Proteins perform their functions usually by interacting with other proteins. Predicting which proteins interact is a fundamental problem. Experimental methods are slow, expensive, and have a high ...rate of error. Many computational methods have been proposed among which sequence-based ones are very promising. However, so far no such method is able to predict effectively the entire human interactome: they require too much time or memory.
We present SPRINT (Scoring PRotein INTeractions), a new sequence-based algorithm and tool for predicting protein-protein interactions. We comprehensively compare SPRINT with state-of-the-art programs on seven most reliable human PPI datasets and show that it is more accurate while running orders of magnitude faster and using very little memory.
SPRINT is the only sequence-based program that can effectively predict the entire human interactome: it requires between 15 and 100 min, depending on the dataset. Our goal is to transform the very challenging problem of predicting the entire human interactome into a routine task.
The source code of SPRINT is freely available from https://github.com/lucian-ilie/SPRINT/ and the datasets and predicted PPIs from www.csd.uwo.ca/faculty/ilie/SPRINT/ .
Using a large cross-sectional dataset comprising of FTSE 350 listed firms, this study investigates whether superior environmental, social and corporate governance (ESG) disclosure affects firm value. ...We find a positive association between ESG disclosure level and firm value, suggesting that improved transparency and accountability and enhanced stakeholder trust play a role in boosting firm value. We also report that higher CEO power enhances the ESG disclosure effect on firm value, indicating that stakeholders associate ESG disclosure from firms with higher CEO power with greater commitment to ESG practice. This evidence is strong and consistent for three different measures of ESG-related disclosure: the ESG, environmental and social disclosure scores. The results are robust to the use of an instrumental variable approach, and the Heckman two-stage estimation procedure.
•Graphene-based nanomaterials are emerging as the next generation’s candidates for biotechnological advancements.•Graphene and its various derivatives have been covered.•The properties of ...graphene-based materials related to biomedical applications have been discussed.•The review emphasizes the up-to-date biomedical applications of graphene-based materials.•It also covers the rising concern about the toxicity of graphene-based materials.
Here, we discuss the biomedical applications of graphene-based nanomaterials (GBNs). We examine graphene and its various derivatives, including graphene, graphene oxides (GOs), reduced graphene oxides (rGOs), graphene quantum dots (GQDs), and graphene composites, and discuss their unique properties related to their biomedical applications. We also summarize the detailed biomedical applications of GBNs, including drug and/or gene delivery, bioimaging, and tissue engineering. We also highlight the toxicity of these nanomaterials.
We propose an indoor visible light communication (VLC) and positioning system using the orthogonal frequency division multiplexing access (OFDMA) scheme, which can provide both indoor positioning and ...communications. Three subcarriers with the maximum received signal intensity with respect to three light-emitting diodes (LEDs) are selected for indoor positioning based on the trilateration algorithm. The experiment results show that the proposed system with quadrature phase shift keying (QPSK) mapping offers a mean positioning error and an error vector magnitude of 1.68 cm and more than 15 dB, respectively.
•Mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) are common in cancer.•KRAS remains a challenging therapeutic target.•Recently, several novel compounds against individual KRAS ...alterations have emerged.•Initial activity of AMG 510 and MRTX 849 appears promising in KRAS G12C NSCLC.•Single agent and combination studies are ongoing to evaluate their safety and efficacy.
Mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) are among the most common aberrations in cancer, including non-small cell lung cancer (NSCLC). The lack of an ideal small molecule binding pocket in the KRAS protein and its high affinity towards the abundance of cellular guanosine triphosphate (GTP) renders the design of specific small molecule drugs challenging. Despite efforts, KRAS remains a challenging therapeutic target.
Among the different known mutations; the KRASG12C (glycine 12 to cysteine) mutation has been considered potentially druggable. Several novel covalent direct inhibitors targeting KRASG12C with similar covalent binding mechanisms are now in clinical trials. Both AMG 510 from Amgen and MRTX849 from Mirati Therapeutics covalently binds to KRASG12C at the cysteine at residue 12, keeping KRASG12C in its inactive GDP-bound state and inhibiting KRAS-dependent signaling. Both inhibitors are being studied as a single agent or as combination with other targets. In addition, two novel KRAS G12C inhibitors JNJ-74699157 and LY3499446 will have entered phase 1 studies by the end of 2019.
