Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural insights into the aPKC regulatory switch mechanism of the human cell polarity protein lethal giant larvae 2

Significance Epithelial cells have a spatially polarized organization. For example, one surface of an intestinal epithelial cell, called the apical side, faces the lumen of the gut and has a membrane composition distinct from those of the basolateral sides. Several proteins that control the development and maintenance of apical-basolateral polarity have been identified, but their molecular mechanisms are poorly understood. Lethal giant larvae (Lgl) is a basolateral polarity protein that is lost selectively from the apical membrane during development, due to its phosphorylation by atypical protein kinase C. Here, we describe the 3D structure of Lgl in both its unmodified and phosphorylated states, and show that phosphorylation of Lgl mediates a structural switch that controls its association with the plasma membrane. Metazoan cell polarity is controlled by a set of highly conserved proteins. Lethal giant larvae (Lgl) functions in apical-basal polarity through phosphorylation-dependent interactions with several other proteins as well as the plasma membrane. Phosphorylation of Lgl by atypical protein kinase C (aPKC), a component of the partitioning-defective (Par) complex in epithelial cells, excludes Lgl from the apical membrane, a crucial step in the establishment of epithelial cell polarity. We present the crystal structures of human Lgl2 in both its unphosphorylated and aPKC-phosphorylated states. Lgl2 adopts a double β-propeller structure that is unchanged by aPKC phosphorylation of an unstructured loop in its second β-propeller, ruling out models of phosphorylation-dependent conformational change. We demonstrate that phosphorylation controls the direct binding of purified Lgl2 to negative phospholipids in vitro. We also show that a coil–helix transition of this region that is promoted by phosphatidylinositol 4,5-bisphosphate (PIP2) is also phosphorylation-dependent, implying a highly effective phosphorylative switch for membrane association.
The degree to which spiritual needs of patients near the end of life are met.

PURPOSE/OBJECTIVES To determine to what degree the spiritual needs of patients near the end of life are met. DESIGN Descriptive. SETTING One inpatient and five outpatient hospices. SAMPLE 62 female and 38 male hospice patients with a mean age of 67 years; 74% were dying from cancer. METHODS Each subject completed the Spiritual Needs Inventory and rated life satisfaction via the Cantril ladder. MAIN RESEARCH VARIABLES Spiritual needs and life satisfaction. FINDINGS Women, patients residing in a nursing home or an inpatient hospice unit, and patients with lower levels of education reported a higher number of unmet spiritual needs. Needs that could be met independently by patients and were not related to functional status were met at a higher rate than those that were dependent on others and on functional status. CONCLUSIONS Spiritual activities are important to patients who are near the end of life, but these patients may have a variety of unmet spiritual needs that depend on many factors, including the care setting. IMPLICATIONS FOR NURSING Nurses must recognize the importance of spirituality to patients near the end of life. Assessment for specific spiritual needs can lead to the development of interventions to meet those needs. Meeting patients' spiritual needs can enhance their quality of life.
On O’Hara knot energies I: Regularity for critical knots

We develop a regularity theory for extremal knots of scale invariant knot energies defined by J. O'hara in 1991. This class contains as a special case the Mobius energy. For the Mobius energy, due to the celebrated work of Freedman, He, and Wang, we have a relatively good understanding. Their approch is crucially based on the invariance of the Mobius energy under Mobius transforms, which fails for all the other O'hara energies. We overcome this difficulty by re-interpreting the scale invariant O'hara knot energies as a nonlinear, nonlocal $L^p$-energy acting on the unit tangent of the knot parametrization. This allows us to draw a connection to the theory of (fractional) harmonic maps into spheres. Using this connection we are able to adapt the regularity theory for degenerate fractional harmonic maps in the critical dimension to prove regularity for minimizers and critical knots of the scale-invariant O'hara knot energies.
Islet amyloidosis in a child with type 1 diabetes

