bluuebunny/crossref_metadata_2025 huggingface dataset:
A Parametric Study of Coupled Hydromechanical Behaviors Induced by Shallow Water Flow in Shallow Sediments in Deepwater Drilling Based on Numerical Modeling
Authors: Guo Xuyang , Jin Yan , Lin Botao
Published: August 2020

Shallow water flow is a geohazard encountered in deepwater drilling. It is often characterized by excessive water flow into the wellbore caused by the pressure difference between overpressured sediments and the wellbore, and it usually leads to serious well control problems and may eventually result in the loss of a well. Many research efforts focused on the identification of shallow water flow zones and the associated water flow in the drilled wellbore. Not many studies investigated the coupled hydromechanical behaviors in sediments during the occurrence of shallow water flow, while such behaviors are directly related to uncontrolled flow in the wellbore and solid deformation. Based on a coupled hydraulic-mechanical model and finite element methods, this work investigates the temporal-spatial evolutions of near-well pressure and stress induced by shallow water flow. Hydraulic behaviors in the deepwater shallow sediments are described by saturated fluid flow in porous media while mechanical behaviors in the sediments are depicted by linear elasticity. Finite element methods are used for the numerical solution to the coupled hydraulic-mechanical formulation. The study then conducts a series of parametric studies to quantitatively understand the effects of relevant parameters on pressure, stress, and uncontrolled flow into the wellbore. Results indicate that overpressure has the most significant impact while Young’s modulus has the most limited impact on spatial-temporal pressure/stress evolutions and the uncontrolled water production in the wellbore. Permeability, porosity, water viscosity, and water compressibility all have certain effects on near-well physical characteristics and wellbore water production. In addition, it is noted that pressure drainage and induced stress are more significant when it is closer to the wellbore. This numerical study helps to quantitatively identify the most influential parameters related to shallow water flow and calculates the water mass flow loaded in the wellbore.
Dual-Source Optimization of the “Diverting Water from the Yangtze River to Tai Lake (DWYRTL)” Project Based on the Euler Method
Authors: Xu Ruichen , Pang Yong , Hu Zhibing , Kaisam John Paul
Published: August 2020

Appropriate water body diversion can improve the water quality of Tai Lake. Excessive diversion of water would, however, dramatically alter the local flow fields, which are not conducive to the growth of aquatic plants and the stability of ecosystems. The current “Diverting Water from the Yangtze River to Tai Lake (DWYRTL)” project uses a single water source, the Wangyu River, for diversion, a model that may significantly affect the nearby flow rate or uniformity of the lake and is not conducive to the long-term stability of the aquatic ecosystem in the Tai Lake district of the eastern part of the lake. In order to simulate the different situations of single- and dual-source water diversions (Wangyu-Xinmeng Rivers) in Tai Lake, we based this study on a three-dimensional hydrodynamic model coupled with the Euler method, which can accurately calculate the water exchange rates in the different districts of Tai Lake. The results show that (1) it is recommended that the total annual diversion of water should not exceed 20 × 108 m3; (2) the wind field is the most important factor determining the distribution of spatial water exchange; (3) under wind-free conditions, the flow rate of a single-source diversion of water is approximately 50% higher than that of dual-source diversion; and (4) water diversion under the prevailing conditions of the northwest wind in winter will reduce the semiexchange period of the eastern part of the lake area from 50 to 30 days, significantly changing the nearby district’s uniformity, leading to ecological risks. Therefore, it is recommended that the dual-source water diversion mode be used in winter and windless season, and single-source water diversion mode be used in other seasons.
ChIP-seq Profiling Identifies Histone Deacetylase 2 Targeting Genes Involved in Immune and Inflammatory Regulation Induced by Calcitonin Gene-Related Peptide in Microglial Cells
Authors: Guo Xingjing , Chen Dan , An Shuhong , Wang Zhaojin
Published: August 2020

Calcitonin gene-related peptide (CGRP) is a mediator of microglial activation at the transcriptional level. The involvement of the epigenetic mechanism in this process is largely undefined. Histone deacetylase (HDAC)1/2 are considered important epigenetic regulators of gene expression in activated microglia. In this study, we examined the effect of CGRP on HDAC2-mediated gene transcription in microglial cells through the chromatin immunoprecipitation sequencing (ChIP-seq) method. Immunofluorescence analysis showed that mouse microglial cells (BV2) expressed CGRP receptor components. Treatment of microglia with CGRP increased HDAC2 protein expression. ChIP-seq data indicated that CGRP remarkably altered promoter enrichments of HDAC2 in microglial cells. We identified 1271 gene promoters, whose HDAC2 enrichments are significantly altered in microglia after CGRP treatment, including 1181 upregulating genes and 90 downregulating genes. Bioinformatics analyses showed that HDAC2-enriched genes were mainly associated with immune- and inflammation-related pathways, such as nitric oxide synthase (NOS) biosynthetic process, retinoic acid-inducible gene- (RIG-) like receptor signaling pathway, and nuclear factor kappa B (NF-κB) signaling pathway. The expression of these key pathways (NOS, RIG-I, and NF-κB) were further verified by Western blot. Taken together, our findings suggest that genes with differential HDAC2 enrichments induced by CGRP function in diverse cellular pathways and many are involved in immune and inflammatory responses.
Effects of Different Rates of Poultry Manure and Split Applications of Urea Fertilizer on Soil Chemical Properties, Growth, and Yield of Maize
Authors: Adekiya Aruna Olasekan , Ogunboye Oluwaseyi Iyabo , Ewulo Babatunde Sunday , Olayanju Adeniyi
Published: August 2020

