bluuebunny/crossref_metadata_2025 huggingface dataset:
State, Urban Space, Race: Late Colonialism and Segregation at the Ikoyi Reservation in Lagos, Nigeria
Authors: Livsey Tim
Published: September 2022

This article studies the Ikoyi reservation in Lagos, Nigeria to assess changing relationships between the colonial state, urban space, and race between 1935 and 1955. Colonial authorities established reservations as special zones to house colonial officials and other white Westerners. The article shows that the Ikoyi reservation was a significant location where a wide range of actors contested relationships between statehood and race. These renegotiations contributed to making a late colonial state, a terminal form of colonial state in which explicitly racialised discourses of statehood and urban space were challenged while implicitly racialised standards and practices often persisted. Through a focus on Ikoyi, the article highlights the important relationships between segregationist projects and late colonial statehood.
Friendship and International Relations in the Himalayas: Bhutan, Britain, and the 1910 Treaty of Punakha
Authors: Kaul Nitasha
Published: September 2022

This article posits that friendship has been a particularly fertile and creative category against the backdrop of imperial expansion and consolidation in the Himalayas. As a small but strategically perceived sovereign Himalayan country, Bhutan's history through the last centuries has been marked simultaneously by imperial and post-colonial asymmetries of power. The term “friendship” is deployed as a key diplomatic category in Bhutan's most significant relationship, that with its much larger neighbour India. However, the origin of this friendship is always traced back to the mid-twentieth-century post-colonial period. In contradistinction to this, I constellate a much longer history of this friendship with a special focus on the landmark 1910 Treaty of Punakha between Bhutan and Britain, which was a key turning point in Bhutan's relations with its southern neighbour (British India at the time). Scholars typically state as a matter of fact that in the year 1910, with the initiative of Political Officer Charles Bell, a treaty was signed between Britain and Bhutan that placed Bhutan's external relations under the guidance of Britain. This present work is situated within the oeuvre of critically rereading imperial sources and evaluating their historical legacies, and is the first detailed scholarly analysis of why this treaty was significant and how it came to be signed. I identify the factors that were at work in how and why the 1910 friendship treaty was realised for imperial British purposes—the interpersonal friendships fostered by the British Political Officers; the threat of China as an Other; and the representation of material and ideational advantages from associating with an imperial power. In making this argument, I analyse the role played by the vocabulary of friendship and draw upon primary archival sources to illustrate the factors that were at work as well as the dissonance between the archival and public rationales provided by Political Officer Bell. The 1910 treaty was signed at a watershed moment after the then-recent installation of a monarchy in Bhutan in 1907, and against the great game backdrop of Qing activities in Tibet and British interests in the region; throughout the twentieth century, the impact of this friendship treaty was of paramount significance, and its shadow continues into the twenty-first century.
Irregular subgraphs
Authors: Alon Noga , Wei Fan
Published: September 2022

We suggest two related conjectures dealing with the existence of spanning irregular subgraphs of graphs. The first asserts that any
$d$
-regular graph on
$n$
vertices contains a spanning subgraph in which the number of vertices of each degree between
$0$
and
$d$
deviates from
$\frac{n}{d+1}$
by at most
$2$
. The second is that every graph on
$n$
vertices with minimum degree
$\delta$
contains a spanning subgraph in which the number of vertices of each degree does not exceed
$\frac{n}{\delta +1}+2$
. Both conjectures remain open, but we prove several asymptotic relaxations for graphs with a large number of vertices
$n$
. In particular we show that if
$d^3 \log n \leq o(n)$
then every
$d$
-regular graph with
$n$
vertices contains a spanning subgraph in which the number of vertices of each degree between
$0$
and
$d$
is
$(1+o(1))\frac{n}{d+1}$
. We also prove that any graph with
$n$
vertices and minimum degree
$\delta$
contains a spanning subgraph in which no degree is repeated more than
$(1+o(1))\frac{n}{\delta +1}+2$
times.
The Conservative Policy Bias of US Senate Malapportionment
Authors: Johnson Richard , Miller Lisa L.
Published: September 2022

The US Senate is unique in the United States and rare internationally for its total disregard of population differences among its representational units. To analyze malapportionment’s policy impact, we devised a hypothetical reapportionment scheme that more closely approximates state population but remains favorable to small states. We developed a formula to reweight senators’ roll-call votes to reflect better state population differences. We recalculated 804 key US Senate votes between 1961 and 2019 and found that state equality in the Senate systematically biases policy outcomes toward Republican preferences.
New institutional economics in Viking studies. Visualising immaterial culture
Authors: Ögren Anders , Hedenstierna-Jonson Charlotte , Ljungkvist John , Raffield Ben , Price Neil
Published: September 2022

In this paper, we argue that closer engagement with the field of new institutional economics (NIE) has the potential to provide researchers with a new theoretical toolbox that can be used to study economic and social practices that are not readily traceable in material culture. NIE assumes that individual actions are based on bounded rationality and that the existence of rules (institutions) and their enforcement – the institutional framework – influences agents’ actions by providing different incentives and probabilities for different choices. Within this theoretical framework, we identify a number of concepts, such ascollective identityandmobile jurisdictions, that seem to fit what we know of Viking age economic systems. In applying these models to the available archaeological and textual data, we outline the ways in which further research could provide a new understanding of economic interaction within a rapidly evolving context of diaspora and change.
Pre-critical archaeology. Speculative realism and symmetrical archaeology
Authors: Govier Eloise
Published: September 2022

