bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinematics of the Hybrid 6-Axis (H6A) manipulator
Authors: Golla Pranathi , Ramesh Shashank , Bandyopadhyay Sandipan
Published: June 2023

This paper presents a comprehensive study of the forward and inverse kinematics of a six-degrees-of-freedom (DoF) spatial manipulator with a novel architecture. Developed by Systemantics India Pvt. Ltd., Bangalore, and designated as the H6A (i.e., Hybrid 6-Axis), this manipulator consists of two arm-like branches, which are attached to a rigid waist at the proximal end and are coupled together via a wrist assembly at the other. Kinematics of the manipulator is challenging due to the presence of two multi-DoF passive joints: a spherical joint in the right arm and a universal in the left. The forward kinematic problem has eight solutions, which are derived analytically in the closed form. The inverse kinematic problem leads to
$160$
solutions and involves the derivation of a
$40$
-degree polynomial equation, whose coefficients are obtained as closed-form symbolic expressions of the pose parameters of the end-effector, thus ensuring the generality of the results over all possible inputs. Furthermore, the analyses performed lead naturally to the conditions for various singularities involved, including certain non-trivial architecture singularities. The results are illustrated via numerical examples which are validated extensively.
Capitalism and the Creation of the U.S. Constitution
Authors: Parisot James
Published: June 2023

This article engages with scholars working on the history of capitalism and with scholars of American political development to form a historical materialist perspective on the creation of the American federal government. First, it returns to the debate about the state in capitalist society to develop an approach for theorizing the relations between class, capitalism, and states. Next, it addresses the position of American capitalism in the 1780s, arguing that it was still in a long transition phase. After this, it reinterprets the Constitutional Convention of 1787 in the context of the long and uneven history of American capitalist development. I argue that the U.S. Constitution created the foundations of a state that would serve capitalist interests, including capitalist slave owners, but, at the same time, provided some space for social relations of production not yet fully subordinated to the power of capitalism to coexist.
Tricuspid valve annular tilt for assessment of pre- and post-intervention right ventricular volume in patients undergoing transcatheter pulmonary valve replacement
Authors: Reddy C. D. , Yokota R. , Punn R.
Published: June 2023

Introduction:

Transcatheter pulmonary valve replacement serves as a successful alternative to surgical replacement of a right ventricle to pulmonary artery conduit. Guidelines for recommending transcatheter pulmonary valve replacement depend on MRI right ventricular volumes, which have been correlated to the echocardiographic measure of right ventricular annular tilt. We aim to assess whether right ventricular annular tilt can be a clinically useful alternative tool in the acute and long-term periods after transcatheter pulmonary valve replacement to assess right ventricular health.

Methods:

We reviewed 70 patients who underwent transcatheter pulmonary valve replacement at a single institution. Echocardiographic measurements were obtained prior to transcatheter pulmonary valve replacement, immediately after transcatheter pulmonary valve replacement, and within 6 months to 1 year after transcatheter pulmonary valve replacement. Right ventricular annular tilt measures the angle of the tricuspid valve plane relative to the mitral valve plane at end-diastole in the apical four-chamber view. Right ventricular fractional area change, right ventricular systolic strain, tissue Doppler velocity, and tricuspid annular plane systolic excursion Z-scores were obtained using published methods.

Results:

Right ventricular annular tilt decreased significantly immediately after transcatheter pulmonary valve replacement (p = 0.0004), and this reduction in right ventricular volume persisted at the mid-term follow-up (p < 0.0001). Fractional area change did not change significantly after transcatheter pulmonary valve replacement while right ventricular global strain improved at mid-term follow-up despite no significant difference immediately after transcatheter pulmonary valve replacement.

Conclusions:

Right ventricular annular tilt decreases both immediately after transcatheter pulmonary valve replacement and at mid-term follow-up. Right ventricular strain also improved after transcatheter pulmonary valve replacement, corresponding to the improved volume load. Right ventricular annular tilt can be considered as an additional echocardiographic factor to assess right ventricular volume and remodeling after transcatheter pulmonary valve replacement.
Living with loss: a cognitive approach to prolonged grief disorder – incorporating complicated, enduring and traumatic grief – ADDENDUM
Authors: Duffy Michael , Wild Jennifer
Published: June 2023

The subject of prolonged, complicated and traumatic grief has become more topical as a consequence of the Covid-19 pandemic. CBT practitioners have been asked to provide effective therapeutic responses for clients with enduring distressing grief reactions. These enduring grief conditions have now been categorised as Prolonged Grief Disorder in the two main mental health classification systems: in the ICD -11 in November 2020 and as a revision to the DSM-5 in 2021. In this paper we draw on our research and clinical experience in applying cognitive therapy for PTSD (CT-PTSD) to traumatic bereavement to derive lessons for the treatment of prolonged grief. During the pandemic the authors of this paper delivered several workshops on prolonged grief disorder (PGD) during which clinicians raised several thought-provoking questions; how do we differentiate between normal and abnormal or pathological grief; how do we categorise pathological grief; how effective are existing therapies and is there a role for CBT; and how do our experiences with Cognitive Therapy for PTSD help with conceptualisation and treatment of PGD. The purpose of this paper is to answer these important questions and in so doing, consider the historical and theoretical concepts relating to complex and traumatic grief, factors that differentiate normal grief from abnormal grief, maintenance factors for PGD and implications for CBT treatments.
Some comments on “A Hermite spline approach for modelling population mortality” by Tang, Li & Tickle (2022)
Authors: Richards Stephen J.
Published: June 2023

