Additional Signal Research Articles

Historical Background of the Origin of the Speeddroop, Additional Control Signals and Analogic Retrofit of a Governor of a Francis Turbine, Using Operational Amplifier IC741

It is well known that governors of turbines, moving synchronous machines are responsible to maintain the rotation of the rotor of the generator constant and then the electric frequency constant, independently of the changes of electric loads connected to the power electric net. This paper treats about the origin and necessity of the permanent and transitory speedoops in the control mash of a governor. First, we develop the historical background origin of a governor. The basic controls actions are studied, and the analogic circuits related, using operational amplifiers. Then, as an easier way, the author uses an analogic generic PID governor to explain how the permanent speedroop is needed to set the power delivered by a hydraulic turbine (Francis) and then the transitory speedroop. Additional control signal as Power Joint Control and Automatic Generation Control-AGC are introduced. As a suggestion, a simple analogic Power Joint Control circuit example, using operational amplifier 741 is given, but not tested in a workbench. The using of the Automatic Control Generation-AGC, a supplementary control, is introduced because of the necessity to correct the frequency deviations. It is also given a simple circuit example of AGC, not tested in a workbench. This paper ends with an analogic retrofit of a governor of Francis turbine of decade of 1960 of 180 MW using analogic electronic. The author employs IC 741 operational amplifier. Prior simulations of the Laplace’s model of the governor were made using Matlab-Simulink. Because of the little acquisition time of the available oscilloscope, the author made a transformation in the original Laplace model that reduced the step response time by a factor of 20 but the methodology and know-how to make an analogic retrofit was conquered. The governor was built and tested in a workbench. The hydraulic circuit was simulated with 741 amp ops. The electronic simulation corresponded to the mathematics simulations showing the success of the analogic retrofit. The physical space needed by the equipment was reduced from the size of a refrigerator to a size of a shoe box. Although an analogic retrofit is considered obsolete today, the analogic retrofit has robustness, and it is cheaper.

Validation of subjective manual palpation using objective physiological recordings of the cranial rhythmic impulse during osteopathic manipulative intervention

Intermediate (IM) band physiology in skin blood flow exhibits parallels with the primary respiratory mechanism (PRM) or cranial rhythmic impulse (CRI), controversial concepts of osteopathy in the cranial field (OCF). Owing to inconsistent manual palpation results, validity of evidence of PRM/CRI activity has been questionable. We therefore tried to validate manual palpation combining instrumented tracking and algorithmic objectivation of frequencies, amplitudes, and phases. Using a standard OCF intervention, cranial vault hold (CVH), two OCF experts palpated and digitally marked CRI frequencies in 25 healthy adults. Autonomic nervous system (ANS) activity in low frequency (LF) and IM band in photoplethysmographic (PPG) forehead skin recordings was probed with momentary frequency of highest amplitude (MFHA) and wavelet amplitude spectra (WAS) in examiners and participants. Palpation errors and frequency expectation bias during CVH were analyzed for phases of MFHA and CRI. Palpated CRI frequencies (0.05–0.08 Hz) correlated highly with mean MFHA frequencies with 1:1 ratio in 77% of participants (LF-responders; 0.072 Hz) and with 2:1 ratio in 23% of participants (IM-responders; 0.147 Hz). WAS analysis in both groups revealed integer number (harmonic) waves in (very) low and IM bands in > 98% of palpated intervals. Phase analyses in participants and examiners suggested synchronization between MFHA and CRI in a subset of LF-responders. IM band physiology in forehead PPG may offer a sensible physiological correlate of palpated CRI activity. Possible coordination or synchronization effects with additional physiological signals and between examiners and participants should be investigated in future studies.

