bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of the Ventilation Transit Time Distribution at the Yap−Mariana Junction Using 39Ar, 85Kr and 14C Tracers
Authors: Gu Ji‐Qiang , Jiang Wei , Tong Amin L. , Yang Guo‐Min , Dong Xi‐Ze , Ritterbusch Florian , Wang Fan , Wang Jianing 
Published: June 2022

AbstractWe report on a multi‐tracer study at the Yap‐Mariana Junction in the western Pacific using three tracers—85Kr, 39Ar, and 14C—with different half‐lives and source functions to the oceans. The vertical profiles of 85Kr and 39Ar are measured using the state‐of‐the‐art Atom Trap Trace Analysis method. This method allows analysis of 85Kr and 39Ar isotopes with samples collected in regular Niskin bottles. Combined with the calculated natural 14C data, we infer the ventilation transit‐time distribution (TTD) at the Yap‐Mariana Junction. The mean ages of the seawater below the thermocline at the Yap‐Mariana Junction are over 1,000 years. Moreover earlier 39Ar and natural 14C data collected in other parts of the Pacific are used to infer the local TTDs and compared with the one at the Yap‐Mariana Junction. The age spectra of the Pacific bottom waters show progressive changes and increasing tails of the old water along the route from south to north. The dominance of the North Pacific Deep Water (NPDW) in the North Pacific and the effect of mixing between old water masses and younger ones at the Yap‐Mariana Junction are reflected from the different shapes of the TTDs at these locations. The TTD shows the oldest water exists at about 2,000 m depth in the North Pacific. The western Pacific shows the highest degree of mixing at 1,000 m depth, while the southern Pacific has the highest degree of mixing close to the bottom.
Global Distribution and Spectral Features of Intense Lightning by the ISUAL Experiment
Authors: Chuang Chia‐Wen , Chen Alfred Bing‐Chih 
Published: June 2022

AbstractDuring the 12 years of the Imager of Sprites and Upper Atmospheric Lightning (ISUAL) experiment onboard the Taiwanese FORMOSAT‐2 satellite (2004/07/01–2016/6/20), 297,349 transient events were recorded, but only 48,414 events (16.3%) were manually classified as transient luminous events (TLEs). Since the main target of ISUAL is to observe TLEs, only the top ∼0.82% of intense lightning can meet the trigger threshold, which means the ISUAL experiment can also serve as a space‐borne intense lightning survey. An autonomous lightning identification algorithm was developed in this work to screen and locate lightning flashes in images, and 292,248 intense lightning discharges were identified successfully. Combining the statistical analysis of lightning events and unique spectral observations of ISUAL, the global distribution of intense lightning with spectral characteristics was constructed. The intense lightning occurrence rate of ISUAL was 1.29 fl s−1, and the land‐to‐ocean ratio 1.27. Intense lightning is most active near the equator, and the bimodal pattern peaks in April and September, different from the typical lightning behavior that occurs in the northern hemisphere during the summertime from July to August. In addition, the spectral statistics show that more than 95% of intense lightning is accompanied by nitrogen band emissions (1PN2, 2PN2, 1NN2+). Far‐ultraviolet photons mainly come from the radiation processes in the mesosphere to the ionosphere, and its radiation flux may correlate with lightning energies. Further, a significant 777.4 nm background enhancement is recognized in South America, which may affect the trigger of space‐borne 777.4 nm lightning surveys.
Joint analysis of functionally related genes yields further candidates associated with Tetralogy of Fallot
Authors: Chelu Alexandru , Williams Simon G. , Keavney Bernard D. , Talavera David 
Published: June 2022