The rise of Symmetrical Archaeology has subtly recast archaeology as the study of things and not the study of the past or past peoples. This new description of the archaeological endeavour is often met with criticism. This paper continues in the critical vein but embraces a different strategy of engagement. Here, second-wave Symmetrical Archaeology is brought to the fore: its historical development explored, its methodology outlined, its current theoretical basis assessed. Part critique, part defence, I consider the logical underpinning of the second-wave, focusing on ontology and agency. Utilizing Levi Bryant’s ontic principle, I attend to these two issues and frame this style of archaeology as Pre-critical Archaeology. A caveat seems necessary: whilst I spend time with Symmetrical Archaeology in this paper, that does not mean I am a convert. Rather, my ambition here is to see things from the point of view of a Symmetrical archaeologist.
Radio-induced malignancies of the scalp in adult after depilatory radiotherapy for tinea capitis in childhood: 137 cases
Authors: Asma Hadhri , Safia Yahyaoui , Semia Zarraa , Ghaiet El Fida Noubbigh , Rim Abidi , Khalil Mahjoubi , Taha Messai , Chiraz Nasr , Mongi Maalej
Published: September 2022

Introduction:

Radiation-induced malignancies are the most feared complications of radiotherapy. Depilatory radiotherapy for ringworm of the scalp in childhood was the cause of an increase in the incidence of skin tumours of the scalp in adults. The aim of our study was to describe the epidemiological, clinical and therapeutic characteristics of radiation-induced skin tumours of the scalp in order to highlight the characteristics of these tumours compared to non-radiation-induced tumours.

Methods:

This is a bi-centric retrospective study, extending over a period of 41 years, which collected 137 patients with 200 tumours of the scalp. These patients were selected after noting a history of depilatory radiotherapy for ringworm in childhood in the clinical records of all patients with scalp tumours.

We studied the epidemiological, clinical, therapeutic and evolving characteristics of this population.

Results:

The average age of consultation was 56·6 years. The sex ratio M/F was 3. Radiation dermatitis was found in 33% of cases. The average latency between depilatory radiotherapy and the appearance of radiation-induced tumours was 42·6 years. Multiple carcinomas (>2 tumours) were observed in 23·3% of cases. In 73% of cases, ulceration was the most frequent macroscopic aspect. The predominant histological type was basal cell carcinoma in 82% of cases. Radiation therapy has been the main treatment modality in 77·3% of cases, followed by surgery in 43% of cases. The appearance of new tumours on the scalp was observed in six patients.

Conclusion:

Radiation-induced tumours of the scalp are comparable in epidemiological and clinical characteristics to non-radiation-induced tumours. However, they may represent a challenge in therapeutic care and require regular monitoring.
Negotiating with organized crime groups: Questions of law, policy and imagination
Authors: Freeman Mark , Casij Peña Mariana
Published: September 2022

Negotiations with organized crime groups occur more often than realized, and raise complex questions of ethics, practice and policy. Currently, law provides few incentives for States to choose the path of negotiation, and thus the political costs and moral hazards remain very high and a mano dura (“firm hand”) approach prevails. This paper examines some of the challenges faced by those who in good faith might initiate or participate in negotiations with such groups, offering an assessment of how those challenges can be mitigated and an inquiry, in particular, into how law and policy might be improved or reimagined to make such negotiation more feasible and effective in contexts of armed conflict or other situations of violence.
Outcome after bilateral deep vein thrombosis
Authors: Fürbringer-Schwarz Aline , Janscak Marie , Jeanneret-Gris Christina R.
Published: September 2022

Summary: Background: The aim of our study was to assess how often deep vein thrombosis (DVT) occurs bilaterally and if this has an impact on the recurrence rate of thromboembolic disease and on the occurrence of malignant tumors. Additionally, the occurrence of pulmonary embolism and mortality of patients was assessed. Patients and methods: For this observational study, we retrospectively screened all patient’s records for DVT, investigated between 2000 and 2017. 2409 patients with the diagnosis of DVT were found. The patients aged between 18 and 89 years old in 2017, received a follow-up questionnaire, asking for thromboembolic recurrence, malignant tumors and pulmonary embolism. 755 patients were included in the follow-up cohort (604 with unilateral, 151 with bilateral DVT). We performed nonparametric tests to assess two group analysis. Results: Bilateral DVT occurred in 19% of the patients in this cohort. Patients with bilateral DVT develop significantly more often cancer, either at the time of diagnosis or in the follow up, compared to patients with unilateral DVT (22.5% vs. 15.4%, p=0.036). They also endure significantly more often pulmonary embolism simultaneously (33.8% vs. 20.8%, p<0.001). Patients with bilateral DVT were significantly older (median 69 years) than patients with unilateral DVT (median 63 years, p<0.001). In addition, patients with bilateral DVT show a higher mortality (9.1% vs. 5.2%, p=0.002), a higher recurrence rate could not be observed. Conclusions: Bilateral DVT is more common than published so far. Patients with bilateral DVT suffer more often from malignant tumors, and are more often diagnosed with pulmonary embolism. The patients with bilateral DVT are older and have a higher mortality. Further investigations should address the issue of recurrent thromboembolic disease in a prospective cohort study.
Numerical Weather Prediction at 200 m Local Resolution Based on an Unstructured Grid Global Model
Authors: Sze Wai‐Pang , Tang Sze‐Chai , Cheung Chi‐Chiu , Tam Chi‐Yung
Published: September 2022

