bluuebunny/crossref_metadata_2025 huggingface dataset:
The Social Cost of Informal Electronic Waste Processing in Southern China
Authors: Boardman Anthony , Geng Jeff , Lam Bruno
Published: February 2020

Large amounts of e-waste are processed “informally” in lower income countries. Such processing releases dangerous pollutants, which increase mortality and reduce cognitive functioning. This paper estimates the social cost of informal e-waste processing in Southern China. This parameter may be “plugged-in” to cost-benefit analyses that evaluate the economic efficiency of policies to reduce informal e-waste processing in China or other lower income countries. It may also be used in the estimation of the social benefits (or costs) of new or proposed e-waste processing policies in higher income countries. We estimate that the social cost of informal e-waste processing in Guiyu is about $529 million. This amount is equivalent to about $423 per tonne (in 2018 US dollars) or $3528 per person, which is over half the gross income per capita of the residents of Guiyu. We also perform sensitivity analysis that varies the estimated mortality outcomes, the value of a statistical life and the amount of e-waste processed.
Mitigation and Predictive Assessment of SET Immunity of Digital Logic Circuits for Space Missions
Authors: Aguiar Ygor Q. , Wrobel Frédéric , Autran Jean-Luc , Leroux Paul , Saigné Frédéric , Pouget Vincent , Touboul Antoine D.
Published: February 2020

Due to the intrinsic masking effects of combinational circuits in digital designs, Single-Event Transient (SET) effects were considered irrelevant compared to the data rupture caused by Single-Event Upset (SEU) effects. However, the importance of considering SET in Very-Large-System-Integration (VLSI) circuits increases given the reduction of the transistor dimensions and the logic data path depth in advanced technology nodes. Accordingly, the threat of SET in electronics systems for space applications must be carefully addressed along with the SEU characterization. In this work, a systematic prediction methodology to assess and improve the SET immunity of digital circuits is presented. Further, the applicability to full-custom and cell-based design methodologies are discussed, and an analysis based on signal probability and pin assignment is proposed to achieve a more application-efficient SET-aware optimization of synthesized circuits. For instance, a SET-aware pin assignment can provide a reduction of 37% and 16% on the SET rate of a NOR gate for a Geostationary Orbit (GEO) and the International Space Station (ISS) orbit, respectively.
Comparative Yield, Fiber Quality and Dry Matter Production of Cotton Planted at Various Densities under Equidistant Row Arrangement
Authors: Khan Nangial , Xing Fangfang , Feng Lu , Wang Zhanbiao , Xin Minghua , Xiong Shiwu , Wang Guoping , Chen Huanxuan , Du Wenli , Li Yabing
Published: February 2020

The number of cotton plants grown per unit area has recently gained attention due to technology expense, high input, and seed cost. Yield consistency across a series of plant populations is an attractive cost-saving option. Field experiments were conducted to compare biomass accumulation, fiber quality, leaf area index, yield and yield components of cotton planted at various densities (D1, 1.5; D2, 3.3; D3, 5.1; D4, 6.9; D5, 8.7; and D6, 10.5 plants m−2). High planting density (D5) produced 21% and 28% more lint yield as compared to low planting density (D1) during both years, respectively. The highest seed cotton yield (4662 kg/ha) and lint yield (1763 kg/ha) were produced by high plant density (D5) while the further increase in the plant population (D6) decreased the yield. The increase in yield of D5 was due to more biomass accumulation in reproductive organs as compared to other treatments. The highest average (19.2 VA gm m−2 d−1) and maximum (21.8 VM gm m−2 d−1) rates of biomass were accumulated in reproductive structures. High boll load per leaf area and leaf area index were observed in high planting density as compared to low, while high dry matter partitioning was recorded in the lowest planting density as compared to other treatments. Plants with low density had 5% greater fiber length as compared to the highest plant density, while the fiber strength and micronaire value were 10% and 15% greater than the lowest plant density. Conclusively, plant density of 8.7 plants m−2 is a promising option for enhanced yield, biomass, and uniform fiber quality of cotton.
Programmed Cell Death Facilitates the Formation of Unisexual Male and Female Flowers in Persimmon (Diospyros kaki Thunb.)
Authors: Wang Liyuan , Li Huawei , Suo Yujing , Han Weijuan , Diao Songfeng , Mai Yini , Sun Peng , Li Fangdong , Fu and Jianmin
Published: February 2020