AbstractAlthough several genes involved in the development of Tetralogy of Fallot have been identified, no genetic diagnosis is available for the majority of patients. Low statistical power may have prevented the identification of further causative genes in gene-by-gene survey analyses. Thus, bigger samples and/or novel analytic approaches may be necessary. We studied if a joint analysis of groups of functionally related genes might be a useful alternative approach. Our reanalysis of whole-exome sequencing data identified 12 groups of genes that exceedingly contribute to the burden of Tetralogy of Fallot. Further analysis of those groups showed that genes with high-impact variants tend to interact with each other. Thus, our results strongly suggest that additional candidate genes may be found by studying the protein interaction network of known causative genes. Moreover, our results show that the joint analysis of functionally related genes can be a useful complementary approach to classical single-gene analyses.
Tipping the balance: toward rational combination therapies to overcome venetoclax resistance in mantle cell lymphoma
Authors: Thus Yvonne J. , Eldering Eric , Kater Arnon P. , Spaargaren Marcel 
Published: June 2022

AbstractMantle cell lymphoma (MCL), an aggressive, but incurable B-cell lymphoma, is genetically characterized by the t(11;14) translocation, resulting in the overexpression of Cyclin D1. In addition, deregulation of the B-cell lymphoma-2 (BCL-2) family proteins BCL-2, B-cell lymphoma-extra large (BCL-XL), and myeloid cell leukemia-1 (MCL-1) is highly common in MCL. This renders these BCL-2 family members attractive targets for therapy; indeed, the BCL-2 inhibitor venetoclax (ABT-199), which already received FDA approval for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), shows promising results in early clinical trials for MCL. However, a significant subset of patients show primary resistance or will develop resistance upon prolonged treatment. Here, we describe the underlying mechanisms of venetoclax resistance in MCL, such as upregulation of BCL-XL or MCL-1, and the recent (clinical) progress in the development of inhibitors for these BCL-2 family members, followed by the transcriptional and (post-)translational (dys)regulation of the BCL-2 family proteins, including the role of the lymphoid organ microenvironment. Based upon these insights, we discuss how rational combinations of venetoclax with other therapies can be exploited to prevent or overcome venetoclax resistance and improve MCL patient outcome.
The role of pancreas to improve hyperglycemia in STZ-induced diabetic rats by thiamine disulfide
Authors: Rad Mahtab Ghanbari , Sharifi Mohammadreza , Meamar Rokhsareh , Soltani Nepton 
Published: June 2022

Abstract
Background
The present study investigated the effect of thiamine disulfide (TD) on the pancreas in terms of hyperglycemia improvement and insulin sensitivity increase in diabetic male rats. We also aimed to study the function of Pdx1 (pancreatic and duodenal homeobox 1) and Glut2 (glucose transporter 2) genes in pancreatic tissue.

Methods
Type 1 diabetes was induced through injection of 60 mg/kg streptozotocin (STZ). The diabetic rats were divided into four groups, namely diabetic control (DC), diabetic treated with thiamine disulfide (D-TD), diabetic treated with insulin (D-insulin), and diabetic treated with TD and insulin (D-insulin+TD). The non-diabetic (NDC) and diabetic groups received a normal diet (14 weeks). Blood glucose level and body weight were measured weekly; insulin tolerance test (ITT) and glucagon tolerance test (GTT) were performed in the last month of the study. The level of serum insulin and glucagon were measured monthly and a hyperglycemic clamp (Insulin Infusion rate (IIR)) was done for all the groups. Pancreas tissue was isolated so that Pdx1and Glut2 genes expression could be measured.

Results
We observed that TD therapy decreased blood glucose level, ITT, and serum glucagon levels in comparison with those of the DC group; it also increased serum insulin levels, IIR, and expression of Pdx1 and Glut2 genes in comparison with those of the DC group.

Conclusion
Administration of TD could improve hyperglycemia in type 1 diabetic animals through improved pancreas function. Therefore, not only does TD have a significant effect on controlling and reducing hyperglycemia in diabetes, but it also has the potential to decrease the dose of insulin administration.
Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy
Authors: Gao Weitong , Wang Xueying , Zhou Yang , Wang Xueqian , Yu Yan 
Published: June 2022