Formula omitted]-Net: Medical image segmentation using efficient and effective deep supervision

Although the existing deep supervised solutions have achieved some great successes in medical image segmentation, they have the following shortcomings; (i) semantic difference problem: since they are obtained by very different convolution or deconvolution processes, the intermediate masks and predictions in deep supervised baselines usually contain semantics with different depth, which thus hinders the models’ learning capabilities; (ii) low learning efficiency problem: additional supervision signals will inevitably make the training of the models more time-consuming. Therefore, in this work, we first propose two deep supervised learning strategies, U-Net-Deep and U-Net-Auto, to overcome the semantic difference problem. Then, to resolve the low learning efficiency problem, upon the above two strategies, we further propose a new deep supervised segmentation model, called μ-Net, to achieve not only effective but also efficient deep supervised medical image segmentation by introducing a tied-weight decoder to generate pseudo-labels with more diverse information and also speed up the convergence in training. Finally, three different types of μ-Net-based deep supervision strategies are explored and a Similarity Principle of Deep Supervision is further derived to guide future research in deep supervised learning. Experimental studies on four public benchmark datasets show that μ-Net greatly outperforms all the state-of-the-art baselines, including the state-of-the-art deeply supervised segmentation models, in terms of both effectiveness and efficiency. Ablation studies sufficiently prove the soundness of the proposed Similarity Principle of Deep Supervision, the necessity and effectiveness of the tied-weight decoder, and using both the segmentation and reconstruction pseudo-labels for deep supervised learning.

A novel allelic donkey β-lactoglobulin I protein isoform generated by a non-AUG translation initiation codon is associated with a nonsynonymous SNP

β-Lactoglobulin I (β-LG I) is one of the most important whey proteins in donkey milk. However, to our knowledge, there has been no study focusing on the full nucleotide sequences of this gene (BLG I). Current investigation of donkey BLG I gene is very limited with only 2 variants (A and B) characterized so far at the protein level. Recently, a new β-LG I variant, with a significantly higher mass (+1,915 Da) than known variants has been detected. In this study, we report the whole nucleotide sequence of the BLG I gene from 2 donkeys, whose milk samples are characterized by the β-LG I SDS-PAGE band with a normal electrophoretic mobility (18,514.25 Da, β-LG I B1 form) the first, and by the presence of a unique β-LG I band with a higher electrophoretic mobility (20,428.5 Da, β-LG I D form) the latter. A high genetic variability was found all over the 2 sequenced BLG I alleles. In particular, 16 polymorphic sites were found in introns, one in the 5' flanking region, 3 SNPs in the 5' untranslated region and one SNP in the coding region (g.458G > A) located at the 40th nucleotide of exon 2 and responsible for the AA substitutions p.Asp28 > Asn in the mature protein. Two SNPs (g.920-922CAC > TGT and g.1871G/A) were genotyped in 93 donkeys of 2 Italian breeds (60 Ragusana and 33 Amiatina, respectively) and the overall frequencies of g.920-922CAC and g.1871A were 0.3065 and 0.043, respectively. Only the rare allele g.1871A was observed to be associated with the slower migrating β-LG I. Considering this genetic diversity and those found in the database, it was possible to deduce at least 5 different alleles (BLG I A, B, B1, C, D) responsible for 4 potential β-LG I translations. Among these alleles, B1 and D are those characterized in the present research, with the D allele of real novel identification. Haplotype data analysis suggests an evolutionary pathway of donkey BLG I gene and a possible phylogenetic map is proposed. Analyses of mRNA secondary structure showed relevant changes in the structures, as consequence of the g.1871G > A polymorphism, that might be responsible for the recognition of an alternative initiation site providing an additional signal peptide. The extension of 19 AA sequence to the mature protein, corresponding to the canonical signal peptide with an additional alanine residue, is sufficient to provide the observed molecular weight of the slower migrating β-LG I encoded by the BLG I D allele.

Evolution of acoustic signals associated with cooperative parental behavior in a poison frog

The emergence of complex social interactions is predicted to be an important selective force in the diversification of communication systems. Parental care presents a key social context in which to study the evolution of novel signals, as care often requires communication and behavioral coordination between parents and is an evolutionary stepping-stone toward increasingly complex social systems. Anuran amphibians (frogs and toads) are a classic model of acoustic communication and the vocal repertoires of many species have been characterized in the contexts of advertisement, courtship, and aggression, yet quantitative descriptions of calls elicited in the context of parental care are lacking. The biparental poison frog, Ranitomeya imitator, exhibits a remarkable parenting behavior in which females, cued by the calls of their male partners, feed tadpoles unfertilized eggs. Here, we characterized and compared calls across three social contexts, for the first time including a parental care context. We found that egg-feeding calls share some properties with both advertisement and courtship calls but also had unique properties. Multivariate analysis revealed high classification success for advertisement and courtship calls but misclassified nearly half of egg feeding calls as either advertisement or courtship calls. Egg feeding and courtship calls both contained less identity information than advertisement calls, as expected for signals used in close-range communication where uncertainty about identity is low and additional signal modalities may be used. Taken together, egg-feeding calls likely borrowed and recombined elements of both ancestral call types to solicit a novel, context-dependent parenting response.