During integrated nutrient management involving poultry manure (PM) and urea fertilizer (UF) for maize (Zea mays L.), it is necessary to investigate the best time to apply UF that will optimize soil chemical properties, growth, and yield of maize. Hence, studies were carried out to investigate the effect of different rates of PM and single and split applications (SA) of UF on soil chemical properties, growth, and yield of maize. The treatment involved three levels of PM (0.0, 4.0, and 8.0 t·ha−1) and four sets of periods of UF: (i) 0 kg N ha-1(control), (ii) 120 kg N ha-1applied at planting (AP), (iii) two SA of 120 kg N ha−1(90 kg N ha-1applied AP + 30 kg N ha-1at thirty days after planting (DAP)), and (iv) three SA of 120 kg N ha-1(60 kg N ha-1applied AP + 30 kg N ha-1thirty DAP + 30 kg N ha-1at tasseling). The 12 treatments were arranged in a randomized complete block design and replicated three times. PM and UF alone and integrating UF with PM improved soil chemical properties, growth, and yield of maize compared with the control. SA of UF three times (60 + 30 + 30) had the most improved soil chemical properties, growth, and yield of maize. Results also showed that maize yielded higher under UF integrated with PM compared with their sole forms. Application of 60 + 30+30 with 8 t ha−1PM (60 + 30+30 + 8 t ha−1PM) or with 4 t ha−1PM treatments showed the highest growth and yield of maize, but due to the bulkiness, handling challenges, and cost of PM, 60 + 30+30 + 4 t ha−1PM is recommended. Therefore, for better growth and yield of maize, after the initial application of PM, UF application should be split-applied in accordance with plant growth and the pattern of uptake to avoid losses by leaching and therefore ensured that N level in the soil is high at the critical stage of N demand.
Quality of Life in Patients with Acromegaly before and after Transsphenoidal Surgical Resection
Authors: Gu Jing , Xiang Shiyuan , He Min , Wang Meng , Gu Yanfang , Li Lingjuan , Yin Zhiwen
Published: August 2020

Objective. We aimed to determine the perioperative changes in the quality of life (QoL) in patients with acromegaly and to reveal the relationship between biochemical indicators and quality of life change after tumor resection. Methods. Patients with acromegaly were enrolled from a tertiary pituitary center. SF-36 scale and AcroQoL scale were used to determine the QoL before and after surgery. We analyzed changes in QoL using a generalized linear model for repeated measurements. We compared the changes in QoL among three groups (remission, active, and discordant group) based on postoperative growth hormone (GH) and insulin-like growth factor-1. Results. 151 patients (75 males and 76 females) diagnosed with acromegaly were included. The average age was 43.9 ± 12.3 years. The median total SF-36 scale was 65.3% (IQR: 63.2%–69.2%). Overall AcroQoL score at baseline was 59.1% (IQR: 51.8%–71.8%). Nadir GH levels (coefficient −0.08, p=0.047), T3 levels (coefficient 2.8, p=0.001), and testosterone levels (coefficient −0.20, p=0.033) in males were independent predictive factors of the total SF-36 score. During the follow-up, the median overall SF-36 score increased to 66.1% at 3 months and 75.3% at 6 months (p<0.001) after surgery. The median overall AcroQoL score increased to 74.5% at 3 months and 77.3% at 6 months (p<0.001) after surgery. At 6-month follow-up, median scores were still less than 70% in appearance, vitality, and mental health dimensions. The QoL after surgery were similar among the three groups, although higher GH and more preoperative somatostatin analogs usage were observed in the active group. Conclusion. In conclusion, acromegalic patients were associated with low QoL, which could be reversed partially by surgery. The improvement was independent of the endocrine remission. Appearance, vitality, and mental health were three major aspects that warrant further attention from physicians and caregivers after surgery.
Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson’s Disease
Authors: Miranda-Díaz Alejandra Guillermina , García-Sánchez Andrés , Cardona-Muñoz Ernesto Germán
Published: August 2020

Oxidative stress plays a fundamental role in the pathogenesis of Parkinson’s disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment’s mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme’s expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.
Renal Tubular Cells from Hibernating Squirrels are Protected against Cisplatin Induced Apoptosis
Authors: Jain Swati , Jani Alkesh
Published: August 2020

