bluuebunny/crossref_metadata_2025 huggingface dataset:
Polypharmacological repurposing approach identifies approved drugs as potential inhibitors of Mycobacterium tuberculosis
Authors: Singh Jasdeep , Quadir Neha , Vashishtha Shubham , Chakraborty Ankan , Alam Anwar , Kundu Bishwajit , Ahmad Uzair , Sundar Durai , Ehtesham Nasreen Z. , Hasnain Seyed E.
Published: June 2023

Mycobacterium tuberculosis (M. tb), the causative pathogen of tuberculosis (TB) remains the leading cause of death from single infectious agent. Furthermore, its evolution to multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains necessitate de novo identification of drug-targets/candidates or to repurpose existing drugs against known targets through drug repurposing. Repurposing of drugs has gained traction recently where orphan drugs are exploited for new indications. In the current study, we have combined drug repurposing with polypharmacological targeting approach to modulate structure–function of multiple proteins in M. tb. Based on previously established essentiality of genes in M. tb, four proteins implicated in acceleration of protein folding (PpiB), chaperone assisted protein folding (MoxR1), microbial replication (RipA) and host immune modulation (S-adenosyl dependent methyltransferase, sMTase) were selected. Genetic diversity analyses in target proteins showed accumulation of mutations outside respective substrate/drug binding sites. Using a composite receptor-template based screening method followed by molecular dynamics simulations, we have identified potential candidates from FDA approved drugs database; Anidulafungin (anti-fungal), Azilsartan (anti-hypertensive) and Degarelix (anti-cancer). Isothermal titration calorimetric analyses showed that the drugs can bind with high affinity to target proteins and interfere with known protein–protein interaction of MoxR1 and RipA. Cell based inhibitory assays of these drugs against M. tb (H37Ra) culture indicates their potential to interfere with pathogen growth and replication. Topographic assessment of drug-treated bacteria showed induction of morphological aberrations in M. tb. The approved candidates may also serve as scaffolds for optimization to future anti-mycobacterial agents which can target MDR strains of M. tb.
GastroNet: A robust attention‐based deep learning and cosine similarity feature selection framework for gastrointestinal disease classification from endoscopic images
Authors: Noor Muhammad Nouman , Nazir Muhammad , Ashraf Imran , Almujally Nouf Abdullah , Aslam Muhammad , Fizzah Jilani Syeda
Published: June 2023

Diseases of the Gastrointestinal (GI) tract significantly affect the quality of human life and have a high fatality rate. Accurate diagnosis of GI diseases plays a pivotal role in healthcare systems. However, processing large amounts of medical image data can be challenging for radiologists and other medical professionals, increasing the risk of inaccurate medical assessments. Computer‐aided Diagnosis systems provide help to doctors for rapid and accurate diagnosis, thus resulting in saving lives. Recently, many techniques are found in the literature that uses deep Convolutional Neural Network (CNN) models for accurate disease classification. However, they have limitations in their ability to detect deformation‐invariant features and lack robustness. The diseased region is highlighted, using attention‐based image generation and superimposition with original images. A lightweight deep CNN model is employed to get significant features. These features are further reduced using a Cosine similarity‐based technique. The proposed framework is assessed using the Kvasir dataset. To verify the effectiveness of the proposed framework, vast experiments are conducted. The overall accuracy of 97.68%, 99.02% precision, 96.37% recall, and an F‐measure of 97.68% are achieved using the 810 significant features. This reduction in features resulted in a significant reduction in classification time. The robustness of the framework can be observed not only in terms of considerable improvement in accuracy, but also in terms of precision as well as recall, and F‐measure.
A graphical technique of controller design and selection of lower and upper bounds in controller design using optimization techniques
Authors: Ahamad Nafees , Chhetri Abhay , Saklani Mayank , Bajaj Mohit , Kotb Hossam , Khan Baseem , Sikander Afzal
Published: June 2023

The regulation and stabilization of a system's output to achieve desired performance and ensure system reliability require the use of different controllers, but selecting appropriate control parameters presents a challenge in ensuring robustness and stability. Proportional–integral–derivative (PID) controllers are popularly used due to their simplicity and effectiveness in addressing these challenges. In this paper, a simple, effective, and efficient, novel graphical technique is proposed to design PID and its variants (PI/PD) controllers, which addresses the challenges in selecting appropriate control parameters. The method involves creating three equispaced vectors for controller parameters , and obtaining a 3D (2D in PI/PD) Cartesian grid of these vectors. All nodes in the grid provide several possible controllers, and integral time squared error (ITSE) is calculated for each controller from the closed‐loop step response of the system. The obtained ITSE is plotted in a 4D (PID) or 3D (PI/PD) graph, and controller parameters corresponding to the minimum value of ITSE are identified. Furthermore, the proposed graphical technique aids in choosing the lower and upper bounds (LB and UB) if the controller is designed using optimization techniques. The better selection of LB and UB reduces the search space resulting in lesser execution time and fewer iterations. To validate the proposed graphical technique, we designed various controllers for widely‐used brush‐less DC and switch reluctance motors in electric vehicles. Additionally, by choosing the LB and UB with the proposed technique, controllers are also designed using three optimization techniques: particle swarm optimization, black widow optimization algorithm, and honey badger algorithm. The obtained controllers using the graphical technique outperformed the optimization techniques in terms of time and frequency domain specifications, and the proposed selection of lower and upper bounds resulted in improved performance in terms of iterations and execution time.
Sexueller Missbrauch von Minderjährigen
Authors: John Anne-Christin
Published: June 2023

