bluuebunny/crossref_metadata_2025 huggingface dataset:
Maprotiline Ameliorates High Glucose-Induced Dysfunction in Renal Glomerular Endothelial Cells
Authors: Zhou Zhihong , Liu Shangjun
Published: March 2022

Maprotiline is an antidepressant that has been found to cause hypoglycemia. However, the effect of maprotiline on diabetic nephropathy (DN) has not been investigated. Here, we explored the effect of maprotiline on human renal glomerular endothelial cells (HRGECs) in response to high glucose (HG) stimulation. We found that maprotiline attenuated HG-induced oxidative stress in HRGECs with decreased reactive oxygen species production and increased superoxide dismutase activity. Maprotiline repressed the HG-induced expression of cyclooxygenases 2 at both mRNA and protein levels in HRGECs. The increased thromboxane B2 level and decreased 6-keto-prostaglandin F1α level induced by HG were significantly attenuated by maprotiline treatment. Maprotiline also prevented the HG-induced increase in the permeability of HRGECs and the decrease in the zonula occludens-1 expression and downregulated HG-induced increase in the expression of protein kinase C-α (PKC-α) in HRGECs. This protective effect of maprotiline on HG-induced HRGECs dysfunction was abolished by overexpression of PKC-α. In conclusion, maprotiline displayed a protective effect on HG-challenged HRGECs, which was mediated by the regulation of PKC-α. These findings provide further evidence for the potential use of maprotiline for the treatment of DN.
Effects of B12 Deficiency Anemia on Radial Peripapillary and Macular Vessel Density: An Optical Coherence Tomography Angiography (OCTA) Study
Authors: Koca Semra , Bozkurt Erhan , Dogan Mustafa , Yavasoglu Filiz , Erogul Özgür , Bulut Ayten Kocaman
Published: March 2022

Background To evaluate the macular and optic disc vascular changes in vitamin B12 deficiency anemia.

Methods A total of 24 patients with vitamin B12 deficiency anemia and 24 healthy controls were involved in this study. All participants were evaluated for central macular thickness
(CMT), peripapillary retina nerve fiber layer (RNFL) thickness, foveal avascular zone (FAZ) area, macular vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus
(DCP), choriocapillaris flow area, and optic disc radial peripapillary capillary (RPC) VD using optic coherence tomography (OCT) and optic coherence tomography angiography (OCTA). Metabolic
parameters were also noted.

Results Temporal RNFL thickness significantly decreased in the B12 deficiency anemia group (p = 0.04). Choriocapillaris flow area (p = 0.045) and macular vessel density in both SCP
(p = 0.022) and DCP (p = 0.018) markedly declined in the study group. Optic disc RPC VD in the B12 deficiency anemia group was lower in all regions compared to that of the control group, but
the difference was not statistically significant (p > 0.05). There were significant positive correlations between choriocapillaris flow area, macular VD, vitamin B12, and hemoglobin.

Conclusion Retinal vascular alterations were observed in B12 deficiency anemia, and OCTA may be beneficial in the diagnosis and follow-up of ocular complications in these cases.
Eine Fallserie wacher Glaukomoperationen mittels Sub-Tenon- oder subkonjunktivaler Anästhesie bei älteren PatientInnen mit Aortenklappenstenose
Authors: Lersch Friedrich , Harte Johannes , Ugen Gesar , Kuonen Astrid
Published: March 2022

Bei zunehmender Alterung unserer Gesellschaft behandeln AnästhesistInnen und AugenchirurgInnen zusehends mehr GlaukompatientInnen, die gleichzeitig an Aortenklappenstenose (AKS) leiden. In
der chirurgischen und anästhesiologischen Therapie erfordert diese Konstellation eine anspruchsvolle gemeinsame Herangehensweise. Wir berichten über 6 Fälle von AKS-PatientInnen, die sich
einer Glaukomoperation in Sub-Tenon-Block oder subkonjunktivaler Anästhesie unterzogen haben. Dabei musste einer Patientin mit intraoperativen Schmerzen wiederholt eine subkonjunktivale
Lokalanästhesie gegeben werden. Die Patientin war anhaltend hypertensiv und es kam zu einer umschriebenen Choroidalblutung. Das komplizierte Follow-up war geprägt durch exorbitante
intraokulare Druckschwankungen und einer sekundären Choroidalblutung. Anästhesiologie und Ophthalmochirurge müssen ihre Strategie aufeinander abstimmen, um den optimalen transmuralen Druck
über die choroidalen Gefäße, aber auch den stenotischen aortalen Ausflusstrakt gewährleisten zu können. Oftmals sind den Klinikern die pathophysiologischen Kernkonzepte der Partnerdisziplin
nicht geläufig. Die Diskussion unserer Fallserie erörtert die differenzierte Herangehensweise beider beteiligter Disziplinen, Pathophysiologie der AKS und der choroidalen Blutung und
besonders jene Arbeitsschritte und therapeutischen Entscheidungen, die zur Sicherheit solcher Hochrisikopatienten gemeinsam angegangen werden müssen.
Analysis of the Thickness of the Outer Retinal Layer Using Optical Coherence Tomography – A Predictor of Visual Acuity in Schizophrenia
Authors: Bozali Erman , Yalinbas Duygu
Published: March 2022

Background The aim of this study was to evaluate the thickness of the outer retinal layer (ORL) together with macular thickness and changes in the retinal nerve fiber layer (RNFL) in
patients with schizophrenia in comparison with healthy controls.

