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At least 829 records · Page 46
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Industrial pollution and cancer in Spain: An important public health issue

Cancer can be caused by exposure to air pollution released by industrial facilities. The European Pollutant Release and Transfer Register (E-PRTR) has made it possible to study exposure to industrial pollution. This study seeks to describe the industrial emissions in the vicinity of Spanish towns and their temporal changes, and review our experience studying industrial pollution and cancer. Data on industrial pollutant sources (2007–2010) were obtained from the E-PRTR registries. Population exposure was estimated by the distance from towns to industrial facilities. We calculated the amount of carcinogens emitted into the air in the proximity (<5 km) of towns and show them in municipal maps. We summarized the most relevant results and conclusions reported by ecological E-PRTR-based on studies of cancer mortality and industrial pollution in Spain and the limitations and result interpretations of these types of studies. There are high amounts of carcinogen emissions in the proximity of towns in the southwest, east and north of the country and the total amount of emitted carcinogens is considerable (e.g. 20 Mt of arsenic, 63 Mt of chromium and 9 Mt of cadmium). Although the emissions of some carcinogens in the proximity of certain towns were reduced during the study period, emissions of benzene, dioxins+furans and polychlorinated biphenyls rose. Moreover, the average population of towns lying within a 5 km radius from emission sources of carcinogens included in the International Agency for Research on Cancer list of carcinogens was 9 million persons. On the other hand, the results of the reviewed studies suggest that those Spanish regions exposed to the pollution released by certain types of industrial facilities have around 17% cancer excess mortality when compared with those unexposed. Moreover, excess mortality is focused on digestive and respiratory tract cancers, leukemias, prostate, breast and ovarian cancers. Despite their limitations, ecological studies are a useful tool in environmental epidemiology, not only for proposing etiological hypotheses about the risk of living close to industrial pollutant sources, but also for providing data to account for situations of higher mortality in specific areas. Nevertheless, the reduction of emissions should be a goal, with special relevance given to establishing limits for known carcinogens and other toxic substances in the environs of population centers, as well as industry-specific emission limits. - Highlights: • The amount of carcinogens emitted into air in proximity to population is considerable. • Some towns near industrial pollutant sources have a cancer mortality excess. • Cancer problems in exposed people are centered on digestive and respiratory systems. • Reduction of emissions should be a goal, specially with recognized carcinogens.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2011

Regional Nodal Involvement and Patterns of Spread Along In-Transit Pathways in Children With Rhabdomyosarcoma of the Extremity: A Report From the Children's Oncology Group;Rhabdomyosarcoma; Regional failure; In-transit nodes; Radiotherapy; Extremity

Purpose: To evaluate the incidence and prognostic factors for regional failure, with attention to the in-transit pathways of spread, in children with nonmetastatic rhabdomyosarcoma of the extremity. Methods and Materials: The Intergroup rhabdomyosarcoma studies III, IV-Pilot, and IV enrolled 226 children with rhabdomyosarcoma of the extremity. Failure at the in-transit (epitrochlear/brachial and popliteal) and proximal (axillary/infraclavicular and inguinal/femoral) lymph nodes was evaluated. The median follow-up for the surviving patients was 10.4 years. Results: Of the 226 children, 55 (24%) had clinical or pathologic evidence of either in-transit and/or proximal lymph node involvement at diagnosis. The actuarial 5-year risk of regional failure was 12%. The prognostic factors for poor regional control were female gender and lymph node involvement at diagnosis. In the 116 patients with a distal extremity primary tumor, 5% had in-transit lymph node involvement at diagnosis. The estimated 5-year incidences of in-transit and proximal nodal failure was 12% and 8%, respectively. The in-transit failure rate was 0% for patients who underwent radiotherapy and/or underwent lymph node sampling of the in-transit nodal site but was 15% for those who did not (p = .07). However, the 5-year event-free survival rate did not differ between these two groups (64% vs. 55%, respectively, p = .47). Conclusion: The high incidence of regional involvement necessitates aggressive identification and treatment of regional lymph nodes in patients with rhabdomyosarcoma of the extremity. In patients with distal extremity tumors, in-transit failures were as common as failures in more proximal regional sites. Patients who underwent complete lymph node staging with appropriate radiotherapy to the in-transit nodal site, if indicated, were at a slightly lower risk of in-transit failure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Detection of Esophageal Fiducial Marker Displacement During Radiation Therapy With a 2-dimensional On-board Imager: Analysis of Internal Margin for Esophageal Cancer

