bluuebunny/crossref_metadata_2025 huggingface dataset:
Vectorial pupil optimization to compensate for a polarization effect at full exposure field in lithography
Authors: Yuan Miao , Sun Yiyu , Wei Pengzhi , Li Zhaoxuan , Liao Guanghui , Li Yaning , Zou Lulu , Li Yanqiu
Published: September 2021

Recently, a single vectorial pupil optimization (VPO) was proposed to compensate for the polarization effect induced by thick mask and image optics at one field point in a lithography system, which does not work at full field points. In this paper, we propose a multi-objective VPO (MOVPO) method to obtain a universal vectorial pupil that can compensate for the polarization aberration at full field points. A novel multi-objective cost function, to the best of our knowledge, is built and includes uneven image pattern errors causing by polarization aberration (PA) at full field points in the MOVPO method. Comprehensive simulations demonstrate that the proposed MOVPO method can effectively improve the consistency of imaging and enlarge the overlapped process window at full field points.
Tunable delay line based on balanced coupled resonators cladded with VO2 films
Authors: Wu Yuda , Li Yi , Peng Chuang , Zhang Xin , Zou Mengdi , Yan Junyi , Zhuang Jiaqing , Mei Jincheng , Wang Xinping
Published: September 2021

A delay line consisting of a balanced side-coupled integrated spaced sequence of resonators and phase change material

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films is employed to realize continuously tunable delays with ultrafast response and low distortion. Simulation results show that a tunable delay of up to 80 ps with a 10% broadening, 150 GHz bandwidth, and 0.087 dB/ps delay loss is achieved from this structure. Taking advantage of photoinduced phase transition of

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films, this device obtains a switching time of less than 0.6 ps and effective compensation for group delay dispersion. This delay line shows advantages in the high-bit-rate all-optical processing systems.
Exposure latitude aware source and mask optimization for extreme ultraviolet lithography
Authors: Zou Lulu , Sun Yiyu , Wei Pengzhi , Yuan Miao , Li Zhaoxuan , Liu Lihui , Li Yanqiu
Published: September 2021

Extreme ultraviolet (EUV) lithography is a new generation of integrated circuit manufacturing technology with great development prospects. EUV lithography has more significant demand for high exposure latitude (EL) due to greater requirements for the stability of the light source. Source and mask optimization (SMO) technology is widely used to compensate for imaging distortion. In this paper, we propose an EL-aware SMO (ELASMO) method that uses a low-resist threshold sensitivity (LRS) penalty function to improve the EL in EUV lithography. Compared to conventional SMO, the proposed ELASMO method can significantly enhance the aerial image contrast, improve the EL, and enlarge the process window while ensuring high imaging fidelity.
Recent advances in supercontinuum generation in specialty optical fibers [Invited]
Authors: Sylvestre T. , Genier E. , Ghosh A. N. , Bowen P. , Genty G. , Troles J. , Mussot A. , Peacock A. C. , Klimczak M. , Heidt A. M. , Travers J. C. , Bang O. , Dudley J. M.
Published: September 2021

The physics and applications of fiber-based supercontinuum (SC) sources have been a subject of intense interest over the last decade, with significant impact on both basic science and industry. New uses for SC sources are also constantly emerging due to their unique properties that combine high brightness, multi-octave frequency bandwidth, fiber delivery, and single-mode output. The last few years have seen significant research efforts focused on extending the wavelength coverage of SC sources towards the 2 to

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molecular fingerprint mid-infrared (MIR) region and in the ultraviolet (UV) down to 100 nm, while also improving stability, noise and coherence, output power, and polarization properties. Here we review a selection of recent advances in SC generation in a range of specialty optical fibers, including fluoride, chalcogenide, telluride, and silicon-core fibers for the MIR; UV-grade silica fibers and gas-filled hollow-core fibers for the UV range; and all-normal dispersion fibers for ultralow-noise coherent SC generation.
Terahertz quantum cascade laser under optical feedback: effects of laser self-pulsations on self-mixing signals
Authors: Qi Xiaoqiong , Bertling Karl , Taimre Thomas , Agnew Gary , Leng Lim Yah , Gillespie Tim , Demić Aleksandar , Dean Paul , He Li Lian , Linfield Edmund H. , Giles Davies A. , Indjin Dragan , Rakić Aleksandar D.
Published: September 2021

In this article, we explore the interplay between the self-pulsations (SPs) and self-mixing (SM) signals generated in terahertz (THz) quantum cascade lasers (QCLs) under optical feedback. We find that optical feedback dynamics in a THz QCL, namely, SPs, modulate the conventional SM interference fringes in a laser feedback interferometry system. The phenomenon of fringe loss in the SM signal — well known in interband diode lasers — was also observed along with pronounced SPs. With an increasing optical feedback strength, SM interference fringes transition from regular fringes at weak feedback (C ≤ 1) to fringes modulated by SPs under moderate feedback (1 < C ≤ 4.6), and then [under strong feedback (C > 4.6)] to a SM waveform with reduced number of fringes modulated by SP, until eventually (under even greater feedback) all the fringes are lost and only SPs are left visible. The transition route described above was identified in simulation when the SM fringes are created either by a moving target or a current modulation of the THz QCL. This SM signal transition route was successfully validated experimentally in a pulsed mode THz QCL with SM fringes created by current modulation during the pulse. The effects of SP dynamics in laser feedback interferometric system investigated in this work not only provides a further understanding of nonlinear dynamics in a THz QCL but also helps to understand the SM waveforms generated in a THz QCLs when they are used for various sensing and imaging applications.
Multiwavelength, picosecond, synchronously pumped, Pb(MoO4)0.2(WO4)0.8 Raman laser oscillating at 12 wavelengths in a range of 1128–1360  nm
Authors: Frank Milan , Smetanin Sergei N. , Jelínek Michal , Vyhlídal David , Gubina Ksenia A. , Shukshin Vladislav E. , Zverev Petr G. , Kubeček Václav
Published: September 2021