Tang et al. (2022) propose a new class of models for stochastic mortality modelling using Hermite splines. There are four useful features of this class that are worth emphasising. First, for single-sex datasets, this new class of projection models can be fitted as a generalised linear model. Second, these models can automatically extrapolate mortality rates to ages above the maximum age of the data set. Third, simpler sub-variants of the models exist for forecasting when one of the variables lacks a clear drift. Finally, a minor reparameterisation increases the quality of long-range forecasts of period mortality.
UNPRINCIPLED
Authors: BELOT GORDON
Published: June 2023

It is widely thought that chance should be understood in reductionist terms: claims about chance should be understood as claims that certain patterns of events are instantiated. There are many possible reductionist theories of chance, differing as to which possible pattern of events they take to be chance-making. It is also widely taken to be a norm of rationality that credence should defer to chance: special cases aside, rationality requires that one’s credence function, when conditionalized on the chance-making facts, should coincide with the objective chance function. It is a shortcoming of a theory of chance if it implies that this norm of rationality is unsatisfiable. The primary goal of this paper is to show, on the basis of considerations concerning computability and inductive learning, that this shortcoming is more common than one would have hoped.
Corona und Drogenhilfe
Authors: Werse Bernd , Klaus Luise
Published: June 2023

Zusammenfassung: Zielsetzung: Untersuchung der Auswirkungen der Covid-19-Pandemie auf Angebote der vor allem niedrigschwelligen Drogenhilfe und Reaktionen der Klientel auf geänderte Angebote. Methodik: Verwendet wurden in erster Linie Daten aus einer asynchronen qualitativen Onlinebefragung für Mitarbeiter_innen der ambulanten Drogenhilfe, ergänzt durch Zahlen aus einer quantitativen Onlinebefragung für dieselbe Zielgruppe. Ergebnisse: Während übliche Infektionsschutzmaßnahmen nahezu überall angewendet wurden, reichte die Spanne der tatsächlichen Auswirkungen von Komplettschließungen bis zu eher geringen Einschränkungen. Schwerpunkte wurden zumeist auf Überlebenshilfe und Straßensozialarbeit gelegt. Beratung wurde oft per Telefon durchgeführt, was für viele Anliegen als sinnvoll erachtet wurde, Beziehungsarbeit aber erschwerte. Vor allem stark verelendete Klient_innen nutzten weiterhin häufig Hilfsangebote. Schlussfolgerungen: Es zeigen sich unterschiedliche Umgangsweisen der Drogenhilfe mit den pandemiebedingten Maßnahmen. Oft entwickelte man kreative Lösungen zur Umsetzung, mit Schwerpunktsetzung auf Existenzsicherung. Sowohl Mitarbeiter_innen als auch Klientel waren durch die Pandemie zahlreichen Belastungen ausgesetzt.
The Online Processing of Hypothetical Events
Authors: Zhan Likan , Zhou Peng
Published: June 2023

Abstract. A conditional statement If P then Q is formed by combining the two propositions P and Q together with the conditional connective If ··· then ···. When embedded under the conditional connective, the two propositions P and Q describe hypothetical events that are not actualized. It remains unclear when such hypothetical thinking is activated in the real-time comprehension of conditional statements. To tackle this problem, we conducted an eye-tracking experiment using the visual world paradigm. Participants’ eye movements on the concurrent image were recorded when they were listening to the auditorily presented conditional statements. Depending on when and what critical information is added into the auditory input, there are four possible temporal slots to observe in the online processing of the conditional statement: the sentential connective If, the antecedent P, the consequent Q, and the processing of the sentence following the conditional. We mainly focused on the first three slots. First, the occurrence of the conditional connective should trigger participants to search in the visual world for the event that could not assign a truth-value to the embedded proposition. Second, if the embedded proposition P can be determined as true by an event, the hypothetical property implied by the connective would prevent the participants from excluding the consideration of other events. The consideration of other events would yield more fixations on the events where the proposition is false.
First Quantification of the Permafrost Heat Sink in the Earth's Climate System
Authors: Nitzbon Jan , Krinner Gerhard , Schneider von Deimling Thomas , Werner Martin , Langer Moritz
Published: June 2023

Due to an imbalance between incoming and outgoing radiation at the top of the atmosphere, excess heat has accumulated in Earth's climate system in recent decades, driving global warming and climatic changes. To date, it has not been quantified how much of this excess heat is used to melt ground ice in permafrost. Here, we diagnose changes in sensible and latent ground heat contents in the northern terrestrial permafrost region from ensemble‐simulations of a tailored land surface model. We find that between 1980 and 2018, about  ZJ of heat, of which  ZJ (44%) were used to melt ground ice, were absorbed by permafrost. Our estimate, which does not yet account for the potentially increased heat uptake due to thermokarst processes in ice‐rich terrain, suggests that permafrost is a persistent heat sink comparable in magnitude to other components of the cryosphere and must be explicitly considered when assessing Earth's energy imbalance.
SuperDARN Observations of the Two Component Model of Ionospheric Convection
Authors: Grocott A. , Walach M.‐T. , Milan S. E.
Published: June 2023

