bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic and genomic characterization of
Methanothermobacter wolfeii
strain BSEL, a CO
2
-capturing archaeon with minimal nutrient requirements
Authors: Ale Enriquez Fuad , Ahring Birgitte K.
Published: April 2024

A new variant of
Methanothermobacter wolfeii
was isolated from an anaerobic digester using enrichment cultivation in anaerobic conditions. The new isolate was taxonomically identified via 16S rRNA gene sequencing and tagged as
M. wolfeii
BSEL. The whole genome of the new variant was sequenced and
de novo
assembled. Genomic variations between the BSEL strain and the type strain were discovered, suggesting evolutionary adaptations of the BSEL strain that conferred advantages while growing under a low concentration of nutrients.
M. wolfeii
BSEL displayed the highest specific growth rate ever reported for the
wolfeii
species (0.27 ± 0.03 h
−1
) using carbon dioxide (CO
2
) as unique carbon source and hydrogen (H
2
) as electron donor.
M. wolfeii
BSEL grew at this rate in an environment with ammonium (NH
4
+
) as sole nitrogen source. The minerals content required to cultivate the BSEL strain was relatively low and resembled the ionic background of tap water without mineral supplements. Optimum growth rate for the new isolate was observed at 64°C and pH 8.3. In this work, it was shown that wastewater from a wastewater treatment facility can be used as a low-cost alternative medium to cultivate
M. wolfeii
BSEL. Continuous gas fermentation fed with a synthetic biogas mimic along with H
2
in a bubble column bioreactor using
M. wolfeii
BSEL as biocatalyst resulted in a CO
2
conversion efficiency of 97% and a final methane (CH
4
) titer of 98.5%
v
, demonstrating the ability of the new strain for upgrading biogas to renewable natural gas.

IMPORTANCE

As a methanogenic archaeon,
Methanothermobacter wolfeii
uses CO
2
as electron acceptor, producing CH
4
as final product. The metabolism of
M. wolfeii
can be harnessed to capture CO
2
from industrial emissions, besides producing a drop-in renewable biofuel to substitute fossil natural gas. If used as biocatalyst in new-generation CO
2
sequestration processes,
M. wolfeii
has the potential to accelerate the decarbonization of the energy generation sector, which is the biggest contributor of CO
2
emissions worldwide. Nonetheless, the development of CO
2
sequestration archaeal-based biotechnology is still limited by an uncertainty in the requirements to cultivate methanogenic archaea and the unknown longevity of archaeal cultures. In this study, we report the adaptation, isolation, and phenotypic characterization of a novel variant of
M. wolfeii
, which is capable of maximum growth with minimal nutrients input. Our findings demonstrate the potential of this variant for the production of renewable natural gas, paving the way for the development of more efficient and sustainable CO
2
sequestration processes.
Virological, innate, and adaptive immune profiles shaped by variation in route and age of host in murine cytomegalovirus infection
Authors: Coplen Christopher P. , Jergovic Mladen , Terner Elana L. , Bradshaw Christine M. , Uhrlaub Jennifer L. , Nikolich Janko Ž.
Published: April 2024

Human cytomegalovirus (hCMV) is a ubiquitous facultative pathogen, which establishes a characteristic latent and reactivating lifelong infection in immunocompetent hosts. Murine CMV (mCMV) infection is widely used as an experimental model of hCMV infection, employed to investigate the causal nature and extent of CMV’s contribution to inflammatory, immunological, and health disturbances in humans. Therefore, mimicking natural human infection in mice would be advantageous to hCMV research. To assess the role of route and age at infection in modeling hCMV in mice, we infected prepubescent and young sexually mature C57BL/6 (B6) mice intranasally (i.n., a likely physiological route in humans) and intraperitoneally (i.p., a frequently used experimental route, possibly akin to transplant-mediated infection). In our hands, both routes led to comparable early viral loads and tissue spreads. However, they yielded differential profiles of innate and adaptive systemic immune activation. Specifically, the younger, prepubescent mice exhibited the strongest natural killer cell activation in the blood in response to i.p. infection. Further, the i.p. infected animals (particularly those infected at 12 weeks) exhibited larger anti-mCMV IgG and greater expansion of circulating CD8
+
T cells specific for both acute (non-inflationary) and latent phase (inflationary) mCMV epitopes. By contrast, tissue immune responses were comparable between i.n. and i.p. groups. Our results illustrate a distinction in the bloodborne immune response profiles across infection routes and ages and are discussed in light of physiological parameters of interaction between CMV, immunity, inflammation, and health over the lifespan.

