Miracle-dz/UniFAR-FTUs huggingface dataset:
Propagation of pop ups in kirigami shells

Significance Kirigami—the Japanese art of cutting paper—has become an emergent tool to realize highly stretchable devices and morphable structures. While kirigami structures are fabricated by simply perforating an array of cuts into a thin sheet, the applied deformation and associated instabilities can be exploited to transform them into complex 3D morphologies. However, to date, such reconfiguration always happen simultaneously through the system. By borrowing ideas from phase-transforming materials, we combine cuts and curvature to realize kirigami structures in which deformation-induced shape reconfiguration initially nucleates near an imperfection and then, under specific conditions, spreads through the system. We envision that such control of the shape transformation could be used to design the next generation of responsive surfaces and smart skins. Kirigami-inspired metamaterials are attracting increasing interest because of their ability to achieve extremely large strains and shape changes via out-of-plane buckling. While in flat kirigami sheets, the ligaments buckle simultaneously as Euler columns, leading to a continuous phase transition; here, we demonstrate that kirigami shells can also support discontinuous phase transitions. Specifically, we show via a combination of experiments, numerical simulations, and theoretical analysis that, in cylindrical kirigami shells, the snapping-induced curvature inversion of the initially bent ligaments results in a pop-up process that first localizes near an imperfection and then, as the deformation is increased, progressively spreads through the structure. Notably, we find that the width of the transition zone as well as the stress at which propagation of the instability is triggered can be controlled by carefully selecting the geometry of the cuts and the curvature of the shell. Our study significantly expands the ability of existing kirigami metamaterials and opens avenues for the design of the next generation of responsive surfaces as demonstrated by the design of a smart skin that significantly enhances the crawling efficiency of a simple linear actuator.
ERK1/2 signaling induces skeletal muscle slow fiber-type switching and reduces muscular dystrophy disease severity

MAPK signaling consists of an array of successively acting kinases. ERK1 and -2 (ERK1/2) are major components of the greater MAPK cascade that transduce growth factor signaling at the cell membrane. Here, we investigated ERK1/2 signaling in skeletal muscle homeostasis and disease. Using mouse genetics, we observed that the muscle-specific expression of a constitutively active MEK1 mutant promotes greater ERK1/2 signaling that mediates fiber-type switching to a slow, oxidative phenotype with type I myosin heavy chain expression. Using a conditional and temporally regulated Cre strategy, as well as Mapk1 (ERK2) and Mapk3 (ERK1) genetically targeted mice, MEK1-ERK2 signaling was shown to underlie this fast-to-slow fiber-type switching in adult skeletal muscle as well as during development. Physiologic assessment of these activated MEK1-ERK1/2 mice showed enhanced metabolic activity and oxygen consumption with greater muscle fatigue resistance. In addition, induction of MEK1-ERK1/2 signaling increased dystrophin and utrophin protein expression in a mouse model of limb-girdle muscle dystrophy and protected myofibers from damage. In summary, sustained MEK1-ERK1/2 activity in skeletal muscle produces a fast-to-slow fiber-type switch that protects from muscular dystrophy, suggesting a therapeutic approach to enhance the metabolic effectiveness of muscle and protect from dystrophic disease.
Effect of Vitamin D Supplementation on Relapse-Free Survival Among Patients With Digestive Tract Cancers: The AMATERASU Randomized Clinical Trial

