bluuebunny/crossref_metadata_2025 huggingface dataset:
Shock‐thermal history of the Agoudal (IIAB) iron meteorite from microstructural studies
Authors: Ray D. , Ghosh S. , Chennaoui Aoudjehane H. , Das S.
Published: October 2019

The Agoudal IIAB iron meteorite exhibits only kamacite grains (~6 mm across) without any taenite. The kamacite is homogeneously enriched with numerous rhabdite inclusions of different size, shape, and composition. In some kamacite domains, this appears frosty due to micron‐scale rhabdite inclusions (~5 to 100 μm) of moderate to high Ni content (~26 to 40 wt%). In addition, all the kamacite grains in matrix are marked with a prominent linear crack formed during an atmospheric break‐up event and subsequently oxidized. This feature, also defined by trails of lowest Ni‐bearing (mean Ni: 23 wt%) mm‐scale rhabdite plates (fractured and oxidized) could be a trace of a pre‐existing γ–α interface. Agoudal experienced a very slow rate of primary cooling ~4 °C Ma−1 estimated from the binary plots of true rhabdite width against corresponding Ni wt% and the computed cooling rate curves after Randich and Goldstein (1978). Chemically, Agoudal iron (Ga: 54 ppm; Ge: 140 ppm; Ir: 0.03 ppm) resembles the Ainsworth iron, the coarsest octahedrite of the IIAB group. Agoudal contains multiple sets of Neumann bands that are formed in space and time at different scales and densities due to multiple impacts with shock magnitude up to 130 kb. Signatures of recrystallization due to postshock low temperature mild reheating at about 400 °C are also locally present.
Differential gene expression in HaCaT cells may account for the various clinical presentation caused by anthropophilic and geophilic dermatophytes infections
Authors: Deng Weiwei , Liang Panpan , Zheng Yue , Su Zhen , Gong Zijian , Chen Jiaqin , Feng Peiying , Chen Jian
Published: October 2019

Background

Despite the worldwide prevalence of dermatophyte infections, only a few genes are reported to be related to dermatophyte infections. In addition, the mechanism by which different ecological dermatophytes infection leads to varying intensity of inflammation remains unclear.

Objectives

To investigate the mechanism of varying intensity of skin inflammation caused by different ecological dermatophytes infection.

Methods

We infected HaCaT cells with anthropophilic and geophilic dermatophytes to mimic various ecological dermatophyte infections. RNA‐sequencing (RNA‐seq) was employed to identify the change in the gene expression of HaCaT cells. To verify the expression of differentially expressed genes (DEGs), we selected 18 HaCaT cells genes to conduct qPCR experiments. In addition, immunoblotting was conducted to validate key genes from the MAPK signalling pathway.

Results

After HaCaT cells were infected with the anthropophilic Trichophyton rubrum (T rubrum) and the geophilic Microsporum gypseum (M gypseum), 118 and 619 differentially expressed genes were identified in HaCaT cells, respectively. These genes may provide a clue as to how keratinocytes respond to anthropophilic and geophilic dermatophytes. We also found that JUN may play a critical role in keratinocytes infected withM gypseum.

Conclusions

Differential gene expression in HaCaT cells may account for the various clinical presentation caused by anthropophilic and geophilic dermatophytes infections. In addition, the intense inflammatory reaction ofM gypseuminfection may be triggered by activating the JNK‐JUN signalling pathway.
C4 and crassulacean acid metabolism within a single leaf: deciphering key components behind a rare photosynthetic adaptation
Authors: Ferrari Renata C. , Bittencourt Priscila P. , Rodrigues Maria A. , Moreno‐Villena Jose J. , Alves Frederico R. R. , Gastaldi Vinícius D. , Boxall Susanna F. , Dever Louisa V. , Demarco Diego , Andrade Sónia C.S. , Edwards Erika J. , Hartwell James , Freschi Luciano
Published: October 2019

Although biochemically related, C4 and crassulacean acid metabolism (CAM) systems are expected to be incompatible. However, Portulaca species, including P. oleracea, operate C4 and CAM within a single leaf, and the mechanisms behind this unique photosynthetic arrangement remain largely unknown.

Here, we employed RNA‐seq to identify candidate genes involved exclusively or shared by C4 or CAM, and provided an in‐depth characterization of their transcript abundance patterns during the drought‐induced photosynthetic transitions in P. oleracea. Data revealed fewer candidate CAM‐specific genes than those recruited to function in C4. The putative CAM‐specific genes were predominantly involved in night‐time primary carboxylation reactions and malate movement across the tonoplast. Analysis of gene transcript‐abundance regulation and photosynthetic physiology indicated that C4 and CAM coexist within a single P. oleracea leaf under mild drought conditions.

Developmental and environmental cues were shown to regulate CAM expression in stems, whereas the shift from C4 to C4‐CAM hybrid photosynthesis in leaves was strictly under environmental control. Moreover, efficient starch turnover was identified as part of the metabolic adjustments required for CAM operation in both organs.

