CD20-targeting in B-cell malignancies: novel prospects for antibodies and combination therapies

Expression of CD20 antigen by the most of transformed B cells is believed to be the driving force for targeting this molecule by using anti-CD20 monoclonal antibodies. While it is true that most lymphoma/leukemia patients can be cured, these regimens are limited by the emergence of treatment resistance. Based on these observations, development of anti-CD20 monoclonal antibodies and combination therapies have been recently proposed, in particular with the aim to optimize the cytotoxic activity. Here we outline a range of new experimental agents concerning the CD20 positive B-cell tumors which provide high benefit from conventional therapy. © 2016, Springer Science+Business Media New York

Plant tissue culture study on two different races of purslane (Portulaca oleracea L.)

This study was performed on two races of purslane; agronomic purslane and wild one. All the explants were cultured on MS basal medium supplement with 30 g/l sucrose, 8 g/l agar and different plant growthregulator. Petioles, shoot tips and leaves of wild purslane and also leaves of agronomic purslane were cultured in different concentrations and combinations of IBA and BAP (Both in the same four levels, 0, 1, 5 and 10 ìM; collectively 16 treatments). On the other hand, nodal segments and shoot tips of agronomic purslane were cultured in different concentrations (4.44, 8.88 and 13.32 ìM) of BAP or kinetin. The regenerated were rooted in the media containing three levels of IBA or IBA (0.0, 2.5 and 5ìM). Results showed that the treatments containing10 ìM IBA in combination with 10 or 5 ìM BAP are suitable for callus induction from leaves of wild purslane. Direct shoot regeneration from shoot tips orpetiole explants of wild purslane was observed only in 10 ìM IBA alone. Also, BAP at level 8.88 ìM was found to be the best treatment to shoot regeneration from nodal segments of agronomic purslane andIBA at level 2.5 ìM was found to be the best treatment for rooting of regenerated shoots in both races of purslane

Use of single-chain antibody derivatives for targeted drug delivery

Single-chain antibodies (scFvs), which contain only the variable domains of full-length antibodies, are relatively small molecules that can be used for selective drug delivery. In this review, we discuss how scFvs help improve the specificity and efficiency of drugs. Small interfering RNA (siRNA) delivery using scFv-drug fusion peptides, siRNA delivery using scFv-conjugated nanoparticles, targeted delivery using scFv-viral peptide-fusion proteins, use of scFv in fusion with cell-penetrating peptides for effective targeted drug delivery, scFv-mediated targeted delivery of inorganic nanoparticles, scFv-mediated increase of tumor killing activity of granulocytes, use of scFv for tumor imaging, site-directed conjugation of scFv molecules to drug carrier systems, use of scFv to relieve pain and use of scFv for increasing drug loading efficiency are among the topics that are discussed here. © 2016, University of Michigan. All rights reserved

Purification and Characterization of Recombinant Darbepoetin Alfa from Leishmania tarentolae

Darbepoetin alfa is a biopharmaceutical glycoprotein that stimulates erythropoiesis and is used to treat anemia, which associated with renal failure and cancer chemotherapy. We herein describe the structural characterization of recombinant darbepoetin alfa produced by Leishmania tarentolae T7-TR host. The DNA expression cassette was integrated into the L. tarentolae genome through homologous recombination. Transformed clones were selected by antibiotic resistance, diagnostic PCRs, and protein expression analysis. The structure of recombinant darbepoetin alfa was analyzed by isoelectric focusing, ultraviolet–visible spectrum, and circular dichroism (CD) spectroscopy. Expression analysis showed the presence of a protein band at 40 kDa, and its expression level was 51.2 mg/ml of culture medium. Darbepoetin alfa have 5 isoforms with varying degree of sialylation. The UV absorption and CD spectra were analogous to original drug (Aranesp), which confirmed that the produced protein was darbepoetin alfa. Potency test results revealed that the purified protein was biologically active. In brief, the structural and biological characteristics of expressed darbepoetin alfa were very similar to Aranesp which has been normally expressed in CHO. Our data also suggest that produced protein has potential to be developed for clinical use. © 2016, Springer Science+Business Media New York

How much should you worry about contaminant neutrons in spatially fractionated grid radiation therapy?

Objectives: Telehealth monitoring applications are latency-sensitive. The current fog-based telehealth monitoring models are mainly focused on the role of the fog computing in improving response time and latency. In this paper, we have introduced a new service called “priority queue” in fog layer, which is programmed to prioritize the events sent by different sources in different environments to assist the cloud layer with reducing response time and latency. Material and Methods: We analyzed the performance of the proposed model in a fog-enabled cloud environment with the IFogSim toolkit. To provide a comparison of cloud and fog computing environments, three parameters namely response time, latency, and network usage were used. We used the Pima Indian diabetes dataset to evaluate the model. Result: The fog layer proved to be very effective in improving the response time while handling emergencies using priority queues. The proposed model reduces response time by 25.8%, latency by 36.18%, bandwidth by 28.17%, and network usage time by 41.4% as compared to the cloud. Conclusion: By combining priority queues, and fog computing in this study, the network usage, latency time, bandwidth, and response time were significantly reduced as compared to cloud computing

Основні віхи розвитку української гірничої термінології

Ідеться про розвиток термінології й номенклатури гірничої справи, зокрема частково шахтобудування, яка активно розвивалася впродовж 20–З0-х рр. ХХ ст. Наголошено на спірних моментах в історії становлення цієї лексичної групи. Зроблено висновок про те, що нині гірнича термінологія української мови практично повністю унормована завдяки ретельній праці лексикографів та фахівців-гірників.The paper examines the ways mining terminology and nomenclature was developed. Special attention is drawn to the period of the 20th – 30th of the 20th century, when the term system was formed. The research focuses on disputable moments in the history of lexical group development; it concludes that mining terminology is normalized in the present-day Ukrainian language thanks to the careful work of lexicographers and mining specialist

HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress

Background Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER) stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC. Methodology and Principal Findings HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R), were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1), as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase. Conclusion and Significance HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch

201