We use a 20 years database of Super Dual Auroral Radar Network (SuperDARN) observations to investigate the two component model of ionospheric convection. A convection pattern is included in the database if it is derived from at least 250 radar vectors and has a distribution of electric potential consistent with Dungey‐cycle twin vortex flow (a negative potential peak in the dusk cell and a positive potential peak in the dawn cell). We extract the locations of the foci of the convection cells from the SuperDARN convection patterns, and compare their dependencies on the north‐south component of the interplanetary magnetic field, IMF BZ, and the SuperMAG auroral electrojet index, SML. We use these parameters to define intervals of expected dayside or nightside dominated reconnection. Our results show that, under conditions favorable for dominant dayside reconnection, the dawn and dusk foci are shifted toward the dayside and that, under conditions favorable for dominant nightside reconnection, the dawn and dusk foci are shifted toward the nightside.
Warming Waters Drive Some Mariners to Piracy
Authors: Kornei Katherine
Published: June 2023

As fish production waxes and wanes with climate change, so too does the risk of maritime piracy in East Africa and the South China Sea.
Forecasting Earthquake-Induced Floods
Authors: Kornei Katherine
Published: June 2023

Surface-rupturing earthquakes can abruptly reroute rivers when fault scarps function like dams. Researchers have now successfully modeled such an event that occurred in New Zealand.
CIPS Observations of Gravity Wave Activity at the Edge of the Polar Vortices and Coupling to the Ionosphere
Authors: Harvey V. L. , Randall C. E. , Goncharenko L. P. , Becker E. , Forbes J. M. , Carstens J. , Xu S. , France J. A. , Zhang S.‐R. , Bailey S. M.
Published: June 2023

A new Cloud Imaging and Particle Size (CIPS) gravity wave (GW) variance data set is available that facilitates automated analysis of GWs entering the mesosphere. This work examines several years of CIPS GW variances from 50 to 55 km in the context of the Arctic and Antarctic polar vortices. CIPS observes highest GW activity in the vortex edge region where horizontal wind speeds are largest, consistent with previously published GW climatologies in the stratosphere and mesosphere. CIPS observes the well‐documented planetary wave (PW)‐1 patterns in GW activity in both hemispheres. In the Northern Hemisphere, maximum GW activity occurs over the North Atlantic and western Europe. In the Southern Hemisphere, maximum GW activity stretches from the Andes over the South Atlantic and Indian Oceans, as expected. In the NH, CIPS GW spatial patterns are highly correlated with horizontal wind speed. In the SH, CIPS GW patterns are less positively correlated with the winds due to increased zonal symmetry and orographic forcing. The Andes Mountains and Antarctic Peninsula, South Georgia Island, Kerguelen/Heard Islands, New Zealand, and Tasmania are persistent sources of orographic GWs. Atmospheric Infrared sounder observations of stratospheric GWs are analyzed alongside CIPS to explore vertical GW coherence and to infer GW propagation and sources. NH midlatitude GW activity is reduced during the January 2021 SSW, as expected. This reduction in GWs leads to a simultaneous reduction in traveling ionospheric disturbances (TIDs), providing more evidence that weak polar vortex events with weak GW activity leads to reduced daytime TID activity.
Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy
Authors: Harvey-Jones Kelly , Lange Frederic , Verma Vinita , Bale Gemma , Meehan Christopher , Avdic-Belltheus Adnan , Hristova Mariya , Sokolska Magdalena , Torrealdea Francisco , Golay Xavier , Parfentyeva Veronika , Durduran Turgut , Bainbridge Alan , Tachtsidis Ilias , Robertson Nicola J. , Mitra Subhabrata
Published: June 2023

Background

Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome.

Methods

Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count.

Results

CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r2 = 0.46, p = 0.004, r2 = 0.45, p = 0.004, respectively), TUNEL cell count (r2 = 0.34, p = 0.02) and predicted both initial insult (r2 = 0.62, p = 0.002) and outcome group (r2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r2 = 0.34, p = 0.01 and r2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r2 = 0.43, p = 0.01).

Conclusion

Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model.

Impact

This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome.

Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.
Targeting transglutaminase 2 mediated exostosin glycosyltransferase 1 signaling in liver cancer stem cells with acyclic retinoid
Authors: Qin Xian-Yang , Furutani Yutaka , Yonezawa Kento , Shimizu Nobutaka , Kato-Murayama Miyuki , Shirouzu Mikako , Xu Yali , Yamano Yumiko , Wada Akimori , Gailhouste Luc , Shrestha Rajan , Takahashi Masataka , Keillor Jeffrey W. , Su Ting , Yu Wenkui , Fujii Shinya , Kagechika Hiroyuki , Dohmae Naoshi , Shirakami Yohei , Shimizu Masahito , Masaki Takahiro , Matsuura Tomokazu , Suzuki Harukazu , Kojima Soichi
Published: June 2023

Transglutaminase 2 (TG2) is a multifunctional protein that promotes or suppresses tumorigenesis, depending on intracellular location and conformational structure. Acyclic retinoid (ACR) is an orally administered vitamin A derivative that prevents hepatocellular carcinoma (HCC) recurrence by targeting liver cancer stem cells (CSCs). In this study, we examined the subcellular location-dependent effects of ACR on TG2 activity at a structural level and characterized the functional role of TG2 and its downstream molecular mechanism in the selective depletion of liver CSCs. A binding assay with high-performance magnetic nanobeads and structural dynamic analysis with native gel electrophoresis and size-exclusion chromatography-coupled multi-angle light scattering or small-angle X-ray scattering showed that ACR binds directly to TG2, induces oligomer formation of TG2, and inhibits the transamidase activity of cytoplasmic TG2 in HCC cells. The loss-of-function of TG2 suppressed the expression of stemness-related genes, spheroid proliferation and selectively induced cell death in an EpCAM+ liver CSC subpopulation in HCC cells. Proteome analysis revealed that TG2 inhibition suppressed the gene and protein expression of exostosin glycosyltransferase 1 (EXT1) and heparan sulfate biosynthesis in HCC cells. In contrast, high levels of ACR increased intracellular Ca2+ concentrations along with an increase in apoptotic cells, which probably contributed to the enhanced transamidase activity of nuclear TG2. This study demonstrates that ACR could act as a novel TG2 inhibitor; TG2-mediated EXT1 signaling is a promising therapeutic target in the prevention of HCC by disrupting liver CSCs.
Clinical and molecular correlation defines activity of physiological pathways in life-sustaining kidney xenotransplantation
Authors: Firl Daniel J. , Lassiter Grace , Hirose Takayuki , Policastro Robert , D’Attilio Ashley , Markmann James F. , Kawai Tatsuo , Hall Katherine C.
Published: June 2023

Porcine kidney xenotransplantation is accelerating towards clinical translation. However, despite the demonstrated ability of porcine kidneys to remove metabolic waste products, questions remain about their ability to faithfully recapitulate renal endocrine functions after transplantation. Here we analyze xenograft growth and function of two kidney dependent endocrine pathways in seventeen cynomolgus macaques after kidney xenotransplantation from gene edited Yucatan minipigs. Xenograft growth, the renin-angiotensinogen aldosterone-system, and the calcium-vitamin D-parathyroid hormone axis are assessed using clinical chemistries data, renin activity and beta-C-terminal-telopeptide assays, kidney graft RNA-sequencing and serial ultrasonography. We demonstrate that xenografts transplanted from minipigs show only modest growth and do not substantially contribute to recipient RAAS pathway activity. However, parathyroid hormone-independent hypercalcemia and hypophosphatemia are observed, suggesting a need for close monitoring and timely intervention during human testing. Further study of these phenotypes is warranted in designing prospective clinical trials.
Pacpaint: a histology-based deep learning model uncovers the extensive intratumor molecular heterogeneity of pancreatic adenocarcinoma
Authors: Saillard Charlie , Delecourt Flore , Schmauch Benoit , Moindrot Olivier , Svrcek Magali , Bardier-Dupas Armelle , Emile Jean Francois , Ayadi Mira , Rebours Vinciane , de Mestier Louis , Hammel Pascal , Neuzillet Cindy , Bachet Jean Baptiste , Iovanna Juan , Dusetti Nelson , Blum Yuna , Richard Magali , Kermezli Yasmina , Paradis Valerie , Zaslavskiy Mikhail , Courtiol Pierre , Kamoun Aurelie , Nicolle Remy , Cros Jerome
Published: June 2023

Two tumor (Classical/Basal) and stroma (Inactive/active) subtypes of Pancreatic adenocarcinoma (PDAC) with prognostic and theragnostic implications have been described. These molecular subtypes were defined by RNAseq, a costly technique sensitive to sample quality and cellularity, not used in routine practice. To allow rapid PDAC molecular subtyping and study PDAC heterogeneity, we develop PACpAInt, a multi-step deep learning model. PACpAInt is trained on a multicentric cohort (n = 202) and validated on 4 independent cohorts including biopsies (surgical cohorts n = 148; 97; 126 / biopsy cohort n = 25), all with transcriptomic data (n = 598) to predict tumor tissue, tumor cells from stroma, and their transcriptomic molecular subtypes, either at the whole slide or tile level (112 µm squares). PACpAInt correctly predicts tumor subtypes at the whole slide level on surgical and biopsies specimens and independently predicts survival. PACpAInt highlights the presence of a minor aggressive Basal contingent that negatively impacts survival in 39% of RNA-defined classical cases. Tile-level analysis ( > 6 millions) redefines PDAC microheterogeneity showing codependencies in the distribution of tumor and stroma subtypes, and demonstrates that, in addition to the Classical and Basal tumors, there are Hybrid tumors that combine the latter subtypes, and Intermediate tumors that may represent a transition state during PDAC evolution.
A heterogeneously integrated lithium niobate-on-silicon nitride photonic platform
Authors: Churaev Mikhail , Wang Rui Ning , Riedhauser Annina , Snigirev Viacheslav , Blésin Terence , Möhl Charles , Anderson Miles H. , Siddharth Anat , Popoff Youri , Drechsler Ute , Caimi Daniele , Hönl Simon , Riemensberger Johann , Liu Junqiu , Seidler Paul , Kippenberg Tobias J.
Published: June 2023