Type I interferons augment regulatory T cell polarization in concert with ancillary cytokine signals.

In the transplant community, research efforts exploring endogenous alternatives to inducing tolerogenic allo-specific immune responses are much needed. In this regard, CD4 + FoxP3+ regulatory T cells (Tregs) are appealing candidates due to their intrinsic natural immunosuppressive qualities. To date, various homeostatic factors that dictate Treg survival and fitness have been elucidated, particularly the non-redundant roles of antigenic CD3ζ/T-cell-receptor, co-stimulatory CD28, and cytokine interleukin (IL-)2 dependent signaling. Many of the additional biological signals that affect Tregs remain to be elucidated, however, especially in the transplant context. Previously, we demonstrated an unexpected link between type I interferons (IFNs) and Tregs in models of multiple myeloma (MM)-where MM plasmacytes escaped immunological surveillance by enhancing type I IFN signaling and precipitating upregulated Treg responses that could be overturned with specific knockdown of type I IFN signaling. Here, we elaborated on these findings by assessing the role of type I IFN signaling (IFN-α and -β) on Treg homeostasis within an alloimmune context. Specifically, we studied the induction of Tregs from naïve CD4 T cells. Using in vitro and in vivo models of murine skin allotransplantation, we found that type I IFN indeed spatiotemporally enhanced the polarization of naïve CD4 T cells into FoxP3+ Tregs. Notably, however, this effect was not independent of, and rather co-dependent on, ancillary cytokine signals including IL-2. These findings provide evidence for the relevance of type I IFN pathway in modulating FoxP3+ Treg responses and, by extension, stipulate an additional means of facilitating Treg fitness via type I IFNs.

Abstract 5693: Cancer cells subvert fibroblast function to promote a growth factor enriched tumor microenvironment in endocrine therapy resistant ER+ breast cancer

Abstract While endocrine therapy (ET) has considerably improved Stage II/III ER+ breast cancer survival rates, resistance emerges in 30-50% of patients. Recent advances have uncovered numerous cancer intrinsic and tumor-microenvironment mediated mechanisms contributing to ET resistance. However, the predominant mechanisms that prevent cure and ultimately lead to development of terminal metastatic cancer remain unknown. To reveal the leading causes of ET resistance in early-stage ER+ breast cancers, we used single-cell RNA sequencing to profile serial tumor biopsies from a larger cohort of patients. Patients received either endocrine therapy (letrozole) alone or in combination with a CDK4/6 cell cycle inhibitor (ribociclib). We examined the evolution of tumor composition, cellular communication, and the phenotypic diversity of tumor-associated cancer and non-cancer cells throughout treatment. Our analyses reveal that ET-resistant tumors are fibroblast- and endothelial-enriched and consistently exhibit broad upregulation of growth factor signaling to cancer cells, with consistent activation of ERBB communication across patient tumors. Fibroblasts emerged as the primary source of these additional growth factor signals. Upregulation of fibroblast growth factor signaling (via NRG1/2, EGF and IGF) was commensurate with differentiation to a mesenchymal cancer-associated-fibroblast (myCAF) phenotype, which was itself stimulated by cancer cells through EGF and TGF signaling. In response to growth factor enrichment, cancer cells of ET-resistant tumors showed activation of MAPK signal transduction and downstream transcription factors promoting proliferation including FOS, JUN and TRIB1. These results indicate that ET resistance emerges in patient tumors when cancer cells subvert fibroblast function to promote a growth factor enriched tumor microenvironment permitting estrogen independent cancer proliferation. Citation Format: Jason I. Griffiths, Patrick A. Cosgrove, Eric Medina Castaneda, Aritro Nath, Jinfeng Chen, Frederick R. Adler, Jeffrey T. Chang, Qamar J. Khan, Andrea H. Bild. Cancer cells subvert fibroblast function to promote a growth factor enriched tumor microenvironment in endocrine therapy resistant ER+ breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5693.

