gebhart/patrepeval huggingface dataset:
Detecting Substrates Bound to the Secondary Multidrug Efflux Pump EmrE by DNP-Enhanced Solid-State NMR (2013)

Escherichia coli EmrE, a homodimeric multidrug antiporter, has been suggested to offer a convenient paradigm for secondary transporters due to its small size. It contains four transmembrane helices and forms a functional dimer. We have probed the specific binding of substrates TPP(+) and MTP(+) to EmrE reconstituted into 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes by (31)P MAS NMR. Our NMR data show that both substrates occupy the same binding pocket but also indicate some degree of heterogeneity of the bound ligand population, reflecting the promiscuous nature of ligand binding by multidrug efflux pumps. Direct interaction between (13)C-labeled TPP(+) and key residues within the EmrE dimer has been probed by through-space (13)C-(13)C correlation spectroscopy. This was made possible by the use of solid-state NMR enhanced by dynamic nuclear polarization (DNP) through which a 19-fold signal enhancement was achieved. Our data provide clear evidence for the long assumed direct interaction between substrates such as TPP(+) and the essential residue E14 in transmembrane helix 1. Our work also demonstrates the power of DNP-enhanced solid-state NMR at low temperatures for the study for secondary transporters, which are highly challenging for conventional NMR detection.
Morphology-controlled synthesis of silver nanostructures via a seed catalysis process (2007)

A novel, effective strategy named 'seed catalysis' has been described here to synthesize silver nanostructures with controllable morphology. Typically, we added Na2S into the reaction system and the Ag2S semiconductor colloids formed at the initial stage would act as both seeds and catalyst in the silver reduction. The morphology of products is controlled by the concentration of Na2S added to the system. Low concentration of Na2S gives nanocubes of 40–50 nm in size, while a high concentration of Na2S is of benefit to obtain nanowires. The growth of the silver crystal is also accelerated by the catalysis of Ag2S. Electron microscopy and UV–vis absorption spectra have been used to investigate the evolution of silver nanowires, and a reasonable mechanism to explain the role of Ag2S seeds has also been suggested. This semiconductor seed catalysis strategy will provide wide applications in the fabrication of metal nanomaterials.
Measuring architectural vulnerability factors (2003)

The continuous exponential growth in transistors per chip as described by Moore's law has spurred tremendous progress in the functionality and performance of semiconductor devices, particularly microprocessors. At the same time, each succeeding technology generation has introduced new obstacles to maintaining this growth rate. Transient faults caused by single-event upsets have emerged as a key challenge likely to gain significantly more importance in the next few design generations. Techniques for dealing with these faults exist, but they come at a cost. Designers need accurate soft-error estimates early in the design cycle to weigh the benefits of error protection techniques against their costs. This article presents a method for generating these estimates.
RETRACTED: Combining PARP-1 Inhibition and Radiation in Ewing Sarcoma Results in Lethal DNA Damage (2013)

Ewing sarcomas (ES) harbor a chromosomal translocation that fuses the EWS gene to an ETS transcription factor, most commonly Friend leukemia integration 1 (FLI1). The EWS-FLI1 fusion protein acts in a positive feedback loop to maintain the expression of PARP-1, which is involved in repair of DNA damage. Here, we examine the effects of PARP-1 inhibition and radiation therapy on Ewing sarcomas. In proliferation assays, the Ewing sarcoma cell lines RD-ES and SK-N-MC were much more sensitive than non-Ewing sarcoma cell lines to the PARP-1 inhibitor olaparib (Ola; IC50 0.5-1 μmol/L vs. >5 μmol/L) and to radiation (IC50 2-4 Gy vs. >6 Gy). PARP-1 inhibition with short hairpin RNA (shRNA) or Ola sensitized Ewing sarcoma cells, but not non-Ewing sarcoma cells, to radiation therapy in both proliferation and colony formation assays. Using the Comet assay, radiation of Ewing sarcoma cells with Ola, compared to without Ola, resulted in more DNA damage at 1 hour (mean tail moment 36-54 vs. 26-28) and sustained DNA damage at 24 hours (24-29 vs. 6-8). This DNA damage led to a 2.9- to 4.0-fold increase in apoptosis and a 1.6- to 2.4-fold increase in cell death. The effect of PARP-1 inhibition and radiation therapy on Ewing sarcoma cells was lost when EWS-FLI1 was silenced by shRNA. A small dose of radiation therapy (4 Gy), when combined with PARP-1 inhibition, stopped the growth of SK-N-MC flank tumors xenografts. In conclusion, PARP-1 inhibition in Ewing sarcomas amplifies the level and duration of DNA damage caused by radiation therapy, leading to synergistic increases in apoptosis and cell death in a EWS-FLI1-dependent manner.
Abstract 2672: Phase 1 pharmacokinetics (PK) & pharmacodynamics (PD) of PEGylated hyaluronidase PH20 (PEGPH20) in patients with solid tumors (2012)

