Using machine learning tools for protein database biocuration assistance

Biocuration in the omics sciences has become paramount, as research in these fields rapidly evolves towards increasingly data-dependent models. As a result, the management of web-accessible publicly-available databases becomes a central task in biological knowledge dissemination. One relevant challenge for biocurators is the unambiguous identification of biological entities. In this study, we illustrate the adequacy of machine learning methods as biocuration assistance tools using a publicly available protein database as an example. This database contains information on G Protein-Coupled Receptors (GPCRs), which are part of eukaryotic cell membranes and relevant in cell communication as well as major drug targets in pharmacology. These receptors are characterized according to subtype labels. Previous analysis of this database provided evidence that some of the receptor sequences could be affected by a case of label noise, as they appeared to be too consistently misclassified by machine learning methods. Here, we extend our analysis to recent and quite substantially modified new versions of the database and reveal their now extremely accurate labeling using several machine learning models and different transformations of the unaligned sequences. These findings support the adequacy of our proposed method to identify problematic labeling cases as a tool for database biocuration.Peer ReviewedPostprint (published version

Development of a Laser-Spark Multicharged Ion System – Application in Shallow Implantation of Sic by Boron and Barium

A novel multicharged ion source, using laser ablation induced plasma coupled with spark discharge, has been investigated in this work. The designed and demonstrated ion source is cost-effective, compact and versatile. Experiments are described with the intention of demonstrating the practicability of ion implantation via laser ion source. Multicharged aluminum ions are generated by a ns Q-switched Nd:YAG laser pulse ablation of an aluminum target in an ultrahigh vacuum. The experiments are conducted using laser pulse energies of 45–90 mJ focused on the Al target surface by a lens with an 80-cm focal length to 0.0024 cm2 spot area and incident at 45° with the Al target surface. With the increase in the laser pulse energy, a slow increase in the number of ions generated is observed. The generation of ions with a higher charge state is also observed with the increase in the laser pulse energy. For 5 kV accelerating voltage applied to the Al target and using laser energy of 90 mJ, up to Al4+ charge is delivered to the detector which is located 140 cm away from the Al target. Raising accelerating voltage increases the charge extraction from the laser plasma and the energy of multicharged ions. The components of a transport line for a laser multicharged ion source are described. Aluminum and carbon multicharged ions are generated by a Q-switched, nanosecond Nd:YAG laser (wavelength λ = 1064 nm, pulse width τ = 7.4 ns, and pulse energy up to 82 mJ) ablation of a target in a vacuum chamber. Time-of-flight and three-grid retarding ion energy analyzers are used to determine the velocity and the charge state of the ions. A three-electrode cylindrical einzel lens is used to focus the ions. At 30 cm from the center of the focusing electrode of the einzel lens, Al1+ and Al2+ have a minimum beam diameter of ∼1.5 mm, while for Al3+ and Al4+ the minimum beam diameter is ∼2.5 mm. The simulation of the ion trajectories is done using SIMION 8.1. A high voltage pulse applied to a set of two parallel deflecting plates is used for the pickup of ions with different charge states according to their time-of-flight. An electrostatic cylindrical ion deflector is used for analysis and selection of charges with specific energy-to-charge ratio. The design of these transport line components and their operation are described. A spark discharge is coupled to a laser multicharged ion source to enhance ion generation. The laser plasma triggers a spark discharge with electrodes located in front of the ablated target. For an aluminum target, the spark discharge results in significant enhancement in the generation of multicharged ions along with higher charge states than observed with the laser source alone. When a Nd:YAG laser pulse (wavelength 1064 nm, pulse width 7.4 ns, pulse energy 72 mJ, laser spot area on target 0.0024 cm2) is used, the total multicharged ions detected by a Faraday cup is 1.0 nC with charge state up to Al3+. When the spark amplification stage is used (0.1 μF capacitor charged to 5.0 kV), the total charge measured increases by a factor of ∼9 with up to Al6+ charge observed. Using laser pulse energy of 