Purpose: To quantify the interfraction displacement of esophageal fiducial markers for primary esophageal cancer radiation therapy. Methods and Materials: Orthogonal 2-dimensional (2D) matching records fused to vertebrae were analyzed in clinically staged T1/2N0 esophageal cancer patients undergoing endoscopic clipping as fiducial metal markers. Displacement of the markers between the digitally reconstructed radiographs and on-board kilovoltage images during radiation therapy was analyzed according to direction and esophageal site. Results: Forty-four patients, with 81 markers (10 proximal, 42 middle, and 29 distal), underwent 367 2D matching sessions during radiation therapy. The mean (SD) absolute marker displacement was 0.26 (0.30) cm in the right–left (RL), 0.50 (0.39) cm in the superior–inferior (SI), and 0.24 (0.21) cm in the anterior–posterior (AP) direction. Displacement was significantly larger in the SI than in the RL and AP directions (P<.0001). In the SI direction, mean absolute displacements of the distal, middle, and proximal esophagus were 0.67 (0.45) cm, 0.42 (0.32) cm, and 0.36 (0.30) cm, respectively. Distal esophagus displacement was significantly larger than those of the middle and proximal esophagus (P<.0001). The estimated internal margin to cover 95% of the cases was 0.75 cm in the RL and AP directions. In the SI direction, the margin was 1.25 cm for the proximal and middle esophagus and 1.75 cm for the distal esophagus. Conclusions: The magnitude of interfraction displacement of esophageal clips was larger in the SI direction, particularly in the distal esophagus, but substantial displacement was observed in other directions and at other esophageal sites. It is practical to take estimated movements into account with internal margins, even if vertebrae-based 2D matching is performed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Minibeam Therapy With Protons and Light Ions: Physical Feasibility and Potential to Reduce Radiation Side Effects and to Facilitate Hypofractionation

Purpose: Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues. As these minibeams penetrate the tissues, they gradually broaden and merge with each other to produce a solid beam. Methods and Materials: Broadening of 0.3-mm-diameter, 109-MeV proton pencil minibeams was measured using a stack of radiochromic films with plastic spacers. Monte Carlo simulations were used to evaluate the broadening in water of minibeams of protons and several light ions and the dose from neutron generated by collimator. Results: A central parameter was tissue depth, where the beam full width at half maximum (FWHM) reached 0.7 mm, beyond which tissue sparing decreases. This depth was 22 mm for 109-MeV protons in a film stack. It was also found by simulations in water to be 23.5 mm for 109 MeV proton pencil minibeams and 26 mm for 116 MeV proton planar minibeams. For light ions, all with 10 cm range in water, that depth increased with particle size; specifically it was 51 mm for Li-7 ions. The ∼2.7% photon equivalent neutron skin dose from the collimator was reduced 7-fold by introducing a gap between the collimator and the skin. Conclusions: Proton minibeams can be implemented at existing particle therapy centers. Because they spare the shallow tissues, they could augment the efficacy of proton therapy and light particle therapy, particularly in treating tumors that benefit from sparing of proximal tissues such as pediatric brain tumors. They should also allow hypofractionated treatment of all tumors by allowing the use of higher incident doses with less concern about proximal tissue damage.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Testosterone complex and non-steroidal ligands of human aromatase

Cytochrome P450 aromatase (AROM) catalyzes the biosynthesis of estrogen from androgen. Previously crystal structures of human AROM in complex with the substrate androstenedione, and inhibitors exemestane, as well as the newly designed steroidal compounds, have been reported. Here, in this paper, we report the first crystal structure of testosterone complex of human placental AROM. Testosterone binds at the androgen-specific heme distal pocket. The polar and hydrophobic interactions with the surrounding residues resemble the interactions observed for other ligands. The heme proximal region comprises the intermolecular interface in AROM, and also the putative interaction surface of its redox partner cytochrome P450 reductase. Unreported previously, the proximal region is characterized by a large surface cavity, unlike most known P450’s. Using five best X-ray data sets from androstenedione and testosterone complexes of AROM, we now unequivocally show the presence of an unexplained ligand electron density inside the proximal cavity. The density is interpreted as ordered five ethylene glycol units of polyethylene glycols used as a solvent for steroids and also in crystallization. Interestingly, polyethylene glycol exhibits weak inhibition of AROM enzyme activity in a time dependent manner. Besides its critical role in the redox partner coupling and electron transfer process, the proximal cavity possibly serves as the interaction site for other molecules that may have regulatory effects on AROM activity. In addition, the new data also reveal a previously unidentified water channel linking the active site to the lipid interface. The channel could be the predicted passage for water molecules involved in catalysis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Proximitized materials

