Polyesters containing 2,4-dihydroxy-6-(2-hydroxypropyl)benzoate and 3-hydroxybutyrate moieties have been isolated from many fungal species. Talaromyces stipitatus was previously reported to produce a ...similar polyester, talapolyester G. The complete genome sequence and the development of bioinformatics tools have enabled the discovery of the biosynthetic potential of this microorganism. Here, a putative biosynthetic gene cluster (BGC) of the polyesters encoding a highly reducing polyketide synthase (HR-PKS) and nonreducing polyketide synthase (NR-PKS), a cytochrome P450 and a regulator, was identified. Although talapolyester G does not require an oxidative step for its biosynthesis, further investigation into the secondary metabolite production of T. stipitatus resulted in isolating two new metabolites called talarodioxadione and talarooxime, in addition to three known compounds, namely 6-hydroxymellein, 15G256α and transtorine that have never been reported from this organism. Interestingly, the biosynthesis of the cyclic polyester 15G256α requires hydroxylation of an inactive methyl group and thus could be a product of the identified gene cluster. The two compounds, talarooxime and transtorine, are probably the catabolic metabolites of tryptophan through the kynurenine pathway. Tryptophan metabolism exists in almost all organisms and has been of interest to many researchers. The biosynthesis of the new oxime is proposed to involve two subsequent N-hydroxylation of 2-aminoacetophenone.
The current standard of care for many patients with HER2-positive breast cancer is neoadjuvant chemotherapy in combination with anti-HER2 agents, based on HER2 amplification as detected by in situ ...hybridization (ISH) or protein immunohistochemistry (IHC). However, hematoxylin & eosin (H&E) tumor stains are more commonly available, and accurate prediction of HER2 status and anti-HER2 treatment response from H&E would reduce costs and increase the speed of treatment selection. Computational algorithms for H&E have been effective in predicting a variety of cancer features and clinical outcomes, including moderate success in predicting HER2 status. In this work, we present a novel convolutional neural network (CNN) approach able to predict HER2 status with increased accuracy over prior methods. We trained a CNN classifier on 188 H&E whole slide images (WSIs) manually annotated for tumor Regions of interest (ROIs) by our pathology team. Our classifier achieved an area under the curve (AUC) of 0.90 in cross-validation of slide-level HER2 status and 0.81 on an independent TCGA test set. Within slides, we observed strong agreement between pathologist annotated ROIs and blinded computational predictions of tumor regions / HER2 status. Moreover, we trained our classifier on pre-treatment samples from 187 HER2+ patients that subsequently received trastuzumab therapy. Our classifier achieved an AUC of 0.80 in a five-fold cross validation. Our work provides an H&E-based algorithm that can predict HER2 status and trastuzumab response in breast cancer at an accuracy that may benefit clinical evaluations.
•2D- photonic crystal fiber (PCF) with surface plasmon resonance (SPR) for refractive index is demonstrated.•Designed sensor is used to perform the pregnancy test.•Pregnant urine with the effective ...refractive indices values of 1.335, 1.34, 1.342 and 1.343 with wavelength from 1.75 µm to 2 µm is performed.•Designed sensor offers the significant sensing performances for the polarized modes.
In the proposed work, a two-dimensional photonic crystal fiber (PCF) based on the surface plasmon resonance (SPR) refractive index sensor has been demonstrated and designed which is so much helpful to gain a better sensitivity response in urine observation. In order to detect the pregnancy, the simulation and analysis have been performed in both normal and pregnant urine with the effective refractive indices values of 1.335, 1.34, 1.342 and 1.343 within the range of working wavelength from 1.75 µm to 2 µm. From this testing sensor, the optical parameters of the dispersion relation, birefringence, coupling length, confinement loss, insertion loss, sensor length, crosstalk, sensitivity response, resonance wavelength, resolution, and sensitivity per line-width have been analyzed. Besides, Finite element method (FEM) is used for the numerical investigations. From this investigation, the highest value of sensitivity response, sensitivity per line-width, and the resolution of 68051.344 nm/RIU, 314 RIU−1, and 9.39 × 10−6 RIU are gained. It is noted that the proposed sensor offers significant sensing performances for the polarized modes. The main goal of this investigation is to develop the concepts of optoelectronics and laser bio-sensor in the field of biological detection systems. As a result, this structure of optical biosensor will be applicable through the modified optical fiber in biological changes.
