Miracle-dz/UniFAR-FTUs huggingface dataset:
Lamivudine: fading into the mists of time

The treatment goal for patients with chronic hepatitis B (CHB) is reducing liver related mortalities from cirrhosis and hepatocellular carcinoma (HCC). For the past 20 years, single or combination regimen of nucleos(t)ide analogues (NUCs) has been widely used for this purpose and partly achieved the treatment goal in CHB patients. Hepatitis B e antigen (HBeAg)-negative CHB has been regarded as challenging to treat owing to the rapid and aggressive progression of the disease. Since the phase 3 study by Lai et al. entecavir has been widely used in treatment-naïve HBeAg-negative CHB patients and showed its higher efficacy than lamivudine in the real world data. International guidelines also recommend entecavir as the preferred choice for first-line agent for CHB patients along with tenofovir disoproxil fumarate, rather than lamivudine. Although the higher efficacy of entecavir compared with lamivudine has reported in previous randomized trial, Lee et al. conducted a randomized controlled trial to compare the ‘long-term’ efficacy and safety during 5 years in treatment-naive HBeAg-negative Korean CHB patients whose genotype are mostly genotype C. In the current issue of Clinical and Molecular Hepatology, this study showed long-term entecavir treatment was superior to lamivudine as quite well expected. Virologic response, defined according to the AASLD guidelines, was achieved in 95.0% of entecavir-treated patients and 47.6% of lamivudine-treated patients (P<0.0001) after 240 weeks of treatment. Notably, 26 (42.6%) of lamivudinetreated patients occurred virologic breakthrough until week 96, whereas only one patient of entecavir-treated patient developed virologic breakthrough. This patient with virologic breakthrough at week 48 did not have resistance to entecavir and was found to have undetectable HBV DNA at week 60 and 192. The demerit of Lee’s study is the small sample size and high drop-out rate as the authors mentioned in discussion. According to the study flow depicted in figure 1, most common cause of drop-out was treatment failure/lack of efficacy (n=24) and belonged to lamivudine-treated group. However, these high drop-outs might be expected in consequence of the lower efficacy and high virologic breakthrough in lamivudine-treated group. Regarding the safety and tolerability, Lee’s study reported both entecavir and lamivudine were well tolerated with a low incidence of adverse events which were not related to the study drugs through 5 year of study period. This accumulates supporting See Article on Page 331 Lamivudine: fading into the mists of time
Performance analysis of a Bipolar Mode JFET (BMFET) with normally off characteristics

The fabrication and the characterization of a family of power Bipolar Mode JFET's (BMFET) is reported. In these devices, blocking voltages up to 1000 V or currents up to 18 A (corresponding to 800 A/cm2) have been obtained. Results allow to get an insight in the physics of operation of the BMFET, to define their theoretical limits of operation, and to understand the reasons for the superior performance of the present device, with respect to the Bipolar Transistor.
Are gender differences in the responses to hypoglycemia relevant to iatrogenic hypoglycemia in type 1 diabetes?

Iatrogenic hypoglycemia is the limiting factor in the glycemic management of type 1 diabetes mellitus (T1DM) and advanced type 2 diabetes mellitus (T2DM) (1). Because of the interplay of relative or absolute therapeutic insulin excess— which must occur from time-to-time because of the pharmacokinetic imperfections of all insulin replacement regimens—and of compromised physiological and behavioral defenses against falling plasma glucose concentrations, the clinical syndromes of defective glucose counterregulation, and hypoglycemia unawareness, hypoglycemia is a barrier to true glycemic control in T1DM (2, 3) and insulin-requiring T2DM (4, 5). As a result, albeit at lower rates, long-term complications of diabetes occur despite aggressive attempts to reduce glycemia. For example, retinopathy developed or progressed in 14% of the patients with T1DM treated intensively (compared with 32% of those treated conventionally) in the Diabetes Control and Complications Trial (2), and a microvascular end point developed in 8% of the patients with T2DM treated intensively (compared with 11% of those treated conventionally) in the United Kingdom Prospective Diabetes Study (4). In the short term, hypoglycemia often
Fibrous Keratin Powder as by-Product of Keratinase Fermentation under Solid State Fermentation using Chicken Feathers as Substrate