Hibernating 13-lined ground squirrels are characterized by tolerance of severe hypothermia and hypoperfusion during torpor, followed by periodic warm reperfusion during IBA, conditions which are lethal to nonhibernating mammals. The aim of the present study was to determine whether protection from apoptosis was specific to torpor arousal cycles during hibernation or will also apply to cisplatin treatment on squirrel renal tubular cells (RTECs) that were procured during hibernation. Squirrel and mouse RTECs were treated with cisplatin, a potent inducer of RTEC apoptosis. Squirrel RTECs subjected to cisplatin had significantly less apoptosis, no cleaved caspase-3, and increased XIAP, pAkt, and pBAD versus mouse RTECs. To determine whether XIAP and Akt1 are necessary for RTEC protection against cisplatin induced apoptotic cell death, gene expression of Akt1 or XIAP was silenced in squirrel RTECs. Squirrel RTECs deficient in Akt1 and XIAP had increased apoptosis and cleaved caspase-3 when treated with cisplatin. Our results thus demonstrates that 13-lined ground squirrel RTECs possess intrinsic intracellular mechanisms by which they protect themselves from apoptotic cell death. Cisplatin induced acute kidney injury (AKI) may be avoided in cancer patients by employing mechanisms used by squirrel RTECs to protect against cisplatin induced tubular cell apoptosis.
Surgical Management for Refractory Bleb Dysesthesia
Authors: Dyrda Agnieszka , Anton Alfonso , Figueroa-Vercellino Juan Pablo , Pazos Marta
Published: August 2020

Purpose. To present long-term results of modified bleb-limiting conjunctivoplasty as a successful treatment for intractable bleb dysesthesia and to review the literature on the surgical management of dysesthetic bleb. Methods. Consecutive case series and literature review. We present four cases of surgically reduced painful blebs. Our technique consisted of the following steps: (1) conjunctival, radial incision to the bare sclera in the desired limit of the bleb; (2) suturing with buried, interrupted sutures at the nearest edge of the filtering bleb; (3) lower limbal peritomy including unwanted area of the extended bleb; (4) dissection and removal of the underlying fibrous tissue when present; (5) conjunctival and resorbable sutures. In addition, a systematic literature review was performed. Only reports presenting outcomes of surgical treatment of bleb dysesthesia after filtering procedure were included in review. Results. Four eyes were included consecutively in the study in a period of 4 years. On average, they developed circumferential bleb dysesthesia 9.3 ± 4.7 months after uneventful combined phacotrabeculectomy with Mitomycin C as primary procedure. Surgical reduction was decided after failure of lubricants in controlling ocular discomfort. Two cases showed a dense fibrous tissue beneath the conjunctiva that was excised to ensure filtration. In all cases, a rapid disappearance of symptoms with very good aesthetic and functional outcome was observed. After 12-month follow-up, patients remained asymptomatic and maintained intraocular pressure of 10.7 ± 1.2 mmHg without treatment. A systematic review of the literature obtained 15 eligible case series (n = 123) with rates of success within 46–100%, favoring less aggressive approaches to reduce bleb size. Conclusion. Bleb dysesthesia is a rare complication of filtering glaucoma surgery. This modified bleb-limiting conjunctivoplasty technique (with removal of subjacent fibrous tissue if present) is able to target the underlying etiology providing ocular discomfort relief while maintaining bleb function and may be considered as first-choice surgical treatment.
An Upper Bound on the Radius of a 3-Vertex-Connected C4-Free Graph
Authors: Fundikwa Blessings T. , Mazorodze Jaya P. , Mukwembi Simon
Published: August 2020

We show that if G is a 3-vertex-connected C4-free graph of order n and radius r, then the inequality r≤2n/9+O1 holds. Moreover, graphs are constructed to show that the bounds are asymptotically sharp.
Early Sialadenitis After Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Prevalence and Predictors
Authors: Riachy Ruba , Ghazal Nisrine , Haidar Mohamad B. , Elamine Ahmad , Nasrallah Mona P.
Published: August 2020

Introduction. Sialadenitis is a frequent occurrence after radioactive iodine therapy (RAI). However, reports on its predictors and risk factors in the Eastern Mediterranean Region (EMRO) are scarce. Aim. This study aimed to identify risk factors for early sialadenitis in patients receiving RAI for differentiated thyroid cancer (DTC) at the American University of Beirut Medical Center. It also aimed to determine the prevalence and characteristics of such patients receiving RAI at our institution. Methods. This was a retrospective study conducted at the American University of Beirut Medical Center. Medical charts were reviewed for all patients 18–79 years of age admitted to receive RAI for DTC between 01/01/2012 and 31/12/2015. Sialadenitis was deemed present if there were any records of neck swelling/pain, dry mouth, or difficulty swallowing within 48 hours of RAI administration. Characteristics between patients with sialadenitis and those without were compared to determine predictors. Results. There were 174 patients admitted to receive RAI, predominantly females (71.3%), with papillary thyroid cancer (93.1%). The majority had lymph node involvement (64.5%). Pretreatment thyroid stimulating hormone (TSH) was greater than 75 mIU/ml in most patients (72.6%). The prevalence of sialadenitis was 20.1% (95% CI (15–27)). Being non-Lebanese and having a positive whole-body scan were associated with sialadenitis and persisted after adjustments (OR = 2.34 and 3.99). Non-Lebanese patients had higher rates of lymph nodes involvement (p value 0.005) and were kept off levothyroxine for longer periods (p value 0.02). Conclusion. The prevalence of sialadenitis at our institution was similar to other reported studies from the world. However, risk factors allude to more iodine exposure in the neck with positive whole-body scan uptake, lymph node involvement, and prolonged period of hypothyroidism.
Research on Extreme Signed Graphs with Minimal Energy in Tricyclic Signed Graphs S(n, n + 2)
Authors: Wang Yajing , Gao Yubin
Published: August 2020

