150 research outputs found
Homogeneous solutions of the heat equation
AbstractWe complete a characterization of homogeneous solutions of the heat equation begun by D. V. Widder. We determine regions of convergence for expansions of temperature functions in terms of the homogeneous solutions
Lysosome Associated Protein Transmembrane 4B-24 Is the Predominant Protein Isoform in Human Tissues and Undergoes Rapid, Nutrient-Regulated Turnover
Studies of lysosome associated protein transmembrane 4B (LAPTM4B) have mainly focused on the 35-kDa isoform and its association with poor prognosis in cancers. Here, by employing a novel monoclonal antibody, the authors found that the 24-kDa LAPTM4B isoform predominated in most, both healthy and malignant, human cells and tissues studied. LAPTM4B-24 lacks the extreme N-terminus and, contrary to LAPTM4B-35, failed to promote cell migration. The endogenous LAPTM4B-24 protein was subject to rapid turnover with a t(1/2) of approximately 1 hour. The protein was degraded by both lysosomal and proteasomal pathways, and its levels were increased by the availability of nutrients and lysosomal ceramide. These findings underscore the pathophysiological relevance of the LAPTM4B-24 isoform and identify it as a dynamically regulated effector in lysosomal nutrient signaling.Peer reviewe
CRISPR accelerates the cancer drug discovery
Emerging cohorts and basic studies have associated certain genetic modifications in cancer patients, such as gene mutation, amplification, or deletion, with the overall survival prognosis, underscoring patients??? genetic background may directly regulate drug sensitivity/resistance during chemotherapies. Understanding the molecular mechanism underpinning drug sensitivity/resistance and further uncovering the effective drugs have been the major ambition in the cancer drug discovery. The emergence and popularity of CRISPR/Cas9 technology have reformed the entire life science research, providing a precise and simplified genome editing tool with unlimited editing possibilities. Furthermore, it presents a powerful tool in cancer drug discovery, which hopefully facilitates us with a rapid and reliable manner in developing novel therapies and understanding the molecular mechanisms of drug sensitivity/resistance. Herein, we summarized the application of CRISPR/Cas9 in drug screening, with the focus on CRISPR/Cas9 mediated gene knockout, gene knock-in, as well as transcriptional modification. Additionally, this review provides the concerns, cautions, and ethnic considerations that need to be taken when applying CRISPR in the drug discovery.Peer reviewe
LAPTM4B-35 promotes cancer cell migration via stimulating integrin beta1 recycling and focal adhesion dynamics
Metastasis is the main cause of cancer patients' death despite tremendous efforts invested in developing the related molecular mechanisms. During cancer cell migration, cells undergo dynamic regulation of filopodia, focal adhesion, and endosome trafficking. Cdc42 is imperative for maintaining cell morphology and filopodia, regulating cell movement. Integrin beta1 activates on the endosome, the majority of which distributes itself on the plasma membrane, indicating that endocytic trafficking is essential for this activity. In cancers, high expression of lysosome-associated protein transmembrane 4B (LAPTM4B) is associated with poor prognosis. LAPTM4B-35 has been reported as displaying plasma membrane distribution and being associated with cancer cell migration. However, the detailed mechanism of its isoform-specific distribution and whether it relates to cell migration remain unknown. Here, we first report and quantify the filopodia localization of LAPTM4B-35: mechanically, that specific interaction with Cdc42 promoted its localization to the filopodia. Furthermore, our data show that LAPTM4B-35 stabilized filopodia and regulated integrin beta1 recycling via interaction and cotrafficking on the endosome. In our zebrafish xenograft model, LAPTM4B-35 stimulated the formation and dynamics of focal adhesion, further promoting cancer cell dissemination, whereas in skin cancer patients, LAPTM4B level correlated with poor prognosis. In short, this study establishes an insight into the mechanism of LAPTM4B-35 filopodia distribution, as well as into its biological effects and its clinical significance, providing a novel target for cancer therapeutics development.Peer reviewe
CoDeF: Content Deformation Fields for Temporally Consistent Video Processing
We present the content deformation field CoDeF as a new type of video
representation, which consists of a canonical content field aggregating the
static contents in the entire video and a temporal deformation field recording
the transformations from the canonical image (i.e., rendered from the canonical
content field) to each individual frame along the time axis.Given a target
video, these two fields are jointly optimized to reconstruct it through a
carefully tailored rendering pipeline.We advisedly introduce some
regularizations into the optimization process, urging the canonical content
field to inherit semantics (e.g., the object shape) from the video.With such a
design, CoDeF naturally supports lifting image algorithms for video processing,
in the sense that one can apply an image algorithm to the canonical image and
effortlessly propagate the outcomes to the entire video with the aid of the
temporal deformation field.We experimentally show that CoDeF is able to lift
image-to-image translation to video-to-video translation and lift keypoint
detection to keypoint tracking without any training.More importantly, thanks to
our lifting strategy that deploys the algorithms on only one image, we achieve
superior cross-frame consistency in processed videos compared to existing
