A ubiquitin-proteasome pathway degrades the inner nuclear membrane protein Bqt4 to maintain nuclear membrane homeostasis.

Aberrant accumulation of inner nuclear membrane (INM) proteins is associated with deformed nuclear morphology and mammalian diseases. However, the mechanisms underlying the maintenance of INM homeostasis remain poorly understood. In this study, we explored the degradation mechanisms of the INM protein Bqt4 in the fission yeast Schizosaccharomyces pombe. We have previously shown that Bqt4 interacts with the transmembrane protein Bqt3 at the INM and is degraded in the absence of Bqt3. Here, we reveal that excess Bqt4, unassociated with Bqt3, is targeted for degradation by the ubiquitin-proteasome system localized in the nucleus and Bqt3 antagonizes this process. The degradation process involves the Doa10 E3 ligase complex at the INM. Bqt4 is a tail-anchored protein and the Cdc48 complex is required for its degradation. The C-terminal transmembrane domain of Bqt4 was necessary and sufficient for proteasome-dependent protein degradation. Accumulation of Bqt4 at the INM impaired cell viability with nuclear envelope deformation, suggesting that quantity control of Bqt4 plays an important role in nuclear membrane homeostasis.

Non-line-of-sight imaging using phasor-field virtual wave optics.

Non-line-of-sight imaging allows objects to be observed when partially or fully occluded from direct view, by analysing indirect diffuse reflections off a secondary relay surface. Despite many potential applications1-9, existing methods lack practical usability because of limitations including the assumption of single scattering only, ideal diffuse reflectance and lack of occlusions within the hidden scene. By contrast, line-of-sight imaging systems do not impose any assumptions about the imaged scene, despite relying on the mathematically simple processes of linear diffractive wave propagation. Here we show that the problem of non-line-of-sight imaging can also be formulated as one of diffractive wave propagation, by introducing a virtual wave field that we term the phasor field. Non-line-of-sight scenes can be imaged from raw time-of-flight data by applying the mathematical operators that model wave propagation in a conventional line-of-sight imaging system. Our method yields a new class of imaging algorithms that mimic the capabilities of line-of-sight cameras. To demonstrate our technique, we derive three imaging algorithms, modelled after three different line-of-sight systems. These algorithms rely on solving a wave diffraction integral, namely the Rayleigh-Sommerfeld diffraction integral. Fast solutions to Rayleigh-Sommerfeld diffraction and its approximations are readily available, benefiting our method. We demonstrate non-line-of-sight imaging of complex scenes with strong multiple scattering and ambient light, arbitrary materials, large depth range and occlusions. Our method handles these challenging cases without explicitly inverting a light-transport model. We believe that our approach will help to unlock the potential of non-line-of-sight imaging and promote the development of relevant applications not restricted to laboratory conditions.

Increasing and widespread vulnerability of intact tropical rainforests to repeated droughts.

Intact tropical rainforests have been exposed to severe droughts in recent decades, which may threaten their integrity, their ability to sequester carbon, and their capacity to provide shelter for biodiversity. However, their response to droughts remains uncertain due to limited high-quality, long-term observations covering extensive areas. Here, we examined how the upper canopy of intact tropical rainforests has responded to drought events globally and during the past 3 decades. By developing a long pantropical time series (1992 to 2018) of monthly radar satellite observations, we show that repeated droughts caused a sustained decline in radar signal in 93%, 84%, and 88% of intact tropical rainforests in the Americas, Africa, and Asia, respectively. Sudden decreases in radar signal were detected around the 1997-1998, 2005, 2010, and 2015 droughts in tropical Americas; 1999-2000, 2004-2005, 2010-2011, and 2015 droughts in tropical Africa; and 1997-1998, 2006, and 2015 droughts in tropical Asia. Rainforests showed similar low resistance (the ability to maintain predrought condition when drought occurs) to severe droughts across continents, but American rainforests consistently showed the lowest resilience (the ability to return to predrought condition after the drought event). Moreover, while the resistance of intact tropical rainforests to drought is decreasing, albeit weakly in tropical Africa and Asia, forest resilience has not increased significantly. Our results therefore suggest the capacity of intact rainforests to withstand future droughts is limited. This has negative implications for climate change mitigation through forest-based climate solutions and the associated pledges made by countries under the Paris Agreement.