The current research efforts in the security domain are essentially inspired by the intention to ensure both healthcare software's security and usability. Practitioners are continuously working on ...techniques that can optimise security while affording the ease of use. Inspite of the numerous efforts by the developers and security experts in this context, the level of usability-security is not the same as it should be. Furthermore, it is important to do more work on the most effective strategies for evaluating and increasing the usable-security of healthcare technology. Quantitative usability and security assessment is an important part of increasing the standards of software security especially with regard to software used in healthcare. This study's objective, in particular, is to evaluate the usability-security of healthcare software. Thereafter, based on the empirical analysis of comprehensive data, the study recommends the strategies that would facilitate in designing healthcare software with optimum security while preserving its' usability. Decision makers often find it difficult to integrate highly secure software with maximum usability while developing the software. Hence, this research endeavour enlists the assimilation of usability and safety with their contributory attributes. Moreover, this study proposes the use of a novel technique of combining the Analytic Network Method (ANP), Fuzzy Sets (FS), and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) to test usability together with security. The researchers employed the suggested methodology on six applications of the hospital management systems in Mecca, Saudi Arabia, to ascertain the utility of the FS-AHP-TOPSIS hybrid solution technique. Usability results along with security assessment corroborated that the most accurate and effective method for evaluating the usable-security of healthcare applications will be this innovative hybrid approach. Most relevantly, these findings will be useful in the security management without impacting the usability for the end users.
In this paper, a novel microstructure quasi-photonic crystal fiber design is proposed. Aimed at a high relative sensitivity, it is targeted for chemical sensing applications in the terahertz regime. ...A rigorous full-vector finite element method-based numerical investigation has been applied by employing an anisotropic perfectly matched layer for optimizing key parameters. Improved relative sensitivity responses of 78.8%, 77.8%, and 69.7% are achieved for targeted analytes ethanol, benzene, and water, respectively, at the operating frequency of f =1.3 THz. Moreover, confinement loss, effective area, power fraction, and numerical aperture are analyzed from 0.8 to 2.0 THz.
Cardiovascular disease is the leading cause of morbidity/mortality worldwide. Metformin is the first therapy offering cardioprotection in type 2 diabetes and non-diabetic animals with unknown ...mechanism. We have shown that metformin improves angiogenesis via affecting expression of growth factors/angiogenic inhibitors in CD34⁺ cells under hyperglycemia-hypoxia. Now we studied the direct effect of physiological dose of metformin on human umbilical vein endothelial cells (HUVEC) under conditions mimicking hypoxia-hyperglycemia. HUVEC migration and apoptosis were studied after induction with euglycemia or hyperglycemia and/or CoCl₂ induced hypoxia in the presence or absence of metformin. HUVEC mRNA was assayed by whole transcript microarrays. Genes were confirmed by qRT-PCR, proteins by western blot, ELISA or flow cytometry. Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (
), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (
), matrix metalloproteinase 16 (
) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia. Therefore, metformin's dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on VEGFR1/R2 leading to activation of cell migration through
and
upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and
, components of VEGF signaling cascades.
The relationship between intervertebral disc degeneration and chronic infection by Propionibacterium acnes is controversial with contradictory evidence available in the literature. Previous studies ...investigating these relationships were under-powered and fraught with methodical differences; moreover, they have not taken into consideration P. acnes' ability to form biofilms or attempted to quantitate the bioburden with regard to determining bacterial counts/genome equivalents as criteria to differentiate true infection from contamination. The aim of this prospective cross-sectional study was to determine the prevalence of P. acnes in patients undergoing lumbar disc microdiscectomy.
The sample consisted of 290 adult patients undergoing lumbar microdiscectomy for symptomatic lumbar disc herniation. An intraoperative biopsy and pre-operative clinical data were taken in all cases. One biopsy fragment was homogenized and used for quantitative anaerobic culture and a second was frozen and used for real-time PCR-based quantification of P. acnes genomes. P. acnes was identified in 115 cases (40%), coagulase-negative staphylococci in 31 cases (11%) and alpha-hemolytic streptococci in 8 cases (3%). P. acnes counts ranged from 100 to 9000 CFU/ml with a median of 400 CFU/ml. The prevalence of intervertebral discs with abundant P. acnes (≥ 1x103 CFU/ml) was 11% (39 cases). There was significant correlation between the bacterial counts obtained by culture and the number of P. acnes genomes detected by real-time PCR (r = 0.4363, p<0.0001).
