Miracle-dz/UniFAR-FTUs huggingface dataset:
Projections in several complex variables

This thesis consists two parts. In the first part, we completely study the heat equation method ofMenikoff-Sjostrand and apply it to the Kohn Laplacian defined on a compact orientable connected CR manifold. We then get the full asymptotic expansion of the Szego projection for (0,q) forms when the Levi formis nondegenerate. This generalizes a result of Boutet de Monvel and Sjostrand for (0,0) forms. Our main tool is Fourier integral operators with complex valued phase functions of Melin and Sjostrand. In the second part, we obtain the full asymptotic expansion of the Bergman projection for (0,q) forms when the Levi form is non-degenerate. This also generalizes a result of Boutet deMonvel and Sjostrand for (0,0) forms. We introduce a new operator analogous to the Kohn Laplacian defined on the boundary of a domain and we apply the heat equation method ofMenikoff and Sjostrand to this operator. We obtain a description of a new Szego projection up to smoothing operators. Finally, by using the Poisson operator, we get our main result.
EFFECT OF ORGANIC AND CHEMICAL FERTILIZERS ON THE NUTRITIONAL COMPOSITION OF Amaranthus spinosus

Organic and chemical fertilizers are used in agriculture as they improve the fertility of soil and the growth of plants. So, the present investigation was designed to determine the effect of different fertilizers on the nutritional value of Amaranthus spinosus plant. The quantity of different fertilizers was used as 500 kg h-1. Some selected parameters of soil such as temperature (29.50 C), moisture (3.5 %), Water holding capacity (74%), pH (8.17), organic carbon % (1.90) and organic matter % (3.28) were measured and analysed. There was no significant variation in these parameters under different fertilizers treatment. The phytochemicals of Organic fertilizers treated plant sample had higher concentration of Alkaloid (1.06), flavonoid (0.89), tannin (1.48) and saponin (1.67), ash (7.75), moisture (87.6) and protein (9.1), Fe (0.054), Zn (0.008), Cu (0.001), Na (0.0080), Ca (113) and Mg (93) when compared to the other fertilizer treatments. Inorganic fertilizer did not show any significant effect on plant growth, while the combination of organic and chemical fertilizers was found to have a significant effect. The results reveal that organic fertilizers or their combination with chemical fertilizer are better for the crops than chemical fertilizers.
Physiological Levels of Estrogen and Progesterone Modulate CR3 expression on, and Neisseria gonorrhoeae Infection of, Primary, Human, Cervical Epithelial Cells

Despite advances made in our understanding of Neisseria gonorrhoeae pathogenesis, factors dictating the divergent presentation of gonococcal disease observed between men and women, in vivo, remain unclear. Clinical data indicate that gonococcal pathogenesis of the female genital tract is influenced by steroid hormones. Notwithstanding, there are limited data addressing how steroid hormones modulate gonococcal pathogenesis. Hence, we investigated the effect(s) of physiological concentrations of estrogens and progestogens on N. gonorrhoeae viability and on complement-mediated infection of primary cervical cells. In contrast to previous studies that showed a bacteriostatic effect of non-physiological concentrations of steroid hormones on gonococci, our data indicate that physiological concentrations of estrogens and progestogens do not inhibit gonococcal growth in vitro or during infection of primary cervical cells. Estradiol promoted complement receptor 3 recruitment to the cervical cell surface and, thus, the ability of gonococci to associate with these cells. Progesterone-predominant assay conditions resulted in decreased expression of Opa proteins by gonococci, increased complement production by cervical cells, and increased iC3b opsonization of gonococci during cervical cell challenge. Collectively, our data support clinical observations and demonstrate that estrogens and progestogens distinctly modulate gonococcal cervical infection.
The mIAA7 degron improves auxin-mediated degradation in Caenorhabditis elegans