Abstract Enzymatic degradation of hyaluronan (HA), a key component of the extracellular matrix (ECM), can enhance tumor perfusion, improve delivery of chemotherapeutics, and enhance the effects of anti-tumor agents. Recombinant human hyaluronidase (rHuPH20), used clinically to facilitate local dispersion and absorption after subcutaneous delivery, is rapidly cleared from the blood after intravenous (IV) injection. To prolong serum residence time, a pegylated form of rHuPH20 was manufactured and shown to have anti-tumor activities in preclinical models (Thompson et al., Mol Cancer Ther 2010). PEGPH20 is a novel agent in early clinical trials to evaluate the safety and biological activities of hyaluronidase-based therapy. Twenty-three patients enrolled in two Phase 1 trials received IV PEGPH20 (0.5 - 50 μg/kg). To assess PEGPH20 PK, serial blood samples were drawn from patients, and plasma concentrations were measured using an in vitro hyaluronidase activity assay (LLOQ 0.3 U/mL). Plasma levels of HA catabolites were measured using a quantitative HPLC method to characterize PD. After a single 50 μg/kg dose, the PEGPH20 PK profile was well described by a two-compartment open model with a low initial distribution volume (V1 ∼ 60 mL/kg) and a terminal half-life of ∼2 days. Observed Cmax and AUC0-8hr values increased with increasing dose, suggesting linearity within the dose range. Model simulations derived from single-dose PK parameters were predictive of plasma concentrations from patients who received twice weekly dosing. There was no evidence for accumulation of PEGPH20 in the plasma after multiple dosing. Systemic concentrations of HA catabolites were measured to assess the PEGPH20 PD. HA levels detected 24 hours post administration increased with increasing dose of PEGPH20. Observed Cmax and AUC0-168hr values were also dose-dependent. After a 50 μg/kg bolus, HA concentrations increased 100-fold above baseline and persisted for &gt;2 weeks. Repeat dosing with PEGPH20 resulted in sustained plasma concentrations of HA catabolites. Inter-patient variability in PD was notably greater than inter-patient variability in PK. Initial clinical PK/PD analysis indicates that systemic exposure after IV PEGPH20 is proportional to dose and is well described by a two-compartment PK model. Dose-dependent increases in HA catabolites provided a quantitative measure of PEGPH20 PD, consistent with the enzymatic activity of hyaluronidase. These data support continued evaluation of PEGPH20 to enhance delivery of anti-tumor agents via modification of the ECM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2672. doi:1538-7445.AM2012-2672
Product Ion Nodes in MS/MS (1994)

Abstract The transmission of ions through an RF-only quadrupole collision cell is affected by both the frequency and voltage applied to the quadrupole. With a change in the RF-only quadrupole collision cell voltage (viz, the collision energy) ion intensities for both parent and product ions determined by a final mass-analyzing quadrupole vary in a modulated fashion. This pattern of ion intensities has been described as quadrupole “nodes”. Ion transmission through the RF-only quadrupole has been carefully investigated here using energy-resolved mass spectrometry with variations in the collision cell pressure and the mass of the ions. A theory is developed to explain the presence of product ion nodes that focuses on ion velocity as the critical parameter in their production.
Method for Combined FDG-PET and Radiographic Imaging of Primary Breast Cancers (2003)