Most varieties of persimmon (Diospyros kaki Thunb.) are gynoecious, while just a few are either monoecious, androgynomonoecious, or androecious. Persimmon flowers initially contain the original androecium and gynoecium followed by arrest of either pistil or stamen primordia before maturity. Abortion of inappropriate primordium in persimmon may be related to programmed cell death (PCD). To test this hypothesis, hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, cyt-c immunohistochemistry (IHC) assay, transmission electron microscopy (TEM) observation, and real-time quantitative polymerase chain reaction (RT-qPCR) were used to clarify the occurrence and molecular regulatory mechanism of PCD in male and female floral buds during the 14 days prior to the second crucial morphological stage when inappropriate sexual primordia were arrested to form unisexual flowers. Accordingly, dead cells in inappropriate sex organs were largely accumulated during the microsporocyte and macrosporocyte period of male and female floral buds, respectively. This may explain the abortion of inappropriate sex organs, leading to unisexual flowers. PCD is necessary for normal growth and development in persimmons, as dead cells could also be observed in the normal flower organs. High levels of a gene homologous to AMC9 may have accelerated the arrest of the pistil primordium during differentiation, leading to male unisexual flowers, and high levels of genes homologous to MeGI, BAG5, AifA, and HSP70 in female floral buds were positively correlated with the arrest of stamen primordium. Future studies may try to transform unisexual flowers into hermaphroditic flowers by the regulation of PCD artificially, which will be helpful to the controlled pollination experiments.
The Biodegradation Role of Saccharomyces cerevisiae against Harmful Effects of Mycotoxin Contaminated Diets on Broiler Performance, Immunity Status, and Carcass characteristics
Authors: Arif Muhammad , Iram Atia , Bhutta Muhammad A. K. , Naiel Mohammed A. E. , Abd El-Hack Mohamed E. , Othman Sarah I. , Allam Ahmed A. , Amer Mahmoud S. , Taha Ayman E.
Published: February 2020

A feeding trial (35 days) was carried out to investigate the effect of Saccharomyces cerevisiae cell wall as a mycotoxin biodegradation agent on the performance, feed efficiency, carcass traits, and immunity response against diseases in broilers fed aflatoxin B1 contaminated diets. For this purpose, 200 one day old broilers were randomly allotted into four groups, each with five replicates (10 birds per replicate). Four starter and finisher experimental rations were formulated by using (A) 0, (B) 1.25, (C) 2.5, and (D) 3.75 g kg−1 of Saccharomyces cerevisiae. Experimental diets were contaminated with aflatoxin B1 (100 ppb kg−1 diet). The experimental chicks were kept under standard managerial conditions, and the vaccination program was followed against infectious bursal disease (IBD), infectious bronchitis (IB), and Newcastle disease (ND) diseases. At the end of the feeding trial, carcass, organ weight, and blood samples were collected randomly to determine the carcass traits and antibody titer against ND and IBD viruses. Throughout the experiment, the addition of 3.75 g kg−1 of the Saccharomyces cerevisiae cell wall (Group-D) in feed resulted in the highest weight gain, final weight, feed intake, and the lowest FCR values followed by C group compared with the other groups. All carcass traits were significantly (p > 0.05) improved by increasing the inclusion levels of Saccharomyces cerevisiae in broiler diets. It could be concluded that the broiler diet supplemented with 2.5 or 3.75 g kg−1 of Saccharomyces cerevisiae as a biodegrading agent resulted in improved growth performance, immunity activity and carcass traits, and supplementation with Saccharomyces cerevisiae at these levels can be used effectively in broiler diets without negatively affecting bird health status.
Intraspecific Motor and Emotional Alignment in Dogs and Wolves: The Basic Building Blocks of Dog–Human Affective Connectedness
Authors: Palagi Elisabetta , Cordoni Giada
Published: February 2020

Involuntary synchronization occurs when individuals perform the same motor action patterns during a very short time lapse. This phenomenon serves an important adaptive value for animals permitting them to socially align with group fellows thus increasing integration and fitness benefits. Rapid mimicry (RM) and yawn contagion (YC) are two behavioral processes intermingled in the animal synchronization domain. Several studies demonstrated that RM and YC are socially modulated being more frequently performed by individuals sharing close relationships. This evidence highlights the relation between RM/YC and emotional contagion that is the capacity of two or more individuals to share the same affective state. In this review, we try to delineate a possible developmental trajectory of emotional sharing phenomena by using, as a model species, the domestic dog (Canis lupus familiaris), a valid example of empathic predisposition towards individuals belonging both to the same and the different species. We contrast available findings on RM and YC in dog–dog and dog–human dyads with those in wolf–wolf dyads, in order to investigate if the ability to emotionally engage with conspecifics (wolf–wolf and dog–dog) is evolutionary rooted in canids and if provides the basis for the development of inter-specific emotional sharing (dog–human).
Applicability of an Unmedicated Feeding Program Aimed to Reduce the Use of Antimicrobials in Nursery Piglets: Impact on Performance and Fecal Microbiota
Authors: López-Colom Paola , Estellé Jordi , Bonet Jordi , Coma Jaume , Martín-Orúe Susana Ma.
Published: February 2020

This study aimed to assess the impact of two different feeding programs, including or not antimicrobials, on gut microbiota development at early ages in commercial pigs. For this, 21-day-old weaned piglets were distributed into 12 pens (6 replicates with 26 pigs each) and fed ad libitum until fattening with: standard commercial formula with antibiotics and zinc oxide (2400 ppm) (AB), and alternative unmedicated feed formula (UN). Subsequently, the animals were moved to the fattening unit (F) receiving a common diet. Pigs were weighed, and feed consumption and diarrhea scores registered. Feces were collected on days 9 (pre-starter), 40 (starter) and 72 (fattening) post-weaning and microbial DNA extracted for 16S rDNA sequencing. Piglets fed UN diets had a worse feed efficiency (p < 0.05) than AB during nursery; however, UN pigs spent less time scouring after weaning (p = 0.098). The structure of fecal community evolved with the age of the animals (p = 0.001), and diet also showed to have a role, particularly in the starter period when UN microbiomes clustered apart from AB, resembling the ecosystems found in the fattening animals. Fibrolytic genera (Fibrobacter, Butyrivibrio, Christellansellaceae) were enriched in UN piglets whereas Lactobacillus characterized AB piglets (adjusted p < 0.05). Overall, this alternative feeding program could anticipate the gut development of piglets despite a lower feed efficiency compared to standard medicalized programs.
Effect of Indigenous Slaughter Methods on the Behavioural Response, Bleeding Efficiency and Cardiac Arrest of Nguni Goats
Authors: Mdletshe Zwelethu Mfanafuthi , Marufu Munyaradzi Christopher , Chimonyo Michael
Published: February 2020

