Violence in transition: Reforms and rights in the Western Balkans

The 1990s saw the breakdown of the former Socialist Federal Republic of Yugoslavia which, since World War II, had developed a distinct economic system that included specific market and socialist self-management principles in production, distribution and decision-making processes. At the same time, the European Union opened up the possibility of full membership if these countries – now politically referred to as the Western Balkans – met the accession criteria claimed as essential to bring about fully-functioning and competitive market economies. The transition and accession processes were supported financially, politically and militarily by Western powers as a shift away from authoritarianism and poverty, while promoting democracy, human rights and individual freedom. This article argues that, contrary to this optimistic discourse, transition in the Western Balkans reflected and incorporated violence at different levels. The article shows that tensions between reforms and rights began in the 1970s, spurred by indebtedness and inequalities, pervading the transition process and deteriorating in the wake of the 2007-2008 global financial crisis. Social policy increasingly became framed along market- efficiency principles, challenging existing entitlements and rights, particularly with regard to education, social security and health. Vulnerable groups, such as the unemployed and the aged, experienced serious shortfalls in support and care. By the second decade of the twenty-first century, social protests against the deterioration in the levels of livelihood and the retrogression of social rights had erupted in several places. Violence was expressed not only in the form of direct bodily harm, but also in control exerted through indebtedness, the destruction of livelihoods, the denial of basic human rights, and the struggle for social justice

Characterization of the sources of protein-ligand affinity: 1-sulfonato-8-(1')anilinonaphthalene binding to intestinal fatty acid binding protein

1-Sulfonato-8-(1')anilinonaphthalene (1,8-ANS) was employed as a fluorescent probe of the fatty acid binding site of recombinant rat intestinal fatty acid binding protein (1-FABP). The enhancement of fluorescence upon binding allowed direct determination of binding affinity by fluorescence titration experiments, and measurement of the effects on that affinity of temperature, pH, and ionic strength. Solvent isotope effects were also determined. These data were compared to results from isothermal titration calorimetry. We obtained values for the enthalpy and entropy of this interaction at a variety of temperatures, and hence determined the change in heat capacity of the system consequent upon binding. The ANS-1-FABP is enthalpically driven; above approximately 14 degrees C it is entropically opposed, but below this temperature the entropy makes a positive contribution to the binding. The changes we observe in both enthalpy and entropy of binding with temperature can be derived from the change in heat capacity upon binding by integration, which demonstrates the internal consistency of our results. Bound ANS is displaced by fatty acids and can itself displace fatty acids bound to I-FABP. The binding site for ANS appears to be inside the solvent-containing cavity observed in the x-ray crystal structure, the same cavity occupied by fatty acid. From the fluorescence spectrum and from an inversion of the Debye-Hueckel formula for the activity coefficients as a function of added salt, we inferred that this cavity is fairly polar in character, which is in keeping with inferences drawn from the x-ray structure. The binding affinity of ANS is considered to be a consequence of both electrostatic and conditional hydrophobic effects. We speculate that the observed change in heat capacity is produced mainly by the displacement of strongly hydrogen-bonded waters from the protein cavity

Hafnium carbide formation in oxygen deficient hafnium oxide thin films

On highly oxygen deficient thin films of hafnium oxide (hafnia, HfO$_{2-x}$) contaminated with adsorbates of carbon oxides, the formation of hafnium carbide (HfC$_x$) at the surface during vacuum annealing at temperatures as low as 600 {\deg}C is reported. Using X-ray photoelectron spectroscopy the evolution of the HfC$_x$ surface layer related to a transformation from insulating into metallic state is monitored in situ. In contrast, for fully stoichiometric HfO$_2$ thin films prepared and measured under identical conditions, the formation of HfC$_x$ was not detectable suggesting that the enhanced adsorption of carbon oxides on oxygen deficient films provides a carbon source for the carbide formation. This shows that a high concentration of oxygen vacancies in carbon contaminated hafnia lowers considerably the formation energy of hafnium carbide. Thus, the presence of a sufficient amount of residual carbon in resistive random access memory devices might lead to a similar carbide formation within the conducting filaments due to Joule heating

Psychiatric blood biomarkers: avoiding jumping to premature negative or positive conclusions

Blood biomarkers may provide a scientifically useful and clinically usable peripheral signal in psychiatry, as they have been doing for other fields of medicine. Jumping to premature conclusions, negative or positive, can create confusion in this field. Reproducibility is a hallmark of good science. We discuss some recent examples from this dynamic field, and show some new data in support of previously published biomarkers for suicidality (SAT1, MARCKS and SKA2). Methodological clarity and rigor in terms of biomarker discovery, validation and testing is needed. We propose a set of principles for what constitutes a good biomarker, similar in spirit to the Koch postulates used at the birth of the field of infectious diseases

A New Biophysical Metric for Interrogating the Information Content in Human Genome Sequence Variation: Proof of Concept

