gebhart/patrepeval huggingface dataset:
Reversible covalent enzyme immobilization methods for reuse of carriers (2017)

Reversible immobilization techniques which allow for multiple use of the carrier are relevant for applications, such as enzymatic microreactors, biosensors with specific setups and for expensive carriers such as superparamagnetic particles. The activity of immobilized enzymes reduces with time, so that the introduction of fresh immobilized enzyme becomes necessary. Thus, methods for reversible immobilization and multiple carrier reuse can help to reduce purchase costs and facilitate reactor construction. In this work, we present a method that makes use of the reduction and oxidation of cystamine, a cleavable linker with disulfide bond and amine functionality. For a proof of principle, α-chymotrypsin was immobilized on polyethylene glycol with terminal epoxy groups using cystamine as a crosslinker. The enzyme was highly active and could be used in repeated cycles. After the enzymatic reaction was demonstrated, α-chymotrypsin was cleaved off the particle by reducing agents. The resulting thiols on the particle surface were oxidized to disulfides by means of cysteamine, the reduction product of cystamine. This way, an almost complete oxidation of surface thiols with cysteamine was possible, restoring amine functionalization for further reactions. Reduction and oxidation were repeated several times without a decrease in the extent of amine coupling. Finally, immobilization of α-chymotrypsin could be repeated with results comparable to first run.
Construction of Counterfactuals and the G-computation Formula (2002)

Robins' causal inference theory assumes existence of treatment specific counterfactual variables so that the observed data augmented by the counterfactual data will satisfy a consistency and a randomization assumption. Gill and Robins [2001] show that the consistency and randomization assumptions do not add any restrictions to the observed data distribution. In particular, they provide a construction of counterfactuals as a function of the observed data distribution. In this paper we provide a construction of counterfactuals as a function of the observed data itself. Our construction provides a new statistical tool for estimation of counterfactual distributions. Robins [1987b] shows that the counterfactual distribution can be identified from the observed data distribution by a G-computation formula under an additional identifiability assumption. He proves this for discrete variables. Gill and Robins [2001] prove the G-computation formula for continuous variable under some additional conditions and modifications of the consistency and the randomization assumptions. We prove that if treatment is discrete, then Robins' G-computation formula holds under the original consistency, randomization assumptions and a generalized version of identifiability assumption.
Heat transfer enhancement by metal foam during nucleate pool boiling of refrigerant/oil mixture at a wide range of oil concentration (2012)

Nucleate pool boiling heat transfer characteristics of refrigerant/oil mixtures on metal foam covers were experimentally investigated at a wide range of oil concentrations. The refrigerant and oil are R113 and VG68, respectively;and the oil concentration varies from 0% to 40%. The copper foams have pores per inch (ppi) of 10 and 20 and porosity from 90% to 98%. Experimental conditions include a saturation pressure of 101 kPa (14.696 psi), and heat flux from 30 to 137 kW m(-2) (2.6417 to 12.064 Btu s(-1) ft(-2)). The experimental results indicate that the nucleate pool boiling heat transfer coefficients on copper foam covers are larger than those on a plain heating surface by a maximum of 450%; the presence of oil deteriorates the nucleate pool boiling heat transfer on copper foam covers by a maximum of 90%. With the increase of oil concentration, the deterioration effect on high ppi metal foams is more obvious than that for low ppi. A correlation for predicting the nucleate pool boiling heat transfer coefficient of refrigerant/oil mixtures on metal foam covers is developed, and it agrees with 90% of the experimental data within a deviation of +/- 30%.
Comparison of Au and Au–Ni Alloys as Contact Materials for MEMS Switches (2009)