Abstract 5105: TIMP1 mediates astrocyte-dependent local immunosuppression in brain metastasis

Abstract Brain metastasis is an unmet clinical need, affecting between 10-30% of cancer patients with 200000 to 400000 newly diagnosis per annum in the US. Recently, several clinical trials have reported benefits using immunotherapy to treat brain metastasis. However, variability of the responses is broad and high benefit is found mainly in asymptomatic brain metastasis, while the benefit is dramatically reduced in the clinically relevant stage. Thus, it is currently unknown how to effectively target symptomatic brain metastases with immunotherapy. We previously reported a clinically relevant protumoral program driven by STAT3 activation in a subpopulation of reactive astrocytes in these advanced stages of the disease. Our current study further exploited the heterogeneity within the metastasis-associated microenvironment as a resource to identify novel therapeutic vulnerabilities to improve the benefits of immunotherapies based on immune checkpoint blocking antibodies (ICB) in symptomatic brain metastasis. Our results demonstrate that reactive astrocytes are strong immunomodulatory cells in brain tumors. We have identified the molecular profile of disease-associated glial cells and defined its connection to modulatory activities on specific lymphocyte populations in experimental brain metastasis as well as human-derived samples. scRNASeq and high content multiplex immunofluorescence allowed us to report a novel local immunomodulatory axis dependent on TIMP1 (astrocytes)/CD63 (CD8 T cells), which is present in brain metastasis patients with high immunoscore and would imply an additional immunosuppressive signal for potential ICB responders in brain metastasis. Genetic and pharmacologic approaches targeting this STAT3-dependent local immunomodulatory axis have allowed us to define the rationale to combine immune checkpoint blockade with a STAT3 inhibitor, which we previously used in patients. We proved that such combined immunotherapy boost the systemic activation of T cells while also preventing the local blockade. Additionally, our comprehensive strategy includes the possibility to stratify patients that are best qualified to benefit from this therapy by measuring TIMP1 in liquid biopsies from CSF. Even more, our data using Patient Derived Organotypic Cultures (PDOC) from fresh brain metastasis neurosurgeries confirms that our therapeutic strategy might benefit brain metastases generated from any primary source. In conclusion, we describe an immunosuppressive mechanism in the brain microenvironment that could explain the lack of response to ICB in patients with advanced brain metastasis. Our finding provides the rationale to implement complementary approaches targeting local immunosuppression to increase the benefit of immunotherapy in symptomatic brain metastasis. Citation Format: Neibla Priego, Pedro García-Gómez, Ana de Pablos-Aragoneses, María Perea-García, Laura Álvaro-Espinosa, Carolina Hernández-Oliver, Elena Martínez-Saez, Ángel Pérez-Núñez, Aurelio Hernández-Laín, Rebeca Sanz-Pamplona, Marc Schmitz, Stephen J. Crocker, Diego Serrano, Asís Palazón, RENACER Red Nacional de Metástasis Cerebral, Manuel Valiente. TIMP1 mediates astrocyte-dependent local immunosuppression in brain metastasis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5105.

10 Gbit/s optical access network system based on PAM8 modulation

In terms of high-speed optical access system, an optical access network system with low-cost and low-complexity based on PAM8 modulated signal is proposed to meet the growing demand of optical access network capacity. Based on the system scheme proposed, an experimental simulation platform of 10 Gbit/s PAM8 modulated signal optical access system is built. In this scheme of the system, the intensity modulation/direct detection (IM/DD) is used to achieve the modulation and demodulation of the signal, and the entire optical access link does not use additional signal amplifier components, reducing the complexity and cost of the system. According to the experimental results, the BER of the received signal has slight changes within a certain transmission distance. And after 20 kilometers of transmission, when the BER of the received signal is close to 1e-4, the receiving sensitivity is lower than -12 dBm. The proposed optical access system has good sensitivity and has good application prospects for future broadband access network.