In this Letter, a mixed

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as a new, to the best of our knowledge, active medium with optimized content for a synchronously pumped multiwavelength Raman laser with a combined frequency shift is presented. The unique structure of this crystal resulted in oscillations at 12 closely spaced output wavelengths in a spectral range from 1128 to 1360 nm. The strongest pulse shortening in comparison with nominally pure scheelite-like crystals has been achieved.
Agiles Studieren – ein Modell für hybride Präsenz‑/Onlinelehre
Authors: Stern Detlef
Published: September 2021

Mit der Pandemiesituation ist es auch für Hochschulen notwendig geworden, flexiblere Lehrformen als die vorherrschende Präsenzlehre anzubieten. Der Umstellungsaufwand hin zu einer reinen digitalen Onlinelehre ist aber erheblich. Auch Studierende sind von diesen gravierenden Umständen betroffen und müssen ihre etablierten, teilweise sehr persönlichen Lernformen anpassen. Häufige Wechsel zwischen Präsenz- und Onlinelehre, zum Beispiel motiviert durch Änderungen der Pandemiesituation, erscheinen für alle Beteiligten nicht einfach.

Ziel dieses Beitrags ist es, mit Agiles Studieren ein Lehr- und Lernformat vorzustellen, das digitales Lehren und Lernen in Präsenz- und Onlinelehre integriert. Der Beitrag gibt einen Überblick zu Prinzipien und Abläufe, wie auch zu Erfahrungen vor und während der Pandemiesituation, insbesondere zu Umstellungsaufwänden und Auswirkungen auf Lernergebnisse.

Seit dem Wintersemester 2013/14 zunächst in der Präsenzlehre eingesetzt, konnte Agiles Studieren seine Leistungsfähigkeit auch in der Pandemiesituation unter Beweis stellen. Geringe Umstellungsaufwände, wie auch gleichbleibende Lernergebnisse trotz gravierender Änderungen im Umfeld, sind zentrale Ergebnisse.
Dyrk1a gene dosage in glutamatergic neurons has key effects in cognitive deficits observed in mouse models of MRD7 and Down syndrome
Authors: Brault Véronique , Nguyen Thu Lan , Flores-Gutiérrez Javier , Iacono Giovanni , Birling Marie-Christine , Lalanne Valérie , Meziane Hamid , Manousopoulou Antigoni , Pavlovic Guillaume , Lindner Loïc , Selloum Mohammed , Sorg Tania , Yu Eugene , Garbis Spiros D. , Hérault Yann
Published: September 2021

Perturbation of the excitation/inhibition (E/I) balance leads to neurodevelopmental diseases including to autism spectrum disorders, intellectual disability, and epilepsy. Loss-of-function mutations in theDYRK1Agene, located on human chromosome 21 (Hsa21,) lead to an intellectual disability syndrome associated with microcephaly, epilepsy, and autistic troubles. Overexpression of DYRK1A, on the other hand, has been linked with learning and memory defects observed in people with Down syndrome (DS).Dyrk1ais expressed in both glutamatergic and GABAergic neurons, but its impact on each neuronal population has not yet been elucidated. Here we investigated the impact ofDyrk1agene copy number variation in glutamatergic neurons using a conditional knockout allele ofDyrk1acrossed with the Tg(Camk2-Cre)4Gsc transgenic mouse. We explored this genetic modification in homozygotes, heterozygotes and combined with the Dp(16Lipi-Zbtb21)1Yey trisomic mouse model to unravel the consequence ofDyrk1adosage from 0 to 3, to understand its role in normal physiology, and in MRD7 and DS. Overall,Dyrk1adosage in postnatal glutamatergic neurons did not impact locomotor activity, working memory or epileptic susceptibility, but revealed thatDyrk1ais involved in long-term explicit memory. Molecular analyses pointed at a deregulation of transcriptional activity through immediate early genes and a role of DYRK1A at the glutamatergic post-synapse by deregulating and interacting with key post-synaptic proteins implicated in mechanism leading to long-term enhanced synaptic plasticity. Altogether, our work gives important information to understand the action of DYRK1A inhibitors and have a better therapeutic approach.
A Bayesian network approach incorporating imputation of missing data enables exploratory analysis of complex causal biological relationships
Authors: Howey Richard , Clark Alexander D. , Naamane Najib , Reynard Louise N. , Pratt Arthur G. , Cordell Heather J.
Published: September 2021