Importance Randomized clinical trials of vitamin D supplementation for secondary prevention in patients with cancer are needed, given positive results of observational studies. Objective To determine whether postoperative vitamin D3 supplementation can improve survival of patients with digestive tract cancers overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels. Design, Setting, and Participants The AMATERASU trial, a randomized, double-blind, placebo-controlled trial conducted at a single university hospital in Japan. Enrollment began in January 2010 and follow-up was completed in February 2018. Patients aged 30 to 90 years with cancers of the digestive tract from the esophagus to the rectum, stages I to III, were recruited. Of 439 eligible patients, 15 declined and 7 were excluded after operation. Interventions Patients were randomized to receive oral supplemental capsules of vitamin D (2000 IU/d; n = 251) or placebo (n = 166) from the first postoperative outpatient visit to until the end of the trial. Main Outcomes and Measures The primary outcome was relapse-free survival time to relapse or death. The secondary outcome was overall survival time to death due to any cause. Subgroups analyzed had baseline serum 25(OH)D levels of 0 to less than 20 ng/mL, 20 to 40 ng/mL, and greater than 40 ng/mL; because of small sample size for the highest-baseline-level group, interactions were tested only between the low- and middle-baseline-level groups. Results All 417 randomized patients (mean age, 66 years; male, 66%; esophageal cancer, 10%; gastric cancer, 42%; colorectal cancer, 48%) were included in the analyses. There was 99.8% follow-up over a median 3.5 (interquartile range, 2.3-5.3) years, with maximal follow-up of 7.6 years. Relapse or death occurred in 50 patients (20%) randomized to vitamin D and 43 patients (26%) randomized to placebo. Death occurred in 37 (15%) in the vitamin D group and 25 (15%) in the placebo group. The 5-year relapse-free survival was 77% with vitamin D vs 69% with placebo (hazard ratio [HR] for relapse or death, 0.76; 95% CI, 0.50-1.14; P = .18). The 5-year overall survival in the vitamin D vs placebo groups was 82% vs 81% (HR for death, 0.95; 95% CI, 0.57-1.57; P = .83). In the subgroup of patients with baseline serum 25(OH)D levels between 20 and 40 ng/mL, the 5-year relapse-free survival was 85% with vitamin D vs 71% with placebo (HR for relapse or death, 0.46; 95% CI, 0.24-0.86; P = .02; P = .04 for interaction). Fractures occurred in 3 patients (1.3%) in the vitamin D group and 5 (3.4%) in the placebo group. Urinary stones occurred in 2 patients (0.9%) in the vitamin D group and 0 in the placebo group. Conclusions and Relevance Among patients with digestive tract cancer, vitamin D supplementation, compared with placebo, did not result in significant improvement in relapse-free survival at 5 years. Trial Registration UMIN Identifier: UMIN000001977
Altered white matter connectivity in young people exposed to childhood abuse: a tract-based spatial statistics (TBSS) and tractography study

Background Childhood abuse is associated with structural brain abnormalities. Few studies have investigated white matter tract abnormalities in medication-naive, drug-free individuals who experienced childhood abuse. We examined the association between childhood abuse and abnormalities in white matter tracts in that population, controlling for psychiatric comorbidities. Methods We collected diffusion tensor imaging data for age- and sex-matched youth with childhood abuse, psychiatric controls (matched for psychiatric diagnoses) and healthy controls. Tract-specific analysis was conducted using tractography. Tract-based spatial statistics (TBSS) was used to assess group differences in fractional anisotropy (FA) at the whole-brain level. Results We included 20 youth who experienced childhood abuse, 18 psychiatric controls and 25 healthy controls in our analysis. Tractography analysis showed abuse-specific reduced tract volume in the inferior longitudinal fasciculus (ILF) and inferior frontal-occipital fasciculus (IFoF) in the abuse group relative to both healthy and psychiatric controls. Furthermore, abnormalities in the left IFoF were associated with greater abuse severity. The TBSS analysis showed significantly reduced FA in a left-hemispheric cluster comprising the ILF, IFoF and corpus callosum splenium in the abuse group relative to healthy and psychiatric controls. Limitations It is unclear to what extent pubertal development, malnutrition and prenatal drug exposure may have influenced the findings. Conclusion Childhood abuse is associated with altered structure of neural pathways connecting the frontal, temporal and occipital cortices that are known to mediate affect and cognitive control. The abuse-specific deficits in the ILF and IFoF suggest that fibre tracts presumably involved in conveying and processing the adverse abusive experience are specifically compromised in this population.
Mesoglycan induces keratinocyte activation by triggering syndecan‐4 pathway and the formation of the annexin A1/S100A11 complex