It is a great challenge to reach sub‐km resolution in numerical weather prediction models without using domain nesting techniques. The Model for Prediction Across Scales – Atmosphere (MPAS‐A) uses an unstructured grid to achieve smooth transition of resolution in a global model. However, a number of model physical parameterization schemes and methods to enhance computational efficiency assume resolution down to about 3 km only. We extended the MPAS‐A model to support resolution down to 200 m and carried out idealized and hindcast numerical experiments over a domain covering Hong Kong. The Shin‐Hong Planetary Boundary Layer scheme was integrated to parameterize partially resolved turbulence in a scale‐aware sense. The quality of static geographical data and land‐water boundary for a coastal urban locale are found to be vital to the forecast accuracy of ground temperature and humidity forecast. Resolving terrain to 200 m, the model is found to be able to simulate the sheltering effect of mountains as well as high wind speed at hill top comparable to station observation. Our results indicate that global model simulations with an unstructured grid can realistically reproduce local weather conditions, suitable for ultra‐high‐resolution predictions and studies.
Morphology of Extreme and Far Ultraviolet Martian Airglow Emissions Observed by the EMUS Instrument on Board the Emirates Mars Mission
Authors: Jain Sonal K. , Deighan Justin , Chaffin Mike , Holsclaw Greg , Lillis Rob , Fillingim Matt , Evans J. Scott , Correira John , AlMatroushi Hessa , Lootah Fatma , England Scott , AlMazmi Hoor , Thiemann Ed , Chamberlin Phil , Eparvier Frank
Published: September 2022

We present the first continuous observations of the extreme and far ultraviolet (EUV and FUV) dayglow emissions measured by Emirates Mars Ultraviolet Spectrometer (EMUS) onboard the Emirates Mars Mission. We found excellent agreement between the previous observations from the Hopkins Ultraviolet Telescope and recent observations by EMUS both in shape and magnitude. We presented the average disk brightness of major EUV and FUV emissions for about 10 months of data from April 2021 to February 2022. The solar activity was mild/minimum during the first half of the period presented in this study, but we noticed significant day‐to‐day variations in the major dayglow emissions independent of solar activity, indicating possible coupling from the lower atmosphere via waves/tides. The solar activity increased significantly during the second half of the study period. Our analysis showed that all major EUV and FUV emissions are highly correlated with solar forcing as well as seasonal changes.
EWR‐Net: Earthquake Waveform Regularization Network for Irregular Station Data Based on Deep Generative Model and ResNet
Authors: Gan Haodong , Pan Xiao , Tang Ke , Hu Nan , Zhang Wei
Published: September 2022

Owing to the limitations of surface conditions, the distribution of earthquake station arrays, even dense arrays, is uneven and spatially irregular. The station intervals are too large with respect to migration algorithm requirements. Therefore, the regularization of irregular station data is an important preprocessing step before imaging. Several methods, such as the curvelet transform method based on the sparse transform, have been developed for regularizing teleseismic data. In this study, we present a novel deep learning (DL) approach for teleseismic waveform regularization in 2D surveys. We designed an earthquake waveform regularization network (EWR‐Net) based on a deep generative model and residual network, consisting of a transposed convolution block, convolution block, and full connection block. The convolution block was variable and adjusted according to different data complexities to improve adaptability. The network was able to capture complex mapping between station locations and waveforms, and could be used to regularize both randomly and regularly sampled data without spatial smoothing. Unlike other DL methods, the EWR‐Net was trained and used for each event. It was trained using recorded teleseismic waveforms at irregular stations, and was then used to predict waveforms at regular stations. To avoid overfitting, L2 regularization, dropout in the full connection block, and early stopping were employed. The test results on both synthetic and field data showed that EWR‐Net could generate more accurate earthquake waveforms at virtual stations than the curvelet method. Reverse‐time migration imaging tests using regularized data demonstrated the feasibility of the proposed method.
Numerical Investigation of Tropical Indian Ocean Barrier Layer Variability
Authors: Valsala Vinu , Prajeesh A. G. , Singh Shikha
Published: September 2022