Dipicolylamine/Metal Complexes that Promote Direct Cell-Membrane Penetration of Octaarginine.

Marked promotion of membrane permeation of a cell-penetrating peptide, octaarginine (R8), was attained by attachment to a single 2,2'-dipicolylamine moiety (DPA-R8) that forms 1:1 complexes with metal ions. Studies using giant unilamellar vesicles demonstrated that DPA targets phospholipids and enhances R8 binding to the membranes in the presence of metal ions. While DPA/Zn(II) complex has been most frequently employed for chelate formation with phosphates, Ni(II) had the most prominent effect on the membrane binding and penetration of DPA-R8. Facile cytosolic distribution of DPA-R8 was also attained in a few minutes in the presence of Ni(II). Analysis of the cellular uptake methods of DPA-R8/Ni(II) suggested the involvement of direct permeation through cell membrane without the use of endocytosis. The applicability of this system to the intracellular delivery of bioactive compounds was exemplified using a peptidomimetic farnesyltransferase inhibitor, FTI277.

A Guanidyl-Based Bivalent Peptidomimetic Inhibits K-Ras Prenylation and Association with c-Raf.

Unusual lipid modification of K-Ras makes Ras-directed cancer therapy a challenging task. Aiming to disrupt electrostatic-driven protein-protein interactions (PPIs) of K-Ras with FTase and GGTase I, a series of bivalent dual inhibitors that recognize the active pocket and the common acidic surface of FTase and GGTase I were designed. The structure-activity-relationship study resulted in 8 b, in which a biphenyl-based peptidomimetic FTI-277 was attached to a guanidyl-containing gallate moiety through an alkyl linker. Cell-based evaluation demonstrated that 8 b exhibited substantial inhibition of K-Ras processing without apparent interference with Rap-1A processing. Fluorescent imaging showed that 8 b disrupts localization of K-Ras to the plasma membrane and impairs interaction with c-Raf, whereas only FTI-277 was found to be inactive. These results suggest that targeting the PPI interface of K-Ras may provide an alternative method of inhibiting K-Ras.

Mapping of Rice Varieties and Sowing Date Using X-Band SAR Data.

Rice is a major staple food for nearly half of the world's population and has a considerable contribution to the global agricultural economy. While spaceborne Synthetic Aperture Radar (SAR) data have proved to have great potential to provide rice cultivation area, few studies have been performed to provide practical information that meets the user requirements. In rice growing regions where the inter-field crop calendar is not uniform such as in the Mekong Delta in Vietnam, knowledge of the start of season on a field basis, along with the planted rice varieties, is very important for correct field management (timing of irrigation, fertilization, chemical treatment, harvest), and for market assessment of the rice production. The objective of this study is to develop methods using SAR data to retrieve in addition to the rice grown area, the sowing date, and the distinction between long and short cycle varieties. This study makes use of X-band SAR data from COSMO-SkyMed acquired from 19 August to 23 November 2013 covering the Chau Thanh and Thoai Son districts in An Giang province, Viet Nam, characterized by a complex cropping pattern. The SAR data have been analyzed as a function of rice parameters, and the temporal and polarization behaviors of the radar backscatter of different rice varieties have been interpreted physically. New backscatter indicators for the detection of rice paddy area, the estimation of the sowing date, and the mapping of the short cycle and long cycle rice varieties have been developed and assessed. Good accuracy has been found with 92% in rice grown area, 96% on rice long or short cycle, and a root mean square error of 4.3 days in sowing date. The results have been discussed regarding the generality of the methods with respect to the rice cultural practices and the SAR data characteristics.

Mixed-Metal Zeolitic Imidazolate Frameworks and their Selective Capture of Wet Carbon Dioxide over Methane.