Wound healing is a dynamic process comprising multiple events, such as inflammation, re‐epithelialization, and tissue remodeling. Re‐epithelialization phase is characterized by the engagement of several cell populations, mainly of keratinocytes that sequentially go through cycles of migration, proliferation, and differentiation to restore skin functions. Troubles can arise during the re‐epithelialization phase of skin wound healing particularly in keratinocyte migration, resulting in chronic non‐healing lesions, which represent a serious clinical problem. Over the last decades, the efforts aimed to find new pharmacological approaches for wound care were made, yet almost all current therapeutic strategies used remain inadequate or even ineffective. As such, it is crucial to identify new drugs that can enable a proper regeneration of the epithelium in wounded skin. Here, we have investigated the effects of the fibrinolytic drug mesoglycan, a glycosaminoglycans mixture derived from porcine intestinal mucosa on HaCaT human keratinocytes that were used as in vitro experimental model of skin re‐epithelialization. We found that mesoglycan induces keratinocyte migration and early differentiation by triggering the syndecan‐4/PKCα pathway and that these effects were at least in part, because of the formation of the annexin A1/S100A11 complex. Our data suggest that mesoglycan may be useful as a new pro‐healing drug for skin wound care.
Design Study for Optimum Multivariable Control System for Wind Tunnel Regulation

II ACKNOWLEDGMENTS . III ثحبلا ةصلاخ . IX NOTATIONS AND ABBREVIATIONS . IX LIST OF FIGURES AND TABELS . IX CHAPTER ONE: Introduction . 1 1.1 Research Background . 1 1.2 Research Problem Statement . 2 1.3 Research Aims and Objectives . 3 1.4 Dissertation Organization . 4 CHAPTER TWO: Wind Tunnels Review . 5 2.1 What is Wind Tunnel . 5 2.1.1 History of Wind Tunnel . 6 2.1.2 Air Flow in Wind Tunnel . 7 2.1.3 Wind Tunnel Application . 7 2.2 Elements of Wind Tunnel. 8 2.3 Types of Wind Tunnel . 9 2.4 Electrical Concerns . 11 2.5 Measurements of Parameters . 12
Association of Head Injury with Brain Amyloid Deposition: The ARIC-PET Study.

Our objective was to examine associations of head injury with total and regional brain amyloid deposition. We performed cross-sectional analyses of 329 non-demented participants (81 with prior head injury) in the Atherosclerosis Risk in Communities-Positron Emission Tomography (ARIC-PET) Study who underwent 18-florbetapir PET imaging in 2012-2014. A history of head injury was defined by self-report or emergency department/hospitalization International Classification of Diseases, Ninth Revision codes. Generalized linear regression models adjusted for demographic, socioeconomic, and dementia/cardiovascular risk factors were used to estimate prevalence ratios (PRs; 95% confidence intervals [CIs]) for elevated (> 1.2) global and regional standard uptake value ratios (SUVRs). Mean age of participants was 76 years, 57% were women, and 43% were black. Head injury was associated with increased prevalence of elevated SUVR >1.2 globally (PR: 1.31; 95% CI: 1.19-1.57), as well as in the orbitofrontal cortex (PR: 1.23); (95% CI: 1.04-1.46), prefrontal cortex (PR: 1.18; 95% CI: 1.00-1.39), superior frontal cortex (PR: 1.24; 95% CI: 1.05-1.48), and posterior cingulate (PR: 1.26; 95% CI: 1.04-1.52). There also was evidence for a dose-response relationship, whereby a history of ≥1 head injury was associated with elevated SUVR >1.2 in the prefrontal cortex and superior frontal cortex compared with persons with a history of one head injury (all, p < 0.05). In conclusion, head injury was associated with increased amyloid deposition globally and in the frontal cortex and posterior cingulate, with suggestion of a dose-response association of head injuries with beta-amyloid deposition. Further work is needed to determine if increased amyloid deposition contributes to dementia in this population.
Genome‐wide association study of six quality traits reveals the association of the TaRPP13L1 gene with flour colour in Chinese bread wheat

Summary Flour colour, kernel hardness, grain protein content and wet gluten content are important quality properties that determine end use in bread wheat. Here, a wheat 90K genotyping assay was used for a genome‐wide association study (GWAS) of the six quality‐related traits in Chinese wheat cultivars in eight environments over four years. A total of 846 significant single nucleotide polymorphisms (SNPs) were identified, explaining approximately 30% of the phenotypic variation on average, and 103 multienvironment‐significant SNPs were detected in more than four environments. Quantitative trait loci (QTL) mapping in the biparent population confirmed some important SNP loci. Moreover, it was determined that some important genes were associated with the six quality traits, including some known functional genes and annotated unknown functional genes. Of the annotated unknown functional genes, it was verified that TaRPP13L1 was associated with flour colour. Wheat cultivars or lines with TaRPP13L1‐B1a showed extremely significantly higher flour redness and lower yellowness than those with TaRPP13L1‐B1b in the Chinese wheat natural population and the doubled haploid (DH) population. Two tetraploid wheat lines with premature stop codons of the TaRPP13L1 gene mutagenized by ethyl methanesulfonate (EMS) showed extremely significantly higher flour redness and lower yellowness than wild type. Our data suggest that the TaRPP13L1 gene plays an important role in modulating wheat flour colour. This study provides useful information for further dissection of the genetic basis of flour colour and also provides valuable genes or genetic loci for marker‐assisted selection to improve the process of breeding quality wheat in China.
Simulation and evaluation of 3D traction force microscopy