Wenn Kinder oder Jugendliche sexuell missbraucht werden, leiden sie meist ihr Leben lang unter den psychischen Folgen. Da die Symptome und Auswirkungen bei jedem Minderjährigen unterschiedlich sein können, müssen Behandlungsansätze individuell angepasst werden. Welche psychischen Konsequenzen ein sexueller Missbrauch haben kann und wie sie mithilfe der Strukturierten Trauma-Intervention therapiert werden können, schildert unsere Autorin.
Pflege von Patienten mit Thoraxdrainagen
Authors: Wiegmann Katharina
Published: June 2023

Wartezeiten zum Lernen nutzen – das ist die Idee der One Minute Wonder. Wir stellen in loser Reihe OMWs zu verschiedenen Themen vor.
Prähabilitative Bewegungstherapie bei
Mammakarzinom
Authors: Neudecker Julia , Asselborn Jana , Behrens Joshua , Jauernig Lars , Baumann Freerk T.
Published: June 2023

Während in den 1970er-Jahren noch körperliche Aktivität
als supportive Therapie in der Onkologie kritisiert und abgelehnt wurde,
gewannen bewegungstherapeutische Interventionen seit den 1990er-Jahren immer
mehr an Bedeutung [3, 9]. Nachdem die Wirksamkeit rehabilitativer
Bewegungsprogramme in der Nachsorge wie auch während der Akuttherapie in
zahlreichen Studien bestätigt wurde, zeigten erste
prähabilitative, bewegungstherapeutische Interventionen positive
Einflüsse auf den postoperativen Genesungsprozess. Dabei werden
Bewegungsprogramme im Zeitraum zwischen der Krebsdiagnose und der operativen
Therapie durchgeführt [15].

Dieses Potenzial zeigt sich auch bei der prähabilitativen
Bewegungstherapie eines Mammakarzinoms. Körperliche Aktivität
ist während einer neoadjuvanten Chemotherapie unter moderater bis
intensiver Belastungsintensität machbar und sicher. Zudem können
sowohl Wundheilungsstörungen und Bewegungsmangelsymptome reduziert, die
körperliche Leistungsfähigkeit und die psychische Verfassung
verbessert sowie eine bewegungsspezifische Gesundheitskompetenz erlangt werden.
Die Anzahl der Krankenhaustage verringern sich, und die Kosten für die
Krankenkasse können gesenkt werden [16].

Trotz der Relevanz dieses neuen Forschungsfeldes werden prähabilitative
Interventionen bei einem Mammakarzinom hauptsächlich durch einzelne
wissenschaftliche Projekte durchgeführt. Es bedarf weiterer
randomisierter, kontrollierter Studien, um die Wirksamkeit der
prähabilitativen Sport- und Bewegungstherapie zu prüfen und
deren Stellenwert für eine Mammakarzinomerkrankung aufzuzeigen.
The Association of Physical Activity Level with Body Awareness and
Balance in Individuals with Ankylosing Spondylitis
Authors: Buke Meryem , Cetisli-Korkmaz Nilufer , Basakci-Calik Bilge , Karasu Ugur
Published: June 2023

Background This study aimed to examine the association of physical
activity level with body awareness and balance in individuals with ankylosing
spondylitis (AS). In addition, the effects of disease-specific parameters on
static and dynamic balance functions were investigated.

Material and Methods Sixty-four volunteers (36 female, 28 male) were
included. AS disease activity, functional level, and spinal mobility were
evaluated with disease-specific indexes. Physical activity level was assessed
with the International Physical Activity Questionnaire, body awareness with the
Body Awareness Questionnaire, static balance with the Single Leg Stance Test,
and dynamic balance with the Timed Up and Go Test and the Four Square Step
Test.

Results There was a relationship between physical activity level and body
awareness (p<0.05), but no correlation was found with the
disease-specific assessments and balance measurements (p>0.05). While
BASFI was found to be significantly associated with both static and dynamic
balance, it was noted that BASMI was just related with FSST (p<0.05),
and BASDAI was not correlated with any balance test (p>0.05).

Conclusion As a result of our study, we observed that physical activity
level was associated with body awareness, but not with balance. Also, it was
recorded that the functional status of individuals with AS is closely related
with static and dynamic balance and dynamic balance is partially influenced by
spinal mobility.
Antibiotics Use and Its Effects on the Establishment of Feeding Tolerance in Preterm Neonates
Authors: Singh Neel K. , Will Lester , Al-Mulaabed Sharef , Ruoss Lauren , li Nan , de La Cruz Diomel , Gurka Matthew , Neu Josef
Published: June 2023

Objective Antibiotics are one of the most widely used medications in today's neonatal intensive care units. Indiscriminate antibiotic usage persists in preterm newborns who are symptomatic due to factors linked to prematurity rather than being septic. Previous studies in older infants suggest that prior antibiotic administration is associated with possible dysmotility and microbial dysbiosis in the intestinal tract. We hypothesize that early antibiotic administration impacts high-risk preterm infants' tolerance to enteral feeding advancement.

Study Design As part of the Routine Early Antibiotic Use in SymptOmatic Preterm Neonates study, symptomatic preterm newborns without maternal infection risk factors were randomized to receive or not receive antibiotics, with C1 receiving antibiotics and C2 not. Of the 55 newborns that underwent pragmatic randomization, 28 preterm neonates in group C1 received antibiotics.

