791 research outputs found
Процес «Спілки Визволення України» та зростання селянського опору в умовах суцільної колективізації
Мета даної роботи полягає у з’ясуванні механізму використання матеріалів
процесу «СВУ» на території сучасної Чернігівщини, пропагандистських цілях та
реакції на нього з боку як населення, лояльного до влади, так і селян, які вперто
чинили опір політиці колективізації
Nuclear DDX3 expression predicts poor outcome in colorectal and breast cancer
Purpose: DEAD box protein 3 (DDX3) is an RNA helicase with oncogenic properties that shuttles between the cytoplasm and nucleus. The majority of DDX3 is found in the cytoplasm, but a subset of tumors has distinct nuclear DDX3 localization of yet unknown biological significance. This study aimed to evaluate the significance of and mechanisms behind nuclear DDX3 expression in colorectal and breast cancer.
Methods: Expression of nuclear DDX3 and the nuclear exporter chromosome region maintenance 1 (CRM1) was evaluated by immunohistochemistry in 304 colorectal and 292 breast cancer patient samples. Correlations between the subcellular localization of DDX3 and CRM1 and the difference in overall survival between patients with and without nuclear DDX3 were studied. In addition, DDX3 mutants were created for in vitro evaluation of the mechanism behind nuclear retention of DDX3.
Results: DDX3 was present in the nucleus of 35% of colorectal and 48% of breast cancer patient samples and was particularly strong in the nucleolus. Nuclear DDX3 correlated with worse overall survival in both colorectal (hazard ratio [HR] 2.34, P<0.001) and breast cancer (HR 2.39, P=0.004) patients. Colorectal cancers with nuclear DDX3 expression more often had cytoplasmic expression of the nuclear exporter CRM1 (relative risk 1.67, P=0.04). In vitro analysis of DDX3 deletion mutants demonstrated that CRM1-mediated export was most dependent on the N-terminal nuclear export signal.
Conclusion: Overall, we conclude that nuclear DDX3 is partially CRM1-mediated and predicts worse survival in colorectal and breast cancer patients, putting it forward as a target for therapeutic intervention with DDX3 inhibitors under development in these cancer types
Criteria for the differentiation between young and old Onchocerca volvulus filariae
Drugs exist that show long-lasting inhibition of embryogenesis and microfilaria production or macrofilaricidal activity against Onchocerca volvulus. Therefore, the patients have to be followed-up for several years. Clinical drug trials have to be performed in areas with ongoing transmission to assess the efficacy on younger worms. In addition, future vaccine trials may also require demonstrating efficacy against establishment of new worms. For the evaluation of the efficacy, it is necessary to differentiate between older worms, which were exposed to the drug, and younger worms newly acquired after drug treatment or vaccination. Here, we describe criteria for the differentiation between young and old filariae based on histological studies of worms with a known age from travellers, or from children, or patients living in areas with interrupted transmission in Burkina Faso, Ghana or Uganda. Older worms were larger and presented degenerated tissues. Gomori's iron stain showed that the worms accumulated more iron with increasing age, first in the gut and later in other organs. Using an antibody against O. volvulus lysosomal aspartic protease, the gut of young worms was stained only weakly; whereas, it was stronger labelled in older worms, accompanied by additional staining of hypodermis and epithelia. Using morphological and immunohistological criteria, it was possible to differentiate young (1–3 years old) from older females and to identify young males
Differential systems associated with tableaux over Lie algebras
We give an account of the construction of exterior differential systems based
on the notion of tableaux over Lie algebras as developed in [Comm. Anal. Geom
14 (2006), 475-496; math.DG/0412169]. The definition of a tableau over a Lie
algebra is revisited and extended in the light of the formalism of the Spencer
cohomology; the question of involutiveness for the associated systems and their
prolongations is addressed; examples are discussed.Comment: 16 pages; to appear in: "Symmetries and Overdetermined Systems of
Partial Differential Equations" (M. Eastwood and W. Miller, Jr., eds.), IMA
Volumes in Mathematics and Its Applications, Springer-Verlag, New Yor
Validation of skeletal muscle mass assessment at the level of the third cervical vertebra in patients with head and neck cancer
Background: Low skeletal muscle mass (SMM) is associated with adverse outcomes. SMM is often assessed at the third lumbar vertebra (L3) on abdominal imaging. Abdominal imaging is not routinely performed in patients with head and neck cancer (HNC). We aim to validate SMM measurement at the level of the third cervical vertebra (C3) on head and neck imaging. Material and methods: Patients with pre-treatment whole-body computed tomography (CT) between 2010 and 2018 were included. Cross-sectional muscle area (CSMA) was manually delineated at the level of C3 and L3. Correlation coefficients and intraclass correlation coefficients (ICCs) were calculated. Cohen's kappa was used to assess the reliability of identifying a patient with low SMM. Results: Two hundred patients were included. Correlation between CSMA at the level of C3 and L3 was good (r = 0.75, p < 0.01). Using a multivariate formula to estimate CSMA at L3, including gender, age, and weight, correlation improved (r = 0.82, p < 0.01). The agreement between estimated and actual CSMA at L3 was good (ICC 0.78, p < 0.01). There was moderate agreement in the identification of patients with low SMM based on the estimated lumbar skeletal muscle mass index (LSMI) and actual LSMI (Cohen's κ: 0.57, 95%CI 0.45–0.69). Conclusions: CSMA at C3 correlates well with CSMA at L3. There is moderate agreement in the identification of patients with low SMM based on the estimated lumbar SMI (based on measurement at C3) and actual LSMI
Case Report: Imaging immune checkpoint inhibitor-induced yin-yang effects in the brain
