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Carbon Fiber Reinforced Polymer (CFRP) composites have emerged as a major class of structural materials that have a significant potential use as a substitute for metals in aerospace, marine, automotive, and architecture due to their higher-strength-to-weight-ratio. CFRP is well suited for various applications, but their mechanical properties such as 'low-velocity impact resistance' are not well studied. In this study, the low-velocity impact resistance of CFRP woven composite was investigated with the help of Charpy impact tests. The CFRP samples were tested at room temperature (22°C) and at low temperature (-20°C). The experimental results indicated about 10% drop in energy-absorbing capability of CFRP samples at low temperatures in comparison to room temperature. The experimental results obtained for the room temperature were validated through finite element simulations using ANSYS® Workbench Explicit Dynamics. The mesh sensitivity analysis was performed to improve the accuracy of the finite element model. The numerical results helped to narrow down on the CFRP material properties that changed with temperature drop. It was found at -20°C, orthotropic Elasticity (Young's moduli in three mutually perpendicular directions) increases for CFRP woven composite as compared to room temperature (22°C), however the CFRP become brittle and there is a significant drop in their toughness. The current outcomes are useful for applications using CFRP under impact loading at low temperatures. [ABSTRACT FROM AUTHOR]

This note presents a vapor-based seeding apparatus, named the external alkali seeding instrument (EASI), which is designed to introduce alkali metal vapors into experimental facilities without using precursors or large auxiliary equipment. The device vaporizes small amounts of alkali metals, potassium in this work, which are then carried away by an inert gas. In a benchtop flow cell, carrier gas flow rate (6– 200 cm 3 / s ) and device temperature (150– 250 ∘ C ) most strongly affected potassium-vapor concentrations. Higher values of either quantity lead to increased potassium-vapor concentrations. When using the EASI to seed a shock tube experiment, vapor-phase potassium was detected immediately after the incident and reflected shockwaves using a laser absorption diagnostic. Mole fraction time histories stay within a factor of 2 over the test time as compared with those from a precursor-based seeding approach, which may span multiple orders of magnitude. This suggests potassium is nearly homogeneously distributed throughout the test gas. This design can be extended to other low-vapor-pressure elements, such as other alkalis or sulfur, with minimal modifications. The EASI simplifies seeding for laboratory experiments targeting potassium and other alkali metals—enabling advances in fundamental spectroscopy, diagnostic development, and chemical kinetics. [ABSTRACT FROM AUTHOR]