Methods This study included 114 eyes of 57 patients diagnosed with schizophrenia and 114 eyes of 57 healthy controls. Central foveal thickness (CFT), central macular thickness (CMT),
and ORL thickness were measured in both groups via the images obtained by spectral-domain optical coherence tomography (SD-OCT). RNFL was also assessed in four quadrants (inferior, superior,
temporal, nasal). CMT measurements were presented as the average thickness of the macula in the central 1 mm area on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. The ORL
thickness was defined as the distance between the external limiting membrane and retinal pigment epithelium at the center of the foveal pit.

Results The mean age of 57 patients was 37 ± 10 years, of whom 34 (60%) were male and 23 (40%) female. No statistically significant difference was found between groups in terms of
age and gender (p = 0.8 for age, p = 0.9 for gender). There was no statistically significant difference in the mean CMT between the two groups (p = 0.1). The mean ORL thickness in the two
groups was 99.8 ± 8.3 and 103.7 ± 6.2, respectively, and was significantly decreased in the schizophrenia group (p = 0.005). RNFL analysis demonstrated significant thinning in the inferior
and superior quadrants compared to healthy controls (p < 0.001 and p = 0.017, respectively).

Conclusions SD-OCT findings – especially ORL and RNFL thickness – may be related to the neurodegenerational changes in schizophrenia.
Immuntherapie bei Brustkrebs
Authors: Würstlein Rachel , Harbeck Nadia
Published: March 2022

Während bei anderen soliden Tumoren Immuntherapie seit Jahren zum
Therapiestandard gehört, steht sie bei Brustkrebs noch ganz am Anfang.
Klinisch relevant ist sie beim triple-negativen Mammakarzinom (TNBC). Seit 2019
ist der PD-L1-Inhibitor (PD-L1: Programmed death-ligand 1) Atezolizumab als
Erstlinientherapie beim metastasierten TNBC zugelassen. Vielversprechende Daten
gibt es auch zur neoadjuvanten Therapie bei TNBC sowohl für Atezolizumab
als auch für den PD1-Inhibitor Pembrolizumab. Studien beim luminalen
frühen Mammakarzinom laufen derzeit. Eine kommentierte
Übersicht.
Ultrastructural Examination of the Corneal Interface after Predescemetic Deep Anterior Lamellar Keratoplasty (DALK) – A Case Report with Light and Transmission Electron
Microscopy
Authors: Berger Tim , Seitz Berthold , Hamon Loïc , Flockerzi Fidelis , Schlötzer-Schrehardt Ursula , Daas Loay
Published: March 2022

Purpose To examine corneal buttons with light and transmission electron microscopy (TEM) to visualize the interface area and highlight the ultrastructural corneal changes after deep
anterior lamellar keratoplasty (DALK).

Methods Two patients underwent excimer laser-assisted penetrating repeat keratoplasty after predescemetic DALK. The corneal buttons were examined by light microscopy and TEM.

Results The light microscopic examination of the corneal buttons revealed fragments of a second Descemetʼs membrane in the central and midperipheral areas (Case 1). In both cases,
visualization of the interface area was not possible by light microscopy. The donor and host stroma were tightly attached without dehiscence. TEM identified the interface area by
irregularities in the collagen distribution between the donor and host stroma. The thickness of the remaining recipient corneal stroma measured approximately 30 µm (Case 1) and 100 µm (Case
2), respectively. In the host stroma, TEM revealed the absence or degeneration of keratocytes, accumulation of amorphous material between the collagen lamellae, and vacuolar inclusions
dispersed in the stroma, forming a band-like zone anterior to Descemetʼs membrane.

Conclusion The interface area after DALK has been mainly investigated by in vivo confocal microscopy. Light microscopy and TEM findings indicate remodeling processes after
DALK that are associated with increased keratocyte degeneration and structural alterations of the extracellular matrix in the host stroma. The choice of surgical method may influence the
postoperative morphological and functional outcome since these findings were primarily apparent in the remaining host stroma. Therefore, complete exposure of Descemetʼs membrane is an
important prognostic factor for the postoperative visual outcome.
New Paradigms for Familiar Diseases: Lessons Learned on Circulatory
Bacterial Signatures in Cardiometabolic Diseases
Authors: Chakaroun Rima , Massier Lucas , Musat Niculina , Kovacs Peter
Published: March 2022

Despite the strongly accumulating evidence for microbial signatures in metabolic
tissues, including the blood, suggesting a novel paradigm for metabolic disease
development, the notion of a core blood bacterial signature in health and
disease remains a contentious concept. Recent studies clearly demonstrate that
under a strict contamination-free environment, methods such as 16 S rRNA
gene sequencing, fluorescence in-situ hybridization, transmission electron
microscopy, and several more, allied with advanced bioinformatics tools, allow
unambiguous detection and quantification of bacteria and bacterial DNA in human
tissues. Bacterial load and compositional changes in the blood have been
reported for numerous disease states, suggesting that bacteria and their
components may partially induce systemic inflammation in cardiometabolic
disease. This concept has been so far primarily based on measurements of
surrogate parameters. It is now highly desirable to translate the current
knowledge into diagnostic, prognostic, and therapeutic approaches.