Results The premature neonates in the randomized groups who received antibiotics and those who did not showed no differences in sustained feeding tolerance.

Conclusion Our investigation of the risk of feeding issues in babies who get antibiotics early in life revealed no differences between neonates who received antibiotics and those who did not when the randomized controlled trial data alone was reviewed. Given the sample sizes, it is uncertain if the preceding analysis is powerful enough to detect differences (a significant percentage of neonates who were randomly assigned to NOT get antibiotics subsequently received early treatment due to changing clinical conditions). This affirms the requirement for a meticulously designed prospective randomized study.

Key Points
Iridium-Catalyzed Asymmetric Allylation of Indoles via Kinetic Resolution of 1-Alken-4-yn-3-ols
Authors: Takeuchi Ryo , Sawano Takahiro , Yasumura Yuki , Kuwabara Kyohei , Sugiura Hikaru , Takahashi Kana , Ishikawa Eri
Published: June 2023

We report the iridium-catalyzed asymmetric allylation of indoles via kinetic resolution of 1-alken-4-yn-3-ols to form chiral 1-alken-4-yn-3-ols and branched allylated products with high selectivity. 1-Alken-4,6-diyn-3-ol was also found to be suitable for this asymmetric allylation and gave the products in high yield and enantioselectivity. Other nucleophiles such as a malonic ester and a thiol, besides indoles, reacted to give allylated products and 1-alken-4-yn-3-ols with high enantioselectivities.
Ruthenium(II)-Catalyzed C–H Annulation of Mandelic Acids with Internal Alkynes to Construct Isocoumarins
Authors: Li Shen Min , Cui Ying Na , Wang Wang Huai , Li Hong Jiang , Du Fang , Zhang Shu Jia
Published: June 2023

A series of isocoumarins were synthesized by a one-pot cyclization reaction with mandelic acids and internal alkynes as raw materials, [RuCl2(p-cymene)]2 as a catalyst, and Cu(OAc)2·H2O as an oxidant under reflux conditions in air. By using the established efficient and reliable reaction conditions, a range of substrates were explored, and it was found that both aromatic aldehydes and aromatic acids also reacted smoothly in this system to give moderate yields of the target products. Furthermore, the mandelic acids were shown to be converted into the corresponding benzoic acids as intermediates in the reaction.
Efficient α-Arylation of α-Fluoro-α-nitrosulfonylmethanes Employing Diaryliodonium Salts
Authors: Mohanan Kishor , Zaheer Mohd Khalid , Vaishanv Narendra Kumar , Kumar Awadhesh , Mishra Sameer , Kant Ruchir
Published: June 2023

Reported herein is an efficient α-arylation of α-fluoro-α-nitro­sulfonylmethanes using diaryliodonium salts. A wide range of α-fluoronitrosulfonylmethane substrates underwent α-arylation smoothly to produce the corresponding adducts bearing a fully substituted fluorocarbon center in good to excellent yields. The protocol was subsequently shown viable for the α-arylation of α-cyano-α-fluorosulfonylmethane derivatives yielding highly valuable cyano building blocks.
The Role of NF-κB, PPAR-α, and PPAR-γ in
Older Adults with Metabolic Syndrome
Authors: Demirdağ Filiz , Yavuzer Serap , Cengiz Mahir , Yavuzer Hakan , Kara Zehra , Ayvacı Adnan , Avcı Suna , Yürüyen Mehmet , Uzun Hafize , Altıparmak Mehmet Rıza , Döventaş Alper , Erdinçler Deniz Suna
Published: June 2023

The etiopathogenesis of metabolic syndrome (MetS) has not been fully understood
yet, and chronic low-grade inflammation is thought to be associated with the
development of complications related to MetS. We aimed to investigate the role
of Nuclear factor Kappa B ( NF-κB ), Peroxisome Proliferator-Activated
Receptor- α and γ (PPAR-α, and PPAR-γ) which are
the main markers of inflammation in older adults with MetS. A total of 269
patients aged≥18, 188 patients with MetS who met the diagnostic criteria
of the International Diabetes Federation, and 81 controls who applied to
geriatrics and general internal medicine outpatient clinics for various reasons
were included in the study. Patients were separated into four groups: young with
MetS (< 60, n=76), elderly with MetS (≥60,
n=96), young control (< 60, n=31), elderly
controls (≥60, n=38). Carotid intima-media thickness (CIMT) and
NF-κB , PPAR-α, and PPAR-γ plasma levels were measured
in all of the participants. Age and sex distribution were similar between MetS
and control groups. C-reactive protein (CRP), NF-κB levels
(p=0.001) and CIMT (p<0,001) of MetS group were significantly
higher than in the control groups. On the other hand, the PPAR-γ
(p=0.008) and PPAR-α (p=0.003) levels were significantly
lower in MetS. ROC analysis revealed that the NF-κB, PPAR-α, and
PPAR-γ could be used to indicate MetS in younger adults (AUC: 0.735,
p<0.000; AUC: 0.653, p=0.003), whereas it could not be an
indicator in older adults (AUC: 0.617, p=0.079; AUC:0.530,
p=0.613). It seems that these markers have important roles in
MetS-related inflammation. In our results, suggest that the indicator feature of
NF-κB , PPAR-α and PPAR-γ in recognizing MetS in young
individuals is lost in older adults with Mets.
Erratum: Einflüsse auf die Familienbildung in Bezug zu Frühgeburtlichkeit
Authors: Rohde Katrin S.
Published: June 2023