Advances in scaling down heterostructures and having an improved interface quality together with atomically thin two-dimensional materials suggest a novel approach to systematically design materials. A given material can be transformed through proximity effects whereby it acquires properties of its neighbors, for example, becoming superconducting, magnetic, topologically nontrivial, or with an enhanced spin–orbit coupling. Such proximity effects not only complement the conventional methods of designing materials by doping or functionalization but also can overcome their various limitations. In proximitized materials, it is possible to realize properties that are not present in any constituent region of the considered heterostructure. While the focus is on magnetic and spin–orbit proximity effects with their applications in spintronics, the outlined principles also provide a broader framework for employing other proximity effects to tailor materials and realize novel phenomena.

36 MATERIALS SCIENCE↗
DOE OSTI2014

Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Ultralow Thermal Conductivity in Diamond-Like Semiconductors: Selective Scattering of Phonons from Antisite Defects

In this work, we discover anomalously low lattice thermal conductivity (<0.25 W/mK at 300 degrees C) in the Hg-containing quaternary diamond-like semiconductors within the Cu2IIBIVTe4 (IIB: Zn, Cd, Hg) (IV: Si, Ge, Sn) set of compositions. Using high-temperature X-ray diffraction, resonant ultrasound spectroscopy, and transport properties, we uncover the critical role of the antisite defects HgCu and CuHg on phonon transport within the Hg-containing systems. Despite the differences in chemistry between Hg and Cu, the high concentration of these antisite defects emerges from the energetic proximity of the kesterite and stannite cation motifs. Our phonon calculations reveal that heavier group IIB elements not only introduce low-lying optical modes, but the subsequent antisite defects also possess unusually strong point defect phonon scattering power. The scattering strength stems from the fundamentally different vibrational modes supported by the constituent elements (e.g., Hg and Cu). Despite the significant impact on the thermal properties, antisite defects do not negatively impact the mobility (>50 cm2/(Vs) at 300 degrees C) in Hg-containing systems, leading to predicted zT > 1.5 in Cu2HgGeTe4 and Cu2HgSnTe4 under optimized doping. In addition to introducing a potentially new p-type thermoelectric material, this work provides (1) a strategy to use the proximity of phase transitions to increase point defect phonon scattering, and (2) a means to quantify the power of a given point defect through inexpensive phonon calculations.

14 SOLAR ENERGY↗
DOE OSTI2021

Spatial organization of FcγR and TLR2/1 on phagosome membranes differentially regulates their synergistic and inhibitory receptor crosstalk

Abstract Many innate immune receptors function collaboratively to detect and elicit immune responses to pathogens, but the physical mechanisms that govern the interaction and signaling crosstalk between the receptors are unclear. In this study, we report that the signaling crosstalk between Fc gamma receptor (FcγR) and Toll-like receptor (TLR)2/1 can be overall synergistic or inhibitory depending on the spatial proximity between the receptor pair on phagosome membranes. Using a geometric manipulation strategy, we physically altered the spatial distribution of FcγR and TLR2 on single phagosomes. We demonstrate that the signaling synergy between FcγR and TLR2/1 depends on the proximity of the receptors and decreases as spatial separation between them increases. However, the inhibitory effect from FcγRIIb on TLR2-dependent signaling is always present and independent of receptor proximity. The overall cell responses are an integration from these two mechanisms. This study presents quantitative evidence that the nanoscale proximity between FcγR and TLR2 functions as a key regulatory mechanism in their signaling crosstalk.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Mass spectrometric imaging as a high-spatial resolution tool for functional genomics: Tissue-specific gene expression of TT7 inferred from heterogeneous distribution of metabolites in Arabidopsis flowers