A presynthesized, square planar copper imidazole complex, [Cu(imidazole)4](NO3)2, was utilized as a precursor in the synthesis of a new series of zeolitic imidazolate frameworks, termed ZIF-202, -203, and -204. The structures of all three members were solved by single-crystal X-ray diffraction analysis, which revealed ZIF-203 and -204 having successfully integrated square planar units within the backbones of their respective frameworks. As a result of this unit, the structures of both ZIF-203 and -204 were found to adopt unprecedented three-dimensional nets, namely, ntn and thl, respectively. One member of this series, ZIF-204, was demonstrated to be highly porous, exhibit exceptional stability in water, and selectively capture CO2 over CH4 under both dry and wet conditions without any loss in performance over three cycles. Remarkably, the regeneration of ZIF-204 was performed under the mild conditions of flowing a pure N2 gas through the material at ambient temperature.

Robust pedestrian detection by combining visible and thermal infrared cameras.

With the development of intelligent surveillance systems, the need for accurate detection of pedestrians by cameras has increased. However, most of the previous studies use a single camera system, either a visible light or thermal camera, and their performances are affected by various factors such as shadow, illumination change, occlusion, and higher background temperatures. To overcome these problems, we propose a new method of detecting pedestrians using a dual camera system that combines visible light and thermal cameras, which are robust in various outdoor environments such as mornings, afternoons, night and rainy days. Our research is novel, compared to previous works, in the following four ways: First, we implement the dual camera system where the axes of visible light and thermal cameras are parallel in the horizontal direction. We obtain a geometric transform matrix that represents the relationship between these two camera axes. Second, two background images for visible light and thermal cameras are adaptively updated based on the pixel difference between an input thermal and pre-stored thermal background images. Third, by background subtraction of thermal image considering the temperature characteristics of background and size filtering with morphological operation, the candidates from whole image (CWI) in the thermal image is obtained. The positions of CWI (obtained by background subtraction and the procedures of shadow removal, morphological operation, size filtering, and filtering of the ratio of height to width) in the visible light image are projected on those in the thermal image by using the geometric transform matrix, and the searching regions for pedestrians are defined in the thermal image. Fourth, within these searching regions, the candidates from the searching image region (CSI) of pedestrians in the thermal image are detected. The final areas of pedestrians are located by combining the detected positions of the CWI and CSI of the thermal image based on OR operation. Experimental results showed that the average precision and recall of detecting pedestrians are 98.13% and 88.98%, respectively.

Human detection based on the generation of a background image by using a far-infrared light camera.

The need for computer vision-based human detection has increased in fields, such as security, intelligent surveillance and monitoring systems. However, performance enhancement of human detection based on visible light cameras is limited, because of factors, such as nonuniform illumination, shadows and low external light in the evening and night. Consequently, human detection based on thermal (far-infrared light) cameras has been considered as an alternative. However, its performance is influenced by the factors, such as low image resolution, low contrast and the large noises of thermal images. It is also affected by the high temperature of backgrounds during the day. To solve these problems, we propose a new method for detecting human areas in thermal camera images. Compared to previous works, the proposed research is novel in the following four aspects. One background image is generated by median and average filtering. Additional filtering procedures based on maximum gray level, size filtering and region erasing are applied to remove the human areas from the background image. Secondly, candidate human regions in the input image are located by combining the pixel and edge difference images between the input and background images. The thresholds for the difference images are adaptively determined based on the brightness of the generated background image. Noise components are removed by component labeling, a morphological operation and size filtering. Third, detected areas that may have more than two human regions are merged or separated based on the information in the horizontal and vertical histograms of the detected area. This procedure is adaptively operated based on the brightness of the generated background image. Fourth, a further procedure for the separation and removal of the candidate human regions is performed based on the size and ratio of the height to width information of the candidate regions considering the camera viewing direction and perspective projection. Experimental results with two types of databases confirm that the proposed method outperforms other methods.

Culture Negative Pasteurella multocida Confirmed Prosthetic Hip Infection using Next-generation Sequencing.

