Plastic crystal neopentylglycol (NPG) exhibits colossal barocaloric effects (BCEs) with record-high entropy changes, offering exciting prospects for the field of solid-state cooling through the ...application of moderate pressures. Here, we show that the intermolecular hydrogen bond plays a key role in the orientational order of NPG molecules, while its broken due to thermal perturbation prominently weakens the activation barrier of orientational disorder. The analysis of hydrogen bond strength, rotational entropy free energy and entropy changes provides insightful understanding of BCEs in order-disorder transition. External pressure reduce the hydsrogen bond length and enhance the activation barrier of orientational disorder, which serves as a route of varying intermolecular interaction to tune the order-disorder transition. Our work provides atomic-scale insights on the orientational order-disorder transition of NPG as the prototypical plastic crystal with BCEs, which is helpful to achieve superior caloric materials by molecular designing in the near future.
Many breakthroughs in the laboratories often do not bridge the gap between research and commercialization. However, silicon photonics bucked the trend, with industry observers estimating the ...commercial market to close in on a billion dollars in 2020 <xref ref-type="bibr" rid="ref45">45 . Silicon photonics leverages the billions of dollars and decades of research poured into silicon semiconductor device processing to enable high yield, robust processing, and most of all, low cost. Silicon is also a good optical material, with transparency in the commercially important infrared wavelength bands, and is a suitable platform for large-scale photonic integrated circuits. Silicon photonics is therefore slated to address the world's ever-increasing needs for bandwidth. It is part of an emerging ecosystem which includes designers, foundries, and integrators. In this paper, we review most of the foundries that presently enable silicon photonics integrated circuits fabrication. Some of these are pilot lines of major research institutes, and others are fully commercial pure-play foundries. Since silicon photonics has been commercially active for some years, foundries have released process design kits (PDK) that contain a standard device library. These libraries represent optimized and well-tested photonic elements, whose performance reflects the stability and maturity of the integration platforms. We will document the early works in silicon photonics, as well as its commercial status. We will provide a comprehensive review of the development of silicon photonics and the foundry services which enable the productization, including various efforts to develop and release PDK devices. In this context, we will report the long-standing efforts and contributions that previously IME/A * STAR and now AMF has dedicated to accelerating this journey.
Cyclic vomiting syndrome (CVS) in children is characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. In the absence of robust data, the treatment of CVS remains ...largely empiric starting with the 2008 NASPGHAN Consensus Statement recommendations of cyproheptadine for children < 5 years of age and amitriptyline for those ≥ 5 years with propranolol serving as the second-line agent. Comprehensive management begins with lifestyle alterations, and extends to medications, supplements, and stress reduction therapies. Standard drug therapy is organized by the four phases of the illness: (1)
interictal
(preventative medications and mitochondrial supplements), (2)
prodromal
(abortive agents), (3)
vomiting
(fluids/energy substrates, antiemetics, analgesics, and sedatives) and (4)
recovery
(supportive care and nutrition). Because the response to treatment is heterogeneous, clinicians often trial several different preventative strategies including NK1 antagonists, cautious titration of amitriptyline to higher doses, anticonvulsants, Ca
2+
-channel blockers, and other TCA antidepressants. When the child remains refractory to treatment, reconsideration of possible missed diagnoses and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities (especially anxiety), specific subphenotype, and when available, genotype. For hospital intervention, IV fluids with 10% dextrose, antiemetics, and analgesics can lessen symptoms while effective sedation in some instances can truncate severe episodes.
Conclusion
: Although management of CVS remains challenging to the clinician, approaches based upon recent literature and accumulated experience with subgroups of patients has led to improved treatment of the refractory and hospitalized patient.
What is Known:
•
Cyclic vomiting syndrome is a complex disorder that remains challenging to manage.
•
Previous therapy has been guided by the NASPGHAN Consensus Statement of 2008.
What is New:
•
New prophylactic approaches include NK1 antagonists and higher dosages of amitriptyline.
•
Strategies based upon comorbidities and subphenotype are helpful in refractory patients.