45 mJ, charge amplification by a factor of ∼13 was observed for a capacitor voltage of 4.5 kV. The spark discharge in-creases the multicharged ion generation without increasing target ablation, which solely results from the laser pulse. This allows for increased multicharged ion generation with relatively low laser energy pulses and less damage to the surface of the target. Laser plasma generated by ablation of an Al target in vacuum is characterized by ion time-of-flight combined with optical emission spectroscopy. A Q-switched Nd:YAG laser (wavelength λ = 1064 nm, pulse width τ ∼ 7 ns, and fluence F ≤ 38 J/cm2) is used to ablate the Al target. Ions are accelerated according to their charge state by the double-layer potential developed at the plasma-vacuum interface. The ion energy distribution follows a shifted Coulomb-Boltzmann distribution. Optical emission spectroscopy of the Al plasma gives significantly lower plasma temperature than the ion temperature obtained from the ion time-of-flight, due to the difference in the temporal and spatial regions of the plasma plume probed by the two methods. Applying an external electric field in the plasma expansion region in a direction parallel to the plume expansion increases the line emission intensity. However, the plasma temperature and density, as measured by optical emission spectroscopy, remain unchanged. Aluminum multicharged ion generation from femtosecond laser ablation is studied. A Ti:sapphire laser (wavelength 800 nm, pulse width ∼100 fs, and maximum laser fluence of 7.6 J/cm2) is used. Ion yield and energy distribution of each charge state are measured. A linear relationship between the ion charge state and the equivalent acceleration energy of the individual ion species is observed and is attributed to the presence of an electric field within the plasma-vacuum boundary that accelerates the ions. The ion energy distribution follows a shifted Coulomb-Boltzmann distribution. For Al1+ and Al2+, the ion energy distributions have two components; the faster one can be attributed to multiphoton laser ionization, while the slower one is possibly due to collisional processes. Ion extraction from the plasma is increased with an applied external electric field, which is interpreted to be due to the retrograde motion of the plasma edge because of the external electric field. Multicharged ion generation by femtosecond laser ablation is compared to previously reported ion generation with nanosecond laser ablation and is shown to require significantly lower laser fluence and generates higher charge states and more energetic ions. Fully-stripped boron ions are generated by a nanosecond Nd:YAG laser (wave-length λ = 1064 nm, pulse width τ = 7 ns, and maximum laser pulse energy E = 175 mJ) ablation of a B target in vacuum. Higher charge states, along with the increase in the number of ions detected, are observed with the increase in the laser fluence. An external electric field between the end of the expansion chamber and a grounded grid is used to extract the ions and accelerate them according to their charge state. For 5 kV accelerating voltage applied to the B target and using a laser fluence of 115 J/cm2, ∼1.5 nC of total charge is delivered to the detector which is located ∼150 cm away from the B target. Ion deflection by an electrostatic field separates the ions from the neutrals and makes this geometry suitable for ion implantation. The developed multicharged ion deposition and implantation system was used to per-form interfacial treatment of the SiC/SiO2 interface using boron and barium ions. SRIM simulation was used to estimate the ion penetration depth in the SiC substrate. The multicharged ions were used for shallow ion implantation in 4H SiC. The optical bandgap of the 4H SiC was reduced due to boron ion implantation. Several MOSCAP devices were fabricated with a combination of boron and barium shallow implantation. High-low C-V measurements were used to characterize the MOSCAPs. Boron implantation affects the flatband voltage significantly, while the effect of barium ion implantation is negligible. Shallow boron implantation in the SiC/SiO2 interface reduces the flatband voltage from 4.5 V to 0.04 V

Evidence for B cell exhaustion in chronic graft-versus-host disease

Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21− B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21− B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naïve (CD27−CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21− B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21− B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21− B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21−CD27−CD10− B cell frequencies as a biomarker of disease severity

