Signature laminar distributions of pathology in frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) with either tau (FTLD-tau) or TDP-43 (FTLD-TDP) inclusions are distinct proteinopathies that frequently cause similar frontotemporal dementia (FTD) clinical syndromes. FTD syndromes often display macroscopic signatures of neurodegeneration at the level of regions and networks, but it is unclear if subregional laminar pathology display patterns unique to proteinopathy or clinical syndrome. We hypothesized that FTLD-tau and FTLD-TDP accumulate pathology in relatively distinct cortical layers independent of clinical syndrome, with greater involvement of lower layers in FTLD-tau. The current study examined 170 patients with either FTLD-tau (n = 73) or FTLD-TDP (n = 97) spanning dementia and motor phenotypes in the FTD spectrum. We digitally measured the percent area occupied by tau and TDP-43 pathology in upper layers (I–III), lower layers (IV–VI), and juxtacortical white matter (WM) from isocortical regions in both hemispheres where available. Linear mixed-effects models compared ratios of upper to lower layer pathology between FTLD groups and investigated relationships with regions, WM pathology, and global cognitive impairment while adjusting for demographics. We found lower ratios of layer pathology in FTLD-tau and higher ratios of layer pathology in FTLD-TDP, reflecting lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology, respectively (p < 0.001). FTLD-tau displayed lower ratios of layer pathology related to greater WM tau pathology (p = 0.002) and to earlier involved/severe pathology regions (p = 0.007). In contrast, FTLD-TDP displayed higher ratios of layer pathology not related to either WM pathology or regional severity. Greater cognitive impairment was associated with higher ratios of layer pathology in FTLD-tau (p = 0.018), but was not related to ratios of layer pathology in FTLD-TDP. Lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology are proteinopathy-specific, regardless of clinical syndromes or regional networks that define these syndromes. Thus, patterns of laminar change may provide a useful anatomical framework for investigating how degeneration of select cells and corresponding laminar circuits influence large-scale networks and clinical symptomology in FTLD.

Frequent Manipulation of Resistance Training Variables Promotes Myofibrillar Spacing Changes in Resistance-Trained Individuals

We sought to determine if manipulating resistance training (RT) variables differentially altered the expression of select sarcoplasmic and myofibril proteins as well as myofibrillar spacing in myofibers. Resistance-trained men (n = 20; 26 ± 3 years old) trained for 8 weeks where a randomized leg performed either a standard (CON) or variable RT protocol (VAR: manipulation of load, volume, muscle action, and rest intervals at each RT session). A pre-training (PRE) vastus lateralis biopsy was obtained from a randomized single leg, and biopsies were obtained from both legs 96 h following the last training bout. The sarcoplasmic protein pool was assayed for proteins involved in energy metabolism, and the myofibril protein pool was assayed for relative myosin heavy chain (MHC) and actin protein abundances. Sections were also histologically analyzed to obtain myofibril spacing characteristics. VAR resulted in ~12% greater volume load (VL) compared to CON (p &lt; 0.001). The mean fiber cross-sectional area increased following both RT protocols [CON: 14.6% (775.5 μm2), p = 0.006; VAR: 13.9% (743.2 μm2), p = 0.01 vs. PRE for both], but without significant differences between protocols (p = 0.79). Neither RT protocol affected a majority of assayed proteins related to energy metabolism, but both training protocols increased hexokinase 2 protein levels and decreased a mitochondrial beta-oxidation marker (VLCAD protein; p &lt; 0.05). Citrate synthase activity levels increased with CON RT (p &lt; 0.05), but not VAR RT. The relative abundance of MHC (summed isoforms) decreased with both training protocols (p &lt; 0.05). However, the relative abundance of actin protein (summed isoforms) decreased with VAR only (13.5 and 9.0%, respectively; p &lt; 0.05). A decrease in percent area occupied by myofibrils was observed from PRE to VAR (−4.87%; p = 0.048), but not for the CON (4.53%; p = 0.979). In contrast, there was an increase in percent area occupied by non-contractile space from PRE to VAR (10.14%; p = 0.048), but not PRE to CON (0.72%; p = 0.979). In conclusion, while both RT protocols increased muscle fiber hypertrophy, a higher volume-load where RT variables were frequently manipulated increased non-contractile spacing in resistance-trained individuals.