The availability of thin-film lithium niobate on insulator (LNOI) and advances in processing have led to the emergence of fully integrated LiNbO3 electro-optic devices. Yet to date, LiNbO3 photonic integrated circuits have mostly been fabricated using non-standard etching techniques and partially etched waveguides, that lack the reproducibility achieved in silicon photonics. Widespread application of thin-film LiNbO3 requires a reliable solution with precise lithographic control. Here we demonstrate a heterogeneously integrated LiNbO3 photonic platform employing wafer-scale bonding of thin-film LiNbO3 to silicon nitride (Si3N4) photonic integrated circuits. The platform maintains the low propagation loss (<0.1 dB/cm) and efficient fiber-to-chip coupling (<2.5 dB per facet) of the Si3N4 waveguides and provides a link between passive Si3N4 circuits and electro-optic components with adiabatic mode converters experiencing insertion losses below 0.1 dB. Using this approach we demonstrate several key applications, thus providing a scalable, foundry-ready solution to complex LiNbO3 integrated photonic circuits.
Parieto-occipital ERP indicators of gut mechanosensation in humans
Authors: Mayeli Ahmad , Al Zoubi Obada , White Evan J. , Chappelle Sheridan , Kuplicki Rayus , Morton Alexa , Bruce Jaimee , Smith Ryan , Feinstein Justin S. , Bodurka Jerzy , Paulus Martin P. , Khalsa Sahib S.
Published: June 2023

Understanding the neural processes governing the human gut-brain connection has been challenging due to the inaccessibility of the body’s interior. Here, we investigated neural responses to gastrointestinal sensation using a minimally invasive mechanosensory probe by quantifying brain, stomach, and perceptual responses following the ingestion of a vibrating capsule. Participants successfully perceived capsule stimulation under two vibration conditions (normal and enhanced), as evidenced by above chance accuracy scores. Perceptual accuracy improved significantly during the enhanced relative to normal stimulation, which was associated with faster stimulation detection and reduced reaction time variability. Capsule stimulation induced late neural responses in parieto-occipital electrodes near the midline. Moreover, these ‘gastric evoked potentials’ showed intensity-dependent increases in amplitude and were significantly correlated with perceptual accuracy. Our results replicated in a separate experiment, and abdominal X-ray imaging localized most capsule stimulations to the gastroduodenal segments. Combined with our prior observation that a Bayesian model is capable of estimating computational parameters of gut-brain mechanosensation, these findings highlight a unique form of enterically-focused sensory monitoring within the human brain, with implications for understanding gut feelings and gut-brain interactions in healthy and clinical populations.
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
Authors: Lenza Maria Pia , Egia-Mendikute Leire , Antoñana-Vildosola Asier , Soares Cátia O. , Coelho Helena , Corzana Francisco , Bosch Alexandre , Manisha Prodhi , Quintana Jon Imanol , Oyenarte Iker , Unione Luca , Moure María Jesús , Azkargorta Mikel , Atxabal Unai , Sobczak Klaudia , Elortza Felix , Sutherland James D. , Barrio Rosa , Marcelo Filipa , Jiménez-Barbero Jesús , Palazon Asis , Ereño-Orbea June
Published: June 2023

Sialic acid-binding Ig-like lectin 15 (Siglec-15) is an immune modulator and emerging cancer immunotherapy target. However, limited understanding of its structure and mechanism of action restrains the development of drug candidates that unleash its full therapeutic potential. In this study, we elucidate the crystal structure of Siglec-15 and its binding epitope via co-crystallization with an anti-Siglec-15 blocking antibody. Using saturation transfer-difference nuclear magnetic resonance (STD-NMR) spectroscopy and molecular dynamics simulations, we reveal Siglec-15 binding mode to α(2,3)- and α(2,6)-linked sialic acids and the cancer-associated sialyl-Tn (STn) glycoform. We demonstrate that binding of Siglec-15 to T cells, which lack STn expression, depends on the presence of α(2,3)- and α(2,6)-linked sialoglycans. Furthermore, we identify the leukocyte integrin CD11b as a Siglec-15 binding partner on human T cells. Collectively, our findings provide an integrated understanding of the structural features of Siglec-15 and emphasize glycosylation as a crucial factor in controlling T cell responses.
Omicron subvariant BA.5 efficiently infects lung cells
Authors: Hoffmann Markus , Wong Lok-Yin Roy , Arora Prerna , Zhang Lu , Rocha Cheila , Odle Abby , Nehlmeier Inga , Kempf Amy , Richter Anja , Halwe Nico Joel , Schön Jacob , Ulrich Lorenz , Hoffmann Donata , Beer Martin , Drosten Christian , Perlman Stanley , Pöhlmann Stefan
Published: June 2023