This review addresses the potential clinical relevance of a blood bacterial
signature pertinent to cardiometabolic diseases and outcomes and new avenues for
translational approaches. It discusses pitfalls related to research in low
bacterial biomass while proposing mitigation strategies for future research and
application approaches.
Zwanghaftes Zweifeln als philosophisch-psychopathologisches Phänomen
Authors: Mavrogiorgou Paraskevi , Juckel Georg
Published: March 2022

Zwanghaftes Zweifeln (zZ) ist ein eher vergessenes und unterschätztes psychopathologisches Phänomen, obgleich er klinisch bei vielen Patienten mit einer Zwangsstörung vorhanden zu sein scheint. Die wenige vorhandene vor allem psychoanalytische und kognitionswissenschaftliche Literatur zum zZ erklärt das Phänomen nicht vollständig und bietet darüber hinaus nur wenig an Behandlungsperspektiven. Hier soll ein anderer Weg vorgeschlagen werden. Das dem Menschen gehörige Zweifeln an der Wahrnehmung von Objekten, Anderen und sich selbst steigert sich als zZ ins Pathologische. Zweifeln wird als ein existenzielles Problem des Menschen angesehen, das als solches zu den Grundfragen der Philosophie seit ihren Anfängen, speziell zum Skeptizismus gehört. Wenn bzgl. dieses Zweifelns Gegengründe gefunden werden könnten, würden sich für die Behandlung von Patienten mit zZ mentale Lösungsstrategien im Rahmen theoretisch vertiefter Psychotherapie einschließlich kognitiver Übungsansätze ergeben.
Synthesis of Diaza[5]helicenes by ortho,ortho′-Fusion of ortho-Terphenyls
Authors: Podlech Joachim , Herzog Stefan , Marten Inka , Weiß Aaron
Published: March 2022

Double ortho-fusion in suitably substituted ortho-terphenyls was used for the synthesis of diaza[5]helicenes. Bis(carboxamido)-substituted ortho-terphenyls can be condensed to 5,9- and 6,9-diaza[5]helicenes, where substituents at the 6,10- and 5,10-positions, respectively­, are introduced with the carboxamido groups. While a twofold­ coupling sequence with intermediate protection of one amino group has to be used for 5,9-diaza[5]helicenes, a more concise sequence avoiding the protection leads to 6,9-diaza[5]helicenes. The simple heating of ortho,ortho′-diazidoterphenyls furnishes 5,8-dihydroindolo[2,3-c]carbazoles, i.e., [5]helicenes with alternating benzene and pyrrole rings.
Diastereoselective Synthesis of Tetrahydrofurano[2,3-g]indolizidines and 8-Aminoindolizidines from l-Asparagine
Authors: Kuntiyong Punlop , Inprung Nantachai , Attanonchai Sineenart , Kheakwanwong Wichita , Bunrod Pijitra , Akkarasamiyo Sunisa
Published: March 2022

8-Aminoindolizidines were synthesized from l-asparagine as the chiral starting material. The key dibenzylamino succinimide intermediate was synthesized in two steps. Three homologs of chiral hydroxy lactams tethered with hydroxyalkenes were synthesized from the succinimide through a sequence involving N-alkylation, cross-olefin metathesis, and hydride reduction. The dibenzylamino group gave stereocontrol of the key N-acyliminium ion cyclization of these hydroxy lactams. 5-Substituted aminoindolizidines were synthesized with high diastereoselectivity at C6. A tandem cyclization of an N-(6-hydroxyhex-3-en-1-yl) γ-hydroxy lactam resulted in the formation of a tetrahydrofurano[2,3-g]indolizidine system.
Stereoselective Synthesis and Applications of Pinane-Based Chiral 1,4-Amino Alcohol Derivatives
Authors: Szakonyi Zsolt , Raji Mounir , Le Tam Minh , Csámpai Antal , Nagy Viktória , Zupkó István
Published: March 2022

A new library of pinane-based 1,4-amino alcohols was synthesised and utilised as chiral ligands in enantioselective diethylzinc addition to benzaldehyde. Aldol condensation of (+)-nopinone, derived from (–)-β-pinene, with 2-pyridinecarboxaldehyde gave the key intermediate α,β-unsaturated ketone, which was transformed in diastereoselective reduction, followed by hydrogenation, resulting in 1,4-amino alcohols. On the other hand, epoxidation of the α,β-unsaturated ketone, followed by reduction and then hydrogenation of the pyridine ring, afforded a mixture of 4-amino-2,3-epoxy-1-ols. Stereoselective hydride reduction of the epoxy ketone and subsequent condensation of the resulting products with substituted benzyl bromides provided quaternary ammonium salts, which were subjected to hydride reduction and then hydrogenation, affording 4-amino-2,3-epoxy-1-ol derivatives containing an N-benzylpiperidine moiety. The inhibition of nucleophile-initiated opening of the oxirane ring was interpreted by a systematic series­ of comparative Hartree–Fock modelling study using the 6-31+G(d,p) basis set. The antiproliferative activities of 4-amino-2,3-epoxy­-1-ol derivatives were examined, and structure–activity relationships were studied from the aspects of the stereochemistry of the oxirane ring, saturation, and substituent effects on the piperidine ring system.
Limiting lithium dendrite growth for performance, safety improvements in batteries
Authors: Ikenson Ben
Published: March 2022

