gebhart/patrepeval huggingface dataset:
Catalytic Ring-Closing Metathesis of Doubly Armed, Bridged Bicyclic Sulfones. Evaluation of Chain Length and Possible Intramolecular SO<sub>2</sub> Group Ligation to the Ruthenium Carbenoid (2000)

Disubstituted bicyclic sulfones 3a−3d, which were prepared by the 2-fold alkylation of 1,6-dilithio-9-thiabicyclo[4.2.1]nonane dioxide, undergo ring-closing metathesis to give a select few of the possible dimers and trimers. Only in the case of 3d were monomeric end products formed. The pronounced diastereoselectivities observed, particularly with the two lowest homologues, are suggested to be kinetically favored because of the operation of internal ruthenium/sulfonyl oxygen coordination during generation of the first intermolecular double bond. This ligation appears to be an important component of the overall reaction in that it serves to maximize unfavorable nonbonded steric interactions when the sulfone bridges adopt a syn relationship. MM3 calculations indicate the anti sulfone dimers also to be thermodynamically favored when n = 3. The preference for the anti sulfone arrangement appears to erode with an increase in the length of the tethers. Not unexpectedly, a ring size dependency is likely at play. The development of a ring-closing metathesis strategy for the incorporation of sulfone groups into stereochemically defined polybicyclic molecules has been realized.
Vitamin D attenuates hyperoxia-induced lung injury through downregulation of Toll-like receptor 4 (2017)

With considerable morbidity and mortality, bronchopulmonary dysplasia (BPD) is a focus of attention in neonatology. Hyperoxia-induced lung injury has long been used as a model of BPD. Among all the signaling pathways involved, Toll-like receptor 4 (TLR4) has been demonstrated to play an important role, and is known to be regulated by vitamin D. This study aimed at elucidating the effect of vitamin D on hyperoxia-induced lung injury and the role of TLR4 in the process. Vitamin D was administered to hyperoxia-treated neonatal rats to investigate changes in the morphology of lungs and expression of pro-inflammatory cytokines, apoptotic proteins and TLR4. Vitamin D attenuated hyperoxia-induced lung injury by protecting the integrity of the lung structure, decreasing extracellular matrix deposition and inhibiting inflammation. The upregulation of TLR4 by hyperoxia was ameliorated by vitamin D and apoptosis was reduced. Vitamin D administration antagonized the activation of TLR4 and therefore alleviated inflammation, reduced apoptosis and preserved lung structure.
Field-emission characteristics and large current density of heavily Si-doped AlN and AlxGa1−xN (0.38⩽x&lt;1) (2001)

From a linear relation between the applied bias and the anode–sample distance, the electric field necessary for field emission (FE) can be obtained reproducibly. For heavily Si-doped AlN and AlxGa1−xN (0.38⩽x&lt;1), the band gap (Al-mole fraction, x), Si-dopant density (NSi), and thickness dependences of the field emission are investigated. After optimizing the sample structure, we obtained a FE current density of 0.22 A/cm2 with a 0.3-mm-diameter rod anode from 0.8-μm-thick Si-doped (NSi:1×1021 cm−3) AlN.
Enzyme-responsive polymeric assemblies, nanoparticles and hydrogels (2012)