The purpose of the study was to demonstrate the feasibility of a hybrid functional/anatomic breast imaging platform with biopsy capability for facilitating lesion detection and diagnosis. This platform consists of an investigative dedicated positron emission mammography (PEM) device mounted on a stereotactic X-ray mammography system, permitting sequential acquisition of mammographic and emission images during a single breast compression. There is automatic coregistration of images from both modalities, and these results can be successfully correlated with histopathologic findings. The potential utility of functional images correlated to anatomic images would include noninvasively detecting clinically and radiographically occult cancers, assessing response to therapy, discriminating between benign and malignant breast masses, and ultimately reducing the number of invasive and costly surgical interventions. A spot-digital mammogram and subsequent PEM image, collected over a 4-minute period, were obtained in a single patient with the breast in compression after intravenous injection of (F-18)-2-deoxy-2-fluoro-D-glucose (FDG) at the time of stereotactic biopsy. The authors conclude that FDG-based lesion localization information may be combined with the lesion X-ray attenuation characteristics using this common imaging platform.
Molecular Characterization of New Selective Peroxisome Proliferator–Activated Receptor γ Modulators With Angiotensin Receptor Blocking Activity (2005)

Selective peroxisome proliferator-activated receptor (PPAR) gamma modulation is a new pharmacological approach that, based on selective receptor-cofactor interactions and target gene regulation, should result in potent insulin sensitization in the absence of PPARgamma-mediated adverse effects. Here, we characterize two angiotensin receptor blockers (ARBs), telmisartan and irbesartan, as new selective PPAR modulators (SPPARMs). Analysis of PPARgamma protein conformation using protease protection showed that telmisartan directly interacts with the receptor, producing a distinct conformational change compared with a glitazone. Glutathione S-transferase pull-down and fluorescence resonance energy transfer assays revealed selective cofactor binding by the ARBs compared with glitazones with an attenuated release of the nuclear receptor corepressor and absence of transcriptional intermediary factor 2 recruitment by ARBs. Consistently, selective cofactor binding resulted in differential gene expression profiles in adipocytes (ARB versus glitazone treated) assessed by oligo microarray analysis. Finally, telmisartan improved insulin sensitivity in diet-induced obese mice in the absence of weight gain. The present study identifies two ARBs as new SPPARMs. SPPARM activity by ARBs could retain the metabolic efficacy of PPARgamma activation with reduction in adverse effects exerting in parallel AT1 receptor blockade. This may provide a new therapeutic option for better cardiovascular risk management in metabolic diseases and may initiate the development of new classes of drugs combining potent antihypertensive and antidiabetic actions.
Performance estimation in drilling using artificial neural networks (2000)

Drilling is often carried out as one of the last steps in the manufacturing production of a part and demands process reliability. The work piece would have undergone extensive machining before and thus the final drilling demands considerable attention. It is apparent that any optimisation made to the drilling process will make manufacturing more productive and improve quality. The estimation of the process outcomes is necessary for reliable optimisation techniques. Traditional methods of performance estimation develop mathematical models and relationships, for individual performance estimation, for a set of process parameters. With advances in on-line control of machine tools there is a need to predict more than one performance feature. Artificial intelligence offers an alternative method for performance estimation and one that can perform simultaneous estimation of more then one performance feature. This project aims to use artificial intelligence, more specifically artificial neural networks (ANN), for the simultaneous prediction of the performance measures of thrust and torque in the conventional drilling process. An initial investigation into the relationship between hole oversize and the vibrations in two planes will also be undertaken. This work is seen as not only a step towards establishing intelligent tools for machining performance estimation, while addressing the mathematical and scientific basis of machining science, but also as a step towards the use of artificial intelligence for on-line control of the conventional drilling process.
Monkey kidney cell growth optimization and poliovirus propagation in microcarrier culture. (1981)

Three monkey kidney cells lines Vero, LLC-MK2 and CV-1 were grown in microcarrier cultures. The carrier support was DEAE-Sephadex gel beads at low anion exchange capacity prepared according to a protocol developed at the Massachusetts Institute of Technology. The growth rate of the cells and the final cell density in microcarrier culture was dependent on the concentration of the beads in culture and on the size of the initial cell inoculum. The efficiency of the microcarrier culture system was compared to that of stationary and roller bottle cultures. The microcarrier culture system was applied to the propagation of polioviruses in the three established monkey kidney cell lines and the yields were compared with those obtained in roller bottle and stationary cultures. The yield of the three types of polioviruses in the various cell lines and culture systems was similar. The use of the microcarrier culture system for anchorage-dependent cells together with the use of continuously propagating cell lines offer great advantage for large-scale cultivation of poliovirus for the preparation of killed poliovirus vaccines.
The tomato <i>Rme1</i> locus is required for <i>Mi‐1</i>‐mediated resistance to root‐knot nematodes and the potato aphid (2001)

