Molecular cloning and expression of novel fibroblast growth factor-2 conjugated with immunodominant domains of pseudomonas exotoxin

Angiogenesis is very important in cancer growth and metastasis. Basic fibroblast growth factor (bFGF) as one of the most important angiogenesis factors is an attractive target for cancer vaccine. Due to low immunogenicity, it cannot stimulate an effective immune response. Theoretically, pseudomonas exotoxin (PE) as a potent immunogenic carrier protein when fused to low immunogenic antigens such as bFGF significantly increased immunogenicity of it. In this study, we tried to molecular cloning and expression of bFGF conjugated with immunodominant domains of pseudomonas exotoxin. The coding sequence of fusion protein composed of bFGF linked to PE domains 1b and 2 using EAAAK poly linker. The KDEL sequence was also used in C-terminal coding sequence. It was synthesized and expressed using recombinant DNA technology in the bacterial expression system. Expression of recombinant protein verified using SDS-PAGE and western blot analyses. Finally, it purified using Ni-affinity chromatography. The band close to 37 kDa in SDS-PAGE and western blot analyses was aligned completely to designed sequence. Purified recombinant protein also showed as a clear single band near to 37 kDa

Folate-conjugated nanoparticles as a potent therapeutic approach in targeted cancer therapy

The selective and efficient drug delivery to tumor cells can remarkably improve different cancer therapeutic approaches. There are several nanoparticles (NPs) which can act as a potent drug carrier for cancer therapy. However, the specific drug delivery to cancer cells is an important issue which should be considered before designing new NPs for in vivo application. It has been shown that cancer cells over-express folate receptor (FR) in order to improve their growth. As normal cells express a significantly lower levels of FR compared to tumor cells, it seems that folate molecules can be used as potent targeting moieties in different nanocarrier-based therapeutic approaches. Moreover, there is evidence which implies folate-conjugated NPs can selectively deliver anti-tumor drugs into cancer cells both in vitro and in vivo. In this review, we will discuss about the efficiency of different folate-conjugated NPs in cancer therapy. © 2015, International Society of Oncology and BioMarkers (ISOBM)

LASEK for the correction of hyperopia with mitomycin C using SCHWIND AMARIS excimer laser: one-year follow-up

AIM: To evaluate the efficacy, safety and predictability of laser-assisted sub-epithelial keratectomy (LASEK) for the correction of hyperopia using the SCHWIND AMARIS platform. METHODS: This retrospective single-surgeon study includes 66 eyes of 33 patients with hyperopia who underwent LASEK with mitomycin C (MMC). The median age of patients was 35.42±1.12y (ranging 18 to 56y). In each patient LASEK was performed using SCHWIND AMARIS excimer laser. Postoperatively clinical outcomes were evaluated in terms of predictability, safety, efficacy, subjective and objective refractions, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA) and adverse events. RESULTS: The mean baseline refraction was 3.2±1.6 diopters (D) (ranging 0 to 7 D). The mean pre-operative and postoperative spherical equivalent (SE) were 2.34±1.76 (ranging -1.25 to 7 D) and 0.30±0.84 (ranging -0.2 to 0.8 D) respectively (P=0.001). The mean hyperopia was 0.63±0.84 D (ranging -1.75 to 2.76 D) 6 to 12mo postoperatively. Likewise, the mean astigmatism was 0.68±0.43 D (range 0 to 2 D) with 51 (77.3) and 15 (22.7) eyes within ±1 and ±0.50 D respectively. The safety index and efficacy index were 1.08 and 1.6 respectively. CONCLUSION: LASEK using SCHWIND AMARIS with MMC yields good visual and refractive results for hyperopia. Moreover, there were no serious complications. Copyright 2015 by the IJO Press