A signed graph is acquired by attaching a sign to each edge of a simple graph, and the signed graphs have been widely used as significant computer models in the study of complex systems. The energy of a signed graph S can be described as the sum of the absolute values of its eigenvalues. In this paper, we characterize tricyclic signed graphs with minimal energy.
LoRa-Based Smart IoT Application for Smart City: An Example of Human Posture Detection
Authors: Han Jinkun , Song Wei , Gozho Amanda , Sung Yunsick , Ji Sumi , Song Liangliang , Wen Long , Zhang Qi
Published: August 2020

Scientists have explored the human body for hundreds of years, and yet more relationships between the behaviors and health are still to be discovered. With the development of data mining, artificial intelligence technology, and human posture detection, it is much more possible to figure out how behaviors and movements influence people’s health and life and how to adjust the relationship between work and rest, which is needed urgently for modern people against this high-speed lifestyle. Using smart technology and daily behaviors to supervise or predict people’s health is a key part of a smart city. In a smart city, these applications involve large groups and high-frequency use, so the system must have low energy consumption, a portable system, and a low cost for long-term detection. To meet these requirements, this paper proposes a posture recognition method based on multisensor and using LoRa technology to build a long-term posture detection system. LoRa WAN technology has the advantages of low cost and long transmission distances. Combining the LoRa transmitting module and sensors, this paper designs wearable clothing to make people comfortable in any given posture. Aiming at LoRa’s low transmitting frequency and small size of data transmission, this paper proposes a multiprocessing method, including data denoising, data enlarging based on sliding windows, feature extraction, and feature selection using Random Forest, to make 4 values retain the most information about 125 data from 9 axes of sensors. The result shows an accuracy of 99.38% of extracted features and 95.06% of selected features with the training of 3239 groups of datasets. To verify the performance of the proposed algorithm, three testers created 500 groups of datasets and the results showed good performance. Hence, due to the energy sustainability of LoRa and the accuracy of recognition, this proposed posture recognition using multisensor and LoRa can work well when facing long-term detection and LoRa fits smart city well when facing long-distance transmission.
Failure Mechanism of Horizontal Layered Rock Slope under the Coupling of Earthquake and Weathering
Authors: Tian Yun , Wang Lin-feng , Jin Hong-hua , Xia Yu-chao , Zeng Biao
Published: August 2020

In order to further reveal the dynamic failure process of horizontal complex layered rock slope in the coupling action of earthquake and weathering, based on the three‐dimensional particle flow software PFC3D, the rock triaxial test was first carried out to obtain the macroscopic rock mechanics parameters. Secondly, PFC3D was used to establish a three‐dimensional discrete element model of slope under 4 modes. Finally, the Wenchuan earthquake wave dynamic input is used to simulate the coupling effect of each model slope on earthquake‐weathering. Under the progressive failure process, the results show that, during the triaxial test, the mudstone particles and sandstone particles exhibited shear failure and tensile failure, respectively. The seismic failure mode of the horizontal complex layered rock slope model is divided into tensile fracture‐horizontal sliding failure (cavity depth 1.5 m and fissure depth 25%), tensile cracking‐caving‐dumping failure (cavity depth 3 m and fissure depth 37.5%), caving‐dumping‐rotation failure (cavity depth 4.5 m and fissure depth 50%), and caving‐slip‐rotation failure (cavity depth 6 m and fissure depth 62.5%), and the maximum vertical displacement of Model 2 can reach 6.2 m, and the maximum positive horizontal displacement is 7.8 m. With the deepening of the weathering degree, the coordination number of the rock block shows the attenuation advance effect and the elevation attenuation effect during the seismic period of 2–15 s. The total energy dissipation of the slope can be divided into two stages: fracture collision and overall collapse. The energy dissipation is more concentrated in the rock fracture collision stage, accounting for 89% to 95% of the total energy.
Fault Tolerant Control Algorithm of Hexarotor UAV
Authors: Jiao Songming , Gao Haiyue , Zheng Xiaokun , Liu Dengpan
Published: August 2020

As the best representative of the current cutting-edge technology, unmanned aerial vehicle (UAV) is widely used in various fields such as electric power inspection, agriculture, forestry and plant protection, fire rescue, and film and television shooting. With the rapid development of UAV, the safety work of UAV has become more important. In order to improve the safety of hexarotor UAV during flight, a fault-tolerant control scheme independent of basic control law and control distribution is designed in this paper. Firstly, the linear active disturbance rejection control (LADRC) was used as the basic control law for attitude control of hexarotor UAV. Secondly, in the case of actuator failure of hexarotor UAV, a fault observer was used to estimate fault information accurately. Then, on this basis, the control distribution matrix was adjusted to reduce the use of the faulty motor, and the purpose of fault-tolerant control was achieved. Finally, simulation experiments and actual flight experiments were carried out to verify the effectiveness of the proposed scheme. Experimental results show that the proposed scheme can improve the robustness of the control system and the flight safety of UAV.
Seismic Analysis of Connections of Buried Continuous Pipelines
Authors: Liu Wei , Huang Chunjie , Wang Yunchang , Shi Peixin
Published: August 2020