Billion tons of chicken feathers are being generated every year from the poultry industry. Ironically, although egg white is one important source of proteins for a human, it only contains 57% of protein, while chicken feathers contains about 980% of protein. However, due to its complex structure, chicken feathers are not consumable by the human. This makes chicken feathers are classified as biowaste material which causes environmental problems. The huge amount of this biomaterial offers a potential raw material for polypeptide and amino acids source. Chicken feathers contains a highly fibrous protein called keratin. X-ray diffraction model of keratin architecture showed supercoiled of helical proteins. The structure is also strengthened by disulphide bonds which make keratin insoluble in water and an organic solvent. Many attempts have been tried to break down the chemical bonds and convert chicken feathers into simple structural materials for sustainable uses. Currently, hydrothermal degradation is a preferable technique to concert chicken feathers into keratin powder because it is cheap for industrial purposes. Enzymatic degradation offers a greener process. We have successfully isolated a Gram-positive bacterium named Bacillus sp. MD24 which is capable of producing keratinase, an enzyme that degrades chicken feathers. In this paper, we described fibrous keratin powder as a by-product of keratinase fermentation by Bacillus sp. MD24 under solid-state fermentation (SSF). Scanning electron micrograph showed a tremendous reduction in the size of keratin after fermentation.
On the Energy Efficiency of IP-over-WDM Networks

In the next years, the Internet will undergo a substantial increase of the capacity required by end-users. Since Internet currently consumes a significant fraction of the world electrical power, reducing the energy consumption of telecom networks is expected to become more and more important. In this paper, we focus on backbone transport networks. We compare three different architectures for IP packet transport based on Wavelength Division Multiplexing (WDM) over optical fiber links (IP-over-WDM networks), namely IP with no Bypass (IP-NB), IP with Bypass (IP-B) and IP with Bypass and Grooming (IP-BG), which differ in their capability of traffic aggregation (grooming) and optical switching. IP-NB performs grooming in every network node, where the traffic is electronically processed and forwarded by the IP routers. IP-B enables switching of wavelength channels directly in the optical domain, thus bypassing the IP packet processing in intermediate IP routers. The IP-BG architecture represents an intermediate solution between the previous two: it provides both grooming capabilities (as IP-NB), in order to exploit network capacity efficiently, and optical switching (as IP-B) to reduce expensive electronic processing. We compare these three solutions, showing the trade-off between the reduction of the power consumption or of the network cost, and we analyze how minimizing one of these two factors can influence the other.
Econometric Analysis of Multivariate Realised QML: Estimation of the Covariation of Equity Prices under Asynchronous Trading

Estimating the covariance between assets using high frequency data is challenging due to market microstructure effects and asynchronous trading. In this paper we develop a multivariate realised quasi maximum likelihood (QML) approach, carrying out inference as if the observations arise from an asynchronously observed vector scaled Brownian model observed with error. Under stochastic volatility the resulting realised QML estimator is positive definite, uses all available data, is consistent and asymptotically mixed normal. The quasi-likelihood is computed using a Kalman filter and optimised using a relatively simple EM algorithm. We also propose an alternative estimator using a factor model, which scales well with the number of assets. We derive the theoretical properties of these estimators and prove that they achieve the efficient rate of convergence. Our estimators are also analysed using Monte Carlo methods and applied to equity data with varying levels of liquidity.
2 Ontology Management

