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1.
Heliyon ; 10(5): e27247, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38463876

ABSTRACT

Thin films of Bi3+ doped LaOCl and LaOF phosphors prepared via the pulsed laser deposition (PLD) technique in vacuum and different argon (Ar) pressures were compared in order to assess their luminescence properties. All peaks of the X-ray diffraction patterns of the films were consistent with the tetragonal structure of the LaOCl and LaOF, but in the case of LaOF the signal was weaker and not all peaks were present, suggesting some preferred orientation. Photoluminescence measurements revealed that the films exhibited emission around 344 nm for LaOCl:Bi and 518 nm for LaOF:Bi under excitations of 266 nm and 263 nm, respectively. The luminescence from the LaOF:Bi sample was less intense compared to the LaOCl:Bi sample prepared under the same conditions, which was also the case for the powder samples. The amount of ablated material present on the substrate was much less for LaOF:Bi compared to LaOCl:Bi, which is attributed to the greater bandgap and hence weaker absorption of the laser pulses for LaOF:Bi. Therefore phosphors based on LaOCl as the host material were found to be preferable over LaOF under the PLD conditions used in this study.

2.
J Magn Reson Imaging ; 2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38156427

ABSTRACT

BACKGROUND: Deep learning has presented great potential in accurate MR image segmentation when enough labeled data are provided for network optimization. However, manually annotating three-dimensional (3D) MR images is tedious and time-consuming, requiring experts with rich domain knowledge and experience. PURPOSE: To build a deep learning method exploring sparse annotations, namely only a single two-dimensional slice label for each 3D training MR image. STUDY TYPE: Retrospective. POPULATION: Three-dimensional MR images of 150 subjects from two publicly available datasets were included. Among them, 50 (1377 image slices) are for prostate segmentation. The other 100 (8800 image slices) are for left atrium segmentation. Five-fold cross-validation experiments were carried out utilizing the first dataset. For the second dataset, 80 subjects were used for training and 20 were used for testing. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T; axial T2-weighted and late gadolinium-enhanced, 3D respiratory navigated, inversion recovery prepared gradient echo pulse sequence. ASSESSMENT: A collaborative learning method by integrating the strengths of semi-supervised and self-supervised learning schemes was developed. The method was trained using labeled central slices and unlabeled noncentral slices. Segmentation performance on testing set was reported quantitatively and qualitatively. STATISTICAL TESTS: Quantitative evaluation metrics including boundary intersection-over-union (B-IoU), Dice similarity coefficient, average symmetric surface distance, and relative absolute volume difference were calculated. Paired t test was performed, and P < 0.05 was considered statistically significant. RESULTS: Compared to fully supervised training with only the labeled central slice, mean teacher, uncertainty-aware mean teacher, deep co-training, interpolation consistency training (ICT), and ambiguity-consensus mean teacher, the proposed method achieved a substantial improvement in segmentation accuracy, increasing the mean B-IoU significantly by more than 10.0% for prostate segmentation (proposed method B-IoU: 70.3% ± 7.6% vs. ICT B-IoU: 60.3% ± 11.2%) and by more than 6.0% for left atrium segmentation (proposed method B-IoU: 66.1% ± 6.8% vs. ICT B-IoU: 60.1% ± 7.1%). DATA CONCLUSIONS: A collaborative learning method trained using sparse annotations can segment prostate and left atrium with high accuracy. LEVEL OF EVIDENCE: 0 TECHNICAL EFFICACY: Stage 1.