ABSTRACT Histopathology based studies of the pancreas obtained from organ donors are increasing our awareness of islet phenotypic heterogeneity during development and aging, as well as in settings of type 1 diabetes, type 2 diabetes, monogenic diabetes or other forms of this metabolic disease. Islet amyloidosis represents a histopathological feature classically ascribed to patients with type 2 diabetes. Herein, the occurrence of islet amyloidosis and its severity are reported in a child with type 1 diabetes along with histological comparisons of islet amyloidosis in two young adults with recent-onset type 1 diabetes. Islet amyloidosis was infrequent yet widely distributed throughout the pancreas in the child with type 1 diabetes and both adults with type 1 diabetes, with no such pathology seen in matched control donors. Analysis of these cases add to the increasing appreciation of islet heterogeneity in children and young adults with type 1 diabetes. Such knowledge also supports a notion that multiple pathophysiological mechanisms underlie the loss of functional β-cell mass in the spectrum of clinical phenotypes in patients with type 1 diabetes.
Association between p53 protein phosphorylated at serine 20 expression and ovarian carcinoma stem cells phenotype: correlation with clinicopathological parameters of ovarian cancer.

Biological behavior of ovarian carcinomas might be results of cellular diversity existing in tumor tissue which consist of differentiated and undifferentiated cells showing stem cells biological properties and function. We examined correlation between p53 protein phosphorylated at serine 20 (p-p53(Ser20)) and CD133, SOX2, Notch1 expression in order to reveal p-p53(Ser20) stemness function in ovarian cancer. p-p53(Ser20), CD133, Notch1, SOX2 expression was analyzed on 104 ovarian carcinomas using immunohistochemical staining. The positive correlation between p53 and p-p53(Ser20) (P=0.02), p53 and SOX2 (P=0.02), p-p53(Ser20) and Notch1 (P=0.03), p-p53(Ser20) and CD133 (P=0.01) expression was observed in ovarian carcinomas. The parallel expression of p-p53(Ser20)/CD133, p-p53(Ser20)/Notch1 reflecting coexpression of these proteins in single carcinoma cell, and p-p53(Ser20)/SOX2 expression was associated with advanced stage and p-p53(Ser20)/Notch1, p53/SOX2, p-p53(Ser20)/SOX2 parallel expression correlated with high tumor grade. The correlation between p-p53(Ser20) and CD133, Notch1, SOX2 expression and clinical parameters indicate, that malignancy and biological behavior of ovarian carcinomas depend on interaction between p-p53(Ser20) and carcinoma stem cells biomarkers expression.
The Development of the Enteropneust Hemichordate Balanoglossus misakiensis Kuwano

Abstract We describe development from fertilization to metamorphosis of the enteropneust hemichor-date Balanoglossus misakiensis. This is the first report to describe the complete development of an indirect-developing hemichordate under laboratory conditions. Mature adults were induced to spawn by shifting the temperature of seawater from 23 to 28°C. Eggs (200 μm diameter) were enclosed within a nonmucilaginous membrane, and dispersed readily in seawater. After artificial insemination, a fertilization envelope was elevated from the egg surface beneath the egg membrane; this was followed by the formation of the first and second polar bodies within the envelope. Zygotes cleaved at 20-min intervals to form blastulae, and gastrulation started 9 h after fertilization. Embryos hatched 1 day after fertilization to become typical feeding tornaria larvae. The larvae metamorphosed 7–10 days after fertilization without undergoing the first (Müller) or forth (Krohn) stage of indirect-developing hemichordate development. Larvae that were not fed failed to metamorphose. Juveniles completed adult body formation within a week of settling in sand at the bottom of the culture tube. We discuss heterochronical modifications of B. misakiensis development, and make the case for this species as a potential model organism for the investigation of indirect-developing hemichordates.
Ethiopathogenic mechanisms of endometriosis-related infertility