The SARS-CoV-2 Omicron subvariants BA.1 and BA.2 exhibit reduced lung cell infection relative to previously circulating SARS-CoV-2 variants, which may account for their reduced pathogenicity. However, it is unclear whether lung cell infection by BA.5, which displaced these variants, remains attenuated. Here, we show that the spike (S) protein of BA.5 exhibits increased cleavage at the S1/S2 site and drives cell-cell fusion and lung cell entry with higher efficiency than its counterparts from BA.1 and BA.2. Increased lung cell entry depends on mutation H69Δ/V70Δ and is associated with efficient replication of BA.5 in cultured lung cells. Further, BA.5 replicates in the lungs of female Balb/c mice and the nasal cavity of female ferrets with much higher efficiency than BA.1. These results suggest that BA.5 has acquired the ability to efficiently infect lung cells, a prerequisite for causing severe disease, suggesting that evolution of Omicron subvariants can result in partial loss of attenuation.
A chip-scale atomic beam clock
Authors: Martinez Gabriela D. , Li Chao , Staron Alexander , Kitching John , Raman Chandra , McGehee William R.
Published: June 2023

Atomic beams are a longstanding technology for atom-based sensors and clocks with widespread use in commercial frequency standards. Here, we report the demonstration of a chip-scale microwave atomic beam clock using coherent population trapping (CPT) interrogation in a passively pumped atomic beam device. The beam device consists of a hermetically sealed vacuum cell fabricated from an anodically bonded stack of glass and Si wafers in which lithographically defined capillaries produce Rb atomic beams and passive pumps maintain the vacuum environment. A prototype chip-scale clock is realized using Ramsey CPT spectroscopy of the atomic beam over a 10 mm distance and demonstrates a fractional frequency stability of ≈1.2 × 10−9/$$\sqrt{\tau }$$τfor integration times, τ, from 1 s to 250 s, limited by detection noise. Optimized atomic beam clocks based on this approach may exceed the long-term stability of existing chip-scale clocks, and leading long-term systematics are predicted to limit the ultimate fractional frequency stability below 10−12.
Augmented temperature fluctuation aggravates muscular atrophy through the gut microbiota
Authors: Liu Ya , Guo Yifan , Liu Zheyu , Feng Xu , Zhou Rui , He Yue , Zhou Haiyan , Peng Hui , Huang Yan
Published: June 2023

Large temperature difference is reported to be a risk factor for human health. However, little evidence has reported the effects of temperature fluctuation on sarcopenia, a senile disease characterized by loss of muscle mass and function. Here, we demonstrate that higher diurnal temperature range in humans has a positive correlation with the prevalence of sarcopenia. Fluctuated temperature exposure (10–25 °C) accelerates muscle atrophy and dampens exercise performance in mid-aged male mice. Interestingly, fluctuated temperature alters the microbiota composition with increased levels ofParabacteroides_distasonis,Duncaniella_dubosiiand decreased levels ofCandidatus_Amulumruptor,Roseburia,Eubacterium. Transplantation of fluctuated temperature-shaped microbiota replays the adverse effects on muscle function. Mechanically, we find that altered microbiota increases circulating aminoadipic acid, a lysine degradation product. Aminoadipic acid damages mitochondrial function through inhibiting mitophagy in vitro. AndEubacteriumsupplementation alleviates muscle atrophy and dysfunction induced by fluctuated temperature. Our results uncover the detrimental impact of fluctuated temperature on muscle function and provide a new clue for gut-muscle axis.
TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress
Authors: Kucińska Marika K. , Fedry Juliette , Galli Carmela , Morone Diego , Raimondi Andrea , Soldà Tatiana , Förster Friedrich , Molinari Maurizio
Published: June 2023

The endoplasmic reticulum (ER) is an organelle of nucleated cells that produces proteins, lipids and oligosaccharides. ER volume and activity are increased upon induction of unfolded protein responses (UPR) and are reduced upon activation of ER-phagy programs. A specialized domain of the ER, the nuclear envelope (NE), protects the cell genome with two juxtaposed lipid bilayers, the inner and outer nuclear membranes (INM and ONM) separated by the perinuclear space (PNS). Here we report that expansion of the mammalian ER upon homeostatic perturbations results in TMX4 reductase-driven disassembly of the LINC complexes connecting INM and ONM and in ONM swelling. The physiologic distance between ONM and INM is restored, upon resolution of the ER stress, by asymmetric autophagy of the NE, which involves the LC3 lipidation machinery, the autophagy receptor SEC62 and the direct capture of ONM-derived vesicles by degradative LAMP1/RAB7-positive endolysosomes in a catabolic pathway mechanistically defined as micro-ONM-phagy.
Mean-shift exploration in shape assembly of robot swarms
Authors: Sun Guibin , Zhou Rui , Ma Zhao , Li Yongqi , Groß Roderich , Chen Zhang , Zhao Shiyu
Published: June 2023

