Collision and fusion of counterpropagating micron-sized optical beams in non-uniformly biased photorefractive crystals

We theoretically investigate collision of optical beams travelling in opposite directions through a centrosymmetric photorefractive crystal biased by a spatially non-uniform voltage. We analytically predict the fusion of counterpropagating solitons in conditions in which the applied voltage is rapidly modulated along the propagation axis, so that self-bending is suppressed by the "restoring symmetry" mechanism. Moreover, when the applied voltage is slowly modulated, we predict that the modified self-bending allows conditions in which the two beams fuse together, forming a curved light-channel splice.Comment: 12 page

Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas

Our analyses of cathepsin H activity levels and protein forms in human colorectal cancers compared to matched control mucosa support the concept that altered proteinase expression patterns may reflect both cancer stage and site. Cathepsin H-specific activity was significantly increased in colorectal cancers compared to control mucosa (P = 0.003;n = 77). Highest specific activities and cancer/normal ratios (C/N) for activity were measured in Dukes' B and C stage carcinomas, cancers involved in local spread and invasion to lymph nodes. In contrast, cathepsin B and L activities analysed in the same paired extracts had been shown to be most frequently elevated in earlier stage carcinomas (Dukes' A and B), confirming that cathepsin H demonstrates a distinct pattern of expression during colorectal cancer progression. Although cathepsin H activities were most commonly elevated in Dukes' C cancers at all colon sites, both specific activity and C/N ratios were significantly higher for cancers of the left colon compared to other colon locations. A subset of 43 paired extracts analysed on Western blots also revealed consistent changes in cathepsin H protein forms in cancers. Normal mucosa typically showed a strong protein doublet at 31 and 29 kDa while cancers demonstrated decreased expression or total loss of the 31 kDa protein (90% of cases), equal or increased expression of the 29-kDa protein (67% of cases) and the new appearance or up-regulation of a cathepsin H band at 22 kDa (78% of cases). C/N ratios for cathepsin H enzyme activity correlated significantly with C/N ratios for the 29 kDa mature single-chain protein form (P< 0.001), with increased activity most commonly associated with elevated expression of 29-kDa cathepsin H but also with up-regulation of the 22-kDa band, suggesting a shift to more fully processed, mature active cathepsin H protein forms in cancers. Changes in cathepsin H expression were also detected by immunohistochemistry as elevated cathepsin H staining in tumour epithelial cells. © 2000 Cancer Research Campaig

Hyperarousal symptoms after traumatic and nontraumatic births

Background: Measurement is critical in postnatal posttraumatic stress disorder (PTSD) because symptoms may be influenced by normal postnatal phenomena such as physiological changes and fatigue. Objective: This study examined: (1) whether hyperarousal symptoms differ between women who have traumatic or nontraumatic births; (2) whether the construct of hyperarousal is coherent in postnatal women; and (3) whether hyperarousal symptoms are useful for identifying women who have traumatic births or PTSD. Methods: A survey of PTSD symptoms in 1,078 women recruited via the community or Internet who completed an online or paper questionnaire measuring childbirth-related PTSD symptoms between 1 and 36 months after birth. Women who had a traumatic birth as defined by DSM-IV criterion A (n = 458) were compared with women who did not have a traumatic birth (n = 591). Results: A one-factor dimension of hyperarousal was identified that included all five hyperarousal items. Diagnostic criteria of two or more hyperarousal symptoms in the previous week were reported by 75.3% of women with traumatic birth and 50.5% of women with nontraumatic births. The difference in mean hyperarousal symptoms between groups was substantial at 0.76 of a standard deviation (Hedge’s g, CI = 0.64, 0.89). A larger difference was observed between women with and without diagnostic PTSD (g = 1.64, CI 1.46, 1.81). However, receiver operating characteristic analyses showed hyperarousal symptoms have poor specificity and alternative ways of calculating symptoms did not improve this. Comparison with other PTSD symptoms found re-experiencing symptoms were most accurate at identifying women with traumatic births. Conclusions: Results suggest hyperarousal symptoms are associated with traumatic birth and are a coherent construct in postnatal women. However, they have poor specificity and should only be used as part of diagnostic criteria, not as a sole indicator

169pselective induction of pd l1 expression in plasma derived exosomes by gemcitabine nab paclitaxel vs folfirinox in pancreas cancer

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Super-crystals in composite ferroelectrics

As atoms and molecules condense to form solids, a crystalline state can emerge with its highly ordered geometry and subnanometric lattice constant. In some physical systems, such as ferroelectric perovskites, a perfect crystalline structure forms even when the condensing substances are non-stoichiometric. The resulting solids have compositional disorder and complex macroscopic properties, such as giant susceptibilities and non-ergodicity. Here, we observe the spontaneous formation of a cubic structure in composite ferroelectric potassium– lithium–tantalate–niobate with micrometric lattice constant, 104 times larger than that of the underlying perovskite lattice. The 3D effect is observed in specifically designed samples in which the substitutional mixture varies periodically along one specific crystal axis. Laser propagation indicates a coherent polarization super-crystal that produces an optical X-ray diffractometry, an ordered mesoscopic state of matter with important implications for critical phenomena and applications in miniaturized 3D optical technologies

CYP17A1 polymorphism c.-362T>C predicts clinical outcome in metastatic castration-resistance prostate cancer patients treated with abiraterone