Introduction: Prosthetic joint infections (PJIs) are a dreaded complication of joint arthroplasty. Zoonotic organisms such as Pasteurella multocida (PM) rarely cause PJIs. Still, these organisms can be challenging to treat due to a low suspicion index and inadequate growth on culture. Next-generation sequencing (NGS) can be used to identify organisms in culture-negative PJIs. This is the first reported case of a PM positive total hip arthroplasty PJI using NGS. Case Report: We report the case of a 70-year-old male presenting with a periprosthetic hip infection. PM was identified in high relative abundance on NGS and grew in culture. Subsequent intraoperative samples were culture negative for Pasteurella, but NGS demonstrated continued presence of Pasteurella. Conclusion: PM is a rare case of PJI, but a high index of suspicion must be maintained in the appropriate clinical context. NGS is a vital tool for the identification of culture-negative organisms like PM.

A narrative review of the relationship between head and neck cancer and obstructive sleep apnea: Clinical studies and statistical analysis.

Obstructive sleep apnea (OSA) is an underestimated and overlooked comorbidity in head and neck cancer (HNC) care. Refining HNC-OSA management requires an improved grasp of the HNC-OSA relationship. Thus, this paper reviews the current course of HNC therapy, causal and associative relationships before and after treatment, and statistical methods quantifying HNC-OSA interactions. This evaluation serves a dual purpose: to support oncologists and sleep physicians in improving the treatment outcomes of patients undergoing HNC treatment by considering OSA as a comorbidity and to assist researchers in selecting suitable analytical models for investigating the correlation between OSA and HNC. The investigation confirms a positive correlation between the apnea-hypopnea index (AHI) and primary tumor size, consistent with prior findings. Case studies also reported new evidence of lipoma and head-neck tumors triggering OSA, and sleep apnea surgery prompting tumor development. This paper provides an overview of existing statistical models and offers suggestions for model selection and a framework for designing experiments that delve into research questions surrounding the link between OSA and HNC across various stages of cancer treatment. Despite progress, understanding the HNC-OSA interplay remains incomplete due to limited histological, molecular, and clinical data. Future studies with longitudinal data are crucial for comprehensive insights.

Development of a computer-based tool to obtain a family health history in Vietnam.

Background: Family health history (FHH) is central to human genomic profiling construction; however, there is no protocol for documenting FHH in a pedigree format in Vietnam.Aim: A "Gia Su Suc Khoe" (GSSK) tool was developed to create a user-friendly interface for collecting FHH and offering diseases' risk assessment.Results: A tool was described (https://giasusuckhoe.vn/) with good feedback from genetic counselors and family-medicine doctors. Among 20 surveys, 100% of respondents noted that the report accurately reflected their FHH and were satisfied with the tool's display. About 74% of familial conditions were covered. Overall, all constructive feedback has been adapted into the updated version.Conclusion: Gia Su Suc Khoe has the potential to significantly improve healthcare delivery and outcomes in Vietnam.

[Box: see text].

NCI's Proteomic Data Commons: A Cloud-Based Proteomics Repository Empowering Comprehensive Cancer Analysis through Cross-Referencing with Genomic and Imaging Data.

Proteomics has emerged as a powerful tool for studying cancer biology, developing diagnostics, and therapies. With the continuous improvement and widespread availability of high-throughput proteomic technologies, the generation of large-scale proteomic data has become more common in cancer research, and there is a growing need for resources that support the sharing and integration of multi-omics datasets. Such datasets require extensive metadata including clinical, biospecimen, and experimental and workflow annotations that are crucial for data interpretation and reanalysis. The need to integrate, analyze, and share these data has led to the development of NCI's Proteomic Data Commons (PDC), accessible at https://pdc.cancer.gov. As a specialized repository within the NCI Cancer Research Data Commons (CRDC), PDC enables researchers to locate and analyze proteomic data from various cancer types and connect with genomic and imaging data available for the same samples in other CRDC nodes. Presently, PDC houses annotated data from more than 160 datasets across 19 cancer types, generated by several large-scale cancer research programs with cohort sizes exceeding 100 samples (tumor and associated normal when available). In this article, we review the current state of PDC in cancer research, discuss the opportunities and challenges associated with data sharing in proteomics, and propose future directions for the resource. SIGNIFICANCE: The Proteomic Data Commons (PDC) plays a crucial role in advancing cancer research by providing a centralized repository of high-quality cancer proteomic data, enriched with extensive clinical annotations. By integrating and cross-referencing with complementary genomic and imaging data, the PDC facilitates multi-omics analyses, driving comprehensive insights, and accelerating discoveries across various cancer types.