3.
Phys Med Biol ; 69(1)2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38035374

ABSTRACT

Objective.Training neural networks for pixel-wise or voxel-wise image segmentation is a challenging task that requires a considerable amount of training samples with highly accurate and densely delineated ground truth maps. This challenge becomes especially prominent in the medical imaging domain, where obtaining reliable annotations for training samples is a difficult, time-consuming, and expert-dependent process. Therefore, developing models that can perform well under the conditions of limited annotated training data is desirable.Approach.In this study, we propose an innovative framework called the extremely sparse annotation neural network (ESA-Net) that learns with only the single central slice label for 3D volumetric segmentation which explores both intra-slice pixel dependencies and inter-slice image correlations with uncertainty estimation. Specifically, ESA-Net consists of four specially designed distinct components: (1) an intra-slice pixel dependency-guided pseudo-label generation module that exploits uncertainty in network predictions while generating pseudo-labels for unlabeled slices with temporal ensembling; (2) an inter-slice image correlation-constrained pseudo-label propagation module which propagates labels from the labeled central slice to unlabeled slices by self-supervised registration with rotation ensembling; (3) a pseudo-label fusion module that fuses the two sets of generated pseudo-labels with voxel-wise uncertainty guidance; and (4) a final segmentation network optimization module to make final predictions with scoring-based label quantification.Main results.Extensive experimental validations have been performed on two popular yet challenging magnetic resonance image segmentation tasks and compared to five state-of-the-art methods.Significance.Results demonstrate that our proposed ESA-Net can consistently achieve better segmentation performances even under the extremely sparse annotation setting, highlighting its effectiveness in exploiting information from unlabeled data.


Subject(s)
Image Processing, Computer-Assisted , Neural Networks, Computer , Uncertainty , Rotation
4.
Ir J Psychol Med ; 39(4): 335-339, 2022 12.
Article in English | MEDLINE | ID: mdl-31543078

ABSTRACT

The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland - CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.


Subject(s)
Hallucinogens , Psychiatry , Humans , Anxiety , Hallucinogens/therapeutic use , Psilocybin/therapeutic use , Quality of Life , Double-Blind Method
5.
Curr Res Microb Sci ; 2: 100053, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34841344

ABSTRACT

Eukaryotic autonomously replicating sequences (ARSs) are composed of three domains, A, B, and C. Domain A is comprised of an ARS consensus sequence (ACS), while the B domain has the DNA unwinding element and the C domain is important for DNA-protein interactions. In Saccharomyces cerevisiae and Kluyveromyces lactis ARS101, the ACS is commonly composed of 11 bp, 5'-(A/T)AAA(C/T)ATAAA(A/T)-3'. This core sequence is essential for S. cerevisiae and K. lactis ARS activity. In this study, we identified ARS-containing sequences from genomic libraries of the yeast Kluyveromyces marxianus DMKU3-1042 and validated their replication activities. The identified K. marxianus DMKU3-1042 ARSs (KmARSs) have very effective replication ability but their sequences are divergent and share no common consensus. We have carried out point mutations, deletions, and base pairs substitutions within the sequences of some of the KmARSs to identify the sequence(s) that influence the replication activity. Consensus sequences same as the 11 bp ACS of S. cerevisiae and K. lactis were not found in all minimum functional KmARSs reported here except KmARS7. Moreover, partial sequences from different KmARSs are interchangeable among each other to retain the ARS activity. We have also specifically identified the essential nucleotides, which are indispensable for replication, within some of the KmARSs. Our deletions analysis revealed that only 21 bp in KmARS18 could retain the ARS activity. The identified KmARSs in this study are unique compared to other yeasts' ARSs, do not share common ACS, and are interchangeable.

6.
Molecules ; 26(7)2021 Mar 29.
Article in English | MEDLINE | ID: mdl-33805491

ABSTRACT

Metabolic reactions that occur at alkylamino moieties may provide insight into the roles of these moieties when they are parts of drug molecules that act at different receptors. N-dealkylation of N,N-dialkylamino moieties has been associated with retaining, attenuation or loss of pharmacologic activities of metabolites compared to their parent drugs. Further, N-dealkylation has resulted in clinically used drugs, activation of prodrugs, change of receptor selectivity, and providing potential for developing fully-fledged drugs. While both secondary and tertiary alkylamino moieties (open chain aliphatic or heterocyclic) are metabolized by CYP450 isozymes oxidative N-dealkylation, only tertiary alkylamino moieties are subject to metabolic N-oxidation by Flavin-containing monooxygenase (FMO) to give N-oxide products. In this review, two aspects will be examined after surveying the metabolism of representative alkylamino-moieties-containing drugs that act at various receptors (i) the pharmacologic activities and relevant physicochemical properties (basicity and polarity) of the metabolites with respect to their parent drugs and (ii) the role of alkylamino moieties on the molecular docking of drugs in receptors. Such information is illuminative in structure-based drug design considering that fully-fledged metabolite drugs and metabolite prodrugs have been, respectively, developed from N-desalkyl and N-oxide metabolites.