The barrier layer (BL) is part of the surface ocean isolated from the local air‐sea exchange processes despite it's great potential to store the heat beneath the mixed layer. The tropical oceans are known for the presence of BL. The interannual variability of the BL of the tropical Indian Ocean is examined in this study with a concomitant analysis of observations and outputs from an ocean general circulation model. The model faithfully reproduces the tropical variability of the dynamics and thermodynamics of the Indian Ocean when compared with observations and other studies. The BL thins (thickens) in the eastern (central‐to‐western) tropical Indian Ocean during the positive phase of the Indian Ocean Dipole Mode (IOD). The individual roles of five major forcing mechanisms on BL‐IOD coupling are examined. The thinning in the east is caused by upward heaving thermocline due to upwelling Kelvin waves during the positive phase of the IOD, causing the isothermal layer to shoal steeper than the mixed layer. The surface freshwater fluxes substantiate the thinning of BL in the east during this time, while the net heat fluxes thin the BL in the entire tropical Indian Ocean. The basin‐wide salinity (temperature) dynamics have widespread and complementary impacts, a BL thickening (thinning) in the equatorial and eastern tropical Indian Ocean during positive IOD years, with the former overwhelming the latter. The thickening of BL in the central‐to‐western tropical Indian Ocean during positive IOD is due to a combined action of salinity and freshwater forcing. The thermocline heaving, temperature and salinity dynamics and buoyancy forcing could explain the net variability of BL in the tropical Indian Ocean almost entirely in the model. The ocean‐only response shows that a BL weakens the shoaling (deepening) of the ocean mixed layer during positive (negative) IOD years in the eastern tropical Indian Ocean. As barrier layers store heat beneath the mixed layer, their role in Indian Ocean weather and climate needs to be examined with coupled model experiments.
Wave Enhanced Overtides in an Idealized Tidal Inlet System
Authors: Rickerich S. , Ross L. , Valle‐Levinson A.
Published: September 2022

Tidal water levels and currents in the shallow water environments of the inner shelf are subject to nonlinear interactions that produce higher frequency harmonics known as overtides, which contribute to the residual transport of scalars. The primary hydrodynamic overtide generating mechanisms (advection, nonlinear continuity and bottom friction) are well known. Yet, other mechanisms may exist in coupled systems characterized by wind waves and barotropic tides. This work uses process‐oriented coupled tides‐waves numerical simulations of an idealized barrier beach domain to study the effect of varying tidal range and wave conditions (height, period, direction) to investigate new mechanisms of overtide generation. Harmonic analysis of results from 92 simulations indicates that an increase in wave height amplifies overtide current velocities in both the alongshore and cross‐shore directions, while changes in wave period and wave direction have a lesser effect. A maximum increase of ∼140% in overtide current velocity magnitudes was observed in domain‐wide averages from a tides only to a coupled tides‐waves simulation. Decomposition of the depth‐averaged momentum balance of the tides only and tides‐waves simulations identify bottom stress, pressure gradient, and bottom wave streaming enhancing overtide generation. Accelerations from wave‐enhanced pressure gradients and bottom wave streaming produce a shoreward bottom current and an offshore directed return flow that persist throughout a semidiurnal tidal cycle, interacting with tidal currents to enhance asymmetries between flood and ebb.
Number‐Size Distribution and CCN Activity of Atmospheric Aerosols in the Western North Pacific During Spring Pre‐Bloom Period: Influences of Terrestrial and Marine Sources
Authors: Kawana Kaori , Miyazaki Yuzo , Omori Yuko , Tanimoto Hiroshi , Kagami Sara , Suzuki Koji , Yamashita Youhei , Nishioka Jun , Deng Yange , Yai Hikari , Mochida Michihiro
Published: September 2022

A cruise observation of atmospheric aerosols and gaseous air/seawater compounds was performed in the western North Pacific during the spring pre‐bloom period. The aerosol size distribution and cloud condensation nuclei (CCN) activity were characterized according to the source type: terrestrial/pollution, marine, and mixed. The CCN activity was represented by the aerosol hygroscopicity parameter (ĸCCNC) from the activation diameter (dact) in water‐vapor supersaturation (SS), which is controlled by the composition of particles with sizes around dact. For marine type, whereas a high hygroscopicity parameter value of 0.86 for accumulation mode (ĸaccum) suggests a strong influence of sea salt and sulfate, a lower value of 0.49 in Aitken mode (ĸAit) suggests the contribution of biogenic organic matter (OM). Lower ĸAit and ĸaccum for terrestrial/pollution type (0.12 and 0.62, respectively) suggests greater contributions of OM. Under the influence of marine sources, ĸCCNC at a dact of ∼110 nm (low SS) was not responsive to the chlorophyll a (Chl‐a) concentration, whereas ĸCCNC at ∼50 nm (high SS) correlated negatively with Chl‐a. The hygroscopicity parameter of OM was estimated as 0.13–0.29 considering the aerosol composition. During a new particle formation event, the ĸCCNC at 0.60% SS increased; nucleated particles grew in size to become CCN. Sensitivity analysis indicated that changes in the size distribution and chemical composition of the aerosol contributed to the increase in CCN concentration. This study highlights the high variability in size distribution and CCN activity of off‐coast aerosols from different sources, including marine biological activities.
Solar Cycle Variability in Coronal Holes and Their Effects on Solar Wind Sources
Authors: Luhmann J. G. , Li Yan , Lee C. O. , Jian L. K. , Arge C. N. , Riley P.
Published: September 2022