Resource-limited farmers slaughter goats without stunning. The objective of the current study was to assess the influence of indigenous slaughter methods used by resource-limited households on slaughter stress-related behaviour, bleeding efficiency, and time to post-slaughter trauma of goats. Thirty clinically healthy castrated Nguni goats aged between 15 to 18 months old with body condition score of three were randomly assigned to three non-stunning informal slaughter methods, (1) transverse neck incision (TNI); (2) suprasternal notch piercing in the direction of the heart (SNP); and (3) under-shoulder-blade chest-floor point-of-elbow (CFP) sticking in the direction of the heart. Ten goats were slaughtered using each method. Slaughter method had no effect (p < 0.05) on stress-related behaviour. Rate of bleeding efficiency was highest (p < 0.05) for SNP slaughtered goats. Time to lose sensibility was lowest (p < 0.05) for goats slaughtered using the CFP (55 s) when compared to SNP (68 s) and TNI (75 s) slaughter methods. Time to post-slaughter trauma was highest (p < 0.05) for SNP (247 s) and lowest for TNI (195 s). These findings suggest that goats slaughtered with SNP experienced rapid death when compared to TNI and SNP slaughter methods. It was concluded that the SNP slaughter method is the most effective slaughter technique because it is associated with higher bleeding efficiency and lower time to lose sensibility before death.
Nitric Oxide Synthase Is Involved in Follicular Development via the PI3K/AKT/FoxO3a Pathway in Neonatal and Immature Rats
Authors: Li Junrong , Zhang Wei , Zhu Shanli , Shi Fangxiong
Published: February 2020

It is assumed that nitric oxide synthase and nitric oxide are involved in the regulation of female reproduction. This study aimed to assess the roles of nitric oxide synthase (NOS) in follicular development. The endothelial NOS (eNOS) inhibitor L-NAME, inducible NOS (iNOS) inhibitor S-Methylisothiourea (SMT) and NOS substrate L-arginine (L-Arg) were used in the NOS inhibition models in vivo. Neonatal female rats were treated with phosphate buffer saline (PBS, control), L-NAME (L-NG-Nitroarginine Methyl Ester, 40 mg/kg), SMT (S-Methylisothiourea, 10 mg/kg), L-NAME + SMT, or L-Arg (L-arginine, 50 mg/kg) via subcutaneous (SC) injection on a daily basis for 19 consecutive days, with the samples being collected on specific postnatal days (PD5, PD10, and PD19). The results indicated that the number of antral follicles, the activity of total-NOS, iNOS, neuronal NOS (nNOS), and eNOS, and the content of NO in the ovary were significantly (p < 0.05) increased in the L-Arg group at PD19, while those in L + S group were significantly (p < 0.05) decreased. Meanwhile, the ovarian expression in the L-Arg group in terms of p-AKT, p-FoxO3a, and LC3-II on PD19 were significantly (p < 0.05) upregulated, while the expressions of PTEN and cleaved Caspase-3 were (p < 0.05) downregulated as a result of NOS/NO generation, respectively. Therefore, the results suggest that NOS is possibly involved in the maturation of follicular development to puberty via the PI3K/AKT/FoxO3a pathway, through follicular autophagia and apoptosis mechanisms.
Preliminary Investigation to Address Pain and Haemorrhage Following the Spaying of Female Cattle
Authors: Yu Audrey , Van der Saag Dominique , Letchford Peter , Windsor Peter , White Peter
Published: February 2020

Multiple physiological and neuroendocrine changes consistent with stress and pain have been demonstrated in cattle spayed via the Willis dropped ovary technique (WDOT). The procedure is routinely conducted without the use of anaesthetics or analgesics and has major implications for animal welfare. This study aimed to evaluate the effect of a topical anaesthetic (TA), haemostatic wound dressing, and meloxicam on pain behaviour and haemorrhage in the acute period following spaying. Yearling Brahman heifers (n = 75) were randomly allocated to the following treatment groups: (1) rectal palpation/control (CON); (2) WDOT spay (S); (3) WDOT spay with meloxicam (SM); (4) WDOT spay with TA (STA); and (5) WDOT spay with TA and meloxicam (STAM). Individual behavioural responses, body weight, packed cell volume (PCV), and total plasma protein (TPP) were monitored for up to 24 h following treatment. Head tucking behaviour and tail stiffness was increased in all spay groups compared to the CON group (p < 0.001), with the lowest proportional increase in the SM group. Rumination was initially reduced in S, SM, and STA heifers compared to CON heifers (p < 0.001), though SM heifers ruminated more than S heifers (p < 0.001). CON and SM heifers stood with an arched back the least, spent the most time eating, and spent less time lying down and more time standing compared to other treatment groups (p < 0.001). There was no significant effect of treatment on weight change (p = 0.519), PCV (p = 0.125) or TPP (p = 0.799). The administration of meloxicam is suggested as an effective, currently available method for improving the welfare of cattle undergoing WDOT spaying.
Frequencies Evaluation of β-Casein Gene Polymorphisms in Dairy Cows Reared in Central Italy
Authors: Sebastiani Carla , Arcangeli Chiara , Ciullo Marcella , Torricelli Martina , Cinti Giulia , Fisichella Stefano , Biagetti Massimo
Published: February 2020