In a large series of patients, the prevalence of discs with abundant P. acnes was 11%. We believe, disc tissue homogenization releases P. acnes from the biofilm so that they can then potentially be cultured, reducing the rate of false-negative cultures. Further, quantification study revealing significant bioburden based on both culture and real-time PCR minimize the likelihood that observed findings are due to contamination and supports the hypothesis P. acnes acts as a pathogen in these cases of degenerative disc disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Modified multi-walled carbon nanotubes (f-MWCNTs) and hydroxyapatite nanorods (n-HA) were reinforced into polypropylene (PP) with the support of a melt compounding approach. Varying composition of ...f-MWCNTs (0.1-0.3 wt.%) and nHA (15-20 wt.%) were reinforced into PP, to obtain biocomposites of different compositions. The morphology, thermal and mechanical characteristics of PP/n-HA/f-MWCNTs were observed. Tensile studies reflected that the addition of f-MWCNTs is advantageous in improving the tensile strength of PP/n-HA nanocomposites but decreases its Young's modulus significantly. Based on the thermal study, the f-MWCNTs and n-HA were known to be adequate to enhance PP's thermal and dimensional stability. Furthermore, MTT studies proved that PP/n-HA/f-MWCNTs are biocompatible. Consequently, f-MWCNTs and n-HA reinforced into PP may be a promising nanocomposite in orthopedics industry applications such as the human subchondral bone i.e. patella and cartilage and fabricating certain light-loaded implants.
Today's healthcare organizations want to implement secure and quality healthcare software as cyber-security is a significant risk factor for healthcare data. Considering security requirements during ...trustworthy healthcare software development process is an essential part of the quality software development. There are several Security Requirements Engineering (SRE) methodologies, framework, process, standards available today. Unfortunately, there is still a necessity to improve these security requirements engineering approaches. Determining the most suitable security requirements engineering method for trustworthy healthcare software development is a challenging process. This study is aimed to present security experts' perspective on the relative importance of the criteria for selecting effective SRE method by utilizing the multi-criteria decision making methods.
The study was planned and conducted to identify the most appropriate SRE approach for quality and trustworthy software development based on the security expert's knowledge and experience. The hierarchical model was evaluated by using fuzzy TOPSIS model. Effective SRE selection criteria were compared in pairs. 25 security experts were asked to response the pairwise criteria comparison form.
The impact of the recognized selection criteria for effective security requirements engineering approaches has been evaluated quantitatively. For each of the 25 participants, comparison matrixes were formed based on the scores of their responses in the form. The consistency ratios (CR) were found to be smaller than 10% (CR = 9.1% < 10%). According to pairwise comparisons result; with a 0.842 closeness coefficient (Ci), STORE methodology is the most effective security requirements engineering approach for trustworthy healthcare software development.
The findings of this research study demonstrate various factors in the decision-making process for the selection of a reliable method for security requirements engineering. This is a significant study that uses multi-criteria decision-making tools, specifically fuzzy TOPSIS, which used to evaluate different SRE methods for secure and trustworthy healthcare application development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We have investigated graphene-based three various refractive index sensors (split ring resonator (SRR), split ring resonator with thin wire (SRRTW), and thin wire (TW) refractive index sensors) for ...the encoding and sensing-based applications. The sensors are designed to detect the presence of hemoglobin biomolecules with high sensitivity. The results are analyzed in the form of transmittance, and electric field and detailed sensitivity analysis is also carried out for the proposed graphene-based refractive index sensors for four various concentrations of hemoglobin biomolecules. We have also investigated the sensor's performance in terms of quality factor, Q, and figure of merit (FOM). The encoding of '0' and '1' is attained by varying the graphene chemical potential fulfilling the one-digit coding. An array of these sensors can then be used for encoding-based applications. The detailed analysis of reported sensors is also carried out by checking the effect of varying physical parameters such as substrate thickness, split ring gap, and thin wire width on tunability. These sensors can be applied in biomedical or encoding-based applications. Experiments are performed using XGBoost regressor to determine, whether simulation time and resources can be reduced by using regression analysis to predict the transmittance values of intermediate frequency or not. Experimental results prove that regression analysis using XGBoost Regressor can reduce the simulation time and resources by at least 70 percent.
PDF