IMPORTANCE

The majority of experiments modeling human cytomegalovirus (hCMV) infection in mice have been carried out using intraperitoneal infection in sexually mature adult mice, which stands in contrast to the large number of humans being infected with human CMV at a young age, most likely via bodily fluids through the nasopharyngeal/oral route. This study examined the impact of the choice of age and route of infection in modeling CMV infection in mice. By comparing young, prepubescent to older sexually mature counterparts, infected either via the intranasal or intraperitoneal route, we discovered substantial differences in deployment and response intensity of different arms of the immune system in systemic control of the virus; tissue responses, by contrast, appeared similar between ages and infection routes.
Draft genome sequence of
Acerihabitans
sp. strain TG2
T
, isolated from an Arctic tundra soil sample
Authors: Shcherbakova V. A. , Zakharyuk A. G. , Trubitsyn V. E.
Published: April 2024

Acerihabitans
sp. type strain TG2
T
(VKM B-3773
T
) is a gram-negative, anaerobic psychrophilic bacterium that was isolated from a tundra soil sample selected by the Bykovsky Peninsula (Russia). This report describes the generation and annotation of the 5.3 Mb draft genome sequence of
Acerihabitans
sp. strain TG2
T
.
Secondary metabolite profiling of
Pseudomonas aeruginosa
isolates reveals rare genomic traits
Authors: Neve Rachel L. , Giedraitis Emily , Akbari Madeline S. , Cohen Shirli , Phelan Vanessa V.
Published: April 2024

Pseudomonas aeruginosa
is a ubiquitous Gram-negative opportunistic pathogen with remarkable phylogenetic and phenotypic variabilities. In this work, we applied classical molecular networking analysis to secondary metabolite profiling data from seven
Pseudomonas aeruginosa
strains, including five clinical isolates from the lung secretions of people with cystic fibrosis (CF). We provide three vignettes illustrating how secondary metabolite profiling aids in the identification of rare genomics traits in
P. aeruginosa
. First, we describe the identification of a previously unreported class of acyl putrescines produced by isolate mFLRO1. Secondary analysis of publicly available metabolomics data revealed that acyl putrescines are produced by <5% of
P. aeruginosa
strains. Second, we show that isolate SH3A does not produce di-rhamnolipids. Whole-genome sequencing and comparative genomics revealed that SH3A cannot produce di-rhamnolipids because its genome belongs to clade 5 of the
P. aeruginosa
phylogenetic tree. Previous phylogenetic analysis of thousands of
P. aeruginosa
strains concluded that <1% of publicly available genome sequences contribute to this clade. Last, we show that isolate SH1B does not produce the phenazine pyocyanin or rhamnolipids because it has a one-base insertion frameshift mutation (678insC) in the gene
rhlR
, which disrupts
rhl
-driven quorum sensing. Secondary analysis of the tens of thousands of publicly available genomes in the National Center for Biotechnology Information (NCBI) and the
Pseudomonas
Genome Database revealed that this mutation was present in only four
P. aeruginosa
genomes. Taken together, this study highlights that secondary metabolite profiling combined with genomic analysis can identify rare genetic traits of
P. aeruginosa
isolates.

IMPORTANCE

Secondary metabolite profiling of five
Pseudomonas aeruginosa
isolates from cystic fibrosis sputum captured three traits present in <1%–5% of publicly available data, pointing to how our current library of
P. aeruginosa
strains may not represent the diversity within this species or the genetic variance that occurs in the CF lung.
Asynchronous Holocene lake evolution in arid mid-latitude Asia is driven by glacial meltwater and variations in Westerlies and the East Asian summer monsoon
Authors: Li Guoqiang , Wang Xiaoyan , Yang He , Jin Ming , Qin Caixin , Wang Yixuan , Jonell Tara N. , Pan Long , Chen Chunzhu , Zhao Wenwei , Zhang Xiaojian , Madsen David B.
Published: April 2024

Understanding the mechanisms driving hydrological change in arid Central Asia over a range of time scales is crucial for making predictions for future changes in fragile desert-lake ecosystems. As of yet, the drivers of hydrological changes in lake systems of arid Central Asia over the Holocene remain largely unexplored. Aibi Lake, fed by rivers originating from the glaciated Tianshan Mountains and terminating in the arid Junggar Basin of northwestern China, presents a perfect natural laboratory to explore lake evolution in context to Holocene climate evolution in arid Central Asia. Here, a single-grain K-feldspar dating method was used to effectively date 20 paleolake shorelines with poorly bleached sediment to constrain lake level evolution over the past 18 k.y. Results indicate that Aibi Lake experienced a rapid increase in water levels, reaching a peak of ~36 m during the early to mid-Holocene period (10–7 ka). Subsequently, the lake level may have shown a general decline during the middle Holocene (7–4 ka), with the lake reaching a low level of less than 10 m at ca. 4 ka. In the late Holocene, lake levels fluctuated by 10–30 m above modern levels during 4–1 ka, with generally low levels of <9 m after 1 ka. The evolution of Aibi Lake underlines a clear out-of-phase relationship between Central Asian lake evolution and Westerlies precipitation changes, where Holocene lake changes were instead more directly controlled by the flux of glacial meltwater from the Tianshan Mountains, driven by change in Northern Hemisphere summer insolation. Glacier meltwater, in combination with variable delivery of Westerlies and East Asian summer monsoon precipitation, are responsible for asynchronous lake evolution trends across Central to East Asia.
Moderate magnitude clockwise rotation of the Yunlong Basin: Implications for synchronous Eocene rotation of the southeastern Tibetan Plateau
Authors: Xu Wanlong , Zhang Dawen , Yan Maodu , Zhang Weilin , Zhang Zhenbei , Xu Zunbo , Zhang Yuwei , Song Chunhui , Fang Xiaomin
Published: April 2024