Being responsive and adaptive to external stimuli is an intrinsic feature characteristic of all living organisms and soft matter. Specifically, responsive polymers can exhibit reversible or irreversible changes in chemical structures and/or physical properties in response to a specific signal input such as pH, temperature, ionic strength, light irradiation, mechanical force, electric and magnetic fields, and analyte of interest (e.g., ions, bioactive molecules, etc.) or an integration of them. The past decade has evidenced tremendous growth in the fundamental research of responsive polymers, and accordingly, diverse applications in fields ranging from drug or gene nanocarriers, imaging, diagnostics, smart actuators, adaptive coatings, to self-healing materials have been explored and suggested. Among a variety of external stimuli that have been utilized for the design of novel responsive polymers, enzymes have recently emerged to be a promising triggering motif. Enzyme-catalyzed reactions are highly selective and efficient toward specific substrates under mild conditions. They are involved in all biological and metabolic processes, serving as the prime protagonists in the chemistry of living organisms at a molecular level. The integration of enzyme-catalyzed reactions with responsive polymers can further broaden the design flexibility and scope of applications by endowing the latter with enhanced triggering specificity and selectivity. In this tutorial review, we describe recent developments concerning enzyme-responsive polymeric assemblies, nanoparticles, and hydrogels by highlighting this research area with selected literature reports. Three different types of systems, namely, enzyme-triggered self-assembly and aggregation of synthetic polymers, enzyme-driven disintegration and structural reorganization of polymeric assemblies and nanoparticles, and enzyme-triggered sol-to-gel and gel-to-sol transitions, are described. Their promising applications in drug controlled release, biocatalysis, imaging, sensing, and diagnostics are also discussed.
RET Exon 11 (G691S) Polymorphism Is Significantly More Frequent in Sporadic Medullary Thyroid Carcinoma Than in the General Population (2004)

The RET protooncogene is constitutively activated by point mutations in hereditary medullary thyroid carcinomas (MTCs). RET somatic point mutations have also been reported in 40-50% of sporadic MTCs. Several single nucleotide polymorphisms of the RET gene have been described in the general population as well as in patients with MTC. These allelic variants do not seem to confer any transforming activity to the tyrosine kinase domain of the RET gene. Because the exon 11 RET polymorphism determines an important aminoacidic variation (G691S), we studied its frequency in 212 subjects, 106 sporadic MTC patients and 106 normal age-, sex-, race-, and geographic origin-matched controls. In 46 cases of sporadic MTCs, we also studied the cosegregation of somatic RET gene mutation and G691S polymorphism as well as the linkage of the polymorphism with RET germline mutation in 60 members of eight multiple endocrine neoplasia type 2 families. The influence of this polymorphism on the RET gene transcription has also been studied. In parallel we analyzed the frequencies of another three neutral polymorphisms (L769L, S836S, S904S). We found a statistically significant (P = 0.029) higher allelic frequency of G691S polymorphism in MTCs (27.83%) than that found in normal controls (18.86%), at variance with the three neutral polymorphisms whose frequencies were not different in patients and controls. With this study we excluded the influence of the G691S polymorphism on RET mRNA expression, the development of the somatic RET mutation, the linkage with the germline RET mutation, the younger onset of the MTCs, and the clinical outcome of the disease. A putative role of the G691S polymorphism as genetic modifier in the normal subjects remains to be established.
Controlling Vehicle Instability Through Stable Handling Envelopes (2011)

Loss of control accidents result in thousands of fatalities in the United States each year. Production stability control systems are highly effective in preventing these accidents, despite their reliance on a hand-tuned response to data from a small set of sensors. However, improvements in sensing offer opportunities to determine stabilizing actions in a more systematic manner. This paper presents an approach that utilizes the yaw-sideslip phase plane to choose boundaries that eliminate unstable and undesirable driving regimes. These boundaries may be varied to obtain desirable performance and driver acceptance and form the basis for a driver assistance system that augments the driver input to maintain the vehicle within the bounds of a safe handling envelope. Experimental results from a model predictive controller used to enforce the envelope boundaries on a steer-by-wire vehicle are presented to demonstrate the viability of this framework for implementing stability boundaries.
Bone Morphogenetic Protein 2-Coated Porous Poly-L-lactic Acid Scaffolds: Release Kinetics and Induction of Pluripotent C3H10T1/2 Cells (1998)

