Miracle-dz/UniFAR-FTUs huggingface dataset:
ESCRT machinery mediates selective microautophagy of endoplasmic reticulum in yeast

ER‐phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER‐phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro‐ER‐phagy has been discovered, the molecules and mechanisms mediating micro‐ER‐phagy remain unknown. Here, we first show that micro‐ER‐phagy in yeast involves the conversion of stacked cisternal ER into multilamellar ER whorls during microautophagic uptake into lysosomes. Second, we identify the conserved Nem1‐Spo7 phosphatase complex and the ESCRT machinery as key components for micro‐ER‐phagy. Third, we demonstrate that macro‐ and micro‐ER‐phagy are parallel pathways with distinct molecular requirements. Finally, we provide evidence that the ESCRT machinery directly functions in scission of the lysosomal membrane to complete the microautophagic uptake of ER. These findings establish a framework for a mechanistic understanding of micro‐ER‐phagy and, thus, a comprehensive appreciation of the role of autophagy in ER homeostasis.
In Situ Bottom-up Synthesis of Porphyrin-based Covalent Organic Frameworks.

Synthesis and processing of two- or three-dimensional covalent organic frameworks (COFs) have been limited by solvent intractability and sluggish condensation kinetics. Here, we report on the electrochemical deposition of poly(5,10,15,20-tetrakis (4-aminophenyl) porphyrin)-covalent organic frameworks (POR-COFs) via formation of phenazine linkages. By adjusting the synthetic parameters, we demonstrate the bottom-up synthesis of COF dendrites. Both experiment and density functional theory (DFT) underline the prominent role of pyridine, not only as a polymerization promoter, but as a stabilizing sublattice, co-crystallizing with the framework. The crucial role of pyridine in dictating the structural properties of such a co-crystal (Py-POR-COF) is discussed. Also, a structure-to-function relationship for this class of materials, governing their electrocatalytic activity for the oxygen reduction reaction (ORR) in alkaline media, is reported.
Online Non-Preemptive Scheduling to Minimize Maximum Weighted Flow-Time on Related Machines

We consider the problem of scheduling jobs to minimize the maximum weighted flow-timeon a set of related machines. When jobs can be preempted this problem is well-understood; forexample, there exists a constant competitive algorithm using speed augmentation. When jobs mustbe scheduled non-preemptively, only hardness results are known. In this paper, we present thefirst online guarantees for the non-preemptive variant. We present the first constant competitivealgorithm for minimizing the maximum weighted flow-time on related machines by relaxing theproblem and assuming that the online algorithm can reject a small fraction of the total weight ofjobs. This is essentially the best result possible given the strong lower bounds on the non-preemptiveproblem without rejection.
Hardness of FO Model-Checking on Random Graphs

It is known that FO model-checking is ﬁxed-parameter tractable on Erdős–Rényi graphs G ( n, p ( n )) if the edge-probability p ( n ) is suﬃciently small [23] ( p ( n ) = O ( n (cid:15) /n ) for every (cid:15) > 0). A natural question to ask is whether this result can be extended to bigger probabilities. We show that for Erdős–Rényi graphs with vertex colors the above stated upper bound by Grohe is the best possible. More speciﬁcally, we show that there is no FO model-checking algorithm with average FPT run time on vertex-colored Erdős–Rényi graphs G ( n, n δ /n ) (0 < δ < 1) unless AW[ ∗ ] ⊆ FPT / poly. This might be the ﬁrst result where parameterized average-case intractability of a natural problem with a natural probability distribution is linked to worst-case complexity assumptions. We further provide hardness results for FO model-checking on other random graph models, including G ( n, 1 / 2) and Chung-Lu graphs, where our intractability results tightly match known tractability results [13]. We also provide lower bounds on the size of shallow clique minors in certain Erdős–Rényi and Chung–Lu graphs.
Concurrent Parameterized Games

Traditional concurrent games on graphs involve a ﬁxed number of players, who take decisions simultaneously, determining the next state of the game. In this paper, we introduce a parameterized variant of concurrent games on graphs, where the parameter is precisely the number of players. Parameterized concurrent games are described by ﬁnite graphs, in which the transitions bear regular languages to describe the possible move combinations that lead from one vertex to another. We consider the problem of determining whether the ﬁrst player, say Eve, has a strategy to ensure a reachability objective against any strategy proﬁle of her opponents as a coalition. In particular Eve’s strategy should be independent of the number of opponents she actually has. Technically, this paper focuses on an a priori simpler setting where the languages labeling transitions only constrain the number of opponents (but not their precise action choices). These constraints are described as semilinear sets, ﬁnite unions of intervals, or intervals. We establish the precise complexities of the parameterized reachability game problem, ranging from PTIME -complete to PSPACE -complete, in a variety of situations depending on the contraints (semilinear predicates, unions of intervals, or intervals) and on the presence or not of non-determinism.
MST4 Predicts Poor Prognosis And Promotes Metastasis By Facilitating Epithelial–Mesenchymal Transition In Gastric Cancer