AbstractIn recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not to ICIs, partly caused by the absence of tumor-infiltrating lymphocytes (TILs), significantly limits the application of ICIs. Converting these immune “cold” tumors into “hot” tumors that may respond to ICIs is an unsolved question in cancer immunotherapy. Since it is a general characteristic of cancers to resist apoptosis, induction of non-apoptotic regulated cell death (RCD) is emerging as a new cancer treatment strategy. Recently, several studies have revealed the interaction between non-apoptotic RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, and necroptosis exhibit synergistic antitumor immune responses while possibly exerting inhibitory effects on antitumor immune responses. Thus, targeted therapies (inducers or inhibitors) against autophagy, ferroptosis, pyroptosis, and necroptosis in combination with immunotherapy may exert potent antitumor activity, even in tumors resistant to ICIs. This review summarizes the multilevel relationship between antitumor immunity and non-apoptotic RCD, including autophagy, ferroptosis, pyroptosis, and necroptosis, and the potential targeting application of non-apoptotic RCD to improve the efficacy of immunotherapy in malignancy.
Cyanophages from a less virulent clade dominate over their sister clade in global oceans
Authors: Maidanik Ilia , Kirzner Shay , Pekarski Irena , Arsenieff Laure , Tahan Ran , Carlson Michael C G , Shitrit Dror , Baran Nava , Goldin Svetlana , Weitz Joshua S , Lindell Debbie 
Published: June 2022

Abstract
Environmental virus communities are highly diverse. However, the infection physiology underlying the evolution of diverse phage lineages and their ecological consequences are largely unknown. T7-like cyanophages are abundant in nature and infect the marine unicellular cyanobacteria, Synechococcus and Prochlorococcus, important primary producers in the oceans. Viruses belonging to this genus are divided into two distinct phylogenetic clades: clade A and clade B. These viruses have narrow host-ranges with clade A phages primarily infecting Synechococcus genotypes, while clade B phages are more diverse and can infect either Synechococcus or Prochlorococcus genotypes. Here we investigated infection properties (life history traits) and environmental abundances of these two clades of T7-like cyanophages. We show that clade A cyanophages have more rapid infection dynamics, larger burst sizes and greater virulence than clade B cyanophages. However, clade B cyanophages were at least 10-fold more abundant in all seasons, and infected more cyanobacteria, than clade A cyanophages in the Red Sea. Models predicted that steady-state cyanophage abundances, infection frequency, and virus-induced mortality, peak at intermediate virulence values. Our findings indicate that differences in infection properties are reflected in virus phylogeny at the clade level. They further indicate that infection properties, together with differences in subclade diversity and host repertoire, have important ecological consequences with the less aggressive, more diverse virus clade having greater ecological impacts.
Honey bee symbiont buffers larvae against nutritional stress and supplements lysine
Authors: Parish Audrey J , Rice Danny W , Tanquary Vicki M , Tennessen Jason M , Newton Irene L G 
Published: June 2022

Abstract
Honey bees have suffered dramatic losses in recent years, largely due to multiple stressors underpinned by poor nutrition [1]. Nutritional stress especially harms larvae, who mature into workers unable to meet the needs of their colony [2]. In this study, we characterize the metabolic capabilities of a honey bee larvae-associated bacterium, Bombella apis (formerly Parasaccharibacter apium), and its effects on the nutritional resilience of larvae. We found that B. apis is the only bacterium associated with larvae that can withstand the antimicrobial larval diet. Further, we found that B. apis can synthesize all essential amino acids and significantly alters the amino acid content of synthetic larval diet, largely by supplying the essential amino acid lysine. Analyses of gene gain/loss across the phylogeny suggest that four amino acid transporters were gained in recent B. apis ancestors. In addition, the transporter LysE is conserved across all sequenced strains of B. apis. Finally, we tested the impact of B. apis on developing honey bee larvae subjected to nutritional stress and found that larvae supplemented with B. apis are bolstered against mass reduction despite limited nutrition. Together, these data suggest a novel role of B. apis as a nutritional mutualist of honey bee larvae.
Dentists´ and Dental Hygienists´ experiences of the Capitation Contract System—the dilemma of conflicting loyalties
Authors: Boberg Emelie , Franzon Bengt , Johannsen Annsofi 
Published: June 2022

Abstract
Objective
The Capitation Contract system (CCS) is a payment model adopted by the Swedish Public Dental Health Service (PDHS). Patients enrolled in the CCS are usually assessed as being at lower risk of dental disease and are more regular dental attenders than those treated by Fee for Service (FFS). With increasing numbers of patients and CCS enrolments, Sweden faces a shortage of dental personnel. Our aim was to analyse dentists´ and dental hygienists´ perceptions and experiences of the capitation contact system.