Production of biodiesel over ZnO-TiO2 bifunctional oxide catalyst supported on natural zeolite

In this paper, biodiesel is produced from palm oil and methanol via the transesterification process over the heterogeneous catalyst. The metal oxide ZnO-TiO2 was impregnated into natural zeolite over the dry impregnation method. The ZnO-TiO2/NZ catalyst was prepared over the dry impregnation method. The catalysts' characteristic was characterized by X-ray diffraction (XRD) and Scanning Electron Microscope (SEM). The biodiesel was analyzed by Fourier-Transform Infrared Spectroscopy (FTIR) and Gas Chromatography-Mass Spectrometry (GC-MS). The results showed a functional group of methyl ester (C=O, carbonyl group) at 1744.51 cm-1. The components of methyl ester such as hexadecanoic acid methyl ester (C17), cis-9-heptadecanoic acid methyl ester (C18), oleic acid methyl ester (C19), are present in the biodiesel with the percent area of 0.05%, 0.08%, 0.63%, 7.06%, 16.3%, respectively, over ZnO-TiO2/NZ catalyst with a metal ratio of 1:1. This catalyst was successful in the transesterification of palm oil to produce biodiesel.

The Myth of Median Nerve in Forearm and Its Role in Double Crush Syndrome: A Cadaveric Study

Purpose: This study aims to histologically compare the median nerve in the arm, forearm, and wrist, to help understand how cervical radiculopathy in a double crush phenomenon causes distal nerve dysfunction at the carpal tunnel and median nerve with concurrent absence of symptoms at the forearm.Methods: The study was performed on 12 fresh cadaveric upper limbs free from any injury or operation. Male cadavers in the age range of 35–40 years were used. The dissection of the median nerve and the histological examination of the specimens from the arm, forearm, and wrist were conducted to evaluate variations in the epineurium thickness (μm), perineurium thickness (μm), number of fascicles per nerve trunk, area percent of myelin covering, and area percent of neurolemmal sheath.Results: Morphometric and statistical results of the cadaveric median nerve trunk revealed that the mean epineurium and perineurium thickness measured in H&amp;E-stained sections in the forearm were significantly greater than those in the arm and wrist specimens. Further, the mean percent area of the myelin covering in the forearm was significantly lower than that in the arm and wrist specimens in the sections stained with osmium oxide (p &lt; 0.001). There were, however, no significant differences in the neurolemmal sheath among the arm, forearm, and wrist specimens in the silver-stained sections.Conclusion: The histological differences explained the high concomitant occurrence of carpal tunnel syndrome (CTS) and cervical radiculopathy and the concurrent absence of symptoms at the forearm. Hence, we suggest cautious evaluation of patients with upper limb symptoms, since the management of these conditions requires a different approach.

Lesion Geometry as Assessed by Optical Coherence Tomography Is Related to Myocardial Ischemia as Determined by Cardiac Magnetic Resonance Imaging

Introduction: Although the relationship between the geometry of coronary stenosis and the presence of myocardial ischemia is well known, the association between stenosis geometry and severity and/or extent of ischemia is still unexplored. Thus, we investigated this relationship using optical coherence tomography (OCT) to assess stenosis parameters and cardiac magnetic resonance imaging (CMR) to determine both extent and severity of ischemia. Methods: We analyzed 55 lesions from 51 patients with stable angina. Pre-interventionally, all patients underwent OCT-analysis of stenosis morphology as well as CMR to determine both the extent and severity of myocardial ischemia. Results: Percent area stenosis (%AS) was significantly associated with ischemic burden (r = 0.416, p = 0.003). Similar results could be obtained for other stenosis parameters as well as for several other parameters assessing the extent of ischemia. Furthermore, OCT-derived stenosis parameters were associated with the product of ischemic burden and severity of ischemia (%AS: r = 0.435, p = 0.002; similar results for other parameters). A Poiseuille’s-law-modelled combination of stenosis length and minimal lumen diameter yielded a good diagnostic efficiency (AUC 0.787) in predicting an ischemic burden >10%. Conclusions: Our data highlight the key role of the geometry of coronary lesions in determining myocardial ischemia.