Various upstream spacecraft have now observed the solar wind conditions affecting the Earth since the 1970s, covering over four solar activity cycles. These measurements provide a long term picture of the related patterns in large scale incident plasma and magnetic field parameters of interest for both interpreting cycles in geospace effects, and understanding how the Sun controls our space environment. This paper focuses on the latter, in part to provide context at the start of the new solar cycle 25, and toward establishing connections between the 1 AU ecliptic solar wind behavior and the unprecedented near‐Sun measurements of heliospheric features on Parker Solar Probe and Solar Orbiter. Magnetograph data‐based potential field source surface models provide a basic picture of how the solar wind sources, including those that give rise to corotating high speed streams in the ecliptic, have changed since the beginning of the record of regular solar wind measurements. In particular, they suggest the contributions from low to mid latitude coronal holes dominate the observed cycles (21–24), especially the weaker cycles (23 and 24), impacting upstream measurement interpretations, modeling, and forecasting considerations. For example, recurring features are affected by differential rotation of the Sun's surface field, which through its effects on the corona, can produce solar wind streams reappearing at ∼25–30 days intervals instead of at the canonical 27.3 days Carrington rotation rate. In addition, the conditions that lead to the corotating stream structure that can dominate periods of low solar activity are seen to be more complicated than suggested by the simple concepts of early studies. The overall results illustrate where in the cycles well‐defined, long‐lived large scale structures can be expected, and the advantages of synoptic displays of 1 AU solar wind parameters for anticipating timings of recurring features.
Mn5+-activated Ca6Ba(PO4)4O near-infrared phosphor and its application in luminescence thermometry
Authors: Dramićanin Miroslav D. , Marciniak Łukasz , Kuzman Sanja , Piotrowski Wojciech , Ristić Zoran , Periša Jovana , Evans Ivana , Mitrić Jelena , Đorđević Vesna , Romčević Nebojša , Brik Mikhail G. , Ma Chong-Geng
Published: September 2022

The near-infrared luminescence of Ca6Ba(PO4)4O:Mn5+ is demonstrated and explained. When excited into the broad and strong absorption band that spans the 500–1000 nm spectral range, this phosphor provides an ultranarrow (FWHM = 5 nm) emission centered at 1140 nm that originates from a spin-forbidden 1E → 3A2 transition with a 37.5% internal quantum efficiency and an excited-state lifetime of about 350 μs. We derived the crystal field and Racah parameters and calculated the appropriate Tanabe–Sugano diagram for this phosphor. We found that 1E emission quenches due to the thermally-assisted cross-over with the 3T2 state and that the relatively high Debye temperature of 783 K of Ca6Ba(PO4)4O facilitates efficient emission. Since Ca6Ba(PO4)4O also provides efficient yellow emission of the Eu2+ dopant, we calculated and explained its electronic band structure, the partial and total density of states, effective Mulliken charges of all ions, elastic constants, Debye temperature, and vibrational spectra. Finally, we demonstrated the application of phosphor in a luminescence intensity ratio thermometry and obtained a relative sensitivity of 1.92%K−1 and a temperature resolution of 0.2 K in the range of physiological temperatures.
Recurrent febrile seizures and serum cytokines: a controlled follow-up study
Authors: Hautala Maria K. , Helander Heli M. , Pokka Tytti M-L , Koskela Ulla V. , Rantala Heikki M. J. , Uhari Matti K. , Korkiamäki Timo J. , Glumoff Virpi , Mikkonen Kirsi H.
Published: September 2022

Background

The role of cytokines in the pathogenesis of febrile seizures (FSs) is unclear, and information regarding cytokine production outside of FS episodes is scarce.

Methods

In our controlled follow-up study of patients with FSs, we compared the levels of 12 serum cytokines after the patients’ first FSs, during febrile episodes without FSs, after recurrent FSs, during healthy periods after FSs, and between patients and controls.

Results

Two-hundred fifty-one patients with first FS participated in the study, of whom 17 (mean age 1.6 years, SD 0.7) with recurrent FSs completed the protocol as required by the sample size calculations. The mean IL-1RA level was higher after the first FSs (2580 pg/mL, SD 1516) than during febrile episodes without FSs (1336 pg/mL, SD 1364, P = 0.006) and healthy periods after FSs (474 pg/mL, SD 901, P = 0.001). IL-1RA levels were also higher during first (2580 pg/mL) and recurrent FSs (2666 pg/mL, SD 1747) in comparison with febrile controls (746 pg/mL, SD 551) (P < 0.001 and P = 0.001, respectively), but there was no difference in the IL-1RA between febrile episodes without FSs and febrile controls.

Conclusions

Patients with FSs produce stronger inflammatory reactions during febrile episodes with FSs compared with febrile episodes without FSs and febrile controls.

Impact

In patients with FSs, IL-1RA was higher following first FS than during febrile episodes without FSs and healthy periods after FSs.

IL-1RA was higher in patients with FSs following first and recurrent FSs than in febrile controls.

There was no significant difference in IL-1RA between febrile episodes of patients without FSs and febrile controls.

Using IL-1RA as a surrogate marker of IL-1 axis activity, our results indicate that patients with FSs produced stronger inflammatory reactions during FS episodes but not during other febrile episodes or healthy periods after FSs.

Cytokines may play a role in pathogenesis of FSs.
Perinatal exposure to UDCA prevents neonatal cholestasis in Cyp2c70-/- mice with human-like bile acids
Authors: de Vries Hilde D. , Palmiotti Anna , Li Rumei , Hovingh Milaine V. , Mulder Niels L. , Koehorst Martijn , Bloks Vincent W. , van Zutphen Tim , Kuipers Folkert , de Boer Jan Freark
Published: September 2022

Background

Cyp2c70-/- mice with a human-like bile acid (BA) composition display features of neonatal cholestasis. We assessed whether perinatal ursodeoxycholic acid (UDCA) exposure prevents neonatal cholestasis in Cyp2c70-/- mice and reduces cholangiopathy development later in life.

