bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination Treatment of Retinoic Acid Plus Focal Adhesion Kinase Inhibitor Prevents Tumor Growth and Breast Cancer Cells Metastasis
Authors: Castro Ana Carla Guijarro , Mondaca Joselina , Fernandez-Muñoz Juan Manuel , Vanderhoeven Fiorella , Uzair Ivonne , Redondo Analia , Zoppino Felipe Carlos Martin , Sanchez Angel Matias , Flamini Marina Ines 
Published: December 2021

Abstract
All-trans retinoic acid (RA) is the primary metabolite of vitamin A and controls the development and homeostasis of organisms and tissues. RA and its natural and synthetic derivatives, known as retinoids, are promising agents in treating and chemoprevention different neoplasias, including breast cancer (BC). Focal adhesion kinase (FAK) is a crucial regulator of cell migration, and its overexpression is associated with the metastatic behavior of tumors. Thus, pharmaceutical FAK inhibitors (FAKi) have been developed to counter its action. In this work, we hypothesize that RA plus FAKi (RA+FAKi) approach could improve inhibition of tumor progression. By in silico analysis, we confirmed RARA, SRC, and PTK2 (encoding RARα, Src, and FAK, respectively) overexpression in all breast cells tested. In metastatic BC cells, we reveal that genes encoding proteins that FAK directly or indirectly modulates are deregulated compared to normal cells. We showed a different pattern of genes up/down-regulated between RA-resistant and RA-sensitive BC cells. In addition, we demonstrated that both RA-resistant BC cells (MDA-MB-231 and MDA-MB-468) display the same behavior after RA treatment, modulating the expression of genes involved in Src-FAK signaling. Furthermore, we demonstrated that although RA and FAKi administered separately decrease viability, adhesion, and migration in mammary adenocarcinoma LM3 cells, their combination exerts a higher effect. We also evidenced that RA effects are extrapolated to other cancer cells, including the human cervical carcinoma cells HeLa. In an orthotopic assay of LM3 tumor growth, RA and FAKi administered separately reduce tumor growth; however, the combined treatment induces the more potent inhibition increasing mice survival. Moreover, in an experimental metastatic assay, RA significantly reduces metastatic lung dissemination of LM3 cells. Overall, these results indicate that RA resistance would reflect deregulation of most RA-target genes, including genes encoding components of the Src-FAK pathway. Our study demonstrates that RA plays an essential role in disrupting BC tumor growth and metastatic dissemination in vitro and in vivo by controlling FAK expression and localization. RA plus FAKi exacerbated these effects suggesting that the sensibility to RA therapies could be increased with FAKi coadministration in BC tumors.
Unraveling the Low Frequency Triggered Electromagnetic Signatures in Potentized Homeopathic Medicine
Authors: Bhargaw Hari N. , Nambison Nisanth , Gupta Manoj , Sharma Mohit , Srivast Avanish , Baghel Prabhat , Ahmed Meraj , Jadhav Mahendra , Gavel Khushwant 
Published: December 2021

Abstract
In the present work, a novel experimental tool was developed to precisely measure the potency levels in various homeopathic medicines, under various excitation frequencies. Electromagnetic responses (output voltages) are detected from the homeopathic medicines in different potencies. These unique electromagnetic responses were captured using an electromagnetic coil at 300 Hz and 4.8 kHz for each potency level developed in-house. Different potencies of Homeopathic medicine Ferrum Metallicum (FM-1X to FM-6X), prepared with α‑lactose monohydrate as its base, exhibited significant and distinct electromagnetic signals. At high excitation frequency, the output signal voltage from high homeopathic potencies had a better resolution compared to the signal obtained at lower frequency. The electromagnetic signal of various homeopathic medicines was also measured, and a distinct output voltage corresponding to each potency level was detected. Our experimental results confirmed that each homeopathic medicine has characteristic electromagnetic signals under excitation/resonance frequency. The results not only provide scientific evidence to easily classify the homeopathic medicine potency but, also helps to understand the science behind the curative action in terms of photon emission of homeopathic medicines.
Determination of Genome Size Differentiation and Ploidy Levels in Some Citrus Rootstock Populations
Authors: POLATÖZ Sefa , Seker Murat , KAYA Çağlar 
Published: December 2021