The Ugandan Anti-Homosexuality Bill of October 2009 caused an international outcry and sparked intense debate in the local and international media. Particularly contentious was its proposal to impose the death penalty for acts of 'aggravated homosexuality'. Through a quantitative content analysis of 176 items from two main daily newspapers, the government-owned New Vision and the privately-owned Daily Monitor, over the period October 2009-June 2010, combined with qualitative interviews with human rights defenders in Uganda, this study explores attempts made by local human rights advocates to influence the media's coverage of the Bill and the extent to which these attempts were successful. The study finds that while there are significant differences between the frequency of reporting on the Bill in the two newspapers, both papers devoted little editorial space to the public health and human rights concerns put forward by local human rights organizations. Despite Uganda's recent and often lauded history of openly addressing HIV/AIDS, human right organizations' attempts to highlight the Bill's potentially adverse effects on the country's ability to tackle the epidemic effectively were only partially successful and, interestingly, awarded much less attention than the potential human rights implications of the proposed change in legislation. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of proliferation in node-negative breast cancer, either in the form of Ki67 or as the main common denominator in different gene expression profiles, has become clearer over the last years. The St Gallen guidelines recommend the use of Ki67 to distinguish between the luminal A and luminal B-like subtypes. Also, data have shown that Ki67 can separate patients with histological grade 2 into two groups with significant difference in prognosis. However, there is no consensus on the methodology for Ki67, and genetic profiling is still expensive. Previous studies have shown a strong prognostic value of the mitosis- and late G2-specific proliferation factors Phosphohistone H3 (PPH3) and mitotic activity index (MAI) in node-negative breast cancer. The present study was set up to study the value of these two factors compared to Ki67, alone and combined. Material and methods: In 221 consecutive premenopausal node-negative breast cancer patients, of whom 87% had received no adjuvant medical treatment, PPH3 was assessed on tissue microarray (TMA), and MAI on whole sections. TMA-data on Ki67 was already available. Cut-offs for MAI, PPH3, and Ki67 were predefined. Cox proportional hazards regression was used to model the impact of the prognostic factors on distant disease-free survival (DDFS). The follow-up was restricted to the first 5 years after diagnosis, a time period during which 34 patients developed distant recurrences. Results: In univariate analysis the strongest prognostic proliferation factor for DDFS was MAI (HR 5.1 95%CI 2.4-11, p < 0.0001), followed by PPH3 (HR 3.7 95%CI 1.8-7.5, p < 0.0001), and Ki67 (HR 2.7 95%CI 1.3-5.4, p = 0.005). ER, PR, HER2, histological grade, and age were also significant prognostic factors. When adding PPH3 to MAI, the prognostic value of MAI was strengthened (HR 6.3 95%CI 2.6-15, p < 0.0001). This corresponded to a 5-year DDFS of 95% for the 57% of the patients who were low risk (95%CI 88-98%), and 71% (95%CI 60-80%) for the 43% high risk patients. Ki67 did however not add any prognostic value to MAI. When stratifying for ER status and histological grade, MAI was a significant prognostic factor in the ER+ patients (HR 15 95%CI 5.1-41, p < 0.0001), as well as in patients with histological grade 2 (HR 11 95%CI 3.2-38, p < 0.0001). In multivariate analysis including HER2, age, and ER, and one proliferation factor at a time, MAI was the only proliferation factor that added independent prognostic value (HR 3.6 95%CI 1.1-11, p = 0.028). Discussion: The present study on node-negative breast cancer patients confirms the strong prognostic value of the proliferation factors MAI and PPH3, in all patients, and more specifically in ER+ patients, and patients with histological grade 2. The study also suggests that by combining two proliferation factors, MAI and PPH3, an even stronger prognostic value is found. Ki67 however, did not add any prognostic value to MAI. Taken together, MAI and PPH3, alone and in combination may be helpful for prognostic considerations and for selection of adjuvant medical treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to validate the prognostic value of a previously defined index (CAGE), combining proliferation (Cyclin A), histological grade, and estrogen receptor (ER) in different subsets of primary breast cancer patients. In the present study, Ki67 was included in the index (KiGE) instead of cyclin A, since it is the generally accepted proliferation marker in clinical routine. Patients and methods: 1,854 chemo-naive patients with primary breast cancer were included. The low KiGE group consisted of histological grade 1 cases and grade 2 cases which were ER-positive and had low Ki67 expression. High KiGE consisted of all other cases. Results: The KiGE index separated patients into groups with different prognosis. In multivariate analysis, KiGE was significantly associated with disease-free survival, when adjusted for age at diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95% confidence interval: 2.6-4.7, P<0.0001). Conclusion: We have validated a prognostic index based on proliferation (Ki67), histological grade and ER, for identification of a low-risk group of patients with N0/N1 primary breast cancer. For this low-risk group, with a five-year distant disease-free survival of 92%, adjuvant chemotherapy will have limited effect and may be avoided. The KiGE index, based on clinically used factors, may challenge the more expensive gene expression profiles. [ABSTRACT FROM AUTHOR]

Clinical syndromes associated with progressive supranuclear palsy-tau pathology now include progressive supranuclear palsy-parkinsonism (PSP-P), in addition to classic Richardson's syndrome (RS) and pure akinesia with gait freezing (PAGF). Although pathological heterogeneity of progressive supranuclear palsy (PSP) has also been established, attempts to correlate this with clinical findings have only rarely provided conclusive results. The aim of this study was to investigate whether regional variations in the types of tau lesions or differences in overall tau load may explain the clinical differences between the RS, PSP-P and PAGF. Quantitative tau pathology assessment was performed in 17 brain regions in 42 cases of pathologically diagnosed PSP (22 RS, 14 PSP-P and 6 PAGF). Neurofibrillary tangles, tufted astrocytes, coiled bodies and thread pathology were quantitated and a grading system was developed separately for each region. Using these grades the overall tau load was calculated in each case. To establish a simplified system for grading the severity of tau pathology, all data were explored to identify the minimum number of regions that satisfactorily summarized the overall tau severity. The subthalamic nucleus, substantia nigra and globus pallidus were consistently the regions most severely affected by tau pathology. The mean severity in all regions of the RS group was higher than in PSP-P and PAGF, and the overall tau load was significantly higher in RS than in PSP-P (P = 0.002). Using only the grade of coiled body + thread lesions in the substantia nigra, caudate and dentate nucleus, a reliable and repeatable 12-tiered grading system was established (PSP-tau score: 0, mild tau pathology, restricted distribution; >7, severe, widespread tau pathology). PSP-tau score was negatively correlated with disease duration (Spearman's rho -0.36, P = 0.028) and time from disease onset to first fall (Spearman's rho -0.49, P = 0.003). The PSP-tau score in PSP-P (median 3, range 0-5) was significantly lower than in RS (median 5, range 2-10, Mann-Whitney U, P < 0.001). The two cases carrying the tau-H2 protective allele had the two lowest PSP-tau scores. We have identified significant pathological differences between the major clinical syndromes associated with PSP-tau pathology and the restricted, mild tau pathology in PSP-P supports its clinical distinction from RS. The grading system we have developed provides an easy-to-use and sensitive tool for the morphological assessment of PSP-tau pathology and allows for consideration of the clinical diversity that is known to occur in PSP. [ABSTRACT FROM AUTHOR]