Auxin-inducible degradation (AID) is a powerful tool for the targeted degradation of proteins with spatiotemporal control. One limitation of the AID system is that not all proteins are degraded efficiently. Here, we demonstrate that an alternative degron sequence, termed mIAA7, improves the efficiency of degradation in C. elegans, as previously reported in human cells. We tested depletion of a series of proteins with various sub-cellular localizations in different tissue types and found that the use of the mIAA7 degron resulted in faster depletion kinetics for five out of six proteins tested. The exception was the nuclear protein HIS-72, which was depleted with similar efficiency as with the conventional AID* degron sequence. The mIAA7 degron also increased the leaky degradation for two of the tested proteins. To overcome this problem, we combined the mIAA7 degron with the C. elegans AID2 system (C.e.AID2), which resulted in complete protein depletion without detectable leaky degradation. Finally, we show that degradation of ERM-1, a highly stable protein that is challenging to deplete, could be improved further by using multiple mIAA7 degrons. Taken together, the mIAA7 degron further increases the power and applicability of the AID system. To facilitate the generation of mIAA7-tagged proteins using CRISPR/Cas9 genome engineering, we generated a toolkit of plasmids for the generation of dsDNA repair templates by PCR.
Melatonin suppression does not automatically alter sleepiness, vigilance, sensory processing, or sleep

Pre-sleep exposure to short-wavelength light suppresses melatonin and decreases sleepiness with activating effects extending to sleep. This has mainly been attributed to melanopic effects, but mechanistic insights are missing. Thus, we investigated whether two light conditions only differing in the melanopic effects (123 vs. 59 lux melanopic EDI) differentially affect sleep besides melatonin. Additionally, we studied whether the light differentially modulates sensory processing during wakefulness and sleep. Twenty-nine healthy volunteers (18-30 years, 15 women) were exposed to two metameric light conditions (high-vs. low-melanopic, ≈60 photopic lux) for 1 hour ending 50 min prior to habitual bed time. This was followed by an 8-h sleep opportunity with polysomnography. Objective sleep measurements were complemented by self-report. Salivary melatonin, subjective sleepiness, and behavioural vigilance were sampled at regular intervals. Sensory processing was evaluated during light exposure and sleep on the basis of neural responses related to violations of expectations in an oddball paradigm. We observed suppression of melatonin by ≈14 % in the high-compared to the low-melanopic condition. However, conditions did not differentially affect sleep, sleep quality, sleepiness, or vigilance. A neural mismatch response was evident during all sleep stages, but not differentially modulated by light. Suppression of melatonin by light targeting the melanopic system does not automatically translate to acutely altered levels of vigilance or sleepiness or to changes in sleep, sleep quality, or basic sensory processing. Given contradicting earlier findings and the retinal anatomy, this may suggest that an interaction between melanopsin and cone-rod signals needs to be considered. Statement of Significance Metameric light allows to mechanistically investigate the contribution of one specific retinal receptor. Using this approach, we here investigated the effects of high-vs. low-melanopic light for 1 hour in the evening at ecologically valid screen illuminance (≈60 photopic lux). Going beyond earlier research, we also investigated effects on sleep. We found that despite significant suppression of melatonin, other endpoints including sleep and sleep quality were not differentially affected. This underlines that melatonin suppression does not automatically translate to alterations of sleep, sleepiness, or vigilance. Further, it suggests that melanopsin effects may need to be studied in the context of cone-rod signals. Future research should thus investigate the relevance of such an interaction, which may vary between endpoints.
Simulation and Real-Time Analysis of Pulse Shapes from segmented HPGe-Detectors

AGATA is a future 4-&pi &gamma - spectrometer consisting of 180 segmented HPGe detectors. In the course of this work a full pulse shape simulation was developed and verified using data from a coincidence scan. The pulse shapes were reproduced within the accuracy of the scanning setup. The chosen approach to pulse shape analysis separates the task into two independent problems. The event time is determined using a neural network with a resolution Fully Informed Particle Swarm algorithm. The location of the highest energetic interaction is resolved within 3 mm for events with up to 3 hit segments and within less than ~5 ms computing time. This is important to harness the full sensitivity and energy resolution of AGATA.
Behavior of cetaceans in the waters south of Pico Island (Azores, Portugal) - data obtained during whale-watching 2020

Land-based and boat-based surveys were conducted to collect data during whale-watching excursions in July/August and October 2020. Occurrence and behavior of cetaceans south of Pico Island (Azores) were determined. 10 species were sighted. The most frequently sighted species were: Sperm whale (Physeter macrocephalus), Sei whale (Balaenoptera borealis), Atlantic spotted dolphin (Stenella frontalis), Common bottlenose dolphin (Tursiops truncatus), and Risso’s dolphin (Grampus griseus). 51 different behaviour patterns were recorded. The majority, 32 behavior, were observed from two or more species. 19 behavioral patterns were observed only once from a single species, Atlantic spotted dolphins showed nine and Sperm whale showed six. The most behavioral patterns were displayed by Stenella frontalis with 26 and Pseudorca crassidens with 22. Interspecific cooperative hunting and intraspecific food sharing were observed, for the latter there were no known observations in the Azores so far.
Life-history diversity in lakes is associated with ecosystem size