These findings provide insights into C4/CAM connectivity and compatibility, contributing to a deeper understanding of alternative ways to engineer CAM into C4 crop species.
Personal and Political Emotions in the Mind of the Diplomat
Authors: Keys Barbara , Yorke Claire
Published: October 2019

Despite growing research on the role of emotions in international relations, little work has analyzed how diplomats and decision‐makers themselves make sense of feelings generated by relationships that have both individual and state‐level implications. Do diplomats consciously experience feelings on behalf of the state? If so, how? How might individual embodied emotions affect how diplomats carry out their roles during negotiations? In the first systematic effort to address and conceptualize these questions empirically, with Henry Kissinger as a case study, we investigate the interplay between the experience of being an individual with personal emotions, on the one hand, and the practice of evaluating performative emotional cues relevant to the state, on the other. We suggest that diplomats recognize some emotional inputs as accruing not to them as individuals but to the state they represent, typically in connection with traditional diplomatic protocols and rituals that are firmly established as state‐level performances. At the same time, however, especially but not exclusively in high‐stakes negotiations involving strong personal relationships, individually embodied feelings with little‐to‐no state relevance can have significant influence on how diplomats define and pursue the national interest.
Restoration of upland hay meadows over an 11‐year chronosequence: an evaluation of the success of green hay transfer
Authors: Sullivan Elizabeth , Hall Noah , Ashton Paul
Published: October 2019

Grassland restoration has become a key tool in addressing the drastic losses of seminatural grassland since the mid‐twentieth century. This study examined the restoration by green hay transfer of upland hay meadows, a particularly scarce and vulnerable habitat, over an 11‐year chronosequence. The community composition of 18 restoration meadows was compared with that of donor reference sites in two study areas in the Pennine region of northern England. The study investigated: differences in community composition between donor and restoration meadows; transfer of upland hay meadow target species; and the effect of time and isolation from neighboring meadows on the community composition of the restoration meadows. Results showed that restoration meadows differed from donor meadows in that some target species were easily transferred whilst others were not found in the restoration meadows, or were at low levels of cover. Time had a significant effect on the community composition of the restoration meadows, but the similarity between restoration sites and donor sites did not increase with time, and the effect of isolation was not significant. The study showed that the green hay transfer method increases botanical diversity and is an important first step in meadow restoration. However, further restoration activity, such as seed addition, is likely to be required if restoration sites are to resemble closely the reference donor sites.
Combined blockade of IL‐25, IL‐33 and TSLP mediates amplified inhibition of airway inflammation and remodelling in a murine model of asthma
Authors: An Gao , Wang Wenjun , Zhang Xin , Huang Qiong , Li Qin , Chen Shihao , Du Xiaonan , Corrigan Chris J. , Huang Kewu , Wang Wei , Chen Yan , Ying Sun
Published: October 2019

Background and objective

Isolated blockade of IL‐25, IL‐33 and thymic stromal lymphopoietin (TSLP) has been shown to reduce airways inflammation and hyperresponsiveness in murine asthma model. The hypothesis that combined blockade of all three cytokines can accomplish this more effectively has never been addressed.

Methods

We studied a murine asthma model employing sensitization and challenge with ovalbumin (OVA) or saline control. To discern the effects of IL‐33 blockade, we compared outcomes in strain identical, wild‐type and IL‐33 receptor (St2
−/−) gene‐deleted mice. We then examined, in the St2
−/− animals, the effects of additional, single or combined blockade of IL‐25 and TSLP with blocking antibodies. Outcomes included airways reactivity, inflammatory cellular infiltration, epithelial cell metaplasia, deposition of fibrosis‐related proteins, local Th2‐type cytokine expression and total and specific serum IgE concentrations measured by ELISA and quantitative immunohistochemistry.

Results

St2
−/− gene deletion significantly reduced airways reactivity, inflammatory cellular infiltration, lung tissue expression of Th2 cytokines and fibrosis related proteins and serum total IgE in response to OVA sensitization and challenge. Additional administration of anti‐IL‐25 and anti‐TSLP blocking antibodies to the St2
−/− mice further significantly reduced inflammation, Th2 cytokine expression, airways fibrosis and IgE production, while anti‐TSLP alone reduced eosinophil infiltration and local IL‐4 expression. The airways inflammatory cellular infiltrate and lung tissue expression of Th2 cytokine, but not fibrosis‐related proteins were also reduced in the presence of isotype identical, control antibodies.

Conclusion

Combined blockade of these three cytokines may better ameliorate airways pathological changes in this murine asthma model, with implications for human asthma.
MYB81, a microspore‐specific GAMYB transcription factor, promotes pollen mitosis I and cell lineage formation in Arabidopsis
Authors: Oh Sung‐Aeong , Hoai Thuong Nguyen Thi , Park Hyo‐Jin , Zhao Mingmin , Twell David , Honys David , Park Soon‐Ki
Published: October 2019