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) known as Lewy body dementias have overlapping clinical and neuropathological features. Neuropathology in both includes combination of Lewy body and Alzheimer's disease (AD) pathology. Cerebral amyloid angiopathy (CAA), often seen in AD, is increasingly recognized for its association with dementia. Aims: This study investigated clinical and neuropathological differences between DLB and PDD. Methods: 52 PDD and 16 DLB cases from the Queen Square Brain Bank (QSBB) for Neurological disorders were included. Comprehensive clinical data of motor and cognitive features were obtained from medical records. Neuropathological assessment included examination of CAA, Lewy body and AD pathology. Results: CAA was more common in DLB than in PDD (P = 0.003). The severity of CAA was greater in DLB than in PDD (P = 0.009), with significantly higher CAA scores in the parietal lobe (P = 0.043), and the occipital lobe (P = 0.008), in DLB than in PDD. The highest CAA scores were observed in cases with APOE ε4/4 and ε2/4. Survival analysis showed worse prognosis in DLB, as DLB reached each clinical milestone sooner than PDD. Absence of dyskinesia in DLB is linked to the significantly lower lifetime cumulative dose of levodopa in comparison with PDD. Conclusions: This is the first study which identified prominent concurrent CAA pathology as a pathological substrate of DLB. More prominent CAA and rapid disease progression as measured by clinical milestones distinguish DLB from PDD. [ABSTRACT FROM AUTHOR]

Aims: There is evidence that accumulation of α‐synuclein (α‐syn) in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) results from impaired removal of α‐syn rather than its overproduction. Kallikrein‐6 (KLK6), calpain‐1 (CAPN1) and cathepsin‐D (CTSD) are among a small number of proteases that cleave α‐syn and are dysregulated in PD and DLB. Our aim in this study was to determine whether protease activity is altered in another α‐synucleinopathy, multiple system atrophy (MSA), and might thereby modulate the regional distribution of α‐syn accumulation. Methods: mRNA and protein level and/or activity of KLK6, CAPN1 and CTSD were measured and assessed in relation to α‐syn load in multiple brain regions (posterior frontal cortex, caudate nucleus, putamen, occipital cortex, pontine base and cerebellar white matter), in MSA (n = 20) and age‐matched postmortem control tissue (n = 20). Results: CTSD activity was elevated in MSA in the pontine base and cerebellar white matter. KLK6 and CAPN1 levels were elevated in MSA in the putamen and cerebellar white matter. However, the activity or level of these proteolytic enzymes did not correlate with the regional distribution of α‐syn. Conclusions: Accumulation of α‐syn in MSA is not due to reduced activity of the proteases we have studied. We suggest that their upregulation is likely to be a compensatory response to increased α‐syn in MSA. [ABSTRACT FROM AUTHOR]