Fabric-based 3D Janus anode structure may enhance next generation of flexible, wearable electronics
Geographical variability of summer- and winter-dominant onshore wind
Authors: Mahmud Zabir , Shiraishi Kenji , Abido Mahmoud Y. , Millstein Dev , Sánchez-Pérez Pedro A. , Kurtz Sarah
Published: March 2022

For each geographical region, one of the biggest challenges in reaching a zero-carbon grid is identifying sources of electricity that match the seasonal profile of the load. Summer-dominant solar electricity generation can often be balanced by winter-dominant wind electricity generation. Together with long-duration storage, balanced solar and wind generation are well positioned to provide reliable renewable electricity. However, in some locations the wind may not complement solar energy so well. For example, currently California's wind turbines produce more electricity during summer than winter, raising the question of whether all future wind plants in California will exhibit the same seasonality. As a response to this question, in this paper, we analyzed the generation from existing California wind plants and simulated potential onshore wind resource for the whole state using a metric that reflects the relative wind resource in winter. Our results indicate that the seasonality of the wind can vary for very small spatial difference with more than half of California showing stronger wind resource in the winter compared with the summer despite the current observation of the opposite trend. This study differentiates the seasonality of potential wind resources to inform the creation of a reliable, 100%-renewable-driven grid.
Hydrodynamic equations for the Ablowitz–Ladik discretization of the nonlinear Schrödinger equation
Authors: Spohn Herbert
Published: March 2022

Ablowitz and Ladik discovered a discretization that preserves the integrability of the nonlinear Schrödinger equation in one dimension. We compute the generalized free energy of this model and determine the generalized Gibbs ensemble averaged fields and their currents. They are linked to the mean-field circular unitary matrix ensemble. The resulting hydrodynamic equations follow the pattern already known from other integrable many-body systems. The discretized modified Korteweg–de-Vries equation is also studied, which turns out to be related to the beta Jacobi log gas.
Variational Ansatz preparation to avoid CNOT-gates on noisy quantum devices for combinatorial optimizations
Authors: Miki Tsukasa , Okita Ryo , Shimada Moe , Tsukayama Daisuke , Shirakashi Jun-ichi
Published: March 2022

The variational quantum eigensolver (VQE), which is a quantum–classical hybrid approach, has latent powers to leverage near-term quantum devices by effectively managing a limited number of qubits with finite coherent lifetimes. While it is generally argued that the quantum approximate optimization algorithm (QAOA), which is a special case of VQE with a variational Ansatz based on the adiabatic theorem, may enable practical applications of noisy quantum devices for classical combinatorial optimizations, the strategy to improve the performance of this algorithm by increasing the circuit depth conflicts with the limited coherence time of near-term quantum devices. Here, we introduce strategies involving the VQE to reduce the circuit resources required for solving combinatorial optimizations. Our concept of a parameterized quantum circuit allows the Ansatz preparation to be achieved by only single-qubit operation. We find that the variational Ansatz without controlled X-gates leads to quick convergence in a classical subroutine used to determine the variational parameters. In addition, the variational Ansatz with optimized parameters maintains performance over the problem sizes both on the numerical simulation and IBM 27-qubit processor “ibm_kawasaki.” Therefore, the variational Ansatz introduced in this study has several advantages considering the total calculation time and performance scaling over the problem sizes. We also show that the variational Ansatz consisting of a lower number of gate operations than that of QAOA can approximate the eigenstates of diagonal Hamiltonians with high accuracy. We illustrate our ideas with a maximum-cut problem and show that near-term quantum applications may be feasible using short-depth circuits.
Analysis of the nonlinear dynamics of a chirping-frequency Alfvén mode in a tokamak equilibrium
Authors: Wang X. , Briguglio S. , Di Troia C. , Falessi M. , Fogaccia G. , Fusco V. , Vlad G. , Zonca F.
Published: March 2022

Chirping Alfvén modes are considered as potentially harmful for the confinement of energetic particles in burning tokamak plasmas. In fact, by changing their frequency, they are able to extract as much power as possible from these particles, possibly increasing their transport. In this paper, the nonlinear evolution of a single-toroidal-number chirping mode is analyzed by numerical particle simulation. The relevant resonant structures are identified by numerical techniques based on the use of a coordinate system including two constants of motion: the magnetic moment and a suitable function of the initial particle coordinates. The analysis is focused on the dynamics of two different resonant structures in the particle phase space: those yielding the largest drive during the linear and the nonlinear phase, respectively. It is shown that, for each resonant structure, a density-flattening region is formed around the respective resonance radius, with a radial width that increases as the mode amplitude grows. It is delimited by two steepened negative density gradients, drifting inwards and outward. If the mode frequency were constant, phase-space density flattening would quench the resonant-structure drive as the steepened gradients leave the original resonance region. The frequency chirping, however, causes the resonance radius and the resonance region to drift inwards. This drift, along with a relevant increase in the resonance width, delays the moment in which the inner density gradient reaches the inner boundary of the resonance region, leaving it. On the other hand, the island evolves consistently with the resonance radius; as a consequence, the steepened density gradient further moves inward. This process continues as long as it allows to keep the steepened gradient within the resonance region. When this is no longer possible, the resonant structure ceases to be effective in driving the mode. To further extract energy from the particles, the mode has to tap a different resonant structure, possibly making use of additional frequency variations.
Slow–fast oscillatory dynamics and phantom attractors in stochastic modeling of biochemical reactions
Authors: Bashkirtseva Irina , Ryashko Lev
Published: March 2022