The clockwise rotation and southeastward extrusion of the southeastern Tibetan Plateau have played important roles in accommodating the uplift and deformation of the plateau. Numerous paleomagnetic studies have suggested post–late Eocene clockwise rotation of the southeastern Tibetan Plateau along the eastern Himalaya syntaxis, whereas few researchers have addressed the specific Eocene deformation, leading to ambiguous interpretations of the tectonic evolution in the region. Herein, we conducted a paleomagnetic study of the Yunlong Formation in the Yunlong Basin, which is Late Cretaceous to early Paleocene in age. In total, 386 oriented samples were collected. Rock magnetic, scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS) analyses revealed detrital carriers, such as hematite and some magnetite. In thermal demagnetization processes, 332 characteristic remanent magnetizations were isolated, which yielded positive reversals and tilt tests, providing a site-mean direction of declination (Ds) = 56.0° ± 2.6°, inclination (Is) = 34.3° ± 3.8°, α95 = 2.7°, k = 91.0, and N = 31 after tilt correction. Magnetostratigraphic analysis was performed, and a depositional age of 79–61 Ma for the section was obtained, which is consistent with the previous paleontological and detrital zircon ages. Compared with the Eurasia reference pole of the period, the data revealed a 45.2° ± 5.1° clockwise rotation of the Yunlong area since 79–61 Ma. The integrated regional paleomagnetic results suggest the occurrence of ~20° of clockwise rotation of the Lanping-Simao terrane during the Eocene, which is similar (in terms of magnitude and time of occurrence) to that of the Gonjo Basin in the eastern Qiangtang terrane. Integrated with other lines of geologic evidence, we propose a new deformation model in which the entire southeastern Tibetan Plateau experienced ~20° of rigid clockwise rotation during the Eocene, followed by subsequent oroclinal bending.
What Can we Learn from Nonequilibrium Response of a Strange Metal?
Authors: Polyak B. A. , Khrapai V. S. , Tikhonov E. S.
Published: April 2024

We critically address the recent experiment by L. Chen et al. [Science 382, 907 (2023)] on nonequilibrium transport and noise in a strange metal YbRh2Si2 patterned into the nanowire shape. In the long device, resistivity, differential resistance and current noise data seem to be consistent allowing us to extract electron–phonon coupling and the temperature dependence of electron–phonon scattering length. The obtained values can be reconciled with the experimental data for the short device only assuming the significant contact resistance. We discuss its possible origin as due to the current redistribution between YbRh2Si2 and its gold covering, and reveal that this redistribution contact resistance should be proportional to the YbRh2Si2 resistivity. We also discuss some subtleties of the noise measurements. Overall, neglecting electron–phonon energy relaxation even in the shortest devices is arguable so that the observed shot noise suppression can hardly be attributed to the failure of quasiparticle concept.
Social history and glaucoma progression: the effect of body mass index, tobacco and alcohol consumption on the rates of structural change in patients with glaucoma
Authors: Youssif Asmaa A , Onyekaba Ndidi-Amaka , Naithani Rizul , Abdelazeem Khaled , Fathalla Ahmed M , Abdel‐Rhaman Mohamed S , Jammal Alessandro A , Medeiros Felipe A
Published: April 2024

Background/aims

Although obesity, tobacco and alcohol consumption were linked to the progression of numerous chronic diseases, an association of these social history aspects with glaucoma progression is not yet determined. This study aims to investigate the effect of body mass index (BMI) and history of tobacco and alcohol use on the rates of retinal nerve fibre layer (RNFL) change over time in glaucoma patients.

Methods

2839 eyes of 1584 patients with glaucoma from the Duke Ophthalmic Registry were included. Patients had at least two spectral-domain optical coherency tomography (SD-OCT) tests over a minimum 6-month follow-up. Self-reported history of alcohol and tobacco consumption was extracted from electronic health records and mean BMI was calculated. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on RNFL change over time.

Results

Mean follow-up time was 4.7±2.1 years, with 5.1±2.2 SD-OCT tests per eye. 43% and 54% of eyes had tobacco or alcohol consumption history, respectively, and 34% were classified as obese. Higher BMI had a protective effect on glaucoma progression (0.014 µm/year slower per each 1 kg/m2higher; p=0.011). Tobacco and alcohol consumption were not significantly associated with RNFL change rates (p=0.473 and p=0.471, respectively). Underweight subjects presented significantly faster rates of structural loss (−0.768 µm/year; p=0.002) compared with normal weight.

Conclusions

In a large clinical population with glaucoma, habits of tobacco and alcohol consumption showed no significant effect on the rates of RNFL change. Higher BMI was significantly associated with slower rates of RNFL loss.
Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients
Authors: Thornton Christina S , Waddell Barbara J , Congly Stephen E , Svishchuk Julianna , Somayaji Ranjani , Fatovich Linda , Isaac Debra , Doucette Karen , Fonseca Kevin , Drews Steven J , Borlang Jamie , Osiowy Carla , Parkins Michael D
Published: April 2024

Objectives

In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers.

Design

All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV.

Results

HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases.