Elastic solution of surface loaded layer with couple and surface stress effects.

In this study, an elastic solution of an axisymmetrically surface-loaded thin layer resting on a rigid substrate is established by taking the surface stress and material microstructural effects into account. Derived solutions provide not only a means to investigate the size effects on the mechanical response but also a set of fundamental solutions essential for tackling contact problems in a micro/nano scale. In the formulation, the couple stress and surface elasticity theories are adopted to simulate the microstructured bulk layer and the surface material, respectively. A general solution of an elastic field within the bulk layer is obtained first by Hankel transform method and subsequently used together with the surface equations and boundary conditions to form a set of conditions essential for determining all unknown constants. After being fully tested with available benchmark solutions, results are used to study the role of surface and couple stresses on the load transferring mechanism to the substrate and its size-dependent characteristic for a wide range of external length scales relative to the internal length scales.

Management of extra-articular fractures of the distal tibia: intramedullary nailing versus plate fixation.

Intramedullary nailing and plate fixation represent two viable approaches to internal fixation of extra-articular fractures of the distal tibia. Although both techniques have demonstrated success in maintaining reduction and promoting stable union, they possess distinct advantages and disadvantages that require careful consideration during surgical planning. Differences in soft-tissue health and construct stability must be considered when choosing between intramedullary nailing and plating of the distal tibia. Recent advances in intramedullary nail design and plate-and-screw fixation systems have further increased the options for management of these fractures. Current evidence supports careful consideration of the risk of soft-tissue complications, residual knee pain, and fracture malalignment in the context of patient and injury characteristics in the selection of the optimal method of fixation.

Assessment of the risk factors associated with type 2 diabetes and prediabetes mellitus: A national survey in Vietnam.

This study aims to estimating the prevalence of type 2 diabetes and prediabetes among adult from 30 to 69 years old and assess the association of risk factor with the conditions. A total of 5244 aged 30 to 69 years old were participated in this cross-sectional study, using nationally representative sampling frame. All participants were taking blood sample to measure fasting blood glucose level and 2-hour postload oral glucose tolerance test by National Hospital of Endocrinology, Vietnam. Multinomial logistic regressions with baseline-category logit models were conducted to identify factors associated with diabetes and prediabetes among respondents. The prediabetes prevalence was in 17.9% and diabetes in 7.3%. Patients who were male (reference group vs female OR = 0.79; 95% CI: 0.64, 0.97), in the 50 to 59 years old group (OR = 1.60; 95% CI: 1.28, 2.00), have hypertension and WHR risk have higher prevalence to have prediabetes (OR = 1.31; 95% CI: 1.12, 1.53; OR = 1.37; 95% CI: 1.11, 1.70, respectively). Male patients (reference group vs female OR = 0.62; 95% CI: 0.45, 0.84), patients who were in 40 to 49; 50 to 59; 60 to 69 years old, those who were housewife (OR = 2.17; 95% CI: 1.43, 3.28; OR = 2.85; 95% CI: 1.91, 4.27; OR = 3.12; 95% CI: 2.08, 4.69; OR = 1.71; 95% CI: 1.22, 2.40, respectively). Diabetes have significant associated with participants have hypertension (OR = 1.19; 95% CI: 1.72, 2.70). The common factor directly related to prediabetes and diabetes in both genders is age. Other factors directly associated with prediabetes and diabetes include BMI, WHR, hypertension, educational level, and job.

Practical Guidance on Basal Insulin Initiation and Titration in Asia: A Delphi-Based Consensus.