A problem of the probabilistic analysis of stochastic phenomena in slow–fast dynamical systems modeling biochemical reactions is considered. We study how multiplicative noise induces systematic shifts of probabilistic distributions and forms “phantom” attractors in nonlinear enzymatic models. The mathematical analysis of the underlying probabilistic mechanism of such stochastic transformations is performed by the “freeze-and-average” method. Our theoretical results are supported by direct numerical simulation.
Sn composition graded GeSn photodetectors on Si substrate with cutoff wavelength of 3.3 μm for mid-infrared Si photonics
Authors: Li Mingming , Zheng Jun , Liu Xiangquan , Zhu Yupeng , Niu Chaoqun , Pang Yaqing , Liu Zhi , Zuo Yuhua , Cheng Buwen
Published: March 2022

The Sn composition graded GeSn layer with Sn content increased from 11% to 14.3% was grown on a Si substrate by molecular beam epitaxy. The structural properties of the GeSn layer are investigated, and the film is gradually relaxed along the thickness, reaching approximately 71.6%. The GeSn p–i–n detectors were fabricated by using a complementary metal oxide semiconductor compatible process. The GeSn detectors demonstrated a cutoff wavelength of approximately 3.3 μm at room temperature with a dark current of 0.3 A/cm2 @ -1 V. At a wavelength of 2000 nm, the GeSn detectors had a responsivity of 110 mA/W and -3 dB bandwidth (f3 dB) about 3 GHz. These results suggest that high Sn content relax GeSn can be grown by MBE and paves the way toward the feasibility of mid-infrared GeSn photonics.
Accuracy of some useful closure relations in combination with the reference interaction site model theory for fluids of single component diatomic molecules
Authors: Miyata Tatsuhiko , Murata Shohei , Sakamoto Megumi , Sasaki Yasushi
Published: March 2022

We examined the accuracy of the reference interaction site model theory in terms of the thermodynamics of fluids consisting of single-component diatomic molecules, where we evaluated the internal energy, pressure, and isothermal compressibility. Two routes were tested for pressure. One is the differentiation of the Helmholtz free energy with respect to the density, and the other is the virial formula. We focused on hypernetted chain (HNC), Kovalenko–Hirata (KH), and Kobryn–Gusarov–Kovalenko (KGK) closure approximations. The most accurate closure relationship among the three is the KGK closure. The HNC and KH closures tend to overestimate the internal energy and pressure from the density derivative of the Helmholtz free energy. Moreover, it was found that the HNC closure significantly overestimated the isothermal compressibility, particularly at low density, or for molecular models with short bond lengths. The applicability of the sigma enlarging bridge (SEB) correction was also tested. After applying the SEB correction to the KH (SEB-KH) closure, a significant improvement was observed in the internal energy even for the model including the Coulomb potential.
Wave reversal mode in permalloy wire-tube nanostructures
Authors: Arciniegas Jaimes Diana M. , Broens Martín I. , Saavedra Eduardo , Luna Noelia Bajales , Escrig Juan
Published: March 2022

We have investigated hysteresis curves and magnetization reversal mechanisms in permalloy wire-tube nanostructures when an external magnetic field is applied perpendicular to the axis of the nanostructure, in the x direction. Our results show that the nanotube reverses its magnetization through the wave reversal mechanism, while the nanowire does so through pseudo-coherent rotation, according to the literature. The wire-tube nanostructure exhibits a more complex reversal mechanism, where each segment begins to revert depending on whether it is a wire or tube segment, but quickly the entire nanostructure adopts the wire segment reversal mechanism as its own, considerably reducing the area within of the hysteresis curve exhibited by the nanostructure. The possibility to alter the magnetization reversal mode in such nanostructures provides an attractive way to control the motion of the magnetic domain walls.
Ballooning satellite populations in low Earth orbit portend changes for science and society
Authors: Feder Toni
Published: March 2022

Technological advances and business incentives far outpace space regulations.
Bevacizumab for blinding eye disease – is it time for the PBS to list for off-label use?
Authors: Heyworth Peter
Published: March 2022

Anti-vascular endothelial growth factor eye injections have become the most accepted and effective treatment for some of the leading causes of blindness. Aflibercept (Eylea; Bayer) is the most expensive item on the Pharmaceutical Benefits Scheme, (PBS) with ranibizumab (Lucentis; Roche/Novartis) ranked eighth. In 2011 the pharmaceutical cost for these treatments was A$237 million – now the figure is A$665 million and climbing. Bevacizumab (Avastin; Roche) is part of the original molecular lineage for a group of biologic agents, which were originally designed for cancer therapy. It is now administered worldwide on an off-label basis and in very large numbers for retinal vascular disease. It has a proven efficacy and safety profile. Bevacizumab is thirty times cheaper than the Therapeutic Goods Administration (TGA)-approved alternatives and its use could reduce PBS costs by hundreds of millions of dollars. Should the TGA be the sole arbiter in the approval of drugs, or should alternative bodies have some say in the approval of off-label usage under such compelling circumstances? Legislation for this approach has been approved in France, the UK, and Italy. Only by eliminating the legal risk to authorising bodies and physicians, and the financial disincentive to the patient associated with off-label use, will drugs such as bevacizumab be more widely adopted.
Seed functional traits in cultivars of tall fescue (
Authors: Riveira Rubin Mailen A. , Ueno Andrea C. , Batlla Diego , Iannone Leopoldo J. , Martínez-Ghersa María A. , Gundel Pedro E.
Published: March 2022