Spark Discharge Coupled Laser Multicharged Ion Source

A spark discharge is coupled to a laser multicharged ion source to enhance ion generation. The laser plasma triggers a spark discharge with electrodes located in front of the ablated target. For an aluminum target, the spark discharge results in significant enhancement in the generation of multicharged ions along with higher charge states than observed with the laser source alone. When a Nd:YAG laser pulse (wavelength 1064 nm, pulse width 7.4 ns, pulse energy 72 mJ, laser spot area on target 0.0024 cm2) is used, the total multicharged ions detected by a Faraday cup is 1.0 nC with charge state up to Al3+. When the spark amplification stage is used (0.1 μF capacitor charged to 5.0 kV), the total charge measured increases by a factor of ∼9 with up to Al6+ charge observed. Using laser pulse energy of 45 mJ, charge amplification by a factor of ∼13 was observed for a capacitor voltage of 4.5 kV. The spark discharge increases the multicharged ion generation without increasing target ablation, which solely results from the laser pulse. This allows for increased multicharged ion generation with relatively low laser energy pulses and less damage to the surface of the target. © 2015 AIP Publishing LLC. [http://dx.doi.org/10.1063/1.4923457

Characterization of Laser-Generated Aluminum Plasma Using Ion Time-of-Flight and Optical Emission Spectroscopy

Laser plasma generated by ablation of an Al target in vacuum is characterized by ion time-of-flight combined with optical emission spectroscopy. A Q-switched Nd:YAG laser (wavelength λ = 1064 nm, pulse width τ ∼ 7 ns, and fluence F ≤ 38 J/cm2) is used to ablate the Al target. Ion yield and energy distribution of each charge state are measured. Ions are accelerated according to their charge state by the double-layer potential developed at the plasma-vacuum interface. The ion energy distribution follows a shifted Coulomb-Boltzmann distribution. Optical emission spectroscopy of the Al plasma gives significantly lower plasma temperature than the ion temperature obtained from the ion time-of-flight, due to the difference in the temporal and spatial regions of the plasma plume probed by the two methods. Applying an external electric field in the plasma expansion region in a direction parallel to the plume expansion increases the line emission intensity. However, the plasma temperature and density, as measured by optical emission spectroscopy, remain unchanged

Aluminum Multicharged Ion Generation from Femtosecond Laser Plasma

Aluminum multicharged ion generation from femtosecond laser ablation is studied. A Ti:sapphire laser (wavelength 800 nm, pulse width ∼100 fs, and maximum laser fluence of 7.6 J/cm2) is used. Ion yield and energy distribution of each charge state are measured. A linear relationship between the ion charge state and the equivalent acceleration energy of the individual ion species is observed and is attributed to the presence of an electric field within the plasma-vacuum boundary that accelerates the ions. The ion energy distribution follows a shifted Coulomb-Boltzmann distribution. For Al1+ and Al2+, the ion energy distributions have two components; the faster one can be attributed to multiphoton laser ionization, while the slower one is possibly due to collisional processes. Ion extraction from the plasma is increased with an applied external electric field, which is interpreted to be due to the retrograde motion of the plasma edge as a result of the external electric field. Multicharged ion generation by femtosecond laser ablation is compared to previously reported ion generation with nanosecond laser ablation and is shown to require significantly lower laser fluence and generates higher charge states and more energetic ions. © 2017 Author(s)

Theoretical and experimental evaluation of the inhibiting power of 4-amino,5-phenyl-1,2,4-triazole,3-thione against corrosion copper in a neutral chloride environment

In this study, we first developed the synthesis of 4-amino-5-phenyl-1,2,4-triazole-3-thione (APTS) and then its identification based on 1H and 13C NMR spectral data.  The product's ability to prevent copper corrosion in a 3% NaCl solution was then evaluated. This work was carried out by stationary and transient electrochemical techniques, supplemented by a theoretical study. The results obtained showed that the APTS provides good protection of copper in the corrosive environment by the formation of a protective layer adsorbed on the metal surface. The inhibitory efficiency achieved is around 98% for a concentration of 10-3M in inhibitor justifying its protective effect. The theoretical study of the interaction of APTS with metallic copper shows that this inhibitor adsorbs on the metallic surface by forming chemical bonds between the metal and the inhibitor. This confirms the experimental result

Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies

Fruity Cafe / Munirah Shaim... [et al.]

Producing and selling healthy fruit drinks in which we are using fresh fruits such as dragon fruit, banana, durian, honey dew, watermelon, papaya and many more. The uniqueness of our fruit drinks is we add the "sunnah foods" such as raisins, dates and many more as the toppings and we did not use any sugar in the juice