Abstract
In plants, knowing the ploidy level of plant material used in breeding studies, and especially for biotechnology applications, carries great importance. The presence of a rapid variety of dynamics in citrus fruits allows their use as rootstock and varieties ensuring adaptability to various climate and soil conditions with different breeding methods. A variety of appropriate rootstocks are used for commercial citrus species. This study investigated the genome sizes and ploidy levels in citrus rootstocks commonly used around the world with flow cytometry in seedling populations. The study used Gou-Tou, C-35, Troyer Citrange, Taiwanica, Citremon, Yuzu, Sunki mandarin, Flying Dragon, Yuma Citrange, Macrophylla and Chinese orange rootstocks. Fresh leaf tissues were mixed with the triploid Tahiti lime leaf tissue, used as standard species, and cell nuclei were isolated. Cells stained with propidium iodide were read with flow cytometry and histograms and cytograms were obtained. According to the obtained results, all seedlings of species had diploid genome volumes. In terms of genome volume, there were differences found between species. Yuzu seedlings were determined to be the species with largest genome volume (0.808 pg/2C), while Flying Dragon trifoliate had smallest genome volume (0.700 pg/2C).
Research on Clean Combustion Technology of EGR-based Flameproof Diesel Engine
Authors: Xiao WANG 
Published: December 2021

Abstract
In view of the serious pollution of NOx emissions from flame-proof diesel engines used in coal mines and its direct and indirect hazards that cannot be ignored, the combustion process of flame-proof diesel engines is analyzed and a combustion mathematical model is established. Subsequently, the clean combustion method based on exhaust gas recirculation (EGR) is adopted, and an EGR clean combustion device is designed, which meets the requirements of the coal mine standard Safety Regulations on Coal Mine . The design content involves: (i) Composition and structure design of EGR system meeting the requirements of flame-proof standards; (ii) The closed forced cooling cycle design of the EGR system. Specifically, the clean combustion process of flame-proof diesel engine based on EGR system is simulated and analyzed by fluid simulation analysis software, and the effects of EGR system on the performance and emission of flame-proof diesel engine under 15 operating modes of three rotational speeds and five loads are obtained. Then, the control strategy and control program of the EGR system of flame-proof diesel engine are compiled based on the mathematical model and simulation results. In addition, the bench test of the flame-proof diesel engine equipped with EGR device is carried out by using this control program in the laboratory, and the control program of EGR system is modified by analyzing the experimental data. Finally, the optimized bench test is carried out by selecting the control program that optimal matches the flame-proof EGR device and the flame-proof diesel engine. The test results suggest that: (i) Under the external characteristic working mode: after installing the EGR system, the power of the flame-proof diesel engine is 58.9kW under the optimized EGR opening, and the highest output torque is 252.3 Nm, and the power performance is slightly lower than that of the original engine; (ii) Under eight operating mode: after installing the EGR system, the weighted average CO emission of the flame-proof diesel engine under the optimized EGR opening is 0.0045%, and the volume concentration is increased by 0.0045% compared with that without the EGR system; the weighted average NOx emission of the flame-proof diesel engine under the optimized EGR opening is 93.35ppm, which is 56.17% lower than that without the EGR system, indicating that the EGR system technology has significantly improved the reduction of NOx emissions of the flame-proof diesel engine; (iii)Under eight operating mode: after installing EGR system, the HC emission of flame-proof diesel engine under optimized EGR opening is basically unchanged compared with that without EGR system, and the soot emission is slightly increased; and (iv) The EGR system meets the requirements of the coal mine standard, and this method and technology can improve the basis for reducing the NOx emission from the tail gas of the underground vehicles in the coal mine.
Weakened Interannual Variability in the Tropical Atlantic
Authors: Verona Laura Sobral , Silva Paulo , Wainer Ilana , Khodri Myriam 
Published: December 2021