The global health burden of diabetes is on the rise and has affected more than half a billion people worldwide, particularly in Southeast Asia, North Africa, Africa, and the Western Pacific, Middle East, and South and Central America regions of the International Diabetes Federation (IDF). Despite many new treatments being available for the management of diabetes, glycemic control remains suboptimal in Asia, compared to the rest of the world. Delay in timely insulin initiation and inadequate titration of insulin are regarded to be some of the important reasons for inadequate glycemic control. Additionally, Asian populations have a distinct phenotype, including a younger age of onset and higher glycemic excursions, suggestive of a lower beta-cell function, as compared to non-Asians. Although there are multiple local and international guidelines on insulin initiation and titration, some of these guidelines can be complex. There is an unmet need for guideline recommendations on basal insulin initiation and titration to be simplified and customized for the Asian population with type 2 diabetes mellitus (T2DM). A unified approach would increase adoption of basal insulin initiation by primary care and family medicine physicians, which in turn would help reduce the inertia to insulin initiation. With this background, a consensus-seeking meeting was conducted with 14 experts from seven Asian countries to delineate appropriate practices for insulin initiation and titration in the Asian context. The key objective was to propose a simple insulin titration algorithm, specific for the Asian population, to improve glycemic control and optimize therapeutic outcomes of people with T2DM on basal insulin. Following a detailed review of literature and current guidelines, and potential barriers to insulin initiation and titration, the experts proposed a simplified insulin titration algorithm based on both physician- and patient-led components. The consensus recommendations of the experts related to basal insulin initiation and titration have been summarized in this article, along with the proposed titration algorithm for optimizing glycemic control in the Asian population with T2DM.

The impact of entrepreneurial leadership on SMEs' performance: the mediating effects of organizational factors.

This research empirically examines the effect of entrepreneurial leadership, entrepreneurial orientation, and technological innovation capability on SMEs' performance. Interestingly, this study investigates the mediating effects of internal organizational factors such as entrepreneurial orientation, team creativity, dynamic capabilities, and competitive advantage on the relationship between entrepreneurial leadership and SMEs' performance. The consistent PLS-SEM approach was applied to analyze valid data collected from 182 small and medium IT enterprises operating at Quang Trung Software City, Ho Chi Minh City, Vietnam. The empirical results reveal that entrepreneurial leadership via the full mediators of team creativity, dynamic capabilities, and competitive advantages can enhance the performance of IT SMEs. While entrepreneurial orientation does not influence SMEs' business performance, technological innovation capabilities can provide some benefits. Besides, entrepreneurial orientation plays no mediation role in the relationship between entrepreneurial leadership and SMEs' performance. Finally, the results allow us to provide meaningful insights and recommendations to manage and promote better entrepreneurial inspiration.

Validation Framework for Sleep Stage Scoring in Wearable Sleep Trackers and Monitors with Polysomnography Ground Truth.

The rapid growth of point-of-care polysomnographic alternatives has necessitated standardized evaluation and validation frameworks. The current average across participant validation methods may overestimate the agreement between wearable sleep tracker devices and polysomnography (PSG) systems because of the high base rate of sleep during the night and the interindividual difference across the sampling population. This study proposes an evaluation framework to assess the aggregating differences of the sleep architecture features and the chronologically epoch-by-epoch mismatch of the wearable sleep tracker devices and the PSG ground truth. An AASM-based sleep stage categorizing method was proposed to standardize the sleep stages scored by different types of wearable trackers. Sleep features and sleep stage architecture were extracted from the PSG and the wearable device's hypnograms. Therefrom, a localized quantifier index was developed to characterize the local mismatch of sleep scoring. We evaluated different commonly used wearable sleep tracking devices with the data collected from 22 different subjects over 30 nights of 8-h sleeping. The proposed localization quantifiers can characterize the chronologically localized mismatches over the sleeping time. The outperformance of the proposed method over existing evaluation methods was reported. The proposed evaluation method can be utilized for the improvement of the sensor design and scoring algorithm.