Buried pipelines serve as a critical component of lifeline systems, such as water and gas supply. They are interconnected to form a network to transport utilities. The connections change the geometry and stiffness of pipelines and impact the seismic response of the pipelines. This paper investigates the influence of connections on the seismic response of buried continuous steel trunk lines. A finite element model is introduced for analyzing the seismic response of buried pipeline networks. The seismic response of continuous steel pipelines with different connections, including cruciform and T‐, K‐, L‐, and Y‐shaped, is analyzed. The impact of site class, pipe diameter, branch angle, and angle of wave incidence on the response of pipe connections is explored. An influence coefficient defined to characterize the strain amplification at the connections is proposed for different forms of connections. Engineering measures to reduce the strain amplification at connections are suggested.
The Influence of Complex Subway Station Construction on High Retaining Walls and Appropriate Countermeasures
Authors: Wang Kai , Li Zhaoping , Xu Xuezhao , Shi Leilei , Zhang Fanbo
Published: August 2020

Anzhen Bridge Station of Beijing metro line 12, which adopts a separated‐island platform constructed by the undermining method, passes along the retaining wall of the North Third Ring Road. A numerical simulation method is adopted to study the deformation laws of the retaining wall under the influence of station construction. The simulation data show that the affected retaining wall will have large settlement and tilt, and countermeasures must be taken. Four countermeasures are formulated, and their control effects are analyzed. The calculation results show that the combination of anchor cables and waist beams can effectively control the tilt of the retaining wall, but the control effect on the absolute settlement is not obvious. The control effect of isolation piles is better than that of foundation grouting. The joint control method of anchor cables combined with waist beams, isolation piles, and deep hole grouting makes the deformation meet the target, and according to this measure, a concept of joint control aiming at the influence of the “source,” “propagation,” and “object” is proposed, which can provide a reference for similar projects with a great difficulty in deformation control.
Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes
Authors: Andreasen Laura J. , Kirk Rikke K. , Fledelius Christian , Yorek Mark A. , Lykkesfeldt Jens , Akerstrom Thorbjorn
Published: August 2020

Introduction. Current clinical guidelines for management of diabetic peripheral neuropathy (DPN) emphasize good glycemic control. However, this has limited effect on prevention of DPN in type 2 diabetic (T2D) patients. This study investigates the effect of insulin treatment on development of DPN in a rat model of T2D to assess the underlying causes leading to DPN. Methods. Twelve-week-old male Sprague-Dawley rats were allocated to a normal chow diet or a 45% kcal high-fat diet. After eight weeks, the high-fat fed animals received a mild dose of streptozotocin to induce hyperglycemia. Four weeks after diabetes induction, the diabetic animals were allocated into three treatment groups receiving either no insulin or insulin-releasing implants in a high or low dose. During the 12-week treatment period, blood glucose and body weight were monitored weekly, whereas Hargreaves’ test was performed four, eight, and 12 weeks after treatment initiation. At study termination, several blood parameters, body composition, and neuropathy endpoints were assessed. Results. Insulin treatment lowered blood glucose in a dose-dependent manner. In addition, both doses of insulin lowered lipids and increased body fat percentage. High-dose insulin treatment attenuated small nerve fiber damage assessed by Hargreaves’ test and intraepidermal nerve fiber density compared to untreated diabetes and low-dose insulin; however, neuropathy was not completely prevented by tight glycemic control. Linear regression analysis revealed that glycemic status, circulating lipids, and sciatic nerve sorbitol level were all negatively associated with the small nerve fiber damage observed. Conclusion. In summary, our data suggest that high-dose insulin treatment attenuates small nerve fiber damage. Furthermore, data also indicate that both poor glycemic control and dyslipidemia are associated with disease progression. Consequently, this rat model of T2D seems to fit well with progression of DPN in humans and could be a relevant preclinical model to use in relation to research investigating treatment opportunities for DPN.
Targeting the Microenvironment to Overcome Gemcitabine Resistance in Pancreatic Cancer
Authors: Carpenter Eileen S. , Steele Nina G. , Pasca di Magliano Marina
Published: August 2020

Pancreatic cancer is characterized by an extensive and complex microenvironment, and is resistant to both chemotherapy and immune checkpoint blockade. The study by Principe and colleagues in this issue of Cancer Research proposes a combinatorial approach based on targeting the very mechanisms of resistance to gemcitabine, a commonly used chemotherapeutic agent. The authors show that gemcitabine treatment causes profound changes in the pancreatic cancer microenvironment, including elevated TGFβ signaling and immune checkpoint expression, as well as increased antigen presentation in tumor cells. Accordingly, they show that the combination of chemotherapy, TGFβ signaling inhibition, and immune checkpoint blockade effectively restores antitumor immunity and results in a significant survival benefit.