Automated Safety & Security Systems for Industrial Application using Self-Healing Approach

The concept of self-healing for hardware systems is studied in this study, and a new approach is offered. In the way they offer healing and recovery abilities, key technologies have been offering imitations to biological entities. Digital systems with inspired uniform architecture offer better fault-tolerance capabilities. The ability of a system to detect and repair flaws or failures is known as self-healing. Given that current self-healing systems are focused on redundancy and spare blocks, one of the key issues with current self-healing approaches is area overhead and scalability for complicated structures. This research proposes a new method for self-healing based on embryonic hardware that does not require the use of spare cells. When compared to alternative techniques that rely on spare cells, the area overhead is reduced. The suggested method entails time multiplexing two functions in a single cell inside a single clock cycle. The proposed technique's reliability is investigated and compared to that of a traditional system with varying failure rates. This method can heal up to 50% of the cells, and each cell can only cover one neighbouring failed cell at a time. The proposed solution has a 9 percent area overhead, which is significantly lower than prior spare cell approaches. The proposed method is tested on two case studies: an ALU array and a neural network.

Probability Assessment of the Mechanical and Low-Cycle Properties of Structural Steels and Aluminium

Key mechanical properties used in low-cycle strength and durability calculations are the strength (proportional limit stress, σpr; relative yield strength, σ0.2; and ultimate tensile stress, σu) and strain properties (proportional limit strain, epr; percent area reduction, ψ; and percent area reduction at failure, ψu). When selecting the key mechanical properties provided in the specifications, an error may be made due to the failure to account for a series of random factors that determine the distribution of properties. The majority of research papers dealing with statistical descriptions of the low-cycle strain properties do not look deeper into the distribution of mechanical properties and the diagram parameters of strain characteristics. This paper provides a description of the distribution patterns of mechanical properties, statistical parameters, and low-cycle fatigue curves. Log-normal distribution generated the lowest values for the coefficient of variation of one of the key statistical indicators, suggesting that log-normal distribution is superior to normal or Weibull distribution in this respect. The distribution of low-cycle strain parameters exceeded the distribution of mechanical properties considerably. Minimum coefficients of variation of the parameters were generated at normal distribution. The statistical analysis showed the lower distribution of the durability parameters compared to the distribution of parameters of the strain diagrams. The findings of the paper enable a revision of the durability and life of the structural elements of in-service facilities subject to elastoplastic loading by assessing the distribution of mechanical characteristics and low-cycle strain parameters as well as the permissible distribution limits.

31 A phase 3 open-label, controlled, randomized trial evaluating the efficacy and safety of a bioengineered allogeneic cellularized construct in patients with deep partial-thickness thermal burns

Introduction Autograft (AG) is the standard of care for treatment of severe burns. While AG provides effective wound closure (WC), the procedure creates a donor site wound prone to pain and scarring. In a phase 1b trial, no deep partial-thickness (DPT) wound treated with a bioengineered allogeneic cellularized construct (BACC) required AG by Day 28 and WC at the BACC site was achieved in 93% of patients by Month (M) 3. This phase 3 study (NCT03005106) evaluated the efficacy and safety of this BACC in patients with DPT burns. Methods Enrolled patients were aged ≥18 years with 3–49% TBSA thermal burns on the torso or extremities. In each patient, two DPT areas (≤2,000 cm2 total) deemed comparable following excision were randomized to treatment with either cryopreserved BACC or AG. Coprimary endpoints were 1) the difference in percent area of BACC treatment site and AG treatment site autografted at M3 and 2) the proportion of patients achieving durable WC of the BACC treatment site without AG at M3. Ranked secondary endpoints were: 1) the difference between BACC and AG donor sites in average donor site pain intensity through Day 14; 2) the difference between BACC and AG donor site cosmesis at M3; and 3) the difference between BACC and AG treatment site cosmesis at M12. Safety assessments were performed in all patients through M12. Results Seventy-one patients were enrolled. By M3, there was a 96% reduction in mean percent area of BACC treatment sites that required AG, compared with AG treatment sites (4.3% vs 102.1%, respectively; P&lt;.0001). BACC treatment resulted in durable WC at M3 without AG in 92% (95% CI: 85.6, 98.8; 59/64) of patients for whom data was available. By M3, mean donor site Patient and Observer Scar Assessment Scale (POSAS) observer total score (±SD) was significantly lower (more like normal skin) for BACC donor sites compared with AG donor sites (6.3 ± 1.71 vs 16.3 ± 7.71; P&lt;.0001). At M12, mean POSAS observer total score (±SD) was 15.6 (± 8.34) for BACC treatment sites compared with 16.3 (± 9.41) for AG treatment sites (P=.4268). The most common BACC-related adverse event (AE) was pruritus, which occurred in 11 (15%) patients. All BACC-related AEs were mild or moderate in severity. Conclusions This phase 3 study achieved both coprimary endpoints, including significant autograft sparing and durable WC in DPT burns. Both donor site pain and donor site cosmesis were favorable outcomes of significantly reduced use of AG in BACC-treated patients. M12 POSAS for BACC did not differ significantly from AG. This BACC may offer a new treatment for severe burns to reduce or eliminate the need for AG. Applicability of Research to Practice This BACC has shown clinical benefit in patients with DPT thermal burns, potentially mitigating donor site morbidity. External Funding Stratatech, a Mallinckrodt Company; Funding and technical support for the Phase 3 clinical study were provided by the Biomedical Advanced Research and Development Authority (BARDA), under the Assistant Secretary for Preparedness and Response, within the U.S. Department of Health and Human Services, under Project BioShield Contract No. HHSO100201500027C.