The majority of proteins in cow’s milk are caseins, which occur in four groups (α-s1, α-s2, β, and k) encoded by different genes (CSN1S1, CSN1S2, CSN2, and CSN3, respectively). In this study, we focused on the β-casein allele variants A1 and A2 due to their influence on milk’s technological characteristics and human health. Digestion of the β-casein variant A1 leads to the formation of β-casomorphin 7 (BCM-7), a bioactive peptide that has been suggested to be a possible cause of various human diseases and associated with low milk digestibility. The potential negative role of the β-casein variant A1 in human health has stimulated the planning of cattle breeding programs based on genetic selection to increase the frequency of the A2 variant, which is associated with increased milk digestibility. The aim of this work was to evaluate the frequencies of the different β-casein variants in Italian Holstein Friesian dairy cows from cattle farms located in central Italy to select a population of A2 homozygous animals. β-casein genotypes were identified by evaluating the presence of single nucleotide polymorphisms (SNPs) of the CSN2 gene using PCR and sequencing analysis. The frequency of the desirable β-casein variant A2 in the studied bovine population was 0.61. The frequency of the undesirable A1 variant in the studied bovine population was 0.30. The frequency of the A2 allele was higher than expected for the breed; therefore, genetic selection for the A2 variant in these animals could be achieved in a fairly short time using A2 homozygous bulls.
Combinatorial Discriminant Analysis Applied to RNAseq Data Reveals a Set of 10 Transcripts as Signatures of Exposure of Cattle to Mycobacterium avium subsp. paratuberculosis
Authors: Malvisi Michela , Curti Nico , Remondini Daniel , De Iorio Maria Grazia , Palazzo Fiorentina , Gandini Gustavo , Vitali Silvia , Polli Michele , Williams John L. , Minozzi Giulietta
Published: February 2020

Paratuberculosis or Johne’s disease in cattle is a chronic granulomatous gastroenteritis caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). Paratuberculosis is not treatable; therefore, the early identification and isolation of infected animals is a key point to reduce its incidence. In this paper, we analyse RNAseq experimental data of 5 ELISA-negative cattle exposed to MAP in a positive herd, compared to 5 negative-unexposed controls. The purpose was to find a small set of differentially expressed genes able to discriminate between exposed animals in a preclinical phase from non-exposed controls. Our results identified 10 transcripts that differentiate between ELISA-negative, clinically healthy, and exposed animals belonging to paratuberculosis-positive herds and negative-unexposed animals. Of the 10 transcripts, five (TRPV4, RIC8B, IL5RA, ERF, CDC40) showed significant differential expression between the three groups while the remaining 5 (RDM1, EPHX1, STAU1, TLE1, ASB8) did not show a significant difference in at least one of the pairwise comparisons. When tested in a larger cohort, these findings may contribute to the development of a new diagnostic test for paratuberculosis based on a gene expression signature. Such a diagnostic tool could allow early interventions to reduce the risk of the infection spreading.
Glucose as a Major Antioxidant: When, What for and Why It Fails?
Authors: Cherkas Andriy , Holota Serhii , Mdzinarashvili Tamaz , Gabbianelli Rosita , Zarkovic Neven
Published: February 2020

A human organism depends on stable glucose blood levels in order to maintain its metabolic needs. Glucose is considered to be the most important energy source, and glycolysis is postulated as a backbone pathway. However, when the glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of the pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. The PPP generates and maintains the levels of nicotinamide adenine dinucleotide phosphate (NADPH) needed for the reduction in oxidized glutathione and protein thiols, the synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. The flux of glucose into a PPP—particularly under extreme oxidative and toxic challenges—is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP+ that is required for the activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain the disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload, and provide new insights into the positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.
Compression Shear Properties of Bonded–Bolted Hybrid Single-Lap Joints of C/C Composites at High Temperature
Authors: Zhang Yanfeng , Zhou Zhengong , Tan Zhiyong
Published: February 2020

Based on previous research, in this paper, the compressive shear failure behavior and mechanical properties of bonded–bolted hybrid single-lap joints of C/C composites at high temperature were studied. The compression shear test was performed on the joints at 800 °C to obtain the load–displacement curve and failure morphology. The failure modes of joints were observed by digital microscopy and scanning electron microscopy. A numerical analysis model was implemented in finite element code Abaqus/Explicit embedded with the user material subroutine (VUMAT). The numerical results were compared with the test results to verify the correctness of the model. The interrelationship of the compression shear loading mechanism and the variations in stress distribution between bonded joints and bonded–bolted hybrid joints at high temperature were explored. The progressive damage of hybrid joints and the variations in the ratio of the bolt load to the total load with displacement were obtained.
Development of a Four-Way Pinch-Type Servo Valve for Pneumatic Actuator
Authors: Tadano Kotaro , Ishida Yasumasa , Takeishi Hisami
Published: February 2020