Abstract 4775: Knockout of Sod2 accelerates KrasG12D-driven formation of pancreatic cancerous lesions

Abstract Recent studies demonstrate that mitochondrially-generated reactive oxygen species (ROS) downstream of oncogenic KRAS drive acinar-to-ductal metaplasia (ADM), a key first step in the pancreatic ductal adenocarcinoma (PDA) progression model. MnSOD/SOD2 is a mitochondrial enzyme that converts superoxide into hydrogen peroxide. Previous studies have shown that SOD2 is biologically relevant to the study of pancreatic cancer. Some patients with a SOD2 polymorphism resulting in less active MnSOD at the mitochondrial matrix are at increased risk of developing pancreatic cancer. Additionally, MnSOD is lost in high-grade human PanIN, further suggesting a role in tumor development. To elucidate the role of MnSOD in pancreatic cancer initiation and progression, we crossed Sod2lox/lox mice into the p48Cre;LSL-KrasG12D (KC) mouse model. We found increased ROS, abundantly more abnormal tissue development and presence of flat lesions indicating accelerated early progression. However, Kaplan Meyer survival analysis of KC and KC;Sod2−/− mice did not indicate faster progression to cancer, suggesting that for later steps additional signaling is needed. In summary, we identify MnSOD as a key antioxidant molecule preventing initiation of PDA. Citation Format: Alicia K. Fleming Martinez, Brandy H. Edenfield, Irene Esposito, Peter Storz. Knockout of Sod2 accelerates KrasG12D-driven formation of pancreatic cancerous lesions. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4775.

Refined Composite Multiscale Phase Rényi Dispersion Entropy for Complexity Measure

Assessing the complexity of signals or dynamical systems is important in disease diagnosis, mechanical system defect, astronomy analysis, and many other fields. Although entropy measures as complexity estimators have greatly improved, the majority of these measures are quite sensitive to specified parameters and are impacted by short data lengths. This paper proposes a novel entropy algorithm to enhance the existing complexity assessment methods based on classical dispersion entropy (DE) and Rényi entropy (RE) by introducing refined composite multiscale coarse-grained treatment and phase transformation. The proposed refined composite multiscale phase Rényi dispersion entropy (PRRCMDE) addresses the flaws of various existing entropy approaches while still incorporating their merits. Several simulated signals from logistic mapping, AR model, MIX process, and additive WGN periodic signals are adopted to examine the performance of PRRCMDE from multiple perspectives. It demonstrates that the efficacy of the suggested algorithm can be increased by modifying the DE and RE parameters to a reasonable range. As a real-world application, the bearings’ varied fault types and levels can also be recognized clearly.

Delineation of G Protein-Coupled Receptor Kinase Phosphorylation Sites within the D1 Dopamine Receptor and Their Roles in Modulating β-Arrestin Binding and Activation.

The D1 dopamine receptor (D1R) is a G protein-coupled receptor that signals through activating adenylyl cyclase and raising intracellular cAMP levels. When activated, the D1R also recruits the scaffolding protein β-arrestin, which promotes receptor desensitization and internalization, as well as additional downstream signaling pathways. These processes are triggered through receptor phosphorylation by G protein-coupled receptor kinases (GRKs), although the precise phosphorylation sites and their role in recruiting β-arrestin to the D1R remains incompletely described. In this study, we have used detailed mutational and in situ phosphorylation analyses to completely identify the GRK-mediated phosphorylation sites on the D1R. Our results indicate that GRKs can phosphorylate 14 serine and threonine residues within the C-terminus and the third intracellular loop (ICL3) of the receptor, and that this occurs in a hierarchical fashion, where phosphorylation of the C-terminus precedes that of the ICL3. Using β-arrestin recruitment assays, we identified a cluster of phosphorylation sites in the proximal region of the C-terminus that drive β-arrestin binding to the D1R. We further provide evidence that phosphorylation sites in the ICL3 are responsible for β-arrestin activation, leading to receptor internalization. Our results suggest that distinct D1R GRK phosphorylation sites are involved in β-arrestin binding and activation.

Extremely Weak Signal Detection Algorithm of Multi-Pixel Photon Detector

For the detection of extremely weak signals in underwater long distance wireless optical communication, the Geiger mode of the multi pixel photon detector has serious pulse superposition effect and Poisson noise, which leads to counting difficulties and affects the measurement accuracy. This paper proposes a deconvolution joint generalized Anscombe transform (DUGAT) detection algorithm. First, the deconvolution filtering technology is used to process the weak signal to reduce the superposition effect and converge the pulse width. Secondly, the noise signal of Poisson+Gaussian (P+G) distribution is converted into Gaussian variable by using generalized Anscombe transform (GAT), which is equivalent to additive Gaussian noise signal. Finally, the symbols are counted by hard decision algorithm. The experimental results show that the sensitivity of this algorithm is improved by 8.57dB and 9.95dB respectively compared with the traditional AR and ML detection algorithms.

Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets

Leveraging linkage disequilibrium (LD) patterns as representative of population substructure enables the discovery of additive association signals in genome-wide association studies (GWASs). Standard GWASs are well-powered to interrogate additive models; however, new approaches are required for invesigating other modes of inheritance such as dominance and epistasis. Epistasis, or non-additive interaction between genes, exists across the genome but often goes undetected because of a lack of statistical power. Furthermore, the adoption of LD pruning as customary in standard GWASs excludes detection of sites that are in LD but might underlie the genetic architecture of complex traits. We hypothesize that uncovering long-range interactions between loci with strong LD due to epistatic selection can elucidate genetic mechanisms underlying common diseases. To investigate this hypothesis, we tested for associations between 23 common diseases and 5,625,845 epistatic SNP-SNP pairs (determined by Ohta's D statistics) in long-range LD (>0.25 cM). Across five disease phenotypes, we identified one significant and four near-significant associations that replicated in two large genotype-phenotype datasets (UK Biobank and eMERGE). The genes that were most likely involved in the replicated associations were (1) members of highly conserved gene families with complex roles in multiple pathways, (2) essential genes, and/or (3) genes that were associated in the literature with complex traits that display variable expressivity. These results support the highly pleiotropic and conserved nature of variants in long-range LD under epistatic selection. Our work supports the hypothesis that epistatic interactions regulate diverse clinical mechanisms and might especially be driving factors in conditions with a wide range of phenotypic outcomes.

Lack of Herpes Virus Entry Mediator Signals in Thymocytes Impairs Conventional CD8 T Cell Selection and Promotes Memory-like CD8 T Cell Development.

Thymocytes having diverse Ag specificities are selected in response to self-MHC-peptide expressed in thymic epithelial cells, which contributes to the formation of a T cell repertoire. However, it is not well understood whether additional signals from epithelial cells are required to drive positive selection. In this study, we found that one of the TNFR superfamily members, herpes virus entry mediator (HVEM), when expressed on thymocytes provides signals for positive selection. HVEM deficiency in double-positive (DP) thymocytes impaired positive selection of CD8 thymocytes. HVEM-deficient thymocytes in OT-1 TCR transgenic mice exhibited significant defects in positive selection and impaired CD69 upregulation of selected thymocytes. HVEM ligands (lymphotoxin-like, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes, and B and T lymphocyte attenuator) were expressed in cortical thymic epithelial cells. Weak TCR ligation combined with HVEM signals enhanced ERK activation in DP thymocytes developed invitro. Insufficient signals for positive selection in HVEM-deficient DP thymocytes led to the development of innate memory-like CD8 T cells expressing high levels of CD122, along with the increased development of PLZF+ NKT cells. These results suggest that thymocytes receive activation signals through HVEM during positive selection. Thus, our findings provide evidence that the threshold of thymocyte positive selection is set by signals from TCR in association with HVEM.

Ketones and the Heart: Metabolic Principles and Therapeutic Implications.

The ketone bodies beta-hydroxybutyrate and acetoacetate are hepatically produced metabolites catabolized in extrahepatic organs. Ketone bodies are a critical cardiac fuel and have diverse roles in the regulation of cellular processes such as metabolism, inflammation, and cellular crosstalk in multiple organs that mediate disease. This review focuses on the role of cardiac ketone metabolism in health and disease with an emphasis on the therapeutic potential of ketosis as a treatment for heart failure (HF). Cardiac metabolic reprogramming, characterized by diminished mitochondrial oxidative metabolism, contributes to cardiac dysfunction and pathologic remodeling during the development of HF. Growing evidence supports an adaptive role for ketone metabolism in HF to promote normal cardiac function and attenuate disease progression. Enhanced cardiac ketone utilization during HF is mediated by increased availability due to systemic ketosis and a cardiac autonomous upregulation of ketolytic enzymes. Therapeutic strategies designed to restore high-capacity fuel metabolism in the heart show promise to address fuel metabolic deficits that underpin the progression of HF. However, the mechanisms involved in the beneficial effects of ketone bodies in HF have yet to be defined and represent important future lines of inquiry. In addition to use as an energy substrate for cardiac mitochondrial oxidation, ketone bodies modulate myocardial utilization of glucose and fatty acids, two vital energy substrates that regulate cardiac function and hypertrophy. The salutary effects of ketone bodies during HF may also include extra-cardiac roles in modulating immune responses, reducing fibrosis, and promoting angiogenesis and vasodilation. Additional pleotropic signaling properties of beta-hydroxybutyrate and AcAc are discussed including epigenetic regulation and protection against oxidative stress. Evidence for the benefit and feasibility of therapeutic ketosis is examined in preclinical and clinical studies. Finally, ongoing clinical trials are reviewed for perspective on translation of ketone therapeutics for the treatment of HF.