In this study, I inspect how ecosystem size drives fish life-history strategies in north temperate lakes. Species were classified as equilibrium, periodic, or opportunistic strategists according to Winemiller and Rose (1992), and species-area curves assembled and compared among strategy types. The smallest lakes were often dominated by only one species, usually an opportunistic strategist. Overall, species richness rose with ecosystem size, but larger ecosystems tended to be dominated by more periodic and equilibrium strategists. Richness of periodic species increased with ecosystem size at a faster rate compared to opportunistic species. Similarly, life-history niche space increased with ecosystem size in accord with species-area relationships, but showed saturation behavior (i.e., life-history niche space became increasingly ‘packed’ in large lakes). As predicted by theory, relative abundances of opportunistic strategists were extremely variable over space and time, whereas abundances of equilibrium and periodic strategists were more stable. Integration of species-area relationships with life-history theory provides insights into community assembly at multiple scales, and has broad conservation applications.
Parallelization with Dual-Trap Single-Column Configuration Maximizes Throughput of Proteomic Analysis

Proteomic analysis on the scale that captures population and biological heterogeneity over hundreds to thousands of samples requires rapid mass spectrometry methods which maximize instrument utilization (IU) and proteome coverage while maintaining precise and reproducible quantification. To achieve this, a short liquid chromatography gradient paired to rapid mass spectrometry data acquisition can be used to reproducibly profile a moderate set of analytes. High throughput profiling at a limited depth is becoming an increasingly utilized strategy for tackling large sample sets but the time spent on loading the sample, flushing the column(s), and re-equilibrating the system reduces the ratio of meaningful data acquired to total operation time and IU. The dual-trap single-column configuration presented here maximizes IU in rapid analysis (15 min per sample) of blood and cell lysates by parallelizing trap column cleaning and sample loading and desalting with analysis of the previous sample. We achieved 90% IU in low micro-flow (9.5 µL/min) analysis of blood while reproducibly quantifying 300-400 proteins and over 6,000 precursor ions. The same IU was achieved for cell lysates, in which over 4,000 proteins (3,000 at CV below 20%) and 40,000 precursor ions were quantified at a rate of 15 minutes/sample. Thus, deployment of this dual-trap single column configuration enables high throughput epidemiological blood-based biomarker cohort studies and cell-based perturbation screening.
BirdVox: Machine listening for bird migration monitoring

The steady decline of avian populations worldwide urgently calls for a cyber-physical system to monitor bird migration at the continental scale. Compared to other sources of information (radar and crowdsourced observations), bioacoustic sensor networks combine low latency with a high taxonomic specificity. However, the scarcity of flight calls in bioacoustic monitoring scenes (below 0.1% of total recording time) requires the automation of audio content analysis. In this article, we address the problem of scaling up the detection and classification of flight calls to a full-season dataset: 6672 hours across nine sensors, yielding around 480 million neural network predictions. Our proposed pipeline, BirdVox, combines multiple machine learning modules to produce per-species flight call counts. We evaluate BirdVox on an annotated subset of the full season (296 hours) and discuss the main sources of estimation error which are inherent to a real-world deployment: mechanical sensor failures, sensitivity to background noise, misdetection, and taxonomic confusion. After developing dedicated solutions to mitigate these sources of error, we demonstrate the usability of BirdVox by reporting a species-specific temporal estimate of flight call activity for the Swainson’s Thrush (Catharus ustulatus).
Inhibition of Tgfβ signaling enables durable ventricular pacing by TBX18 gene transfer