This paper reports on a comparison of gold and gold-nickel alloys as contact materials for microelectromechanical systems (MEMS) switches. Pure gold is commonly used as the contact material in low-force metal-contact MEMS switches. The top two failure mechanisms of these switches are wear and stiction, which may be related to the material softness and the relatively high surface adhesion, respectively. Alloying gold with another metal introduces new processing options to strengthen the material against wear and reduce surface adhesion. In this paper, the properties of Au-Ni alloys were investigated as the lower contact electrode was controlled by adjusting the nickel content and thermal processing conditions. A unique and efficient switching degradation test was conducted on the alloy samples, using pure gold upper microcontacts. Solid-solution Au-Ni samples showed reduced wear rate but increased contact resistance, while two-phase Au-Ni (20 at.% Ni) showed a substantial improvement of switching reliability with only a small increase of contact resistance. Discussion of the effects of phase separation, surface topography, hardness, and electrical resistivity on contact resistance and switch degradation is also included.
Durable Scar Size Reduction Due to Allogeneic Mesenchymal Stem Cell Therapy Regulates Whole‐Chamber Remodeling (2013)

Intramyocardial injection of allogeneic MSCs leads to a sustained and progressive reduction in infarct size, which in turn drives reverse remodeling and increases in ejection fraction. These findings support ongoing biological activity of cell therapy for substantial periods and suggest optimal end points for future clinical trials.
ChemInform Abstract: Cage Dimeric 4‐Aryl‐1,4‐dihydropyridines as Promising Lead Structures for the Development of a Novel Class of HIV‐1 Protease Inhibitors. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Outcomes of Metallic Stents for Malignant Ureteral Obstruction (2012)

Failure rates with a metallic stent are similar to those historically observed with traditional polyurethane based stents in malignant ureteral obstruction. The invasion of prostate cancer in the bladder significantly increases the risk of failure. Patients should be counseled and observed for subcapsular hematoma formation with this device.
Sampling-based tree search with discrete abstractions for motion planning with dynamics and temporal logic (2014)

This paper presents an efficient approach for planning collision-free, dynamically-feasible, and low-cost motion trajectories that satisfy task specifications given as formulas in a temporal logic, namely Syntactically Co-Safe Linear Temporal Logic (LTL). The planner is geared toward high-dimensional mobile robots with nonlinear dynamics operating in complex environments. The planner incorporates physics-based engines for accurate simulations of rigid-body dynamics. To obtain computational efficiency and generate low-cost solutions, the planner first imposes a discrete abstraction by combining an automaton representing the LTL formula with a workspace decomposition. The planner then uses the discrete abstraction to induce a partition of a sampling-based motion tree being expanded in the state space into equivalence classes. Each equivalence class captures the progress made toward achieving the temporal logic specifications. Heuristics defined over the abstraction are used to estimate the feasibility of expanding the motion tree from these equivalence classes and reaching an accepting automaton state. Costs are adjusted based on progress made, giving the planner the flexibility to make rapid progress while discovering new ways to expand the search. Comparisons to related work show statistically significant computational speedups and reduced solution costs.
Mechanisms of Transmembrane Transport of Oligonucleotides (2003)

The fact that antisense Oligonucleotides can reach target mRNAs within cells is really quite remarkable from a membrane transport perspective. Cell membranes are designed by nature to be very impermeable to large, polar molecules such as Oligonucleotides, unless specific transport pathways are available. For charged Oligonucleotides, there is good evidence that initial accumulation in cells is largely due to some form of endocytosis (Akhtar and Juliano, 1992; Bennett, 1998; Stein and Cheng, 1993; Wagner, 1994). Studies using fluorescent conjugates (Beltinger et al., 1995; Shoji et al., 1991; Stein and Cheng, 1993; Wagner, 1994) have shown that Oligonucleotides taken up by intact cells have a punctate cytoplasmic distribution, and are initially localized in cytoplasmic vesicles that are probably endosomes; in most cases little fluorescence is associated with the nucleus. However, when fluorescent Oligonucleotides are microinjected directly into the cytoplasm they rapidly redistribute to the nucleus (Fisher et al., 1993; Leonetti et al., 1991). Therefore, intact Oligonucleotides leaking out of endosomes would be expected to accumulate rapidly in the nucleus, but this is not seen in most cells, indicating very limited transfer of Oligonucleotides from endosomal to cytoplasmic compartments. However, since antisense effects clearly do occur, some transfer must take place. Oligonucleotides not only accumulate in endosomes, but they can also recycle back to the cell surface and be released; this seems to be particularly true for material accumulating in so-called ‘shallow’ endosomal compartments (Stein and Cheng, 1993; see also Chapter 9). Although many cells take up Oligonucleotides via endocytosis, some interesting recent studies have suggested that the endocytotic rates for Oligonucleotides are different for the apical and basolateral regions of polarized epithelial cells (Takakura et al., 1998).
Surfactant controlled magnesium oxide synthesis for base catalysis (2015)