Bayesian networks can be used to identify possible causal relationships between variables based on their conditional dependencies and independencies, which can be particularly useful in complex biological scenarios with many measured variables. Here we propose two improvements to an existing method for Bayesian network analysis, designed to increase the power to detect potential causal relationships between variables (including potentially a mixture of both discrete and continuous variables). Our first improvement relates to the treatment of missing data. When there is missing data, the standard approach is to remove every individual with any missing data before performing analysis. This can be wasteful and undesirable when there are many individuals with missing data, perhaps with only one or a few variables missing. This motivates the use of imputation. We present a new imputation method that uses a version of nearest neighbour imputation, whereby missing data from one individual is replaced with data from another individual, their nearest neighbour. For each individual with missing data, the subsets of variables to be used to select the nearest neighbour are chosen by sampling without replacement the complete data and estimating a best fit Bayesian network. We show that this approach leads to marked improvements in the recall and precision of directed edges in the final network identified, and we illustrate the approach through application to data from a recent study investigating the causal relationship between methylation and gene expression in early inflammatory arthritis patients. We also describe a second improvement in the form of a pseudo-Bayesian approach for upweighting certain network edges, which can be useful when there is prior evidence concerning their directions.
Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II
Authors: Baig Mohammad S. , Dou Yimo , Bergey Benjamin G. , Bahar Russell , Burgener Justin M. , Moallem Marjan , McNeil James B. , Akhter Akhi , Burke Giovanni L. , Sri Theivakadadcham Veroni S. , Richard Patricia , D’Amours Damien , Rosonina Emanuel
Published: September 2021

Transcription-related proteins are frequently identified as targets of sumoylation, including multiple subunits of the RNA polymerase II (RNAPII) general transcription factors (GTFs). However, it is not known how sumoylation affects GTFs or whether they are sumoylated when they assemble at promoters to facilitate RNAPII recruitment and transcription initiation. To explore how sumoylation can regulate transcription genome-wide, we performed SUMO ChIP-seq in yeast and found, in agreement with others, that most chromatin-associated sumoylated proteins are detected at genes encoding tRNAs and ribosomal proteins (RPGs). However, we also detected 147 robust SUMO peaks at promoters of non-ribosomal protein-coding genes (non-RPGs), indicating that sumoylation also regulates this gene class. Importantly, SUMO peaks at non-RPGs align specifically with binding sites of GTFs, but not other promoter-associated proteins, indicating that it is GTFs specifically that are sumoylated there. Predominantly, non-RPGs with SUMO peaks are among the most highly transcribed, have high levels of TFIIF, and show reduced RNAPII levels when cellular sumoylation is impaired, linking sumoylation with elevated transcription. However, detection of promoter-associated SUMO by ChIP might be limited to sites with high levels of substrate GTFs, and promoter-associated sumoylation at non-RPGs may actually be far more widespread than we detected. Among GTFs, we found that TFIIF is a major target of sumoylation, specifically at lysines 60/61 of its Tfg1 subunit, and elevating Tfg1 sumoylation resulted in decreased interaction of TFIIF with RNAPII. Interestingly, both reducing promoter-associated sumoylation, in a sumoylation-deficient Tfg1-K60/61R mutant strain, and elevating promoter-associated SUMO levels, by constitutively tethering SUMO to Tfg1, resulted in reduced RNAPII occupancy at non-RPGs. This implies that dynamic GTF sumoylation at non-RPG promoters, not simply the presence or absence of SUMO, is important for maintaining elevated transcription. Together, our findings reveal a novel mechanism of regulating the basal transcription machinery through sumoylation of promoter-bound GTFs.
Prevalence of diarrhoeal pathogens among children under five years of age with and without diarrhoea in Guinea-Bissau
Authors: Mero Sointu , Timonen Suvi , Lääveri Tinja , Løfberg Sandra , Kirveskari Juha , Ursing Johan , Rombo Lars , Kofoed Poul-Erik , Kantele Anu
Published: September 2021

Background

Childhood diarrhoea, a major cause of morbidity and mortality in low-income regions, remains scarcely studied in many countries, such as Guinea-Bissau. Stool sample drying enables later qPCR analyses of pathogens without concern about electricity shortages.

Methods

Dried stool samples of children under five years treated at the Bandim Health Centre in Bissau, Guinea-Bissau were screened by qPCR for nine enteric bacteria, five viruses, and four parasites. The findings of children having and not having diarrhoea were compared in age groups 0–11 and 12–59 months.

Results

Of the 429 children– 228 with and 201 without diarrhoea– 96.9% and 93.5% had bacterial, 62.7% and 44.3% viral, and 52.6% and 48.3% parasitic pathogen findings, respectively. Enteroaggregarive Escherichia coli (EAEC; 60.5% versus 66.7%), enteropathogenic E. coli (EPEC; 61.4% versus 62.7%), Campylobacter (53.2% versus 51.8%), and enterotoxigenic E. coli (ETEC; 54.4% versus 44.3%) were the most common bacterial pathogens. Diarrhoea was associated with enteroinvasive E. coli (EIEC)/Shigella (63.3%), ETEC (54.4%), astrovirus (75.0%), norovirus GII (72.6%) and Cryptosporidium (71.2%). The only pathogen associated with severe diarrhoea was EIEC/Shigella (p<0.001). EAEC was found more frequent among the infants, and EIEC/Shigella, Giardia duodenalis and Dientamoeba fragilis among the older children.

Conclusions

Stool pathogens proved common among all the children regardless of them having diarrhoea or not.
Role of T cells during the cerebral infection with Trypanosoma brucei
Authors: Olivera Gabriela C. , Vetter Leonie , Tesoriero Chiara , Del Gallo Federico , Hedberg Gustav , Basile Juan , Rottenberg Martin E.
Published: September 2021

The infection by Trypanosoma brucei brucei (T.b.b.), a protozoan parasite, is characterized by an early-systemic stage followed by a late stage in which parasites invade the brain parenchyma in a T cell-dependent manner.