Implantable cardiac pacemaker devices are generally effective for patients with symptomatic bradyarrhythmia. However, device-dependent cardiac pacing is far from ideal and often inadequate, particularly for pediatric patients who need to go through invasive revision of the indwelling hardware. Biological pacemakers have been proposed as device-free alternatives to the current treatment, but sustained, unwavering biological pacing beyond days after the biologic delivery has not been demonstrated. We have previously demonstrated that re-expression of an embryonic transcription factor, TBX18, could reprogram ventricular cardiomyocytes into induced pacemaker myocytes (iPMs). Here, we report that exogenous expression of TBX18 per se leads to severe fibrosis in situ, impairing the iPMs’ ability to pace together. Acute fibrosis is accompanied with proliferation and activation of cardiac fibroblasts via Tgfβ-Smad2/3 pathway. Small molecule inhibition of Tgfβ signaling mitigated the interstitial remodeling, independent from TBX18-induced iPM reprogramming at the single-cell level. Direct and focal gene transfer of TBX18 into the left ventricular myocardium created ventricular pacing in a rat model of chronic atrioventricular block, but such activity began to wane in a week. In contrast, a combination therapy consisting of TBX18 gene transfer and Tgfβ inhibition enabled sustained biological pacing beyond the four-week study period. Our data demonstrate that inhibition of Tgfβ signaling suffices to achieve durable cardiac pacing by TBX18-induced biological pacemakers.
Route of self-amplifying mRNA vaccination modulates the establishment of pulmonary resident memory CD8 and CD4 T cells

Respiratory tract resident memory T cells (Trm), typically generated by local vaccination or infection, can accelerate control of pulmonary infections that evade neutralizing antibody. It is unknown whether mRNA vaccination establishes respiratory Trm. We generated a self-amplifying mRNA vaccine encoding the influenza A virus nucleoprotein that is encapsulated in modified dendron-based nanoparticles. Here we report how routes of immunization in mice, including contralateral versus ipsilateral intramuscular boosts, or intravenous and intranasal routes, influence influenza-specific cell-mediated and humoral immunity. Parabiotic surgeries revealed that intramuscular immunization was sufficient to establish CD8 Trm in lung and draining lymph node. Contralateral, compared to ipsilateral, intramuscular boosting broadened the distribution of LN Trm and T follicular helper cells, but slightly diminished resulting levels of serum antibody. Intranasal mRNA delivery established modest circulating CD8 and CD4 T cell memory, but augmented distribution to the respiratory mucosa. Of note, combining intramuscular immunizations with an intranasal mRNA boost achieved high levels of both circulating T cell memory and lung Trm. Thus, routes of mRNA vaccination influence humoral and cell-mediated immunity, and intramuscular prime-boosting establishes lung Trm that can be further enhanced by an additional intranasal immunization.
Spontaneous variations in arousal modulate subsequent visual processing and local field potential dynamics in the ferret during quiet wakefulness

Behavioral states affect neuronal responses throughout the cortex and influence visual processing. Quiet wakefulness (QW) is a behavioral state during which subjects are quiescent, but awake and connected to the environment. Here, we examined the effects of pre-stimulus arousal variability on post-stimulus neural activity in primary visual cortex (V1) and posterior parietal cortex (PPc) in awake ferrets, using the pupil diameter as an indicator of arousal. We observed that during low arousal, low- frequency power increases during visual stimulation, and that the peak alpha frequency shifted depending on the arousal state. High arousal increased gamma power as well as low-frequency inter- and intra-areal coherence. Using a simplified model of laminar circuits, we show that this connectivity pattern is compatible with feedback signals targeting infragranular layers in area PPc and supragranular layers in V1. Neurons in V1 displayed higher firing rates at their preferred orientations on high-arousal trials. Broad-spiking cells in V1 entrained to high-frequency oscillations (>80 Hz), whereas narrow-spiking neurons phase-locked to low (12-18 Hz) and high-frequency (>80 Hz) rhythms. These results indicate that the variability and sensitivity of post-stimulus cortical responses and coherence depend on the pre-stimulus behavioral state and account for the neuronal response variability observed during repeated stimulation.
SARS-CoV-2 impacts the transcriptome and epigenome at the maternal-fetal interface in pregnancy

During pregnancy, the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent works show increased incidences of adverse pregnancy outcomes in COVID-19 patients; however, the mechanism remains unclear. Here, we analyzed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from COVID-19 patients and control samples, we discovered aberrant immune activation and angiogenesis patterns in patients. Surprisingly, retrotransposons were dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced significant changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications. One-Sentence Summary Pregnant COVID-19 patients show placental epigenetic and transcriptional changes, associated with adverse pregnancy outcomes.
A Multitrait Locus Regulates Sarbecovirus Pathogenesis

Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. ABSTRACT Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.