Ontologies are considered a key technology enabling semantic interoperability and integration of data and processes. We are now entering a phase of knowledge system development, in which ontologies are produced in larger numbers and exhibit greater complexity. Ontology management infrastructures are needed for the increasing development of semantic applications especially in the corporate semantic web, which comprises the application of semantic technologies in an enterprise environment. In this chapter, we present a generic system architecture for an ontology management infrastructure that supports the construction of semantic applications. Such an ontology management infrastructure is expected to be generic and flexible in its design, comprehensive in its functionality in order to meet the requirements of a wide spectrum of semantic applications. To illustrate typical requirements of a semantic application, we start with a short scenario of semantic integration and search: Bob works as technology analyst for an IT company. His daily work includes research on new technological trends, market developments and competitors of his clients. Bob's company maintains a digital library that gives access to a repository of internal surveys and analysis documents. The company also has a license with an academic research database which is accessed via a separate interface. Depending on his work context, Bob uses the topic hierarchies, the full-text search func-tionalities or metadata search facilities provided by the two libraries to get access to the relevant data. However, Bob is often annoyed by the differing topic hierarchies and metadata schemes used by the two libraries as well as by a cumbersome syntax for posing metadata queries.
Measuring task performance using gaze regions

We present a novel method for measuring task performance using gaze regions, i.e., scene regions fixated by a subject as he or she performs a familiar manual task. The scene regions are learned as a bag of features representation, using library lookup based on the Histogram of Oriented Gradients feature descriptor [1]. By establishing a set of task-specific exemplar models, i.e., models sourced from Pareto optimal sequences, the approach recognizes the local optima within a set of task-specific unlabeled models by estimating the distance (of each unlabeled model) to the exemplar models. During testing, the method is evaluated against a dataset of egocentric sequences, each containing gaze data, belonging to three manual skill-based activities. The results show perfect classification's accuracy on several proposed schemes.
Exact and approximate rebinning algorithms for 3-D PET data

This paper presents two new rebinning algorithms for the reconstruction of three-dimensional (3-D) positron emission tomography (PET) data. A rebinning algorithm is one that first sorts the 3-D data into an ordinary two-dimensional (2-D) data set containing one sinogram for each transaxial slice to be reconstructed; the 3-D image is then recovered by applying to each slice a 2-D reconstruction method such as filtered-backprojection. This approach allows a significant speedup of 3-D reconstruction, which is particularly useful for applications involving dynamic acquisitions or whole-body imaging. The first new algorithm is obtained by discretizing an exact analytical inversion formula. The second algorithm, called the Fourier rebinning algorithm (FORE), is approximate but allows an efficient implementation based on taking 2-D Fourier transforms of the data. This second algorithm was implemented and applied to data acquired with the new generation of PET systems and also to simulated data for a scanner with an 18/spl deg/ axial aperture. The reconstructed images were compared to those obtained with the 3-D reprojection algorithm (3DRP) which is the standard "exact" 3-D filtered-backprojection method. Results demonstrate that FORE provides a reliable alternative to 3DRP, while at the same time achieving an order of magnitude reduction in processing time.
Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases

Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase (PTK) that associates with integrin receptors and participates in extracellular matrix-mediated signal transduction events. We showed previously that the c-Src nonreceptor PTK and the Grb2 SH2/SH3 adaptor protein bound directly to FAK after fibronectin stimulation (D. D. Schlaepfer, S.K. Hanks, T. Hunter, and P. van der Geer, Nature [London] 372:786-791, 1994). Here, we present evidence that c-Src association with FAK is required for Grb2 binding to FAK. Using a tryptic phosphopeptide mapping approach, the in vivo phosphorylation of the Grb2 binding site on FAK (Tyr-925) was detected after fibronectin stimulation of NIH 3T3 cells and was constitutively phosphorylated in v-Src-transformed NIH 3T3 cells. In vitro, c-Src phosphorylated FAK Tyr-925 in a glutathione S-transferase-FAK C-terminal domain fusion protein, whereas FAK did not. Using epitope-tagged FAK constructs, transiently expressed in human 293 cells, we determined the effect of site-directed mutations on c-Src and Grb2 binding to FAK. Mutation of FAK Tyr-925 disrupted Grb2 binding, whereas mutation of the c-Src binding site on FAK (Tyr-397) disrupted both c-Src and Grb2 binding to FAK in vivo. These results support a model whereby Src-family PTKs are recruited to FAK and focal adhesions following integrin-induced autophosphorylation and exposure of FAK Tyr-397. Src-family binding and phosphorylation of FAK at Tyr-925 creates a Grb2 SH2-domain binding site and provides a link to the activation of the Ras signal transduction pathway. In Src-transformed cells, this pathway may be constitutively activated as a result of FAK Tyr-925 phosphorylation in the absence of integrin stimulation.
Asymptomatic Elite Adolescent Tennis Players' Signs of Tendinosis in Their Dominant Shoulder Compared With Their Nondominant Shoulder.

