446 research outputs found
Coherent Excitation of X-Ray Fluorescence and Interference of Radiation at the Output of Polycapillary Structures
No full textThe diffraction of long-wavelength X rays with the energy corresponding to the region of anomalous dispersion near the Si L2,3 absorption edges transmitted through microchannel plates has been studied both experimentally and theoretically. The radiation of a finite antenna array, as well as the processes of excitation of X-ray fluorescence and propagation of waves in hollow waveguide structures, has been mathematically simulated. The model describes a polycapillary structure consisting of noninteracting emitters, which are hollow channels of a microchannel plate. It has been shown that coherently excited X-ray fluorescence propagates primarily in the direction of the zeroth diffraction order
The type 2 diabetes mellitus susceptibility gene, TCF7L2, is associated with schizophrenia in an Arab-Israeli family sample
No full textDOCK4 and CEACAM21 as novel schizophrenia candidate genes in the Jewish population
No full textIt is well accepted that schizophrenia has a strong genetic component.
Several genome-wide association studies (GWASs) of schizophrenia have
been published in recent years; most of them population based with a
case-control design. Nevertheless, identifying the specific genetic
variants which contribute to susceptibility to the disorder remains a
challenging task. A family-based GWAS strategy may be helpful in the
identification of schizophrenia susceptibility genes since it is
protected against population stratification, enables better accounting
for genotyping errors and is more sensitive for identification of rare
variants which have a very low frequency in the general population. In
this project we implemented a family-based GWAS of schizophrenia in a
sample of 107 Jewish-Israeli families. We found one genome-wide
significant association in the intron of the DOCK4 gene (rs2074127, p
value=1.134 x 10(-7)) and six additional nominally significant
association signals with p<1 x 10(-5). One of the top single nucleotide
polymorphisms (p<1 x 10(-5)) which is located in the predicted intron of
the CEACAM21 gene was significantly replicated in independent
family-based sample of Arab-Israeli origin (rs4803480: p value=0.002;
combined p value=9.61 x 10(-8)), surviving correction for multiple
testing. Both DOCK4 and CEACAM21 are biologically reasonable candidate
genes for schizophrenia although generalizability of the association of
DOCK4 with schizophrenia should be investigated in further studies. In
addition, gene-wide significant associations were found within three
schizophrenia candidate genes: PGBD1, RELN and PRODH, replicating
previously reported associations. By application of a family-based
strategy to GWAS, our study revealed new schizophrenia susceptibility
loci in the Jewish-Israeli population
Association of nicotine dependence susceptibility gene, CHRNA5, with Parkinson's disease age at onset : gene and smoking status interaction
No full textBACKGROUND: Smoking is a well documented environmental factor that reduces susceptibility to Parkinson's disease (PD). Several genetic variants within the nicotinic cholinergic receptor gene cluster, CHRNA5-CHRNA3-CHRNB4 have been reported to be associated with nicotine dependence (ND), and this association has been validated in multiple studies. OBJECTIVES: Due to the inverse correlation between smoking and PD susceptibility, we investigated whether ND-related genetic variants are associated with age at onset (AAO) of PD among smokers. METHODS: We performed a genetic association study in a sample of 677 Italian PD patients, ages 34-76. 438 had never smoked (NS), and 239 were current or past smokers (ever-smokers, ES). Three independent SNPs within the CHRNA5-CHRNA3-CHRNB4 gene cluster (rs588765, rs16969968, rs578776) were analyzed for association with AAO. RESULTS: We demonstrated an interaction between the rs588765 SNP and smoking status (NS vs. ES) that was nominally significant in its effect on PD AAO (p = 0.04). The rs588765 ND risk allele 'C' was associated with delayed AAO among ES (even when smoking intensity variables are accounted for), but had no significant effect among NS. In the ES group, a dominant model of inheritance was observed: carriers of the 'CC' genotype presented delayed AAO compared to carriers of the 'CT' or 'TT' genotypes. CONCLUSION: Our preliminary results suggest that the ND risk variant, rs588765, has a protective effect in PD, and is associated with later AAO, but only when the individual was previously exposed to nicotine. This may be explained by modulating the neuroprotective effect of chronic nicotine exposure against striatal dopaminergic damage. Further validation studies in additional populations are required
Association of the type 2 diabetes mellitus susceptibility gene, TCF7L2, with schizophrenia in an Arab-Israeli family sample.