Pneumatic servo valves are key components of pneumatic servo systems. Multi-degree-of-freedom systems, such as robot systems, utilize many servo valves to control their actuators. However, conventional servo valves always consume air due to leakage even when the pneumatic actuator is not moving. Hence, the consumption flow rate of the entire system corresponds to a heavy load on the air compressor. Reduction in the leakage of servo valves contributes to lower requirements for the air compressor and saves energy. In this study, we develop a four-way pinch- type pneumatic servo valve that controls flow rates by pinching air tubes to realize a leak-free servo valve. A cam to control the aperture of the flow channel is newly designed, and a control system is established. Measurement results indicate high linearity in static flow characteristics and high dynamic characteristics corresponding to 30 Hz. We experimentally confirm a good position tracking property in the position control of a pneumatic cylinder by using the developed valve. Finally, evaluation results of air consumption in a robotic control application indicate that the developed valve contributes to a significant reduction in air consumption compared to that of a conventional spool-type valve.
Investigation of a Bragg Grating-Based Fabry–Perot Structure Inscribed Using Femtosecond Laser Micromachining in an Adiabatic Fiber Taper
Authors: Madan Aayush , Yap Stephanie Hui Kit , Paulose Varghese , Chang Wonkeun , Shum Perry Ping , Hao Jianzhong
Published: February 2020

This paper presents the fabrication of a fiber Bragg grating (FBG)-based Fabry–Perot (FP) structure (7 mm total length) in an adiabatic fiber taper, investigates its strain and temperature characteristics, and compares the sensing characteristics with a standard polyimide coated FBG sensor. Firstly, a simulation of the said structure is presented, followed by the fabrication of an adiabatic fiber taper having the outer diameter reduced to 70 μ m (core diameter to 4.7 μ m). Next, the sensing structure, composed of two identical uniform FBG spaced apart by a small gap, is directly inscribed point-by-point using infrared femtosecond laser (fs-laser) micromachining. Lastly, the strain and temperature behavior for a range up to 3400 μ ε and 225 ° C, respectively, are investigated for the fabricated sensor and the FBG, and compared. The fabricated sensor attains a higher strain sensitivity (2.32 pm/ μ ε ) than the FBG (0.73 pm/ μ ε ), while both the sensors experience similar sensitivity to temperature (8.85 pm/ ° C). The potential applications of such sensors include continuous health monitoring where precise strain detection is required.
A Biomimetic Drug Delivery System Targeting Tumor Hypoxia in Triple-Negative Breast Cancers
Authors: Tatiparti Katyayani , Rauf Mohd Ahmar , Sau Samaresh , Iyer Arun K.
Published: February 2020

Triple-negative breast cancer (TNBC) is amongst the most challenging tumor subtypes because it presents itself without the estrogen, progesterone, and HER2 receptors. Hence, assessing new markers is an essential requirement for enhancing its targeted treatment. The survival of TNBC relies upon the advancement of hypoxia that contributes to treatment resistance, immune response resistance, and tumor stroma arrangement. Here, we explored bovine serum albumin (BSA) nanoparticle encapsulating the anti-cancer drug Paclitaxel (PTX) for cell-killing mediated by tumor hypoxia. For targeting hypoxia, we conjugated Acetazolamide (ATZ) with BSA nanoparticle that encapsulated PTX (referred hereon as BSA-PTX-ATZ) utilizing copper-free click chemistry, specifically the Strain-Promoted Alkyne Azide Cycloaddition (SPAAC). The in-vitro cell killing study uncovered that BSA-PTX-ATZ is more productive contrasted with free PTX. The evaluations of the physio-chemical properties of BSA-PTX-ATZ proves that the shelf-life is approximately two months when stored either at room or freezing temperatures or under refrigerated conditions. There is no leakage of PTX from the formulation during that period, while their nanoparticulate nature remained undisturbed. The BSA-PTX-ATZ nanoparticles indicated altogether higher cell killing in hypoxic conditions contrasted with normoxia proposing the hypoxia-mediated delivery mechanism of the activity of the formulation. Higher cell uptake found with fluorescent-marked BSA-PTX-ATZ shows CA-IX mediated cell uptake, substantiated by the prominent apoptotic cell death contrasted with free PTX.
Spherical Cavity Expansion Approach for the Study of Rigid-Penetrator’s Impact Problems
Authors: Buchely Mario , Marañon Alejandro
Published: February 2020

In recent years, Spherical Cavity Expansion (SCE) theory has been extensively utilized to model dynamic deformation processes related to indentation and penetration problems in many fields. In this review, the SCE theory is introduced by explaining the different mathematical features of this theory, its solution, and a potential application to model the penetration of a rigid penetrator into a deformable target. First, a chronologically literature review of the most common models used to study this kind of penetration problems is introduced, focusing on the SCE theory. Then, the engineering model of penetration is presented using the SCE approach. The model is then compared and validated with some FE numerical simulations and with previous penetration results. It is concluded that this engineering model based on the SCE theory can be utilized to predict the projectile deceleration and penetration depth into the semi-infinite and finite targets impacted by rigid penetrators.
On the Numerical Solution of Ordinary, Interval and Fuzzy Differential Equations by Use of F-Transform
Authors: Radi Davide , Sorini Laerte , Stefanini Luciano
Published: February 2020

