Molecular Features and Clinical Management of Hereditary Gynecological Cancers

Hereditary gynecological cancers are caused by several inherited genes. Tumors that arise in the female reproductive system, such as ovaries and the uterus, overlap with hereditary cancers. Several hereditary cancer-related genes are important because they might lead to therapeutic targets. Treatment of hereditary cancers should be updated in line with the advent of various new methods of evaluation. Next-generation sequencing has led to rapid, economical genetic analyses that have prompted a concomitant and significant paradigm shift with respect to hereditary cancers. Molecular tumor profiling is an epochal method for determining therapeutic targets. Clinical treatment strategies are now being designed based on biomarkers based on tumor profiling. Furthermore, the National Comprehensive Cancer Network (NCCN) guidelines significantly changed the genetic testing process in 2020 to initially consider multi-gene panel (MGP) evaluation. Here, we reviewed the molecular features and clinical management of hereditary gynecological malignancies, such as hereditary breast and ovarian cancer (HBOC), and Lynch, Li–Fraumeni, Cowden, and Peutz–Jeghers syndromes. We also reviewed cancer-susceptible genes revealed by MGP tests.     

Planar‐Chiral Cyclopentadienyl‐Ruthenium‐Catalyzed Regio‐ and Enantioselective Asymmetric Allylic Alkylation of Silyl Enolates under Unusually Mild Conditions

We report the asymmetric allylic alkylation of allylic chlorides with silyl enolates as a carbon nucleophile using a planar‐chiral cyclopentadienyl‐ruthenium (Cp′Ru) catalyst. The reaction proceeds under unusually mild conditions to give the desired branched products with complete regioselectivity and high enantioselectivity, and reactive functional groups, such as aldehyde, can be tolerated. In this reaction system, Cp′Ru plays an important role in activating both silyl enolate and allylic chloride.

     

Monte Carlo criticality analysis under material distribution uncertainty

Analysis framework under material distribution uncertainty is not yet established for the Monte Carlo (MC) criticality calculation of continuously mixed media formed via molten core concrete interaction. To approach this issue, one group cross-sections have specifically been prepared for burned fuel, stainless steel and concrete, and the effect of spatially continuous variation of volume fractions is inspected. Trigonometric functions and randomized Weierstrass functions (RWFs) are utilized to represent the spatially continuous variation. Here, trigonometric functions enable the amount of each material to be exactly preserved, and RWF is a randomized trigonometric series that can be generated within specified upper and lower bounds. With these functions, one can assess the influence of indeterminate material distribution. MC particle transport is conducted using the delta-tracking. Numerical results indicate that the effective multiplication factor (k_eff) under RWF variation can depart significantly from the k_eff of a reference uniform medium. These numerical results also show that the deterministic modeling of spatial variation provides a bound measure for extreme results from random realizations.     

Brownian bridge and statistical error estimation in Monte Carlo reactor calculation

Brownian bridge (BB) is an effective vehicle in processing an output series in Monte Carlo (MC) simulation. However, most estimators based on BB cost the capability of on-the-fly monitoring. Here, on-the-fly implies that statistical error can be computed at every generation except some initial generations. In this work, on-the-fly estimation of standard deviation by the way of BB, which maintains a fixed storage size of tallies, has been investigated within a framework of the iterated integration of simulation output (IISO). Numerical tests on the MC power distribution calculation of a pressurized water reactor core reveal that the IISO approach with a relatively few number of integrations performs fairly well on average. The bias of statistical error can be managed to be about 10% or less.     

A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Antihypertensive Effect of Salt-Free Soy Sauce,a New Fermented Seasoning,in Spontaneously Hypertensive Rats

ABSTRACT: In this study, we focused on the antihypertensive effect of newly fermented salt-free soy sauce (SFS) in spontaneously hypertensive rats (SHRs). A 13-wk oral administration of SFS was performed daily in 8- to 21-wk-old SHRs with a dose of 200 mg/kg of body weight/d. The systolic (SBP) and diastolic (DBP) blood pressures were measured for each week during the experimental period. As a result, a significant (P < 0.01) BP lowering effect was observed from the 5th d to the end of the experiment in the SFS group compared with the control group (ΔSBP_21-wk: 27 mmHg, ΔDBP_21-wk: 20 mmHg). In contrast to such substantial effect by SFS intake, angiotensin I-converting enzyme activities in blood and local organs as well as pharmaceutical parameters such as serum Na⁺ or K⁺ level did not show any significant difference between in both SFS and control groups. Vasoconstriction experiment using thoracic aorta rings from 21-wk SHRs provided an interesting result that the rings from the SFS group evoked a >2-fold higher increase in the angiotensin II-stimulated constrictive response compared with the rings from the control group (P = 0.012), which suggested that the SFS-intake would be effective in possessing a higher vessel tone. Practical Application: In this study, we investigated the antihypertensive effect of newly fermented SFS in SHRs. As a result of 13-wk SFS-administration, we found a significant antihypertensive effect of the SFS. This finding strongly demonstrates that the developed SFS would be greatly beneficial for health and useful for health-related industries.     

Batch estimation of statistical errors in the Monte Carlo calculation of local powers

Batch methodology is among the techniques for computing the standard deviation of sample mean and is applicable to any output series from stationary iteration cycles. In the present article, three forms of the methodology are investigated: non-overlapping batch means (NBM), which dates back to Conway (1963), overlapping batch means (OBM) by Meketon and Schmeiser (1984), and standardized time series (STS) by Schruben (1983). In particular, they are applied to the MC calculation of local powers of a pressurized water reactor. The numerical results reveal that the performance of NBM is equivalent to that of OBM, whereas STS performs poorly for small batch sizes. It is also shown that OBM can be improved based on the method of autocovariance bias correction. For a computational condition leading to 0.5–1.5% statistical errors, the improved OBM for a batch size of 10% of the stationary iteration cycle length yields 88–103% of the reference value of standard deviation at tally cells where the sample standard deviation yields 22–36% of the same reference value.     

Development and experimental study of a novel pruning robot

This article presents the development of a timberjack-like pruning robot. The climbing principal is an imitation of the climbing approach of timberjacks in Japan. The robot’s main features include having its center of mass outside the tree, and an innovative climbing strategy fusing straight and spiral climbs. This novel design brings both lightweight and high climbing speed features to the pruning robot. We report our progress in developing the robot, focusing on straight climbing, behavior on uneven surfaces, and pruning.     

Microstructural Changes During Plastic Deformation and Corrosion Properties of Biomedical Co-20Cr-15W-10Ni Alloy Heat-Treated at 873 K

Metallurgical and Materials Transactions A - Microstructural changes were observed during the plastic deformation of ASTM F90 Co-20Cr-15W-10Ni (mass&nbsp;pct) alloy heat-treated at...