Given the rapid clinical development of 4 direct covalent KRAS G12C inhibitors within a short period of time, understanding the similarities and differences among these will be important to determine the best treatment option based on tumor specific response (NSCLC versus colorectal carcinoma), potential resistance mechanisms (i.e. anticipated acquired mutation at the cysteine 12 residue) and central nervous system (CNS) activity. Additionally, further investigation evaluating the efficacy and safety of combination therapies with agents such as immune checkpoint inhibitors will be important next steps.
We experimentally demonstrate an indoor visible light positioning system based on optical camera communications, in which the transmitted coordinate data are spatially separated and demodulated by a ...camera. The receiver's position is calculated based on the coordinates of light-emitting diodes in the real word and in the image. The experimental results show that the proposed system with under-sampled phase shift keying modulation offers an error free data transmission and mean positioning errors of 5.0 and 6.6 cm for h of 120 and 180 cm, respectively.
Exosomes, naturally derived nanovesicles secreted from various cell types, can serve as an effective platform for the delivery of various cargoes, because of their intrinsic ability such as long ...blood circulation and immune escapinge. However, unlike conventional synthetic nanoparticles, drug release from exosomes at defined targets is not controllable. Moreover, endowing exosomes with satisfactory cancer‐targeting ability is highly challenging. Here, for the first time, a biological and synthetic hybrid designer exosome is described with photoresponsive functionalities based on a donor cell‐assisted membrane modification strategy. Practically, the designer exosome effectively accumulates at target tumor sites via dual ligand‐mediated endocytosis. Then the localized hyperthermia induced by the conjunct gold nanorods under near‐infrared irradiation impacts the permeability of exosome membrane to enhance drug release from exosomes, thus inhibiting tumor relapse in a programmable manner. The designer exosome combines the merits of both synthetic materials and the natural nanovesicles. It not only preserves the intrinsic functionalities of native exosome, but also gains multiple abilities for efficient tumor targeting, controlled release, and thermal therapy like synthetic nanocarriers. The versatile designer exosome can provide functional platforms by engineering with more multifarious functionalities from synthetic materials to achieve individualized precise cancer therapy in the future.
A biological and synthetic hybrid designer exosome is presented with photoresponsive functionalities based on a donor cell‐assisted membrane modification strategy. The dual ligand engineered exosomes are shown to significantly increase accumulation at the target tumor site and can burst release drug under controllable near‐infrared irradiation in vitro and in vivo.
Abstract Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant ...isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genistein is mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-κB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen- and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells.
This study investigated how social networking sites (SNSs) use by Chinese international students in Japan influenced their perceived social capital and psychological well-being. In addition, it ...examined how, as sojourners, Chinese international students' perceived acculturative stress varied. Data were collected from 142 Chinese international students. The results indicated that the intensity of SNS use was unable to predict individuals' perceived social capital and psychological well-being. The effect of SNS use varied according to the functions it serves. Specifically, SNS use for social and informational functions (SIF) increased individuals' levels of perceived bridging social capital and perceived life satisfaction, while SNS use for entertaining recreational functions (ERF) was unable to predict perceived social capital but increased individuals' levels of loneliness. It was also found that, in the intercultural environment, Chinese international students' levels of perceived acculturative stress were decreased by their perceived bonding social capital and increased by their perceived loneliness but had no relationship with their SNS use. Findings of the study suggest that individuals using SNSs to stay informed and connected will benefit with regard to their social network building and psychological well-being.
In many developmental and pathological processes, including cellular migration during normal development and invasion in cancer metastasis, cells are required to withstand severe deformations. The ...structural integrity of eukaryotic cells under small deformations has been known to depend on the cytoskeleton including actin filaments (F-actin), microtubules (MT), and intermediate filaments (IFs). However, it remains unclear how cells resist severe deformations since both F-actin and microtubules yield or disassemble under moderate strains. Using vimentin containing IFs (VIFs) as a model for studying the large family of IF proteins, we demonstrate that they dominate cytoplasmic mechanics and maintain cell viability at large deformations. Our results show that cytoskeletal VIFs form a stretchable, hyperelastic network in living cells. This network works synergistically with other cytoplasmic components, substantially enhancing the strength, stretchability, resilience, and toughness of cells. Moreover, we find the hyperelastic VIF network, together with other quickly recoverable cytoskeletal components, forms a mechanically robust structure which can mechanically recover after damage.
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