Conclusion

PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required.
Tetracyclines enhance antitumor T-cell immunity via the Zap70 signaling pathway
Authors: Tone Mari , Iwahori Kota , Hirata Michinari , Ueyama Azumi , Tani Akiyoshi , Haruta Jun-Ichi , Takeda Yoshito , Shintani Yasushi , Kumanogoh Atsushi , Wada Hisashi
Published: April 2024

Background

Cancer immunotherapy including immune checkpoint inhibitors is only effective for a limited population of patients with cancer. Therefore, the development of novel cancer immunotherapy is anticipated. In preliminary studies, we demonstrated that tetracyclines enhanced T-cell responses. Therefore, we herein investigated the efficacy of tetracyclines on antitumor T-cell responses by human peripheral T cells, murine models, and the lung tumor tissues of patients with non-small cell lung cancer (NSCLC), with a focus on signaling pathways in T cells.

Methods

The cytotoxicity of peripheral and lung tumor-infiltrated human T cells against tumor cells was assessed by using bispecific T-cell engager (BiTE) technology (BiTE-assay system). The effects of tetracyclines on T cells in the peripheral blood of healthy donors and the tumor tissues of patients with NSCLC were examined using the BiTE-assay system in comparison with anti-programmed cell death-1 (PD-1) antibody, nivolumab. T-cell signaling molecules were analyzed by flow cytometry, ELISA, and qRT-PCR. To investigate the in vivo antitumor effects of tetracyclines, tetracyclines were administered orally to BALB/c mice engrafted with murine tumor cell lines, either in the presence or absence of anti-mouse CD8 inhibitors.

Results

The results obtained revealed that tetracyclines enhanced antitumor T-cell cytotoxicity with the upregulation of granzyme B and increased secretion of interferon-γ in human peripheral T cells and the lung tumor tissues of patients with NSCLC. The analysis of T-cell signaling showed that CD69 in both CD4+and CD8+T cells was upregulated by minocycline. Downstream of T-cell receptor signaling, Zap70 phosphorylation and Nur77 were also upregulated by minocycline in the early phase after T-cell activation. These changes were not observed in T cells treated with anti-PD-1 antibodies under the same conditions. The administration of tetracyclines exhibited antitumor efficacy with the upregulation of CD69 and increases in tumor antigen-specific T cells in murine tumor models. These changes were canceled by the administration of anti-mouse CD8 inhibitors.

Conclusions

In conclusion, tetracyclines enhanced antitumor T-cell immunity via Zap70 signaling. These results will contribute to the development of novel cancer immunotherapy.
Minimally invasive management of thoracic trauma: current evidence and guidelines
Authors: Lewis Meghan R , Georgoff Patrick
Published: April 2024

Minimally invasive procedures are being increasingly proposed for trauma. Injuries to the chest wall and/or lung have historically been managed by drainage with a large bore thoracostomy tube, while cardiac injuries have mandated sternotomy. These treatments are associated with significant patient discomfort. Percutaneous placement of small ‘pigtail’ catheters was initially designed for drainage of simple pericardial fluid. Their use subsequently expanded to drainage of the pleural cavity. The role of pigtail catheters for primary treatment of traumatic pneumothorax and hemopneumothorax has increased, while their use for pericardial fluid after trauma remains controversial. Pericardial windows have alternatively been purposed as a minimally invasive treatment option for possible hemopericardium. The aim of this article is to review the current evidence and guidelines for minimally invasive management of chest trauma.
Victory out of tragedy: organ donation
Authors: Salim Ali , Cotton Bryan A
Published: April 2024

Major improvements in trauma care during the last decade have improved survival rates in the severely injured. The unintended consequence is the presentation of patients with non-survivable injuries in a time frame in which intervention is considered and often employed due to prognostic uncertainty. In light of this, discerning survivability in these patients remains increasingly problematic. Evidence-based cut-points of futility can guide early decisions for discontinuing aggressive treatment and use of precious resources in severely injured patients arriving in extremis.
Weak cosmic censorship conjecture and black hole shadow for black hole with generalized uncertainty principle
Authors: Tang Meirong
Published: April 2024

Based on string theory, loop quantum gravity, black hole physics, and other theories of quantum gravity, physicists have proposed generalized uncertainty principle (GUP) modifications. In this work, within the framework of GUP gravity theory, we successfully derive an exact solution to Einstein’s field equation, and discuss the possibility of using EHT to test GUP and how GUP changes the weak cosmic censorship conjecture for black holes. We analyze two different ways of constructing GUP rotating black holes (model I and model II). Model I takes into account the modification of mass by GUP, i.e., the change in mass by quantization of space, and the resulting GUP rotating black hole metric (18) is similar in form to the Kerr black hole metric. Model II takes into account the modification of the rotating black hole when GUP is an external field, where GUP acts like an electric charge, and the resulting GUP rotating black hole metric (19) is similar in form to the Kerr–Newman black hole metric. The difference between (18) and (19) in the spacetime linear structure provides a basis for us to examine the physical nature of GUP rotating black holes from observation. By analyzing the shadow shape of the GUP rotating black hole, we discover intriguing characteristics regarding the impact of first-order and second-order momentum correction coefficients on the black hole’s shadow shape. These findings will be instrumental in future GUP testing using EHT. Additionally, by incident test particle and scalar field with a rotating GUP black hole, the weak cosmic censorship conjecture is not violated in either extreme black holes or near-extreme black holes.
A NEW PERSPECTIVE ON THE NONLINEAR DATE–JIMBO–KASHIWARA–MIWA EQUATION IN FRACTAL MEDIA
Authors: SUN JIANSHE
Published: April 2024