Laser desorption/ionization (LDI) mass spectrometry imaging (MSI) was used to acquire chemical images of flavonoid metabolites on the surface of wild-type and mutant (tt7) Arabidopsis thaliana flowers. Flavonoids were localized to the petals and carpels of flowers, with tissue heterogeneity in the petals. Specifically, kaempferol and/or its glycosides were abundant in the distal region of petals and quercetin and its downstream flavonoids were highly enriched in the more proximal region of petals. As a result of a mutation in the TT7 gene which blocks the conversion of dihydrokaempferol to dihydroquercetin, the downstream metabolites, quercetin, isohamnetin, and their glycosides, were not observed in the mutant flowers. Instead, the metabolites in an alternative pathway, kaempferol and/or its glycosides, were as highly abundant on the proximal region of the petals as in the distal region. In addition, the combined flavonoid amounts on the proximal region of petals in the wild-type are almost equivalent to the amounts of kaempferol and/or its glycosides in the mutant. This strongly suggests that the expression of the TT7 gene is localized on the proximal part of the petal while the other genes in the upper stream pathway are evenly expressed throughout the petal. Most importantly, this work demonstrates MSI of metabolites can be utilized for the localization of gene expression.

47 OTHER INSTRUMENTATION↗
DOE OSTI2015

Proton-detected 3D {sup 1}H/{sup 13}C/{sup 1}H correlation experiment for structural analysis in rigid solids under ultrafast-MAS above 60 kHz

A proton-detected 3D {sup 1}H/{sup 13}C/{sup 1}H chemical shift correlation experiment is proposed for the assignment of chemical shift resonances, identification of {sup 13}C-{sup 1}H connectivities, and proximities of {sup 13}C-{sup 1}H and {sup 1}H-{sup 1}H nuclei under ultrafast magic-angle-spinning (ultrafast-MAS) conditions. Ultrafast-MAS is used to suppress all anisotropic interactions including {sup 1}H-{sup 1}H dipolar couplings, while the finite-pulse radio frequency driven dipolar recoupling (fp-RFDR) pulse sequence is used to recouple dipolar couplings among protons and the insensitive nuclei enhanced by polarization transfer technique is used to transfer magnetization between heteronuclear spins. The 3D experiment eliminates signals from non-carbon-bonded protons and non-proton-bonded carbons to enhance spectral resolution. The 2D (F1/F3) {sup 1}H/{sup 1}H and 2D {sup 13}C/{sup 1}H (F2/F3) chemical shift correlation spectra extracted from the 3D spectrum enable the identification of {sup 1}H-{sup 1}H proximity and {sup 13}C-{sup 1}H connectivity. In addition, the 2D (F1/F2) {sup 1}H/{sup 13}C chemical shift correlation spectrum, incorporated with proton magnetization exchange via the fp-RFDR recoupling of {sup 1}H-{sup 1}H dipolar couplings, enables the measurement of proximities between {sup 13}C and even the remote non-carbon-bonded protons. The 3D experiment also gives three-spin proximities of {sup 1}H-{sup 1}H-{sup 13}C chains. Experimental results obtained from powder samples of L-alanine and L-histidine ⋅ H{sub 2}O ⋅ HCl demonstrate the efficiency of the 3D experiment.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

New Hybrid Model for Evaluating the Frequency-Dependent Leakage Inductance of a Variable Inductance Transformer (VIT)

Skin and proximity effects can cause a significant drop in the effective leakage inductance of a transformer when the operating frequency is increased. Although the magnetic image method-based double-2-D model can calculate the lowfrequency leakage inductance with sufficient accuracy, it is inherently a frequency-independent model. While Dowell’s 1-D model uses frequency-dependent relations to account for both skin and proximity effects, its accuracy is severely affected by the assumed winding geometry. In this paper, a hybrid model is proposed that uses superposition to combine a modified Dowell’s model with the double-2-D model. The proposed model is investigated on a variable inductance transformer (VIT)—a partially-filled transformer whose leakage inductance can be varied by moving one of the windings mechanically. The frequency-dependent leakage inductances of the VIT evaluated using the hybrid model are in excellent agreement with the corresponding finite element method (FEM) simulated and experimentally measured values, thereby validating the proposed hybrid model.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2014

