gebhart/patrepeval huggingface dataset:
In vitro aging of dental composites in water—Effect of degree of conversion, filler volume, and filler/matrix coupling (1998)

The purpose of this study was to evaluate the long-term effect of aging in water on the physical properties of experimental composites having systematically controlled differences in degree of conversion (DC), filler volume fraction (Vf), and percentage of silane-treated fillers. Composites were made with a 50% Bis-GMA:50% TEGDMA light-cured resin and a 1–2 μm (average size) strontium glass filler (+ 5 wt% SiO2 microfiller). For composites A–E, the DC was varied from 56–66% by changing the curing time; for D and F–I, the Vf was varied from 28–62 vol%; and for D and J–M, the percent of fillers with a silane coupling agent (γ-MPS) was varied from 20–100%. Fracture toughness (KIc), flexure strength (FS), elastic modulus (E), and hardness (KHN) were tested after soaking in water at 37°C for 1 day, 6 months, 1 year, and 2 years. The KIc was reduced 20–30% for all composites after 6 months, with minimal changes thereafter. The FS was reduced for several composites at 6 months, but only those with poor cure (A and B) were lower at 2 years than they were initially. The E was not reduced for most composites. Hardness was reduced for most composites after 6 months, but many returned to their original levels at 2 years. Long-term aging in water caused a reduction in the KIc, independent of composition, but had little effect on other properties, suggesting limited degradation of composites in water. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 465–472, 1998.
Influence of OprM expression on multiple antibiotic resistance in Pseudomonas aeruginosa (1997)

MexA-MexB-OprM is an efflux system in Pseudomonas aeruginosa. OprM overproduced from the cloned gene was able to complement OprM-deficient mutants but did not alter the resistance of a wild-type P. aeruginosa strain to the different antimicrobial agents tested. This suggests that OprM cannot function by itself to efflux antibiotics, including beta-lactams targeted to the periplasm.
Design, synthesis and biological evaluation of tamoxifen-fusion compounds for the optimization of MASPIT, a three-hybrid target deconvolution assay (2014)

Methods that allow high throughput identification of cellular targets of biologically active small molecules are valuable assets in pharmaceutical research. They are useful in mechanism of action studies of hits identified via phenotypic screening. Alternatively, they may uncover ‘off-target’ proteins of established drugs, that may contribute to their therapeutic efficacy or unwanted side effects. Finally, such methods also allow to identify potential novel therapeutic applications of existing drugs.
Incidental De-novo Cerebral Micro-hemorrhages are Predictive of Future Symptomatic Macro-hemorrhages after Surgical Revascularization in Moyamoya Disease (2020)

Li, Yiping MD; Steinberg, Gary K MD, PhD; Esene, Ignatius N MD, MS, MPH; Bigder, Mark G MD; Mandel, Mauricio MD, PhD Author Information
Wire‐Like Tip‐To‐Tip Linked Assemblies of CdSe‐CdS Quantum Rods Promoted on Supramolecular Nanofibers of Hybrid Organo‐ and Hydrogels (2019)

Abstract A variety of core‐shell CdSe‐CdS nanorods or quantum rods (QRs), both sphere (CdSe) in rod (CdS) and rod (CdSe) in rod (CdS) have been synthesized in a seeded‐growth approach using a very efficient and highly thermally stable steroidal cadmium precursor replacing the more common CdO: cadmium deoxycholate. The core‐shell QRs display high photoluminescence quantum yields (40–75%) and high molar absorption co‐efficient (ϵ=10 6 M −1 cm −1 ). Sphere‐in‐rods QRs can be co‐assembled with the organogelator diethylaminolithocholyl iodide in 1,2‐dichlorobenzene and with the hydrogelator calcium cholate in water to form hybrid gels. These organic‐inorganic hybrid soft materials are translucent and brightly red‐luminescent. The nanofibers composing the gel network act as a scaffold to support the dispersed QRs and impede their self‐aggregation. Furthermore, formation of original wire‐like assemblies of the nanorods is promoted in these gels, in particular in the hydrogel. This orientation occurs by a QR tip‐to‐tip interaction and is proposed to be driven by the amphiphilic behaviour of the QRs: laterally capped by negatively charged TGA (thioglycolic acid) ligands and un‐capped on the tips due to TGA unbinding. The combination of nanofiber‐forming hydrogelators and elongated quantum rods is promising in the perspective to form hybrid nanostructures with anisotropic optic or electronic properties.
Qualitative Reasoning with Modelica Models (2014)

