Assessing a Hydrodynamic Description for Instabilities in Highly Dissipative, Freely Cooling Granular Gases

An intriguing phenomenon displayed by granular flows and predicted by kinetic-theory-based models is the instability known as particle "clustering," which refers to the tendency of dissipative grains to form transient, loose regions of relatively high concentration. In this work, we assess a modified-Sonine approximation recently proposed [Garz\'o et al., Physica A 376, 94 (2007)] for a granular gas via an examination of system stability. In particular, we determine the critical length scale associated with the onset of two types of instabilities -vortices and clusters- via stability analyses of the Navier-Stokes-order hydrodynamic equations by using the expressions of the transport coefficients obtained from both the standard and the modified-Sonine approximations. We examine the impact of both Sonine approximations over a range of solids fraction \phi <0.2 for small restitution coefficients e=0.25--0.4, where the standard and modified theories exhibit discrepancies. The theoretical predictions for the critical length scales are compared to molecular dynamics (MD) simulations, of which a small percentage were not considered due to inelastic collapse. Results show excellent quantitative agreement between MD and the modified-Sonine theory, while the standard theory loses accuracy for this highly dissipative parameter space. The modified theory also remedies a (highdissipation) qualitative mismatch between the standard theory and MD for the instability that forms more readily. Furthermore, the evolution of cluster size is briefly examined via MD, indicating that domain-size clusters may remain stable or halve in size, depending on system parameters.Comment: 4 figures; to be published in Phys. Rev.

Ocean access beneath the southwest tributary of Pine Island Glacier, West Antarctica

The catchments of Pine Island Glacier and Thwaites Glacier in the Amundsen Sea Embayment are two of the largest, most rapidly changing, and potentially unstable sectors of the West Antarctic Ice Sheet. They are also neighboring outlets, separated by the topographically unconfined eastern shear margin of Thwaites Glacier and the southwest tributary of Pine Island Glacier. This tributary begins just downstream of the eastern shear margin and flows into the Pine Island ice shelf. As a result, it is a potential locus of interaction between the two glaciers and could result in cross-catchment feedback during the retreat of either. Here, we analyze relative basal reflectivity profiles from three radar sounding survey lines collected using the UTIG HiCARS radar system in 2004 and CReSIS MCoRDS radar system in 2012 and 2014 to investigate the extent and character of ocean access beneath the southwest tributary. These profiles provide evidence of ocean access ~12 km inland of the 1992–2011 InSAR-derived grounding line by 2014, suggesting either retreat since 2011 or the intrusion of ocean water kilometers inland of the grounding line

Multisystem synthesis of radar sounding observations of the Amundsen Sea sector from the 2004‐2005 field season

The Amundsen Sea Embayment of the West Antarctic Ice Sheet contains Thwaites and Pine Island Glaciers, two of the most rapidly changing glaciers in Antarctica. To date, Pine Island and Thwaites Glaciers have only been observed by independent airborne radar sounding surveys, but a combined cross-basin analysis that investigates the basal conditions across the Pine Island-Thwaites Glaciers boundary has not been performed. Here, we combine two radar surveys and correct for their differences in system parameters to produce unified englacial attenuation and basal relative reflectivity maps spanning both Pine Island and Thwaites Glaciers. Relative reflectivities range from -24.8 to +37.4 dB with the highest values beneath fast-flowing ice at the ice sheet margin. By comparing our reflectivity results with previously derived radar specularity and trailing bed echoes at Thwaites Glacier, we find a highly diverse subglacial landscape and hydrologic condition that evolve along flow. Together, these findings highlight the potential for joint airborne radar analysis with ground-based seismic and geomorphological observations to understand variations in the bed properties and cross-catchment interactions of ice streams and outlet glaciers

Redefining the MED13L syndrome

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits

Yeast surface display platform for rapid discovery of conformationally selective nanobodies

Camelid single-domain antibody fragments ('nanobodies') provide the remarkable specificity of antibodies within a single 15-kDa immunoglobulin VHH domain. This unique feature has enabled applications ranging from use as biochemical tools to therapeutic agents. Nanobodies have emerged as especially useful tools in protein structural biology, facilitating studies of conformationally dynamic proteins such as G-protein-coupled receptors (GPCRs). Nearly all nanobodies available to date have been obtained by animal immunization, a bottleneck restricting many applications of this technology. To solve this problem, we report a fully in vitro platform for nanobody discovery based on yeast surface display. We provide a blueprint for identifying nanobodies, demonstrate the utility of the library by crystallizing a nanobody with its antigen, and most importantly, we utilize the platform to discover conformationally selective nanobodies to two distinct human GPCRs. To facilitate broad deployment of this platform, the library and associated protocols are freely available for nonprofit research

Yeast surface display platform for rapid discovery of conformationally selective nanobodies.

Camelid single-domain antibody fragments ('nanobodies') provide the remarkable specificity of antibodies within a single 15-kDa immunoglobulin VHH domain. This unique feature has enabled applications ranging from use as biochemical tools to therapeutic agents. Nanobodies have emerged as especially useful tools in protein structural biology, facilitating studies of conformationally dynamic proteins such as G-protein-coupled receptors (GPCRs). Nearly all nanobodies available to date have been obtained by animal immunization, a bottleneck restricting many applications of this technology. To solve this problem, we report a fully in vitro platform for nanobody discovery based on yeast surface display. We provide a blueprint for identifying nanobodies, demonstrate the utility of the library by crystallizing a nanobody with its antigen, and most importantly, we utilize the platform to discover conformationally selective nanobodies to two distinct human GPCRs. To facilitate broad deployment of this platform, the library and associated protocols are freely available for nonprofit research

Disruption of the Serine/Threonine Kinase 9 Gene Causes Severe X-Linked Infantile Spasms and Mental Retardation

X-linked West syndrome, also called “X-linked infantile spasms” (ISSX), is characterized by early-onset generalized seizures, hypsarrhythmia, and mental retardation. Recently, we have shown that the majority of the X-linked families with infantile spasms carry mutations in the aristaless-related homeobox gene (ARX), which maps to the Xp21.3-p22.1 interval, and that the clinical picture in these patients can vary from mild mental retardation to severe ISSX with additional neurological abnormalities. Here, we report a study of two severely affected female patients with apparently de novo balanced X;autosome translocations, both disrupting the serine-threonine kinase 9 (STK9) gene, which maps distal to ARX in the Xp22.3 region. We show that STK9 is subject to X-inactivation in normal female somatic cells and is functionally absent in the two patients, because of preferential inactivation of the normal X. Disruption of the same gene in two unrelated patients who have identical phenotypes (consisting of early-onset severe infantile spasms, profound global developmental arrest, hypsarrhythmia, and severe mental retardation) strongly suggests that lack of functional STK9 protein causes severe ISSX and that STK9 is a second X-chromosomal locus for this disorder