See related article by Principe et al., p. 3101
PIM Kinase Inhibitors Block the Growth of Primary T-cell Acute Lymphoblastic Leukemia: Resistance Pathways Identified by Network Modeling Analysis
Authors: Lim James T. , Singh Neha , Leuvano Libia A. , Calvert Valerie S. , Petricoin Emanuel F. , Teachey David T. , Lock Richard B. , Padi Megha , Kraft Andrew S. , Padi Sathish K.R.
Published: August 2020

Despite significant progress in understanding the genetic landscape of T-cell acute lymphoblastic leukemia (T-ALL), the discovery of novel therapeutic targets has been difficult. Our results demonstrate that the levels of PIM1 protein kinase is elevated in early T-cell precursor ALL (ETP-ALL) but not in mature T-ALL primary samples. Small-molecule PIM inhibitor (PIMi) treatment decreases leukemia burden in ETP-ALL. However, treatment of animals carrying ETP-ALL with PIMi was not curative. To model other pathways that could be targeted to complement PIMi activity, HSB-2 cells, previously characterized as a PIMi-sensitive T-ALL cell line, were grown in increasing doses of PIMi. Gene set enrichment analysis of RNA sequencing data and functional enrichment of network modules demonstrated that the HOXA9, mTOR, MYC, NFκB, and PI3K-AKT pathways were activated in HSB-2 cells after long-term PIM inhibition. Reverse phase protein array–based pathway activation mapping demonstrated alterations in the mTOR, PI3K-AKT, and NFκB pathways, as well. PIMi-tolerant HSB-2 cells contained phosphorylated RelA-S536 consistent with activation of the NFκB pathway. The combination of NFκB and PIMis markedly reduced the proliferation in PIMi-resistant leukemic cells showing that this pathway plays an important role in driving the growth of T-ALL. Together these results demonstrate key pathways that are activated when HSB-2 cell line develop resistance to PIMi and suggest pathways that can be rationally targeted in combination with PIM kinases to inhibit T-ALL growth.
A LHFPL3-AS1/miR-580-3p/STAT3 Feedback Loop Promotes the Malignancy in Melanoma via Activation of JAK2/STAT3 Signaling
Authors: Peng Qian , Liu Linbo , Pei Hui , Zhang Jianwen , Chen Minjing , Zhai Xiaomei
Published: August 2020

Melanoma is one of the severe skin cancers, accounting for three fourths of all deaths caused by skin cancers and gathering attention from researchers. Previous studies have elucidated that long noncoding RNAs (lncRNA) engage actively in tissue physiology and disease development, especially in tumorigenesis. LncRNA LHFPL3 antisense RNA 1 (LHFPL3-AS1) has rarely been mentioned in researches regarding cancers; therefore, the underlying role and function of LHFPL3-AS1 in melanoma arouse our interest. Data from our work suggested that LHFPL3-AS1 expression was markedly elevated in melanoma tissues and cells. Of note, patients with melanoma with high level of LHFPL3-AS1 were burdened with unfavorable prognosis. Functionally, it has been revealed that LHFPL3-AS1 exerted pro-growth, pro-invasion, and pro-EMT functions in melanoma. Mechanistically, it was figured out that LHFPL3-AS1 could be transcriptionally activated by STAT3. In turn, LHFPL3-AS1 served as a sponge of miR-580-3p to augment STAT3 expression, resulting in activated JAK2/STAT3 signaling pathway in melanoma.

Implications:

Our study revealed a novel positive feedback loop LHFPL3-AS1/miR-580-3p/STAT3 in melanoma, which might contribute to finding potential therapeutic targets for melanoma.
Phosphorylation of PLCγ1 by EphA2 Receptor Tyrosine Kinase Promotes Tumor Growth in Lung Cancer
Authors: Song Wenqiang , Kim Laura C. , Han Wei , Hou Yuan , Edwards Deanna N. , Wang Shan , Blackwell Timothy S. , Cheng Feixiong , Brantley-Sieders Dana M. , Chen Jin
Published: August 2020

EphA2 receptor tyrosine kinase (RTK) is often expressed at high levels in cancer and has been shown to regulate tumor growth and metastasis across multiple tumor types, including non–small cell lung cancer. A number of signaling pathways downstream of EphA2 RTK have been identified; however, mechanisms of EphA2 proximal downstream signals are less well characterized. In this study, we used a yeast-two-hybrid screen to identify phospholipase C gamma 1 (PLCγ1) as a novel EphA2 interactor. EphA2 interacts with PLCγ1 and the kinase activity of EphA2 was required for phosphorylation of PLCγ1. In human lung cancer cells, genetic or pharmacologic inhibition of EphA2 decreased phosphorylation of PLCγ1 and loss of PLCγ1 inhibited tumor cell growth in vitro. Knockout of PLCγ1 by CRISPR-mediated genome editing also impaired tumor growth in a KrasG12D-p53-Lkb1 murine lung tumor model. Collectively, these data show that the EphA2-PLCγ1 signaling axis promotes tumor growth of lung cancer and provides rationale for disruption of this signaling axis as a potential therapeutic option.