video-to-video translation approaches, and even manage to track non-rigid
objects like water and smog.Project page can be found at
https://qiuyu96.github.io/CoDeF/.Comment: Project Webpage: https://qiuyu96.github.io/CoDeF/, Code:
https://github.com/qiuyu96/CoDe
Neural Dependencies Emerging from Learning Massive Categories
This work presents two astonishing findings on neural networks learned for
large-scale image classification. 1) Given a well-trained model, the logits
predicted for some category can be directly obtained by linearly combining the
predictions of a few other categories, which we call \textbf{neural
dependency}. 2) Neural dependencies exist not only within a single model, but
even between two independently learned models, regardless of their
architectures. Towards a theoretical analysis of such phenomena, we demonstrate
that identifying neural dependencies is equivalent to solving the Covariance
Lasso (CovLasso) regression problem proposed in this paper. Through
investigating the properties of the problem solution, we confirm that neural
dependency is guaranteed by a redundant logit covariance matrix, which
condition is easily met given massive categories, and that neural dependency is
highly sparse, implying that one category correlates to only a few others. We
further empirically show the potential of neural dependencies in understanding
internal data correlations, generalizing models to unseen categories, and
improving model robustness with a dependency-derived regularizer. Code for this
work will be made publicly available
Linear Positional Isomer Sorting in Nonporous Adaptive Crystals of a Pillar[5]arene
Here we show a new adsorptive separation
approach using nonporous
adaptive crystals of a pillar[5]Âarene. Desolvated perethylated pillar[5]Âarene
crystals (<b>EtP5</b>α) with a nonporous character selectively
adsorb 1-pentene (<b>1-Pe</b>) over its positional isomer 2-pentene
(<b>2-Pe</b>), leading to a structural change from <b>EtP5</b>α to <b>1-Pe</b> loaded structure (<b>1-Pe</b>@<b>EtP5</b>). The purity of <b>1-Pe</b> reaches 98.7% in just
one cycle and <b>EtP5</b>α can be reused without losing
separation performance
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Mechanochemical synthesis of pillar[5]quinone derived multi-microporous organic polymers for radioactive organic iodide capture and storage.
The incorporation of supramolecular macrocycles into porous organic polymers may endow the material with enhanced uptake of specific guests through host-guest interactions. Here we report a solvent and catalyst-free mechanochemical synthesis of pillar[5]quinone (P5Q) derived multi-microporous organic polymers with hydrophenazine linkages (MHP-P5Q), which show a unique 3-step N2 adsorption isotherm. In comparison with analogous microporous hydrophenazine-linked organic polymers (MHPs) obtained using simple twofold benzoquinones, MHP-P5Q is demonstrated to have a superior performance in radioactive iodomethane (CH3I) capture and storage. Mechanistic studies show that the rigid pillar[5]arene cavity has additional binding sites though host-guest interactions as well as the halogen bond (-I⋯N = C-) and chemical adsorption in the multi-microporous MHP-P5Q mainly account for the rapid and high-capacity adsorption and long-term storage of CH3I
Femoral neck system vs. cannulated screws on treating femoral neck fracture: a meta-analysis and system review
ObjectiveThis meta-analysis aimed to compare the relative safety and efficacy of cannulated compression screw (CCS) and femoral neck system (FNS) in treating patients with femoral neck fractures and to provide evidence-based medical evidence for FNS in treating femoral neck fractures.MethodsPubMed, Embase, Cochrane, and China National Knowledge Infrastructure databases were searched to collect outcomes related to femoral neck fractures treated with FNS and CCS, including time to fracture healing, incidence of non-union, incidence of osteonecrosis of the femoral head, incidence of failure of internal fixation, rate of femoral neck shortening, Harris hip score, Barthel index, operative time, intraoperative blood loss, fluoroscopy frequency, and complications. A meta-analysis was performed using RevManv5.4 (The Cochrane Collaboration) and Stata v14.0 software.ResultsThis analysis included 21 studies involving 1,347 patients. The results showed that FNS was superior to CCS in terms of fracture healing time [mean difference (MD) = −0.75, 95% CI = (−1.04, −0.46), P < 0.05], incidence of bone non-union [odds ratio (OR) = 0.53, 95% CI = (0.29, 0.98), P = 0.04], incidence of osteonecrosis of the femoral head [OR = 0.49, 95% CI = (0.28, 0.86), P = 0.01], incidence of internal fixation failure [OR = 0.30, 95% CI = (0.18, 0.52), P < 0.05], rate of femoral neck shortening [OR = 0.38, 95% CI = (0.27, 0.54), P > 0.05], Harris hip score [MD = 3.31, 95% CI = (1.99, 4.63), P < 0.001], Barthel index [MD =  4.31, 95% CI = (3.02, 5.61), P < 0.05], intraoperative bleeding [MD = 14.72, 95% CI = (8.52, 20.92), P < 0.05], fluoroscopy frequency [OR = 0.53, 95% CI = (0.29, 0.98), P = 0.04], and complications [OR = 0.31, 95% CI = (0.22, 0.45), P < 0.05]. The difference between FNS and CCS in operative time was not statistically significant [MD = −2.41, 95% CI = (−6.88, 2.05), P = 0.29].ConclusionFNS treatment of femoral neck fracture can shorten the fracture healing time; reduce the incidence and translucent rate of bone non-union, osteonecrosis of the femoral head, and internal fixation failure; reduce intraoperative blood loss and postoperative complications; and improve hip joint function and activity. We are confident in the findings that FNS, an effective and safe procedure for internal fixation of femoral neck fractures, is superior to CCS
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