Induction of a pluripotent C3H10T1/2 (Tl/2) stem cell line down the osteoblastic lineage was demonstrated in vitro using a three-dimensional, porous poly-L-lactic acid (PLLA) scaffold containing bone morphogenetic protein 2 (rhBMP-2). PLLA sponges (100 kDa) were fabricated using a solvent casting/particulate leaching method. C3H10T1/2 cells (5 × 105) and BMP (2.2–6.6 µg) were suspended in collagen I gel and seeded on the scaffold, or rhBMP-2 was precoated on the scaffold and followed by cell seeding. rhBMP-2 release from cell-free rhBMP-2-coated scaffolds, measured directly by enzyme-linked immunosorbant assay (ELISA) and indirectly by alkaline phosphatase assay of Tl/2 cells treated with rhBMP-2-conditioned media, showed release from scaffolds for up to 14 days, with no difference between suspension and precoat groups. Cell-seeded samples were evaluated at 7, 14, and 28 days by histology and scanning electron microscopy, which revealed morphological differences between rhBMP-2 and non-BMP groups. Cells remained viable throughout the study, and osteocalcin immunofluorescence, used to test for osteoinduction, showed a time- and dose-dependent osteocalcin expression in all rhBMP-2 groups, with no staining observed in non-BMP controls. In summary, a single initial dose of rhBMP-2 within a three-dimensional PLLA scaffold was sufficient to induce pluripotent Tl/2 cells to differentiate into the osteoblastic lineage. The availability of tissue-enginered substitutes would simplify bone-grafting procedures.
Retroviruses and cancer (2000)

Retroviruses are relevant to oncologists in three distinct ways. First, human retroviruses as infectious pathogens lead to the development of cancer. Neoplasia may result from the direct infection and transformation of the precursor tumor cell by the retrovirus, as is evident in adult T-cell leukemia caused by the human T-cell lymphotropic virus type I (HTLV-I) (see Chapter 12). Neoplasia may also develop as an indirect consequence of retrovirus infection, as seen in acquired immune deficiency syndrome (AIDS) following infection by human immunodeficiency virus (HIV). In this case, the retroviral genome does not infect or persist in the tumor cells; rather immunodeficiency allows cells infected by oncogenic herpesviruses to proliferate as “opportunistic neoplasms” analogous to opportunistic infections. Secreted retroviral proteins, such as Tat, might also play a role in HIV oncogenesis.
Thermally Active Surfaces in Architecture (2010)

In the architecture profession's ongoing quest for sustainability, it is often the most fundamental practices that require rethinking. Thermally Active Surfaces in Architecture, the groundbreaking new study by 2009 Rome Prize-winning architect Kiel Moe, argues that water, with its higher density, is far better at capturing and channeling energy than air. By separating the heating and cooling of a building from its ventilation, the building's structure itself becomes the primary thermal system. This transformation of energy and building practices triggers a cascading set of possibilities for a building's health, structure, and durability. The first and only book of its kind, Thermally Active Surfaces in Architecture details ten contemporary case studies, from some of today's most innovative architects.
Summary of the Third Workshop on Metallization for Crystalline Silicon Solar Cells (2012)

S.2-13
A Lithium-Based Admixture for ASR Control that Does Not Increase the Pore Solution pH (1997)

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Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer (2008)

Proton beam radiotherapy exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic second cancer. The aim of this study was to explore strategies to reduce stray radiation dose to a patient receiving a 76 Gy proton beam treatment for cancer of the prostate. The whole-body effective dose from stray radiation, E, was estimated using detailed Monte Carlo simulations of a passively scattered proton treatment unit and an anthropomorphic phantom. The predicted value of E was 567 mSv, of which 320 mSv was attributed to leakage from the treatment unit; the remainder arose from scattered radiation that originated within the patient. Modest modifications of the treatment unit reduced E by 212 mSv. Surprisingly, E from a modified passive-scattering device was only slightly higher (109 mSv) than from a nozzle with no leakage, e.g., that which may be approached with a spot-scanning technique. These results add to the body of evidence supporting the suitability of passively scattered proton beams for the treatment of prostate cancer, confirm that the effective dose from stray radiation was not excessive, and, importantly, show that it can be substantially reduced by modest enhancements to the treatment unit.
Comparison of Mixed Linear Complementarity Problem Solvers for Multibody Simulations with Contact (2018)

The trade-off between accuracy and computational performance is one of the central conflicts in real-time multibody simulations, much of which can be attributed to the method used to solve the constrained multibody equations. This paper examines four mixed linear complementarity problem (MLCP) algorithms when they are applied to physical problems involving frictional contact. We consider several different, and challenging, test cases such as grasping, stability of static models, closed loops, and long chains of bodies. The solver parameters are tuned for these simulations and the results are evaluated in terms of numerical accuracy and computational performance. The objective of this paper is to determine the accuracy properties of each solver, find the appropriate method for a defined task, and thus draw conclusions regarding the applicability of each method.
Assembling self-supporting structures (2014)