No full textMany reports in different populations have demonstrated linkage of the 10q24-q26 region to schizophrenia, thus encouraging further analysis of this locus for detection of specific schizophrenia genes. Our group previously reported linkage of the 10q24-q26 region to schizophrenia in a unique, homogeneous sample of Arab-Israeli families with multiple schizophrenia-affected individuals, under a dominant model of inheritance. To further explore this candidate region and identify specific susceptibility variants within it, we performed re-analysis of the 10q24-26 genotype data, taken from our previous genome-wide association study (GWAS) (Alkelai et al, 2011). We analyzed 2089 SNPs in an extended sample of 57 Arab Israeli families (189 genotyped individuals), under the dominant model of inheritance, which best fits this locus according to previously performed MOD score analysis. We found significant association with schizophrenia of the TCF7L2 gene intronic SNP, rs12573128, (p = 7.01×10⁻⁶) and of the nearby intergenic SNP, rs1033772, (p = 6.59×10⁻⁶) which is positioned between TCF7L2 and HABP2. TCF7L2 is one of the best confirmed susceptibility genes for type 2 diabetes (T2D) among different ethnic groups, has a role in pancreatic beta cell function and may contribute to the comorbidity of schizophrenia and T2D. These preliminary results independently support previous findings regarding a possible role of TCF7L2 in susceptibility to schizophrenia, and strengthen the importance of integrating linkage analysis models of inheritance while performing association analyses in regions of interest. Further validation studies in additional populations are required
The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression
No full textDespite extensive research, the current theories on serotonergic dysfunctions
and cortisol hypersecretion do not provide sufficient explanations for the nature
of depression. Rational treatments aimed at causal factors of depression are not
available yet. With the currently available antidepressant drugs, which mainly target
serotonin, less than two thirds of depressed patients achieve remission. There is now
evidence that inflammatory and neurodegenerative (I&ND) processes play an
important role in depression and that enhanced neurodegeneration in depression
may–at least partly–be caused by inflammatory processes. Multiple inflammatorycytokines,
oxygen radical damage, tryptophan catabolites–and neurodegenerative
biomarkers have been established in patients with depression and these findings are
corroborated by animal models of depression. A number of vulnerability factors maypredispose towards depression by enhancing inflammatory reactions, e.g. lower
peptidase activities (dipeptidyl-peptidase IV, DPP IV), lower omega-3 polyunsaturated
levels and an increased gut permeability (leaky gut). The cytokine hypothesis
considers that external, e.g. psychosocial stressors, and internal stressors, e.g. organic
inflammatory disorders or conditions, such as the postpartum period, may trigger
depression via inflammatory processes. Most if not all antidepressants have specific
anti-inflammatory effects, while restoration of decreased neurogenesis, which may be
induced by inflammatory processes, may be related to the therapeutic efficacy of
antidepressant treatments. Future research to disentangle the complex etiology of
depression calls for a powerful paradigm shift, i.e. by means of a high throughput-high
quality screening, including functional genetics and genotyping microarrays;
established and novel animal and ex vivo–in vitro models for depression, such as
new transgenic mouse models and endophenotype-based animal models, specific cell
lines, in vivo and ex vivo electroporation, and organotypic brain slice culture models.
This screening will allow to: 1) discover new I&ND biomarkers, both at the level
of gene expression and the phenotype; and elucidate the underlying molecular
I&ND pathways causing depression; and 2) identify new therapeutic targets in the
I&ND pathways; develop new anti-I&ND drugs for these targets; select existing
anti-I&ND drugs or substances that could augment the efficacy of antidepressants;
and predict therapeutic response by genetic I&ND profiles
Retelling Tales: Patience Agbabi\u27s Queering of Chaucer\u27s The Man of Law\u27s Tale
No full textGeoffrey Chaucer’s The Canterbury Tales is recognized as a formative text within the canon of English literature. Because of his widely known status, Chaucer and his writings have become the central focus of many medievalists; this does not simply mean the increased presence of critical writings, but also creative works that are inspired by The Canterbury Tales. Patience Agbabi’s Telling Tales is a contemporary poetic retelling of The Canterbury Tales in which she explores the origins of ideas such as diaspora, colonization, racialized thinking, social hierarchy, and binary thinking, only to question these ideas in her own writing. Author Seth Lerer argues, “Constructing literary systems entails positing not just a present of performance but a past of cultural identity. It necessitates the self-conscious invention of a history to literature and, in turn, a definition of the poet’s self-appointed role in mediating that history to a present reading, commissioning, or judging community” (Lerer 4). Although Lerer is discussing the ratification of Chaucer into the modern canon of English literature, he is creating a clear line of historical foundations for the practice of rewriting. Agbabi is continuing Chaucer’s practice of drawing on his own surroundings to create a tale of the present. Patience Agbabi rewrites “The Man of Law’s Tale” into a queer and transnational tale by extracting points of origin from the Middle Ages and rewriting them from a contemporary point of view
An Exploratory Study on Conversational Agents Using Dynamic Conversation Styles
No full textThis study aims to examine the effect of dynamically aligning the conversation style to the user’s preference in a conversational agent environment. We suggest a technique to identify the user’s preferred conversation style, by scoring statements based on their writing style. We designed a within-subject experiment intended to measure the user engagement and satisfaction (with style alignment × without style alignment). We found an increase in self reported satisfaction ratings and reflect on how familiarity with the entity behind the chatbot may affect the preference of the conversational style. We finish this study with concrete suggestions to designers and developers of future chatbots and how should the alignment of conversation style be assigned and adaptedCSE3000 Research ProjectComputer Science and Engineerin
Supplementary Figure S4 from Tumor Cell–Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression
No full textSupplementary Figure S4. Deletion of LERER in MenaINV affects tumor growth in a xenograft model.</p
Convergent genetic and functional evidence for association of the AHI1 gene with susceptibility to schizophrenia
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