Endometriosis is a highly prevalent disease among women of reproductive age and is frequently associated to infertility. However, the mechanisms underlying endometriosis-related infertility are still not completely known. Several studies have been conducted in order to elucidate this question. Besides anatomical changes that may impair gametes and embryo transport along the tubes; a smaller ovarian reserve due to advanced endometriosis and endometriomas; and a dysregulated hypothalamic-pituitary-ovarian axis, there are pieces of evidence suggesting that the peritoneal ectopic endometrial foci may induce a local inflammatory response, with the recruitment of macrophages, cytokine release, and reactive oxygen species generation, leading to a pro-oxidant peritoneal microenvironment. These alterations may be systemically reflected and also affect the follicular microenvironment. A harmful follicular fluid may disrupt cumulus cells functions and, consequently, compromise oocyte competence. There is also evidence suggesting that the peritoneal fluid of women with endometriosis may alter sperm function. Reduced endometrial receptivity is also pointed as a possible mechanism involved in endometriosis-related infertility, which needs further investigation.
Online Voltage Control in Distribution Systems With Multiple Voltage Regulating Devices

Voltage regulation in distribution systems is typically performed with the aid of multiple voltage regulating devices, such as on-load tap changer and step voltage regulators. These devices are conventionally tuned and locally coordinated using Volt/VAR optimization strategies in accordance with the time-graded operation. However, in case of distribution systems with distributed generation (DG), there could be a possibility of simultaneous responses of DG and multiple voltage regulators for correcting the target bus voltage, thereby resulting in operational conflicts. This paper proposes an online voltage control strategy for a realistic distribution system containing a synchronous machine-based renewable DG unit and other voltage regulating devices. The proposed strategy minimizes the operational conflicts by prioritizing the operations of different regulating devices while maximizing the voltage regulation support by the DG. It is tested on an interconnected medium voltage distribution system, present in New South Wales, Australia, through time-domain simulation studies. The results have demonstrated that voltage control for a distribution feeder can effectively be achieved on a real-time basis through the application of the proposed control strategy.
A Surprisingly Robust Trick for the Winograd Schema Challenge

The Winograd Schema Challenge (WSC) dataset WSC273 and its inference counterpart WNLI are popular benchmarks for natural language understanding and commonsense reasoning. In this paper, we show that the performance of three language models on WSC273 strongly improves when fine-tuned on a similar pronoun disambiguation problem dataset (denoted WSCR). We additionally generate a large unsupervised WSC-like dataset. By fine-tuning the BERT language model both on the introduced and on the WSCR dataset, we achieve overall accuracies of 72.2% and 71.9% on WSC273 and WNLI, improving the previous state-of-the-art solutions by 8.5% and 6.8%, respectively. Furthermore, our fine-tuned models are also consistently more robust on the “complex” subsets of WSC273, introduced by Trichelair et al. (2018).
The Intention‐to‐Treat Effect of Bridging Treatments in the Setting of Milan Criteria–In Patients Waiting for Liver Transplantation

In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria (MC), the benefit of locoregional therapies (LRTs) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing risk analysis, risk factors for HCC‐dependent LT failure, defined as pretransplant tumor‐related delisting or posttransplant recurrence. The study was registered at www.clinicaltrials. gov (identification number NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IPTW) analysis was used: 1083 MC‐in patients (no LRT = 182; LRT = 901) were balanced using 8 variables: age, sex, Model for End‐Stage Liver Disease (MELD) value, hepatitis C virus status, hepatitis B virus status, largest lesion diameter, number of nodules, and alpha‐fetoprotein (AFP). All the covariates were available at the first referral. After the IPTW, a pseudo‐population of 2019 patients listed for LT was analyzed, comparing 2 homogeneous groups of untreated (n = 1077) and LRT‐treated (n = 942) patients. Tumor progression after LRT was the most important independent risk factor for HCC‐dependent failure (subhazard ratio [SHR], 5.62; P < 0.001). Other independent risk factors were major tumor diameter, AFP, MELD, patient age, male sex, and period of wait‐list registration. One single LRT was protective compared with no treatment (SHR, 0.51; P < 0.001). The positive effect was still observed when 2‐3 treatments were performed (SHR, 0.66; P = 0.02), but it was lost in the case of ≥4 LRTs (SHR, 0.80; P = 0.27). In conclusion, for MC‐in patients, up to 3 LRTs are beneficial for success in intention‐to‐treat LT patients, with a 49% to 34% reduction in failure risk compared with untreated patients. This benefit is lost if more LRTs are required. A poor response to LRT is associated with a higher risk for HCC‐dependent transplant failure.
Results of Pediatric Oncology Group Protocol 8104 for Infants with Stages D and DS Neuroblastoma

