A matrix isolation and computational study of molecular palladium fluorides : does PdF₆ exist?

Palladium atoms generated by thermal evaporation and laser ablation were reacted with and trapped in F₂ /Ar, F₂ /Ne, and neat F₂ matrices. The products were characterized by electronic absorption and infrared spectroscopy, together with relativistic density functional theory calculations as well as coupled cluster calculations. Vibrational modes at 540 and 617 cm⁻¹ in argon matrices were assigned to molecular PdF and PdF₂ , and a band at 692 cm⁻¹ was assigned to molecular PdF₄ . A band at 624 cm⁻¹ can be assigned to either PdF₃ or PdF₆, with the former preferred from experimental considerations. Although calculations might support the latter assignment, our conclusion is that in these detailed experiments there is no convincing evidence for PdF₆

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain

PURPOSE: We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA). METHODS: Variants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development. RESULTS: Recent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in PRKAR1B. In our cohort, de novo origin of the PRKAR1B variants could be confirmed in five of six individuals, and four carried the same heterozygous de novo variant c.1003C\u3eT (p.Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia have been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C\u3eT variant. PRKAR1B expression in the brain was demonstrated during human embryonal development. Additionally, in vitro analyses revealed altered basal PKA activity in cells transfected with variant-harboring PRKAR1B expression constructs. CONCLUSION: Our study provides strong evidence for a PRKAR1B-related neurodevelopmental disorder

Adapting the Finetech-Brindley sacral anterior root stimulator for bioelectronic medicine

The Finetech-Brindley Sacral Anterior Root Stimulator (SARS) is a low cost and reliable system. The architecture has been used for various bioelectric treatments, including several thousand implanted systems for restoring bladder function following spinal cord injury (SCI). Extending the operational frequency range would expand the capability of the system; enabling, for example, the exploration of eliminating the rhizotomy through an electrical nerve block. The distributed architecture of the SARS system enables stimulation parameters to be adjusted without modifying the implant design or manufacturing. To explore the design degrees-of-freedom, a circuit simulation was created and validated using a modified SARS system that supported stimulation frequencies up to 600 Hz. The simulation was also used to explore high frequency (up to 30kHz) behaviour, and to determine the constraints on charge delivered at the higher rates. A key constraint found was the DC blocking capacitors, designed originally for low frequency operation, not fully discharging within a shortened stimulation period. Within these current implant constraints, we demonstrate the potential capability for higher frequency operation that is consistent with presynaptic stimulation block, and also define targeted circuit improvements for future extension of stimulation capability

Impacts of parameterized orographic drag on the Northern Hemisphere winter circulation

A recent intercomparison exercise proposed by the Working Group for Numerical Experimentation (WGNE) revealed that the parameterized, or unresolved, surface stress in weather forecast models is highly model-dependent, especially over orography. Models of comparable resolution differ over land by as much as 20% in zonal mean total subgrid surface stress (Ttot). The way Ttot is partitioned between the different parameterizations is also model-dependent. In this study, we simulated in a particular model an increase in Ttot comparable with the spread found in the WGNE intercomparison. This increase was simulated in two ways, namely by increasing independently the contributions to Ttot of the turbulent orographic form drag scheme (TOFD) and of the orographic low-level blocking scheme (BLOCK). Increasing the parameterized orographic drag leads to significant changes in surface pressure, zonal wind and temperature in the Northern Hemisphere during winter both in 10 day weather forecasts and in seasonal integrations. However, the magnitude of these changes in circulation strongly depends on which scheme is modified. In 10 day forecasts, stronger changes are found when the TOFD stress is increased, while on seasonal time scales the effects are of comparable magnitude, although different in detail. At these time scales, the BLOCK scheme affects the lower stratosphere winds through changes in the resolved planetary waves which are associated with surface impacts, while the TOFD effects are mostly limited to the lower troposphere. The partitioning of Ttot between the two schemes appears to play an important role at all time scales

Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle.

Chromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10-50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1-5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses

Using the surface profiles of modern ice masses to inform palaeo-glacier reconstructions

Morphometric study of modern ice masses is useful because many reconstructions of glaciers traditionally draw on their shape for guidance Here we analyse data derived from the surface profiles of 200 modern ice masses-valley glaciers icefields ice caps and ice sheets with length scales from 10(0) to 10(3) km-from different parts of the world Four profile attributes are investigated relief span and two parameters C* and C that result from using Nye s (1952) theoretical parabola as a profile descriptor C* and C respectively measure each profile s aspect ratio and steepness and are found to decrease in size and variability with span This dependence quantifies the competing influences of unconstrained spreading behaviour of ice flow and bed topography on the profile shape of ice masses which becomes more parabolic as span Increases (with C* and C tending to low values of 2 5-3 3 m(1/2)) The same data reveal coherent minimum bounds in C* and C for modern ice masses that we develop into two new methods of palaeo glacier reconstruction In the first method glacial limits are known from moraines and the bounds are used to constrain the lowest palaeo ice surface consistent with modern profiles We give an example of applying this method over a three-dimensional glacial landscape in Kamchatka In the second method we test the plausibility of existing reconstructions by comparing their C* and C against the modern minimum bounds Of the 86 published palaeo ice masses that we put to this test 88% are found to be plausible The search for other morphometric constraints will help us formalise glacier reconstructions and reduce their uncertainty and subjectiveness (C) 2010 Elsevier Ltd All rights reserve

Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues.