An interesting property of the inverse F-transform f ^ of a continuous function f on a given interval [ a , b ] says that the integrals of f ^ and f on [ a , b ] coincide. Furthermore, the same property can be established for the restrictions of the functions to all subintervals [ a , p k ] of the fuzzy partition of [ a , b ] used to define the F-transform. Based on this fact, we propose a new method for the numerical solution of ordinary differential equations (initial-value ordinary differential equation (ODE)) obtained by approximating the derivative x · ( t ) via F-transform, then computing (an approximation of) the solution x ( t ) by exact integration. For an ODE, a global second-order approximation is obtained. A similar construction is then applied to interval-valued and (level-wise) fuzzy differential equations in the setting of generalized differentiability (gH-derivative). Properties of the new method are analyzed and a computational section illustrates the performance of the obtained procedures, in comparison with well-known efficient algorithms.
Oral HPV16 Prevalence in Oral Potentially Malignant Disorders and Oral Cavity Cancers
Authors: Tang Kai Dun , Menezes Lilian , Baeten Kurt , Walsh Laurence J. , Whitfield Bernard C. S. , Batstone Martin D. , Kenny Liz , Frazer Ian H. , Scheper Gert C. , Punyadeera Chamindie
Published: February 2020

The role of human papillomavirus type 16 (HPV16) in oral potentially malignant disorders (OPMD) and oral cavity carcinoma (OC) is still under debate. We investigated HPV16 prevalence in unstimulated saliva, oral rinse samples, oral swabs and tumour biopsies collected from OPMD (n = 83) and OC (n = 106) patients. HPV16 genotype, viral load, physical status (episomal vs. integrated) and tumour p16INK4a expression were determined. Oral HPV16 prevalence was higher in OC than in OPMD, but this difference was not statistically significant (7.5% (8/106) versus 3.6% (3/83), odds ratio (OR): 2.18, 95% confidence interval (CI): 0.56, 8.48, p = 0.26). There was a significant association (p < 0.05) between oral HPV16 infection and heavy tobacco consumption. Real-time PCR results indicated that no integration events occurred in either OPMD or OC cases based on the HPV16 E2/E6 ratio. HPV16 positive OPMD and OC patients had similar HPV16 E2 and E6 viral loads. The inter-rater agreement between tumour p16INK4a expression and oral HPV16 infection was considered as fair (k = 0.361) for OC. Our data suggest that the involvement of HPV16 in oral carcinogenesis is limited.
Arsenic Toxicity: Molecular Targets and Therapeutic Agents
Authors: Nurchi Valeria M. , Buha Djordjevic Aleksandra , Crisponi Guido , Alexander Jan , Bjørklund Geir , Aaseth Jan
Published: February 2020

High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.
Permanent Photodynamic Activation of the Cholecystokinin 2 Receptor
Authors: Tang Wen Zhu , Cui Zong Jie
Published: February 2020

The cholecystokinin 2 receptor (CCK2R) is expressed in the central nervous system and peripheral tissues, playing an important role in higher nervous and gastrointestinal functions, pain sensation, and cancer growth. CCK2R is reversibly activated by cholecystokinin or gastrin, but whether it can be activated permanently is not known. In this work, we found that CCK2R expressed ectopically in CHO-K1 cells was permanently activated in the dark by sulfonated aluminum phthalocyanine (SALPC/AlPcS4, 10–1000 nM), as monitored by Fura-2 fluorescent calcium imaging. Permanent CCK2R activation was also observed with AlPcS2, but not PcS4. CCK2R previously exposed to SALPC (3 and 10 nM) was sensitized by subsequent light irradiation (>580 nm, 31.5 mW·cm−2). After the genetically encoded protein photosensitizer mini singlet oxygen generator (miniSOG) was fused to the N-terminus of CCK2R and expressed in CHO-K1 cells, light irradiation (450 nm, 85 mW·cm−2) activated in-frame CCK2R (miniSOG-CCK2R), permanently triggering persistent calcium oscillations blocked by the CCK2R antagonist YM 022 (30 nM). From these data, it is concluded that SALPC is a long-lasting CCK2R agonist in the dark, and CCK2R is photogenetically activated permanently with miniSOG as photosensitizer. These properties of SALPC and CCK2R could be used to study CCK2R physiology and possibly for pain and cancer therapies.
Mitigation of Glucolipotoxicity-Induced Apoptosis, Mitochondrial Dysfunction, and Metabolic Stress by N-Acetyl Cysteine in Pancreatic β-Cells
Authors: Alnahdi Arwa , John Annie , Raza Haider
Published: February 2020

