115 research outputs found
Image Registration and Deep NeuroFuzzy Networks for Mitigating Atmospheric Turbulence Effects in Consumer-Based Optical Imaging
Consumer-based optical imaging systems are characterized as big data processing systems, which are drastically affected by atmospheric turbulences that add geometric distortions and blur effect to the images when used in outdoor condition. Physics-grounded simulators have been proposed recently to generate synthetic data but the generalization to the real-world turbulent images is not so good. In this paper, we combine the characteristics of image registration, deep neurofuzzy methods, and channel-attention based discriminative learning strategy to propose image registration, neurofuzzy based denoising, and deblurring network (RND2Net). The RND2Net is designed on a principle that it does not require turbulent image pairs (ground truth images) to train the network, which closely resembles the real-world situation used as consumer devices. The registration module focuses on the region-based fusion techniques while the denoising and deblurring module incorporates deep neurofuzzy network along with dense residual blocks and channel attention mechanism to train the network. The RND2Net is also designed to reduce the noise and blur effect from images, while generalizing on the down-stream tasks, such as text recognition. Experimental results show that the RND2Net yields better performance quantitatively as qualitatively on synthetic and real-world datasets in comparison to existing state-of-the-art methods
The minimal adjoint-SU (5) x Z(4) GUT model
An extension of the adjoint SU (5) model with a flavour symmetry based on the Z(4) group is investigated. The Z(4) symmetry is introduced with the aim of leading the up-and down-quark mass matrices to the Nearest-Neighbour-Interaction form. As a consequence of the discrete symmetry embedded in the SU (5) gauge group, the charged lepton mass matrix also gets the same form. Within this model, light neutrinos get their masses through type-I, type-III and one-loop radiative seesaw mechanisms, implemented, respectively, via a singlet, a triplet and an octet from the adjoint fermionic 24 fields. It is demonstrated that the neutrino phenomenology forces the introduction of at least three 24 fermionic multiplets. The symmetry SU (5) x Z(4) allows only two viable zero textures for the effective neutrino mass matrix. It is showed that one texture is only compatible with normal hierarchy and the other with inverted hierarchy in the light neutrino mass spectrum. Finally, it is also demonstrated that Z(4) freezes out the possibility of proton decay through exchange of coloured Higgs triplets at tree-level
Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV
Peer reviewe
Discrete family symmetry, Higgs mediators and theta_{13}
We present a new (supersymmetric) framework for obtaining an excellent
description of quark, charged lepton and neutrino masses and mixings from a
Delta(6n^2) family symmetry with multiplet assignments consistent with an
underlying SO(10) Grand Unification. It employs a Higgs mediator sector in
place of the usual Froggatt-Nielsen messengers, with quark and lepton
messengers, and provides significant improvements over existing models of this
type having unsuppressed Yukawa couplings to the third generation and a
simplified vacuum alignment mechanism. The neutrino mass differences are
naturally less hierarchical than those of the quarks and charged leptons.
