Compositionally Graded Cathode Material with Long‐Term Cycling Stability for Electric Vehicles Application

Al is introduced into a compositionally graded cathode with average composition of Li[Ni_0.61Co_0.12Mn_0.27]O₂ (FCG61) whose Ni and Mn concentrations are designed to vary continuously within the cathode particle. The Al‐substituted full concentration gradient (Al‐FCG61) cathode is tested for 3000 cycles in a full‐cell, mainly to gauge its viability for daily charge/discharge cycles during the service life of electric vehicles (≈10 years). The Al‐substitution enables the Al‐FCG61 cathode to maintain 84% of its initial capacity even after 3000 cycles. It is demonstrated that the Al‐substitution strengthens the grain boundaries, substantiated by the mechanical strength data, thereby delaying the nucleation of microcracks at the phase boundaries which is shown to be the main reason for the cathode failure during long‐term cycling. It also shows that the Al‐substitution decreases the cation mixing and suppresses the deleterious formation of the secondary phase that likely initiates the microcracks. Unlike an NCA cathode, whose depth of discharge (DOD) must be limited to 60% for long‐term cycling, the proposed Al‐FCG61 cathode is cycled at 100% DOD for 3000 cycles to fully utilize its available capacity for maximum energy density and subsequent reduction in cost of the battery.     

The fatty acid chain elongase,Elovl1, is required for kidney and swim bladder development during zebrafish embryogenesis

Very long chain fatty acids are required for sphingolipid synthesis, lipid homeostasis, myelin formation, epidermal permeability, and retinal function. Seven different enzymes are known to be involved in the elongation cycle of fatty acids, with different chain-length specificities. Elovl1 is one of those enzymes whose function has been linked mainly to the synthesis of sphingolipids and the epidermal barrier. However, the role of Elovl1 in organogenesis is not clear. In zebrafish, 2 Elovl1 genes, elovl1a and elovl1b, are highly expressed in the swim bladder, and elovl1b is also expressed in the kidney. We found that both elovl1 knockdown embryos contain increased levels of long chain fatty acids from carbon number 14 to 20 as compared to control embryos. Oil-Red-O staining shows that yolk lipid consumption is greatly reduced, whereas lipid droplets accumulate within the swim bladder. Notably, knockdown of either elovl1a or elovl1b affects the expression of genes involved in swim bladder development and impairs inflation of the swim bladder. Consistent with its expression in the pronephros, knockdown of elovl1b alone affects the expression of genes required for kidney development and reduces renal clearance. Our findings strongly suggest that both elovl1 genes are a key determinant of swim bladder and kidney development in zebrafish, which may be comparatively applicable to lung and kidney development in humans.     

Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity

Myotubularin-related protein 1 (MTMR1) is a phosphatase that belongs to the tyrosine/dual-specificity phosphatase superfamily. MTMR1 has been shown to use phosphatidylinositol 3-monophosphate (PI(3)P) and/or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P₂) as substrates. Here, we determined the crystal structure of human MTMR1. The refined model consists of the Pleckstrin homology (PH)-GRAM and phosphatase (PTP) domains. The overall structure was highly similar to the previously reported MTMR2 structure. Interestingly, two phosphate molecules were coordinated by strictly conserved residues located in the C(X)₅R motif of the active site. Additionally, our biochemical studies confirmed the substrate specificity of MTMR1 for PI(3)P and PI(3,5)P₂ over other phosphatidylinositol phosphates. Our structural and enzymatic analyses provide insight into the catalytic mechanism and biochemical properties of MTMR1.     

Acoustic Characteristics of Stridor in Multiple System Atrophy

Nocturnal stridor is a breathing disorder prevalent in patients with multiple system atrophy (MSA). An improved understanding of this breathing disorder is essential since nocturnal stridor carries a poor prognosis (an increased risk of sudden death). In this study, we aimed to classify types of stridor by sound analysis and to reveal their clinical significance. Patients who met the criteria for probable MSA and had undergone polysomnography (PSG) were recruited. Patients were then assessed clinically with sleep questionnaires, including the Pittsburgh Sleep Quality Index, and the Hoehn and Yahr scale. Nocturnal stridor and snoring were analyzed with the Multi-Dimensional Voice Program. Nocturnal stridor was recorded in 22 patients and snoring in 18 patients using the PSG. Waveforms of stridors were classified into rhythmic or semirhythmic after analysis of the oscillogram. Formants and harmonics were observed in both types of stridor, but not in snoring. Of the 22 patients diagnosed with stridor during the present study, fifteen have subsequently died, with the time to death after the PSG study being 1.9 ± 1.4 years (range 0.8 to 5.0 years). The rhythmic waveform group presented higher scores on the Hoehn and Yahr scale and the survival outcome of this group was lower compared to the semirhythmic waveform group (p = 0.030, p = 0.014). In the Kaplan Meier’s survival curve, the outcome of patients with rhythmic waveform was significantly less favorable than the outcome of patients with semirhythmic waveform (log-rank test, p < 0.001). Stridor in MSA can be classified into rhythmic and semirhythmic types and the rhythmic component signifies a poorer outcome.     