The tomato Mi-1 gene confers resistance against root-knot nematodes (Meloidogyne spp.) and a biotype of the potato aphid (Macrosiphum euphorbiae). Four mutagenized Mi-1/Mi-1 tomato populations were generated and screened for altered root-knot nematode resistance. Four independent mutants belonging to two phenotypic classes were isolated. One mutant was chosen for further analyzes; rme1 (for resistance to Meloidogyne) exhibited levels of infection comparable with those found on susceptible controls. Molecular and genetic data confirmed that rme1 has a single recessive mutation in a locus different from Mi-1. Cross-sections through galls formed by feeding nematodes on rme1 roots were identical to sections from galls of susceptible tomato roots. In addition to nematode susceptibility, infestation of rme1 plants with the potato aphid showed that this mutation also abolished aphid resistance. To determine whether Rme1 functions in a general disease-resistance pathway, the response against Fusarium oxysporum f.sp. lycopersici race 2, mediated by the I-2 resistance gene, was studied. Both rme1 and the wild type plants were equally resistant to the fungal pathogen. These results indicate that Rme1 does not play a general role in disease resistance but may be specific for Mi-1-mediated resistance.
Salivary collagenase. Origin, characteristics and relationship to periodontal health (1990)

Saliva collected from subjects with healthy and with diseased periodontium was assayed for collagenase activity by incubation at 25 degrees C with soluble type I, II or III collagen. The degradation products were analyzed by separation in SDS-polyacrylamide gel electrophoresis followed either by protein staining or by exposure of the dried gel to X-ray film in the case of radioactively labeled type I collagen. Collagenase of vertebrate type was detected in the whole saliva of all subjects but not in parotid, sublingual or submandibular fluids. Most of the collagenase was in the soluble fraction of saliva that also contained factors which both activated and inhibited the enzyme. The salivary collagenase resembled the collagenase of human PMNs and gingival sulcular fluid in its molecular size of 70,000 daltons, in its activation by gold thioglucose and in its tendency to degrade types I and II collagens over type III collagen. Before periodontal treatment, the saliva of periodontitis patients had significantly higher collagenase than after treatment. In periodontitis, collagenase existed mainly in the active form, while in the healthy mouths most of the enzyme was latent but could be activated by sulfhydryl reagents or proteolytically with trypsin, and chymotrypsin but not by human plasma kallikrein or plasmin. In some of the samples from untreated periodontitis patients bacterial collagenase may have been present in small quantities. Most of the collagenase in the saliva from all subjects appeared to originate from PMNs entering the oral cavity through the gingival sulcus.
Magnetite Colloidal Nanocrystals: A Facile Pathway To Prepare Mesoporous Hematite Thin Films for Photoelectrochemical Water Splitting (2011)

In this study, we demonstrate an alternative and promising way to produce hematite photoanodes with high performance and without the addition of doping or catalytic coating. In this approach, we processed hematite thin films using a colloidal dispersion of magnetite nanocrystals as the precursor. The photoelectrochemical characterization shows that the colloidal approach used to process an undoped hematite photoanode produced a high-performance electrode for water photooxidation with an onset potential as low as 0.8 V(RHE). This value is comparable to the best results reported in the literature for a hematite photoanode modified with catalytic materials. We demonstrate that pure hematite thin films reach 1.1 mA·cm(-2) at 1.23 V(RHE) with back-side illumination.
Creating an Artificial Two-Dimensional Skyrmion Crystal by Nanopatterning (2013)

A Skyrmion crystal typically arises from helical spin structures induced by the Dzyaloshinskii-Moriya interaction. Experimentally its physical exploration has been impeded because it is a rarity and is found only within a narrow temperature and magnetic field range. We present a method for the assembly of a two-dimensional Skyrmion crystal based upon a combination of a perpendicularly magnetized film and nanopatterned arrays of magnetic vortices that are geometrically confined within nanodisks. The practical feasibility of the method is validated by micromagnetic simulations and computed Skyrmion number per unit cell. We also quantify a wide range in temperature and field strength over which the Skyrmion crystal can be stabilized without the need for any intrinsic Dzyaloshinskii-Moriya interactions, which otherwise is needed to underpin the arrangement as is the case in the very few known Skyrmion crystal cases. Thus, our suggested scheme involves a qualitative breakthrough that comes with a substantial quantitative advance.
Hydrothermal Syntheses and Single-Crystal Structures of Some Novel Guanidinium−Zinc−Phosphates (1997)