Material and methods
Eleven dentists and dental hygienists from three Swedish regions participated in online qualitative interviews conducted according to the Grounded Theory methodology.

Results
When working with CCS the informants tried hard ´to find a balance between attitudes, compliance with guidelines and clinical resources´. Not all patients were offered CCS, even though they qualified: among other determinants were the informants’ interpretations of guidelines and regulations, clinical resources, and patient interest.

Conclusions
When dental resources are in balance, the informants appreciate the CCS and consider it to be favourable to patient health but are aware of conflicting loyalties of their dual roles of insurance sales agent and care provider. The informants´ individual mindset affects which patients are offered CCS enrolment.
Enantioselective Cu-catalyzed double hydroboration of alkynes to access chiral gem-diborylalkanes
Authors: Jin Shengnan , Li Jinxia , Liu Kang , Ding Wei-Yi , Wang Shuai , Huang Xiujuan , Li Xue , Yu Peiyuan , Song Qiuling 
Published: June 2022

AbstractChiral organoborons are of great value in asymmetric synthesis, functional materials, and medicinal chemistry. The development of chiral bis(boryl) alkanes, especially optically enriched 1,1-diboron compounds, has been greatly inhibited by the lack of direct synthetic protocols. Therefore, it is very challenging to develop a simple and effective strategy to obtain chiral 1,1-diborylalkanes. Herein, we develop an enantioselective copper-catalyzed cascade double hydroboration of terminal alkynes and highly enantioenriched gem-diborylalkanes were readily obtained. Our strategy uses simple terminal alkynes and two different boranes to construct valuable chiral gem-bis(boryl) alkanes with one catalytic and one ligand pattern, which represents the simplest and most straightforward strategy for constructing such chiral gem-diborons.
Closed-loop optimization of fast trapped-ion shuttling with sub-quanta excitation
Authors: Sterk Jonathan D. , Coakley Henry , Goldberg Joshua , Hietala Vincent , Lechtenberg Jason , McGuinness Hayden , McMurtrey Daniel , Parazzoli L. Paul , Van Der Wall Jay , Stick Daniel 
Published: June 2022

AbstractShuttling ions at high speed and with low motional excitation is essential for realizing fast and high-fidelity algorithms in many trapped-ion-based quantum computing architectures. Achieving such performance is challenging due to the sensitivity of an ion to electric fields and the unknown and imperfect environmental and control variables that create them. Here we implement a closed-loop optimization of the voltage waveforms that control the trajectory and axial frequency of an ion during transport in order to minimize the final motional excitation. The resulting waveforms realize fast round-trip transport of a trapped ion across multiple electrodes at speeds of 0.5 electrodes per microsecond (35 m﻿·s−1 for a one-way transport of 210 μm in 6 μs) with a maximum of 0.36 ± 0.08 mean quanta gain. This sub-quanta gain is independent of the phase of the secular motion at the distal location, obviating the need for an electric field impulse or time delay to eliminate the coherent motion.
NETISCE: a network-based tool for cell fate reprogramming
Authors: Marazzi Lauren , Shah Milan , Balakrishnan Shreedula , Patil Ananya , Vera-Licona Paola 
Published: June 2022