Will community calcification reflect reef accretion on future, degraded coral reefs?

Coral bleaching events continue to drive the degradation of coral reefs worldwide, causing a shift in the benthic community from coral to algae dominated ecosystems. Critically, this shift may decrease the capacity of degraded coral reef communities to maintain net positive accretion during warming-driven stress events (e.g., reef-wide coral bleaching). Here we measured rates of net ecosystem calcification (NEC) and net ecosystem production (NEP) on a degraded coral reef lagoon community (coral cover 20 %) during a reef-wide bleaching event in February of 2020 at Heron Island on the Great Barrier Reef. We found that during this bleaching event, rates of community NEP and NEC across replicate transects remained positive and did not change in response to bleaching. Repeated benthic surveys over a period of 20 d indicated an increase in the percent area of bleached coral tissue, corroborated by relatively low Symbiodiniaceae densities (~0.6 × 106 cm−2) and dark-adapted photosynthetic yields in photosystem II of corals (~0.5) sampled along each transect over this period. Given that a clear decline in coral health was not reflected in the overall community NEC estimates, it is possible that elevated temperatures in the water column that compromise coral health enhanced the thermodynamic favourability for calcification in other, ahermatypic benthic calcifiers. These data suggest that positive NEC on degraded reefs may not equate to the net positive accretion of reef structure in a future, warmer ocean. Critically, our study highlights that if coral cover continues to decline as predicted, NEC may no longer be an appropriate proxy for reef growth as the proportion of the community NEC signal owed to ahermatypic calcification increases and coral dominance on the reef decreases.

Spatiotemporal change and attribution of potential evapotranspiration over China from 1901 to 2100

Global warming has accelerated surface water loss around the world. This study investigates in detail the change and attribution of potential evapotranspiration (PET) across China from 1901 to 2100 by the Hargreaves model, based on a 1-km temperature dataset downscaled from the low-spatial-resolution datasets using a Delta downscaling framework. Results showed that (1) relative to 1961–1990, PET increased by 0.62% in the historic period (1901–2017) and 6.43–12.89% for the future period (2018–2100), suggesting considerable future drying for China. Moreover, these increments had strong spatial variations and the largest increases were detected in high-elevation regions; (2) PET over entire China demonstrated a nonsignificant upward trend during the historic period and significant upward trends for the future period. For each period and GCM, significant upward PET trends occupied a much larger percent area than significant downward trends; (3) PET variations during the historic period were most sensitive to mean temperature (TMP), while in the future period it was more sensitive to maximum temperature (TMX), suggesting a change in the primary sensitivity factor due to global warming; (4) minimum temperature (TMN) made the largest contribution (45%) to PET variations during the historic period, while TMX had the largest contribution (36–40%) in the future period. Therefore, the primary contributing factor might transform from TMN to TMX under climate change; and (5) PET variations exhibited strong spatial heterogeneity, detected on fine geographic scales, due to the use of downscaled dataset. Overall, the results present a deep insight for planning coping strategies of global warming in China.