The mild-condition hydrothermal syntheses and single-crystal structures of three new guanidinium zinc phosphates are reported. CN3H6·Zn2(HPO4)2H2PO4 and (CN3H6)2·Zn(HPO4)2 are built up from three-dimensional Zn/P/O frameworks encapsulating guanidinium cations in 12-ring channel systems. The latter material has the lowest nodal-framework-atom density per unit volume of any open-framework phase characterized so far. (CN3H6)6·Zn2(OH)(PO4)3·H2O is a one-dimensional phase with respect to Zn/P/O connectivity and has a unique triply bridged tetrahedral chain connectivity for simple phosphates. Crystal data: CN3H6·Zn2(HPO4)2H2PO4, Mr = 478.78, monoclinic, space group P21 (No. 4), a = 5.1318(4) Å, b = 7.8411(7) Å, c = 16.510(1) Å, β = 90.110(7)°, V = 664.36(8) Å3, Z = 2, R = 2.43%, Rw = 2.67% [2608 observed reflections with I > 3σ(I)]. (CN3H6)2·Zn(HPO4)2, Mr = 377.50, orthorhombic, space group Pna21 (No. 33), a = 10.447(2) Å, b = 12.349(2) Å, c = 10.225(2) Å, V = 1319.2(5) Å3, Z = 4, R = 3.26%, Rw = 3.32% [2252 observed reflections with I > 3σ(I)]. (CN3H6)6·Zn2(OH)(PO4)3·H2O, Mr = 811.17, trigonal, space group R3̄ (No. 148), a = 20.016(7) Å, c = 13.955(6) Å, V = 4842(4) Å3, Z = 6, R = 5.31%, Rw = 5.52% [630 observed reflections with I > 3σ(I)].
CE (2015)

As new research has increased our understanding of epilepsy and the challenges patients with epilepsy face, the role of the nurse as an educator and advocate has grown. This article, the second in a two-part series, addresses the most important aspects of assessing and caring for patients with epilepsy-highlighting the seizure first-aid instructions that all family members of a patient with epilepsy should have; the teaching points to share with parents of young children with epilepsy; and online epilepsy resources for patients, family members, and health care professionals. The authors also discuss current medical, surgical, neurostimulatory, and dietary approaches to epilepsy treatment.
HWT - hybrid watershed transform: optimal combination of hierarchical interactive and automated image segmentation (2007)

In quantitative medical imaging and therapy planning, the optimal combination of automated and interactively defined information is crucial for image segmentation methods to be both efficient and effective. We propose to combine an efficient hierarchical region merging scheme that collects per-region statistics across hierarchy levels with a trainable classification engine that facilitates automated region labeling based on an arbitrary number of reference segmentations. When applying the classification engine, we propose to use a corridor of non-classified regions resulting in a sparse labeling with extremely low false-classification rate, and to attribute labels to the remaining basins through successive merging with ready-labeled basins. The proposed hierarchical region merging scheme also permits to efficiently include interactively defined labels. We denominate this general approach as Hybrid Hierarchical Interactive Image Segmentation Scheme (HIS<sup>2</sup>). More specifically, we present an extension of the Interactive Watershed Transform, which we combine with a trainable two-class Support Vector Machine based on Gaussian radial basis functions. Finally, we present a novel asymmetric marker scheme, which provides a powerful means of regionally correcting remaining inaccuracies while preserving full detail of the automatic labeling procedure. We denominate the complete algorithm as Hybrid Watershed Transform (HWT), which we apply to one challenging segmentation problem in clinical imaging, namely efficient bone removal in large computed tomography angiographic data sets. Efficiency and accuracy of the proposed methodology is evaluated on multi-slice images from nine different sites. As a result, its ability to rapidly and automatically generate robust and precise segmentation results in combination with a versatile manual correction mechanism could be proven without requiring specific anatomical or geometrical models.