TH-C-19A-11: Toward An Optimized Multi-Point Scintillation Detector

Purpose: The purpose of this work is to characterize a 2-points mPSDs' optical chain using a spectral analysis to help selecting the optimal components for the detector. Methods: Twenty different 2-points mPSD combinations were built using 4 plastic scintillators (BCF10, BCF12, BCF60, BC430; St-Gobain) and quantum dots (QDs). The scintillator is said to be proximal when near the photodetector, and distal otherwise. A 15m optical fiber (ESKA GH-4001) was coupled to the scintillating component and connected to a spectrometer (Shamrock, Andor and QEPro, OceanOptics). These scintillation components were irradiated at 125kVp; a spectrum for each scintillator was obtained by irradiation of individual scintillator and shielding the second component, thus talking into account light propagation in all components and interfaces. The combined total spectrum was also acquired and involved simultaneous irradiation of the two scintillators for each possible combination. The shape and intensity were characterized. Results: QDs in proximal position absorb almost all the light signal from distal plastic scintillators and emit in its own emission wavelength, with 100% of the signal in the QD range (625–700nm) for the combination BCF12/QD. However, discrimination is possible when QD is in distal position in combination with blue scintillators, total signal being 73% in the blue range (400-550nm) and 27% in QD range. Similar results are obtained with the orange scintillator (BC430). For optimal signal intensity, BCF12 should always be in proximal position, e.g. having 50% more intensity when coupled with BCF60 in distal position (BCF12/BCF60) compared to the BCF60/BCF12 combination. Conclusion: Different combinations of plastic scintillators and QD were built and their emission spectra were studied. We established a preferential order for the scintillating components in the context of an optimized 2-points mPSD. In short, the components with higher wavelength emission spectrum should be distal and lower wavelength in the proximal position.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2019

Observation of a Majorana zero mode in a topologically protected edge channel

Superconducting proximity pairing in helical edge modes, such as those of topological insulators, is predicted to provide a unique platform for realizing Majorana zero modes (MZMs). We used scanning tunneling microscopy measurements to probe the influence of proximity-induced superconductivity and magnetism on the helical hinge states of bismuth(111) films grown on a superconducting niobium substrate and decorated with magnetic iron clusters. Consistent with model calculations, our measurements revealed the emergence of a localized MZM at the interface between the superconducting helical edge channel and the iron clusters, with a strong magnetization component along the edge. Our experiments also resolve the MZM’s spin signature, which distinguishes it from trivial in-gap states that may accidentally occur at zero energy in a superconductor.

Science & Technology - Other Topics↗
DOE OSTI2021

Biomechanical Comparison of Anatomic Restoration of the Ulnar Footprint vs Traditional Ulnar Tunnels in Ulnar Collateral Ligament Reconstruction

Background: Current techniques for ulnar collateral ligament (UCL) reconstruction do not reproduce the anatomic ulnar footprint of the UCL. The purpose of this study was to describe a novel UCL reconstruction technique that utilizes proximal-to-distal ulnar bone tunnels to better re-create the anatomy of the UCL and to compare the biomechanical profile at time zero among this technique, the native UCL, and the traditional docking technique. Hypothesis: The biomechanical profile of the anatomic technique is similar to the native UCL and traditional docking technique. Study Design: Controlled laboratory study. Methods: Ten matched cadaveric elbows were potted with the forearm in neutral rotation. The palmaris longus tendon graft was harvested, and bones were sectioned 14 cm proximal and distal to the elbow joint. Specimen testing included (1) native UCL testing performed at 90° of flexion with 0.5 N·m of valgus moment preload, (2) cyclic loading from 0.5 to 5 N·m of valgus moment for 1000 cycles at 1 Hz, and (3) load to failure at 0.2 mm/s. Elbows then underwent UCL reconstruction with 1 elbow of each pair receiving the classic docking technique using either anatomic (proximal to distal) or traditional (anterior to posterior) tunnel locations. Specimen testing was then repeated as described. Results: There were no differences in maximum load at failure between the anatomic and traditional tunnel location techniques (mean ± SD, 34.90 ± 10.65 vs 37.28 ± 14.26 N·m; P = .644) or when including the native UCL (45.83 ± 17.03 N·m; P = .099). Additionally, there were no differences in valgus angle after 1000 cycles across the anatomic technique (4.58°± 1.47°), traditional technique (4.08°± 1.28°), and native UCL (4.07°± 1.99°). The anatomic group and the native UCL had similar valgus angles at failure (24.13°± 5.86° vs 20.13°± 5.70°; P = .083), while the traditional group had a higher valgus angle at failure when compared with the native UCL (24.88°± 6.18° vs 19.44°± 5.86°; P = .015). Conclusion: In this cadaveric model, UCL reconstruction with the docking technique utilizing proximal-to-distal ulnar tunnels better restored the ulnar footprint while providing valgus stability comparable with reconstruction with the docking technique using traditional anterior-to-posterior ulnar tunnel locations. These results suggest that utilization of the anatomic tunnel location in UCL reconstruction has similar biomechanical properties to the traditional method at the time of initial fixation (ie, not accounting for healing after reconstruction in vivo) while keeping the ulnar tunnels farther from the ulnar nerve. Further studies are warranted to determine if an anatomically based UCL reconstruction results in differing outcomes than traditional reconstruction techniques. Clinical Relevance: Current UCL reconstruction techniques do not accurately re-create the ulnar UCL footprint. The UCL is a dynamic constraint to valgus loads at the elbow, and a more anatomic reconstruction may afford more natural joint kinematics. This more anatomic technique performs similarly to the traditional docking technique at time zero, and the results of this study may offer a starting point for future in vivo studies.

