Germline BAP1 mutations predispose to renal cell carcinomas.

The genetic cause of some familial nonsyndromic renal cell carcinomas (RCC) defined by at least two affected first-degree relatives is unknown. By combining whole-exome sequencing and tumor profiling in a family prone to cases of RCC, we identified a germline BAP1 mutation c.277A>G (p.Thr93Ala) as the probable genetic basis of RCC predisposition. This mutation segregated with all four RCC-affected relatives. Furthermore, BAP1 was found to be inactivated in RCC-affected individuals from this family. No BAP1 mutations were identified in 32 familial cases presenting with only RCC. We then screened for germline BAP1 deleterious mutations in familial aggregations of cancers within the spectrum of the recently described BAP1-associated tumor predisposition syndrome, including uveal melanoma, malignant pleural mesothelioma, and cutaneous melanoma. Among the 11 families that included individuals identified as carrying germline deleterious BAP1 mutations, 6 families presented with 9 RCC-affected individuals, demonstrating a significantly increased risk for RCC. This strongly argues that RCC belongs to the BAP1 syndrome and that BAP1 is a RCC-predisposition gene.

The entropies of adsorbed molecules.

Adsorbed molecules are involved in many reactions on solid surface that are of great technological importance. As such, there has been tremendous effort worldwide to learn how to predict reaction rates and equilibrium constants for reactions involving adsorbed molecules. Theoretical calculation of both the rate and equilibrium constants for such reactions requires knowing the entropy and enthalpy of the adsorbed molecule. While much effort has been devoted to measuring and calculating the enthalpies of well-defined adsorbates, few measurements of the entropies of adsorbates have been reported. We present here a new way to determine the standard entropies of adsorbed molecules (S(ad)(0)) on single crystal surfaces from temperature programmed desorption data, prove its accuracy by comparison to entropies measured by equilibrium methods, and apply it to published data to extract new entropies. Most importantly, when combined with reported entropies, we find that at high coverage, they linearly track the entropy of the gas-phase molecule at the same temperature (T), such that S(ad)(0)(T) = 0.70 S(gas)(0)(T) - 3.3R (R = the gas constant), with a standard deviation of only 2R over a range of 50R. These entropies, which are ~2/3 of the gas, are huge compared to most theoretical predictions. This result can be extended to reliably predict prefactors in the Arrhenius rate constant for surface reactions involving such species, as proven here for desorption.

Deep brain activation patterns involved in virtual gait without and with a doorway: An fMRI study.

The human gait program involves many brain areas such as motor cortices, cerebellum, basal ganglia, brainstem, and spinal cord. The mesencephalic locomotor region (MLR), which contains the pedunculopontine (PPN) and cuneiform (CN) nuclei, is thought to be one of the key supraspinal gait generators. In daily life activities, gait primarily occurs in complex conditions, such as through narrow spaces, or while changing direction or performing motor or cognitive tasks. Here, we aim to explore the activity of these subcortical brain areas while walking through narrow spaces, using functional MRI in healthy volunteers and designing a virtual reality task mimicking walking down a hallway, without and with an open doorway to walk through. As a control, we used a virtual moving walkway in the same environment. Twenty healthy volunteers were scanned. Fifteen subjects were selected for second level analysis based on their ability to activate motor cortices. Using the contrast Gait versus Walkway, we found activated clusters in motor cortices, cerebellum, red nucleus, thalamus, and the left MLR including the CN and PPN. Using the contrast Gait with Doorway versus Walkway with Doorway, we found activated clusters in motor cortices, left putamen, left internal pallidum, left substantia nigra, right subthalamic area, and bilateral MLR involving the CN and PPN. Our results suggest that unobstructed gait involves a motor network including the PPN whereas gait through a narrow space requires the additional participation of basal ganglia and bilateral MLR, which may encode environmental cues to adapt locomotion.

Anchored metal nanoparticles: effects of support and size on their energy, sintering resistance and reactivity.

Many catalysts consist of metal nanoparticles anchored to the surfaces of oxide supports. These are key elements in technologies for the clean production and use of fuels and chemicals. We show here that the chemical reactivity of the surface metal atoms on these nanoparticles is closely related to their chemical potential: the higher their chemical potential, the more strongly they bond to small adsorbates. Controlling their chemical potential by tuning the structural details of the material can thus be used to tune their reactivity. As their chemical potential increases, this also makes the metal surface less noble, effectively pushing its behavior upwards and to the left in the periodic table. Also, when the metal atoms are in a nanoparticle with higher chemical potential, they experience a larger thermodynamic driving force to sinter. Calorimetric measurements of metal vapor adsorption energies onto clean oxide surfaces in ultrahigh vacuum show that the chemical potential increases with decreasing particle size below 6 nm, and, for a given size, decreases with the adhesion energy between the metal and its support, Eadh. The structural factors that control the metal/oxide adhesion energy are thus also keys for tuning catalytic performance. For a given oxide, Eadh increases with (deltaHsub,M--deltaHf,MOx)/OmegaM2/3 for the metal, where deltaHsub,M is its heat of sublimation, deltaHf,MOx is the standard heat of formation of that metal's most stable oxide (per mole of metal), and OmegaM is the atomic volume of the bulk solid metal. The value deltaHsub,M--deltaHf,MOx equals the heat of formation of that metal's oxide from a gaseous metal atom plus O2(g), so it reflects the strength of the chemical bonds which that metal atom can make to oxygen, and OmegaM2/3 simply normalizes this energy to the area per metal atom, since Eadh is the adhesion energy per unit area. For a given metal, Eadh to different clean oxide surfaces increases as: MgO(100) approximately TiO2(110) < or = alpha-Al2O3(0001) < CeO2-x(111) < or = Fe3O4(111). Oxygen vacancies also increase Eadh, but surface hydroxyl groups appear to decrease Eadh, even though they increase the initial heat of metal adsorption.

Adsorption calorimetry during metal vapor deposition on single crystal surfaces: increased flux, reduced optical radiation, and real-time flux and reflectivity measurements.

Thin films of metals and other materials are often grown by physical vapor deposition. To understand such processes, it is desirable to measure the adsorption energy of the deposited species as the film grows, especially when grown on single crystal substrates where the structure of the adsorbed species, evolving interface, and thin film are more homogeneous and well-defined in structure. Our group previously described in this journal an adsorption calorimeter capable of such measurements on single-crystal surfaces under the clean conditions of ultrahigh vacuum [J. T. Stuckless, N. A. Frei, and C. T. Campbell, Rev. Sci. Instrum. 69, 2427 (1998)]. Here we describe several improvements to that original design that allow for heat measurements with ~18-fold smaller standard deviation, greater absolute accuracy in energy calibration, and, most importantly, measurements of the adsorption of lower vapor-pressure materials which would have previously been impossible. These improvements are accomplished by: (1) using an electron beam evaporator instead of a Knudsen cell to generate the metal vapor at the source of the pulsed atomic beam, (2) changing the atomic beam design to decrease the relative amount of optical radiation that accompanies evaporation, (3) adding an off-axis quartz crystal microbalance for real-time measurement of the flux of the atomic beam during calorimetry experiments, and (4) adding capabilities for in situ relative diffuse optical reflectivity determinations (necessary for heat signal calibration). These improvements are not limited to adsorption calorimetry during metal deposition, but also could be applied to better study film growth of other elements and even molecular adsorbates.