Subject(s)
Amines/chemistry , Amines/pharmacology , Pharmaceutical Preparations/chemistry , Biochemical Phenomena , Dealkylation , Oxidation-Reduction
7.
Bioorg Chem ; 100: 103937, 2020 07.
Article in English | MEDLINE | ID: mdl-32460178

ABSTRACT

In treating wounds, long lasting infection is considered the major impediment. Drugs are rendered ineffective by pathogenic microorganisms via antibiotic resistance and calls for designing and development of new drugs. Herein, we report synthesis of eight different N-alkylated pyridine-based organic salts QAS 1-8 and their antibacterial, antibiofilm and wound healing activities. 3-(2-R-hydrazinecarbonyl)-1-propylpyridinium Bromide was the parent compound while R group was varying in each salt composed of different aromatic aldehyde moieties. In the antibacterial activity against S. aureus and E. coli, amoxicillin shows IC50 near to 25 µg/mL inhibiting 58 ± 0.4% S. aureus while ceftriaxone inhibited 55 ± 0.5% E. coli at a concentration of 10 µg/mL. The highest IC50 (56 ± 0.5% against S. aureus; 55 ± 0.5% against E. coli) was shown by compound QAS 7 at the concentration of 100 µg/mL; followed by the QAS 6 (55 ± 0.5% against E. coli) and QAS 2 (55 ± 0.5% against E. coli). In the antibiofilm activity, QAS 6, QAS 1 and QAS 8 inhibited 58 ± 0.4% S. aureus at a concentration of 75 µg/mL, while QAS 2 inhibited E. coli at the same concentration and amount. QAS 7, 3 and 1 inhibited almost 90% while QAS 6 inhibited 95 ± 1.1%of E. coli at a concentration of 250 µg/mL. Highest MBIC was provided by QAS 7 (52 ± 0.4%) against S. aureus at a concentration of 50 µg/mL that is very near to the standard amoxicillin. Antibacterial and antibiofilm activity results were also supported by the atomic force microscopy (AFM). In the wound healing activity, QAS 8 healed 90.8 ± 4.3% of the wound in 21 days with an average period of epithelialization (POE) of 19 ± 1.4 days; that is far better than povidone iodine ointment (81.5 ± 3.3% of the wound in the 21 days with 22.4 ± 2.9 days of POE). It is concluded from this study that the synthesized compounds QAS 2, 7 and 8 can be used for further mechanistic studies to be employed as antibacterial, antibiofilm and wound healing agents.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Pyridines/chemistry , Wound Healing/drug effects , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Escherichia coli/physiology , Mice , Microbial Sensitivity Tests , Microscopy, Atomic Force , Pyridines/chemical synthesis , Pyridines/pharmacology , Salts/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Structure-Activity Relationship
8.
Molecules ; 25(8)2020 Apr 22.
Article in English | MEDLINE | ID: mdl-32331223

ABSTRACT

Alkyl moieties-open chain or cyclic, linear, or branched-are common in drug molecules. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some hydroxy metabolites, which are equiactive with their parent drugs, have been developed into ester prodrugs while carboxy metabolites, which are equiactive to their parent drugs, have been developed into drugs as per se. In this review, we present and discuss the above state of affairs for a variety of drug classes, using selected drug members to show the effect on pharmacologic activity as well as dependence of the metabolic change on drug molecular structure. The review provides a basis for informed predictions of (i) structural features required for metabolic hydroxy and carboxy functionalization of alkyl moieties in existing or planned small drug molecules, and (ii) pharmacologic activity of the metabolites resulting from hydroxy and/or carboxy functionalization of alkyl moieties.