Various studies have shown an association between single nucleotide polymorphisms (SNPs) and common disease. We hypothesize that information encoded in the structure of SNP haploblock variation illumines molecular pathways and cellular mechanisms involved in the regulation of host adaptation to the environment. We developed and utilized the normalized information content (NIC), a novel metric based on SNP haploblock variation. We found that all SNP haploblocks with statistically low information content contained putative transcription factor binding sites and microRNA motifs. We were able to translate a biophysical, mathematical measure of common variants into a deeper understanding of the life sciences through analysis of biochemical patterns associated with SNP haploblock variation. We submit that this new metric, NIC, may be useful in decoding the functional significance of common variation in the human genome and in analyzing the regulation of molecular pathways involved in host adaptation to environmental pathogens.Comment: 13 page

Review of the phenotype of early-onset generalised progressive dystonia due to mutations in KMT2B

In 2016, two research groups independently identified microdeletions and pathogenic variants in the lysine-specific histone methyltransferase 2B gene, KMT2B in patients with early-onset progressive dystonia. KMT2B-dystonia (DYT28) is emerging as an important and frequent cause of childhood-onset progressive generalised dystonia and is estimated to potentially account for up to 10% of early-onset generalised dystonia. Herein, we review variants in KMT2B associated with dystonia, as well as the clinical phenotype, treatment and underlying disease mechanisms. Furthermore, in context of this newly identified condition, we summarise our approach to the genetic investigation of paediatric dystonia

GABRB3 mutations: a new and emerging cause of early infantile epileptic encephalopathy

The gamma-aminobutyric acid type A receptor β3 gene (GABRB3) encodes the β3-subunit of the gamma-aminobutyric acid type A (GABAA ) receptor, which mediates inhibitory signalling within the central nervous system. Recently, GABRB3 mutations have been identified in a few patients with infantile spasms and Lennox-Gastaut syndrome. We report the clinical and electrographic features of a novel case of GABRB3-related early-onset epileptic encephalopathy. Our patient presented with neonatal hypotonia and feeding difficulties, then developed pharmacoresistant epileptic encephalopathy, characterized by multiple seizure types from 3 months of age. Electroencephalography demonstrated ictal generalized and interictal multifocal epileptiform abnormalities. Using a SureSelectXT custom multiple gene panel covering 48 early infantile epileptic encephalopathy/developmental delay genes, a novel de novo GABRB3 heterozygous missense mutation, c.860C>T (p.Thr287Ile), was identified and confirmed on Sanger sequencing. GABRB3 is an emerging cause of early-onset epilepsy. Novel genetic technologies, such as whole-exome/genome sequencing and multiple gene panels, will undoubtedly identify further cases, allowing more detailed electroclinical delineation of the GABRB3-related genotypic and phenotypic spectra

Ellis-van Creveld syndrome in an Indian child: a case report

Ellis-van Creveld syndrome is a rare congenital genetic disorder having autosomal recessive inheritance. It is a syndrome affecting the Amish population of Pennsylvania in USA with prevalence rate of 1/5,000 live at birth. In non-Amish population, the birth prevalence is 7/1,000,000. The syndrome is characterized by bilateral postaxial polydactyly of the hands, chondrodysplasia of long bones resulting in acromesomelic dwarfism, ectodermal dysplasia affecting nails as well as teeth and congenital heart malformation. There were very rare reports of this syndrome in dentistry. The present case focuses on the striking and constant oral findings of these patients, which are the main diagnostic features of this syndrome. Since the oral manifestations affect the esthetic, speech, and jaw growth of the child, the dentists have an important role to play in proper management of such case

Locality-oblivious cache organization leveraging single-cycle multi-hop NoCs

Locality has always been a critical factor in on-chip data placement on CMPs as accessing further-away caches has in the past been more costly than accessing nearby ones. Substantial research on locality-aware designs have thus focused on keeping a copy of the data private. However, this complicatesthe problem of data tracking and search/invalidation; tracking the state of a line at all on-chip caches at a directory or performing full-chip broadcasts are both non-scalable and extremely expensive solutions. In this paper, we make the case for Locality-Oblivious Cache Organization (LOCO), a CMP cache organization that leverages the on-chip network to create virtual single-cycle paths between distant caches, thus redefining the notion of locality. LOCO is a clustered cache organization, supporting both homogeneous and heterogeneous cluster sizes, and provides near single-cycle accesses to data anywhere within the cluster, just like a private cache. Globally, LOCO dynamically creates a virtual mesh connecting all the clusters, and performs an efficient global data search and migration over this virtual mesh, without having to resort to full-chip broadcasts or perform expensive directory lookups. Trace-driven and full system simulations running SPLASH-2 and PARSEC benchmarks show that LOCO improves application run time by up to 44.5% over baseline private and shared cache.Semiconductor Research CorporationUnited States. Defense Advanced Research Projects Agency (Semiconductor Technology Advanced Research Network