Qualitative reasoning can play an important role in early stage design. Currently, engineers explore the design space using simulation models built in languages such as Modelica. To make qualitative reasoning useful to them, designs specified in their languages must be translated into a qualitative modeling language for analysis. The contribution of this paper is a sound and effective mapping between Modelica and qualitative reasoning. To achieve a sound mapping, we extend envisioning, the process of generating all relevant qualitative behaviors, to support Modelica's declarative events. For an effective mapping, we identify three classes of additional constraints that should be inferred from the Modelica representation thereby exponentially reducing the number of unrealizable trajectories. We support this contribution with examples and a case study.
A phase II study of lapatinib and capecitabine in second-line treatment of metastatic pancreatic cancer. (2012)

e14569 Background: The anti-EGFR therapy erlotinib was FDA approved for the treatment of patients with advanced pancreas cancer. Human epidermal growth factor receptor 2 (HER-2), a member of the ErbB family of growth factor receptor tyrosine kinases to which EGFR belongs, is found overexpressed in 20% of pancreatic cancers . Targeting EGFR and HER-2 with separate specific monoclonal antibodies showed synergistic inhibition of pancreatic cancer tumor progression in mice bearing xenograft of human pancreatic cancer cell lines. We performed an open-label single arm phase II study to evaluate the combination of lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2, and capecitabine in the second-line treatment of metastatic pancreatic cancer. Methods: Patients with metastatic, unresectable, gemcitabine-refractory pancreatic cancer with adequate performance status (ECOG 0-2) and normal hepatic and renal function were eligible. Patients received lapatinib 1,250 mg PO daily, and capecitabine 1,000 mg/m 2 PO twice daily on days 1-14 of each 21-day cycle. Restaging studies were performed every 2 cycles. The primary endpoint was median overall survival (OS). Secondary endpoints included response rate (RR) and progression free survival (PFS). Results: Between 9-2009 and 8-2011, 17 patients received treatment. Six of 17 patients (24%) had disease progression after 2 cycles, 2 of 17 patients (12%) progressed after 4 cycles and 4 of 17 patients (24%) had stable disease and received more than 6 cycles. The median number of treatment cycles was 3 (range 1-22 cycles). The median PFS was 9 weeks (95% CI 7.1-18.9). Median OS was 25 weeks (95% CI 11 -34). Grade 3 nausea, vomiting in 3 patients (17%), grade 3 diarrhea in 2 patients (12%), grade 3 limb edema in 1 patient (6%), and grade 3 fatigue in 1 patient (6%). Serum was collected at baseline, three weeks and time of disease progression for microRNA analysis to identify biomarkers correlated with clinical outcome. Conclusions: The combination of lapatinib and capecitabine is a tolerated regimen for patients with gemcitabine-refractory metastatic pancreatic cancer. Some patients were able to receive 6 or more cycles of therapy. Molecular analysis of patients’ biosamples is ongoing.
Design and Development of Passive and Active Force Feedback Systems Using Magnetorheological Fluids (2003)

Recently, haptic devices have been in use to increase the effectiveness of human-machine interfaces. On the forefront of this technology are passive, force-feedback controllers that resist or even limit motion. This motion control can be the result of a manipulator coming into contact with an object in either the virtual or physical world. Thus, an end-user can get both visual and tactile feedback on system operations. Furthermore, an active force-feedback controller can not only resist motion, but also create a reactive force that the user can sense. This active force-feedback is essential for delicate operations, such as telerobotic surgery, where a doctor needs to feel the difference between a spongy muscle and a hard bone. However, such haptic devices need to be simple and fast, so that they will not interfere with the existing system dynamics. A promising solution employs magnetorheological (MR) fluids in an active force-feedback controller. MR fluids feature a rheological change that is brought about when micron-sized particles within the fluid are exposed to a magnetic field. This change happens within milliseconds and can be used to create resistance quickly and easily. MR fluids can also be combined in a motor driven clutch mechanism to provide active resistance to the user with a force proportional to what the manipulator is experiencing. This paper will show the model development, design, construction, and control implementation of passive and active force-feedback devices.
A low noise local oscillator for wireless regional area network applications (2015)