Subject(s)
Alkylating Agents/chemistry , Pharmaceutical Preparations/chemistry , Drug Development , Hydroxylation , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/chemistry , Metabolic Networks and Pathways , Molecular Structure , Pharmaceutical Preparations/classification , Structure-Activity Relationship , Sulfonylurea Compounds/administration & dosage , Sulfonylurea Compounds/chemistry
10.
Artif Cells Nanomed Biotechnol ; 46(sup3): S1204-S1214, 2018.
Article in English | MEDLINE | ID: mdl-30453792

ABSTRACT

Supramolecular macrocycles-based drug delivery systems are receiving wider recognition due to their self-assembly into nanostructures with unique characteristics. This study reports synthesis of resorcinarene-based novel and biocompatible amphiphilic supramolecular macrocycle that self-assembles into nano-vesicular system for Amphotericin B (Am-B) delivery, a model hydrophobic drug. The macrocycle was synthesized through a two-step reaction and was characterized with 1 H NMR and mass spectrometric techniques. Its biocompatibility was assessed in cancer cell lines, blood and animals. Its critical micelle concentration (CMC) was determined using UV spectrophotometer. Am-B loaded in novel macrocycle-based vesicles were examined according to their shape, size, surface charge, drug entrapment efficiency and excepients compatibility using atomic force microscope (AFM), Zetasizer, HPLC and FT-IR spectroscopy. Drug-loaded vesicles were also investigated for their in-vitro release, stability and in-vivo oral bioavailability in rabbits. The macrocycle was found to be nontoxic against cancer cells, haemo-compatible and safe in mice and revealed lower CMC. It formed mono-dispersed spherical shape vesicles of 174.4 ± 3.78 nm in mean size. Vesicles entrapped 92.05 ± 4.39% drug and were stable upon storage with gastric-simulated fluid and increased the drug oral bioavailability in rabbits. Results confirmed novel macrocycle as biocompatible vesicular nanocarrier for enhancing the oral bioavailability of lipophilic drugs.


Subject(s)
Amphotericin B , Drug Carriers , Nanoparticles , Administration, Oral , Amphotericin B/chemistry , Amphotericin B/pharmacokinetics , Amphotericin B/pharmacology , Animals , Cell Line, Tumor , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Humans , Mice , NIH 3T3 Cells , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Rabbits
11.
Molecules ; 23(9)2018 Aug 23.
Article in English | MEDLINE | ID: mdl-30142909

ABSTRACT

Drug functionalization through the formation of hydrophilic groups is the norm in the phase I metabolism of drugs for the modification of drug action. The reactions involved are mainly oxidative, catalyzed mostly by cytochrome P450 (CYP) isoenzymes. The benzene ring, whether phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand, the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e., the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e., the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retention, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues are presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design, and drug development.


Subject(s)
Cytochrome P-450 Enzyme System/chemistry , Cytochrome P-450 Enzyme System/metabolism , Analgesics, Opioid/chemistry , Codeine/chemistry , Isoenzymes/chemistry , Isoenzymes/metabolism , Oxidation-Reduction
12.
Asian J Neurosurg ; 13(2): 201-211, 2018.
Article in English | MEDLINE | ID: mdl-29682009

ABSTRACT

The etiology of up to 95% of cerebral aneurysms may be accounted for by hemodynamically-induced factors that create vascular injury. The purpose of this review is to describe key physical properties that stents have and how they affect cerebral aneurysms. We performed a two-step screening process. First, a structured search was performed using the PubMed database. The following search terms and keywords were used: "Hemodynamics," "wall shear stress (WSS)," "velocity," "viscosity," "cerebral aneurysm," "intracranial aneurysm," "stent," "flow diverter," "stent porosity," "stent geometry," "stent configuration," and "stent design." Reports were considered if they included original data, discussed hemodynamic changes after stent-based treatment of cerebral aneurysms, examined the hemodynamic effects of stent deployment, and/or described the geometric characteristics of both stents and the aneurysms they were used to treat. The search strategy yielded a total of 122 articles, 61 were excluded after screening the titles and abstracts. Additional articles were then identified by cross-checking reference lists. The final collection of 97 articles demonstrates that the geometric characteristics and configurations of deployed stents influenced hemodynamic parameters such as aneurysmal WSS, inflow, and pressure. The geometric characteristics of the aneurysm and its position also had significant influences on intra-aneurysmal hemodynamics after treatment. In conclusion, changes in specific aneurysmal hemodynamic parameters that result from stenting relate to a number of factors including the geometric properties and configurations of deployed stents, the geometric properties of the aneurysm, and the pretreatment hemodynamics.

