Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated ...cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPV-related cancers. Whereas testing and prevention of cervical cancer have significantly improved over past decades, anogenital cancers remain more difficult to confirm. Current clinical trials including patients with HPV-related cancers focus on finding proper testing for all HPV-associated cancers as well as improve the currently applied treatments. The HPV viral oncoproteins, E6 and E7, lead to degradation of, respectively, p53 and pRb resulting in entering the S phase without G1 arrest. These high-risk HPV viral oncogenes alter numerous cellular processes, including DNA repair, angiogenesis, and/or apoptosis, which eventually result in carcinogenesis. Additionally, a comprehensive analysis of gene expression and alteration among a panel of DNA double strand breaks (DSB) repair genes in HPV-negative and HPV-positive HNC cancers reveals differences pointing to HPV-dependent modifications of DNA repair processes in these cancers. In this review, we discuss the current knowledge regarding HPV-related cancers, current screening, and treatment options as well as DNA damage response-related biological aspects of the HPV infection and clinical trials.
The increasing popularity of carbon nanotubes has created a demand for greater scientific understanding of the characteristics of thermal transport in nanostructured materials. However, the effects ...of impurities, misalignments, and structure factors on the thermal conductivity of carbon nanotube films and fibers are still poorly understood. Carbon nanotube films and fibers were produced, and the parallel thermal conductance technique was employed to determine the thermal conductivity. The effects of carbon nanotube structure, purity, and alignment on the thermal conductivity of carbon films and fibers were investigated to understand the characteristics of thermal transport in the nanostructured material. The importance of bulk density and cross-sectional area was determined experimentally. The results indicated that the prepared carbon nanotube films and fibers are very efficient at conducting heat. The structure, purity, and alignment of carbon nanotubes play a fundamentally important role in determining the heat conduction properties of carbon films and fibers. Single-walled carbon nanotube films and fibers generally have high thermal conductivity. The presence of non-carbonaceous impurities degrades the thermal performance due to the low degree of bundle contact. The thermal conductivity may present power law dependence with temperature. The specific thermal conductivity decreases with increasing bulk density. At room temperature, a maximum specific thermal conductivity is obtained but Umklapp scattering occurs. The specific thermal conductivity of carbon nanotube fibers is significantly higher than that of carbon nanotube films due to the increased degree of bundle alignment.
Many attempts have been made to improve heat transfer for thermally integrated microchannel reforming reactors. However, the mechanisms for the effects of design factors on heat transfer ...characteristics are still not fully understood. This study relates to a thermochemical process for producing hydrogen by the catalytic endothermic reaction of methanol with steam in a thermally integrated microchannel reforming reactor. Computational fluid dynamics simulations are conducted to better understand the consumption, generation, and exchange of thermal energy between endothermic and exothermic processes in the reactor. The effects of wall heat conduction properties and channel dimensions on heat transfer characteristics and reactor performance are investigated. Thermodynamic analysis is performed based on specific enthalpy to better understand the evolution of thermal energy in the reactor. The results indicate that the thermal conductivity of the channel walls is fundamentally important. Materials with high thermal conductivity are preferred for the channel walls. Thermally conductive ceramics and metals are well-suited. Wall materials with poor heat conduction properties degrade the reactor performance. Reaction heat flux profiles are considerably affected by channel dimensions. The peak reaction heat flux increases with the channel dimensions while maintaining the flow rates. The change in specific enthalpy is positive for the exothermic reaction and negative for the endothermic reaction. The change in specific sensible enthalpy is always positive. Design recommendations are made to improve thermal performance for the reactor.
Abstract
Protein remote homology detection is one of the most fundamental and central problems for the studies of protein structures and functions, aiming to detect the distantly evolutionary ...relationships among proteins via computational methods. During the past decades, many computational approaches have been proposed to solve this important task. These methods have made a substantial contribution to protein remote homology detection. Therefore, it is necessary to give a comprehensive review and comparison on these computational methods. In this article, we divide these computational approaches into three categories, including alignment methods, discriminative methods and ranking methods. Their advantages and disadvantages are discussed in a comprehensive perspective, and their performance is compared on widely used benchmark data sets. Finally, some open questions in this field are further explored and discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Protein remote homology detection is one of the fundamental problems in computational biology, aiming to find protein sequences in a database of known structures that are evolutionarily related to a ...given query protein. Some computational methods treat this problem as a ranking problem and achieve the state-of-the-art performance, such as PSI-BLAST, HHblits and ProtEmbed. This raises the possibility to combine these methods to improve the predictive performance. In this regard, we are to propose a new computational method called ProtDec-LTR for protein remote homology detection, which is able to combine various ranking methods in a supervised manner via using the Learning to Rank (LTR) algorithm derived from natural language processing.