Magnesium oxide catalysts were used to investigate the influence of novel preparative techniques for surface site control on activity.
A variable-threshold voltage technique to enhance the linearity of folding-integration/cyclic cascaded ADCs (2016)

A variable-threshold voltage technique for folding-integration (FI) analog-to-digital converters (ADCs) with 1-bit quantizer is proposed to enhance the linearity of folding-integration/cyclic cascaded (FICC) ADCs. Based on the modeling and analysis of behavioral operation of FICC ADCs, a variable-threshold voltage is applied to the 1-bit sub-ADC of FI operation to decrease errors from offset of comparator and imperfect amplification of switch-capacitor amplifier. The variable-threshold voltage is designed to be automatically adjustable by measurement and feedback control according to the scale of input signal of FICC ADC. The effectiveness of proposed technique is confirmed by behavioral-level simulation. Then the technique is implemented and simulated in 65nm CMOS technology.
On clarification of haze in polypropylene (2016)

The mechanism of reducing light scattering in isotactic polypropylene (i-PP), through the addition of so-called clarifying agents, is studied with small-angle light scattering (SALS) and scanning electron microscopy (SEM). The clarifying agents used in this study depict monotectic phase behavior with i-PP, crystallizing in a relatively narrow concentration range in a nanofibrillar network, providing an ultrahigh nucleation density in the i-PP melt. It is found that the clarifying effect, a dramatically increased transparency and reduced haze, that occurs within the aforementioned additive concentration range, coincides with a change in morphology from strongly scattering spherulites to shish-kebab-like crystalline structures, as evidenced by in situ SALS measurements and confirmed by SEM images. A simple scaling law, relating the diameter of the shish-kebab structures to the fibril diameter and volume fraction of the clarifying agent is proposed, suggesting that the performance of a (fibril-forming) clarifying agent will improve by reducing the fibril diameter and/or increasing the volume concentration of the clarifying agent. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 865–874
Ion beam induced charge imaging for the failure analysis of semiconductor devices (2002)

Ion Beam Induced Charge (IBIC) imaging is an emerging technique with potential applications in failure analysis of semiconductor devices. The large penetration depth of the high energy proton beams used in IBIC ensures accessibility of active device regions in multilevel metal chips unlike the low energy electron beam in the SEM based Electron Beam Induced Current (EBIC) imaging technique. New contrast mechanisms observed for the first time in IBIC imaging are presented. IBIC images are compared with the EBIC images and it is shown that additional contrast mechanisms occurring in IBIC enable it to be used as a useful failure analysis tool.
Program for Seminar Series on "Science, Policy and Politics- Biofuel in Brussels" (2008)

This seminar series consists of five separate but interrelated sessions, all dealing with different aspects of the topic. The seminars are open for all interested PhD students. Each session is coordinated by one or two members of the PhD-group at Stockholm Resilience Centre, but all participants are contributing to the discussion. More literature than what is indicated here might be added, so if you are interested in participating, please contact the coordinator/s for the specific session in beforehand (see email below).
Use of Mixture Models in a Microarray-Based Screening Procedure for Detecting Differentially Represented Yeast Mutants (2003)

