to risk-stratify patient outcomes based on patient comorbidities that are associated with a higher incidence of musculoskeletal infection, healthcare organizations are disincentivized to care for moderate- to high-risk patients. Reducing the cost of treating musculoskeletal infection also depends on incentivizing innovations in infection prevention.
Intracellular signaling mechanisms responsive to laser-induced photochemical and thermal stress (2005)

The cells of the retinal pigment epithelium (RPE) are subject to photo-oxidative stress arising from the interaction of incident light with lipofuscin, melanin, and other pigment granules in the RPE cytoplasm. Specific genotypic responses to these stressors are controlled by transcription factors, such as NF-&#954;B (RelA/p50 dimer). The effects of CW laser exposures on NF-&#954;B nuclear translocation have been studied in a line of human-derived RPE cells (hTERT-RPE) that develop melanin pigmentation in culture. The cells were exposed to the CW emission of an Argon-ion laser for 10 m at 0.5 W/cm<sup>2</sup>, a range previously shown to produce oxidation of cellular proteins, DNA, and antioxidants. NF-&#954;B dimer was measured in nuclear extracts by an electrophoretic mobility shift assay. NF-&#954;B nuclear translocation exhibited a modest, early peak at 1 h, and a larger, late peak at 24 h. NF-&#954;B activation could be reduced only by some antioxidants; for example, 20 mM N-acetyl-L-cysteine or 100 &#956;M pyrrolidine dithiocarbamate were ineffective, while 500 &#956;M ascorbic acid was highly effective. These results indicate that interaction of the laser with the RPE melanin granules is a likely source of oxidative reactions, and that the induction of photoxidative stress activates NF-&#954;B, but it remains to be determined if NF-&#954;B is pro- or anti-apoptotic in the RPE cell.
Distributed optimization with arbitrary local solvers (2017)

With the growth of data and necessity for distributed optimization methods, solvers that work well on a single machine must be re-designed to leverage distributed computation. Recent work in this area has been limited by focusing heavily on developing highly specific methods for the distributed environment. These special-purpose methods are often unable to fully leverage the competitive performance of their well-tuned and customized single machine counterparts. Further, they are unable to easily integrate improvements that continue to be made to single machine methods. To this end, we present a framework for distributed optimization that both allows the flexibility of arbitrary solvers to be used on each (single) machine locally and yet maintains competitive performance against other state-of-the-art special-purpose distributed methods. We give strong primal-dual convergence rate guarantees for our framework that hold for arbitrary local solvers. We demonstrate the impact of local solver selection both theoretically and in an extensive experimental comparison. Finally, we provide thorough implementation details for our framework, highlighting areas for practical performance gains.
Photon number generation with the visible light photon counter (2004)

The Visible Light Photon Counter (VLPC) has the capability to discriminate photon number states, in contrast to conventional photon counters which can only detect the presence or absence of photons. We use this capability, along with the process of parametric down-conversion, to generate photon number states. We first investigate single photon generation, using a modified Hanbury-Brown Twiss (HBT) intensity interferometer to verify the single photon nature of the light. We then use a second VLPC to experimentally demonstrate generation of 2,3 and 4 photons with high fidelity. We investigate the effect of the detection efficiency of the VLPC on the generation rate and fidelity of the created states.
Structured illumination diffraction phase microscopy for broadband, subdiffraction resolution, quantitative phase imaging (2014)

Structured illumination microscopy (SIM) is an established technique that allows subdiffraction resolution imaging by heterodyning high sample frequencies into the system's passband via structured illumination. However, until now, SIM has been typically used to achieve subdiffraction resolution for intensity-based imaging. Here, we present a novel optical setup that uses structured illumination with a broadband light source to obtain noise-reduced, subdiffraction resolution, quantitative phase imaging (QPM) of cells. We compare this with a previous work for subdiffraction QPM imaging via SIM that used a laser source, and was thus still corrupted by coherent noise.
A 28GS/s 6b pseudo segmented current steering DAC in 90nm CMOS (2011)