Die Familienbildungsphase ist eine prägende Zeit für alle Beteiligten – und ein Bildungsprozess im doppelten Sinn: Die Familie konstituiert sich (neu) und die Familienmitglieder erleben sich in vielfältigen Lern- und Bildungsprozessen. Besondere Herausforderungen erleben hier Familien Frühgeborener sowie schwer kranker Reifgeborener. Um sie in ihrer Situationsbewältigung zu unterstützen, braucht es fundierte und situationsorientierte Angebote der psychosozialen Begleitung, die als bedeutsam für das gesamte Familiensystem erscheint.
Spin–valley splitting and spontaneous valley polarization in antiferromagnetic Mn2P2X3Y3 monolayers
Authors: Xu Yushuo , Liu Hongling , Dai Ying , Huang Baibiao , Wei Wei
Published: June 2023

In the current stage, valley-contrasting physics is mainly rooted in nonmagnetic and/or ferromagnetic hexagonal lattices and is rarely used to observe the simultaneous spin and valley polarization in antiferromagnetic materials. In this work, we propose a general scheme that can be achieved easily in experiments to break the PT joint symmetry of antiferromagnetic structures, that is, introducing an out-of-plane potential gradient to realize spin–valley splitting and spontaneous valley polarization. In combination of the model analysis and first-principles calculations, we translate the concept into Mn2P2X3Y3 monolayers and clarify the valley-related physics. It is obvious that our finding significantly extends the scope of valleytronics in both theory and experiments.
Efficient forecasting of chaotic systems with block-diagonal and binary reservoir computing
Authors: Ma Haochun , Prosperino Davide , Haluszczynski Alexander , Räth Christoph
Published: June 2023

The prediction of complex nonlinear dynamical systems with the help of machine learning has become increasingly popular in different areas of science. In particular, reservoir computers, also known as echo-state networks, turned out to be a very powerful approach, especially for the reproduction of nonlinear systems. The reservoir, the key component of this method, is usually constructed as a sparse, random network that serves as a memory for the system. In this work, we introduce block-diagonal reservoirs, which implies that a reservoir can be composed of multiple smaller reservoirs, each with its own dynamics. Furthermore, we take out the randomness of the reservoir by using matrices of ones for the individual blocks. This breaks with the widespread interpretation of the reservoir as a single network. In the example of the Lorenz and Halvorsen systems, we analyze the performance of block-diagonal reservoirs and their sensitivity to hyperparameters. We find that the performance is comparable to sparse random networks and discuss the implications with regard to scalability, explainability, and hardware realizations of reservoir computers.
Extreme rotational events in a forced-damped nonlinear pendulum
Authors: Pal Tapas Kumar , Ray Arnob , Nag Chowdhury Sayantan , Ghosh Dibakar
Published: June 2023

Since Galileo’s time, the pendulum has evolved into one of the most exciting physical objects in mathematical modeling due to its vast range of applications for studying various oscillatory dynamics, including bifurcations and chaos, under various interests. This well-deserved focus aids in comprehending various oscillatory physical phenomena that can be reduced to the equations of the pendulum. The present article focuses on the rotational dynamics of the two-dimensional forced-damped pendulum under the influence of the ac and dc torque. Interestingly, we are able to detect a range of the pendulum’s length for which the angular velocity exhibits a few intermittent extreme rotational events that deviate significantly from a certain well-defined threshold. The statistics of the return intervals between these extreme rotational events are supported by our data to be spread exponentially at a specific pendulum’s length beyond which the external dc and ac torque are no longer sufficient for a full rotation around the pivot. The numerical results show a sudden increase in the size of the chaotic attractor due to interior crisis, which is the source of instability that is responsible for triggering large amplitude events in our system. We also notice the occurrence of phase slips with the appearance of extreme rotational events when the phase difference between the instantaneous phase of the system and the externally applied ac torque is observed.
Cytokine supplemented maturation medium improved development to term following somatic cell nuclear transfer (SCNT) in cattle
Authors: Keim Jacob , Liu Ying , Regouski Misha , Stott Rusty , Singina Galina N. , White Kenneth L. , Polejaeva Irina A.
Published: June 2023

Context In vitro maturation is an important process in the production of embryos. It has been shown that three cytokines, fibroblast growth factor 2, leukemia inhibitory factor and insulin-like growth factor 1 (FLI), increased efficiency of in vitro maturation, somatic cell nuclear transfer (SCNT) blastocyst production, and in vivo development of genetically engineered piglets. Aims Assess effects of FLI on oocyte maturation, quality of oocytes, and embryo development in bovine in vitro fertilisation (IVF) and SCNT. Key results Cytokine supplementation resulted in significant increases in maturation rates and decreased levels of reactive oxygen species. Oocytes matured in FLI had increased blastocyst rates when used in IVF (35.6% vs 27.3%, P < 0.05) and SCNT (40.6% vs 25.7%, P < 0.05). SCNT blastocysts contained significantly more inner cell mass and trophectodermal cells when compared to the control group. Importantly, SCNT embryos derived from oocytes matured in FLI medium resulted in a four-fold increase in full-term development compared to control medium (23.3% vs 5.3%, P < 0.05). Relative mRNA expression analysis of 37 genes associated with embryonic and fetal development revealed one gene had differential transcript abundance in metaphase II oocytes, nine genes at the 8-cell stage, 10 genes at the blastocyst stage in IVF embryos and four genes at the blastocyst stage in SCNT embryos. Conclusions Cytokine supplementation increased efficiency of in vitro production of IVF and SCNT embryos and in vivo development of SCNT embryos to term. Implications Cytokine supplementation is beneficial to embryo culture systems, which may shed light on requirements of early embryo development.
An inducible hACE2 transgenic mouse model recapitulates SARS-CoV-2 infection and pathogenesis in vivo
Authors: Liu Kuo , Tang Muxue , Xu Wei , Meng Xinfeng , Jin Hengwei , Han Maoying , Pu Jing , Li Yutang , Jiao Fanke , Sun Ruilin , Shen Ruling , Lui Kathy O. , Lu Lu , Zhou Bin
Published: June 2023