Background Metastasis is the main cause for gastric cancer (GC)-related deaths. Better understanding of GC metastatic mechanism would provide novel diagnostic markers and therapeutic targets. Though it has been reported that mammalian sterile-20-like kinase 4 (MST4) exerts the oncogenic role in other tumors, the prognostic value and biological role of MST4 in GC are still unknown. Methods The expression level of MST4 in GC was analyzed by using TCGA database. Then, Western blot and polymerase chain reaction (PCR) were used to determine the MST4 expression in GC tissues and cell lines. Immunohistochemistry was performed to investigate the expression of proteins in human GC tissues, and its correlation with clinicopathologic parameters as well as the prognosis for patients with GC was analyzed. In addition, the biological function and its molecular mechanism of MST4 in GC were investigated by in vitro and in vivo assays. Results It demonstrated that MST4 expression was significantly upregulated in GC tissues and cell lines. High expression of MST4 was correlated with aggressive clinicopathological parameters such as lymph node metastasis, lymphovascular invasion (all P < 0.05). GC patients with high MST4 expression had both shorter overall survival (OS) and disease-free survival (DFS) than those with low MST4 expression (all P < 0.05). MST4 expression was an independent and significant risk factor for OS and DFS of GC patients (all P < 0.05). Results of functional experiments showed that MST4 could promote GC cells migration, invasion in vitro and metastasis in vivo. In terms of mechanism, MST4 promoted metastasis by facilitating epithelial–mesenchymal transition (EMT) through activating Ezrin pathway in GC. Further studies indicate that down-regulated miR-124-3p expression contributes to upregulated MST4 expression in GC. Conclusion Our data showed that MST4 predicts poor prognosis and promotes metastasis by facilitating epithelial–mesenchymal transition in GC. Therefore, our study suggests that MST4 can be used as a valuable prognostic biomarker and a potential therapeutic target in GC.
Recours aux urgences des patients suivis pour une maladie de Crohn : facteurs de risque et prise en charge

La maladie de Crohn (MC) est une pathologie chronique a risque de complication. Le recours au service d'accueil des urgences (SAU) a considerablement augmente ces dernieres annees. Les objectifs de notre etude sont d’identifier et de decrire, au sein d’une population de patients atteints de MC, suivis au CHU de Rouen, ceux ayant recours au SAU et d’en identifier les principaux facteurs de risque. Methodes : Les patients ayant consulte pour une MC, dans le service d’Hepato-gastro-enterologie du CHU de Rouen entre novembre 2013 et novembre 2014, ont ete inclus. L'analyse des donnees a ete realisee retrospectivement grâce au logiciel informatique CDP2 du CHU. Resultats : Au total, 638 patients ont ete inclus. Parmi eux, 49.8% (n=318) ont eu recours au moins une fois au SAU depuis le debut de leur suivi au CHU. En analyse multivariee, les facteurs de risque de recours au SAU sont : la localisation ileale ou ileo colique au diagnostic (OR=1.32, p=0.04), le changement de phenotype au cours de l'evolution (OR=1.28, p=0.02) et la duree d'evolution de la maladie (OR=1.32, p=0.02). L’exposition aux antiTNFα diminue de moitie le risque de recours au SAU (OR=0.44, p<0.0001) mais augmente le risque de passage au SAU pour une complication infectieuse (OR=2.78, p=0.001). Un TDM abdominal a ete realise au SAU chez 23.7% des patients (n=141). Un antecedent de chirurgie abdominale et un phenotype perforant ont ete identifies comme facteurs predictifs de complication au TDM en analyse univariee. Conclusion : Dans notre serie, un patient sur deux atteint d’une MC a deja consulte au SAU. Le risque de recours au SAU est lie au phenotype de la maladie et notamment aux changements de phenotype. L’exposition aux antiTNFα diminue le recours au SAU mais augmente le risque de passage au SAU pour une complication infectieuse.
Causes of conflict between clinical and administrative staff in hospitals