BACKGROUND: Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on the parent of origin and is typically regulated by differential DNA methylation inherited from gametes. Imprinting is pervasive in murine extra-embryonic lineages, and uniquely, the imprinting of several genes has been found to be conferred non-canonically through maternally inherited repressive histone modification H3K27me3. However, the underlying regulatory mechanisms of non-canonical imprinting in post-implantation development remain unexplored. RESULTS: We identify imprinted regions in post-implantation epiblast and extra-embryonic ectoderm (ExE) by assaying allelic histone modifications (H3K4me3, H3K36me3, H3K27me3), gene expression, and DNA methylation in reciprocal C57BL/6 and CAST hybrid embryos. We distinguish loci with DNA methylation-dependent (canonical) and independent (non-canonical) imprinting by assaying hybrid embryos with ablated maternally inherited DNA methylation. We find that non-canonical imprints are localized to endogenous retrovirus-K (ERVK) long terminal repeats (LTRs), which act as imprinted promoters specifically in extra-embryonic lineages. Transcribed ERVK LTRs are CpG-rich and located in close proximity to gene promoters, and imprinting status is determined by their epigenetic patterning in the oocyte. Finally, we show that oocyte-derived H3K27me3 associated with non-canonical imprints is not maintained beyond pre-implantation development at these elements and is replaced by secondary imprinted DNA methylation on the maternal allele in post-implantation ExE, while being completely silenced by bi-allelic DNA methylation in the epiblast. CONCLUSIONS: This study reveals distinct epigenetic mechanisms regulating non-canonical imprinted gene expression between embryonic and extra-embryonic development and identifies an integral role for ERVK LTR repetitive elements

Recognition of the Major Histocompatibility Complex (MHC) class Ib molecule H2-Q10 by the natural killer cell receptor Ly49C

Murine natural killer (NK) cells are regulated by the interaction of Ly49 receptors with major histocompatibility complex class I molecules (MHC-I). Although the ligands for inhibitory Ly49 were considered to be restricted to classical MHC (MHC-Ia), we have shown that the non-classical MHC molecule (MHC-Ib) H2-M3 was a ligand for the inhibitory Ly49A. Here we establish that another MHC-Ib, H2-Q10, is a bona fide ligand for the inhibitory Ly49C receptor. H2-Q10 bound to Ly49C with a marginally lower affinity (∼5 μm) than that observed between Ly49C and MHC-Ia (H-2Kb/H-2Dd, both ∼1 μm), and this recognition could be prevented by cis interactions with H-2K in situ. To understand the molecular details underpinning Ly49·MHC-Ib recognition, we determined the crystal structures of H2-Q10 and Ly49C bound H2-Q10. Unliganded H2-Q10 adopted a classical MHC-I fold and possessed a peptide-binding groove that exhibited features similar to those found in MHC-Ia, explaining the diverse peptide binding repertoire of H2-Q10. Ly49C bound to H2-Q10 underneath the peptide binding platform to a region that encompassed residues from the α1, α2, and α3 domains, as well as the associated β2-microglobulin subunit. This docking mode was conserved with that previously observed for Ly49C·H-2Kb. Indeed, structure-guided mutation of Ly49C indicated that Ly49C·H2-Q10 and Ly49C·H-2Kb possess similar energetic footprints focused around residues located within the Ly49C β4-stand and L5 loop, which contact the underside of the peptide-binding platform floor. Our data provide a structural basis for Ly49·MHC-Ib recognition and demonstrate that MHC-Ib represent an extended family of ligands for Ly49 molecules

Analisis Pengaruh Budaya Organisasi Dan Kompensasi Terhadap Kinerja Karyawan Dengan Motivasi Sebagai Variabel Intervening (Studi Kasus Pada PT. Lg Bagian Penjualan Indonesia Semarang)

The problems that occurred in the employee portion of sales LG Indonesia Semarang is adecline in performance is indicated by not achieving the target for 2015. The employeeperformance and motivation is also thought to be influenced by factors of organizationalculture and also compensation deemed not feasible by most employees. This study aimedto analyze the influence of organizational culture on the motivation and compensationand employee performance parts sales LG Indonesia Semarang. The population used inthis study were all employees of LG Indonesia Semarang. The sampling technique usedwas purposive sampling. Criteria samples taken were all employees of the salesdepartment LG Indonesia Semarang who have worked more than two years are 71nurses. The method of collecting the data in this study using questionnaires andinterviews. Methods of data analysis using path analysis. Based on the research,organizational culture and compensation have a positive effect on motivation andperformance, while motivation is also a positive effect on performance. Based on theresults Sobel Test to determine whether there is mediating the relationship between theindependent and dependent variables, it is known that motivation mediates the effect ofcompensation and organizational culture on performance