Abstract
Climate variability in the Tropical Atlantic is complex with strong ocean-atmosphere coupling, where the sea surface temperature (SST) variability impacts the hydroclimate of the surrounding continents. We observe a decrease in the variability of the Tropical Atlantic after 1970 in both CMIP6 models and observations. Most of the Tropical Atlantic interannual variability is explained by its equatorial (Atlantic Zonal Mode, AZM) and meridional (Atlantic Meridional Mode, AMM) modes of variability. The observed wind relaxation after 1970 in both the equatorial and Tropical North Atlantic (TNA) plays a role in the decreased variability. Concerning the AZM, a widespread warming trend is observed in the equatorial Atlantic accompanied by a weakening trend of the trade winds. This drives a weakening in the Bjerknes Feedback by deepening the thermocline in the eastern equatorial Atlantic and increasing the thermal damping. Even though individually the TNA and Tropical South Atlantic (TSA) show increased variability, the observed asymmetric warming in the Tropical Atlantic and relaxed northeast trade winds after the 70s play a role in decreasing the AMM variability. This configuration leads to positive Wind-Evaporation-SST (WES) feedback, increasing further the TNA SST, preventing AMM from changing phases as before 1970. Associated with it, the African Sahel shows a positive precipitation trend and the Intertropical Convergence Zone tends to shift northward, which acts on maintaining the increased precipitation.
A Novel Hybrid Peptide Composed of LfcinB6 and KR-12-a4 With Enhanced Antimicrobial, Anti-Inflammatory and Anti-Biofilm Activities
Authors: Ajish Chelladurai , Yang Sungtae , Kumar S. Dinesh , Kim Eun Young , Min Hye Jung , Lee Chul Won , Shin Sung-Heui , Shin Song Yub 
Published: December 2021

Abstract
Hybridizing two known antimicrobial peptides (AMPs) is a simple and effective strategy for designing antimicrobial agents with enhanced cell selectivity against bacterial cells. Here, we generated a hybrid peptide Lf-KR in which LfcinB6 and KR-12-a4 were linked with a Pro hinge to obtain a novel AMP with potent antimicrobial, anti-inflammatory, and anti-biofilm activities. Lf-KR exerted superior cell selectivity for bacterial cells over sheep red blood cells. Lf-KR showed broad-spectrum antimicrobial activities (MIC: 4–8 mM) against tested 12 bacterial strains and retained its antimicrobial activity in the presence of salts at physiological concentrations. Membrane depolarization and dye leakage assays showed that the enhanced antimicrobial activity of Lf-KR was due to increased permeabilization and depolarization of microbial membranes. Lf-KR significantly inhibited the expression and production of pro-inflammatory cytokines (NO and TNF-a) in LPS-stimulated mouse macrophage RAW264.7 cells. In addition, Lf-KR showed a powerful eradication effect on preformed multidrug-resistant Pseudomonas aeruginosa (MDRPA) biofilms. We confirmed using confocal laser scanning microscopy that a large portion of the preformed MDRPA biofilm structure was perturbed by the addition of Lf-KR. Collectively, our results suggest that Lf-KR can be an antimicrobial, anti-inflammatory, and anti-biofilm candidate as a pharmaceutical agent.
Boussinesq's Equations for (2+1)-Dimensional Surface Gravity Waves in an Ideal Fluid Model
Authors: Karczewska Anna , Rozmej Piotr 
Published: December 2021