Purpose We determined the complete response and survival rates for infants with disseminated (state D) neuroblastoma that followed therapy identical to that for regional disease. In those infants whose disease excluded cortical bone metastases (state DS), we determined complete response rates achieved either spontaneously or with stage D therapy. Patients and Methods Eight-eight patients with metastatic disease received induction chemotherapy followed by a second operation, the results of which determined additional therapy. Twenty-five patients were observed after diagnosis, without chemotherapy, until a second operation. Results The complete response (CR) rates for patients with stage D discase after induction chemotherapy and postinduction surgery were 26% and 52%, respectively, and for immediately treated patients with stage DS disease 69% and 77%, respectively. Fifty-four percent of initially observed patients with stage DS disease achieved CR after a second operation; 44% were never treated beyond these two operations. Five-year actuarial survival rates for patients with stage D and for all those with stage DS disease were 60% (SE = 6%) and 90% (SE = 5%), respectively. Conclusions Improved survival rates for patients with stage D disease were achieved on this protocol but remained considerably lower than those for infants with less extensive disease. Rates of survival for patients with stage DS disease were achieved with therapy less aggressive than in published series.
Repeated evolution of drag reduction at the air–water interface in diving kingfishers

Piscivorous birds have a unique suite of adaptations to forage under the water. One method aerial birds use to catch fish is the plunge dive, wherein birds dive from a height to overcome drag and buoyancy in the water. The kingfishers are a well-known clade that contains both terrestrially foraging and plunge-diving species, allowing us to test for morphological and performance differences between foraging guilds in an evolutionary context. Diving species have narrower bills in the dorsoventral and sagittal plane and longer bills (size-corrected data, n = 71 species, p < 0.01 for all). Although these differences are confounded by phylogeny (phylogenetically corrected ANOVA for dorsoventral p = 0.26 and length p = 0.14), beak width in the sagittal plane remains statistically different (p < 0.001). We examined the effects of beak morphology on plunge performance by physically simulating dives with three-dimensional printed models of beaks coupled with an accelerometer, and through computational fluid dynamics (CFD). From physically simulated dives of bill models, diving species have lower peak decelerations, and thus enter the water more quickly, than terrestrial and mixed-foraging species (ANOVA p = 0.002), and this result remains unaffected by phylogeny (phylogenetically corrected ANOVA p = 0.05). CFD analyses confirm these trends in three representative species and indicate that the morphology between the beak and head is a key site for reducing drag in aquatic species.
Surface Modification of Cellulose Nanocrystals with Succinic Anhydride

The surface modification of cellulose nanocrystals (CNC) is a key intermediate step in the development of new functionalities and the tailoring of nanomaterial properties for specific applications. In the area of polymeric nanocomposites, apart from good interfacial adhesion, the high thermal stability of cellulose nanomaterial is vitally required for the stable processing and improvement of material properties. In this respect, the heterogeneous esterification of CNC with succinic anhydride was investigated in this work in order to obtain CNC with optimised surface and thermal properties. The influence of reaction parameters, such as time, temperature, and molar ratio of reagents, on the structure, morphology and thermal properties, were systematically studied over a wide range of values by DLS, FTIR, XPS, WAXD, SEM and TGA methods. It was found that the degree of surface substitution of CNC increased with the molar ratio of succinic anhydride to cellulose hydroxyl groups (SA:OH), as well as the reaction time, whilst the temperature of reaction showed a moderate effect on the degree of esterification in the range of 70–110 °C. The studies on the thermal stability of modified nanoparticles indicated that there is a critical extent of surface esterification below which only a slight decrease of the initial temperature of degradation was observed in pyrolytic and oxidative atmospheres. A significant reduction of CNC thermal stability was observed only for the longest reaction time (240 min) and the highest molar ratio of SA:OH. This illustrates the possibility of manufacturing thermally stable, succinylated, CNC by controlling the reaction conditions and the degree of esterification.
Advances in Chemical and Biological Methods to Identify Microorganisms—From Past to Present