Sexual reproduction in flowering plants relies on the production of haploid gametophytes that consist of germline and supporting cells. During male gametophyte development, the asymmetric mitotic division of an undetermined unicellular microspore segregates these two cell lineages. To explore genetic regulation underlying this process, we screened for pollen cell patterning mutants and isolated the heterozygous myb81‐1 mutant that sheds ~50% abnormal pollen. Typically, myb81‐1 microspores fail to undergo pollen mitosis I (PMI) and arrest at polarized stage with a single central vacuole. Although most myb81‐1 microspores degenerate without division, a small fraction divides at later stages and fails to acquire correct cell fates. The myb81‐1 allele is transmitted normally through the female, but rarely through pollen. We show that myb81‐1 phenotypes result from impaired function of the GAMYB transcription factor MYB81. The MYB81 promoter shows microspore‐specific activity and a MYB81–RFP fusion protein is only expressed in a narrow window prior to PMI. Ectopic expression of MYB81 driven by various promoters can severely impair vegetative or reproductive development, reflecting the strict microspore‐specific control of MYB81. Our data demonstrate that MYB81 has a key role in the developmental progression of microspores, enabling formation of the two male cell lineages that are essential for sexual reproduction in Arabidopsis.
The conserved 3′ Angio‐domain defines a superfamily of short interspersed nuclear elements (SINEs) in higher plants
Authors: Seibt Kathrin M. , Schmidt Thomas , Heitkam Tony
Published: October 2019

Repetitive sequences are ubiquitous components of eukaryotic genomes affecting genome size and evolution as well as gene regulation. Among them, short interspersed nuclear elements (SINEs) are non‐coding retrotransposons usually shorter than 1000 bp. They contain only few short conserved structural motifs, in particular an internal promoter derived from cellular RNAs and a mostly AT‐rich 3′ tail, whereas the remaining regions are highly variable. SINEs emerge and vanish during evolution, and often diversify into numerous families and subfamilies that are usually specific for only a limited number of species. In contrast, at the 3′ end of multiple plant SINEs we detected the highly conserved ‘Angio‐domain’. This 37 bp segment defines the Angio‐SINE superfamily, which encompasses 24 plant SINE families widely distributed across 13 orders within the plant kingdom. We retrieved 28 433 full‐length Angio‐SINE copies from genome assemblies of 46 plant species, frequently located in genes. Compensatory mutations in and adjacent to the Angio‐domain imply selective restraints maintaining its RNA structure. Angio‐SINE families share segmental sequence similarities, indicating a modular evolution with strong Angio‐domain preservation. We suggest that the conserved domain contributes to the evolutionary success of Angio‐SINEs through either structural interactions between SINE RNA and proteins increasing their transpositional efficiency, or by enhancing their accumulation in genes.
The role of FDI in structural change: Evidence from Mexico
Authors: Mühlen Henning , Escobar Octavio
Published: October 2019

Foreign direct investment (FDI) flows to Mexico are substantial and play an important role in the Mexican economy since the mid‐1990s. These investments reflect the activities of multinational firms that shape to some extent the economic landscape and sectoral structure in this host country. We illustrate that there is considerable variation in the amounts of FDI and structural change within the country and across time. Based on this, the paper's main purpose is to analyse whether there is a significant impact of FDI on structural change. We conduct an empirical analysis covering the period 2006–16. We use the fixed‐effects estimator where the unit of observation is a Mexican state for which we calculate structural change from the reallocation of labour between sectors. The results suggest that (if any) there is a positive effect from FDI on growth‐enhancing structural change. This effect depends critically on the lag structure of FDI. Moreover, there is some evidence that the positive effect (a) arises from FDI flows in the industry sector and (b) is present for medium and low‐skilled labour reallocation.
Removal processes of indicator organisms and opportunistic pathogens in an anaerobic digester‐constructed wetland system
Authors: Khouja Ibtissem , M’Hiri Fadhel , Ouzari Hadda‐Imene , Saidi Neila
Published: October 2019

Factors affecting the removal of opportunistic pathogens were evaluated in a hybrid constructed wetland (CW2) treating rural wastewater. The correlations between the bacterial population and the environmental variables showed that bacteria discharge was the result of abiotic factors change such as temperature (T), electrical conductivity (EC), dissolved oxygen (DO), organic matter and nutrient availability, as well as biotic factors like antagonism and competition with the native microbial community. However, the contribution of each factor depends on bacteria nature, on the influence of wetland design, availability of oxygen, season, presence of plant, and wastewater composition. Higher removals rates of biochemical oxygen demand BOD5 (94.64 ± 3.92%), chemical oxygen demand COD (90.91 ± 6.81%), total suspended solids TSS (98.05 ± 1.18%), nitrogen (total Kjeldahl nitrogen TKN (81.78 ± 11.01%), ammonia nitrogen

(92.17 ± 6.56%), orthophosphate

(79.73 ± 10.41%) and bacteria (>98%) were observed in CW2.
Differences in neurocognitive performance and metabolic and inflammatory indices in male adults with obesity as a function of regular exercise
Authors: Tsai Chia‐Liang , Pan Chien‐Yu , Chen Fu‐Chen , Huang Tsang‐Hai , Tsai Meng‐Che , Chuang Chih‐Yao
Published: October 2019

New Findings

What is the central question of this study?

Does regular exercise have benefits with regard to the neurocognitive problems related to obesity and are regular‐exercise‐induced neurocognitive changes associated with changes in the levels of metabolic/inflammatory biomarkers?

What is the main finding and its importance?