The fascinating collective behaviors of biological systems have inspired extensive studies on shape assembly of robot swarms. Here, we propose a strategy for shape assembly of robot swarms based on the idea of mean-shift exploration: when a robot is surrounded by neighboring robots and unoccupied locations, it would actively give up its current location by exploring the highest density of nearby unoccupied locations in the desired shape. This idea is realized by adapting the mean-shift algorithm, which is an optimization technique widely used in machine learning for locating the maxima of a density function. The proposed strategy empowers robot swarms to assemble highly complex shapes with strong adaptability, as verified by experiments with swarms of 50 ground robots. The comparison between the proposed strategy and the state-of-the-art demonstrates its high efficiency especially for large-scale swarms. The proposed strategy can also be adapted to generate interesting behaviors including shape regeneration, cooperative cargo transportation, and complex environment exploration.
Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis
Authors: Xie Tian , Liu Peng , Wu Xinyue , Dong Feitong , Zhang Zike , Yue Jian , Mahawar Usha , Farooq Faheem , Vohra Hisham , Fang Qi , Liu Wenchen , Wattenberg Binks W. , Gong Xin
Published: June 2023

The ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is the initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here we show that purified human SPT-ORMDL complexes are inhibited by the central sphingolipid metabolite ceramide. We have solved the cryo-EM structure of the SPT-ORMDL3 complex in a ceramide-bound state. Structure-guided mutational analyses reveal the essential function of this ceramide binding site for the suppression of SPT activity. Structural studies indicate that ceramide can induce and lock the N-terminus of ORMDL3 into an inhibitory conformation. Furthermore, we demonstrate that childhood amyotrophic lateral sclerosis (ALS) variants in the SPTLC1 subunit cause impaired ceramide sensing in the SPT-ORMDL3 mutants. Our work elucidates the molecular basis of ceramide sensing by the SPT-ORMDL complex for establishing sphingolipid homeostasis and indicates an important role of impaired ceramide sensing in disease development.
d-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation
Authors: Folorunso Oluwarotimi O. , Brown Stephanie E. , Baruah Jugajyoti , Harvey Theresa L. , Jami Shekib A. , Radzishevsky Inna , Wolosker Herman , McNally James M. , Gray John A. , Vasudevan Anju , Balu Darrick T.
Published: June 2023

The proper development and function of telencephalic GABAergic interneurons is critical for maintaining the excitation and inhibition (E/I) balance in cortical circuits. Glutamate contributes to cortical interneuron (CIN) development viaN-methyl-d-aspartate receptors (NMDARs). NMDAR activation requires the binding of a co-agonist, either glycine ord-serine.d-serine (co-agonist at many mature forebrain synapses) is racemized by the neuronal enzyme serine racemase (SR) froml-serine. We utilized constitutive SR knockout (SR−/−) mice to investigate the effect ofd-serine availability on the development of CINs and inhibitory synapses in the prelimbic cortex (PrL). We found that most immature Lhx6 + CINs expressed SR and the obligatory NMDAR subunit NR1. At embryonic day 15, SR−/−mice had an accumulation of GABA and increased mitotic proliferation in the ganglionic eminence and fewerGad1 + (glutamic acid decarboxylase 67 kDa; GAD67) cells in the E18 neocortex. Lhx6 + cells develop into parvalbumin (PV+) and somatostatin (Sst+) CINs. In the PrL of postnatal day (PND) 16 SR−/−mice, there was a significant decrease in GAD67+ and PV+, but not SST + CIN density, which was associated with reduced inhibitory postsynaptic potentials in layer 2/3 pyramidal neurons. These results demonstrate that D-serine availability is essential for prenatal CIN development and postnatal cortical circuit maturation.
A multiscale analysis of heatwaves and urban heat islands in the western U.S. during the summer of 2021
Authors: Chen Kaiyu , Boomsma Jacob , Holmes Heather A.
Published: June 2023

Extreme heat events are occurring more frequently and with greater intensity due to climate change. They result in increased heat stress to populations causing human health impacts and heat-related deaths. The urban environment can also exacerbate heat stress because of man-made materials and increased population density. Here we investigate the extreme heatwaves in the western U.S. during the summer of 2021. We show the atmospheric scale interactions and spatiotemporal dynamics that contribute to increased temperatures across the region for both urban and rural environments. In 2021, daytime maximum temperatures during heat events in eight major cities were 10–20 °C higher than the 10-year average maximum temperature. We discuss the temperature impacts associated with processes across scales: climate or long-term change, the El Niño–Southern Oscillation, synoptic high-pressure systems, mesoscale ocean/lake breezes, and urban climate (i.e., urban heat islands). Our findings demonstrate the importance of scale interactions impacting extreme heat and the need for holistic approaches in heat mitigation strategies.
Patient-reported distress at a cancer center during the COVID-19 pandemic
Authors: Shah Manan P. , Rosenthal Sarah W. , Roy Mohana , Khaki Ali Raza , Hernandez-Boussard Tina , Ramchandran Kavitha
Published: June 2023