Background: Abiraterone became&nbsp;a standard hormonal therapy for patients with metastatic castration-resistance prostate cancer (mCRPC). However, patients may experience primary resistance to treatment. To date, few predictive biomarkers of efficacy have been identified. Our aim was to investigate the association between the&nbsp;single nucleotide polymorphism (SNP) c.-362T&gt;C&nbsp;in the&nbsp;CYP17A1 gene, and clinical outcome in mCRPC patients treated with abiraterone. Patients and methods: mCRPC patients candidate to receive abiraterone were enrolled in the present retrospective pharmacogenetic study. Based on a literature selection, CYP17A1 rs2486758 (c.-362T &gt; C) was selected and analysed by real-time PCR on genomic DNA extracted from whole blood. Univariate analysis was performed to test the association between the&nbsp;SNP and treatment-related clinical outcomes. Results: Sixty mCRPC patients were enrolled in the present study. Patients carrying the mutant CYP17A1 c.-362CT/CC genotypes showed a shorter median progression-free survival (PFS) and prostate-specific antigen-PFS (PSA-PFS) compared to patients carrying the TT genotype (10.7 vs 14.2&nbsp;months and 8 vs 16&nbsp;months, respectively;&nbsp;p = 0.04). No association between the selected SNP and the overall survival was found. Conclusions: These findings suggest an association between CYP17A1 c.-362T&gt;C&nbsp;polymorphism and poorer clinical outcome with abiraterone for mCRPC patients. However, further validations on larger cohort of patients are needed to confirm its role as a predictive biomarker for abiraterone resistance

Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds

Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38, P=1.03 × 10−4), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35, P=9.08 × 10−5), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component

Characterization of childhood trauma, hippocampal mediation and Cannabis use in a large dataset of psychosis and non-psychosis individuals

Background Cannabis use (CA) and childhood trauma (CT) independently increase the risk of earlier psychosis onset; but their interaction in relation to psychosis risk and association with endocannabinoid-receptor rich brain regions, i.e. the hippocampus (HP), remains unclear. The objective was to determine whether lower age of psychosis onset (AgePsyOnset) is associated with CA and CT through mediation by the HP volumes, and genetic risk, as measured by schizophrenia polygene scores (SZ-PGRS). Methods Cross-sectional, case-control, multicenter sample from 5 metropolitan US regions. Participants (n = 1185) included 397 controls not affected by psychosis (HC); 209 participants with bipolar disorder type-1; 279 with schizoaffective disorder; and 300 with schizophrenia (DSM IV-TR). CT was assessed using the Childhood Trauma Questionnaire (CTQ); CA was assessed by self-reports and trained clinical interviewers. Assessment included neuroimaging, symptomatology, cognition and calculation of the SZ polygenic risk score (SZ-PGRS). Results In survival analysis, CT and CA exposure interact to be associated with lower AgePsyOnset. At high CT or CA, CT or CA are individually sufficient to affect AgePsyOnset. CT relation with AgePsyOnset is mediated in part by the HP in CA users before AgePsyOnset. CA before AgePsyOnset is associated with higher SZ-PGRS and correlated with younger age at CA usage. Discussion CA and CT interact to increase risk when moderate; while severe CT and/or CA abuse/dependence are each sufficient to affect AgePsyOnset, indicating a ceiling effect. Probands with/out CA before AgePsyOnset differ on biological variables, suggesting divergent pathways to psychosis

Integrating Liquid Biopsy and Radiomics to Monitor Clonal Heterogeneity of EGFR-Positive Non-Small Cell Lung Cancer

Background: EGFR-positive Non-small Cell Lung Cancer (NSCLC) is a dynamic entity and tumor progression and resistance to tyrosine kinase inhibitors (TKIs) arise from the accumulation, over time and across different disease sites, of subclonal genetic mutations. For instance, the occurrence of EGFR T790M is associated with resistance to gefitinib, erlotinib, and afatinib, while EGFR C797S causes osimertinib to lose activity. Sensitive technologies as radiomics and liquid biopsy have great potential to monitor tumor heterogeneity since they are both minimally invasive, easy to perform, and can be repeated over patient’s follow-up, enabling the extraction of valuable information. Yet, to date, there are no reported cases associating liquid biopsy and radiomics during treatment. Case presentation: In this case series, seven patients with metastatic EGFR-positive NSCLC have been monitored during target therapy. Plasma-derived cell free DNA (cfDNA) was analyzed by a digital droplet PCR (ddPCR), while radiomic analyses were performed using the validated LifeX® software on computed tomography (CT)-images. The dynamics of EGFR mutations in cfDNA was compared with that of radiomic features. Then, for each EGFR mutation, a radiomic signature was defines as the sum of the most predictive features, weighted by their corresponding regression coefficients for the least absolute shrinkage and selection operator (LASSO) model. The receiver operating characteristic (ROC) curves were computed to estimate their diagnostic performance. The signatures achieved promising performance on predicting the presence of EGFR mutations (R2 = 0.447, p &lt;0.001 EGFR activating mutations R2 = 0.301, p = 0.003 for T790M; and R2 = 0.354, p = 0.001 for activating plus resistance mutations), confirmed by ROC analysis. Conclusion: To our knowledge, these are the first cases to highlight a potentially promising strategy to detect clonal heterogeneity and ultimately identify patients at risk of progression during treatment. Together, radiomics and liquid biopsy could detect the appearance of new mutations and therefore suggest new therapeutic management

expression of tk1 and cdk9 in plasma derived exosomes is associated with clinical response to cdk4 6 inhibitors in breast cancer

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