Abstract Measuring cell-generated forces by Traction Force Microscopy (TFM) has become a standard tool in cell mechanobiology. Although widely used in two dimensional (2D) experiments, only a few methods exist to measure traction in three-dimensional (3D) cell culture, since 3D volumetric high-resolution microscopy and more demanding computational approaches are required. Although it is commonly known that the selected experimental and computational setup highly influence the quality and accuracy of the results, no existing methods can adequately assess the errors involved in this process. We present a fully integrated simulation and evaluation platform that allows one to simulate TFM images and quantify errors of an applied approach for traction stress reconstruction, in order to improve experiments that attempt to measure mechanical interaction in cellular systems. In this context, we show that a careful parameter selection can decrease the reconstructed traction error by up to 40%.
Long pulse 1,064‐nm neodymium‐doped yttrium aluminum garnet laser in aesthetic dermatology

Long pulse 1,064‐nm neodymium‐doped yttrium aluminum garnet (Nd:YAG) laser is a very versatile laser due to its deep penetration and absorption by hemoglobin, melanin, and water, which has gained increasing popularity over recent years for the treatment of leg veins and permanent hair removal as well as skin rejuvenation. The long‐pulse Nd:YAG laser was appointed as treatment of choice for the treatment of 0.5–3.0 mm deoxygenated, unsightly leg veins. Hair removal is another application of long pulse Nd:YAG lasers, and decreased light absorption by melanin at 1,064 nm reduces the risk of pigmentary side effects, which makes long pulse Nd:YAG laser the safest laser in darker skin types. The long pulse Nd:YAG lasers are also being employed for skin rejuvenation based on their ability to heat dermal water and stimulate collagen production. We have reviewed the parameters of Nd:YAG laser and shared our experiences in these indications that may be useful for good clinical response with minimal side effects.
Leukemia Inhibitory Factor Promotes Castration-resistant Prostate Cancer and Neuroendocrine Differentiation by Activated ZBTB46

Purpose: The molecular targets for castration-resistant prostate cancer (CRPC) are unknown because the disease inevitably recurs, and therapeutic approaches for patients with CRPC remain less well understood. We sought to investigate regulatory mechanisms that result in increased therapeutic resistance, which is associated with neuroendocrine differentiation of prostate cancer and linked to dysregulation of the androgen-responsive pathway. Experimental Design: The underlying intracellular mechanism that sustains the oncogenic network involved in neuroendocrine differentiation and therapeutic resistance of prostate cancer was evaluated to investigate and identify effectors. Multiple sets of samples with prostate adenocarcinomas and CRPC were assessed via IHC and other assays. Results: We demonstrated that leukemia inhibitory factor (LIF) was induced by androgen deprivation therapy (ADT) and was upregulated by ZBTB46 in prostate cancer to promote CRPC and neuroendocrine differentiation. LIF was found to be induced in patients with prostate cancer after ADT and was associated with enriched nuclear ZBTB46 staining in high-grade prostate tumors. In prostate cancer cells, high ZBTB46 output was responsible for the activation of LIF-STAT3 signaling and neuroendocrine-like features. The abundance of LIF was mediated by ADT-induced ZBTB46 through a physical interaction with the regulatory sequence of LIF. Analysis of serum from patients showed that cases of higher tumor grade and metastatic prostate cancer exhibited higher LIF titers. Conclusions: Our findings suggest that LIF is a potent serum biomarker for diagnosing advanced prostate cancer and that targeting the ZBTB46–LIF axis may therefore inhibit CRPC development and neuroendocrine differentiation after ADT.
“It felt like unfinished business, it feels like that's finished now”: Women's experiences of decision making around contralateral prophylactic mastectomy (CPM)