Assessments of health-related quality of life (HRQOL) are conducted by health systems to improve patient-centered care. Studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019–3/15/2020, surge1: 6/17/2020–9/7/2020, valley1: 9/8/2020–11/16/2020, surge2: 11/17/2020–3/2/2021, and valley2: 3/3/2021–6/15/2021). A total of 25,192 surveys among 7209 patients were included in the study. Mean GMH score for patients before the COVID-19 pandemic (50.57) was similar to those during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. At this comprehensive cancer center, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores.
Influence of ecological traits on spatio-temporal dynamics of an elasmobranch community in a heavily exploited basin
Authors: Maioli Federico , Weigel Benjamin , Chiarabelli Elettra , Manfredi Chiara , Anibaldi Alessandra , Isailović Igor , Vrgoč Nedo , Casini Michele
Published: June 2023

Elasmobranchs, which include sharks and batoids, play critical roles in maintaining the integrity and stability of marine food webs. However, these cartilaginous fish are among the most threatened vertebrate lineages due to their widespread depletion. Consequently, understanding dynamics and predicting changes of elasmobranch communities are major research topics in conservation ecology. Here, we leverage long-term catch data from a standardized bottom trawl survey conducted from 1996 to 2019, to evaluate the spatio-temporal dynamics of the elasmobranch community in the heavily exploited Adriatic Sea, where these fish have historically been depleted. We use joint species distribution modeling to quantify the responses of the species to environmental variation while also including important traits such as species age at first maturity, reproductive mode, trophic level, and phylogenetic information. We present spatio-temporal changes in the species community and associated modification of the trait composition, highlighting strong spatial and depth-mediated patterning. We observed an overall increase in the abundance of the dominant elasmobranch species, except for spurdog, which has shown a continued decline. However, our results showed that the present community displays lower age at first maturity and a smaller fraction of viviparous species compared to the earlier observed community due to changes in species’ relative abundance. The selected traits contributed considerably to explaining community patterns, suggesting that the integration of trait-based approaches in elasmobranch community analyses can aid efforts to conserve this important lineage of fish.
Reference-based cell type matching of in situ image-based spatial transcriptomics data on primary visual cortex of mouse brain
Authors: Zhang Yun , Miller Jeremy A. , Park Jeongbin , Lelieveldt Boudewijn P. , Long Brian , Abdelaal Tamim , Aevermann Brian D. , Biancalani Tommaso , Comiter Charles , Dzyubachyk Oleh , Eggermont Jeroen , Langseth Christoffer Mattsson , Petukhov Viktor , Scalia Gabriele , Vaishnav Eeshit Dhaval , Zhao Yilin , Lein Ed S. , Scheuermann Richard H.
Published: June 2023

With the advent of multiplex fluorescence in situ hybridization (FISH) and in situ RNA sequencing technologies, spatial transcriptomics analysis is advancing rapidly, providing spatial location and gene expression information about cells in tissue sections at single cell resolution. Cell type classification of these spatially-resolved cells can be inferred by matching the spatial transcriptomics data to reference atlases derived from single cell RNA-sequencing (scRNA-seq) in which cell types are defined by differences in their gene expression profiles. However, robust cell type matching of the spatially-resolved cells to reference scRNA-seq atlases is challenging due to the intrinsic differences in resolution between the spatial and scRNA-seq data. In this study, we systematically evaluated six computational algorithms for cell type matching across four image-based spatial transcriptomics experimental protocols (MERFISH, smFISH, BaristaSeq, and ExSeq) conducted on the same mouse primary visual cortex (VISp) brain region. We find that many cells are assigned as the same type by multiple cell type matching algorithms and are present in spatial patterns previously reported from scRNA-seq studies in VISp. Furthermore, by combining the results of individual matching strategies into consensus cell type assignments, we see even greater alignment with biological expectations. We present two ensemble meta-analysis strategies used in this study and share the consensus cell type matching results in the Cytosplore Viewer (https://viewer.cytosplore.org) for interactive visualization and data exploration. The consensus matching can also guide spatial data analysis using SSAM, allowing segmentation-free cell type assignment.
Therapeutic potential of stem cells and acitretin on inflammatory signaling pathway-associated genes regulated by miRNAs 146a and 155 in AD-like rats
Authors: Elzayat Emad M. , Shahien Sherif A. , El-Sherif Ahmed A. , Hosney Mohamed
Published: June 2023

Alzheimer’s disease (AD) is one of the most common causes of dementia. Several drugs are used to improve the symptoms, but do not stop AD progression. There are more promising treatments that may have a significant role in AD diagnosis and treatment such as miRNAs and stem cells. The present study aims to develop a new approach for AD treatment by mesenchymal stem cells (MSCs) and/or acitretin with special reference to inflammatory signaling pathway as NF-kB and its regulator miRNAs in AD-like rat model. Fourty-five male albino rats were allotted for the present study. The experimental periods were divided into induction, withdrawal, and therapeutic phases. Expression levels of miR-146a, miR-155, necrotic, growth and inflammatory genes were assessed using RT-qPCR. Histopathological examination of brain tissues was performed in different rat groups. The normal physiological, molecular, and histopathological levels were restored after treatment with MSCs and/or acitretin. The present study demonstrates that the miR-146a and miR-155 might be used as promising biomarkers for AD. MSCs and/or acitretin proved their therapeutic potential in restoring the expression levels of targeted miRNAs and their related genes concerning NF-kB signaling pathway.