Chang, Edward S.↗
DOE OSTI2021

A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-α (TGF-α), to the initiation of intracellular signaling pathways. EGFR binds to EGF and TGF-α with similar affinity, but generates different signals from these ligands. To address the mechanistic basis of this phenomenon, we have carried out cryo-EM analyses of human EGFR bound to EGF and TGF-α. We show that the extracellular module adopts an ensemble of dimeric conformations when bound to either EGF or TGF-α. The two extreme states of this ensemble represent distinct ligand-bound quaternary structures in which the membrane-proximal tips of the extracellular module are either juxtaposed or separated. EGF and TGF-α differ in their ability to maintain the conformation with the membrane-proximal tips of the extracellular module separated, and this conformation is stabilized preferentially by an oncogenic EGFR mutation. Close proximity of the transmembrane helices at the junction with the extracellular module has been associated previously with increased EGFR activity. Our results show how EGFR can couple the binding of different ligands to differential modulation of this proximity, thereby suggesting a molecular mechanism for the generation of ligand-sensitive differential outputs in this receptor family.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1989

Magneto-inductive skin sensor for robot collision avoidance: A new development

Safety is a primary concern for robots operating in space. The tri-mode sensor addresses that concern by employing a collision avoidance/management skin around the robot arms. This rf-based skin sensor is at present a dual mode (proximity and tactile). The third mode, pyroelectric, will complement the other two. The proximity mode permits the robot to sense an intruding object, to range the object, and to detect the edges of the object. The tactile mode permits the robot to sense when it has contacted an object, where on the arm it has made contact, and provides a three-dimensional image of the shape of the contact impression. The pyroelectric mode will be added to permit the robot arm to detect the proximity of a hot object and to add sensing redundancy to the two other modes. The rf-modes of the sensing skin are presented. These modes employ a highly efficient magnetic material (amorphous metal) in a sensing technique. This results in a flexible sensor array which uses a primarily inductive configuration to permit both capacitive and magnetoinductive sensing of object; thus optimizing performance in both proximity and tactile modes with the same sensing skin. The fundamental operating principles, design particulars, and theoretical models are provided to aid in the description and understanding of this sensor. Test results are also given.

Chauhan, D. S.↗
NASA NTRS2001

Compact Dexterous Robotic Hand

A compact robotic hand includes a palm housing, a wrist section, and a forearm section. The palm housing supports a plurality of fingers and one or more movable palm members that cooperate with the fingers to grasp and/or release an object. Each flexible finger comprises a plurality of hingedly connected segments, including a proximal segment pivotally connected to the palm housing. The proximal finger segment includes at least one groove defining first and second cam surfaces for engagement with a cable. A plurality of lead screw assemblies each carried by the palm housing are supplied with power from a flexible shaft rotated by an actuator and output linear motion to a cable move a finger. The cable is secured within a respective groove and enables each finger to move between an opened and closed position. A decoupling assembly pivotally connected to a proximal finger segment enables a cable connected thereto to control movement of an intermediate and distal finger segment independent of movement of the proximal finger segment. The dexterous robotic hand closely resembles the function of a human hand yet is light weight and capable of grasping both heavy and light objects with a high degree of precision.

Lovchik, Christopher Scott↗