Methods

Cyp2c70+/- males were crossed with Cyp2c70+/- females fed either a regular chow diet or a 0.1% UDCA-containing diet during breeding, gestation, and suckling. Cholestasis and liver function parameters were assessed in their Cyp2c70-/- and wild-type offspring at 3 and 8 weeks of age.

Results

Three-week-old Cyp2c70-/- pups showed features of neonatal cholestasis, including elevated plasma BAs and transaminases, which were completely prevented in Cyp2c70-/- pups upon perinatal UDCA exposure. In addition, UDCA administration to the dams corrected altered hepatic gene expression patterns in Cyp2c70-/- pups, reduced markers of fibrogenesis and inflammation, and prevented cholangiocyte proliferation. Yet, these beneficial effects of perinatal UDCA exposure were not retained into adulthood upon discontinuation of treatment.

Conclusion

Perinatal exposure of Cyp2c70-/- mice to UDCA has beneficial effects on liver function parameters, supporting a direct role of BA hydrophobicity in the development of neonatal cholestasis in these mice. However, prevention of neonatal cholestasis in Cyp2c70-/- mice has no long-lasting effects on liver pathophysiology.

Impact

This is the first study showing that perinatal UDCA exposure prevents features of neonatal cholestasis that are observed in mice with a human-like bile acid composition, i.e., Cyp2c70-/- mice.

Perinatal UDCA exposure of Cyp2c70-/- pups leads to UDCA enrichment in their circulating bile acid pool and, consequently, to a reduced hydrophobicity of biliary bile acids.

Perinatal UDCA exposure of Cyp2c70-/- pups has no long-lasting effects on the development of cholangiopathy after discontinuation of treatment.

The results in this study expand current knowledge regarding acute and long-lasting effects of UDCA treatment in early life.
Neurological examination at 32-weeks postmenstrual age predicts 12-month cognitive outcomes in very preterm-born infants
Authors: Huf Isabel U. , Baque Emmah , Colditz Paul B. , Chatfield Mark D. , Ware Robert S. , Boyd Roslyn N. , George Joanne M.
Published: September 2022

Background

To determine the diagnostic accuracy of Hammersmith Neonatal Neurological Examination (HNNE) at 30–32 weeks postmenstrual age (PMA, ‘Early’) and term equivalent age (TEA) in infants born <31 weeks PMA to predict cognitive outcomes at 12 months corrected age (CA).

Methods

Prospective cohort study of 119 infants (73 males; median 28.4 weeks gestational age at birth) who underwent Early and TEA HNNE. At 12 months CA, 104 participants completed Bayley Scales of Infant and Toddler Development, 3rd Edition, (Bayley-III). Optimum cut-off points for each HNNE subscale were determined to establish diagnostic accuracy for predicting adverse cognitive outcomes on the Bayley-III Cognitive Composite Scale (≤85).

Results

The best diagnostic accuracy for HNNE total score at 30–32 weeks PMA predicting cognitive impairment occurred at cut-off ≤16.7 (sensitivity (Se) = 71%, specificity (Sp) = 51%). The Abnormal Signs subscale demonstrated the best balance of sensitivity/specificity combination (Se = 71%, Sp = 71%; cut-off ≤1.5). For HNNE at TEA, the total score at cut-off ≤24.5 had Se = 71% and Sp = 47% for predicting cognitive impairment. The Tone Patterns subscale demonstrated the strongest diagnostic accuracy at TEA (Se = 71%, Sp = 63%; cut-off ≤3).

Conclusions

Early and TEA HNNE demonstrated moderate diagnostic accuracy for cognitive outcomes at 12-months CA in infants born <31 weeks gestational age.

Clinical Trial Registration: Australian New Zealand Clinical Trials Registry; Trial Registration Number: ACTRN12613000280707; web address of trial: http://www.ANZCTR.org.au/ACTRN12613000280707.aspx.

Impact

Early Hammersmith Neonatal Neurological Examination (HNNE) assessment at 30–32 weeks postmenstrual age has moderate diagnostic accuracy for cognitive outcomes at 12 months corrected age in infants born <31 weeks gestation.

Early HNNE at 30–32 weeks has stronger predictive validity than HNNE at term equivalent age.

Early HNNE may provide an early marker for risk-stratification to optimise the planning of post-discharge support and follow-up services for infants born preterm.
Structural and functional retinal alterations in patients with paranoid schizophrenia
Authors: Friedel Evelyn B. N. , Hahn Hannah-Tabea , Maier Simon , Küchlin Sebastian , Reich Michael , Runge Kimon , Bach Michael , Heinrich Sven P. , Kornmeier Jürgen , Endres Dominique , Ebert Dieter , Domschke Katharina , Tebartz van Elst Ludger , Nickel Kathrin
Published: September 2022