In this paper, we first created a fractal Date–Jimbo–Kashiwara–Miwa (FDJKM) long ripple wave model in a non-smooth boundary or microgravity space recorded. Using fractal semi-inverse skill (FSIS) and fractal traveling wave transformation (FTWT), the fractal variational principle (FVP) was derived, and the strong minimum necessary circumstance was attested with the He Wierstrass function. We have discovered two distinct solitary wave solutions, the square form of the hyperbolic secant function and the hyperbolic secant function form. Then, soliton solutions are cultivated through FVP and the minimum steady state condition. Finally, the influences of non-smooth boundaries on solitons were tackled, and the properties of the solution were demonstrated through three-dimensional contour lines. Fractal dimension can impact waveforms, but cannot affect their vertex values. The presentation of soliton solutions (SWS) using techniques is not only laudable but also noteworthy. The technique employed can also be used to investigate solitary wave solutions of other local fractional calculus partial differential equations.
ATTACK VULNERABILITY OF FRACTAL SCALE-FREE NETWORK
Authors: GUO FEIYAN , QI LIN , FAN YING
Published: April 2024

An in-depth analysis of the attack vulnerability of fractal scale-free networks is of great significance for designing robust networks. Previous studies have mainly focused on the impact of fractal property on attack vulnerability of scale-free networks under static node attacks, while we extend the study to the cases of various types of targeted attacks, and explore the relationship between the attack vulnerability of fractal scale-free networks and the fractal dimension. A hierarchical multiplicative growth model is first proposed to generate scale-free networks with the same structural properties except for the fractal dimension. Furthermore, the fractal dimension of the network is calculated using two methods, namely, the box-covering method and the cluster-growing method, to exclude the possibility of differences in conclusions caused by the methods of calculating the fractal dimension for the subsequent relationship analysis. Finally, four attack strategies are used to attack the network, and the network performance is quantitatively measured by three structural indicators. Results on model networks show that compared to non-fractal modular networks, fractal scale-free networks are more robust to both static and dynamic targeted attacks on nodes and links, and the robustness of the network increases as the fractal dimension decreases. However, there is a cost in that as the fractal dimension decreases, the network becomes less efficient and more vulnerable to random failures on links. These findings contribute to a deeper understanding of the impact of fractal property on scale-free network performance and may be useful for designing resilient infrastructures.
Neogene erosion surfaces and the Andean uplift in northern Peru
Authors: Wilson J.J.
Published: April 2024

The Andean flank in central Peru is characterized by stepped profiles involving up to 20 surfaces and pediments resulting from multiple episodes of uplift and erosion. The study area exhibits the same sequence of surfaces and pediments. The erosional features are also recognized in the Eastern Cordillera in northern Peru. This paper focuses on the seven highest features in the range
c.
2800–4700 m. Remnants of the four surfaces higher than 3800 m, which were formed during the interval
c.
18–12 Ma, are only found south of latitude 6–6.5° S. The Miocene metallogenic belt associated with the Western Cordillera terminates abruptly at that same latitude. The area north of
c.
6° S does not have any features higher than
c.
3500 m, which is interpreted as indicating a later initiation of uplift. It also lacks any sign of magmatic activity. On the basis of these factors, the Central Andes are considered to terminate at
c.
6° S, the ranges to the north being assigned to the Northern Andes. Once episodic uplift was initiated in the area north of 6° S, it continued at the same rhythm as in the region to the south. There was no apparent change in the pattern of episodic uplift when the normal subduction regime changed to a flat-slab regime at
c.
11 Ma, probably as a result of the subduction of the Inca Plateau. The distribution of the erosion surfaces indicates that episodic uplift affected the whole of the Andean Block in northern Peru. It appears that the individual episodes occurred simultaneously and produced the same amount of uplift over the whole width of the cordilleras. There is no sign of any interruption in the process, implying a continuous orogeny from the Mid-Miocene onwards.
Convexity in Real-time Bidding and Related Problems
Authors: Kinnear Ryan , Mazumdar Ravi R , Marbach Peter
Published: April 2024

We study problems arising in real-time auction markets, common in e-commerce and computational advertising, where bidders face the problem of calculating optimal bids. We focus upon a contract management problem where a demand aggregator is subject to multiple contractual obligations requiring them to acquire items of heterogeneous types at a specified rate and where they will seek to fulfill these obligations at minimum cost. Our main results show that, through a transformation of variables, this problem can be formulated as a convex optimization problem, for both first and second price auctions. The resulting duality theory admits rich structure and interpretations. Additionally, we show that the transformation of variables can be used to guarantee the convexity of optimal bidding problems studied by other authors, who did not leverage convexity in their analysis. The main point of our work is to emphasize that the natural convexity properties arising in first and second price auctions are not being fully exploited. Finally, we show direct analogies to problems in financial markets: the expected cost of bidding in second price auctions is formally identical to certain transaction costs when submitting market orders, and that a related conjugate function arises in dark pool financial markets.
Integrating Large-Scale Protein Structure Prediction into Human Genetics Research
Authors: Correa Marrero Miguel , Jänes Jürgen , Baptista Delora , Beltrao Pedro
Published: April 2024

