Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Methanol Synthesis with Steel Mill Gases: Performance Investigations in an On-Site Technical Center

An on-site laboratory with direct access to cleaned and conditioned steel mill gases was recently put into operation. The long-term performance and stability of Clariant's MegaMax®800 methanol synthesis catalyst utilizing steel mill gases is currently being investigated. First test results revealed that in order to investigate deactivation mechanisms arising from particular properties of the cleaned steel mill gases, the overlaying effect of thermal deactivation of the catalyst has to be minimized.     

Discharge coefficient for vertical sluice gate under submerged condition using contraction and energy loss coefficients

A novel method is suggested for the determination of flow discharge in vertical sluice gates with considerably small bias. First, in order to derive an equation for the discharge coefficient, energy-momentum equations are implemented to define the physical realization of the phenomenon. Afterward, the discharge coefficient is presented in terms of contraction and energy loss coefficients. Subsequently, discharge coefficient, contraction, and energy loss coefficients were determined through an implicit optimization technique on the data. Data analysis illustrated that there is a meaningful power relationship between the contraction and energy loss coefficients. Thereafter, dimensional analysis is performed and an explicit best-fit regression equation is developed for defining the energy loss coefficient. The obtained equations for contraction and energy loss coefficients were then used in the computation of the discharge coefficient and determination of the flow discharge in the vertical sluice gate. The performance of the developed approach is validated against the selected benchmarks existing in the literature.     

Hereditary Prostate Cancer: Genes Related,Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.     

Flow conditioning system for tri-sonic high pressure aerothermal testing

Blowdown testing offers a cost-effective experimental tool to replicate the aerothermal conditions in numerous high speed systems. The wind tunnel must replicate the inlet operating conditions, while the spatial and time dependent inlet flow conditions should be assessed carefully. This paper provides a design methodology and rules that ensure adequate flow conditioning in high inlet pressure wind tunnels suitable for subsonic and supersonic operation with mass-flow limits ranging from 1 kg/s to 25 kg/s, Reynolds numbers from 10³ (1/m) to 4x10⁷ (1/m), and Mach numbers from 0.01 up to 6. The quality of the proposed flow conditioning system was evaluated using stereo PIV measurements combined with hotwire, Pitot probe, and total flow temperature traverses.     

Rapid Hormetic Responses of Photosystem II Photochemistry of Clary Sage to Cadmium Exposure

Five-day exposure of clary sage (Salvia sclarea L.) to 100 μM cadmium (Cd) in hydroponics was sufficient to increase Cd concentrations significantly in roots and aboveground parts and affect negatively whole plant levels of calcium (Ca) and magnesium (Mg), since Cd competes for Ca channels, while reduced Mg concentrations are associated with increased Cd tolerance. Total zinc (Zn), copper (Cu), and iron (Fe) uptake increased but their translocation to the aboveground parts decreased. Despite the substantial levels of Cd in leaves, without any observed defects on chloroplast ultrastructure, an enhanced photosystem II (PSII) efficiency was observed, with a higher fraction of absorbed light energy to be directed to photochemistry (Φ_PSΙΙ). The concomitant increase in the photoprotective mechanism of non-photochemical quenching of photosynthesis (NPQ) resulted in an important decrease in the dissipated non-regulated energy (Φ_NO), modifying the homeostasis of reactive oxygen species (ROS), through a decreased singlet oxygen (¹O₂) formation. A basal ROS level was detected in control plant leaves for optimal growth, while a low increased level of ROS under 5 days Cd exposure seemed to be beneficial for triggering defense responses, and a high level of ROS out of the boundaries (8 days Cd exposure), was harmful to plants. Thus, when clary sage was exposed to Cd for a short period, tolerance mechanisms were triggered. However, exposure to a combination of Cd and high light or to Cd alone (8 days) resulted in an inhibition of PSII functionality, indicating Cd toxicity. Thus, the rapid activation of PSII functionality at short time exposure and the inhibition at longer duration suggests a hormetic response and describes these effects in terms of “adaptive response” and “toxicity”, respectively.     

FPGA互连测试中的反馈桥接故障覆盖问题

现场可编程门阵列(FPGA)内部资源众多,其中互连资源出现故障的概率远远高于片内其他资源,而在以往许多互连测试研究中,所生成的测试配置存在无法覆盖反馈桥接故障的难题,所以较难有测试配置实现故障列表的100%覆盖。因此通过约束桥接故障只发生在单个查找表(LUT)内的信号线上,并结合单项函数,对反馈桥接故障模型进行优化改进,从根本上解决难题；然后对优化后的反馈桥接故障设置相应的约束条件,再使用布尔可满足性理论(SAT)生成满足约束条件的测试配置。采用优化后的故障模型对ISCAS"89基准电路进行了测试配置生成实验,结果表明生成的测试向量解决了反馈桥接故障的覆盖难题,并且在实现故障列表的100%覆盖下,优化后的故障模型所需要的测试配置数最少。     

Destructive and non-destructive evaluation of concrete for optimum sand to aggregate volume ratio

Aggregates are the biggest contributor to concrete volume and are a crucial parameter in dictating its mechanical properties. As such, a detailed experimental investigation was carried out to evaluate the effect of sand-to-aggregate volume ratio (s/a) on the mechanical properties of concrete utilizing both destructive and non-destructive testing (employing UPV (ultrasonic pulse velocity) measurements). For investigation, standard cylindrical concrete samples were made with different s/a (0.36, 0.40, 0.44, 0.48, 0.52, and 0.56), cement content (340 and 450 kg/m³), water-to-cement ratio (0.45 and 0.50), and maximum aggregate size (12 and 19 mm). The effect of these design parameters on the 7, 14, and 28 d compressive strength, tensile strength, elastic modulus, and UPV of concrete were assessed. The careful analysis demonstrates that aggregate proportions and size need to be optimized for formulating mix designs; optimum ratios of s/a were found to be 0.40 and 0.44 for the maximum aggregate size of 12 and 19 mm, respectively, irrespective of the W/C (water-to-cement) and cement content.     

对于厚度70mm〜140mm焊缝超声检测的讨论

超声检测作为一种面积型缺陷的有效检测方法,被广泛应用在气化炉、除氧器、汽包等的焊缝检测上。随着近年来电厂、化工厂对质量的要求提升,确保焊缝质量就成了生产制造厂的重点。对于这些重型容器,焊缝厚度普遍在70mm~140mm,在这个厚度区间,采取的多道焊接,工艺控制不严很容易产生缺陷。无损检测标准的制定只是简单的对此厚度划分两个区间,并未给出划定此区间的依据。本文通过实际检测气化炉、除氧器、汽包等焊缝来讨论超声检测在厚度70mm?140mm区间的划定依据。