Although obese individuals with regular exercise showed higher C‐reactive protein levels as compared to the healthy‐weight individuals, only the obese individuals with a sedentary lifestyle showed deviant neurocognitive performance and higher metabolic and tumour necrosis factor‐α levels. The P3 amplitude was correlated with the levels of leptin in the obese individuals with regular activity, implicating that the potential mechanism of neurocognitive facilitation as a result of regular exercise could be reduced serum leptin levels.

Obesity has been shown to be highly associated with deterioration in executive functions, elevated energy metabolic indices and low‐grade systemic inflammation. Exercise has the capacity to reduce these negative phenomena. This work examined the effect of regular exercise on neurocognitive deficits and metabolic/inflammatory markers in obesity. Fifty‐four participants were divided into three groups: healthy‐weight (HW), obesity with regular exercise (ORE) and obesity with sedentary lifestyle (OSL), according to their BMI and frequency of exercise. Dual‐energy X‐ray absorptiometry was applied to assess the whole‐body composition of the participants. The assessment included neurocognitive measures during the Posner paradigm test and fasting blood measurements. Relative to the HW group, only the OSL group showed significantly longer reaction times and smaller P3 amplitudes, even when controlling for the cardiorespiratory fitness co‐variable. Although the OSL group exhibited a greater N2 amplitude than the HW group, when controlling for cardiorespiratory fitness the difference between the two groups disappeared. The OSL group showed greater levels of metabolic indices (i.e. leptin, insulin and glucose) than the HW group. The three groups had comparable interleukin (IL)‐1β and IL‐6 levels. However, the ORE and OSL groups showed higher levels of C‐reactive protein than the HW group. The OSL group exhibited higher tumour necrosis factor‐α levels than the HW and ORE groups. P3 amplitude was negatively correlated with the levels of leptin in the ORE group. Individuals with obesity can still obtain advantages with regard to neurocognitive and metabolic/inflammatory indices through engaging in regular exercise, possibly due to reduced serum leptin levels.
Calculation of acoustic radiation modes by using spherical waves and generalized singular value decomposition
Authors: Liu Jiawei , Liu Yangfan , Bolton J. Stuart
Published: October 2019

Acoustic radiation modes (ARMs) have been widely used in noise control engineering owing to their convenient sound-power characteristics. However, the evaluation of ARMs for non-regular structures can be computationally intensive: it usually involves solving the boundary integral equation (BIE) by using the boundary element method in order to obtain the sound power radiation resistance matrix, followed by a singular value decomposition to obtain the radiation modes. The proposed procedure involves projecting spherical harmonics onto an enclosing surface, followed by the application of generalized singular value decomposition, with the result that the need to solve the BIE is eliminated, which potentially reduces the computational effort significantly.
Staphylococcus aureus Infects Osteoclasts and Replicates Intracellularly
Authors: Krauss Jennifer L. , Roper Philip M. , Ballard Anna , Shih Chien-Cheng , Fitzpatrick James A. J. , Cassat James E. , Ng Pei Ying , Pavlos Nathan J. , Veis Deborah J.
Published: October 2019

The inflammation of bone tissue is called osteomyelitis, and most cases are caused by an infection with the bacterium
Staphylococcus aureus
. To date, the bone-building cells, osteoblasts, have been implicated in the progression of these infections, but not much is known about how the bone-resorbing cells, osteoclasts, participate. In this study, we show that
S. aureus
can infect osteoclasts and proliferate inside these cells, whereas bone-residing macrophages, immune cells related to osteoclasts, destroy the bacteria. These findings elucidate a unique role for osteoclasts to harbor bacteria during infection, providing a possible mechanism by which bacteria could evade destruction by the immune system.
LA-MC-ICP-MS U-Pb dating of low-U garnets reveals multiple episodes of skarn formation in the volcanic-hosted iron mineralization system, Awulale belt, Central Asia
Authors: Yan Shuang , Zhou Renjie , Niu He-Cai , Feng Yue-xing , Nguyen Ai Duc , Zhao Zhen-hua , Yang Wu-Bin , Dong Qian , Zhao Jian-xin
Published: October 2019

Volcanic-hosted iron deposits of the eastern Awulale metallogenetic belt in Central Asia possess a reserve of over 1.2 billion tons of iron ores and constitute one of the most important basements for high-grade iron resources in China. Skarns are widespread in these deposits and closely associated with iron mineralization. The ages of these skarns are unclear, and their genesis remains debated, preventing further investigation into their metallogenic processes. We focused on garnets in nine ore-bearing skarns from three large-scale iron deposits (Chagangnuoer, Dunde, and Beizhan) in the eastern Awulale belt. U-Pb dating was conducted on these garnets using our in-house reference material, the Taochong garnet (TC-13, Pb-Pb isochron age: 126.2 ± 2.3 Ma, initial 207Pb/206Pb ratio: 0.845 ± 0.022). Laser-ablation–multicollector–inductively coupled plasma–mass spectrometry (LA-MC-ICP-MS) was employed in the garnet U-Pb dating, and high-precision U-Pb ages (0.3%–1.6%) were obtained, highlighting the advantages of LA-MC-ICP-MS in dating low-U minerals. The garnet U-Pb ages of the nine skarn samples fall into three groups, i.e., 329.0 ± 5.1–326 ± 3.3 Ma (two samples), 316.3 ± 2.9–311.2 ± 2.4 Ma (six samples), and 295.6 ± 1.0 Ma (one sample), implying three episodes of skarn alteration in the volcanic-hosted iron mineralization system. The first and second episodes of skarns formed as a result of contact metasomatism between coeval volcanic rocks and limestone, and they have economically important iron mineralization. The third was likely caused by a local postcollision granitic intrusion, but its metallogenic potential deserves further assessment.
Gallstone ileus managed with enterolithotomy
Authors: Dunphy Louise , Al-Shoek Ihsan
Published: October 2019