Here we found that early after infection effector-memory T cells were predominant among brain T cells, whereas, during the encephalitic stage T cells acquired a tissue resident memory phenotype (TRM) and expressed PD1. Both CD4 and CD8 T cells were independently redundant for the penetration of T.b.b. and other leukocytes into the brain parenchyma. The role of lymphoid cells during the T.b.b. infection was studied by comparing T- and B-cell deficient rag1-/- and WT mice. Early after infection, parasites located in circumventricular organs, brain structures with increased vascular permeability, particularly in the median eminence (ME), paced closed to the sleep-wake regulatory arcuate nucleus of the hypothalamus (Arc). Whereas parasite levels in the ME were higher in rag1-/- than in WT mice, leukocytes were instead reduced. Rag1-/- infected mice showed increased levels of meca32 mRNA coding for a blood /hypothalamus endothelial molecule absent in the blood-brain-barrier (BBB). Both immune and metabolic transcripts were elevated in the ME/Arc of WT and rag1-/- mice early after infection, except for ifng mRNA, which levels were only increased in WT mice. Finally, using a non-invasive sleep-wake cycle assessment method we proposed a putative role of lymphocytes in mediating sleep alterations during the infection with T.b.b.

Thus, the majority of T cells in the brain during the early stage of T.b.b. infection expressed an effector-memory phenotype while TRM cells developed in the late stage of infection. T cells and parasites invade the ME/Arc altering the metabolic and inflammatory responses during the early stage of infection and modulating sleep disturbances.
Autoimmunity to phosphatidylserine and anemia in African Trypanosome infections
Authors: Rivera-Correa Juan , Verdi Joseph , Sherman Julian , Sternberg Jeremy M. , Raper Jayne , Rodriguez Ana
Published: September 2021

Anemia caused by trypanosome infection is poorly understood. Autoimmunity duringTrypanosoma bruceiinfection was proposed to have a role during anemia, but the mechanisms involved during this pathology have not been elucidated. In mouse models and human patients infected with malaria parasites, atypical B-cells promote anemia through the secretion of autoimmune anti-phosphatidylserine (anti-PS) antibodies that bind to uninfected erythrocytes and facilitate their clearance. Using mouse models of two trypanosome infections,Trypanosoma bruceiandTrypanosoma cruzi, we assessed levels of autoantibodies and anemia. Our results indicate that acuteT.bruceiinfection, but notT.cruzi, leads to early increased levels of plasma autoantibodies against different auto antigens tested (PS, DNA and erythrocyte lysate) and expansion of atypical B cells (ABCs) that secrete these autoantibodies.In vitrostudies confirmed that a lysate ofT.brucei, but notT.cruzi, could directly promote the expansion of these ABCs. PS exposure on erythrocyte plasma membrane seems to be an important contributor to anemia by delaying erythrocyte recovery since treatment with an agent that prevents binding to it (Annexin V) ameliorated anemia inT.brucei-infected mice. Analysis of the plasma of patients with human African trypanosomiasis (HAT) revealed high levels of anti-PS antibodies that correlated with anemia. Altogether these results suggest a relation between autoimmunity against PS and anemia in both mice and patients infected withT.brucei.
Mining nematode protein secretomes to explain lifestyle and host specificity
Authors: Tritten Lucienne , Ballesteros Cristina , Beech Robin , Geary Timothy G. , Moreno Yovany
Published: September 2021

Parasitic nematodes are highly successful pathogens, inflicting disease on humans, animals and plants. Despite great differences in their life cycles, host preference and transmission modes, these parasites share a common capacity to manipulate their host’s immune system. This is at least partly achieved through the release of excretory/secretory proteins, the most well-characterized component of nematode secretomes, that are comprised of functionally diverse molecules. In this work, we analyzed published protein secretomes of parasitic nematodes to identify common patterns as well as species-specific traits. The 20 selected organisms span 4 nematode clades, including plant pathogens, animal parasites, and the free-living species Caenorhabditis elegans. Transthyretin-like proteins were the only component common to all adult secretomes; many other protein classes overlapped across multiple datasets. The glycolytic enzymes aldolase and enolase were present in all parasitic species, but missing from C. elegans. Secretomes from larval stages showed less overlap between species. Although comparison of secretome composition across species and life-cycle stages is challenged by the use of different methods and depths of sequencing among studies, our workflow enabled the identification of conserved protein families and pinpointed elements that may have evolved as to enable parasitism. This strategy, extended to more secretomes, may be exploited to prioritize therapeutic targets in the future.
Litter expansion alters metabolic homeostasis in a sex specific manner
Authors: Kurup Kavitha , Mann Shivani N. , Jackson Jordan , Matyi Stephanie , Ranjo-Bishop Michelle , Freeman Willard M. , Stout Michael B. , Richardson Arlan , Unnikrishnan Archana
Published: September 2021