The last five years have seen impressive progress in deep learning models applied to protein research. Most notably, sequence-based structure predictions have seen transformative gains in the form of AlphaFold2 and related approaches. Millions of missense protein variants in the human population lack annotations, and these computational methods are a valuable means to prioritize variants for further analysis. Here, we review the recent progress in deep learning models applied to the prediction of protein structure and protein variants, with particular emphasis on their implications for human genetics and health. Improved prediction of protein structures facilitates annotations of the impact of variants on protein stability, protein–protein interaction interfaces, and small-molecule binding pockets. Moreover, it contributes to the study of host–pathogen interactions and the characterization of protein function. As genome sequencing in large cohorts becomes increasingly prevalent, we believe that better integration of state-of-the-art protein informatics technologies into human genetics research is of paramount importance.
The Sociology of Entrepreneurship Revisited
Authors: Botelho Tristan L. , Gulati Ranjay , Sorenson Olav
Published: April 2024

Over the last two decades, the sociology of entrepreneurship has exploded as an area of academic inquiry. Most of this research has been focused on understanding the environmental conditions that promote entrepreneurship and processes related to the initial formation of an organization. Despite this surge in activity, many important questions remain open. Only more recently have scholars begun to turn their attention to what happens to organizations, and the people connected to them, as they mature and move through the life cycle of entrepreneurship. These open questions, moreover, connect to many classic themes in the literature on careers, organizational sociology, stratification, and work and occupations. Using a framework that focuses on three phases of the entrepreneurial life cycle—pre-entry, entry, and post-entry—we summarize sociological research on entrepreneurship and highlight opportunities for future research.
Impact of LiAl Nucleation Kinetics on the Microstructural Evolution of Aluminum Foil Anodes in Lithium-ion Batteries
Authors: Trejo Caitlin , Scanlan Kevin , Manthiram Arumugam
Published: April 2024

Aluminum foil anodes have the potential to significantly improve the energy density, safety, cost, and sustainability of Li-ion batteries (LIB). However, their adoption is limited by their notoriously poor cycle life, and the dramatic structural transformations of Al foil anodes during formation and cycling remain poorly understood. In this work, we investigate how the nucleation and growth kinetics of LiAl control the microstructural evolution and cycle life of Al foil anodes. First, we demonstrate the unique sensitivity of Al foil anodes to the cell design and cycling conditions and emphasize the necessity of electrochemical testing in practical full cells. Operando electrochemical impedance spectroscopy (EIS) is combined with scanning electron microscope (SEM) imaging of the lithiated foils to elucidate the relationships between LiAl nucleation kinetics and the resulting LiAl microstructure. Particularly, we investigate the effects of annealing the pristine foils, and controlling the overpotential and temperature during formation, showing that as-rolled foils lithiated at high overpotentials give a columnar LiAl microstructure. Finally, we show that uncontrolled LiAl nucleation during cycling quickly destroys this favorable columnar structure, and a significant improvement in cycle life of LiFePO4 || Al full cells is achieved by limiting the depth-of-discharge to <75%.
Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types
Authors: Jones Lipinski Rachel A. , Stancill Jennifer S. , Nuñez Raymundo , Wynia-Smith Sarah L. , Sprague Daniel J. , Nord Joshua A. , Bird Amir , Corbett John A. , Smith Brian C.
Published: April 2024

Inhibition of BET bromodomains is a novel potential strategy to prevent and treat diabetes mellitus. However, BET inhibitors have negative side effects. We synthesized a BET inhibitor expected to exploit the high zinc concentration in β cells to accumulate in β cells. We show our inhibitor targeted pancreatic endocrine cells; however, it was less effective in immune cells. A control inhibitor showed the opposite effect. These findings help us understand how to target specific cells in diabetes treatment.
A Compact Isolated CR Antenna System for Application in C-Band
Authors: Parida Rajeev K. , Almawgani Abdulkarem H. M. , Muduli Arjuna , Panda Dhruba C. , Alhawari Adam R. H. , Pal Amrindra , Abdullah M. M. , Albargi Hasan B.
Published: April 2024

In this work, a dual-port antenna system is simulated and fabricated for cognitive radio (CR) application. The proposed system comprises a tapered-fed monopole ultra-wideband (UWB) sensing antenna and a dual-narrowband (NB) communicating antenna. For miniaturization, the UWB sensing antenna is placed on the front side of the communicating antenna. The sensing operation takes place over 2.1–12 GHz. The E-shaped dual-band antenna operates at 3.9 GHz and 6.04 GHz. The envelope correlation coefficient (ECC) and isolation are measured to be lower than 0.12 and greater than 18 dB, respectively, within the range of acceptable values for both parameters. The antenna prototype was fabricated and tested experimentally to confirm the simulation’s findings. The outcomes of both the simulation and the testing revealed a definite consistency. This work gives a miniaturized model and good isolation, which is appropriate for C-band applications.
A Bibliometric Analysis of Study of Associations of Certain Genotypes with the Cardiovascular Form of Diabetic Neuropathy
Authors: Bekenova Nazira B. , Vochshenkova Tamara A. , Ablakimova Nurgul , Zhylkybekova Aliya , Mussin Nadiar M. , Albayev Rustam K. , Kaliyev Asset A. , Tamadon Amin
Published: April 2024