Fast detection and identification of microorganisms is a challenging and significant feature from industry to medicine. Standard approaches are known to be very time-consuming and labor-intensive (e.g., culture media and biochemical tests). Conversely, screening techniques demand a quick and low-cost grouping of bacterial/fungal isolates and current analysis call for broad reports of microorganisms, involving the application of molecular techniques (e.g., 16S ribosomal RNA gene sequencing based on polymerase chain reaction). The goal of this review is to present the past and the present methods of detection and identification of microorganisms, and to discuss their advantages and their limitations.
Unsupervised Deep Power Saving and Contrast Enhancement for OLED Displays

Various power saving and contrast enhancement (PSCE) techniques have been applied to an organic light emitting diode (OLED) display for reducing the power demands of the display while preserving the image quality. In this paper, we propose a new deep learning-based PSCE scheme that can save power consumed by the OLED display while enhancing the contrast of the displayed image. In the proposed method, the power consumption is saved by simply reducing the brightness a certain ratio, whereas the perceived visual quality is preserved as much as possible by enhancing the contrast of the image using a convolutional neural network (CNN). Furthermore, our CNN can learn the PSCE technique without a reference image by unsupervised learning. Experimental results show that the proposed method is superior to conventional ones in terms of image quality assessment metrics such as a visual saliency-induced index (VSI) and a measure of enhancement (EME).
Opioid receptor‐like 1 (ORL1) receptor binding and the biological properties of Ac‐Arg‐Tyr‐Tyr‐Arg‐Ile‐Arg‐NH2 and its analogs

Hexapeptides such as Ac‐Arg‐Tyr‐Tyr‐Arg‐Ile‐Lys‐NH2 and Ac‐Arg‐Tyr‐Tyr‐Arg‐Trp‐Arg‐NH2 have been isolated from a combinatorial peptide library as small peptide ligands for the opioid peptide‐like 1 (ORL1) receptor. To investigate the detailed structural requirements of hexapeptides, 25 analogs of these hexapeptides, based on the novel analog Ac‐Arg‐Tyr‐Tyr‐Arg‐Ile‐Arg‐NH2 (1), were synthesized and tested for their ORL1 receptor affinity and agonist/antagonist activity on mouse vas deferens (MVD) tissues. Analog 1 and its Cit6‐analog (10) were found to possess high affinity to the ORL1 receptor, comparable to that of nociceptin/orphanin FQ, and exhibited potent antagonist activity (pA2 values of 7.77 for 1 and 7.51 for 10, which are higher than that of [NPhe1]nociceptin(1–13)‐NH2 (6.90) on MVD assay. It was also found that the amino acid residue in position 5 plays a key role in agonist/antagonist activity, i.e. an L‐configuration aliphatic amino acid is required for potent antagonist activity, while a nonchiral or D‐configuration residue produces potent agonist activity. These lines of evidence may provide insight into the mechanisms controlling agonist/antagonist switching in the ORL1 receptor, and may also serve to help developing more potent ORL1 agonists and antagonists. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
MiR‐21‐5p regulates mycobacterial survival and inflammatory responses by targeting Bcl‐2 and TLR4 in Mycobacterium tuberculosis‐infected macrophages

To date, very little is known about the role of microRNA‐21‐5p (miR‐21‐5p) in Mycobacterium tuberculosis (M.tb)‐infected macrophages. Here, we show that M.tb infection of RAW264.7 and THP‐1 cells increases the expression of miR‐21‐5p. MiR‐21‐5p enhances M.tb survival and apoptosis, and attenuates the secretion of inflammatory cytokines, including interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α in M.tb‐infected macrophages. Dual‐luciferase reporter assay revealed that the 3′‐UTR of B‐cell lymphoma 2 (Bcl‐2) or toll‐like receptor 4 (TLR4) is a direct target of miR‐21‐5p. Enforced expressions of Bcl‐2 or TLR4 partially attenuate the suppressive effects of miR‐21‐5p on cell viability and inflammatory cytokines, and effectively decrease bacterial burden. Therefore, the present study highlights a novel role for miR‐21‐5p in regulation of mycobacterial survival and inflammatory responses by targeting Bcl‐2 and TLR4 in M.tb‐infected macrophages.