Nutritional manipulations early in life have been shown to influence growth rate and elicit long lasting effects which in turn has been found to impact lifespan. Therefore, we studied the long-term effects of pre-weaning dietary restriction implemented by litter expansion (4, 6, 8, 10, and 12 pups per dam: LS4, LS6, LS8, LS10, LS12) on male and female C57BL/6J mice. After weaning, these mice were fed ad libitum a commercial lab chow for the 15-month duration of the study. The male mice from large litter size (LS12) were significantly leaner and had reduced total fat mass compared to the normal size litters (LS 6) starting from weaning through to 15 months of age. Male LS10 & 12 mice also showed significant reduction in their fat depot masses at 15 months of age: gonadal, subcutaneous, and brown fat whereas the females did not mimic these findings. At 9 months of age, only male LS12 mice showed improved glucose tolerance and male LS12 mice also showed improved insulin tolerance starting at 5 months of age. In addition, we found that the male LS8, 10 & 12 mice at 15 months of age showed significantly reduced IGF-1 levels in the serum and various other organs (liver, gastrocnemius and brain cortex). Interestingly, the female LS8, 10, 12 mice showed a different pattern with reduced IGF-1 levels in serum, liver and gastrocnemius but not in the brain cortex. Similarly, the litter expanded mice showed sex specific response to levels of FGF21 and adiponectin with only the male mice showing increased FGF21 and adiponectin levels at 15 months of age. In summary, our data show that, litter expansion results in long-lasting metabolic changes that are age and sex dependent with the male mice showing an early and robust response compared to female mice.
Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma
Authors: Gao Yasheen , Wang Melinda , Guo Xiaojia , Hu Joanna , Chen Tian-min , Finn Sade´ M. B. , Lacy Jill , Kunstman John W. , Cha Charles H. , Bellin Melena D. , Robert Marie E. , Desir Gary V. , Gorelick Fred S.
Published: September 2021

Dysregulated expression of the secretory protein renalase can promote pancreatic ductal adenocarcinoma (PDAC) growth in animal models. We characterized renalase expression in premalignant and malignant PDAC tissue and investigated whether plasma renalase levels corresponded to clinical PDAC characteristics. Renalase immunohistochemistry was used to determine the presence and distribution of renalase in normal pancreas, chronic pancreatitis, PDAC precursor lesions, and PDAC tissues. Associations between pretreatment plasma renalase and PDAC clinical status were assessed in patients with varied clinical stages of PDAC and included tumor characteristics, surgical resection in locally advanced/borderline resectable PDAC, and overall survival. Data were retrospectively obtained and correlated using non-parametric analysis. Little to no renalase was detected by histochemistry in the normal pancreatic head in the absence of abdominal trauma. In chronic pancreatitis, renalase immunoreactivity localized to peri-acinar spindle-shaped cells in some samples. It was also widely present in PDAC precursor lesions and PDAC tissue. Among 240 patients with PDAC, elevated plasma renalase levels were associated with worse tumor characteristics, including greater angiolymphatic invasion (80.0% vs. 58.1%, p = 0.012) and greater node positive disease (76.5% vs. 56.5%, p = 0.024). Overall survival was worse in patients with high plasma renalase levels with median follow-up of 27.70 months vs. 65.03 months (p < 0.001). Renalase levels also predicted whether patients with locally advanced/borderline resectable PDAC underwent resection (AUC 0.674; 95%CI 0.42–0.82, p = 0.04). Overall tissue renalase was increased in both premalignant and malignant PDAC tissues compared to normal pancreas. Elevated plasma renalase levels were associated with advanced tumor characteristics, decreased overall survival, and reduced resectability in patients with locally advanced/borderline resectable PDAC. These studies show that renalase levels are increased in premalignant pancreatic tissues and that its levels in plasma correspond to the clinical behavior of PDAC.
Suppressor effect of catechol-O-methyltransferase gene in prostate cancer
Authors: Hashimoto Yutaka , Shiina Marisa , Maekawa Shigekatsu , Kato Taku , Shahryari Varahram , Kulkarni Priyanka , Dasgupta Pritha , Yamamura Soichiro , Saini Sharanjot , Tabatabai Z. Laura , Dahiya Rajvir , Tanaka Yuichiro
Published: September 2021

Catechol-estrogens can cause genetic mutations and to counteract their oncogenicity, the catechol-O-methyltransferase (COMT) gene is capable of neutralizing these reactive compounds. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both the Cancer Genome Atlas (TCGA) and immunohistochemical analysis of clinical specimens demonstrated a reduction of COMT expression in prostate cancer. Also, western analyses of prostate cancer cell lines show COMT levels to be minimal in DuPro and DU145 and thus, these cells were used for further analyses. Re-expression of COMT led to suppressed migration ability (wound healing assay) and enhanced apoptosis (flow cytometric analyses), and when challenged with 4-hydroxyestradiol, a marked reduction of cell proliferation (MTT assay) was observed. Xenograft growth in athymic mice also resulted in inhibition due to COMT. As a mechanism, western analyses show cleaved CASP3 and BID were increased whereas XIAP and cIAP2 were reduced due to COMT. As COMT expression is low in prostate cancer, its regulation was determined. Databases identified several miRNAs capable of binding COMT and of these, miR-195 was observed to be increased in prostate cancer according to TCGA. Real-time PCR validated upregulation of miR-195 in clinical prostate cancer specimens as well as DuPro and DU145 and interestingly, luciferase reporter showed miR-195 capable of binding COMT and overexpressing miR-195 could reduce COMT in cells. These results demonstrate COMT to play a protective role by activating the apoptosis pathway and for miR-195 to regulate its expression. COMT may thus be a potential biomarker and gene of interest for therapeutic development for prostate cancer.
Anthropogenic factors are stronger drivers of patterns of endemic plant diversity on Hainan Island of China than natural environmental factors
Authors: Zhu Zhi-Xin , Nizamani Mir Muhammad , Harris A. J. , Wang Hua-Feng
Published: September 2021