Abstract
We study the problem of gravity surface wa\-ves for the ideal fluid model in (2+1)-dimensional case. We apply a systematic procedure for deriving the Boussinesq equations for a prescribed relationship between the orders of four expansion parameters, the amplitude parameter $\alpha$, the long-wavelength parameter $\beta$, the transverse wavelength parameter $\gamma$, and the bottom variation parameter $\delta$. We also take into account surface tension effects when relevant. For all considered cases, the (2+1)-dimensional Boussinesq equations can not be reduced to a single nonlinear wave equation for surface elevation function. On the other hand, they can be reduced to a single, highly nonlinear partial differential equation for an auxiliary function $f(x,y,t)$ which determines the velocity potential but is not directly observed quantity. The solution $f$ of this equation, if known, determines the surface elevation function. We also show that limiting the obtained the Boussinesq equations to (1+1)-dimensions one recovers well-known cases of the KdV, extended KdV, fifth-order KdV, and Gardner equations.PACS 02.30.Jr · 05.45.-a · 47.35.Bb · 47.35.Fg
Streams’ and Springs’ Biophysical Dynamics as Structuring Elements of Future Urban Development: Systemic Strategies for Spatial Planning - A Case Study in Uberlândia, MG, Brazil
Authors: Figueiredo-Cunha Julia , Tardin-Coelho Raquel 
Published: December 2021

Abstract
Historically, water bodies were gradually conditioned by unsustainable spatial planning practices, which led to conflicting and fragmented relationships between urban development and water dynamics. Streams and springs are more vulnerable to urban interventions and less identified as protagonists of urban structuring than rivers. However, they present the potential to guide urban development regarding their broad capillarity, easy manipulation and close relationship with urban fabrics, especially in developing country fast-urbanisation reality. Also, there is a demand for more holistic and practical approaches regarding water dynamics and urban development alternatives that can add value to water-centred initiatives focused on water management. This article proposes a methodological framework focused on formulating systemic spatial planning strategies (land-use and urban design guidelines) based on streams’ and springs’ spatially and functionally biophysical dynamics as structuring elements of future urban development towards composing one urban-eco system. The following principles guide the planning strategies: a) to guarantee water dynamics whole functioning as constraints to urban land-use definition; b) to promote potential functional and spatial integration between the urban fabric and water bodies that guide the configuration of urban fabrics according to the whole functioning of water dynamics. The spatial planning strategies show the potential to be systematically applied throughout a city, systemically addressing and integrating water dynamics and urban development issues towards a more sustainable and resilient reality, on a broader scale perspective and not only on-site symptoms.
Low-Temperature Plasma Short-Exposure to Decontaminate Peri-Implantitis-Related Multispecies Biofilms on Titanium Surfaces
Authors: Panariello Beatriz H. D. , Mody Drashty P. , Eckert George J. , Coelho Paulo G. , Duarte Simone 
Published: December 2021

Abstract
Peri-implantitis is a bacteria-initiated infection that as yet has no effective treatment. A novel approach to treat peri-implantitis is the use of low-temperature plasma (LTP). LTP disrupts the biofilm while conditioning the surrounding host environment for bone growth around the infected implant. The goal of this study was to evaluate the antimicrobial properties of LTP on newly formed (24-h) and mature (7-days) peri-implant-related biofilms. Biofilm was composed of Actinomyces naeslundii (ATCC 12104), Porphyromonas gingivalis (W83), Streptococcus oralis (ATCC 35037), and Veillonella dispar (ATCC 17748). They were cultivated in brain heart infusion supplemented with 1% yeast extract, hemin (0.5 mg/mL), and menadione (5 mg/mL) and kept at 37⁰C in anaerobic conditions for 24-h. The species were mixed for a final concentration of ~105 colony forming units (CFU)/mL (OD=0.01), and the bacterial suspension was transferred to 24-well plates containing titanium specimens. Biofilms were treated with LTP for 1, 3, and 5 min at 3 or 10 mm from plasma-tip to sample. Controls were no treatment (Negative control=NC) and argon-flow at the same LTP conditions. Positive controls were 14 g/mL amoxicillin and 140 µg/mL metronidazole individually or combined, and 0.12% chlorhexidine. Biofilms were evaluated by CFU, confocal laser scanning microscopy (CLSM), and Fluorescence in situ Hybridization (FISH). Wilcoxon Signed-Rank and Wilcoxon Rank Sum tests were applied (α = 0.05). Bacterial growth was observed in all no-treatment groups corroborated by FISH. LTP treatment significantly reduced all bacteria species when compared to the NC in both tested periods and in all treatment combinations (p≤0.016), these results were corroborated by CLSM. There were no significant differences during biofilm development, between 24-h, 3, and 7 days within each LTP treatment, or among the bacteria within each LTP treatment (p≥0.05). LTP application is effective to reduce peri-implantitis-related multispecies biofilms on titanium surfaces.
Closed-Wound Negative Pressure Therapy Dressing After Loop Ostomy Closure.
Authors: Curchod P. , Clerc D. , J.Jurt  , Hubner M. , Hahnloser D. , Demartines N. , Grass F. 
Published: December 2021