Context Tall fescue (Schedonorus arundinaceus) is one of the most important cultivated forage grasses in temperate regions but its association with some Epichloë fungal endophytes usually makes it unsuitable for livestock feeding due to toxic alkaloids. However, re-inoculation of plants with non-toxic endophytes can result in positive effects for livestock feeding. Aims Assess the effects of the non-toxic AR584 endophyte on seed viability and germination in two tall fescue cultivars. Methods The effects of AR584 endophyte (presence/absence) and tall fescue cultivar (INIA Aurora/Taita) were evaluated on seed viability and germination responses across a range of temperature and water availability regimes. Response to constant temperature and water availability was characterised by the thermal-time and hydro-time models, respectively. Key results Under accelerated aging conditions, endophyte presence reduced seed viability in cultivar Taita. For both cultivars, endophyte-infected seeds showed a lower germination rate than endophyte-free seeds, except for INIA Aurora under low incubation temperatures. Also, endophyte-infected seeds in both cultivars displayed lower germination rates and final germination as the water potential was lowered. Conclusions A strong cultivar-by-endophyte interaction for seed germination indicates the need to understand how specific cultivar-endophyte combinations best fit a given environmental condition, as defined by temperature and water availability. Implications The information we present can be valuable not only for farmers who have to decide what to cultivate but also for seed companies that have to preserve seed quality.
Prediction-error neurons in circuits with multiple neuron types: Formation, refinement, and functional implications
Authors: Hertäg Loreen , Clopath Claudia
Published: March 2022

Significance

An influential idea in neuroscience is that neural circuits do not only passively process sensory information but rather actively compare them with predictions thereof. A core element of this comparison is prediction-error neurons, the activity of which only changes upon mismatches between actual and predicted sensory stimuli. While it has been shown that these prediction-error neurons come in different variants, it is largely unresolved how they are simultaneously formed and shaped by highly interconnected neural networks. By using a computational model, we study the circuit-level mechanisms that give rise to different variants of prediction-error neurons. Our results shed light on the formation, refinement, and robustness of prediction-error circuits, an important step toward a better understanding of predictive processing.
A vasculature niche orchestrates stromal cell phenotype through PDGF signaling: Importance in human fibrotic disease
Authors: Layton Thomas B. , Williams Lynn , Yang Nan , Zhang Mingjun , Lee Carl , Feldmann Marc , Trujillo Glenda , Furniss Dominic , Nanchahal Jagdeep
Published: March 2022

Significance

Tissue fibrotic diseases, for example of the liver and lung, represent a huge unmet medical need. In this study, using single-cell RNA sequencing, cytometry by time of flight (CyTOF), tissue imaging, and functional assays, we identify a complex vascular niche in Dupuytren’s disease (DD), a common localized fibrotic condition of the palm, where early-disease-stage tissue can be accessed readily. We uncover a population of myofibroblast precursors within the pericyte compartment and demonstrate that the endothelium instructs the differentiation of functionally distinct stromal cells, thereby orchestrating discrete microenvironments in the fibrotic milieu. Together, these findings provide a basis for the concept of targeting blood vessel signaling to control the progression of human fibrosis.
The vitality of Angolar
Authors: Bouchard Marie-Eve
Published: March 2022

This article examines Santomeans’ attitudes toward Angolares, a minority creole-speaking community descendant of
maroons on São Tomé Island, and their language. The status of Angolar varies from vigorous to shifting, depending on the source,
and according to Maurer (2013), it is unclear whether Angolar is being passed on to new
generations. In this article, it is argued that Angolares are shifting toward Portuguese, a process that has already commenced
among Santomeans living in the capital. Since prevailing attitudes regarding a language are important for its use and maintenance,
this study investigates the transmission of attitudes, beliefs and stereotypes as a possible explanation for the actual shift
toward Portuguese in the country. Based on ethnography, analysis of interview excerpts, and questionnaires, an account of the
attitudes held by Santomeans is provided, showing how different attitudes toward Angolares are intertwined and point toward rural,
creole-speaking Angolares as being the lowest on the social scale of the island. This article demonstrates how attitudes held by
Forros, the dominant ethnolinguistic group on São Tomé Island, as well as by Angolares themselves, may negatively impact the
maintenance of Angolar Creole.
The presence of animals in Jaume Roig’s Espill (1460)
Authors: Llorca Francesc , Martín Llúcia
Published: March 2022

The subject of this study is the use of animals in Jaume Roig’s Espill, a lengthy discourse on the dangers of love, written in Catalan in about 1460. The author presents a fictional autobiographical story in tetrasyllabic verses in which the main character details his negative experiences with women and encourages a life devoted to contemplation and chastity after having received a lesson from King Solomon in a dream. The antifeminine speech in Espill is presented in short verses and uses satire to exaggerate the deceptiveness of female behaviour. Animal symbolism plays an important role, as women’s negative behaviours are compared with animals often associated with negative characteristics. The traits that bestiaries conferred on each animal are appropriate to antifeminine discourse, and many of the species are mentioned using the female gender. The animals that appear in Espill are not only symbolic but are also taken from daily life and include those used in gastronomy, medicine, and cosmetics. This demonstrates the author’s remarkable familiarity with the environment of the Kingdom of Valencia.
L’animal est proverbial
Authors: Marangoni Alessandra
Published: March 2022