Experimental results on a widely used benchmark dataset showed that ProtDec-LTR can achieve an ROC1 score of 0.8442 and an ROC50 score of 0.9023 outperforming all the individual predictors and some state-of-the-art methods. These results indicate that it is correct to treat protein remote homology detection as a ranking problem, and predictive performance improvement can be achieved by combining different ranking approaches in a supervised manner via using LTR.
For users' convenience, the software tools of three basic ranking predictors and Learning to Rank algorithm were provided at http://bioinformatics.hitsz.edu.cn/ProtDec-LTR/home/
bliu@insun.hit.edu.cn
Supplementary data are available at Bioinformatics online.
Abstract
Developing high-quality NIR-II fluorophores (emission in 1000–1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, ...yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO
2
is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO
2
to render the nanoprobe BTPE-NO
2
@F127. The pathological levels of H
2
O
2
in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.
Protein remote homology detection plays a vital role in studies of protein structures and functions. Almost all of the traditional machine leaning methods require fixed length features to represent ...the protein sequences. However, it is never an easy task to extract the discriminative features with limited knowledge of proteins. On the other hand, deep learning technique has demonstrated its advantage in automatically learning representations. It is worthwhile to explore the applications of deep learning techniques to the protein remote homology detection.
In this study, we employ the Bidirectional Long Short-Term Memory (BLSTM) to learn effective features from pseudo proteins, also propose a predictor called ProDec-BLSTM: it includes input layer, bidirectional LSTM, time distributed dense layer and output layer. This neural network can automatically extract the discriminative features by using bidirectional LSTM and the time distributed dense layer.
Experimental results on a widely-used benchmark dataset show that ProDec-BLSTM outperforms other related methods in terms of both the mean ROC and mean ROC50 scores. This promising result shows that ProDec-BLSTM is a useful tool for protein remote homology detection. Furthermore, the hidden patterns learnt by ProDec-BLSTM can be interpreted and visualized, and therefore, additional useful information can be obtained.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The RAD51 recombinase plays a central role in homologous recombination (HR), which is critical for repair of DNA double-strand breaks, maintenance of genomic stability, and prevention of ...developmental disorders and cancer. Here, we report the identification of an RAD51-binding protein fidgetin-like 1 (FIGNL1). FIGNL1 specifically interacts with RAD51 through its conserved RAD51 binding domain. Cells depleted of FIGNL1 show defective HR repair. Interestingly, FIGNL1 is recruited to sites of DNA damage in a manner that is independent of breast cancer 2, early onset RAD51, and probably, RAD51 paralogs. Conversely, FIGNL1 depletion does not affect the loading of RAD51 onto ssDNA. Our additional analysis uncovered KIAA0146, also known as scaffolding protein involved in DNA repair (SPIDR), as a binding partner of FIGNL1 and established that KIAA0146/SPIDR acts with FIGNL1 in HR repair. Collectively, our study uncovers a protein complex, which consists of FIGNL1 and KIAA0146/SPIDR, in DNA repair and provides potential directions for cancer diagnosis and therapy.
Mutations in HepA-related protein (HARP) are the only identified causes of Schimke immunoosseous dysplasia (SIOD). HARP has a unique annealing helicase activity in vitro, but the in vivo functional ...significance remains unknown. Here, we demonstrated that HARP is recruited to stalled replication forks via its direct interaction with Replication protein A (RPA). Cells with HARP depletion displayed increased spontaneous DNA damage and G2/M arrest, suggesting that HARP normally acts to stabilize stalled replication forks. Our data place the annealing helicase activity of HARP at replication forks and propose that SIOD syndrome may be caused by the destabilization of replication forks during cell proliferation.
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