This work develops a high performance wideband and low noise local oscillator (LO) for wireless regional area network (WRAN) applications. The WRAN system uses the white spaces of the 50-860 MHz TV spectrum for increasing the spectrum efficiency. To cover such wideband operating range, we proposed a novel LO technique. This technique not only increases the operating range but also decreases the phase noise of the LO. Experimental results show that the proposed LO can achieves a wide operating range from 50 MHz to 1 GHz. The phase noise of the LO at 1 MHz offset frequency is as low as -131 and -132 dBc/Hz at 50 MHz and 1 GHz, respectively.
Charge Separation in a Nonfluorescent Donor−Acceptor Dyad Derived from Boron Dipyrromethene Dye, Leading to Photocurrent Generation (2005)

Boron dipyrromethene (BODIPY), which is commonly used as an energy absorbing and transferring antenna\nmolecule, has been modified to contain an electron donor moiety, 8-(2,4,5-trimethoxyphenyl)-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-&lt;i&gt;s&lt;/i&gt;-indacene (&lt;b&gt;MEOPHBDP&lt;/b&gt;). The photoinduced electron transfer from\na 2,4,5-trimethoxyphenyl moiety to a BODIPY moiety of &lt;b&gt;MEOPHBDP&lt;/b&gt; in acetonitrile was observed by\nfemtosecond laser flash photolysis measurements. The lifetime of the charge-separated state of &lt;b&gt;MEOPHBDP&lt;/b&gt;\nwas 59 ps at 298 K. The dye-sensitized solar cells (DSSC) were prepared using &lt;b&gt;MEOPHBDP&lt;/b&gt; with carboxylic\nacid (&lt;b&gt;MEOPHBDP&lt;/b&gt;−&lt;b&gt;COOH&lt;/b&gt;) and a reference BODIPY dye having no electron donor moiety. The photovoltaic\nmeasurements were performed using a standard two-electrode system consisting of a working electrode and\na Pt sputtered electrode in methoxyacetonitrile containing 0.5 M iodide and 0.05 M I&lt;sub&gt;2&lt;/sub&gt;. The photoelectrochemical\nproperties of DSSC with &lt;b&gt;MEOPHBDP&lt;/b&gt; are compared with those with a reference BODIPY dye.
Studies on the Replication of the Ring Opened Formamidopyrimidine, Fapy·dG in Escherichia coli (2007)

Fapy.dG is produced in DNA as a result of oxidative stress from a precursor that also forms OxodG. Bypass of Fapy.dG in a shuttle vector in COS-7 cells produces G --> T transversions slightly more frequently than does OxodG (Kalam, M. A., et al. (2006) Nucleic Acids Res. 34, 2305). The effect of Fapy.dG on replication in Escherichia coli was studied by transfecting M13mp7(L2) bacteriophage DNA containing the lesion within the lacZ gene in 4 local sequence contexts. For comparison, experiments were carried out side-by-side on OxodG. The efficiency of lesion bypass was determined relative to that of a genome containing native nucleotides. Fapy.dG was bypassed less efficiently than OxodG. Bypass efficiency of Fapy.dG and OxodG increased modestly in SOS-induced cells. Mutation frequencies at the site of the lesions in the originally transfected genomes were determined using the REAP assay (Delaney, J. C., Essigmann, J. M. (2006) Methods Enzymol. 408, 1). G --> T transversions were the only mutations observed above background when either Fapy.dG or OxodG was bypassed. OxodG mutation frequencies ranged from 3.1% to 9.8%, whereas the G --> T transversion frequencies observed upon Fapy.dG bypass were <or=1.9% in wild-type E. coli. In contrast to OxodG bypass, Fapy.dG mutation frequencies were unaffected by carrying out experiments in mutM/mutY cells. Overall, these experiments suggest that Fapy.dG is at most weakly mutagenic in E. coli. Steady-state kinetic experiments using the Klenow fragment of DNA polymerase I from E. coli suggest that a low dA misincorporation frequency opposite Fapy.dG and inefficient extension of a Fapy.dG:dA base pair work synergistically to minimize the levels of G --> T transversions.
A model of the aged lung epithelium in idiopathic pulmonary fibrosis (2021)