Implications:

The EphA2-PLCG1 signaling axis promotes tumor growth of non–small cell lung cancer and can potentially be targeted as a therapeutic option.
Benign Liver Tumors
Authors: Oldhafer Karl J. , Habbel Victoria , Horling Katja , Makridis Georgios , Wagner Kim Caroline
Published: August 2020

Background: Due to the frequent use of medical imaging including ultrasonography, the incidence of benign liver tumors has increased. There is a large variety of different solid benign liver tumors, of which hemangioma, focal nodular hyperplasia (FNH), and hepatocellular adenoma (HCA) are the most frequent. Advanced imaging techniques allow precise diagnosis in most of the patients, which reduces the need for biopsies only to limited cases. Patients with benign liver tumors are mostly asymptomatic and do not need any kind of treatment. Symptoms can be abdominal pain and pressure effects on adjacent structures. The 2 most serious complications are bleeding and malignant transformation. Summary: This review focuses on hepatic hemangioma (HH), FNH, and HCA, and provides an overview on clinical presentations, surgical and interventional treatment, as well as conservative management. Treatment options for HHs, if indicated, include liver resection, radiofrequency ablation, and transarterial catheter embolization, and should be carefully weighed against possible complications. FNH is the most frequent benign liver tumor without any risk of malignant transformation, and treatment should only be restricted to symptomatic patients. HCA is associated with the use of oral contraceptives or other steroid medications. Unlike other benign liver tumors, HCA may be complicated by malignant transformation. HCAs have been divided into 6 subtypes based on molecular and pathological features with different risk of complication. Key Message: The vast majority of benign liver tumors remain asymptomatic, do not increase in size, and rarely need treatment. Biopsies are usually not needed as accurate diagnosis can be obtained using modern imaging techniques.
Differences in Serum Alkaline Phosphatase Levels in Infants with Spontaneous Intestinal Perforation versus Necrotizing Enterocolitis with Perforation
Authors: Barseghyan Karine , Gayer Christopher , Azhibekov Timur
Published: August 2020

Introduction: Data on laboratory markers of spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) remain sparse. Objective: To compare serum alkaline phosphatase levels in infants with bowel perforation secondary to SIP versus surgical NEC, and then investigate the possible role of serum alkaline phosphatase in differentiating infants with these conditions. Methods: A retrospective case-control study of infants admitted with bowel perforation from 2005 to 2015. Demographic and prenatal data, postnatal exposures, and clinical, laboratory, and radiographic findings were extracted from inpatient medical records and analyzed using regression analysis. Results: Of 114 outborn infants included, 48 infants had SIP (cases) and 66 had NEC (controls). Upon admission from the referring hospital, the serum alkaline phosphatase level was significantly higher in infants with SIP, i.e., a median value of 782 versus236 U/L in NEC patients (p < 0.0001), with an adjusted odds ratio (OR) of 4.3 (p < 0.05) when the level was >500 U/L in multivariate regression model. Infants with SIP had significantly younger gestational age, presented earlier in life, primarily with pneumoperitoneum, and had greater exposure to steroids and indomethacin compared to infants with NEC. Alkaline phosphatase levels decreased rapidly in infants with SIP following admission. Conclusion: A transient increase in serum alkaline phosphatase level is independently associated with SIP when compared to NEC. Studies to confirm the role of alkaline phosphatase in the diagnosis of SIP are necessary and have potentially significant clinical and prognostic implications.
Clinical Impact of the Epithelial-Mesenchymal Transition in Lung Cancer as a Biomarker Assisting in Therapeutic Decisions
Authors: Ancel Julien , Dewolf Maxime , Deslée Gaëtan , Nawrocky-Raby Béatrice , Dalstein Véronique , Gilles Christine , Polette Myriam
Published: August 2020

Lung cancer is one of the most common solid cancers and represents the leading cause of cancer death worldwide. Over the last decade, research on the epithelial-mesenchymal transition (EMT) in lung cancer has gained increasing attention. Here, we review clinical and histological features of non-small-cell lung cancer associated with EMT. We then aimed to establish potential clinical implications of EMT in current therapeutic options, including surgery, radiation, targeted therapy against oncogenic drivers, and immunotherapy.
Support-vector machine and naïve bayes based diagnostic analytic of harmonic source identification
Authors: Hatta Jopri Mohd , Rahim Abdullah Abdul , Too Jingwei , Sutikno Tole , Nikolovski Srete , Manap Mustafa
Published: August 2020

A harmonic source diagnostic analytic is a vital to identify the location and type of harmonic source in the power system. This paper introduces a comparison of machine learning (ML) algorithm which are support vector machine (SVM) and Naïve Bayes (NB). Voltage and current features are used as the input for ML are extracted from time-frequency representation (TFR) of S-transform. Several unique cases of harmonic source location are considered, whereas harmonic voltage and harmonic current source type-load are used in the diagnosing process. To identify the best ML, the performance measurement of the propose method including accuracy, specificity, sensitivity, and F-measure are calculated. The adequacy of the proposed methodology is tested and verified on IEEE 4-bust test feeder and each ML algorithm is executed for 10 times due to different partitions and to prevent any overfitting result.
A novel comprehensive database for arabic and english off-line handwritten digits recognition
Authors: Subhi Abdalkafor Ahmed , Kareem Awad Waleed , Ali Alheeti Khattab M.
Published: August 2020