Although gallstone disease is classically associated with the inflammatory sequela of cholecystitis, other presentations include gallstone ileus, Mirizzi syndrome, Bouveret syndrome and gallstone ileus. Gallstone ileus occurs when a gallstone passes from a cholecystoduodenal fistula into the gastrointestinal tract and causes obstruction, usually at the ileocaecal valve. It represents an uncommon complication of cholelithiasis, accounting for 1%–4% of all cases of mechanical bowel obstruction and 25% of all cases in individuals aged >65 years. It has a female predilection. Clinical presentation depends on the site of the obstruction. Diagnosis can prove challenging with the diagnosis rendered in 50% of cases intraoperatively. The authors present the case of a 79-year-old woman with a 10-day history of abdominal pain, nausea, vomiting and episodes of loose stools. An abdominal radiograph showed mildly distended right small bowel loops. Further investigation with a CT of the abdomen and pelvis demonstrated small bowel obstruction secondary to a 3.3 cm calculus within the small bowel. She underwent a laparotomy and a 5.0×2.5 cm gallstone was evident, causing complete obstruction. An enterolithotomy was performed. Her postoperative course was complicated by Mobitz type II heart block requiring pacemaker insertion. This paper will provide an overview of the clinical presentation, investigations and management of gallstone ileus. It provides a cautionary reminder of considering gallstone ileus in the differential diagnosis in elderly patients presenting with bowel obstruction and a history of gallstone disease.
Epidemiology of atrial fibrillation in northeast China: a cross-sectional study, 2017–2019
Authors: Xing Liying , Lin Min , Du Zhi , Jing Li , Tian Yuanmeng , Yan Han , Ren Guocheng , Dong Yingna , Sun Qun , Dai Dong , Shi Lei , Chen Hongyun , Liu Shuang
Published: October 2019

Objective

To evaluate the epidemiology of atrial fibrillation (AF) in northeast China.

Methods

This cross-sectional survey using a multistage, stratified and cluster random sampling method was conducted in Liaoning Province between September 2017 and March 2019. A total of 18 796 participants (28.9% urban, 71.1% rural) aged ≥40 years were included. All participants completed a questionnaire and underwent a physical examination and ECG. AF was diagnosed according to history and ECG findings.

Results

The overall AF prevalence was 1.1%; it increased steeply with age. AF was more prevalent in men than in women (1.5% vs 0.9%, p<0.001); however, the difference between urban and rural areas was not significant (1.3% vs 1.1%, p=0.228). Among the AF population, the overall AF awareness rate was 52.6%, higher in women than in men (61.5% vs 44.1%, p=0.011); however, the difference between areas was not statistically significant (60.0% vs 49.0%, p=0.129). According to the CHA2DS-VASc score, almost all (90.2%, 194/215) of our subjects required oral anticoagulant (OAC) therapy; however, only 4.1% actually received it. Moreover, hypertension (66.5%), dyslipidaemia (32.6%) and diabetes (24.2%) were highly prevalent in patients with AF, but their control rates were unacceptably low (7.0%, 8.6% and 28.8%, respectively).

Conclusions

The burden of AF in northeast China was substantial. Underuse of OAC therapy and uncontrolled comorbidities will likely contribute to the cardiovascular outcomes of patients with AF in the coming decades. Long-term management strategies for AF and related risk factors are required in northeast China.
Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality
Authors: Pérez Ruiz Fernando , Richette Pascal , Stack Austin G , Karra Gurunath Ravichandra , García de Yébenes Ma Jesus , Carmona Loreto
Published: October 2019

Objective

To determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.

Methods

Prospective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.

Results

Of 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).

Conclusions

Failure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.
Constructions of nearly holomorphic Siegel modular forms of degree two
Authors: Horinaga Shuji
Published: October 2019

Pitale, Saha and Schmidt studied the representation theoretic aspects of nearly holomorphic modular forms. By their theory, we obtain a classification of [Formula: see text]-modules which occur in the space of nearly holomorphic modular forms. In this paper, we give two constructions of nearly holomorphic Siegel modular forms of degree [Formula: see text] which generate reducible indecomposable modules. One construction is given by the Rankin–Cohen bracket of Shimura’s Eisenstein series and the other by Klingen Eisenstein series.
A Memory Efficient, Multiplierless & Modular VLSI Architecture of 1D/2D Re-Configurable 9/7 & 5/3 DWT Filters Using Distributed Arithmetic
Authors: Chakraborty Anirban , Banerjee Ayan
Published: October 2019