BACKGROUND: Providing the high-quality services in hospitals depends on to minimize conflict between all members within a health team. This study aimed to identify the causes of conflicts experienced by clinical and administrative staff in hospitals. METHODS: A cross-sectional study was carried out in 2018. The sample included 320 clinical and administrative staff from six hospitals affiliated to Ardabil University of Medical Sciences that were selected using two-step clustering sampling method. Data collection was accomplished by self-administered questionnaires. Descriptive statistics, t-test, and ANOVA were used for data analysis. RESULTS: Total conflict score revealed that clinical staff had higher levels of perceived conflict than administrative staff. In terms of organizational position, the study results showed a significant difference in the reported conflict between nurse groups and other groups (physicians and paramedical, administrative, financial, and logistic staff). The most important causes of conflict in the viewpoint of clinical staff were organizational and job characteristics (3.54 ± 1.28), poor management (3.51 ± 1.12), and inefficient communication system (3.42 ± 1.33). For administrative staff, on the other hand, poor management (3.18 ± 1.33), inefficient communication system (3.17 ± 1.36), and attitudes and perceptions (3.06 ± 1.41) were shown to be paramount factors. CONCLUSION: Clinical and administrative staff of hospitals are like parts of a train track. The irrational relationship between them will result in distortion and lower quality of services. Therefore, effective strategies to decrease staffs’ experience of conflict need to be developed. This might create a healthier and more productive work environment which positively affects the care quality.
Percutaneous collagen induction (microneedling) for the management of non-atrophic scars: literature review

Introduction: Percutaneous collagen induction (PCI) or needling techniques are increasingly popular in the reconstructive and aesthetic arena. The underlying mechanisms of action rest on producing a pattern of non-ablative and non-confluent puncture wound pattern to the dermis with a resulting regenerative effect to the skin. Methods: A detailed English literature review was conducted using PubMed Medline, Embase and Web of Science; the manuscripts were appraised and classified according to level of evidence as well risk of bias. Results are presented in descending order of evidence for non-atrophic scars. Discussion: On the basis of level 1 evidence currently available, the combination of needling and silicone gel can improve the short-term pliability, height and vascularity of hypertrophic and keloid scars. According to level 2 evidence, needling alongside spray keratinocytes can produce a statistically significant improvement to patient/observer scar ratings and improve pigmentation in hypopigmented burn scars at 12-month follow-up. Results from mixed cohort studies also point towards needling having a beneficial effect on fat graft retention. Level 3 data suggest that needling can render significant resurfacing effects to both mature and actively hypertrophic burn scars at 12-month follow-up based on objective scar scales; furthermore, favourable histological changes are seen, including better collagen alignment in the dermis and increased epidermal thickness. Conclusion: Needling techniques are promising adjuncts to non-atrophic scar management. Further research with long-term follow-up and comparative design protocols incorporating other resurfacing modalities is warranted before the exact value of needling is delineated in scar management protocols. Lay Summary Needling techniques are increasingly popular and involve the use of a device to produce numerous tiny perforations in the skin, stimulate collagen production and resurface the treated area. We undertook this study to find out whether the use of needling can have a beneficial effect on scars that are raised (hypertrophic and keloidal). We conclude that, at present, there is some evidence that needling in combination with silicone gel can improve the appearance of bulky scars in the short term; additionally needling can enhance the appearance of discoloured burn scars if used in combination with spray skin cell preparations and improve the take of fat transferred to the treated area. There are also a number of studies that have confirmed the beneficial effects of needling in the architecture of treated skin, which include improved skin structure and increased collagen production. Further research is eagerly awaited to determine the exact position of needling techniques in scar management protocols.
Biloma At The Lesser Sac Post Laparoscopic Cholecystectomy

Abstract Biloma after a laparoscopic cholecystectomy is a result of injury to the biliary tree. Most commonly the injury is due to an inadequately secured cystic duct stump, an accessory bile duct which seen in 2% of patients or duct of Luschka. In this case we describe biloma at the lesser sac after laparoscopic cholecystectomy.
Tanshinone IIA Reverses Gefitinib-Resistance In Human Non-Small-Cell Lung Cancer Via Regulation Of VEGFR/Akt Pathway