The recognition of Arabic handwritten is received at the same interest as other Latin languages. In Optical Character Recognition (OCR), handwriting Arabic recognition is considered as one of the critical and difficult tasks in the various scientific area. The main issues of this matter were due to the lack of public Arabic handwriting databases and the cursive nature of Arabic writing. In this paper, a new benchmark database is built for the Arabic and English off-line handwritten digits Recognition. The original form is divided into three groups: Arabic digits, English digits, and word Arabic digits which written five times by 100 different academic staff and students of university writers. Our database contains 14500 images; divided into two subsets of training and testing to help researchers through evaluating and comparing results obtained from their systems. 
Comprehensive learning particle swarm optimization for sizing and placement of distributed generation for network loss reduction
Authors: Karunarathne Eshan , Pasupuleti Jagadeesh , Ekanayake Janaka , Almeida Dilini
Published: August 2020

With the technological advancements, Distributed Generation (DG) has become a common method of overwhelming the issues like power losses and voltage drops which accompanies with the leaf of the feeders of radial distribution networks. Many researchers have used several optimization techniques and tools which could be used to locate and size the DG units in the system. Particle Swarm Optimization (PSO) is one of the famous optimization techniques. However, the premature convergence is identified as a fundamental adverse effect of this optimization technique. Therefore, the optimization problem can direct the objective function to a local minimum. This paper presents a variant of PSO techniques, “Comprehensive Learning Particle Swarm Optimization (CLPSO)” to determine the optimal placement and sizing of the DGs, which uses a novel learning strategy whereby all other particles’ historical best information and learning probability value are used to update a particle’s velocity. The CLPSO particles learn from one exampler for few iterations, instead of learing from global and personal best values in every iteration in PSO and this technique retains the swarm's variability to avoid premature convergence. A detailed analysis was conducted for the IEEE 33 bus system. The comparison results have revealed a higher convergence and an accuracy than the PSO.
The effect of network size and density to the choice of zone radius in ZRP
Authors: M. Haglan Hussein , Yussof Salman , Al-Ani Khalid W. , Shaker Jassim Hothefa , A. Jasm Dhamea
Published: August 2020

Mobile Ad hoc Network (MANET) is a network that consists of several nodes that connect without using a permanent infrastructure. Each node in MANET moves inside and outside of the network freely and randomly. The free and random movements of nodes may cause the topology of the network to change constantly. Therefore, the task of finding routes between nodes is a big challenge. Routing protocols in MANET can be divided into three categories, namely, proactive, reactive and hybrid routing protocols. Hybrid routing protocols such as the Zone Routing Protocol (ZRP) combines the advantages of both proactive and reactive routing protocols by dividing the network area into many overlapping zones. Data transmission to nodes within the zone is done using a proactive routing mechanism, while data transmission to nodes outside the zone is done using a reactive routing mechanism. The zone radius in ZRP determines how much proactive and reactive routing is used, and therefore plays a key role in determining the performance of the network. In this paper, the performance of the ZRP routing protocol is evaluated using the NS2.33 network simulator. The focus of the research is to evaluate the ZRP performance concerning the network size and density to identify an optimum ZRP zone size that will provide good performance. The performance is evaluated by using four performance metrics which are normalized routing load, average end-to-end delay, throughput, and packet delivery fraction. The results show that ZRP produces the best performance when the zone radius size is equal to two hops.
Performance analysis of millimeter wave 5G networks for outdoor environment: propagation perspectives
Authors: Al-Falahy Naser , AlMahamdy Mohammed , M. Mahmood Ali
Published: August 2020

To cope with the massive growth in global mobile data traffic for 2020 and beyond, the Fifth Generation (5G) system is required to be developed as the current 4G system is expected to fall short behind the provision of such growth. 5G systems is anticipated to use millimeter wave (mm-wave) frequency bands (20 to 90) GHz, due to the availability of wide chunk of unexploited bandwidth. This is revolutionary step to use these bands because of their very different propagation conditions, atmospheric absorption and hardware constraints. However, such challenges could be compensated by means of beamforming/beamsteering and larger antenna array. In this paper, a comparative study aided with ray-tracing simulation has been performed to assess the feasibility of mm-wave in 5G system. Propagation characteristics of the 28GHz and 73 GHz bands have been studied and compared in a street canyon outdoor environment to simulate 5G outdoor mobile access. Simulation results were shown along with their comparison for both of the aforementioned frequencies. The results of propagation comparison have been reported in terms of path loss, k-factor, delay spread and received power for both 28 and 73 GHz bands.
Efficient time reversal strategy for MISO-OFDM systems
Authors: Maaz Issam , Alabed Samer
Published: August 2020

In this work, we are interested in implementing, developing, and evaluating a time reversal strategy for a multiple-input single-output orthogonal frequency division multiplexing system. This strategy enjoys a good trade-off between the computational complexity and performance in terms of bit error rate where it offers a good coding gain by forming a beam in the direction of the destination at a price of channel state information available at the transmitter. In time reversal technique, a higher coding and diversity gain can be achieved by increasing the number of transmitting antennas, which focuses the formed beam to the direction of the destination antenna. By achieving this, the received signal-to-noise ratio can be maximized which makes time reversal a good candidate for multiple-input single-output systems while keeping a low complexity. The performance of the proposed system is evaluated in terms of bit error rate where our simulations show that the proposed strategy enjoys the full diversity gain, which is equal to the number of transmitting antennas. Moreover, a robust channel estimation technique is proposed to improve the overall system in terms of bit error rate.