The roles of natural and anthropogenic factors in contributing to the organization of biodiversity at large and small scales have long been challenging to disentangle, and doing so has never been attempted for the island province of Hainan in China based on patterns of taxonomic and phylogenetic diversity. Therefore, in this study, we evaluated the taxonomic and phylogenetic diversity of endemic plants on the island as a function of anthropogenic and natural variables based on non-metric multi-dimensional scaling (NMDS) ordination and generated generalized linear models (GLMs). We found that the highest phylogenetic diversity (1006) and the lowest mean phylogenetic distance (515.5) was in the provincial capital, Haikou. The NMDS analyses indicated that taxonomic diversity was significantly correlated with industrial revenue (p= 0.006) and population (p= 0.004). Furthermore, most phylogenetic diversity indices were strongly correlated with population and agricultural revenue, while the sampled natural environmental variables were not significantly correlated with plant diversity indices. These findings indicate that anthropogenic factors are the main present-day driving forces of plant diversity in Hainan, though we did detect a significant latitudinal diversity gradient of richness that likely reflects the historical roles of natural environmental factors in the organization of biodiversity on the island. Overall, our results are alarming for biodiversity of the island and indicate that conservation and sustainable use of endemic plant species must be made a critical priority.
Policy options for surgical mentoring: Lessons from Zambia based on stakeholder consultation and systems science
Authors: Broekhuizen Henk , Ifeanyichi Martilord , Cheelo Mweene , Drury Grace , Pittalis Chiara , Rouwette Etiënne , Mbambiko Michael , Kachimba John , Brugha Ruairí , Gajewski Jakub , Bijlmakers Leon
Published: September 2021

Background

Supervision by surgical specialists is beneficial because they can impart skills to district hospital-level surgical teams. The SURG-Africa project in Zambia comprises a mentoring trial in selected districts, involving two provincial-level mentoring teams. The aim of this paper is to explore policy options for embedding such surgical mentoring in existing policy structures through a participatory modeling approach.

Methods

Four group model building workshops were held, two each in district and central hospitals. Participants worked in a variety of institutions and had clinical and/or administrative backgrounds. Two independent reviewers compared the causal loop diagrams (CLDs) that resulted from these workshops in a pairwise fashion to construct an integrated CLD. Graph theory was used to analyze the integrated CLD, and dynamic system behavior was explored using the Method to Analyse Relations between Variables using Enriched Loops (MARVEL) method.

Results

The establishment of a provincial mentoring faculty, in collaboration with key stakeholders, would be a necessary step to coordinate and sustain surgical mentoring and to monitor district-level surgical performance. Quarterly surgical mentoring reviews at the provincial level are recommended to evaluate and, if needed, adapt mentoring. District hospital administrators need to closely monitor mentee motivation.

Conclusions

Surgical mentoring can play a key role in scaling up district-level surgery but its implementation is complex and requires designated provincial level coordination and regular contact with relevant stakeholders.
Emergency of Tsallis statistics in fractal networks
Authors: Deppman Airton , Andrade-II Evandro Oliveira
Published: September 2021

Scale-free networks constitute a fast-developing field that has already provided us with important tools to understand natural and social phenomena. From biological systems to environmental modifications, from quantum fields to high energy collisions, or from the number of contacts one person has, on average, to the flux of vehicles in the streets of urban centres, all these complex, non-linear problems are better understood under the light of the scale-free network’s properties. A few mechanisms have been found to explain the emergence of scale invariance in complex networks, and here we discuss a mechanism based on the way information is locally spread among agents in a scale-free network. We show that the correct description of the information dynamics is given in terms of the q-exponential function, with the power-law behaviour arising in the asymptotic limit. This result shows that the best statistical approach to the information dynamics is given by Tsallis Statistics. We discuss the main properties of the information spreading process in the network and analyse the role and behaviour of some of the parameters as the number of agents increases. The different mechanisms for optimization of the information spread are discussed.
Transcriptome profiling reveals new insights into the roles of neuronal nitric oxide synthase on macrophage polarization towards classically activated phenotype
Authors: Chang Pingan , Gao Hao , Sun Quan , He Xiaohong , Huang Feifei
Published: September 2021

In response to various stimuli, naïve macrophages usually polarize to M1 (classically activated) or M2 (alternatively activated) cells with distinct biological functions. Neuronal nitric oxide synthase (NOS1) is involved in M1 macrophage polarization at an early stage. Here, we show for the first time that NOS1 is dispensable for M2 macrophage polarization for the first time. Further, differentially expressed genes (DEGs) regulated by NOS1 signaling in M1-polarized macrophages stimulated with lipopolysaccharide (LPS) were characterized by transcriptome analysis of wild-type (WT) and NOS1 knockout mouse macrophages. Thousands of affected genes were detected 2 h post LPS challenge, and this wide-ranging effect became greater with a longer stimulation time (8 h post LPS). NOS1 deficiency caused dysregulated expression of hundreds of LPS-responsive genes. Most DEGs were enriched in biological processes related to transcription and regulation of the immune and inflammatory response. At 2 h post-LPS, the toll-like receptor (TLR) signaling pathway, cytokine–cytokine receptor interaction, and NOD-like receptor signaling pathway were the major pathways affected, whereas the main pathways affected at 8 h post-LPS were Th1 and Th2 cell differentiation, FoxO, and AMPK signaling pathway. Identified DEGs were validated by real-time quantitative PCR and interacted in a complicated signaling pathway network. Collectively, our data show that NOS1 is dispensable for M2 macrophage polarization and reveal novel insights in the role of NOS1 signaling at different stages of M1 macrophage polarization through distinct TLR4 plasma membrane-localized and endosome-internalized signaling pathways.
PMMA bone cement containing long releasing silica-based chlorhexidine nanocarriers
Authors: Al Thaher Yazan , Alotaibi Hadil Faris , Yang Lirong , Prokopovich Polina
Published: September 2021