Desynchronization of Theta-Phase Gamma-Amplitude Coupling during a Mental Arithmetic Task in Children with Attention Deficit/Hyperactivity Disorder

Introduction

Theta-phase gamma-amplitude coupling (TGC) measurement has recently received attention as a feasible method of assessing brain functions such as neuronal interactions. The purpose of this electroencephalographic (EEG) study is to understand the mechanisms underlying the deficits in attentional control in children with attention deficit/hyperactivity disorder (ADHD) by comparing the power spectra and TGC at rest and during a mental arithmetic task.

Methods

Nineteen-channel EEGs were recorded from 97 volunteers (including 53 subjects with ADHD) from a camp for hyperactive children under two conditions (rest and task performance). The EEG power spectra and the TGC data were analyzed. Correlation analyses between the Intermediate Visual and Auditory (IVA) continuous performance test (CPT) scores and EEG parameters were performed.

Results

No significant difference in the power spectra was detected between the groups at rest and during task performance. However, TGC was reduced during the arithmetic task in the ADHD group compared with the normal group (F = 16.70, p < 0.001). The TGC values positively correlated with the IVA CPT scores but negatively correlated with theta power.

Conclusions

Our findings suggest that desynchronization of TGC occurred during the arithmetic task in ADHD children. TGC in ADHD children is expected to serve as a promising neurophysiological marker of network deactivation during attention-demanding tasks.     

Acute High-Dose and Chronic Lifetime Exposure to Alcohol Consumption and Differentiated Thyroid Cancer: T-CALOS Korea

Background

This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC).

Methods

The Thyroid Cancer Longitudinal Study (T-CALOS) included 2,258 DTC patients (449 men and 1,809 women) and 22,580 healthy participants (4,490 men and 18,090 women) who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated using conditional regression models.

Results

While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion) was associated with increased risks in men (OR = 2.22, 95%CI = 1.27–3.87) and women (OR = 3.61, 95%CI = 1.52–8.58) compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31–40 years: OR = 1.58, 95%CI = 1.10–2.28; 41+ years: OR = 3.46, 95%CI = 2.06–5.80) and women (31–40 years: OR = 2.18, 95%CI = 1.62–2.92; 41+ years: OR = 2.71, 95%CI = 1.36–5.05) compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage.

Conclusion

The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC.     

Risk Factors Associated with Discordant Ki-67 Levels between Preoperative Biopsy and Postoperative Surgical Specimens in Breast Cancers

Purpose

The Ki-67 labelling index is significant for the management of breast cancer. However, the concordance of Ki-67 expression between preoperative biopsy and postoperative surgical specimens has not been well evaluated. This study aimed to find the correlation in Ki-67 expression between biopsy and surgical specimens and to determine the clinicopathological risk factors associated with discordant values.

Patients and Methods

Ki-67 levels were immunohistochemically measured using paired biopsy and surgical specimens in 310 breast cancer patients between 2008 and 2013. ΔKi-67 was calculated by postoperative Ki-67 minus preoperative levels. The outliers of ΔKi-67 were defined as [lower quartile of ΔKi-67–1.5 × interquartile range (IQR)] or (upper quartile + 1.5 × IQR) and were evaluated according to clinicopathological parameters by logistic regression analysis.

Results

The median preoperative and postoperative Ki-67 levels were 10 (IQR, 15) and 10 (IQR, 25), respectively. Correlation of Ki-67 levels between the two specimens indicated a moderately positive relationship (coefficient = 0.676). Of 310 patients, 44 (14.2%) showed outliers of ΔKi-67 (range, ≤-20 or ≥28). A significant association with poor prognostic factors was found among these patients. Multivariate analysis determined that significant risk factors for outliers of ΔKi-67 were tumor size >1 cm, negative progesterone receptor (PR) expression, grade III cancer, and age ≤35 years. Among 171 patients with luminal human epidermal growth factor receptor 2-negative tumors, breast cancer subtype according to preoperative or postoperative Ki-67 levels discordantly changed in 46 (26.9%) patients and a significant proportion of patients with discordant cases had ≥1 risk factor.

Conclusion

Ki-67 expression showed a substantial concordance between biopsy and surgical specimens. Extremely discordant Ki-67 levels may be associated with aggressive tumor biology. In patients with luminal subtype disease, clinical application of Ki-67 values should be cautious considering types of specimens and clinicopathological risk factors.     

Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus

Background

The “gold standard” for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine.

Methods

199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation.

Results

An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4β7⁺ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4β7⁺ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7⁺ IgA^- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus.

Discussion

Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program.