Dans un cadre culturel solidement fondé sur l’imitation de la tradition, que rend pourtant mouvant une langue en évolution rapide, le texte de Guillaume Haudent constitue à la fois un document du savoir ésopique à l’époque humaniste et une expression de la volonté divulgatrice qui règle un tel bagage de connaissances exemplaires. Mettre en langue vulgaire, et donc à la portée d’un public plus vaste, une production ésopique qui circule en latin parmi les savants, signifie l’illustrer à travers des vignettes, multiplier ses enseignements moraux et en venir à prouver la parenté qui existe entre fable et proverbe. Le moyen français, dans sa variété normande, est partie intégrante de ce long et patient travail de popularisation de la fable, moyennant un vers décasyllabique ou octosyllabique qui accompagne de son rythme monotone une vaste entreprise didactique née en marge du circuit libraire parisien-lyonnais.
The expansion of capitalist agricultural production and social reproduction of rural labour: contradictions within the logic of capital accumulation in Mozambique
Authors: Muianga Carlos
Published: March 2022

In Mozambique, policy discourses supporting the expansion of large-scale capitalist agriculture have largely focused on its potential to increase agricultural production and productivity. In particular, they have highlighted the potential contribution to rural employment and income, and their impacts on poverty reduction. Yet in focusing narrowly on these dynamics, they have ignored the contradictions of social reproduction of labour often associated with the expansion of capitalist production. This paper explores these contradictions by considering primary and secondary evidence from two contexts of expansion of large-scale capitalist agriculture in Mozambique. It argues that these contradictions have manifested in diverse forms, reflecting the extent to which forms of expansion and (re)organisation of sectors of capitalist agricultural production, and the associated forms of labour exploitation, have affected different spheres of social reproduction of labour in these contexts. Moreover, the paper suggests, they have reproduced more broadly, as the expansion/intensification of the extractive logic of accumulation has compromised ‘alternative’ spaces of social reproduction.
Financialisation, narrow specialisation of production and capital accumulation in Mozambique
Authors: Castel-Branco Carlos Nuno , Maia Diogo
Published: March 2022

The article argues that the historical conditions under which national capitalism developed in post-independence Mozambique pushed the economy towards growing financialisation and narrower specialisation of production around increasingly basic and simple activities. In post-independence Mozambique, national capitalism rose from the ashes of state-centred accumulation built around the dominant social structures of production inherited from colonialism, under the impulse of neoliberal economic reforms and heavy dependency on inflows of private international finance. The speculative dynamics of accumulation prevented diversification and more complex industrialisation which, in turn, reinforced the role of financialisation as a means to and form of accumulation of capital. The paper argues that changing these dynamics of accumulation requires conscious industrial strategies focused on diversification and articulation of production, which cannot be achieved without challenging the extractive mode of accumulation and the power relationships associated with it.
Class, politics and dynamic accumulation processes around the Sino-Mozambican rice project in the lower Limpopo, 2005–2014
Authors: Ganho Ana Sofia
Published: March 2022

This study levels an international political economy lens at the development of the Sino-Mozambican rice project in the lower Limpopo, by examining how class relations shaped and were shaped by global trends, Chinese resources and Mozambican dynamic accumulation interests. The Sino-Mozambican rice project (2005–2014) is analysed as three projects benefiting different groups, with a focus on producer selection and allocation of means of production, in dialogue with the historical dynamics of agrarian accumulation and the political economy of Mozambique. The paper argues that the project has served the expansionist interests of the ruling capitalist group associated with central government circles, limiting land-based possibilities at province level. In addition, the plan to locally transform small producers into rural capitalists through ‘modern’ Chinese methods has failed to confront the historical interdependence of the commercial and so-called family sectors and the diversity of livelihood sources for the reproduction of food and labour.
Human autoantibodies underlying infectious diseases
Authors: Puel Anne , Bastard Paul , Bustamante Jacinta , Casanova Jean-Laurent
Published: March 2022

The vast interindividual clinical variability observed in any microbial infection—ranging from silent infection to lethal disease—is increasingly being explained by human genetic and immunological determinants. Autoantibodies neutralizing specific cytokines underlie the same infectious diseases as inborn errors of the corresponding cytokine or response pathway. Autoantibodies against type I IFNs underlie COVID-19 pneumonia and adverse reactions to the live attenuated yellow fever virus vaccine. Autoantibodies against type II IFN underlie severe disease caused by environmental or tuberculous mycobacteria, and other intra-macrophagic microbes. Autoantibodies against IL-17A/F and IL-6 are less common and underlie mucocutaneous candidiasis and staphylococcal diseases, respectively. Inborn errors of and autoantibodies against GM-CSF underlie pulmonary alveolar proteinosis; associated infections are less well characterized. In individual patients, autoantibodies against cytokines preexist infection with the pathogen concerned and underlie the infectious disease. Human antibody-driven autoimmunity can interfere with cytokines that are essential for protective immunity to specific infectious agents but that are otherwise redundant, thereby underlying specific infectious diseases.
Preparation of colloidal nanoparticles PVA-PHEMA from hydrolysis of copolymers of PVAc-PHEMA as anticancer drug carriers
Authors: Shahrousvand Mohsen , Hajikhani Mohsen , Nazari Leila , Aghelinejad Amitis , Shahrousvand Mohammad , Irani Mohammad , Rostami Amir
Published: March 2022