13.
Phys Rev Lett ; 119(9): 094802, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28949569

ABSTRACT

A general orbital-angular-momentum (OAM) mode selection principle is put forward involving the rotationally symmetric superposition of chiral states. This principle is not only capable of explaining the operation of vortex generating elements such as spiral zone plate holograms, but more importantly, it enables the systematic and flexible generation of structured OAM waves in general. This is demonstrated both experimentally and theoretically in the context of electron vortex beams using rotationally symmetric binary amplitude chiral sieve masks.

14.
Int J Lab Hematol ; 39(3): 272-278, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28444873

ABSTRACT

BACKGROUND: There are no longitudinal data on the changes in hematologic, hepatic, and renal function findings in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: This is a retrospective cohort study of 16 MERS-CoV patients, to describe the hematological, hepatic, and renal findings of patients with MERS-CoV. RESULTS: During the 21 days of observation, there was no significant change in the hepatic panel or creatinine tests. There was a significant increase in the mean ± SD of the white blood cell count from 8.3 ± 4.6 to 14.53 ± 7 (P value = 0.001) and an increase in mean ± SD of the absolute neutrophil count from 6.33 ± 4.2 to 12 ± 5.5 (P value = 0.015). Leukocytosis was observed in 31% (5/16) of the patients on day 1 and in 80% (4/5) on day 21. Transient leukopenia developed in 6% (1/16) of the patients on day 1 and in 13% (1/8) on day 8. None of the patients had neutropenia. Lymphopenia was a prominent feature with a rate of 44% (7/16) of the patients on day 1 and 60% (3/5) on day 21. Lymphocytosis was not a feature of MERS-CoV infection. Thrombocytopenia developed in 31% (5/16) of the patients on day 1 and 40% (2/5) on day 21. Thrombocytosis was not a prominent feature and was observed in 6% (1/16) of the patients on day 1 and 17% (1/6) on day 9. CONCLUSIONS: Patients with MERS-CoV infection showed variable hematologic parameters over time. Lymphocytosis and neutropenia were not features of MERS-CoV infection.


Subject(s)
Coronavirus Infections/blood , Kidney/metabolism , Liver/metabolism , Middle East Respiratory Syndrome Coronavirus , Coronavirus Infections/pathology , Female , Hospitalization , Humans , Kidney/pathology , Kidney Function Tests , Leukocyte Count , Leukocytosis/blood , Leukocytosis/virology , Liver/pathology , Male , Retrospective Studies , Thrombocytopenia/blood , Thrombocytopenia/virology
15.
Philos Trans A Math Phys Eng Sci ; 375(2087)2017 Feb 28.
Article in English | MEDLINE | ID: mdl-28069769

ABSTRACT

Electron vortex beams constitute the first class of matter vortex beams which are currently routinely produced in the laboratory. Here, we briefly review the progress of this nascent field and put forward a natural quantum basis set which we show is suitable for the description of electron vortex beams. The normal modes are truncated Bessel beams (TBBs) defined in the aperture plane or the Fourier transform of the transverse structure of the TBBs (FT-TBBs) in the focal plane of a lens with the said aperture. As these modes are eigenfunctions of the axial orbital angular momentum operator, they can provide a complete description of the two-dimensional transverse distribution of the wave function of any electron vortex beam in such a system, in analogy with the prominent role Laguerre-Gaussian (LG) beams played in the description of optical vortex beams. The characteristics of the normal modes of TBBs and FT-TBBs are described, including the quantized orbital angular momentum (in terms of the winding number l) and the radial index p>0. We present the experimental realization of such beams using computer-generated holograms. The mode analysis can be carried out using astigmatic transformation optics, demonstrating close analogy with the astigmatic mode transformation between LG and Hermite-Gaussian beams.This article is part of the themed issue 'Optical orbital angular momentum'.