The classical manifestation of COVID-19 is pulmonary infection. After host cell entry via human angiotensin–converting enzyme II (hACE2), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can infect pulmonary epithelial cells, especially the AT2 (alveolar type II) cells that are crucial for maintaining normal lung function. However, previous hACE2 transgenic models have failed to specifically and efficiently target the cell types that express hACE2 in humans, especially AT2 cells. In this study, we report an inducible, transgenic hACE2 mouse line and showcase three examples for specifically expressing hACE2 in three different lung epithelial cells, including AT2 cells, club cells, and ciliated cells. Moreover, all these mice models develop severe pneumonia after SARS-CoV-2 infection. This study demonstrates that the hACE2 model can be used to precisely study any cell type of interest with regard to COVID-19-related pathologies.
A values-aligned intervention fosters growth mindset–supportive teaching and reduces inequality in educational outcomes
Authors: Hecht Cameron A. , Bryan Christopher J. , Yeager David S.
Published: June 2023

Group-based educational disparities are smaller in classrooms where teachers express a belief that students can improve their abilities. However, a scalable method for motivating teachers to adopt such growth mindset–supportive teaching practices has remained elusive. In part, this is because teachers often already face overwhelming demands on their time and attention and have reason to be skeptical of the professional development advice they receive from researchers and other experts. We designed an intervention that overcame these obstacles and successfully motivated high-school teachers to adopt specific practices that support students’ growth mindsets. The intervention used the values-alignment approach. This approach motivates behavioral change by framing a desired behavior as aligned with a core value—one that is an important criterion for status and admiration in the relevant social reference group. First, using qualitative interviews and a nationally representative survey of teachers, we identified a relevant core value: inspiring students’ enthusiastic engagement with learning. Next, we designed a ~45-min, self-administered, online intervention that persuaded teachers to view growth mindset–supportive practices as a way to foster such student engagement and thus live up to that value. We randomly assigned 155 teachers (5,393 students) to receive the intervention and 164 teachers (6,167 students) to receive a control module. The growth mindset–supportive teaching intervention successfully promoted teachers’ adoption of the suggested practices, overcoming major barriers to changing teachers’ classroom practices that other scalable approaches have failed to surmount. The intervention also substantially improved student achievement in socioeconomically disadvantaged classes, reducing inequality in educational outcomes.
Anthropogenic climate change impacts exacerbate summer forest fires in California
Authors: Turco Marco , Abatzoglou John T. , Herrera Sixto , Zhuang Yizhou , Jerez Sonia , Lucas Donald D. , AghaKouchak Amir , Cvijanovic Ivana
Published: June 2023

Record-breaking summer forest fires have become a regular occurrence in California. Observations indicate a fivefold increase in summer burned area (BA) in forests in northern and central California during 1996 to 2021 relative to 1971 to 1995. While the higher temperature and increased dryness have been suggested to be the leading causes of increased BA, the extent to which BA changes are due to natural variability or anthropogenic climate change remains unresolved. Here, we develop a climate-driven model of summer BA evolution in California and combine it with natural-only and historical climate simulations to assess the importance of anthropogenic climate change on increased BA. Our results indicate that nearly all the observed increase in BA is due to anthropogenic climate change as historical model simulations accounting for anthropogenic forcing yield 172% (range 84 to 310%) more area burned than simulations with natural forcing only. We detect the signal of combined historical forcing on the observed BA emerging in 2001 with no detectable influence of the natural forcing alone. In addition, even when considering fuel limitations from fire-fuel feedbacks, a 3 to 52% increase in BA relative to the last decades is expected in the next decades (2031 to 2050), highlighting the need for proactive adaptations.
Robust acoustic trapping and perturbation of single-cell microswimmers illuminate three-dimensional swimming and ciliary coordination
Authors: Cui Mingyang , Dutcher Susan K. , Bayly Philip V. , Meacham J. Mark
Published: June 2023