A pseudo segmented twofold time-interleaved 6-bit digital-to-analog converter (DAC) occupies 0.28 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> chip area in a standard 90 nm CMOS technology. The DAC enables sampling rates up to 28 GS/s with a power consumption of 2.25 W at a -2.5 V power supply. The output bandwidth is at least 14 GHz. The integral non-linearity (INL) and the differential non-linearity (DNL) are 0.8 LSB and 1 LSB respectively. The estimated effective number of bit (ENOB) at 25 GS/s are 5.5-bit at DC and 4.6-bit at the Nyquist frequency.
Discrete LIN28 binding sites in mature messenger RNA sequences reveals regulation of a network of splicing factors and downstream alternative splicing patterns (2012)

LIN28 is a conserved RNA binding protein important for pluripotency, reprogramming and oncogenesis. Studies thus far have focused primarily on the roles of LIN28 through its regulation of the microRNA (miRNA) let‐7. Here, our goal was to identify and characterize the network of mature messenger RNA targets of LIN28 in order to explain its let‐7 independent regulatory mechanisms. Using UV cross‐linking and immunoprecipitation of the LIN28 protein followed by high‐throughput sequencing (CLIP‐seq) we have identified direct LIN28 binding regions on target RNAs in human embryonic stem cells and somatic cells expressing exogenous LIN28. We found that in addition to hundreds of miRNAs, LIN28 directly binds to thousands of human mRNA genes, including LIN28 itself and dozens of splicing regulators. Furthermore, we confirm in a set of targets that this binding results in an increase in translation. Finally, splicing‐sensitive junction arrays demonstrated that LIN28 over‐expression causes widespread downstream alternative splicing differences. These findings show that LIN28 contributes to cellular homeostasis via direct mRNA interactions and downstream AS events, alterations of which may result in cancer and differentiation.
Multipolar analysis of linear and nonlinear unidirectional response from plasmonic dimers (2015)

We develop the retrieval procedure for linear and nonlinear polarizabilities of plasmonic nanodimers and present examples of unidirectional scattering and nonlinear unidirectional generation from such geometries. Related effective parameters of periodic dimer arrangements are discussed.
Dual-band dual-polarized high-gain Resonant Cavity Antenna (2011)

In this paper, a novel method is presented for designing a dual-band dual-polarized high-gain Resonant Cavity Antennas (RCA). The design procedure is also explained. The RCA includes two layers of dipole arrays each situated at a designed height above the ground plane of a microstrip patch antenna. The lower band has a gain of 22.1 dB with the vertical polarization (pol V) at 10.1 GHz and the upper band has a gain of 16 dB with horizontal polarization (pol H) at 11.9 GHz. The cross polarization is below 37 dB at each band.
Crystal Plasticity Finite Element Analysis of Loading-Unloading Behaviour in Magnesium Alloy Sheet (2010)

Magnesium alloy sheets exhibit strong inelastic response during unloading. In this study crystal plasticity finite element analysis of loading‐unloading behaviour during uniaxial tension in a rolled magnesium alloy sheet was carried out, and the mechanism of this inelastic response was examined in detail in terms of macroscopic and mesoscopic deformations. The unloading behaviour obtained by the simulation was in good agreement with the experiment in terms of variation with stress of instantaneous tangent modulus during unloading. Variations of activities of each family of slip systems during the deformation showed that the activation of basal slip systems is the largest during unloading, and the slip direction during unloading is opposite from during loading. These results indicated that one of the factors of the inelastic behaviour during unloading is the fact that the basal slip systems are easily activated during unloading because of their low strengths.
Effects of fluorinated substituents on the refractive index and optical radiation resistance of methacrylates (1993)

Abstract Novel fluorinated methacrylate polymers were synthesized. The purpose was to produce polymers with low refractive indices and increased resistance to optical radiation damage. Six different fluorinated substituents were appended on the monomer before polymerization. Optical‐quality samples were prepared, and their transmission spectra, through 0.8 cm thick samples, were obtained. Each sample was tested for refractive index and glass transition temperature. The samples absorbed 10 MRad gamma radiation from a 60 Co source in an air environment; their transmission spectra were recorded immediately after irradiation and again after seven days had elapsed. As expected, increasing the fluorine content in the side chains resulted in decreased refractive indices. Fluorine content also influenced optical radiation stability. One polymer, poly(1H,1H‐heptafluorobutyl methacrylate) retained superior UV/visible transmission after irradiation. © 1993 John Wiley &amp; Sons, Inc.
Extrapolation of highly accelerated electromigration tests on copper to operation conditions (2003)