Dedicated hardware for “Discrete Wavelet Transform” (DWT) is at high demand for real-time imaging operations in any standalone electronic devices, as DWT is being extensively utilized for most of the transform-domain imagery applications. Various DWT algorithms exist in the literature facilitating its software implementations which are generally unsuitable for real-time imaging in any stand-alone devices due to their power intensiveness and huge computation time. In this paper, a convolutional DWT-based pipelined and tunable VLSI architecture of Daubechies 9/7 and 5/3 DWT filter is presented. Our proposed architecture, which mingles the advantages of convolutional and lifting DWT while discarding their notable disadvantages, is made area and memory efficient by exploiting “Distributed Arithmetic’ (DA) in our own ingenious way. Almost 90% reduction in the memory size than other notable architectures is reported. In our proposed architecture, both the 9/7 and 5/3 DWT filters can be realized with a selection input, “mode”. With the introduction of DA, pipelining and parallelism are easily incorporated into our proposed 1D/2D DWT architectures. The area requirement and critical path delay are reduced to almost 38.3% and 50% than that of the latest remarkable designs. The performance of the proposed VLSI architecture also excels in real-time applications.
Discovering intermediate massive black holes through tidally disrupted stars
Authors: Toscani Martina , Lodato Giuseppe , Rossi Elena Maria
Published: October 2019

Stars are spheres of gas held together by self-gravity. When flying by a black hole, however, the star self-binding force can be overwhelmed by the black hole tides and the star can be torn apart. This is a physically rich and fascinating event which will be described by first introducing the concept of black hole from a mathematical point of view. We will then dive into the physics of the tidal disruption and proceed describing the accompanying electromagnetic flare and gravitational wave burst in the frequency range of the Laser Interferometer Space Antenna. This empowers such events to discover the elusive black holes with mass intermediate between the solar and the million/billion solar masses.
Flatness properties of S-posets with an approach to down-closed subposets
Authors: Khosravi Roghaieh , Sedaghatjoo Mojtaba
Published: October 2019

In this paper, we investigate the notion of dc-po-flat [Formula: see text]-posets as the ones for which the associated tensor functors transfer merely down-closed embeddings (embeddings with down-closed images in codomains) to embeddings. We investigate derived flatness notions in regard to dc-po-flatness in parallel with po-flatness notions and give examples to clarify new notions and their implications. As the characterization of flat acts by means of embeddings into cyclic acts, stated by Fleischer, is not valid for [Formula: see text]-posets, it eventuates in introducing the new notion of cyclical po-flatness, situated strictly between weak po-flatness and po-flatness, though, we express a counterpart characterization for dc-po-flatness. At the end, we expose relationships between some po-flatness properties and regular injectivity.
Mechanisms, Applications, and Challenges of Insect RNA Interference
Authors: Zhu Kun Yan , Palli Subba Reddy
Published: October 2019

The RNA interference (RNAi) triggered by short/small interfering RNA (siRNA) was discovered in nematodes and found to function in most living organisms. RNAi has been widely used as a research tool to study gene functions and has shown great potential for the development of novel pest management strategies. RNAi is highly efficient and systemic in coleopterans but highly variable or inefficient in many other insects. Differences in double-stranded RNA (dsRNA) degradation, cellular uptake, inter- and intracellular transports, processing of dsRNA to siRNA, and RNA-induced silencing complex formation influence RNAi efficiency. The basic dsRNA delivery methods include microinjection, feeding, and soaking. To improve dsRNA delivery, various new technologies, including cationic liposome–assisted, nanoparticle-enabled, symbiont-mediated, and plant-mediated deliveries, have been developed. Major challenges to widespread use of RNAi in insect pest management include variable RNAi efficiency among insects, lack of reliable dsRNA delivery methods, off-target and nontarget effects, and potential development of resistance in insect populations.
Intestinal Stem Cell Aging: Origins and Interventions
Authors: Jasper Heinrich
Published: October 2019

Regenerative processes that maintain the function of the gastrointestinal (GI) epithelium are critical for health and survival of multicellular organisms. In insects and vertebrates, intestinal stem cells (ISCs) regenerate the GI epithelium. ISC function is regulated by intrinsic, local, and systemic stimuli to adjust regeneration to tissue demands. These control mechanisms decline with age, resulting in significant perturbation of intestinal homeostasis. Processes that lead to this decline have been explored intensively in Drosophila melanogaster in recent years and are now starting to be characterized in mammalian models. This review presents a model for age-related regenerative decline in the fly intestine and discusses recent findings that start to establish molecular mechanisms of age-related decline of mammalian ISC function.
Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with obstructive sleep apnea
Authors: Nicholl David D. M. , Hanly Patrick J. , Zalucky Ann A. , Handley George B. , Sola Darlene Y. , Ahmed Sofia B.
Published: October 2019

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na+-replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (>4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post-CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at Δ30 min: −100 ± 27 vs. −161 ± 25 mL/min, P = 0.007, and RPF at Δ60 min: −138 ± 27 vs. −206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men.
Parenterial iron sucrose-induced renal preconditioning: differential ferritin heavy and light chain expression in plasma, urine, and internal organs
Authors: Johnson Ali C. , Gooley Ted , Guillem Alvaro , Keyser Jeff , Rasmussen Henrik , Singh Bhupinder , Zager Richard A.
Published: October 2019