We report a label-free acoustic microfluidic method to confine single, cilia-driven swimming cells in space without limiting their rotational degrees of freedom. Our platform integrates a surface acoustic wave (SAW) actuator and bulk acoustic wave (BAW) trapping array to enable multiplexed analysis with high spatial resolution and trapping forces that are strong enough to hold individual microswimmers. The hybrid BAW/SAW acoustic tweezers employ high-efficiency mode conversion to achieve submicron image resolution while compensating for parasitic system losses to immersion oil in contact with the microfluidic chip. We use the platform to quantify cilia and cell body motion for wildtype biciliate cells, investigating effects of environmental variables like temperature and viscosity on ciliary beating, synchronization, and three-dimensional helical swimming. We confirm and expand upon the existing understanding of these phenomena, for example determining that increasing viscosity promotes asynchronous beating. Motile cilia are subcellular organelles that propel microorganisms or direct fluid and particulate flow. Thus, cilia are critical to cell survival and human health. The unicellular alga
Chlamydomonas reinhardtii
is widely used to investigate the mechanisms underlying ciliary beating and coordination. However, freely swimming cells are difficult to image with sufficient resolution to capture cilia motion, necessitating that the cell body be held during experiments. Acoustic confinement is a compelling alternative to use of a micropipette, or to magnetic, electrical, and optical trapping that may modify the cells and affect their behavior. Beyond establishing our approach to studying microswimmers, we demonstrate a unique ability to mechanically perturb cells via rapid acoustic positioning.
Dissection of DNA damage and repair pathways in live cells by femtosecond laser microirradiation and free-electron modeling
Authors: Schmalz Michael , Liang Xiao-Xuan , Wieser Ines , Gruschel Caroline , Muskalla Lukas , Stöckl Martin Thomas , Nitschke Roland , Linz Norbert , Leitenstorfer Alfred , Vogel Alfred , Ferrando-May Elisa
Published: June 2023

Understanding and predicting the outcome of the interaction of light with DNA has a significant impact on the study of DNA repair and radiotherapy. We report on a combination of femtosecond pulsed laser microirradiation at different wavelengths, quantitative imaging, and numerical modeling that yields a comprehensive picture of photon-mediated and free-electron-mediated DNA damage pathways in live cells. Laser irradiation was performed under highly standardized conditions at four wavelengths between 515 nm and 1,030 nm, enabling to study two-photon photochemical and free-electron-mediated DNA damage in situ. We quantitatively assessed cyclobutane pyrimidine dimer (CPD) and γH2AX-specific immunofluorescence signals to calibrate the damage threshold dose at these wavelengths and performed a comparative analysis of the recruitment of DNA repair factors xeroderma pigmentosum complementation group C (XPC) and Nijmegen breakage syndrome 1 (Nbs1). Our results show that two-photon-induced photochemical CPD generation dominates at 515 nm, while electron-mediated damage dominates at wavelengths ≥620 nm. The recruitment analysis revealed a cross talk between nucleotide excision and homologous recombination DNA repair pathways at 515 nm. Numerical simulations predicted electron densities and electron energy spectra, which govern the yield functions of a variety of direct electron-mediated DNA damage pathways and of indirect damage by
•
OH radicals resulting from laser and electron interactions with water. Combining these data with information on free electron–DNA interactions gained in artificial systems, we provide a conceptual framework for the interpretation of the wavelength dependence of laser-induced DNA damage that may guide the selection of irradiation parameters in studies and applications that require the selective induction of DNA lesions.
The nitrate transporter NRT2.1 directly antagonizes PIN7-mediated auxin transport for root growth adaptation
Authors: Wang Yalu , Yuan Zhi , Wang Jinyi , Xiao Huixin , Wan Lu , Li Lanxin , Guo Yan , Gong Zhizhong , Friml Jiří , Zhang Jing
Published: June 2023

As a crucial nitrogen source, nitrate (NO
3
−
) is a key nutrient for plants. Accordingly, root systems adapt to maximize NO
3
−
availability, a developmental regulation also involving the phytohormone auxin. Nonetheless, the molecular mechanisms underlying this regulation remain poorly understood. Here, we identify
low-nitrate-resistant mutant
(
lonr
) in Arabidopsis (
Arabidopsis thaliana
), whose root growth fails to adapt to low-NO
3
−
conditions.
lonr2
is defective in the high-affinity NO
3
−
transporter NRT2.1.
lonr2
(
nrt2.1
) mutants exhibit defects in polar auxin transport, and their low-NO
3
−
-induced root phenotype depends on the PIN7 auxin exporter activity. NRT2.1 directly associates with PIN7 and antagonizes PIN7-mediated auxin efflux depending on NO
3
−
levels. These results reveal a mechanism by which NRT2.1 in response to NO
3
−
limitation directly regulates auxin transport activity and, thus, root growth. This adaptive mechanism contributes to the root developmental plasticity to help plants cope with changes in NO
3
−
availability.
Twins, income, and happiness: Evidence from China
Authors: Ye Maoliang , Zhang Junsen , Li Hongbin
Published: June 2023

We estimate the causal effect of income on happiness using a unique dataset of Chinese twins. This allows us to address omitted variable bias and measurement errors. Our findings show that individual income has a large positive effect on happiness, with a doubling of income resulting in an increase of 0.26 scales or 0.37 SDs in the four-scale happiness measure. We also find that income matters most for males and the middle-aged. Our results highlight the importance of accounting for various biases when studying the relationship between socioeconomic status and subjective well-being.
Directional dipole dice enabled by anisotropic chirality
Authors: Cheng Yuqiong , Oyesina Kayode Adedotun , Xue Bo , Lei Dangyuan , Wong Alex M. H. , Wang Shubo
Published: June 2023