The novel pH-responsive polymer nanoparticles have been widely used for drug delivery and cancer therapy. The pH-sensitive nanoparticles include chemical structures that can accept or donate protons in response to an environmental pH change. Polybases which mostly contain alkaline groups such as amines and hydroxy, accept protons at low pH and are neutral at higher pH values. This study aimed to prepare pH-sensitive colloidal amphiphilic poly(vinyl alcohol-2-hydroxyethyl methacrylate) (PVA-PHEMA) copolymers in cancer therapy applications. For this purpose, poly(vinyl acetate-2-hydroxyethyl methacrylate) (PVAc-PHEMA) copolymer nanoparticles were synthesized in different polymerization medium fractions from water and methanol and different monomer feed concentration. Then acetate groups were hydrolyzed, and the PHEMA-PVA nanoparticles were synthesized. The nanoparticles were further characterized using dynamic light scattering, Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis to identify the structural and morphological changes. The Methotrexate (MTX) was loaded into the nanoparticles, and drug release kinetics were evaluated. The results confirmed that PHEMA-PVA copolymeric nanoparticles could be favorably used in cancer therapy.
Foundations of plasmas for medical applications
Authors: von Woedtke T , Laroussi M , Gherardi M
Published: March 2022

Plasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids like water or physiological saline by a CAP source is performed in order to study specific biological activities. A basic understanding of the interaction between plasma and liquids and bio-interfaces is essential to follow biological plasma effects. Charged species, metastable species, and other atomic and molecular reactive species first produced in the main plasma ignition are transported to the discharge afterglow to finally be exposed to the biological targets. Contact with these liquid-dominated bio-interfaces generates other secondary reactive oxygen and nitrogen species (ROS, RNS). Both ROS and RNS possess strong oxidative properties and can trigger redox-related signalling pathways in cells and tissue, leading to various impacts of therapeutic relevance. Dependent on the intensity of plasma exposure, redox balance in cells can be influenced in a way that oxidative eustress leads to stimulation of cellular processes or oxidative distress leads to cell death. Currently, clinical CAP application is realized mainly in wound healing. The use of plasma in cancer treatment (i.e. plasma oncology) is a currently emerging field of research. Future perspectives and challenges in plasma medicine are mainly directed towards the control and optimization of CAP devices, to broaden and establish its medical applications, and to open up new plasma-based therapies in medicine.
Threshold-voltage bias-instability in SiC MOSFETs: effects of stress temperature and level on oxide charge buildup and recovery
Authors: Ghosh Amartya K , Hao Jifa , Cook Michael , Suliman Samia A , Wang Xinyu , Awadelkarim Osama O
Published: March 2022

In this study we performed slow and fast bias temperature instability (BTI) measurements on n-channel silicon carbide (SiC) metal-oxide-SiC field effect transistors. Threshold voltage (V
th) shifts as well as recovery observed during and after stress applied at different temperatures and stress levels were used to understand the dynamics of charge trapping/capture and detrapping/emission at gate oxide defects. It is deduced from the results that no new defects are created by the stress at the levels used in this study and V
th shifts are due to the injected electron capture and trapping at existing oxide border traps. Positive gate-voltage BTI induced V
th shift is observed to follow a power law on stress time with an exponent, n, dependent on stress temperature and level, such that 0.03 ⩽ n ⩽ 0.09. Electron emission and/or defect interactions are found to proceed with a low activation energy of the order of 0.01 eV and are suggested to be responsible for oxide charge reduction and, consequently, V
th recovery.
Improving the reliability of MOS capacitor on 4H-SiC (0001) with phosphorus diffused polysilicon gate
Authors: Wan Caiping , Zhang Yuanhao , Lu Wenhao , Ge Niannian , Ye Tianchun , Xu Hengyu
Published: March 2022

The interface states and reliability of 4H-SiC metal-oxide-semiconductor field effect transistors (MOSFETs) with thermal gate oxides have been researched widely. Several reports have researched the gate oxide process itself, but the effects of subsequent processes should not be ignored. In this paper, the reliability of thermal gate oxide films followed by polysilicon gate (poly-gate) process, which are widely used in MOSFET manufacture, and Al gates were compared. The poly-gate samples markedly affected the performance measured by time-zero dielectric breakdown and time-dependent dielectric breakdown methods because the phosphorus content diffused during poly-gate formatting; this was especially advantageous in reducing leakage current and improving the charge-to-breakdown (Q
BD). After electronic characteristics measurements, scanning electron microscopy cross-sections were also used to analyze the breakdown mechanism. We observed an intermediate layer between the Al gate and the oxide that may cause the barrier height to be smaller than that of the poly-gate. The Al work function and polysilicon Fermi level determine the gate leakage currents and the resultant gate oxide reliability, whereas the Al2O3 gate sample has a smaller work function offset (0.7 eV) than ideal Al gate and poly-gate samples. The results imply that the reliability of the Al gate samples may be an intrinsic problem.