Background Gefitinib-resistance is a primary obstacle for the treatment of non-small-cell lung cancer (NSCLC). It has been shown that tanshinone IIA (Tan IIA) could induce apoptosis of NSCLC cells. However, the role of combination of gefitinib with Tan IIA on gefitinib-resistance NSCLC cells remains unclear. Thus, this study aimed to investigate the role of combination on the proliferation, apoptosis and invasion of gefitinib-resistance NSCLC cells. Methods CCK-8, flow cytometric and transwell assays were applied to detect proliferation, apoptosis and invasion in gefitinib-resistance NSCLC cells, respectively. In addition, Western blotting assay was used to detect the expressions of p-EGFR, p-VEGFR2, and p-Akt in HCC827/gefitinib cells. Results In this study, Tan IIA enhanced the cytotoxic effect of gefitinib in gefitinib-resistance NSCLC cells. In addition, the inhibitory effects of gefitinib on the proliferation, migration and invasion of gefitinib-resistance NSCLC cells were enhanced in the presence of Tan IIA. Moreover, Tan IIA enhanced the pro-apoptotic effect of gefitinib in gefitinib-resistance NSCLC cells via increasing the level of cleaved caspase 3. Meanwhile, Tan IIA enhanced the sensitivity of HCC827/gefitinib cells to gefitinib via downregulation of the VEGFR2/Akt pathway. In vivo experiments further confirmed that combination of gefitinib with Tan IIA inhibited tumor growth in mouse xenograft model of HCC827/gefitinib. Conclusion We found that Tan IIA could enhance gefitinib sensitivity in gefitinib-resistance NSCLC cells. Therefore, combination of gefitinib with Tan IIA might be considered as a therapeutic approach for the treatment of gefitinib-resistant NSCLC.
Doxorubicin/Cisplatin-Loaded Superparamagnetic Nanoparticles As A Stimuli-Responsive Co-Delivery System For Chemo-Photothermal Therapy

Introduction To date, numerous iron-based nanostructures have been designed for cancer therapy applications. Although some of them were promising for clinical applications, few efforts have been made to maximize the therapeutic index of these carriers. Herein, PEGylated silica-coated iron oxide nanoparticles (PS-IONs) were introduced as multipurpose stimuli-responsive co-delivery nanocarriers for a combination of dual-drug chemotherapy and photothermal therapy. Methods Superparamagnetic iron oxide nanoparticles were synthesized via the sonochemical method and coated by a thin layer of silica. The nanostructures were then further modified with a layer of di-carboxylate polyethylene glycol (6 kDa) and carboxylate-methoxy polyethylene glycol (6 kDa) to improve their stability, biocompatibility, and drug loading capability. Doxorubicin (DOX) and cisplatin (CDDP) were loaded on the PS-IONs through the interactions between the drug molecules and polyethylene glycol. Results The PS-IONs demonstrated excellent cellular uptake, cytocompatibility, and hemocompatibility at the practical dosage. Furthermore, in addition to being an appropriate MRI agent, PS-IONs demonstrated superb photothermal property in 0.5 W/cm2 of 808 nm laser irradiation. The release of both drugs was effectively triggered by pH and NIR irradiation. As a result of the intracellular combination chemotherapy and 10 min of safe power laser irradiation, the highest cytotoxicity for iron-based nanocarriers (97.3±0.8%) was achieved. Conclusion The results of this study indicate the great potential of PS-IONs as a multifunctional targeted co-delivery system for cancer theranostic application and the advantage of employing proper combination therapy for cancer eradication.
Thermal kinetics and thermodynamics of the dehydration reaction of Mg3(PO4)2·22H2O

Mg 3 (PO 4 ) 2 ·22H 2 O lost its crystal water in the temperature range of 40 - 200°C and the calcined sample was identified as Mg 3 (PO 4 ) 2 , was a notable for its further treatments in optical and electrical applications. Dehydration process was studied using non-isothermal thermogravimetry (TG) applying model-fitting method. Different mechanism models (chemical reaction order, diffusion and phase interfacial reaction) were applied. The activation energies calculated for the dehydration reaction; and average of activation energy was found as 160 kJ/mol. The better kinetic model of the dehydration reaction for Mg 3 (PO 4 ) 2 ·22H 2 O was selected as F3 (chemical reaction - third order). The thermodynamic functions (ΔH, ΔG and ΔS) of the dehydration reaction were calculated by the activated complex theory and found that the process was endothermic, non-spontaneous and fast.
The release of surface-anchored α-tectorin, an apical extracellular matrix protein, mediates tectorial membrane organization