Compared to aluminum the electromigration resistance of copper is higher. This leads to longer test times. Higher acceleration factors are needed to reach reasonable test times. Because of the oven hardware there is a limitation in the stress temperature for standard iso-current tests on package level at 350/spl deg/C. Self-heated test methods, such as SWEAT and accelerated iso-current test on wafer level, use Joule-heating to to reach stress temperatures up to 600/spl deg/C and therefore to much lower test times. For aluminum a qualitative analysis with these tests has already been conducted successfully. It would be a major advantage, if quantitative analysis, e.g. extrapolation to operation conditions, would be feasible. During this investigation, we have used three different electromigration stress methods, iso-current test on package level, iso-current test on wafer level and SWEAT, with different stress conditions on the same structure and material. We show an extrapolation of all of the results of the different test methods to operation conditions and a way to calculate the necessary Black's parameters from the results of the highly accelerated self-heated tests.
Quantum statistics of the decay of a Raman soliton (1992)

Recent studies of soliton formation in a Raman amplifier by a \ensuremath{\pi} phase shift have shown that the soliton will decay if the input Stokes beam is off resonance. Initial experiments indicated that this soliton decay is related to frequency shifts of the input Stokes beam that result from quantum fluctuations. In this paper we use the quantum statistics of the Raman spectral fluctuations to compare the predicted decay statistics of the soliton decay with the experimentally measured distribution. We find that, as conjectured, the soliton decay is directly related to the statistics of the initiating quantum fluctuations.
On the uncertainties of decentralized controllers in a transfer production line (2000)

Abstract In this paper, an information theoretic approach is applied to analyze the performance of a decentralized control system. The control system plays the role of a correcting device which decreases the uncertainties associated with state variables of a production line by applying an appropriate “correcting signal” for each deviation from the target. In particular, a distributed feedback control policy is considered to govern a transfer production line, which consists of machines and buffers and processes a single part type in response to a stochastic demand. It is shown how the uncertainty of the demand propagates dynamically into the production system, causing uncertainties associated with buffer levels and machine production rates. The paper proposes upper estimates for these uncertainties as functions of the demand variance, parameters of the distributed controllers and some physical properties of the production line. The bounds are based on dynamic entropy measures of the system state and the control variables. Some practical implications into the area of decentralized controller design are proposed, an information-economical analysis is presented and a numerical study is performed.
Wireless NoC as Interconnection Backbone for Multicore Chips: Promises and Challenges (2012)

Current commercial systems-on-chips (SoCs) designs integrate an increasingly large number of predesigned cores and their number is predicted to increase significantly in the near future. For example, molecular-scale computing promises single or even multiple order-of-magnitude improvements in device densities. The network-on-chip (NoC) is an enabling technology for integration of large numbers of embedded cores on a single die. The existing method of implementing a NoC with planar metal interconnects is deficient due to high latency and significant power consumption arising out of long multi-hop links used in data exchange. The latency, power consumption and interconnect routing problems of conventional NoCs can be addressed by replacing or augmenting multi-hop wired paths with high-bandwidth single-hop long-range wireless links. This opens up new opportunities for detailed investigations into the design of wireless NoCs (WiNoCs) with on-chip antennas, suitable transceivers and routers. Moreover, as it is an emerging technology, the on-chip wireless links also need to overcome significant challenges pertaining to reliable integration. In this paper, we present various challenges and emerging solutions regarding the design of an efficient and reliable WiNoC architecture.
Interfacial Character and Electronic Passivation in Amorphous Thin ‐Film Alumina for Si Photovoltaics (2014)

This chapter contains sections titled: Introduction Experimental Methods Results Discussion Conclusions Acknowledgments
Correlation between acetylator phenotypes and genotypes of polymorphic arylamine N-acetyltransferase in human liver. (1990)