Increasing numbers of women in the United Kingdom are choosing to have a contralateral prophylactic mastectomy (CPM) after diagnosis of breast cancer. Whilst research suggests that many experience high rates of psychological well‐being after CPM, professional guidelines suggest CPM is “not required” for the majority of unilateral breast cancer patients, and some individuals consider the surgery to be controversial. Existing research has explored patients' reasons for seeking CPM; however, little is known about their experiences of decision making. This study aimed to investigate women's experiences of decision making around CPM in the United Kingdom.
Islet cells are the source of Wnts that can induce beta‐cell proliferation in vitro

Wnt proteins act mainly as paracrine signals regulating cell proliferation and differentiation. The canonical Wnt pathway has recently been associated with pancreas development and the onset of type 2 diabetes in rodent and human but the underlying mechanisms are still unclear. The aim of this work was threefold: (a) to screen for Wnt expressed by murine pancreas/islet cells, (b) to investigate whether the Wnt gene expression profile can be changed in hyperplastic islets from type 2 prediabetic mice (fed a high‐fat diet), and (c) to verify whether soluble factors (namely Wnts) released by pancreatic islets affect insulin secretion and proliferation of a beta‐cell line in vitro condition. The majority of the Wnt subtypes are expressed by islet cells, such as Wnts 2, 2b, 3, 3a, 4, 5a, 5b, 6, 7a, 7b, 8a, 8b, 9a, 9b, and 11, while in the whole pancreas homogenates were found the same subtypes, except Wnts 3, 6, 7a, and 7b. Among all the Wnts, the Wnts 3a and 5b showed a significantly increased gene expression in hyperplastic islets from prediabetic mice compared with those from control mice. Furthermore, we observed that coculture with hyperplastic or nonhyperplastic islets did not change the secretory function of the mouse insulinoma clone 6 (MIN6) beta cells but induced a significant increase in cell proliferation in this lineage, which was partially blocked by the IWR‐1 and IWP‐2 Wnt inhibitors. In conclusion, we demonstrated that murine pancreas/islet cells can secrete Wnts, and that islet‐released Wnts may participate in the regulation of beta‐cell mass under normal and prediabetic conditions.
TNF-α Drives the CCL4 Expression in Human Monocytic Cells: Involvement of the SAPK/JNK and NF-κB Signaling Pathways.

BACKGROUND/AIMS Increased circulatory levels of both TNF-α and CCL4/MIP-1β are found in metabolic diseases. However, it is unclear whether TNF-α which is a signature proinflammatory cytokine involved in metabolic inflammation, can induce/promote the expression of CCL4. METHODS THP-1 human monocytic cells and THP-1-derived macrophages were stimulated with TNF-α and LPS-treatment as a positive control. CCL4 mRNA/protein expression was measured using qRT-PCR/ELISA, respectively. Stress-activated protein kinases (SAPK)/ c-Jun N-terminal kinase (JNK) activity was determined using the assay kit. Mechanistic pathways were studied using anti-TNFR1/2 antibodies, pharmacological inhibitors, siRNAs, and NF-κB/AP-1 reporter-expressing THP-1-XBlue cells. Phosphorylation of signaling molecules was assessed by Western blotting. RESULTS TNF-α induces CCL4 expression at mRNA and protein levels, in both THP-1 monocytic cells and macrophages (P<0.05). TNF-α-driven CCL4 production was markedly abrogated by pre-treatment with anti-TNFR1/2 neutralizing antibodies. TNF-α treatment induced phosphorylation of SAPK/JNK, c-Jun, and NF-κB. Genetic and/or pharmacologic inhibition of SAPK/JNK and NF-κB pathways suppressed the TNF-α-induced CCL4 expression (P<0.05). NF-κB/AP-1 activity was found to be significantly increased in TNFα-treated SEAP reporter-expressing monocytic cells. CONCLUSION These data suggest that TNF-α drives CCL4 expression in THP-1 monocytic cells/macrophages via the activation of SAPK/JNK and NF-κB pathways. The findings may provide new insights into understanding the regulatory role of TNF-α in augmenting CCL4 expression during inflammatory conditions.