Abstract: Using conventional MRI the subthalamic nucleus (STN) is not clearly defined. Our objective was to define the anatomy of the STN using 9.4T MRI of post mortem tissue with histological validation. Spin-echo (SE) and 3D gradient-echo (GE) images were obtained at 9.4T in 8 post mortem tissue blocks and compared directly with corresponding histological slides prepared with Luxol Fast Blue/Cresyl Violet (LFB/CV) in 4 cases and Perl stain in 3. The variability of the STN anatomy was studied using internal reference points. The anatomy of the STN and surrounding structures was demonstrated in all three anatomical planes using 9.4T MR images in concordance with LFB/CV stained histological sections. Signal hypointensity was seen in 6/8 cases in the anterior and medial STN that corresponded with regions of more intense Perl staining. There was significant variability in the volume, shape and location of the borders of the STN. Using 9.4T MRI, the internal signal characteristics and borders of the STN are clearly defined and significant anatomical variability is apparent. Direct visualisation of the STN is possible using high field MRI and this is particularly relevant, given its anatomical variability, for planning deep brain stimulation. [Copyright &y& Elsevier]

Background. HER2 is a treatment predictive factor for the effect of trastuzumab and associated with poor prognosis in breast cancer. The analysis of HER2 must be performed with good quality, with regard to both the immunohistochemical (IHC) and in situ hybridization (ISH) analysis. Material and methods. A tissue microarray (TMA) including 11 breast cancer samples was sent twice (once in 2005 and again in 2006) to 24 pathology departments in Sweden. A questionnaire was also sent to the departments in 2006. Results. With IHC, all departments reported the same results (0/1+ vs. 2+ vs. 3 + ) for three (2005) and six samples (2006). The mean kappa-value increased from 0.67 to 0.77, indicating a good reproducibility at both occasions. With fluorescence-ISH (FISH), the 11 departments using this technique reported the same results (amplified vs. normal) for nine (2005) and ten samples (2006). The mean kappa-value showed very good reproducibility both 2005 and 2006 (0.92 and 0.96, respectively). Based on the answers from the participating departments, the questionnaire revealed that 31% of primary breast cancer diagnosed in 2006 (n = 5 043) were 2 + /3+. FISH analysis of 2+ confirmed 12% of the samples to be amplified. The corresponding figure for 3 + was 90%. In total, 14.3% of the samples were HER2 positive (2+ and amplified, or 3 + ). Discussion. The results obtained in this study indicate that the reproducibility for HER2 analysis is good (IHC) and very good (FISH) between the pathology departments in Sweden using TMA-based tumor samples. In 2006, 14.3% of invasive breast cancers were HER2 positive. [ABSTRACT FROM AUTHOR]

Pathological inclusions containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in the tauopathies, which include Alzheimer's disease, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Tau isoform composition and cellular and regional distribution as well as morphology of these inclusions vary in each disorder. Recently, several pathological missense and exon 10 splice-donor site mutations of the tau gene were iden-tified in FTDP-17. Exon 10 codes for the second of four microtubule-binding repeat domains. The splice-site mutations result in increased inclusion of exon 10 which causes a relative increase in tau isoforms containing four microtubule-binding repeat domains over those containing three repeat domains. This could be a central aetiological mechanism in FTDP-17 and, perhaps, other related tauopathies. We have investigated changes in the ratio and distribution of three-repeat and four-repeat tau in the different tauopathies as a basis of the phenotypic range of these disorders and the selective vulnerability of different subsets of neurones. In this study, we have developed two monoclonal antibodies, RD3 and RD4 that effectively distinguish these closely related tau isoforms. These new isoform-specific antibodies are useful tools for analysing tau isoform expression and distribution as well as pathological changes in the human brain. [ABSTRACT FROM AUTHOR]

The use of dried blood spots (DBS) in preclinical studies has seen an enormous increase over the past two years. Despite its positive impact on the 3Rs (reduce, replace and refine), its uptake in exploratory drug discovery has been limited due mainly to protracted method development time in bioanalysis but also the need for small volumes (<20 µL) to be sampled manually. Automatic blood sampling technology such as the DiLab® AccuSampler® is widely used in drug discovery to facilitate exploratory rodent-based pharmacokinetic and pharmacokinetic/pharmacodynamic studies with minimal animal handling. Propranolol was orally administered to a Han-Wistar rat attached to either a standard DiLab® AccuSampler® or a retrofitted unit designed to directly collect the DBS samples. In all, 50 or 20 µL blood samples were then collected via the standard or retrofitted unit, respectively, at six timepoints over a 7 h period. After drying and storage the DBS samples were analysed for propranolol via liquid chromatography-mass spectrometry. In this report we demonstrate that a standard DiLab® AccuSampler® can be easily retrofitted to facilitate automatic dried blood spot sampling and that time--concentration data generated from these samples are equivalent to that from manually spotted samples. [ABSTRACT FROM AUTHOR]