Glucolipotoxicity caused by hyperglycemia and hyperlipidemia are the common features of diabetes-induced complications. Metabolic adaptation, particularly in energy metabolism; mitochondrial dysfunction; and increased inflammatory and oxidative stress responses are considered to be the main characteristics of diabetes and metabolic syndrome. However, due to various fluctuating endogenous and exogenous stimuli, the precise role of these factors under in vivo conditions is not clearly understood. In the present study, we used pancreatic β-cells, Rin-5F, to elucidate the molecular and metabolic changes in glucolipotoxicity. Cells treated with high glucose (25 mM) and high palmitic acid (up to 0.3 mM) for 24 h exhibited increased caspase/poly-ADP ribose polymerase (PARP)-dependent apoptosis followed by DNA fragmentation, alterations in mitochondrial membrane permeability, and bioenergetics, accompanied by alterations in glycolytic and mitochondrial energy metabolism. Our results also demonstrated alterations in the expression of mammalian target of rapamycin (mTOR)/5′ adenosine monophosphate-activated protein kinase (AMPK)-dependent apoptotic and autophagy markers. Furthermore, pre-treatment of cells with 10 mM N-acetyl cysteine attenuated the deleterious effects of high glucose and high palmitic acid with improved cellular functions and survival. These results suggest that the presence of high energy metabolites enhance mitochondrial dysfunction and apoptosis by suppressing autophagy and adapting energy metabolism, mediated, at least in part, via enhanced oxidative DNA damage and mTOR/AMPK-dependent cell signaling.
The Role of Reactive Oxygen Species in Arsenic Toxicity
Authors: Hu Yuxin , Li Jin , Lou Bin , Wu Ruirui , Wang Gang , Lu Chunwei , Wang Huihui , Pi Jingbo , Xu Yuanyuan
Published: February 2020

Arsenic poisoning is a global health problem. Chronic exposure to arsenic has been associated with the development of a wide range of diseases and health problems in humans. Arsenic exposure induces the generation of intracellular reactive oxygen species (ROS), which mediate multiple changes to cell behavior by altering signaling pathways and epigenetic modifications, or cause direct oxidative damage to molecules. Antioxidants with the potential to reduce ROS levels have been shown to ameliorate arsenic-induced lesions. However, emerging evidence suggests that constructive activation of antioxidative pathways and decreased ROS levels contribute to chronic arsenic toxicity in some cases. This review details the pathways involved in arsenic-induced redox imbalance, as well as current studies on prophylaxis and treatment strategies using antioxidants.
The Kinetics of Amyloid Fibril Formation by de Novo Protein Albebetin and Its Mutant Variants
Authors: Balobanov Vitalii , Chertkova Rita , Egorova Anna , Dolgikh Dmitry , Bychkova Valentina , Kirpichnikov Mikhail
Published: February 2020

Engineering of amyloid structures is one of the new perspective areas of protein engineering. Studying the process of amyloid formation can help find ways to manage it in the interests of medicine and biotechnology. One of the promising candidates for the structural basis of artificial functional amyloid fibrils is albebetin (ABB), an artificial protein engineered under the leadership of O.B. Ptitsyn. Various aspects of the amyloid formation of this protein and some methods for controlling this process are investigated in this paper. Four stages of amyloid fibrils formation by this protein from the first non-fibrillar aggregates to mature fibrils and large micron-sized complexes have been described in detail. Dependence of albebetin amyloids formation on external conditions and some mutations also have been described. The introduction of similar point mutations in the two structurally identical α-β-β motifs of ABB lead to different amiloidogenesis kinetics. The inhibitory effect of a disulfide bond and high pH on amyloid fibrils formation, that can be used to control this process, was shown. The results of this work are a good basis for the further design and use of ABB-based amyloid constructs.
Structural Dynamics of Lytic Polysaccharide Monooxygenase during Catalysis
Authors: Filandr Frantisek , Kavan Daniel , Kracher Daniel , Laurent Christophe V.F.P. , Ludwig Roland , Man Petr , Halada Petr
Published: February 2020

Lytic polysaccharide monooxygenases (LPMOs) are industrially important oxidoreductases employed in lignocellulose saccharification. Using advanced time-resolved mass spectrometric techniques, we elucidated the structural determinants for substrate-mediated stabilization of the fungal LPMO9C from Neurospora crassa during catalysis. LPMOs require a reduction in the active-site copper for catalytic activity. We show that copper reduction in NcLPMO9C leads to structural rearrangements and compaction around the active site. However, longer exposure to the reducing agent ascorbic acid also initiated an uncoupling reaction of the bound oxygen species, leading to oxidative damage, partial unfolding, and even fragmentation of NcLPMO9C. Interestingly, no changes in the hydrogen/deuterium exchange rate were detected upon incubation of oxidized or reduced LPMO with crystalline cellulose, indicating that the LPMO-substrate interactions are mainly side-chain mediated and neither affect intraprotein hydrogen bonding nor induce significant shielding of the protein surface. On the other hand, we observed a protective effect of the substrate, which slowed down the autooxidative damage induced by the uncoupling reaction. These observations further complement the picture of structural changes during LPMO catalysis.
Optimization of Catechin and Proanthocyanidin Recovery from Grape Seeds Using Microwave-Assisted Extraction
Authors: Chen Jing , Thilakarathna W. P. D. Wass , Astatkie Tessema , Rupasinghe H. P. Vasantha
Published: February 2020