Abstract
Purpose: Closed-wound negative pressure wound therapy (NPWT) dressings were recently introduced with the purpose to reduce incisional surgical site infections (iSSI) in high-risk wounds.The aim of this study was to compare iSSI rates in patients after ostomy closure with and without additional application of a closed-wound NPWT dressing.Methods: Single-center retrospective analysis of consecutive patients undergoing ileo- or colostomy closure over an 8-year period (January 2013 - January 2021). Intradermal absorbable sutures were used in all patients. Since November 2018, all patients (study group) received a NPWT device for a maximum of 5 days postoperatively (PICO® Smith and Nephew).Primary outcome was iSSI rate within 30 days of surgery. Data was retrieved from the institutional enhanced recovery after surgery (ERAS) database, with standardized complication assessment by trained abstractors.Results: In total, 85 patients (25%) in the study group were comparable with 252 (75%) patients in the control group regarding demographics (age, gender, body mass index, ASA score), ostomy type and anastomotic technique (all p>0.05). Median time to NPWT removal was 4 (IQR 3-5) days. Incisional SSI were observed in 4 patients (4.7%) in the study group and in 27 patients (10.7%) in the control group (p=0.097).Conclusion: These preliminary results suggest a potential benefit of systematic application of the NPWT device after loop ostomy closure. A randomized controlled study is needed to confirm these findings.
A Pragmatic Pharmacophore Informatics Strategy to Discover New Potent Inhibitors Against Pim-3
Authors: Peddi Sudhir Reddy , Kundenapally Ramalingam , Sivan Sree Kanth , Somadi Gururaj , manga vijjulatha 
Published: December 2021

Abstract
Pim-3 (proviral integration site moloney murine leukemia virus-3) is an oncogene which encodes proteins belonging to serine/threonine kinase family, and PIM subfamily. It is generally over expressed in epithelial and hematological tumors. It is known to involve in numerous cellular functions such as cell growth, differentiation, survival, tumorigenesis and apoptosis. It also plays a crucial role in regulation of signal transduction cascades. Therefore it emerged as a hopefultherapeutic target for cancer treatment. In current study, indole derivatives having potent inhibitory activity against Pim 3 were taken and pharmacophore based virtual screening was carried out. A five point pharmacophore hypothesis with one hydrogen bond acceptor, one hydrogen bond donor and three aromatic rings i.e., ADRRR was developed with acceptable R2and Q2 values of 0.913 and 0.748 respectively. It was employed as a query and screening was conducted against Asinex and Otava lead library databases to screen out potent drug like candidates. The obtained compounds were subjected to SP, XP docking using 3D model of pim-3 which was constructed through comparative homology modelling and finally binding free energies were calculated for top hits. The docking and binding free energy studies revealed that six hit molecules showed higher binding energy in comparison to the best active molecule. Finally, MD simulations of the top hit with highest binding energy was carried out which indicated that the obtained hit N1 formed a stable complex with pim-3. We believe that these combined protocols will be helpful and cooperative to discover and design more potent pim-3 inhibitors in near future.