Human trisomies can alter cellular phenotypes and produce congenital abnormalities such as Down syndrome (DS). Here we have generated induced pluripotent stem cells (iPSCs) from DS fibroblasts and ...introduced a TKNEO transgene into one copy of chromosome 21 by gene targeting. When selecting against TKNEO, spontaneous chromosome loss was the most common cause for survival, with a frequency of ∼10−4, while point mutations, epigenetic silencing, and TKNEO deletions occurred at lower frequencies in this unbiased comparison of inactivating mutations. Mitotic recombination events resulting in extended loss of heterozygosity were not observed in DS iPSCs. The derived, disomic cells proliferated faster and produced more endothelia in vivo than their otherwise isogenic trisomic counterparts, but in vitro hematopoietic differentiation was not consistently altered. Our study describes a targeted removal of a human trisomy, which could prove useful in both clinical and research applications.
► Trisomy correction in Down syndrome iPSCs by gene targeting and negative selection ► Chromosome loss more frequent than other types of mutations ► Comparison of isogenic disomic and trisomic cell lines ► Trisomy 21 slows iPSC proliferation and reduces endothelial differentiation
Abstract
We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. ...We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
Considerable evidences have shown that autophagy has an important role in tumor chemoresistance. However, it is still unknown whether the lncRNA HULC (highly upregulated in liver cancer) is involved ...in autophagy and chemoresistance of hepatocellular carcinoma (HCC). In this study, we for the first time demonstrated that treatment with antitumor reagents such as oxaliplatin, 5-fluorouracil and pirarubicin (THP) dramatically induced HULC expression and protective autophagy. Silencing of HULC sensitized HCC cells to the three antitumor reagents via inhibiting protective autophagy. Ectopic expression of HULC elicited the autophagy of HCC cells through stabilizing silent information regulator 1 (Sirt1) protein. The investigation for the corresponding mechanism by which HULC stabilized Sirt1 revealed that HULC upregulated ubiquitin-specific peptidase 22 (USP22), leading to the decrease of ubiquitin-mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chains from Sirt1. Moreover, we found that miR-6825-5p, miR-6845-5p and miR-6886-3p could decrease the level of USP22 protein by binding to the 3'-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. In addition, we showed that the level of HULC was positively correlated with that of Sirt1 protein in human HCC tissues. Collectively, our data reveals that the pathway 'HULC/USP22/Sirt1/ protective autophagy' attenuates the sensitivity of HCC cells to chemotherapeutic agents, suggesting that this pathway may be a novel target for developing sensitizing strategy to HCC chemotherapy.
ABSTRACT
Objectives:
Eosinophilic esophagitis (EoE) is an immune‐mediated chronic inflammatory disorder triggered by food antigen(s). A 6‐food elimination diet (SFED) excluding cow's milk, soy, ...wheat, egg, peanuts/tree nuts, and seafood has been shown to induce remission in a majority of children with EoE. The goal of the present study was to identify specific food antigens responsible for eosinophilic esophageal inflammation in children with EoE who had achieved histological remission with the SFED.
Patients and Methods:
In this analysis, we retrospectively analyzed children with EoE who completed subsequent single‐food reintroductions that led to identification of foods causing disease recurrence. Repeat upper endoscopy with biopsies was performed after single‐food introductions. Recurrence of esophageal eosinophilia following a food reintroduction identified that food antigen as a cause of EoE.
Results:
A total of 36/46 (25 M/11F) children who were initially successfully treated with SFED completed this trial; the mean age was 7.6 ± 4.3 years. The most common foods identified were 25 to cow's milk (74%), 8 to wheat (26%), 4 to eggs (17%), 3 to soy (10%), and 1 to peanut (6%). Milk was 8 times more likely to cause EoE compared with wheat, the next most common food (95% confidence interval 2.41–26.62, P = 0.0007).
Conclusions:
Serial single‐food reintroductions following induction of histological remission with the SFED can lead to the identification of specific causal food antigen(s) in EoE. Cow's milk was the most common food identified in subjects with EoE treated with SFED. A subset of children with EoE may develop tolerance to their food sensitivities while on the SFED.
Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
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