MyoRing implantation in keratoconic patients: 3 years follow-up data

Purpose: To evaluate long-term follow-up data on implantation of a full-ring intra-corneal implant (MyoRing) for management of keratoconus. Methods: A total of 40 keratoconic eyes of 37 consecutive patients who had undergone MyoRing implantation using the Pocket Maker microkeratome (Dioptex, GmbH, Linz, Austria) and completed 3 years of follow-up appointments were included in this retrospective study. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction and keratometry (K) readings were measured and evaluated preoperatively, and 3 years, postoperatively. Results: No intraoperative complications were observed in this case series. Three years postoperatively, there was a significant improvement in UDVA, CDVA, K readings, spherical equivalent (SE), and manifest sphere and cylinder (P < 0.05 for all comparisons). UDVA was significantly improved from 1.14 ± 0.27 to 0.30 ± 0.21 LogMAR (P = 0.001), CDVA was also improved from 0.52 ± 0.23 to 0.18 ± 0.12 LogMAR (P = 0.001), SE was decreased by 4.35 diopters (D) and average keratometric values were reduced by 2.34 D (P = 0.001). Overall, 81 of subjects were moderately to highly satisfied 3 years after surgery and 64.90 agreed to have the fellow eye implanted with MyoRing. Conclusion: MyoRing implantation using the Pocket Maker microkeratome was found to be a minimally invasive procedure for improving visual acuity and refraction in the majority of the patients with keratoconus. © 2016 Journal of Ophthalmic and Vision Research

Specific Electrogram Characteristics Identify the Extra-Pulmonary Vein Arrhythmogenic Sources of Persistent Atrial Fibrillation – Characterization of the Arrhythmogenic Electrogram Patterns During Atrial Fibrillation and Sinus Rhythm

Identification of atrial sites that perpetuate atrial fibrillation (AF), and ablation thereof terminates AF, is challenging. We hypothesized that specific electrogram (EGM) characteristics identify AF-termination sites (AFTS). Twenty-one patients in whom low-voltage-guided ablation after pulmonary vein isolation terminated clinical persistent AF were included. Patients were included if short RF-delivery for <8sec at a given atrial site was associated with acute termination of clinical persistent AF. EGM-characteristics at 21 AFTS, 105 targeted sites without termination and 105 non-targeted control sites were analyzed. Alteration of EGM-characteristics by local fibrosis was evaluated in a three-dimensional high resolution (100 µm)-computational AF model. AFTS demonstrated lower EGM-voltage, higher EGM-cycle-length-coverage, shorter AF-cycle-length and higher pattern consistency than control sites (0.49 ± 0.39 mV vs. 0.83 ± 0.76 mV, p < 0.0001; 79 ± 16% vs. 59 ± 22%, p = 0.0022; 173 ± 49 ms vs. 198 ± 34 ms, p = 0.047; 80% vs. 30%, p < 0.01). Among targeted sites, AFTS had higher EGM-cycle-length coverage, shorter local AF-cycle-length and higher pattern consistency than targeted sites without AF-termination (79 ± 16% vs. 63 ± 23%, p = 0.02; 173 ± 49 ms vs. 210 ± 44 ms, p = 0.002; 80% vs. 40%, p = 0.01). Low voltage (0.52 ± 0.3 mV) fractionated EGMs (79 ± 24 ms) with delayed components in sinus rhythm (‘atrial late potentials’, respectively ‘ALP’) were observed at 71% of AFTS. EGMs recorded from fibrotic areas in computational models demonstrated comparable EGM-characteristics both in simulated AF and sinus rhythm. AFTS may therefore be identified by locally consistent, fractionated low-voltage EGMs with high cycle-length-coverage and rapid activity in AF, with low-voltage, fractionated EGMs with delayed components/ ‘atrial late potentials’ (ALP) persisting in sinus rhythm

Tools for BIM-GIS integration (IFC georeferencing and conversions): Results from the GeoBIM benchmark 2019

The integration of 3D city models with Building Information Models (BIM), coined as GeoBIM, facilitates improved data support to several applications, e.g., 3D map updates, building permits issuing, detailed city analysis, infrastructure design, context-based building design, to name a few. To solve the integration, several issues need to be tackled and solved, i.e., harmonization of features, interoperability, format conversions, integration of procedures. The GeoBIM benchmark 2019, funded by ISPRS and EuroSDR, evaluated the state of implementation of tools addressing some of those issues. In particular, in the part of the benchmark described in this paper, the application of georeferencing to Industry Foundation Classes (IFC) models and making consistent conversions between 3D city models and BIM are investigated, considering the OGC CityGML and buildingSMART IFC as reference standards. In the benchmark, sample datasets in the two reference standards were provided. External volunteers were asked to describe and test georeferencing procedures for IFC models and conversion tools between CityGML and IFC. From the analysis of the delivered answers and processed datasets, it was possible to notice that while there are tools and procedures available to support georeferencing and data conversion, comprehensive definition of the requirements, clear rules to perform such two tasks, as well as solid technological solutions implementing them, are still lacking in functionalities. Those specific issues can be a sensible starting point for planning the next GeoBIM integration agendas