This bibliometric analysis explores the landscape of research on the associations between specific genotypes and the cardiovascular form of diabetic neuropathy. Diabetes mellitus (DM) is a major contributor to premature mortality, primarily due to increased susceptibility to cardiovascular diseases. The global prevalence of DM is rising, with projections indicating further increases. Diabetic neuropathy, a complication of DM, includes the cardiovascular subtype, posing challenges in diagnosis and management. Understanding the genetic basis of cardiovascular diabetic neuropathy is crucial for targeted therapeutic interventions. The study utilizes bibliometric analysis to synthesize existing literature, identify trends, and guide future research. The Scopus database was searched, applying inclusion criteria for English articles related to genotypes and cardiovascular diabetic neuropathy. The analysis reveals a dynamic field with a notable impact, collaborative efforts, and multidimensional aspects. Publication trends over 1997-2023 demonstrate fluctuating research intensity. Top journals, authors, and affiliations are highlighted, emphasizing global contributions. Keyword analysis reveals thematic trends, and citation analysis identifies influential documents. Limitations include database biases, incomplete metadata, and search query specificity. The urgent need to explore genetic factors in cardiovascular diabetic neuropathy aligns with the increasing global diabetes burden. This analysis provides a comprehensive overview, contributing to the broader discourse on diabetic neuropathy research.
Spectral Domain and Angiography Optical Coherence Tomography in Parkinson’s Disease: Structural And Vascular Changes in the Retina Correlate with Disease Severity and Progression
Authors: Di Maio Laura Giovanna , Cennamo Gilda , Montorio Daniela , De Michele Giovanna , Palmieri Gianluigi Rosario , Baratto Luigi , Perillo Sandra , Giglio Augusta , Filla Alessandro , Brescia Morra Vincenzo , De Michele Giuseppe , Costagliola Ciro , De Rosa Anna
Published: April 2024

Background. Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, and muscle rigidity. Visual disturbances have been also described among non‐motor features. Objective. We aimed to investigate the structural and vascular changes in the retinal and choroidal vascular networks, and to assess any relationship with motor and non‐motor symptoms (NMS) in PD patients. Methods. Ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), and subfoveal choroidal thickness (SFCT) were examined using spectral domain‐optical coherence tomography (SD‐OCT). The vessel density (VD) of retinal and choriocapillary vascular networks in macular area and the foveal avascular zone (FAZ) area were evaluated by OCT angiography (OCTA). All patients underwent clinical evaluation using motor section of the Unified PD Rating Scale (UPDRS‐III) and the Hoehn and Yahr (HY) scale. Results. A total of 48 eyes from 24 PD patients and 50 eyes from 25 controls were assessed. At SD‐OCT, GCC and RNFL were more significantly thin in patients compared to controls. At OCTA exam, PD subjects showed lower values in VD of superficial capillary plexus (SCP) and radial peripapillary capillary plexus in comparison to controls, whereas FAZ area resulted in a significant increase in the patient group. We found a negative correlation between the age at onset and VD of SCP, and between HY score and RNFL thickness and FAZ. UPDRS‐III score was negatively correlated with VD of deep capillary plexus. Discussion. The impairment of retinal structure and microvasculature seems to correlate with disease severity and progression in PD. Retinal anomalies can be considered as non‐motor manifestations that could occur already in the early stage of the disease.
Effects of Internal Pressure on Urban Water Supply Pipeline Leakage-Induced Soil Subsidence Mechanisms
Authors: Cui Jingyu , Liu Fengyin , Chen Ruidi , Wang Shuangshuang , Pu Cheng , Zhao Xu
Published: April 2024

After the rupture of pressurized water supply pipes in urban underground areas, seepage-induced ground subsidence becomes a severe geological hazard. Understanding the permeation and diffusion patterns of water in soil is crucial for deciphering the mechanisms underlying soil settlement and damage. Notably, the pressure within water supply pipes significantly influences the settlement and damage of the soil. Therefore, this study simulated experiments on soil settlement and damage caused by water seepage from a preexisting damaged pipeline under various internal pipe pressure conditions using an indoor model apparatus. The results indicate that the internal pressure of the pipe significantly influences the settlement of the soil. High-pressure seepage causes noticeable erosion in the soil, forming cavities within it. In contrast, low-pressure seepage results in water diffusing in an ellipsoidal pattern, leading to the formation of circular surface cracks. The degree of surface settlement increases with higher pipe pressure. The onset of subsidence at a specific point on the ground is not directly related to whether the moistening front within the soil has reached that point horizontally. Instead, it is associated with the moisture content below the subsidence point within the soil. The research results further illustrate the water diffusion and moisture content increase processes after water seepage from pipes with different pressures, revealing the influence of pipe pressure on the degree and form of soil settlement damage and clarifying the relationship between water diffusion and settlement in the soil.
The Influence of Prefermentation Skin Contact, Stabulation, and Skin Fermentation on the Aromatic Behaviour and Phenolic Compounds of Important Austrian White Wine Cultivars
Authors: Philipp Christian , Eder Phillip , Sari Sezer , Korntheuer Karin , Eder Reinhard
Published: April 2024