Self-supporting structures are prominent in historical and contemporary architecture due to advantageous structural properties and efficient use of material. Computer graphics research has recently contributed new design tools that allow creating and interactively exploring self-supporting freeform designs. However, the physical construction of such freeform structures remains challenging, even on small scales. Current construction processes require extensive formwork during assembly, which quickly leads to prohibitively high construction costs for realizations on a building scale. This greatly limits the practical impact of the existing freeform design tools. We propose to replace the commonly used dense formwork with a sparse set of temporary chains. Our method enables gradual construction of the masonry model in stable sections and drastically reduces the material requirements and construction costs. We analyze the input using a variational method to find stable sections, and devise a computationally tractable divide-and-conquer strategy for the combinatorial problem of finding an optimal construction sequence. We validate our method on 3D printed models, demonstrate an application to the restoration of historical models, and create designs of recreational, collaborative self-supporting puzzles.
Small Interfering RNA Knocks Down the Molecular Target of Alendronate, Farnesyl Pyrophosphate Synthase, in Osteoclast and Osteoblast Cultures (2010)

Farnesyl pyrophosphate synthase (FPPS), an enzyme in the mevalonate pathway, is the inhibition target of alendronate, a potent FDA-approved nitrogen-containing bisphosphonate (N-BP) drug, at the molecular level. Alendronate not only inhibits osteoclasts but also has been reported to positively affect osteoblasts. This study assesses the knockdown effects of siRNA targeting FPPS compared with alendronate in both osteoclast and osteoblast cultures. Primary murine bone marrow cell-induced osteoclasts and the preosteoblast MC3T3-E1 cell line were used to assess effects of anti-FPPS siRNA compared with alendronate. Results show that both FPPS mRNA message and protein knockdown in serum-based culture is correlated with reduced osteoclast viability. FPPS siRNA is more potent than 10 μM alendronate, but less potent than 50 μM alendronate on reducing osteoclast viability. Despite FPPS knockdown, no significant changes were observed in osteoblast proliferation. FPPS knockdown promotes osteoblast differentiation significantly but not cell mineral deposition. However, compared with 50 μM alendronate dosing, FPPS siRNA does not exhibit cytotoxic effects on osteoblasts while producing significant effects on ostoblast differentiation. Both siRNA and alendronate at tested concentrations do not have significant effects on cultured osteoblast mineralization. Overall, results indicate that siRNA against FPPS could be useful for selectively inhibiting osteoclast-mediated bone resorption and improving bone mass maintenance by influencing both osteoclasts and osteoblasts in distinct ways.
Brief Report: Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in Patients With IgG4‐Related Disease (2013)

The prozone effect may lead to major underestimations of IgG4 concentrations in patients with IgG4-RD and offers a potential explanation for the poor correlation observed between disease activity and serum IgG4 levels in some patients. This phenomenon should be considered if the serum IgG4 measurement appears discordant with the clinicopathologic diagnosis and the clinical assessment of disease activity.
A Novel Adenoviral Hybrid-vector System Carrying a Plasmid Replicon for Safe and Efficient Cell and Gene Therapeutic Applications (2013)