16.
J Biomech Eng ; 138(2): 021011, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26593324

ABSTRACT

Embolic coiling is one of the most effective treatments for cerebral aneurysms (CAs), largely due to the hemodynamic modifications that the treatment effects in the aneurysmal environment. However, coiling can have very different hemodynamic outcomes in aneurysms with different geometries. Previous work in the field of biofluid mechanics has demonstrated on a general level that geometry is a driving factor behind aneurysmal hemodynamics. The goal of this study was to relate two specific geometric factors that describe CAs (i.e., dome size (DS) and parent-vessel contact-angle (PV-CA)) and one factor that describes treatment (i.e., coil packing density (PD)) to three clinically relevant hemodynamic responses (i.e., aneurysmal root-mean-square velocity (Vrms), aneurysmal wall shear stress (WSS), and cross-neck flow (CNF)). Idealized models of basilar tip aneurysms were created in both virtual and physical forms to satisfy two-level multifactorial experimental designs. Steady and pulsatile flow hemodynamics were then evaluated in the virtual models using computational fluid dynamics (CFD) (before and after virtual treatment with finite element (FE) embolic coil models), and hemodynamics were also evaluated in the physical models using particle image velocimetry (PIV) (before and after treatment with actual embolic coils). Results showed that among the factors considered, PD made the greatest contributions to effects on hemodynamic responses in and around the aneurysmal sac (i.e., Vrms and WSS), while DS made the greatest contributions to effects on hemodynamics at the neck (i.e., CNF). Results also showed that while a geometric factor (e.g., PV-CA) may play a relatively minor role in dictating hemodynamics in the untreated case, the same factor can play a much greater role after coiling. We consider the significance of these findings in the context of aneurysmal recurrence and rupture, and explore potential roles for the proposed methods in endovascular treatment planning.


Subject(s)
Computer Simulation , Endovascular Procedures/instrumentation , Finite Element Analysis , Hemodynamics , Intracranial Aneurysm/physiopathology , Intracranial Aneurysm/therapy , Treatment Outcome
17.
Yeast ; 31(1): 29-46, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24307396

ABSTRACT

The cloning of DNA fragments into vectors or host genomes has traditionally been performed using Escherichia coli with restriction enzymes and DNA ligase or homologous recombination-based reactions. We report here a novel DNA cloning method that does not require DNA end processing or homologous recombination, but that ensures highly accurate cloning. The method exploits the efficient non-homologous end-joining (NHEJ) activity of the yeast Kluyveromyces marxianus and consists of a novel functional marker selection system. First, to demonstrate the applicability of NHEJ to DNA cloning, a C-terminal-truncated non-functional ura3 selection marker and the truncated region were PCR-amplified separately, mixed and directly used for the transformation. URA3(+) transformants appeared on the selection plates, indicating that the two DNA fragments were correctly joined by NHEJ to generate a functional URA3 gene that had inserted into the yeast chromosome. To develop the cloning system, the shortest URA3 C-terminal encoding sequence that could restore the function of a truncated non-functional ura3 was determined by deletion analysis, and was included in the primers to amplify target DNAs for cloning. Transformation with PCR-amplified target DNAs and C-terminal truncated ura3 produced numerous transformant colonies, in which a functional URA3 gene was generated and was integrated into the chromosome with the target DNAs. Several K. marxianus circular plasmids with different selection markers were also developed for NHEJ-based cloning and recombinant DNA construction. The one-step DNA cloning method developed here is a relatively simple and reliable procedure among the DNA cloning systems developed to date.


Subject(s)
Cloning, Molecular/methods , Kluyveromyces/genetics , Recombination, Genetic , Selection, Genetic , Transformation, Genetic , Plasmids , Saccharomyces cerevisiae Proteins/genetics
18.
J Biomech Eng ; 136(2): 021013, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24337100