Southern blot analysis was performed with genomic DNAs from 86 human subjects using the 32P-labeled cDNA for polymorphic arylamine N-acetyltransferase (EC 2.3.1.5) in human liver recently cloned in our laboratory. Three types of N-acetyltransferase gene were identified. Gene 1 contains a 5.5-kilobase (kb) KpnI fragment with a BamHI site; gene 2 contains a 5.5-kb KpnI fragment without a BamHI site; and gene 3 contains a 5.0-kb KpnI fragment with a BamHI site. The combination of these three genes generated five genotypes. Acetylator phenotypes were determined in 29 healthy volunteers by isoniazid loading tests, and they were classified as rapid (10 subjects), intermediate (16 subjects), or slow (3 subjects) acetylators. Rapid acetylators were homozygotes of gene 1. Intermediate acetylators were heterozygotes of either genes 1 and 2 or genes 1 and 3. There were two exceptional cases who were classified as intermediate acetylators but were homozygotes of gene 1. Slow acetylators were either heterozygote of genes 2 and 3 or homozygotes of gene 3. These results indicate that gene 1 corresponds to high N-acetyltransferase activity, while gene 2 and gene 3 give rise to low N-acetyltransferase activity.
Nucleoprotein-based nanoscale assembly (1997)

A system for addressing in the construction of macromolecular assemblies can be based on the biospecificity of DNA (cytosine-5) methyltransferases and the capacity of these enzymes to form abortive covalent complexes at targeted 5-fluorocytosine residues in DNA. Using this system, macromolecular assemblies have been created using two representative methyltransferases: M-HhaI and M x MspI. When 5-fluorocytosine (F) is placed at the targeted cytosine in each recognition sequence in a synthetic oligodeoxynucleotide (GFGC for M x HhaI or FCGG for M x MspI), we show that the first recognition sequence becomes an address for M x HhaI, while the second sequence becomes an address for M x MspI. A chimeric enzyme containing a dodecapeptide antigen linked to the C terminus of M-HhaI retained its recognition specificity. That specificity served to address the linked peptide to the GFGC recognition site in DNA. With this assembly system components can be placed in a preselected order on the DNA helix. Axial spacing for adjacent addresses can be guided by the observed kinetic footprint of each methyltransferase. Axial rotation of the addressable protein can be guided by the screw axis of the DNA helix. The system has significant potential in the general construction of macromolecular assemblies. We anticipate that these assemblies will be useful in the construction of regular protein arrays for structural analysis, in the construction of protein-DNA systems as models of chromatin and the synaptonemal complex, and in the construction of macromolecular devices.
Pseudotargeted Metabolomics Method and Its Application in Serum Biomarker Discovery for Hepatocellular Carcinoma Based on Ultra High-Performance Liquid Chromatography/Triple Quadrupole Mass Spectrometry (2013)

Untargeted analysis performed using full-scan mass spectrometry (MS) coupled with liquid chromatography (LC) is commonly used in metabolomics. Although they are commonly employed, full-scan MS methods such as quadrupole-time-of-flight (Q-TOF) MS have been restricted by various factors including their limited linear range and complicated data processing. LC coupled with triple quadrupole (QQQ) MS operated in the multiple reaction monitoring (MRM) mode is the gold standard for metabolite quantification; however, only known metabolites are generally quantified, limiting its applications in metabolomic analysis. In this study, a pseudotargeted approach was proposed to perform serum metabolomic analysis using an ultra high-performance liquid chromatography (UHPLC)/QQQ MS system operated in the MRM mode, for which the MRM ion pairs were acquired from the serum samples through untargeted tandem MS using UHPLC/Q-TOF MS. The UHPLC/QQQ MRM MS-based pseudotargeted method displayed better repeatability and wider linear range than the traditional UHPLC/Q-TOF MS-based untargeted metabolomics method, and no complicated peak alignment was required. The developed method was applied to discover serum biomarkers for patients with hepatocellular carcinoma (HCC). Patients with HCC had decreased lysophosphatidylcholine, increased long-chain and decreased medium-chain acylcarnitines, and increased aromatic and decreased branched-chain amino acid levels compared to healthy controls. The novelty of this work is that it provides an approach to acquire MRM ion pairs from real samples, is not limited to metabolite standards, and it provides a foundation to achieve pseudotargeted metabolomic analysis on the widely used LC/QQQ MS platform.