In dividing cells, the two aims a gene therapeutic approach should accomplish are efficient nuclear delivery and retention of therapeutic DNA. For stable transgene expression, therapeutic DNA can either be maintained by somatic integration or episomal persistence of which the latter approach would diminish the risk of insertional mutagenesis. As most monosystems fail to fulfill both tasks with equal efficiency, hybrid-vector systems represent promising alternatives. Our hybrid-vector system synergizes high-capacity adenoviral vectors (HCAdV) for efficient delivery and the scaffold/matrix attachment region (S/MAR)-based pEPito plasmid replicon for episomal persistence. After proving that this plasmid replicon can be excised from adenovirus in vitro, colony forming assays were performed. We found an increased number of colonies of up to sevenfold in cells that received the functional plasmid replicon proving that the hybrid-vector system is functional. Transgene expression could be maintained for 6 weeks and the extrachromosomal plasmid replicon was rescued. To show efficacy in vivo, the adenoviral hybrid-vector system was injected into C57Bl/6 mice. We found that the plasmid replicon can be released from adenoviral DNA in murine liver resulting in long-term transgene expression. In conclusion, we demonstrate the efficacy of our novel HCAdV-pEPito hybrid-vector system in vitro and in vivo.Molecular Therapy-Nucleic Acids (2013) 2, e83; doi:10.1038/mtna.2013.11; published online 2 April 2013.
Extracellular matrix as target for antitumor therapy (2015)

The aim of the present review is to survey the accumulated knowledge on the extracellular matrix (ECM) of tumors referring to its putative utility as therapeutic target. Following the traditional observation on the extensive morphological alteration in the tumor-affected tissue, the well-documented aberrant cellular regulation indicated that ECM components have an active role in tumor progression. However, due to the diverse functions and variable expression of proteoglycans, matrix proteins, and integrins, it is rather difficult to identify a comprehensive therapeutic target among ECM components. At present, the elevated level of heparanase and the prominent expression of αvβ5 integrin are considered as promising therapeutic targets. The inhibition of glycosaminoglycan offers another promising approach in the treatment of those tumors which are stimulated by proteoglycans. It can be ascertained that a selective ECM inhibitor would be a great asset to control metastasis driven by ECM-mediated signaling.
Development of an Optical Distance Sensor for Robots (1982)

A description is given of the development of an optical distance sensor for robots. The surface of an object is illuminated by light coming through a pinhole, and the light reffected on the surface is guided into a photosensor array by another pinhole. Based on the position of the photosensor unit that detects a magnitude greater than that detected by any other unit, the distance between the surface and the sensor head is determined geometrically, without influence from circumferential illumination or other conditions of an object such as irregularity, reflectivity, and orientation. This sensor is quite powerful and should have a wide variety of practical uses. Both analytic and experimental results are presented.
Fc Receptor-Positive Cells in Remyelinating Multiple Sclerosis Lesions (2006)

The capacity for spontaneous remyelination in cases of multiple sclerosis (MS) is limited and lesions are not fully repaired. Recent evidence has shown that oligodendrocyte precursor cells and immature oligodendrocytes (OPC/iOligs) are preserved in MS lesions. Induced differentiation of these cells into myelinating cells may ultimately lead to a novel remyelination therapy. A previous study showed that the gamma chain of immunoglobulin Fc receptors (FcRgamma), expressed in OPC/iOligs, is essential for their differentiation. Whether FcRgamma is expressed in preserved OPC/iOligs within MS lesions, however, remains uncertain. In the present study, we examined 10 autopsy cases of MS for the expression of FcRgamma both in remyelinating areas and demyelinated plaques. The expression of FcRgamma was confirmed in both OPC/iOligs and microglia in MS lesions. Statistical analysis showed that the density of FcRgamma-positive OPC/iOligs was approximately 3 times greater in remyelinating areas compared with demyelinated plaques; the opposite was true of FcRgamma-positive microglia. The distribution of FcRgamma-negative OPC/iOligs did not differ between the 2 types of lesions. Thus, an increase in FcRgamma-positive OPC/iOligs and a decrease in FcRgamma-positive microglia, but not in FcRgamma-negative OPC/iOligs, are associated with spontaneous remyelination in MS brains, suggesting a possible role for FcRgamma in the induction of remyelination.
General-Purpose 3V CMOS Operational Amplifier with a New Constant-Transconductance Input Stage (1997)

Design trade-offs for a low-voltage two-stage amplifier in the HP CMOS14 process are presented and some of the issues of low-voltage analog design are discussed. The design of a new constant-transconductance input stage that has a rail-to-rail common-mode input range is described, along with the rail-to-rail class-AB output stage. The performance specifications and area of this amplifier are compared with a similar design in a previous process, CMOS34.