Prosthetic joint infections (PJI) are still an extremely concerning eventuality after joint replacement surgery; growing antibiotic resistance is also limiting the prophylactic and treatment options. Chlorhexidine (a widely used topical non-antibiotic antimicrobial compound) coatings on silica nanoparticles capable of prolonged drug release have been successfully developed and characterised. Such nanocarriers were incorporated into commercial formulation PMMA bone cement (Cemex), without adversely affecting the mechanical performance. Moreover, the bone cement containing the developed nanocarriers showed superior antimicrobial activity against different bacterial species encountered in PJI, including clinical isolates already resistant to gentamicin. Cytocompatibility tests also showed non inferior performance of the bone cements containing chlorhexidine releasing silica nanocarriers to the equivalent commercial formulation.
Does nicotine exposure during adolescence modify the course of schizophrenia-like symptoms? Behavioral analysis in a phencyclidine-induced mice model
Authors: Dutra-Tavares Ana Carolina , Manhães Alex C. , Semeão Keila A. , Maia Julyana G. , Couto Luciana A. , Filgueiras Claudio C. , Ribeiro-Carvalho Anderson , Abreu-Villaça Yael
Published: September 2021

The first symptoms of schizophrenia (SCHZ) are usually observed during adolescence, a developmental period during which first exposure to psychoactive drugs also occurs. These epidemiological findings point to adolescence as critical for nicotine addiction and SCHZ comorbidity, however it is not clear whether exposure to nicotine during this period has a detrimental impact on the development of SCHZ symptoms since there is a lack of studies that investigate the interactions between these conditions during this period of development. To elucidate the impact of a short course of nicotine exposure across the spectrum of SCHZ-like symptoms, we used a phencyclidine-induced adolescent mice model of SCHZ (2.5mg/Kg, s.c., daily, postnatal day (PN) 38-PN52; 10mg/Kg on PN53), combined with an established model of nicotine minipump infusions (24mg/Kg/day, PN37-44). Behavioral assessment began 4 days after the end of nicotine exposure (PN48) using the following tests: open field to assess the hyperlocomotion phenotype; novel object recognition, a declarative memory task; three-chamber sociability, to verify social interaction and prepulse inhibition, a measure of sensorimotor gating. Phencyclidine exposure evoked deficits in all analyzed behaviors. Nicotine history reduced the magnitude of phencyclidine-evoked hyperlocomotion and impeded the development of locomotor sensitization. It also mitigated the deficient sociability elicited by phencyclidine. In contrast, memory and sensorimotor gating deficits evoked by phencyclidine were neither improved nor worsened by nicotine history. In conclusion, our results show for the first time that nicotine history, restricted to a short period during adolescence, does not worsen SCHZ-like symptoms evoked by a phencyclidine-induced mice model.
Interferon beta for the treatment of multiple sclerosis in the Campania Region of Italy: Merging the real-life to routinely collected healthcare data
Authors: Moccia Marcello , Affinito Giuseppina , Capacchione Antonio , Lanzillo Roberta , Carotenuto Antonio , Montella Emma , Triassi Maria , Morra Vincenzo Brescia , Palladino Raffaele
Published: September 2021

Background

We aim to overcome limitations of previous clinical and population-based studies by merging a clinical registry to routinely-collected healthcare data, and to specifically describe differences in clinical outcomes, healthcare resource utilization and costs between interferon beta formulations for multiple sclerosis (MS).

Methods

We included 850 patients with MS treated with interferon beta formulations, from 2015 to 2019, seen at the MS Clinical Care and Research Centre (Federico II University of Naples, Italy) and with linkage to routinely-collected healthcare data (prescription data, hospital admissions, outpatient services). We extracted and computed clinical outcomes (relapses, 6-month EDSS progression using a roving EDSS as reference), persistence (time spent on a specific interferon beta formulation), adherence (medication possession ratio (MPR)), healthcare resource utilization and costs (annualized hospitalization rate (AHR), costs for hospital admissions and DMTs). To evaluate differences between interferon beta formulations, we used linear regression (adherence), Poisson regression (AHR), mixed-effect regression (costs), and Cox-regression models (time varying variables); covariates were age, sex, treatment duration, baseline EDSS and adherence.

Results

Looking at clinical outcomes, rates of relapses and EDSS progression were lower than studies run on previous cohorts; there was no differences in relapse risk between interferon beta formulations. Risk of discontinuation was higher for Betaferon®/Extavia® (HR = 3.28; 95%CI = 2.11, 5.12; p<0.01). Adherence was lower for Betaferon®/Extavia® (Coeff = -0.05; 95%CI = -0.10, -0.01; p = 0.02), and Avonex® (Coeff = -0.06; 95%CI = -0.11, -0.02; p<0.01), when compared with Rebif® and Plegridy® (Coeff = 0.08; 95%CI = 0.01, 0.16; p = 0.02). AHR and costs for MS hospital admissions were higher for Betaferon®/Extavia® (IRR = 2.38; 95%CI = 1.01, 5.55; p = 0.04; Coeff = 14.95; 95%CI = 1.39, 28.51; p = 0.03).