Short-term effects of repetitive transcranial magnetic stimulation on sleep bruxism:a pilot study

The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on patients with sleep bruxism (SB). Twelve patients with SB were included in an open, single-intervention pilot study. rTMS at 1 Hz and an intensity of 80% of the active motor threshold was applied to the ‘hot spot' of the masseter muscle representation at the primary motor cortex bilaterally for 20 min per side each day for 5 consecutive days. The jaw-closing muscle electromyographic (EMG) activity during sleep was recorded with a portable EMG recorder at baseline, during rTMS treatment and at follow-up for 5 days. In addition, patients scored their jaw-closing muscle soreness on a 0–10 numerical rating scale (NRS). Data were analysed with analysis of variance. The intensity of the EMG activity was suppressed during and after rTMS compared to the baseline (P = 0.04; P = 0.02, respectively). The NRS score of soreness decreased significantly during and after rTMS compared with baseline (P < 0.01). These findings indicated a significant inhibition of jaw-closing muscle activity during sleep along with a decrease of muscle soreness. This pilot study raises the possibility of therapeutic benefits from rTMS in patients with bruxism and calls for further and more controlled studies

Distribution of shallow NV centers in diamond revealed by photoluminescence spectroscopy and nanomachining

We performed nanomachining combined with photoluminescence spectroscopy to understand the depth distribution of nitrogen-vacancy (NV) centers formed by low energy nitrogen ion irradiation of the diamond surface. NV− and NV0 fluorescence signals collected from the surface progressively machined by a diamond tip in an atomic force microscope (AFM) initially rise to a maximum at 5 nm depth before returning to background levels at 10 nm. This maximum corresponds to the defect depth distribution predicted by a SRIM simulation using a 2.5 keV implantation energy per nitrogen atom. Full extinguishing of implantation produced NV− and NV0 zero phonon line peaks occurred beyond 10 nm machining depth, coinciding with the end of easy surface material removal and onset of significant tip wear. The wear ratio of for NV active, ion irradiated diamond compared to the single-crystal diamond tip was surprisingly found to be 22:1. The reported results constitute the first integrated study of in-situ machining and wear characterization via optical properties of the diamond surface containing shallow formed NV centers. We discuss possible metrology applications for diamond tools used in precision manufacturing

E2 ubiquitin-conjugating enzymes in cancer: Implications for immunotherapeutic interventions

Despite the medical advances of the 21st century, the incidence of cancer continues to increase and the search for a universal cure remains a major health challenge. Our lack of understanding the complex pathophysiology of the tumor microenvironment has hindered the development and efficiency of anti-cancer therapeutic strategies. The tumor microenvironment, composed of multiple cellular and non-cellular components, enables tumor-promoting processes such as proliferation, angiogenesis, migration and invasion, metastasis, and drug resistance. The ubiquitin-mediated degradation system is involved in several physiologic processes including cell cycling, signal transduction, receptor downregulation, endocytosis and transcriptional regulation. Ubiquitination includes attachment of ubiquitin to target proteins via E1 (activating), E2 (conjugating) and E3 (ligating) enzymes. Several studies have shown that E2 enzymes are dysregulated in variety of cancers. Multiple investigations have demonstrated the involvement of E2s in various tumor-promoting processes including DNA repair, cell cycle progression, apoptosis and oncogenic signaling. E2 enzymes consist of 40 members that facilitate ubiquitin-substrate conjugation thereby modulating the stability and interaction of various proteins. As such, E2s are potential biomarkers as diagnostic, prognostic and therapeutic tools. In this review, we discuss the role of E2s in modulating various types of cancer