An evaluation of ECG data fusion algorithms for wearable IoT sensors

In wearable sensing, accurate estimation of physiological parameters is paramount, although these signals can be corrupted by noise. The fusion of data from multiple sensor sources has the potential to enhance accuracy, even in the presence of disruptive noise. This paper aims to introduce and compare various existing state-of-the-art and novel data fusion techniques to improve the reliability of heart rate estimation. The comparisons were implemented using the MIT-BIH Arrhythmia database with additive noise signals taken from MIT Noise Stress Test Database. When it comes to the challenging low signal-to-noise ratio (SNR) regions, the Kalman fusion and the α-trim mean filtering approach exhibits the best performance. The Kalman fusion approach dominates when both channels are corrupted, while the α-trim mean filtering elimination algorithm takes the lead when at least one channel is clean. To make the most of these strengths, we have developed an innovative algorithm that can switch between the two fusion methods based on a signal quality indicator (SQI) that serves as a surrogate SNR. This algorithm outperforms the baseline 2-channel RR-interval averaging approach by ≃54% and ≃21% at SNRs of 20dB and −20dB respectively. Moreover, it outperforms other cutting-edge heart rate estimation methods.

Splenic stromal niches in homeostasis and immunity.

The spleen is a gatekeeper of systemic immunity where immune responses against blood-borne pathogens are initiated and sustained. Non-haematopoietic stromal cells construct microanatomical niches in the spleen that make diverse contributions to physiological spleen functions and regulate the homeostasis of immune cells. Additional signals from spleen autonomic nerves also modify immune responses. Recent insight into the diversity of the splenic fibroblastic stromal cells has revised our understanding of how these cells help to orchestrate splenic responses to infection and contribute to immune responses. In this Review, we examine our current understanding of how stromal niches and neuroimmune circuits direct the immunological functions of the spleen, with a focus on T cell immunity.

Multiverse: Multilingual Evidence for Fake News Detection

The rapid spread of deceptive information on the internet can have severe and irreparable consequences. As a result, it is important to develop technology that can detect fake news. Although significant progress has been made in this area, current methods are limited because they focus only on one language and do not incorporate multilingual information. In this work, we propose Multiverse-a new feature based on multilingual evidence that can be used for fake news detection and improve existing approaches. Our hypothesis that cross-lingual evidence can be used as a feature for fake news detection is supported by manual experiments based on a set of true (legit) and fake news. Furthermore, we compared our fake news classification system based on the proposed feature with several baselines on two multi-domain datasets of general-topic news and one fake COVID-19 news dataset, showing that (in combination with linguistic features) it yields significant improvements over the baseline models, bringing additional useful signals to the classifier.

HIP 67506 C: MagAO-X confirmation of a new low-mass stellar companion to HIP 67506 A

ABSTRACT We report the confirmation of HIP 67506 C, a new stellar companion to HIP 67506 A. We previously reported a candidate signal at 2λ/D (240 mas) in L′ in MagAO/Clio imaging using the binary differential imaging technique. Several additional indirect signals showed that the candidate signal merited follow-up: significant astrometric acceleration in Gaia DR3, Hipparcos–Gaia proper motion anomaly, and overluminosity compared to single main-sequence stars. We confirmed the companion, HIP 67506 C, at 0.1 arcsec with MagAO-X in 2022 April. We characterized HIP 67506 C MagAO-X photometry and astrometry, and estimated spectral-type K7-M2; we also re-evaluated HIP 67506 A in light of the close companion. Additionally, we show that a previously identified 9 arcsec companion, HIP 67506 B, is a much further distant unassociated background star. We also discuss the utility of indirect signposts in identifying small inner working angle candidate companions.