We describe the use of a statistical model in a genome-wide microarray-based yeast genetic screen performed by imposing different genetic selections on thousands of yeast mutants in parallel. A mixture model is fitted to data obtained from oligonucleotide arrays hybridized to 20-mer oligonucleotide "barcodes'' and a procedure based on the fitted model is used to search for mutants differentially represented under experimental and control conditions. The fitted stochastic model provides a way to assess uncertainty. We demonstrate the usefulness of the model by applying it to the problem of screening for components of the nonhomologous end joining (NHEJ) pathway and identified known components of the NHEJ pathway.
miRNA expression in human lung cancer and fetal lung: a comparative study (2013)

Trabalho apresentado na São Paulo Advanced School of Comparative Oncology, Águas de São Pedro, SP, 2012.
Reverse Engineering Configurations of Neural Text Generation Models (2020)

This paper seeks to develop a deeper understanding of the fundamental properties of neural text generations models. The study of artifacts that emerge in machine generated text as a result of modeling choices is a nascent research area. Previously, the extent and degree to which these artifacts surface in generated text has not been well studied. In the spirit of better understanding generative text models and their artifacts, we propose the new task of distinguishing which of several variants of a given model generated a piece of text, and we conduct an extensive suite of diagnostic tests to observe whether modeling choices (e.g., sampling methods, top-$k$ probabilities, model architectures, etc.) leave detectable artifacts in the text they generate. Our key finding, which is backed by a rigorous set of experiments, is that such artifacts are present and that different modeling choices can be inferred by observing the generated text alone. This suggests that neural text generators may be more sensitive to various modeling choices than previously thought.
Carbon‐Nanotube‐Based Thermoelectric Materials and Devices (2018)

Conversion of waste heat to voltage has the potential to significantly reduce the carbon footprint of a number of critical energy sectors, such as the transportation and electricity-generation sectors, and manufacturing processes. Thermal energy is also an abundant low-flux source that can be harnessed to power portable/wearable electronic devices and critical components in remote off-grid locations. As such, a number of different inorganic and organic materials are being explored for their potential in thermoelectric-energy-harvesting devices. Carbon-based thermoelectric materials are particularly attractive due to their use of nontoxic, abundant source-materials, their amenability to high-throughput solution-phase fabrication routes, and the high specific energy (i.e., W g<sup>-1</sup> ) enabled by their low mass. Single-walled carbon nanotubes (SWCNTs) represent a unique 1D carbon allotrope with structural, electrical, and thermal properties that enable efficient thermoelectric-energy conversion. Here, the progress made toward understanding the fundamental thermoelectric properties of SWCNTs, nanotube-based composites, and thermoelectric devices prepared from these materials is reviewed in detail. This progress illuminates the tremendous potential that carbon-nanotube-based materials and composites have for producing high-performance next-generation devices for thermoelectric-energy harvesting.
Phase II study of S-1 plus irinotecan and oxaliplatin for refractory, heavily treated metastatic colorectal cancer (2008)