Many varietal aromas of wine are located in the berry skin. In the present study, we evaluated four important Austrian grape varieties: Grüner Veltliner, Sauvignon Blanc, Traminer, and Pinot Blanc. We assessed whether prefermentation skin contact, fermentation with the skin (only for Grüner Veltliner), and stabulation (lees stirring; only for Sauvignon Blanc, Traminer, and Pinot Blanc) could enhance the varietal aromas of the different grape cultivars. The aim was to intensify the varietal aromas without extracting the undesirable phenols. We performed a detailed analytical characterisation of approximately 100 volatile and phenolic compounds as well as a sensory characterisation. Although mash fermentation significantly increased the spicy aromas of Grüner Veltliner, which are affected by climate change (especially the sesquiterpene rotundone), it markedly decreased the fruitiness and increased the bitterness; therefore, it cannot be recommended for this cultivar. For Sauvignon Blanc, stabulation is a possible option; the varietal aromas (thiols and methoxypyrazines) were increased in the final wines of these variants. For Pinot Blanc and Traminer, prefermentation skin contact yielded the best results: for Traminer, it produced the highest content of monoterpenes (especially z-rose oxide), and for Pinot Blanc, it produced the highest content of ethyl esters. To summarise, stabulation will not completely replace classic skin contact, and mash fermentation is certainly not an alternative for the production of standard Grüner Veltliner wine. However, additional investigations are necessary with regard to other grape varieties, terroirs, and vintages before we can make final recommendations.
The Multiobjective Control Based on Tolerance Optimization in a Multienergy System
Authors: Ma Suliang , Li Yaxin , Jiang Yuan , Wu Yiwen , Sha Guanglin
Published: April 2024

To address the issue of multiobjective control in multienergy systems with diverse operational objectives, a two-stage optimization framework based on expected point tolerance has been proposed in this paper. In the first stage, a single objective function is used for optimization control to obtain the expected point of the multiobjective optimization problem. Then, in the second stage, by defining the allowable deviation between each optimization objective and the expected point, the original multiobjective optimization problem is transformed into a single objective optimization problem solution with tolerance measurement. Finally, in the simulation scene of a multienergy system, it is demonstrated that compared with the optimal results under each single objective method, the proposed method increases power line loss, maximum voltage deviation, new energy consumption, and economy by 2.22, 2.30, 1.02, and 2.45 times, respectively. Compared with the suboptimal results, the proposed method reduces power line loss by 22.26, 1.74, 1.09, and 0.97 times, respectively. Combining the shape of the Pareto frontier, it is demonstrated that the proposed method can comprehensively consider the needs of multiple power optimization objectives for forming a more reasonable and effective system optimization scheduling and also provide a new approach for solving multiobjective optimization problems.
Table S1 from Fibroblasts in the Aged Pancreas Drive Pancreatic Cancer Progression
Authors: Zabransky Daniel J. , Chhabra Yash , Fane Mitchell E. , Kartalia Emma , Leatherman James M. , Hüser Laura , Zimmerman Jacquelyn W. , Delitto Daniel , Han Song , Armstrong Todd D. , Charmsaz Soren , Guinn Samantha , Pramod Sneha , Thompson Elizabeth D. , Hughes Steven J. , O'Connell Jennifer , Egan Josephine M. , Jaffee Elizabeth M. , Weeraratna Ashani T.
Published: April 2024

Supplementary Table 1
Supplementary Figure S5 from TFE3-Splicing Factor Fusions Represent Functional Drivers and Druggable Targets in Translocation Renal Cell Carcinoma
Authors: Damayanti Nur P. , Cordova Ricardo A. , Rupert Christopher , Delle Fontane Ilaria , Shen Li , Orsi Sabrina , Klunk Angela J. , Linehan W. Marston , Staschke Kirk A. , Hollenhorst Peter C. , Heppner David E. , Pili Roberto
Published: April 2024

Supplementary Figure S5
Figure S1 from ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts
Authors: Hu Bomiao , Wiesehöfer Marc , de Miguel Fernando J. , Liu Zongzhi , Chan Lok-Hei , Choi Jungmin , Melnick Mary Ann , Arnal Estape Anna , Walther Zenta , Zhao Dejian , Lopez-Giraldez Francesc , Wurtz Anna , Cai Guoping , Fan Rong , Gettinger Scott , Xiao Andrew , Yan Qin , Homer Robert , Nguyen Don X. , Politi Katerina
Published: April 2024

Effects of erlotinib and TKI withdrawal on PDX growth.
Supplementary Figure 5 from Targeting the Epigenetic Reader ENL Inhibits Super-Enhancer–Driven Oncogenic Transcription and Synergizes with BET Inhibition to Suppress Tumor Progression
Authors: Chen Yongheng , Ying Ying , Ma Wenlong , Ma Hongchao , Shi Liang , Gao Xuefeng , Jia Min , Li Meiqi , Song Xiaoman , Kong Weixiao , Chen Wei , Zheng Xiangyi , Muluh Tobias Achu , Wang Xiaobin , Wang Maolin , Shu Xing-sheng
Published: April 2024

Related to Figure 5.