Similarly the lepton mixing angles are much larger than those in the quark
sector and have an approximate tri-bi-maximal (TB) mixing form for theta_{12}
and theta_{23}. However the mixing angle theta_{13} is naturally much larger
than in pure TB mixing and can be consistent with the value found in recent
experiments. The magnitude of theta_{13} is correlated with a the predicted
deviation of theta_{23} from bi-maximal mixing. The model has light familon
fields that can significantly modify the associated SUSY phenomenology.Comment: v3: accepted in JHE
Kinetics and Ligand-Binding Preferences of Mycobacterium tuberculosis Thymidylate Synthases, ThyA and ThyX
Mycobacterium tuberculosis kills approximately 2 million people each year and presents an urgent need to identify new targets and new antitubercular drugs. Thymidylate synthase (TS) enzymes from other species offer good targets for drug development and the M. tuberculosis genome contains two putative TS enzymes, a conventional ThyA and a flavin-based ThyX. In M. tuberculosis, both TS enzymes have been implicated as essential for growth, either based on drug-resistance studies or genome-wide mutagenesis screens. To facilitate future small molecule inhibitors against these proteins, a detailed enzymatic characterization was necessary.After cloning, overexpression, and purification, the thymidylate-synthesizing ability of ThyA and ThyX gene products were directly confirmed by HPLC analysis of reaction products and substrate saturation kinetics were established. 5-Fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) was a potent inhibitor of both ThyA and ThyX, offering important clues to double-targeting strategies. In contrast, the folate-based 1843U89 was a potent inhibitor of ThyA but not ThyX suggesting that it should be possible to find ThyX-specific antifolates. A turnover-dependent kinetic assay, combined with the active-site titration approach of Ackermann and Potter, revealed that both M. tuberculosis enzymes had very low k(cat) values. One possible explanation for the low catalytic activity of M. tuberculosis ThyX is that its true biological substrates remain to be identified. Alternatively, this slow-growing pathogen, with low demands for TMP, may have evolved to down-regulate TS activities by altering the turnover rate of individual enzyme molecules, perhaps to preserve total protein quantities for other purposes. In many organisms, TS is often used as a part of larger complexes of macromolecules that control replication and DNA repair.Thus, the present enzymatic characterization of ThyA and ThyX from M. tuberculosis provides a framework for future development of cell-active inhibitors and the biological roles of these TS enzymes in M. tuberculosis
The therapeutic potential of a series of orally bioavailable anti-angiogenic microtubule disruptors as therapy for hormone-independent prostate and breast cancers
Therapies for hormone-independent prostate and breast cancer are limited, with the effectiveness of the taxanes compromised by toxicity, lack of oral bioavailability and drug resistance. This study aims to identify and characterise new microtubule disruptors, which may have improved efficacy relative to the taxanes in hormone-independent cancer. 2-Methoxy-3-O-sulphamoyl-17β-cyanomethyl-oestra-1,3,5(10)-triene (STX641), 2-methoxy-3-hydroxy-17β-cyanomethyl-oestra-1,3,5(10)-triene (STX640) and 2-methoxyoestradiol-3,17-O,O-bis-sulphamate (STX140) were all potent inhibitors of cell proliferation in a panel of prostate and breast cancer cell lines. STX641 and STX640 significantly inhibited tumour growth in the MDA-MB-231 xenograft model. STX641 inhibited both in vitro and in vivo angiogenesis. Despite good in vivo activity, STX641 was not as potent in vivo as STX140. Therefore, STX140 was evaluated in the prostate hormone-independent PC-3 xenograft model. STX140 had superior efficacy to docetaxel, 2-MeOE2 and bevacizumab. In contrast to vinorelbine, no significant toxicity was observed. Furthermore, STX140 could be dosed daily over a 60-day period leading to tumour regression and complete responses, which were maintained after the cessation of dosing. This study demonstrates that STX641 and STX140 have considerable potential for the treatment of hormone-independent breast and prostate cancer. In contrast to the taxanes, STX140 can be dosed orally, with no toxicity being observed even after prolonged daily dosing
Knowledge, attitudes and practice of primary health care physicians towards hepatitis B virus in Al-Jouf province, Saudi Arabia
Identification of Chromosomal Genes in Yersinia pestis that Influence Type III Secretion and Delivery of Yops into Target Cells
Pathogenic Yersinia species possess a type III secretion system, which is required for the delivery of effector Yop proteins into target cells during infection. Genes encoding the type III secretion machinery, its substrates, and several regulatory proteins all reside on a 70-Kb virulence plasmid. Genes encoded in the chromosome of yersiniae are thought to play important roles in bacterial perception of host environments and in the coordinated activation of the type III secretion pathway. Here, we investigate the contribution of chromosomal genes to the complex regulatory process controlling type III secretion in Yersinia pestis. Using transposon mutagenesis, we identified five chromosomal genes required for expression or secretion of Yops in laboratory media. Four out of the five chromosomal mutants were defective to various extents at injecting Yops into tissue culture cells. Interestingly, we found one mutant that was not able to secrete in vitro but was fully competent for injecting Yops into host cells, suggesting independent mechanisms for activation of the secretion apparatus. When tested in a mouse model of plague disease, three mutants were avirulent, whereas two strains were severely attenuated. Together these results demonstrate the importance of Y. pestis chromosomal genes in the proper function of type III secretion and in the pathogenesis of plague
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
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