Directional radiation and scattering play an essential role in light manipulation for various applications in integrated nanophotonics, antenna and metasurface designs, quantum optics, etc. The most elemental system with this property is the class of directional dipoles, including the circular dipole, Huygens dipole, and Janus dipole. A unified realization of all three dipole types and a mechanism to freely switch among them are previously unreported, yet highly desirable for developing compact and multifunctional directional sources. Here, we theoretically and experimentally demonstrate that the synergy of chirality and anisotropy can give rise to all three directional dipoles in one structure at the same frequency under linearly polarized plane wave excitations. This mechanism enables a simple helix particle to serve as a directional dipole dice (DDD), achieving selective manipulation of optical directionality via different “faces” of the particle. We employ three “faces” of the DDD to realize face-multiplexed routing of guided waves in three orthogonal directions with the directionality determined by spin, power flow, and reactive power, respectively. This construction of the complete directionality space can enable high-dimensional control of both near-field and far-field directionality with broad applications in photonic integrated circuits, quantum information processing, and subwavelength-resolution imaging.
Histidine-rich protein II nanoparticle delivery of heme iron load drives endothelial inflammation in cerebral malaria
Authors: Nguyen Suong T. , Du Daniel , Wychrij Daniel , Cain Matthew D. , Wu Qingping , Klein Robyn S. , Russo Ilaria , Goldberg Daniel E.
Published: June 2023

Histidine-rich protein II (HRPII) is secreted by
Plasmodium falciparum
 during the blood stage of malaria infection. High plasma levels of HRPII are associated with cerebral malaria, a severe and highly fatal complication of malaria. HRPII has been shown to induce vascular leakage, the hallmark of cerebral malaria, in blood–brain barrier (BBB) and animal models. We have discovered an important mechanism for BBB disruption that is driven by unique features of HRPII. By characterizing serum from infected patients and HRPII produced by
P. falciparum
parasites in culture, we found that HRPII exists in large multimeric particles of 14 polypeptides that are richly laden with up to 700 hemes per particle. Heme loading of HRPII is required for efficient binding and internalization via caveolin-mediated endocytosis in hCMEC/D3 cerebral microvascular endothelial cells. Upon acidification of endolysosomes, two-thirds of the hemes are released from acid-labile binding sites and metabolized by heme oxygenase 1, generating ferric iron and reactive oxygen species. Subsequent activation of the NLRP3 inflammasome and IL-1β secretion resulted in endothelial leakage. Inhibition of these pathways with heme sequestration, iron chelation, or anti-inflammatory drugs protected the integrity of the BBB culture model from HRPII:heme. Increased cerebral vascular permeability was seen after injection of young mice with heme-loaded HRPII (HRPII:heme) but not with heme-depleted HRPII. We propose that during severe malaria infection, HRPII:heme nanoparticles in the bloodstream deliver an overwhelming iron load to endothelial cells to cause vascular inflammation and edema. Disrupting this process is an opportunity for targeted adjunctive therapies to reduce the morbidity and mortality of cerebral malaria.
Criticizing for the public interest and aligning with others
Authors: Badarneh Muhammad A. , Damiri Malak
Published: June 2023

This study examines the speech act of criticizing in online comments on the COVID-19 lockdown breaches in Jordan
in 2020. Drawing on speech act theory and the face-saving perspective of politeness, the study investigates the strategies used to
criticize these breaches. The analysis of 356 online comments revealed that Jordanians used ten strategies to criticize these
lockdown breaches: Insulting, Appealing to the divine, Intertextuality, Rhetorical questions, Stylized threats, Framing criticism
as request, Framing criticism as advice-giving, Framing criticism as warning, Invoking legal authority, and Invoking religious
‘haram’. These criticisms were driven by safeguarding the collective interests of community members rather than merely expressing
personal condemnation of the breaches. The breaches were constructed in these criticisms as communally reproachable, legally
answerable, and religiously proscribed. Given their public nature, these criticisms appear to be motivated not by politeness but
by expressing strong emotions, showing in-group solidarity, and aligning with other community members.
Effect of cage bias and electron emission on the two-electron temperature groups in a hot cathode discharge
Authors: Sangma Jocelyn , Sharma Narayan , Chakraborty Monojit , Bandyopadhyay Mainak
Published: June 2023

In the target multi-pole magnetic cage of the double plasma device, where the plasma diffuses through the magnetic filter after its production in the source region, the effect of the cage biasing, introduction of auxiliary filament and accelerating voltage on the control of the temperature and density of the two-electron groups in a hydrogen bi-Maxwellian plasma is carried out. This control of the electron groups in turn will help to enhance the negative ion density. In the absence of biasing voltage, the density of low-energy electrons and high-energy electrons were of the orders ∼1014 m−3 and ∼1012 m−3 respectively. As the cage is biased negatively, these values increased to an order of ∼1016 m−3 and ∼1013 m−3 respectively. With negative cage biasing, the temperature of the high energy electrons was ∼5 eV and low energy electrons ∼0.6 eV. The introduction of an auxiliary electron source in the target region together with the application of an accelerating voltage along with biasing voltage further increased the density of low-energy electrons to ∼4 × 1016 m−3.
Annealing effect on cds nanowalls grown by chemical bath deposition on glass substrate
Authors: Yildirim E , Ozmen S Ildan , Havare Ali Kemal , Gubur H Metin
Published: June 2023