Idiopathic pulmonary fibrosis (IPF) is an age-related disorder that carries a universally poor prognosis and is thought to arise from repetitive micro injuries to the alveolar epithelium. To date, a major factor limiting our understanding of IPF is a deficiency of disease models, particularly <i>in vitro</i> models that can recapitulate the full complement of molecular attributes in the human condition. In this study, we aimed to develop a model that more closely resembles the aberrant IPF lung epithelium. By exposing mouse alveolar epithelial cells to repeated, low doses of bleomycin, instead of usual one-time exposures, we uncovered changes strikingly similar to those in the IPF lung epithelium. This included the acquisition of multiple phenotypic and functional characteristics of senescent cells and the adoption of previously described changes in mitochondrial homeostasis, including alterations in redox balance, energy production and activity of the mitochondrial unfolded protein response. We also uncovered dramatic changes in cellular metabolism and detected a profound loss of proteostasis, as characterized by the accumulation of cytoplasmic protein aggregates, dysregulated expression of chaperone proteins and decreased activity of the ubiquitin proteasome system. In summary, we describe an <i>in vitro</i> model that closely resembles the aberrant lung epithelium in IPF. We propose that this simple yet powerful tool could help uncover new biological mechanisms and assist in developing new pharmacological tools to treat the disease.
Hand pointing is accurate following adaptation of saccadic gain (2010)

The visual system uses two major sources of information to determine the direction of an object in space: extra-retinal signals from ocular muscles and retinal cues. The influence of extra-retinal signals on estimates of perceived space is unclear. Saccade amplitude can be adapted quickly using a double-step paradigm. Extra-retinal factors are thought to be responsible for the resulting change in saccade size and its influence on perceived direction. An alternative hypothesis is that retinal signals undergo adaptation. In order to determine which of these accounts is correct, we asked subjects to point with the unseen hand to brief visual targets at eccentricities of 5, 10, 12, 15 and 20 degrees. There were two conditions: (1) the subject made a saccade toward the intended target and then pointed towards the remembered target location, and (2) the subject pointed at the flashed target without making a saccade. Subjects performed this task before and after saccade adaptation. Although saccades were adapted to 1/3 of their original size, subjects still pointed towards the correct location of the flashed target under both conditions. This suggests that the assumption of extra-retinal adaptation is correct, and that retinal signals are not altered by double-step saccade adaptation.
Detecting Out-Of-Context Objects Using Graph Contextual Reasoning Network (2022)

This paper presents an approach for detecting out-of-context (OOC) objects in images. Given an image with a set of objects, our goal is to determine if an object is inconsistent with the contextual relations and detect the OOC object with a bounding box. In this work, we consider common contextual relations such as co-occurrence relations, the relative size of an object with respect to other objects, and the position of the object in the scene. We posit that contextual cues are useful to determine object labels for in-context objects and inconsistent context cues are detrimental to determining object labels for out-of-context objects. To realize this hypothesis, we propose a graph contextual reasoning network (GCRN) to detect OOC objects. GCRN consists of two separate graphs to predict object labels based on the contextual cues in the image: 1) a representation graph to learn object features based on the neighboring objects and 2) a context graph to explicitly capture contextual cues from the neighboring objects. GCRN explicitly captures the contextual cues to improve the detection of in-context objects and identify objects that violate contextual relations. In order to evaluate our approach, we create a large-scale dataset by adding OOC object instances to the COCO images. We also evaluate on recent OCD benchmark. Our results show that GCRN outperforms competitive baselines in detecting OOC objects and correctly detecting in-context objects. Code and data: https://nusci.csl.sri.com/project/trinity-ooc
Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to sequential disruption of mTORC1 and mTORC2 (2012)

Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), improves insulin sensitivity in acute studies in vitro and in vivo by disrupting a negative feedback loop mediated by S6 kinase. We find that rapamycin has a clear biphasic effect on insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the first hour that declines to almost complete insulin resistance by 24-48 h. We and others have recently observed that chronic rapamycin treatment induces insulin resistance in rodents, at least in part due to disruption of mTORC2, an mTOR-containing complex that is not acutely sensitive to the drug. Chronic rapamycin treatment may also impair insulin action via the inhibition of mTORC1-dependent mitochondrial biogenesis and activity, which could result in a buildup of lipid intermediates that are known to trigger insulin resistance. We confirmed that rapamycin inhibits expression of PGC-1α, a key mitochondrial transcription factor, and acutely reduces respiration rate in myotubes. However, rapamycin did not stimulate phosphorylation of PKCθ, a central mediator of lipid-induced insulin resistance. Instead, we found dramatic disruption of mTORC2, which coincided with the onset of insulin resistance. Selective inhibition of mTORC1 or mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor, respectively) confirmed that mitochondrial effects of rapamycin are mTORC1-dependent, whereas insulin resistance was recapitulated only by knockdown of mTORC2. Thus, mTORC2 disruption, rather than inhibition of mitochondria, causes insulin resistance in rapamycin-treated myotubes, and this system may serve as a useful model to understand the effects of rapamycin on mTOR signaling in vivo.
Synthesis and biochemical properties of a new photoactivatable cholesterol analog 7,7-azocholestanol and its linoleate ester in Chinese hamster ovary cell lines (2002)

We report the chemical synthesis of a new photoactivatable cholesterol analog 7,7-azocholestanol (AC) and its linoleate ester (ACL). We also examined the biochemical properties of the sterol and its ester by employing several different mutant Chinese hamster ovary (CHO) cell lines with defined abnormalities in cholesterol metabolism as tools. AC mimics cholesterol in supporting the growth of a mutant cell line (M19) that requires cholesterol for growth. In normal cells, tritiated ACL present in low-density lipoprotein (LDL) was hydrolyzed and reesterified in a manner similar to tritiated cholesteryl linoleate (CL) in LDL. Also, in the mutant cell line (AC29) lacking the enzyme acyl-coenzyme A:cholesterol acyltransferase or in the mutant cell line (CT60) defective in the Niemann-Pick type C1 protein, the hydrolysis of ACL in LDL was normal, but the reesterification of the liberated AC was defective. Therefore, the metabolism of ACL in LDL is very similar to that of CL in LDL. Tritium-labeled AC delivered to intact CHO cells as a cyclodextrin complex was shown to photoaffinity label several discrete polypeptides, including caveolin-1. These results demonstrate AC as an effective reagent for studying cholesterol-protein interactions involved in intracellular cholesterol trafficking.
In Vivo Tracking Techniques for Cellular Regeneration, Replacement, and Redirection (2012)

Cellular therapy can be defined as the transplantation of living cells for the treatment of medical conditions. Three main objectives of cellular therapy are regeneration of damaged tissue, replacement of function by secretion of biologically active molecules, and redirection of aberrant processes. Given the complex nature of these approaches, in vivo tracking of the transplanted cells is critical to evaluate their potential benefit and to optimize treatment strategies. Recent advances are reviewed that enable in vivo cell tracking as an important adjunct to implement cellular therapy in clinical practice.
A novel series of non‐quaternary oxadiazoles acting as full agonists at muscarinic receptors (1990)

1 A novel series of non-quaternary oxadiazole-based muscarinic agonists demonstrated high affinity for muscarinic receptors. 2. These agonists possessed high efficacy in the nanomolar range at muscarinic receptors in the superior cervical ganglion, atrium and ileum but did not show selectivity across the tissue preparations. 3. Two amino oxadiazoles, one from a quinuclidine series (L-660,863) and one from a 1-azanorbornane series (L-670,207) possessed a high ratio of potency for displacing the binding of [3H]-N-methyl-scopolamine ([3H]-NMS) to potency for displacing the agonist [3H]-oxotremorine-M cortex. 4. The two azanorbornane derivatives L-670,548 and L-670,207 stimulated the turnover of phosphatidylinositol in the cortex with a potency higher than that obtained with any other known muscarinic agonist (ED50 0.26 and 0.18 microM respectively). 5. The maximum response obtained with L-670,207 was greater than that observed for carbachol but was comparable to that of the natural ligand acetylcholine. 6. These oxadiazole muscarinic agonists are among the most potent and efficacious non-quaternary muscarinic agonists ever described.