BackgroundTreatment with immune checkpoint inhibitors (ICI) can induce durable responses in cancer patients, but it is commonly associated with serious immune-related side effects. Both effects are suggested to be mediated by CD8+ T-cell infiltration. Whole body CD8+ T-cell distribution can be visualized by PET imaging of a 89Zr-labeled anti-humanCD8a minibody, currently investigated in a phase 2b trial.Main bodyAn adult patient diagnosed with metastatic melanoma developed ICI-related hypophysitis after two courses of combined immunotherapy (ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) at 3 weeks interval). On a [89Zr]Zr-crefmirlimab berdoxam PET/CT scan, made 8 days before clinical symptoms occurred, increased CD8+ T-cell infiltration in the pituitary gland was detected. Simultaneously, tracer uptake in a cerebral metastasis was increased, indicating ICI-induced tumor infiltration by CD8+ T-cells.ConclusionsThe observations in this case report underscore the role of CD8+ T-cell in non-tumor tissues in ICI-related toxicity. In addition, it illustrates a potential role for molecular imaging by PET/CT for investigation and monitoring of ICI-induced effects
Variability in fluvial suspended and streambed sediment phosphorus fractions among small agricultural streams
Agriculture is a major source of sediment and particulate phosphorus (P) inputs to freshwaters. Distinguishing between P fractions in sediment can aid in understanding its eutrophication risk. Although streams and rivers are important parts of the P cycle in agricultural catchments, streambed sediment and especially fluvial suspended sediment (FSS) and its P fractions are less studied. To address this knowledge gap, seasonal variations in FSS P fractions and their relation to water quality and streambed sediment were examined in three Swedish agricultural headwater catchments over 2 yr. Sequential fractionation was used to characterize P fractions in both streambed sediment and FSS. All catchments had similar annual P losses (0.4-0.8 kg ha(-1)), suspended solids (124-183 mg L-1), and FSS total P concentrations (1.15-1.19 mg g(-1)). However, distribution of P fractions and the dominant P fractions in FSS differed among catchments (p < .05), which was most likely dependent on differences in catchment geology, clay content, external P sources, and flow conditions. The most prominent seasonal pattern in all catchments was found for iron-bound P, with high concentrations during low summer flows and low concentrations during winter high flows. Streambed sediment P fractions were in the same concentration ranges as in FSS, and the distribution of the fractions differed between catchments. This study highlights the need to quantify P fractions, not just total P in FSS, to obtain a more complete understanding of the eutrophication risk posed by agricultural sediment losses
Homeomorphic Embedding for Online Termination of Symbolic Methods
Well-quasi orders in general, and homeomorphic embedding in particular, have gained popularity to ensure the termination of techniques for program analysis, specialisation, transformation, and verification. In this paper we survey and discuss this use of homeomorphic embedding and clarify the advantages of such an approach over one using well-founded orders. We also discuss various extensions of the homeomorphic embedding relation. We conclude with a study of homeomorphic embedding in the context of metaprogramming, presenting some new (positive and negative) results and open problems
Periprostatic fat measured on computed tomography as a marker for prostate cancer aggressiveness
Contains fulltext :
89797.pdf (publisher's version ) (Closed access)OBJECTIVE: Several reports found that obesity was associated with prostate cancer (PC) aggressiveness among men treated with radical prostatectomy or radiotherapy. Studies concerning this issue have basically relied on body mass index (BMI), as a marker for general obesity. Because visceral fat is the most metabolic active fat, we sought to evaluate if periprostatic fat measured on a computed tomography (CT) is a better marker than BMI to predict PC aggressiveness in a Dutch population who underwent brachytherapy for localized PC. PATIENTS AND METHODS: Of the 902 patients who underwent brachytherapy, 725 CT scans were available. Subcutaneous fat thickness (CFT), periprostatic fat area (cm(2)) and fat-density (%) were determined on the CT scan. Patients were stratified into three groups: 75 percentile of the fat-density. Associations between the three fat-density subgroups and BMI and PC aggressiveness were examined. RESULTS: 237 patients were classified as having normal weight (37.2%), 320 as overweight (50.2%) and 80 as obese (12.6%). There was a strong significant association between BMI and fat-density and CFT. The strongest correlation was seen between BMI and CFT (Pearson r coefficient = 0.71). Logistic regression analysis revealed no statistically significant association between the different fat measurements and the risk of having a high-risk disease. CONCLUSIONS: Periprostatic fat and fat-density as measured with CT were not correlated with PC aggressiveness in patients receiving brachytherapy. However, 31% of the patients with a normal BMI had a fat-density of >75 percentile of the periprostatic fat-density.01 december 201
The ternary invariant differential operators acting on the spaces of weighted densities
Over n-dimensional manifolds, I classify ternary differential operators
acting on the spaces of weighted densities and invariant with respect to the
Lie algebra of vector fields. For n=1, some of these operators can be expressed
in terms of the de Rham exterior differential, the Poisson bracket, the Grozman
operator and the Feigin-Fuchs anti-symmetric operators; four of the operators
are new, up to dualizations and permutations. For n>1, I list multidimensional
conformal tranvectors, i.e.,operators acting on the spaces of weighted
densities and invariant with respect to o(p+1,q+1), where p+q=n. Except for the
scalar operator, these conformally invariant operators are not invariant with
respect to the whole Lie algebra of vector fields.Comment: 13 pages, no figures, to appear in Theor. Math. Phy
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