Surface expression and release of α-tectorin are required for the organization of collagen bundles of the tectorial membrane. The tectorial membrane (TM) is an apical extracellular matrix (ECM) that hovers over the cochlear sensory epithelium and plays an essential role in auditory transduction. The TM forms facing the luminal endolymph-filled space and exhibits complex ultrastructure. Contrary to the current extracellular assembly model, which posits that secreted collagen fibrils and ECM components self-arrange in the extracellular space, we show that surface tethering of α-tectorin (TECTA) via a glycosylphosphatidylinositol anchor is essential to prevent diffusion of secreted TM components. In the absence of surface-tethered TECTA, collagen fibrils aggregate randomly and fail to recruit TM glycoproteins. Conversely, conversion of TECTA into a transmembrane form results in a layer of collagens on the epithelial surface that fails to form a multilayered structure. We propose a three-dimensional printing model for TM morphogenesis: A new layer of ECM is printed on the cell surface concomitant with the release of a preestablished layer to generate the multilayered TM.
Using a natural experiment to assess the effect ofspatial barriers on health service utilization.

vi Chapter 1: Introduction 1 1.1 Health Reforms and Accessibility . 1 1.2 A Natural Experiment in the MidCentral District . 4 1.3 Research Objectives . 8 1.4 Ethics Approval . 8 1.5 Thesis Structure . 9 Chapter 2: Accessibility of Health Services 10 2.1 The Organisation of New Zealand Health Delivery . 10 2.2 Factors that Affect Access . 11 2.2.1 Aspatial Factors . 12 2.2.2 Spatial Factors . 16 2.3 Spatial Accessibility . 20 2.4 Existing Literature . 22 2.4.1 Potential versus Realised Access . 23 2.4.2 The Nearest Service Fallacy . 23 2.4.3 Ecological Studies . 24 2.4.4 Heterogeneous Populations . 25 2.4. 5 Geographic Generalisations . 26 2.4. 6 Characteristics of Rural Versus Urban Meshblock Calculations . 27 2.4. 7 Euclidean Travel Times . 27 2.4. 8 Road Network Travel Times . 29 2.5 Existing Road Network Models . 31 2.5. 1 New Zealand Models . 31 2.5. 2 International Models . 33 Chapter 3: Utilisation Metrics in Health Care 36 3.1 Utilisation as a Metric . 38 3.2 Emergency Department Attendance . 38 3.2.1 Attendance . 38 3.2.2 Presentation Urgency and Triage Scores . 40 3.3 Hospital Admissions . 40 3.3.1 Length of Stay . 41 3.3.2 Case Complexity . 42 3.4 Outpatient Appointments . 43 3.4.1 Attendance . 43 3.4.2 Non-attendance . 44 3.5 General Practice Utilisation . 44 Chapter 4: Method: Data Quality 46 4.1 Tools and Standards . 46 4.2 Last-Best-Known Geocoding . 48 4.2.1 Last-Best-Known Process . 51 4.3 Corrective Geocoding . 51 4.3.1 Data Conversion . 53 4.3.2 Loading and Formatting Address Data . 55 4.3.3 Address Standardisation . 56 4.3.4 Matching . 59 4.3.5 Geocoding . 60 4.3. 6 Validation . 61 4.4 Developing a Travel Time Model . 62 4.4.1 Existing Attributes . 62 4.4.2 Deriving Journey Segments . 64 4.4.3 Deriving A Sinuosity Index . 64 4.4.4 Deriving Weighted Mean Sinuosity Index . 65 4.4. 5 Deriving Intersection Density . 65 4.4. 6 Deriving Elevation Data . 66 4.4. 7 Deriving Maximum and Total Turning Angles . 67
Detecting and understanding differentiation of microarray expression data

xiv Chapter 1: Introduction 1 1.1 Gene expression and Microarray technologies . 1 1.2 Types of Microarrays . 3 1.3 Microarray data analysis . 5 Chapter 2: Sub-array normalization for oligonucleotide array 8 2.1 Background . 8 2.2 Normalization approaches for oligonucleotide array . 9 2.2.1 Loess normalization . 10 2.2.2 Contrast normalization . 11 2.2.3 Quantiles normalization . 11 2.2.4 Qspline normalization . 12 2.2. 5 Invariantset normalization . 12 2.3 Introduction to Sub-Sub normalization . 13 2.3. 1 Differentiation fraction . 13 2.3. 2 Spatial pattern . 14 2.4 Methods . 15 2.4. 1 Statistical principle of normalization . 15 2.4. 2 Differentiation fraction and undifferentiated probe set . 16 2.4. 3 Spatial pattern and sub-arrays . 17 2.4. 4 Parameterization . 17 2.4. 5 Simple least trimmed squares . 17