CONTEXT Tennis is an asymmetric overhead sport with specific muscle-activation patterns, especially eccentrically in the rotator cuff. Magnetic resonance imaging (MRI) findings in asymptomatic adolescent elite tennis players have not previously been reported. OBJECTIVE The first aim of the study was to describe MRI findings regarding adaptations or abnormalities, as well as muscle cross-sectional area (CSA), of the rotator cuff. The second aim of the study was to investigate the rotator cuff based on the interpretation of the MRI scans as normal versus abnormal, with the subdivision based on the grade of tendinosis, and its association with eccentric rotator cuff strength in the dominant arm (DA) of the asymptomatic elite adolescent tennis player. SETTING Testing environment at the radiology department of Medicinsk Röntgen AB. PATIENTS OR OTHER PARTICIPANTS Thirty-five asymptomatic elite tennis players (age = 17.4 ± 2.7 years) were selected based on ranking and exposure time. INTERVENTION(S) We assessed MRI scans and measured the CSA of the rotator cuff muscle. The non-DA (NDA) was used as a control. In addition, eccentric testing of the external rotators of the DA was performed with a handheld dynamometer. RESULTS The DA and NDA displayed different frequencies of infraspinatus tendinosis (grade 1 changes) (P < .05). Rotator cuff measurements revealed larger infraspinatus and teres minor CSA (P < .05) in the DA than in the NDA. Mean eccentric external-rotation strength in the DA stratified by normal tendon and tendinosis was not different between groups (P = .723). CONCLUSIONS Asymptomatic adolescent elite tennis players demonstrated infraspinatus tendinosis more frequently in the DA than in the NDA. Clinicians must recognize these tendon changes in order to modify conditioning and performance programs appropriately.
ULTRASOUND-ASSISTED EXTRACTION OF PHOTOSYNTHETIC PIGMENTS FROM DRIED DILL (ANETHUM GRAVEOLENS)

Extraction is an important step in studies involving the isolation of active compounds from plant materials. Ultrasound assisted extraction (UAE) is a simple, inexpensive and efficient technique due to shortened extraction time and reduced organic solvent consumption compared with other extraction method. Chlorophyll extracts are used extensively as dye in coloring inks, resins, soaps and waxes, edible fats, cosmetics, lotions perfume. Some experimental data suggest also that chlorophyll may ameliorate drug side effects, may have some anti-mutagenic and anti-carcinogenic potential and it may help protect against some toxins. The aim of this study was to determine the influence of ultrasound extraction parameters, like acetone volume (80%, 90%, 100%), ultrasounds exposure time and ratio solvent/material on the extraction of photosynthetic pigments from dill (Anethum graveolens). Ultraviolet spectroscopy was used to evaluate the efficiency of this extraction method and it was also used to quantitatively analyse the extracted chlorophylls and carotenoids. Results show that the extraction efficiency of photosynthetic pigments from dried dill was higher when using acetone 90% comparative to the other two concentrations, because the highest level of total chlorophyll obtained was of 4,53mg/g dried dill in acetone 90% after 15 min. exposure to ultrasounds. The results suggest that UAE method is an efficient technique for extraction of photosynthetic pigments.
Single image defocus estimation by modified gaussian function