15116 Background: Three-drug combination of fluoropyrimidine, irinotecan and oxaliplatin is known to be active for metastatic colorectal cancer (mCRC). In vitro synergy has been reported with each drug, thus combination of all 3-drug may overcome refractoriness to each other. We had performed phase I study to determine doses of phase II study of S-1 plus irinotecan and oxaliplatin (TIROX) for untreated mCRC, favorable responses were also observed in heavily-treated mCRC in phase I. We performed a phase II study of TIROX to evaluate efficacy and safety in refractory, heavily treated mCRC patients (pts) with no further treatment option. Methods: Pts with refractory to all of 3 drugs, age ≥ 18 yrs, PS 0–2, ≥ 1 measurable lesion(s) and adequate organ functions were eligible. S-1 was given 40 mg/m2 twice a day on D1–14, oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2 on D1 every 3 weeks. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression free survival (PFS) and overall survival (OS). Results: Between Mar 2007 and Nov 2007, 19 pts (of 18 planned) were enrolled; median age 50 yrs; M/F 12/7; PS 0/1/2 5/13/1; colon/rectum 11/8. Median OS from initial diagnosis of mCRC to the TIROX was 20.9 months (mo) and G1 sensory neuropathy was noted in 15 pts at baseline. TIROX was their 3rd line regimen in 3 (15.8%), 4th in 13 (57.9%) and ≥ 5th in 3 pts (15.8%). Bevacizumab and cetuximab was exposed previously to 4 and 7 pts, respectively. By intent-to-treat analysis, ORR was 21.1% (95% CI, 8.7 - 43.7) and disease control rate was 52.6% (95% CI 31.5 - 72.8) with 4 PRs and 6 SDs. The median duration of disease control was 4.3 mo (95% CI 1.7–6.9). Median PFS was 2.6 mo (95% CI 2.2 - 2.9) and median OS was not reached with median FU of 7.5 mo. G3/4 toxicities per pt included neutropenia (5, 26.3%), leucopenia (3, 15.8%), febrile neutropenia (2, 10.5%), thrombocytopenia (1, 5.3%), diarrhea (2, 10.5%) and fatigue (2, 10.5%). Conclusions: TIROX seemed to be feasible for refractory, heavily-treated mCRC pts. Combination of previously exposed agents may have activity against refractory mCRC and could be an alternative for pts with good PS but no further treatment options. No significant financial relationships to disclose.
Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders (2018)

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.
A small molecule human PD-1/PD-L1 inhibitor promotes T cell immune activation and reduces tumor growth in a preclinical model (2018)

Background: In recent years, antibody-based therapies targeting the Programmed cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) immune checkpoint axis have gained tremendous success in cancer immunotherapy. We embarked on an effort to identify and develop small molecules capable of targeting this immune checkpoint, with an aim to provide new therapeutic options with improved anticancer immune responses, increased tumor penetration, shorter half-life to better managing immune related adverse events, and lower cost of goods. Methods: We developed a number of small molecule inhibitors based on the crystal structure of human PD-1/PD-L1 complex. Active compounds were first identified by an ELISA assay measuring inhibition of the PD-1/PD-L1 interaction, followed by functional cell-based reporter and mixed lymphocyte reaction (MLR) assays. Since these inhibitors specifically block human PD-1/PD-L1 interaction, we co-implanted A375 human melanoma cells along with human peripheral blood mononuclear cells (PBMCs) into immunodeficient NOD/SCID mice to test their efficacy in vivo. Results: We have obtained potent human PD-1/PD-L1 inhibitors with marked activities in both the cell-based reporter and MLR assays. Moreover, lead compound CCX4503 reduced tumor growth in vivo to a similar extent as the positive control anti-human PD-L1 antibody. Anti-tumor activity was completely dependent on the presence of human PBMCs. The tumor microenvironment analysis indicated that the anti-tumor activity of CCX4503 was accompanied by a significantly higher CD8+ T-Cell/CD4+ T-cell ratio. An X-ray structure of CCX4503 co-crystallized with PD-L1 provided information about the structural basis by which the compound disrupts the PD-1/PD-L1 immune checkpoint interaction. Conclusions: We have identified and advanced unique small molecule inhibitors of human PD-1/PD-L1 by rational design. Molecules resulting from these efforts, such as CCX4503, exhibited marked inhibition of the PD-1/PD-L1 interaction and signaling in vitro, and also clear anti-tumor effects in an animal model system in vivo. Legal entity responsible for the study: ChemoCentryx, Inc., Mountain View, CA. Funding: ChemoCentryx, Inc., Mountain View, CA. Disclosure: M. Vilalta Colomer, S. Li, V. Malathong, C. Lange, D. McMurtrie, J. Yang, H. Roth, J. McMahon, J.J. Campbell, L.S. Ertl, R. Ong, Y. Wang, N. Zhao, S. Yau, T. Dang, P. Zhang, T.J. Schall, R. Singh: Full-time employee of ChemoCentryx. S. Punna: Stock holder: ChemoCentryx.