AbstractThe search for effective therapeutic targets in fields like regenerative medicine and cancer research has generated interest in cell fate reprogramming. This cellular reprogramming paradigm can drive cells to a desired target state from any initial state. However, methods for identifying reprogramming targets remain limited for biological systems that lack large sets of experimental data or a dynamical characterization. We present NETISCE, a novel computational tool for identifying cell fate reprogramming targets in static networks. In combination with machine learning algorithms, NETISCE estimates the attractor landscape and predicts reprogramming targets using signal flow analysis and feedback vertex set control, respectively. Through validations in studies of cell fate reprogramming from developmental, stem cell, and cancer biology, we show that NETISCE can predict previously identified cell fate reprogramming targets and identify potentially novel combinations of targets. NETISCE extends cell fate reprogramming studies to larger-scale biological networks without the need for full model parameterization and can be implemented by experimental and computational biologists to identify parts of a biological system relevant to the desired reprogramming task.
Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer
Authors: Becker Winston R. , Nevins Stephanie A. , Chen Derek C. , Chiu Roxanne , Horning Aaron M. , Guha Tuhin K. , Laquindanum Rozelle , Mills Meredith , Chaib Hassan , Ladabaum Uri , Longacre Teri , Shen Jeanne , Esplin Edward D. , Kundaje Anshul , Ford James M. , Curtis Christina , Snyder Michael P. , Greenleaf William J. 
Published: June 2022

AbstractTo chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.
Pseudomonas response regulators produced in an E. coli heterologous expression host exhibit host-derived post-translational phosphorylation
Authors: Garber Megan E. , Fregoso Rodrigo , Lake Julie , Kakouridis Anne , Mukhopadhyay Aindrila 
Published: June 2022

AbstractIn this report, we systematically characterize 32 response regulators (RRs) from a metal tolerant groundwater isolate, Pseudomonas stutzeri RCH2 to assess the impact of host-derived post-translational phosphorylation. As observed by distinct shifted bands in a phos-tag gel, 12 of the 24 detected RRs show homogenous mixtures of phosphorylated proteins or heterogenous mixtures of unphosphorylated and phosphorylated proteins. By evaluating the phosphorylation state of CzcR and CopR II under varying assay parameters, we found that changes to pH and exogenous addition of phospho-donors (e.g. acetyl phosphate) have little to no effect on phosphorylation state. By applying protein production conditions that decrease the pool of intracellular acetyl-phosphate in E. coli, we found a reduction in the phosphorylated population of CopR II when magnesium was added to the medium, but observed no change in phosphorylated population when CopR II is expressed in E. coli BL21 (DE3) ∆pta, a mutant with a metabolic disruption to the acetyl-phosphate pathway. Therefore, the specific mechanism of post-translational phosphorylation of RRs in E. coli remains obscure. These findings show the importance of characterizing the phosphorylation state of proteins when heterologously expressed, since their biochemical and physiological properties can be dependent on post-translational modification.
GABAergic CA1 neurons are more stable following context changes than glutamatergic cells
Authors: Schuette Peter J. , Ikebara Juliane M. , Maesta-Pereira Sandra , Torossian Anita , Sethi Ekayana , Kihara Alexandre H. , Kao Jonathan C. , Reis Fernando M. C. V. , Adhikari Avishek 
Published: June 2022

AbstractThe CA1 region of the hippocampus contains both glutamatergic pyramidal cells and GABAergic interneurons. Numerous reports have characterized glutamatergic CAMK2A cell activity, showing how these cells respond to environmental changes such as local cue rotation and context re-sizing. Additionally, the long-term stability of spatial encoding and turnover of these cells across days is also well-characterized. In contrast, these classic hippocampal experiments have never been conducted with CA1 GABAergic cells. Here, we use chronic calcium imaging of male and female mice to compare the neural activity of VGAT and CAMK2A cells during exploration of unaltered environments and also during exposure to contexts before and after rotating and changing the length of the context across multiple recording days. Intriguingly, compared to CAMK2A cells, VGAT cells showed decreased remapping induced by environmental changes, such as context rotations and contextual length resizing. However, GABAergic neurons were also less likely than glutamatergic neurons to remain active and exhibit consistent place coding across recording days. Interestingly, despite showing significant spatial remapping across days, GABAergic cells had stable speed encoding between days. Thus, compared to glutamatergic cells, spatial encoding of GABAergic cells is more stable during within-session environmental perturbations, but is less stable across days. These insights may be crucial in accurately modeling the features and constraints of hippocampal dynamics in spatial coding.