ABSTRACT

Whether treated surgically or with endovascular techniques, large and giant cerebral aneurysms are particularly difficult to treat. Nevertheless, high porosity stents can be used to accomplish stent-assisted coiling and even standalone stent-based treatments that have been shown to improve the occlusion of such aneurysms. Further, stent assisted coiling can reduce the incidence of complications that sometimes result from embolic coiling (e.g., neck remnants and thromboembolism). However, in treating cerebral aneurysms at bifurcation termini, it remains unclear which configuration of high porosity stents will result in the most advantageous hemodynamic environment. The goal of this study was to compare how three different stent configurations affected fluid dynamics in a large patient-specific aneurysm model. Three common stent configurations were deployed into the model: a half-Y, a full-Y, and a crossbar configuration. Particle image velocimetry was used to examine post-treatment flow patterns and quantify root-mean-squared velocity magnitude (VRMS) within the aneurysmal sac. While each configuration did reduce VRMS within the aneurysm, the full-Y configuration resulted in the greatest reduction across all flow conditions (an average of 56% with respect to the untreated case). The experimental results agreed well with clinical follow up after treatment with the full-Y configuration; there was evidence of thrombosis within the sac from the stents alone before coil embolization was performed. A computational simulation of the full-Y configuration aligned well with the experimental and in vivo findings, indicating potential for clinically useful prediction of post-treatment hemodynamics. This study found that applying different stent configurations resulted in considerably different fluid dynamics in an anatomically accurate aneurysm model and that the full-Y configuration performed best. The study indicates that knowledge of how stent configurations will affect post-treatment hemodynamics could be important in interventional planning and demonstrates the capability for such planning based on novel computational tools.


Subject(s)
Cerebral Arteries/physiopathology , Cerebral Arteries/surgery , Cerebrovascular Circulation , Intracranial Aneurysm/physiopathology , Intracranial Aneurysm/surgery , Models, Cardiovascular , Stents , Blood Flow Velocity , Blood Vessel Prosthesis , Computer Simulation , Equipment Failure Analysis , Humans , Porosity , Prosthesis Design , Treatment Outcome
19.
J Biomech ; 46(16): 2809-16, 2013 Nov 15.
Article in English | MEDLINE | ID: mdl-24119679

ABSTRACT

Endovascular coiling is the most common treatment for cerebral aneurysms. During the treatment, a sequence of embolic coils with different stiffness, shapes, sizes, and lengths is deployed to fill the aneurysmal sac. Although coil packing density has been clinically correlated with treatment success, many studies have also reported success at low packing densities, as well as recurrence at high packing densities. Such reports indicate that other factors may influence treatment success. In this study, we used a novel finite element approach and computational fluid dynamics (CFD) to investigate the effects of packing density, coil shape, aneurysmal neck size, and parent vessel flow rate on aneurysmal hemodynamics. The study examines a testbed of 80 unique CFD simulations of post-treatment flows in idealized basilar tip aneurysm models. Simulated coil deployments were validated against in vitro and in vivo deployments. Among the investigated factors, packing density had the largest effect on intra-aneurysmal velocities. However, multifactor analysis of variance showed that coil shape can also have considerable effects, depending on packing density and neck size. Further, linear regression analysis showed an inverse relationship between mean void diameter in the aneurysm and mean intra-aneurysmal velocities, which underscores the importance of coil distribution and thus coil shape. Our study suggests that while packing density plays a key role in determining post-treatment hemodynamics, other factors such as coil shape, aneurysmal geometry, and parent vessel flow may also be very important.


Subject(s)
Endovascular Procedures/instrumentation , Finite Element Analysis , Hemodynamics , Intracranial Aneurysm/physiopathology , Intracranial Aneurysm/therapy , Models, Cardiovascular , Analysis of Variance , Embolic Protection Devices , Equipment Design , Humans , Hydrodynamics
20.
Phys Rev Lett ; 110(8): 083002, 2013 Feb 22.
Article in English | MEDLINE | ID: mdl-23473140

ABSTRACT

We show that the normally weak optical quadrupole interaction in atoms is enhanced significantly when the atom interacts at near resonance with an optical vortex. In particular, the forces and torque acting on the atom are shown here to scale up with the square of the winding number l of the vortex. Because the integer l can be arranged to be large, this property allows for processes involving dipole-forbidden, but quadrupole-allowed, transitions in atoms, such as cesium and oxygen, to come into play. We show that the mechanical effects of vortex light on atoms involving translational and rotational motion as well as trapping should be significantly enhanced for quadrupole transitions and present novel features with useful implications for the emerging field of atomtronics.

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