This paper focuses on the structural, morphological, and optical properties of the CdS thin films on the glass substrate with the effect of annealing. Chemical bath deposition (CBD) is a basic technique that is used in this work to form CdS thin films. The films′ (d) thickness is calculated to be 400 nm. According to the XRD results, the particle sizes for the as-deposited and the annealed CdS film are 15.15 nm and 16.56 nm, respectively. The SEM images of formed nanowalls in the films were compared for both the as-deposited and the annealed CdS structure. It was attained with the Raman spectroscopy analysis that as-deposited and annealed films include the LO phonon modes of the CdS. Moreover, FT-IR analysis was performed to determine the hydroxide ion (OH-) behavior depending on the annealing effect. The optical band gap energy of the annealed CdS nanowalls reduced from 2.31 eV to 2.19 eV, according to the UV measurements. Additionally, the Hall Effect is used to assess the conductivity and resistivity of as-deposited and annealed films. This work demonstrated that CdS films readily form nanowalls at 85 °C.
Advanced electrochemical potential monitoring for improved understanding of electrical neurostimulation protocols
Authors: Doering Moritz , Kieninger Jochen , Kübler Julian , Hofmann Ulrich G , Rupitsch Stefan J , Urban Gerald A , Weltin Andreas
Published: June 2023

Objective. Current-controlled neurostimulation is increasingly used in the clinical treatment of neurological disorders and widely applied in neural prostheses such as cochlear implants. Despite its importance, time-dependent potential traces of electrodes during microsecond-scale current pulses, especially with respect to a reference electrode (RE), are not precisely understood. However, this knowledge is critical to predict contributions of chemical reactions at the electrodes, and ultimately electrode stability, biocompatibility, and stimulation safety and efficacy. Approach. We assessed the electrochemistry of neurostimulation protocols in vitro with Pt microelectrodes from millisecond (classical electroanalysis) to microsecond (neurostimulation) timescales. We developed a dual-channel instrumentation amplifier to include a RE in neurostimulation setups. Uniquely, we combined potential measurements with potentiostatic prepolarization to control and investigate the surface status, which is not possible in typical stimulation setups. Main results. We thoroughly validated the instrumentation and highlighted the importance of monitoring individual electrochemical electrode potentials in different configurations of neurostimulation. We investigated electrode processes such as oxide formation and oxygen reduction by chronopotentiometry, bridging the gap between milli- and microsecond timescales. Our results demonstrate how much impact on potential traces the electrode’s initial surface state and electrochemical surface processes have, even on a microsecond scale. Significance. Our unique use of preconditioning in combination with stimulation reveals that interpreting potential traces with respect to electrode processes is misleading without rigorous control of the electrode’s surface state. Especially in vivo, where the microenvironment is unknown, simply measuring the voltage between two electrodes cannot accurately reflect the electrode’s state and processes. Potential boundaries determine charge transfer, corrosion, and alterations of the electrode/tissue interface such as pH and oxygenation, particularly in long-term in vivo use. Our findings are relevant for all use-cases of constant-current stimulation, strongly advocating for electrochemical in situ investigations in many applications like the development of new electrode materials and stimulation methods.
Hepatoprotective Effects of Sukari Dates Extract (Phoenix dactylifera L.) Against ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) Profile in Male Wistar Rats After Induced by Meloxicam
Authors: Kadir R W , Anshar A R , Nurdin M A
Published: June 2023

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) that is frequently administered to animals as an analgesic, antipyretic, and anti-inflammatory medication. Meloxicam overdose and liver damage can occur if taken for an extended period of time without first consulting a veterinarian. Sukari dates extract can neutralize the effects of free radicals and protect the liver when taken orally. After being induced by a toxic dose of meloxicam, the purpose of this study is to demonstrate that the administration of sukari dates extract may reduce the profile of ALT and AST. 24 male wistar rats were used in this laboratory experiment, which was divided into four groups (n=6). Positive control group (K2) received 30 mg/kg BW meloxicam and 1% Na CMC, while treatment group 1 (P1) received 500 mg/kg BW sukari dates extract and 30 mg/kg BW meloxicam. Treatment group 2 (P2) received 1000 mg/kg BW sukari dates extract and 30 mg/kg BW meloxicam. The negative control group (K1) received 1% Na CMC. The study lasted for 12 days, and on the 12th day, blood samples were taken for analysis. The ALT profile decreased to 67.17 U/L and 63.00 U/L in P1 and P2, respectively, and the AST profile decreased to 142.83 U/L and 125.83 U/L. As a result, it can be concluded that toxic doses of meloxicam can cause sukari dates extract to reduce ALT and AST profiles.
Pathology of Plasmodium berghei-Infected Mice Liver Treated with Extract of Breadfruit Peel (Artocarpus communis)
Authors: Wahyuwardani S , Wardhana A H , Putra G I S , Putri R
Published: June 2023

The protozoan parasite Plasmodium infection can cause malaria in both humans and animals. There are reports about the resistance to certain antimalarial medications. Therefore, searching for alternative medicine, such as herbal remedies, is important. This study focused on the pathophysiology of the livers of mice infected intraperitoneally with Plasmodium berghei and the efficacy of ethanol extract from breadfruit peel. Fifty male DDY mice weighing 25 and 35 grams were placed into five treatment groups. The treatment group was infected with P. berghei and administered with breadfruit peel extract at 100 mg/kg: 200 mg/kg, and 300 mg/kg, respectively, for P1, P2, and P3, P4 treated with 100 mg/kg of Doxycycline and the P5 group received no therapy. After one and two weeks, five mice from each group terminated, and then Histopathological of the liver organs were observed and scored microscopically. The results indicated that Plasmodium infection produced varied degrees of liver damage in mice. The liver’s gross pathology revealed hepatomegaly, a deeper hue than normal animal liver, and flattened edges. After two weeks of infection, histopathological examination revealed that breadfruit extract could lower the amount of Plasmodium in the liver, as indicated by decreased hemozoin, and the l iver in the healing process.