Grape seed extract (GSE) is a rich source of condensed flavonoid tannins, also called proanthocyanidins (PACs). The high molecular weight of polymeric PAC limits their biological activity due to poor bioavailability. The present study was undertaken to explore the potential applicability of microwave-assisted extraction (MAE) to convert GSE-PAC into monomeric catechins. A central composite design (CCD) was used to optimize the processing conditions for the MAE. The maximum total yield of monomeric catechins (catechin, epicatechin, and epicatechin gallate) and PAC were 8.2 mg/g dry weight (DW) and 56.4 mg catechin equivalence (CE)/g DW, respectively. The optimized MAE condition was 94% ethanol, 170 °C temperature, and a duration of 55 min. Compared to the results for PACs extracted via conventional extraction (Con) (94% ethanol; shaking at 25 °C for 55 min), MAE yielded 3.9-fold more monomeric catechins and 5.5-fold more PACs. The MAE showed higher antioxidant capacity and α-glucosidase inhibitory activity than that of the conventional extract, suggesting the potential use of the MAE products of grape seeds as a functional food ingredient and nutraceutical.
Student Disaffection: The Contribution of Greek In-service Kindergarten Teachers in Engaging Each Preschooler in Learning
Authors: Sakellariou Maria , Tsiara Efthymia
Published: February 2020

Engaging each student in learning comprises a continuous challenge and concern for the contemporary teacher. Educational research confirms the alarming increase of the disengaged students, relating student disaffection to adverse effects on students’ academic development. In the present research through one-on-one, semi-structured interviews, we investigate 80 Greek in-service kindergarten teachers’ opinions with regards to the significance of engaging the disengaged students in learning activities in preschool environments. The interviews based on Creswell’s (2009) interview model, incorporate open-ended and close-ended questions that offer a well-rounded view of the subject. Qualitative and quantitative data analysis of teachers’ opinions show that engaging each disengaged preschooler has multiple benefits on students’ academic development, class climate, and cohesion, and teacher’s self-efficacy, as well. Specifically, teachers’ engaging actions offer students the opportunity to develop their abilities, self-efficacy, and sense of belonging. The interviewees also recognise that increased student engagement levels decisively affect teachers—students’ interactions, offering at the same time clear feedback to the teacher.
TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy
Authors: Kim Jin Won , Min Ahrum , Im Seock-Ah , Jang Hyemin , Kim Yu Jin , Kim Hee-Jun , Lee Kyung-Hun , Kim Tae-Yong , Lee Keun Wook , Oh Do-Youn , Kim Jee-Hyun , Bang Yung-Jue
Published: February 2020

The aim of this study was to elucidate the carryover effect of olaparib to subsequent chemotherapy and its underlying mechanisms. We generated olaparib-resistant SNU-484, SNU-601, SNU-668, and KATO-III gastric cancer cell lines and confirmed their resistance by cell viability and colony forming assays. Notably, olaparib-resistant cell lines displayed cross-resistance to cisplatin except for KATO-III. Inversely, olaparib-resistant SNU-484, SNU-668, and KATO-III were more sensitive to irinotecan than their parental cells. However, sensitivity to paclitaxel remained unaltered. There were compensatory changes in the ATM/ATR axis and p-Chk1/2 protein expression. ERCC1 was also induced in olaparib-resistant SNU-484, SNU-601, and SNU-668, which showed cross-resistance to cisplatin. Olaparib-resistant cells showed tyrosyl-DNA phosphodiesterase 1 (TDP1) downregulation with higher topoisomerase 1 (TOP1) activity, which is a target of irinotecan. These changes of TOP1 and TDP1 in olaparib-resistant cells was confirmed as the underlying mechanism for increased irinotecan sensitivity through manipulated gene expression of TOP1 and TDP1 by specific plasmid transfection and siRNA. The patient-derived xenograft model established from the patient who acquired resistance to olaparib with BRCA2 mutation showed increased sensitivity in irinotecan. In conclusion, the carryover effects of olaparib to improve antitumor effect of subsequent irinotecan were demonstrated. These effects should be considered when determining the subsequent therapy with olaparib.
Combination of Decitabine and Entinostat Synergistically Inhibits Urothelial Bladder Cancer Cells via Activation of FoxO1
Authors: Wang Chenyin , Hamacher Alexandra , Petzsch Patrick , Köhrer Karl , Niegisch Günter , Hoffmann Michèle J. , Schulz Wolfgang A. , Kassack Matthias U.
Published: February 2020

Occurrence of cisplatin-resistance in bladder cancer is frequent and results in disease progression. Thus, novel therapeutic approaches are a high medical need for patients suffering from chemotherapy failure. The purpose of this study was to test the combination of the DNA methyltransferase inhibitor decitabine (DAC) with the histone deacetylase inhibitor entinostat (ENT) in bladder cancer cells with different platinum sensitivities: J82, cisplatin-resistant J82CisR, and RT-112. Intermittent treatment of J82 cells with cisplatin resulted in the six-fold more cisplatin-resistant cell line J82CisR. Combinations of DAC and/or ENT plus cisplatin could not reverse chemoresistance. However, the combination of DAC and ENT acted cytotoxic in a highly synergistic manner as shown by Chou-Talalay analysis via induction of apoptosis and cell cycle arrest. Importantly, this effect was cancer cell-selective as no synergism was found for the combination in the non-cancerous urothelial cell line HBLAK. Expression analysis indicated that epigenetic treatment led to up-regulation of forkhead box class O1 (FoxO1) and further activated proapoptotic Bim and the cell cycle regulator p21 and reduced expression of survivin in J82CisR. In conclusion, the combination of DAC and ENT is highly synergistic and has a promising potential for therapy of bladder cancer, particularly in cases with platinum resistance.