Experimental data suggest that iron sucrose (FeS) injection, used either alone or in combination with other prooxidants, can induce “renal preconditioning,” in part by upregulating cytoprotective ferritin levels. However, the rapidity, degree, composition (heavy vs. light chain), and renal ferritin changes after FeS administration in humans remain to be defined. To address these issues, healthy human volunteers ( n = 9) and patients with stage 3–4 chronic kidney disease( n = 9) were injected once with FeS (120, 240, or 360 mg). Plasma ferritin was measured from 0 to 8 days postinjection as an overall index of ferritin generation. Urinary ferritin served as a “biomarker” of renal ferritin production. FeS induced rapid (≤2 h), dose-dependent, plasma ferritin increases in all study participants, peaking at approximately three to five times baseline within 24–48 h. Significant urinary ferritin increases (~3 times), without dose-dependent increases in albuminuria, neutrophil gelatinase-associated lipocalin, or N-acetyl-β-d-glucosaminidase excretion, were observed. Western blot analysis with ferritin heavy chain (Fhc)- and light chain (Flc)-specific antibodies demonstrated that FeS raised plasma Flc but not Fhc levels. Conversely, FeS increased both Fhc and Flc in urine. To assess sites of FeS-induced ferritin generation, organs from FeS-treated mice were probed for Fhc, Flc, and their mRNAs. FeS predominantly raised hepatic Flc. Conversely, marked Fhc and Flc elevations developed in the kidney and spleen. No cardiopulmonary ferritin increases occurred. Ferritin mRNAs remained unchanged throughout, implying posttranscriptional ferritin production. We conclude that FeS induces rapid, dramatic, and differential Fhc and Flc upregulation in organs. Renal Fhc and Flc increases, in the absence of nephrotoxicity, suggest potential FeS utility as a clinical renal “preconditioning” agent.
High-Performance Emulator for Fixed Photovoltaic Panels
Authors: Mallal Youssef , El Bahir Lhoussain , Hassboun Touria
Published: October 2019

This paper presents the design and implementation of a photovoltaic emulator, based on an accurate mathematical model of a photovoltaic panel, instead of the look-up table method. The latter requires more memory for increasing accuracy and considering all the desired environmental situations. Furthermore, the proposed approach takes into account the incidence solar angle, as an input parameter, to offer the possibility of evaluating daily losses for different values of tilt angle. The validation of the proposed emulator is carried out by comparing in real-time, both the studied panel output and the emulator output, under variable load, temperature, and irradiation levels. The emulator is able to operate online with connected solar radiation and temperature sensors or offline with recorded measurement vectors. The practical tests were performed on a prototype designed using a MATLAB C MEX S-function, dSPACE board 1104, and a controlled DC/DC converter. The results showed that the emulator was able to behave accurately as the studied photovoltaic panel.
Possible Roles of IL-33 in the Innate-Adaptive Immune Crosstalk of Psoriasis Pathogenesis
Authors: Cannavò Serafinella Patrizia , Bertino Lucrezia , Di Salvo Eleonora , Papaianni Valeria , Ventura-Spagnolo Elvira , Gangemi Sebastiano
Published: October 2019

Background. IL-33 belongs to the IL-1 family, playing a role in several biologic processes as well as in the pathogenesis of different diseases, including skin pathologies. It acts as an alarmin, released by damaged cells. Binding to a ST2 receptor, it stimulates many immune cells such as ILC2 and Th2 cells. IL-33/ST2 axis seems to be involved in Th17 response. According to this, a review was performed to analyze if IL-33 even interplay in the onset of psoriasis, a Th1/Th17 inflammatory disease. Methods. Data obtained from the included articles are study author name, publication date, group studied, clinical and biological variables, laboratory tests, and outcome of interest of the study. Results. Data are obtained from the 19 studies identified, which assessed the association between IL-33 and psoriasis. Discussion. It seems to promote the innate-adaptive immune crosstalk: it could induce mast cells and neutrophil response after being released by injured keratinocytes and after stimulation by some cytokines, in particular TNFα, INFγ, and IL-17A. In addition, it seems to be involved from the onset of disease to the development of comorbidities, as psoriatic arthritis. Conclusion. The core of the future research on psoriasis could be to fully understand the role of this complex cytokine, in order also to find a new therapeutic approach.
Functional Loss of ATRX and TERC Activates Alternative Lengthening of Telomeres (ALT) in LAPC4 Prostate Cancer Cells
Authors: Graham Mindy K. , Kim Jiyoung , Da Joseph , Brosnan-Cashman Jacqueline A. , Rizzo Anthony , Baena Del Valle Javier A. , Chia Lionel , Rubenstein Michael , Davis Christine , Zheng Qizhi , Cope Leslie , Considine Michael , Haffner Michael C. , De Marzo Angelo M. , Meeker Alan K. , Heaphy Christopher M.
Published: October 2019