Ophthalmological methods have increasingly raised the interest of neuropsychiatric specialists. While the integrity of the retinal cell functions can be evaluated with the electroretinogram (ERG), optical coherence tomography (OCT) allows a structural investigation of retinal layer thicknesses. Previous studies indicate possible functional and structural retinal alterations in patients with schizophrenia. Twenty-five patients with paranoid schizophrenia and 25 healthy controls (HC) matched for age, sex, and smoking status participated in this study. Both, ERG and OCT were applied to obtain further insights into functional and structural retinal alterations. A significantly reduced a-wave amplitude and thickness of the corresponding para- and perifoveal outer nuclear layer (ONL) was detected in patients with paranoid schizophrenia with a positive correlation between both measurement parameters. Amplitude and peak time of the photopic negative response (PhNR) and thickness of the parafoveal ganglion cell layer (GCL) were decreased in patients with schizophrenia compared to HC. Our results show both structural and functional retinal differences between patients with paranoid schizophrenia and HC. We therefore recommend the comprehensive assessment of the visual system of patients with schizophrenia, especially to further investigate the effect of antipsychotic medication, the duration of illness, or other factors such as inflammatory or neurodegenerative processes. Moreover, longitudinal studies are required to investigate whether the functional alterations precede the structural changes.
Pairwise genetic meta-analyses between schizophrenia and substance dependence phenotypes reveals novel association signals with pharmacological significance
Authors: Greco Laura A. , Reay William R. , Dayas Christopher V. , Cairns Murray J.
Published: September 2022

Almost half of individuals diagnosed with schizophrenia also present with a substance use disorder, however, little is known about potential molecular mechanisms underlying this comorbidity. We used genetic analyses to enhance our understanding of the molecular overlap between these conditions. Our analyses revealed a positive genetic correlation between schizophrenia and the following dependence phenotypes: alcohol (rg = 0.368, SE = 0.076,P = 1.61 × 10−6), cannabis use disorder (rg = 0.309, SE = 0.033,P = 1.97 × 10−20) and nicotine (rg = 0.117, SE = 0.043,P = 7.0 × 10−3), as well as drinks per week (rg = 0.087, SE = 0.021,P = 6.36 × 10−5), cigarettes per day (rg = 0.11, SE = 0.024,P = 4.93 × 10−6) and life-time cannabis use (rg = 0.234, SE = 0.029,P = 3.74 × 10−15). We further constructed latent causal variable (LCV) models to test for partial genetic causality and found evidence for a potential causal relationship between alcohol dependence and schizophrenia (GCP = 0.6, SE = 0.22,P = 1.6 × 10−3). This putative causal effect with schizophrenia was not seen using a continuous phenotype of drinks consumed per week, suggesting that distinct molecular mechanisms underlying dependence are involved in the relationship between alcohol and schizophrenia. To localise the specific genetic overlap between schizophrenia and substance use disorders (SUDs), we conducted a gene-based and gene-set pairwise meta-analysis between schizophrenia and each of the four individual substance dependence phenotypes in up to 790,806 individuals. These bivariate meta-analyses identified 44 associations not observed in the individual GWAS, including five shared genes that play a key role in early central nervous system development. The results from this study further supports the existence of underlying shared biology that drives the overlap in substance dependence in schizophrenia, including specific biological systems related to metabolism and neuronal function.
Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
Authors: Khatamzas Elham , Antwerpen Markus H. , Rehn Alexandra , Graf Alexander , Hellmuth Johannes Christian , Hollaus Alexandra , Mohr Anne-Wiebe , Gaitzsch Erik , Weiglein Tobias , Georgi Enrico , Scherer Clemens , Stecher Stephanie-Susanne , Gruetzner Stefanie , Blum Helmut , Krebs Stefan , Reischer Anna , Leutbecher Alexandra , Subklewe Marion , Dick Andrea , Zange Sabine , Girl Philipp , Müller Katharina , Weigert Oliver , Hopfner Karl-Peter , Stemmler Hans-Joachim , von Bergwelt-Baildon Michael , Keppler Oliver T. , Wölfel Roman , Muenchhoff Maximilian , Moosmann Andreas
Published: September 2022

Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.
Using multiple sampling strategies to estimate SARS-CoV-2 epidemiological parameters from genomic sequencing data
Authors: Inward Rhys P. D. , Parag Kris V. , Faria Nuno R.
Published: September 2022

The choice of viral sequences used in genetic and epidemiological analysis is important as it can induce biases that detract from the value of these rich datasets. This raises questions about how a set of sequences should be chosen for analysis. We provide insights on these largely understudied problems using SARS-CoV-2 genomic sequences from Hong Kong, China, and the Amazonas State, Brazil. We consider multiple sampling schemes which were used to estimate Rt and rt as well as related R0 and date of origin parameters. We find that both Rt and rt are sensitive to changes in sampling whilst R0 and the date of origin are relatively robust. Moreover, we find that analysis using unsampled datasets result in the most biased Rt and rt estimates for both our Hong Kong and Amazonas case studies. We highlight that sampling strategy choices may be an influential yet neglected component of sequencing analysis pipelines.
Hardware implementation of Bayesian network based on two-dimensional memtransistors
Authors: Zheng Yikai , Ravichandran Harikrishnan , Schranghamer Thomas F. , Trainor Nicholas , Redwing Joan M. , Das Saptarshi
Published: September 2022