Conclusions

We have showed the feasibility of merging routinely-collected healthcare data to a clinical registry for future MS research, and have confirmed interferon beta formulations play an important role in the management of MS, with positive clinical outcomes. Differences between interferon beta formulations are mostly driven by adherence and healthcare resource utilization.
Drag resistance: Necropolitics, queer survival and a Balkan counterpublics
Authors: Anna T.
Published: September 2021

Taking the murder of Greek HIV+ and queer activist Zak Kostopoulos as its starting point – an exercise of necropolitical power in broad daylight – this article explores the work of drag queens in Greece and their aesthetic/political choices. It interprets their performances as tactics of survival and resistance and as creative responses to queer trauma. The role of queerfeminist spaces, cultural events and collectives also is examined as a response to the increasing right-wing turn in the country’s political scene – itself the result of the financial crisis of 2008. It imports José Esteban Muñoz’s disidentifications and counterpublics, Elizabeth Freeman’s erotohistoriography and Achille Mbembe’s necropolitics into the Greek/Balkan context and analyses the particular configurations and intersections of sexualities, genders, statehood, race, class and religion in Greece. It then examines disidentifications and counterpublics as empowering practices of community forming, offering glimpses of a queer Balkan counterpublics and the tools employed towards its making (humour, parody, reclaiming, disidentification, mourning and embodied pleasures).
Transformación en el paisaje de la comarca de Antequera (Málaga) durante el transcurso del siglo XV al siglo XVI
Authors: Cobos Rodríguez José Juan
Published: September 2021

La necesidad del ser humano de obtener más tierras de cultivo llevó a la transformación del paisaje natural de un sector central de la actual Andalucía a finales de la Edad Media, entre los siglos XV y XVI, como es la comarca de Antequera al norte de la provincia de Málaga (Andalucía, España). En este trabajo comprobamos, gracias a la documentación de archivo analizada, cómo este proceso afectó a una vegetación original (encina, alcornoque, matorral) y a una fauna salvaje (lobos, ciervos, tal vez osos) que fueron desapareciendo. Un monte mediterráneo, considerado en ocasiones un espacio de poco provecho, es el escenario donde se producen los cambios que lo convierten en tierras adecuadas para la explotación agrícola, dotadas, incluso, de agua. De este modo, un paisaje caracterizado por cierta diversidad natural pasará a ser humanizado, a ser dominado por la sociedad castellana de aquel momento, hasta lograr una imagen más uniforme del mismo. Un importante crecimiento de población llevó a que se realizaran diversos procesos de reparto de tierras que provocaron la transformación del monte o bosque en espacios para el cultivo, después de un duro trabajo campesino. Sin embargo, este proceso no estuvo exento de polémica, con vecinos a favor y en contra de tales roturaciones sobre zonas que hasta entonces habían sido de aprovechamiento común.
Aprovechamiento de recursos forestales en la Edad Media: una apuesta interdisciplinar para su estudio en zonas de media montaña mediterránea
Authors: Sancho Planas Marta
Published: September 2021

El objetivo de este artículo es destacar la importancia de la explotación de los recursos forestales en época medieval, a menudo ignorada y muy poco tratada en los textos especializados en este período. El principal obstáculo para el estudio de este tipo de actividades reside en la escasez de fuentes y la poca concreción de estas. Por ello se hace necesaria la utilización de fuentes muy diversas. La metodología empleada parte de la selección y análisis de documentación medieval con el fin de encontrar indicios de estas actividades (topónimos, productos…), posteriormente se ha recopilado información procedente de la arqueología, la iconografía y la etnología y se han establecido comparaciones de los datos obtenidos. Por lo que respecta al ámbito geográfico nos centramos en la zona correspondiente a la Cataluña actual. Se trata de un territorio caracterizado por un relieve accidentado en el que las tierras llanas son muy escasas. El clima mediterráneo que le es característico se ve alterado por la presencia de los Pirineos y la extensa línea de costa favorece los contactos a través del mar. Cronológicamente procuramos focalizar muestro estudio en la alta edad media, aunque no siempre nos ha sido posible encontrar datos correspondientes a dicho período por lo que a menudo debemos recurrir a fuentes de cronología posterior. El resultado final es la identificación de una gran variedad de actividades productivas, de recolección y semiagrícolas, que aprovechan los recursos forestales y que muestran un cierto equilibrio con otras actividades como la agricultura y la ganadería.
Zonas de pasto y gestión de marjales en balad Balansiya. Unas hipótesis para el estudio de la ganadería andalusí desde la arqueología del paisaje
Authors: Esquilache Martí Ferran
Published: September 2021

La ganadería andalusí es un tema difícil de estudiar por la falta de fuentes escritas. Sin embargo, combinando la documentación de época cristiana y análisis del paisaje se puede aportar información que permite presentar hipótesis. Este es el objetivo del presente trabajo, identificar algunas zonas de pasto en territorio valenciano y, a través de análisis paisajísticos, presentar hipótesis sobre su uso y gestión en época andalusí. En este sentido, se propone que había un movimiento del ganado local por dentro de los términos de las alquerías, buscando combinar distintos tipos de pasto –de marjal y de montaña– para complementar la dieta de los animales y no agotar los pastos. Aunque es posible que también se moviesen por los términos de las aljamas vecinas gracias a los pactos entre comunidades rurales. Además, se plantea la posibilidad de que hubiese habido trashumancia de ganado entre las montañas del interior y los marjales de la costa, basada en acuerdos tribales, especialmente entre las montañas del sistema Ibérico y los marjales de la costa valenciana. Finalmente, se identifica una privatización de los espacios comunales durante el período final andalusí, con la formación de rahales de las elites para su explotación al margen de las alquerías.