A key hallmark of cancer, unlimited replication, requires cancer cells to evade both replicative senescence and potentially lethal chromosomal instability induced by telomere dysfunction. The majority of cancers overcome these critical barriers by upregulating telomerase, a telomere-specific reverse transcriptase. However, a subset of cancers maintains telomere lengths by the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. The presence of ALT is strongly associated with recurrent cancer-specific somatic inactivating mutations in the ATRX-DAXX chromatin-remodeling complex. Here, we generate an ALT-positive adenocarcinoma cell line following functional inactivation of ATRX and telomerase in a telomerase-positive adenocarcinoma cell line. Inactivating mutations in ATRX were introduced using CRISPR-cas9 nickase into two prostate cancer cell lines, LAPC-4 (derived from a lymph node metastasis) and CWR22Rv1 (sourced from a xenograft established from a primary prostate cancer). In LAPC-4, but not CWR22Rv1, abolishing ATRX was sufficient to induce multiple ALT-associated hallmarks, including the presence of ALT-associated promyelocytic leukemia bodies (APB), extrachromosomal telomere C-circles, and dramatic telomere length heterogeneity. However, telomerase activity was still present in these ATRXKO cells. Telomerase activity was subsequently crippled in these LAPC-4 ATRXKO cells by introducing mutations in the TERC locus, the essential RNA component of telomerase. These LAPC-4 ATRXKO TERCmut cells continued to proliferate long-term and retained ALT-associated hallmarks, thereby demonstrating their reliance on the ALT mechanism for telomere maintenance.

Implications:

These prostate cancer cell line models provide a unique system to explore the distinct molecular alterations that occur upon induction of ALT, and may be useful tools to screen for ALT-specific therapies.
Trifluridine/Tipiracil plus Oxaliplatin Improves PD-1 Blockade in Colorectal Cancer by Inducing Immunogenic Cell Death and Depleting Macrophages
Authors: Limagne Emeric , Thibaudin Marion , Nuttin Lisa , Spill Aodrenn , Derangère Valentin , Fumet Jean-David , Amellal Nadia , Peranzoni Elisa , Cattan Valérie , Ghiringhelli François
Published: October 2019

Trifluridine/tipiracil (FTD/TPI) is a new antimetabolite agent used to treat chemorefractory metastatic colorectal cancer. FTD/TPI induced immunogenic cell death (ICD) in vitro in the microsatellite-stable (MSS) CT26 mouse colon carcinoma cell line, as well as in various human MSS colorectal cancer cell lines (SW620, Caco-2, and Colo-320). The combination of FTD/TPI with oxaliplatin synergized to promote ICD. In vivo, the combination was able to induce ICD, but not the single agents, although all treatment groups showed T-cell dependency. In addition, FTD/TPI and oxaliplatin did not affect regulatory T cells or myeloid-derived suppressor cells but eliminated type-2 tumor-associated macrophages (TAM2), resulting in higher cytotoxic CD8+ T-cell infiltration and activation. This effect was concomitantly associated with PD-L1 expression on tumor cells and PD-1 induction on CD8+ T cells, leading to secondary T-cell exhaustion. Finally, although anti–PD-1 was unable to synergize with FTD/TPI or oxaliplatin monotherapy, concomitant administration of anti–PD-1 to FTD/TPI and oxaliplatin enhanced the antitumor efficacy of the double chemotherapy. Our study showed a novel immunomodulatory role of FTD/TPI and oxaliplatin in depleting TAM2. The combination of oxaliplatin and FTD/TPI induced ICD in vivo, providing a rationale for the use of these drugs to eliminate immunosuppressive cells and boost checkpoint efficacy in patients with metastatic colorectal cancer.
Prothrombin Complex Concentrate before Urgent Surgery in Patients Treated with Rivaroxaban and Apixaban
Authors: Barzilai Merav , Kirgner Ilya , Steimatzky Arza , Salzer Gotler Dalit , Belnick Yulia , Shacham-Abulafia Adi , Avivi Irit , Raanani Pia , Yahalom Vered , Nakav Sigal , Varon David , Yussim Ethan , Bachar Gil N. , Spectre Galia
Published: October 2019

Introduction: Patients treated with direct Xa inhibitors may require urgent surgery. Administration of prothrombin complex concentrate (PCC) in this setting is common; however, it is based on limited experience in healthy volunteers. Objective: To characterize the population receiving PCC for apixaban/rivaroxaban reversal prior to an urgent surgery and evaluate its efficacy and safety. Methods: This was a retrospective study in 2 tertiary hospitals. Bleeding was evaluated based on surgical reports, hemoglobin drop, and the use of blood products or additional PCC during 48 h. Safety measures were thrombotic complications and 30-day mortality. Results: Sixty-two patients aged 80.7 ± 9 years, treated with apixaban (39.63%) or rivaroxaban (23.37%), received PCC before an urgent surgery/procedure. Most underwent abdominal operation (61%), orthopedic surgery (13%), or transhepatic cholecystostomy insertion (10%). Bleeding during surgery was reported in 3 patients (5%), no patient required additional PCC, and 16 patients (26%) received packed cells (median: 1 unit, range: 1–5). The 30-day mortality and thrombosis rates were 21% (n = 13) and 3% (n = 2), respectively. The cause of death was related to the primary disease, most commonly sepsis. No patient died due to bleeding/thrombosis. Conclusions: Our results support the use of PCC to achieve hemostasis in patients treated with Xa inhibitors prior to an urgent surgery.