Bayesian networks (BNs) find widespread application in many real-world probabilistic problems including diagnostics, forecasting, computer vision, etc. The basic computing primitive for BNs is a stochastic bit (s-bit) generator that can control the probability of obtaining ‘1’ in a binary bit-stream. While silicon-based complementary metal-oxide-semiconductor (CMOS) technology can be used for hardware implementation of BNs, the lack of inherent stochasticity makes it area and energy inefficient. On the other hand, memristors and spintronic devices offer inherent stochasticity but lack computing ability beyond simple vector matrix multiplication due to their two-terminal nature and rely on extensive CMOS peripherals for BN implementation, which limits area and energy efficiency. Here, we circumvent these challenges by introducing a hardware platform based on 2D memtransistors. First, we experimentally demonstrate a low-power and compact s-bit generator circuit that exploits cycle-to-cycle fluctuation in the post-programmed conductance state of 2D memtransistors. Next, the s-bit generators are monolithically integrated with 2D memtransistor-based logic gates to implement BNs. Our findings highlight the potential for 2D memtransistor-based integrated circuits for non-von Neumann computing applications.
Activation of stably silenced genes by recruitment of a synthetic de-methylating module
Authors: Chan Wing Fuk , Coughlan Hannah D. , Chen Yunshun , Keenan Christine R. , Smyth Gordon K. , Perkins Andrew C. , Johanson Timothy M. , Allan Rhys S.
Published: September 2022

Stably silenced genes that display a high level of CpG dinucleotide methylation are refractory to the current generation of dCas9-based activation systems. To counter this, we create an improved activation system by coupling the catalytic domain of DNA demethylating enzyme TET1 with transcriptional activators (TETact). We show that TETact demethylation-coupled activation is able to induce transcription of suppressed genes, both individually and simultaneously in cells, and has utility across a number of cell types. Furthermore, we show that TETact can effectively reactivate embryonic haemoglobin genes in non-erythroid cells. We anticipate that TETact will expand the existing CRISPR toolbox and be valuable for functional studies, genetic screens and potential therapeutics.
A fungal tolerance trait and selective inhibitors proffer HMG-CoA reductase as a herbicide mode-of-action
Authors: Haywood Joel , Breese Karen J. , Zhang Jingjing , Waters Mark T. , Bond Charles S. , Stubbs Keith A. , Mylne Joshua S.
Published: September 2022

Decades of intense herbicide use has led to resistance in weeds. Without innovative weed management practices and new herbicidal modes of action, the unabated rise of herbicide resistance will undoubtedly place further stress upon food security. HMGR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) is the rate limiting enzyme of the eukaryotic mevalonate pathway successfully targeted by statins to treat hypercholesterolemia in humans. As HMGR inhibitors have been shown to be herbicidal, HMGR could represent a mode of action target for the development of herbicides. Here, we present the crystal structure of a HMGR fromArabidopsis thaliana(AtHMG1) which exhibits a wider active site than previously determined structures from different species. This plant conserved feature enables the rational design of specific HMGR inhibitors and we develop a tolerance trait through sequence analysis of fungal gene clusters. These results suggest HMGR to be a viable herbicide target modifiable to provide a tolerance trait.
Noise-resilient and high-speed deep learning with coherent silicon photonics
Authors: Mourgias-Alexandris G. , Moralis-Pegios M. , Tsakyridis A. , Simos S. , Dabos G. , Totovic A. , Passalis N. , Kirtas M. , Rutirawut T. , Gardes F. Y. , Tefas A. , Pleros N.
Published: September 2022

The explosive growth of deep learning applications has triggered a new era in computing hardware, targeting the efficient deployment of multiply-and-accumulate operations. In this realm, integrated photonics have come to the foreground as a promising energy efficient deep learning technology platform for enabling ultra-high compute rates. However, despite integrated photonic neural network layouts have already penetrated successfully the deep learning era, their compute rate and noise-related characteristics are still far beyond their promise for high-speed photonic engines. Herein, we demonstrate experimentally a noise-resilient deep learning coherent photonic neural network layout that operates at 10GMAC/sec/axon compute rates and follows a noise-resilient training model. The coherent photonic neural network has been fabricated as a silicon photonic chip and its MNIST classification performance was experimentally evaluated to support accuracy values of >99% and >98% at 5 and 10GMAC/sec/axon, respectively, offering 6× higher on-chip compute rates and >7% accuracy improvement over state-of-the-art coherent implementations.
Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
Authors: Diot Cédric , García-González Aurian P. , Vieira Andre F. , Walker Melissa , Honeywell Megan , Doyle Hailey , Ponomarova Olga , Rivera Yomari , Na Huimin , Zhang Hefei , Lee Michael , Olsen Carissa P. , Walhout Albertha J. M.
Published: September 2022

Tamoxifen is a selective estrogen receptor (ER) modulator that is used to treat ER-positive breast cancer, but that at high doses kills both ER-positive and ER-negative breast cancer cells. We recapitulate this off-target effect in Caenorhabditis elegans, which does not have an ER ortholog. We find that different bacteria dramatically modulate tamoxifen toxicity in C. elegans, with a three-order of magnitude difference between animals fed Escherichia coli, Comamonas aquatica, and Bacillus subtilis. Remarkably, host fatty acid (FA) biosynthesis mitigates tamoxifen toxicity, and different bacteria provide the animal with different FAs, resulting in distinct FA profiles. Surprisingly these bacteria modulate tamoxifen toxicity by different death mechanisms, some of which are modulated by FA supplementation and others by antioxidants. Together, this work reveals a complex interplay between microbiota, FA metabolism and tamoxifen toxicity that may provide a blueprint for similar studies in more complex mammals.