This article presents an algorithm to estimate the defocus blur from a single image. Most of the existing methods estimate the defocus blur at edge locations, which further involves the reblurring process. For this purpose, existing methods use the traditional Gaussian function in the phase of reblurring but it is found that the traditional Gaussian kernel is sensitive to the edges and can cause loss of edges information. Hence, there are more chances of missing spatially varying blur at edge locations. We offer the repeated averaging filters as an alternative to the traditional Gaussian function, which is more effective, and estimate the spatially varying defocus blur at edge locations. By using repeated averaging filters, a blur sparse map is computed. The obtained sparse map is propagated by integration of superpixels segmentation and transductive inference to estimate full defocus blur map. Our adopted method of repeated averaging filters has less computational time of defocus blur map estimation and has better visual estimates of the final defocus recovered map. Moreover, it has surpassed many previous state‐of‐the‐art proposed systems in terms of quantative analysis.
Combined PET–CT and axillary lymph node marking with radioactive iodine seeds (MARI procedure) for tailored axillary treatment in node‐positive breast cancer after neoadjuvant therapy

The treatment of axillary lymph node metastases after neoadjuvant systemic therapy (NST) remains debatable and axillary lymph node dissection (ALND) is still the standard of care. Marking axillary lymph nodes with radioactive iodine seeds (MARI procedure) is accurate in restaging the axilla after NST (false‐negative rate 7 per cent). Here, the potential of tailored axillary treatment, determined by combining the results of PET–CT before NST with those of the MARI procedure after NST, was analysed.
Ceramic microparticles and capsules via microfluidic processing of a preceramic polymer

We have developed a robust technique to fabricate monodispersed solid and porous ceramic particles and capsules from single and double emulsion drops composed of silsesquioxane preceramic polymer. A microcapillary microfluidic device was used to generate the monodispersed drops. In this device, two round capillaries are aligned facing each other inside a square capillary. Three fluids are needed to generate the double emulsions. The inner fluid, which flows through the input capillary, and the middle fluid, which flows through the void space between the square and inner fluid capillaries, form a coaxial co-flow in a direction that is opposite to the flow of the outer fluid. As the three fluids are forced through the exit capillary, the inner and middle fluids break into monodispersed double emulsion drops in a single-step process, at rates of up to 2000 drops s−1. Once the drops are generated, the silsesquioxane is cross-linked in solution and the cross-linked particles are dried and pyrolysed in an inert atmosphere to form oxycarbide glass particles. Particles with diameters ranging from 30 to 180 µm, shell thicknesses ranging from 10 to 50 µm and shell pore diameters ranging from 1 to 10 µm were easily prepared by changing fluid flow rates, device dimensions and fluid composition. The produced particles and capsules can be used in their polymeric state or pyrolysed to ceramic. This technique can be extended to other preceramic polymers and can be used to generate unique core–shell multimaterial particles.
Interannual Variability of Sea Surface Height over the Black Sea: Relation to Climatic Patterns

Sea surface height (SSH) variability is presented over the Black Sea during 1993-2005. The 1/4° × 1/4° resolution daily SSH fields are formed using optimal interpolation of available altimeter data. SSH variability reveals distinct maxima in the eastern and western basins, reflecting variations in the corresponding gyres. A joint examination of SSH and sea surface tem- perature (SST) indicates strong relationship between the two only in winter, with correlations as high as 0.6 or more. This would reflect a steric change in sea surface height due to thermal expansion averaged over a relatively deep winter mixed layer. Newly developed SSH fields also demonstrate a switch to the positive mode of SSH starting from the end of 1996 lasting ≈4 yr. Such a climatic shift is found to be strongly related to large-scale teleconnection patterns. Finally, the daily SSH and SST anomaly fields presented in this paper can supplement various applications in the Black Sea, such as examination of biological production and mesoscale eddy dynamics.