Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurophotonic tools for microscopic measurements and manipulation: status report

Abstract. Neurophotonics was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, Neurophotonics’ agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.
Cefotaxime Exposure Selects Mutations within the CA-Domain of envZ Which Promote Antibiotic Resistance but Repress Biofilm Formation in Salmonella

Understanding mechanisms of antibiotic resistance is crucial to guide how best to use antibiotics to minimize emergence of resistance. We used a laboratory evolution system to study how Salmonella responds to cefotaxime in both planktonic and biofilm conditions. ABSTRACT Cephalosporins are important beta lactam antibiotics, but resistance can be mediated by various mechanisms including production of beta lactamase enzymes, changes in membrane permeability or active efflux. We used an evolution model to study how Salmonella adapts to subinhibitory concentrations of cefotaxime in planktonic and biofilm conditions and characterized the mechanisms underpinning this adaptation. We found that Salmonella rapidly adapts to subinhibitory concentrations of cefotaxime via selection of multiple mutations within the CA-domain region of EnvZ. We showed that changes in this domain affect the ATPase activity of the enzyme and in turn impact OmpC, OmpF porin expression and hence membrane permeability leading to increased tolerance to cefotaxime and low-level resistance to different classes of antibiotics. Adaptation to cefotaxime through EnvZ also resulted in a significant cost to biofilm formation due to downregulation of curli. We assessed the role of the mutations identified on the activity of EnvZ by genetic characterization, biochemistry and in silico analysis and confirmed that they are responsible for the observed phenotypes. We observed that sublethal cefotaxime exposure selected for heterogeneity in populations with only a subpopulation carrying mutations within EnvZ and being resistant to cefotaxime. Population structure and composition dynamically changed depending on the presence of the selection pressure, once selected, resistant subpopulations were maintained even in extended passage without drug. IMPORTANCE Understanding mechanisms of antibiotic resistance is crucial to guide how best to use antibiotics to minimize emergence of resistance. We used a laboratory evolution system to study how Salmonella responds to cefotaxime in both planktonic and biofilm conditions. In both contexts, we observed rapid selection of mutants within a single hot spot within envZ. The mutations selected altered EnvZ which in turn triggers changes in porin production at the outer membrane. Emergence of mutations within this region was repeatedly observed in parallel lineages in different conditions. We used a combination of genetics, biochemistry, phenotyping and structural analysis to understand the mechanisms. This data show that the changes we observe provide resistance to cefotaxime but come at a cost to biofilm formation and the fitness of mutants changes greatly depending on the presence or absence of a selective drug. Studying how resistance emerges can inform selective outcomes in the real world.
For the road: calibrated maternal investment in light of extracellular symbiont transmission

Faithful transmission of beneficial symbionts is critical for the persistence of mutualisms. Many insect groups rely on extracellular routes that require microbial symbionts to survive outside the host during transfer. However, given a prolonged aposymbiotic phase in offspring, how do mothers mitigate the risk of symbiont loss due to unsuccessful transmission? Here, we investigated symbiont regulation and reacquisition during extracellular transfer in the tortoise beetle, Chelymorpha alternans (Coleoptera: Cassidinae). Like many cassidines, C. alternans relies on egg caplets to vertically propagate its obligate symbiont Candidatus Stammera capleta. On average, each caplet is supplied with 12 symbiont-bearing spheres where Stammera is embedded. We observe limited deviation (±2.3) in the number of spheres allocated to each caplet, indicating strict maternal control over symbiont supply. Larvae acquire Stammera 1 day prior to eclosion but are unable to do so after hatching, suggesting that a specific developmental window governs symbiont uptake. Experimentally manipulating the number of spheres available to each egg revealed that a single sphere is sufficient to ensure successful colonization by Stammera relative to the 12 typically packaged within a caplet. Collectively, our findings shed light on a tightly regulated symbiont transmission cycle optimized to ensure extracellular transfer.
Dietary shifts may underpin the recovery of a large carnivore population

Supporting the recovery of large carnivores is a popular yet challenging endeavour. Estuarine crocodiles in Australia are a large carnivore conservation success story, with the population having extensively recovered from past heavy exploitation. Here, we explored if dietary changes had accompanied this large population recovery by comparing the isotopes δ13C and δ15N in bones of crocodiles sampled 40 to 55 years ago (small population) with bones from contemporary individuals (large population). We found that δ13C and δ15N values were significantly lower in contemporary crocodiles than in the historical cohort, inferring a shift in prey preference away from marine and into terrestrial food webs. We propose that an increase in intraspecific competition within the recovering crocodile population, alongside an increased abundance of feral ungulates occupying the floodplains, may have resulted in the crocodile population shifting to feed predominantly upon terrestrial food sources. The number of feral pigs consumed to sustain and grow crocodile biomass may help suppress pig population growth and increase the flow of terrestrially derived nutrients into aquatic ecosystems. The study highlights the significance of prey availability in contributing to large carnivore population recovery.
The Effects of Preferred Music and Its Timing on Performance, Pacing, and Psychophysiological Responses During the 6‐min Test

Abstract The aim of this study was to investigate the effects of listening to preferred music during a warm up or exercise, on performance during a 6-min all-out exercise test (6-MT) in young adult males. Twenty-five healthy males volunteered to participate in this study. Following a within subject design, participants performed three test conditions (MDT: music during the test; MDW: music during the warm-up; WM: without music) in random order. Outcomes included mean running speed over the 6-min test (MRS6), total distance covered (TDC), heart rate responses (HRpeak, HRmean), blood lactate (3-min after the test), and the rating of perceived exertion (RPE); additionally, feeling scale scores were recorded. Listening to preferred music during running resulted in significant TDC (Δ↑10%, p=0.006, ES=0.80) and MRS6 (Δ↑14%, p=0.012, ES=1.02) improvement during the 6-MT, improvement was also noted for the warm-up with music condition (TDC:Δ↑8%, p=0.028, ES=0.63; MRS6:Δ↑8%, p=0.032, ES=0.61). A similar reverse “J-shaped” pacing profile was detected during the three conditions. Blood lactate was lower in the MDT condition by 8% (p=0.01, ES=1.10), but not the MDW condition, compared to MW. In addition, no statistically significant differences were found between the test sessions for the HR, RPE, and feeling scale scores. In conclusion, listening to music during exercise testing would be more beneficial for optimal TDC and MRS6 performances compared to MDW and WM.
Linear stability analysis of Taylor bubble motion in downward flowing liquids in vertical tubes

Abstract Taylor bubbles are a feature of the slug flow regime in gas–liquid flows in vertical pipes. Their dynamics exhibits a number of transitions such as symmetry breaking in the bubble shape and wake when rising in downward flowing and stagnant liquids, respectively, as well as breakup in sufficiently turbulent environments. Motivated by the need to examine the stability of a Taylor bubble in liquids, a systematic numerical study of a steadily moving Taylor bubble in stagnant and flowing liquids is carried out, characterised by the dimensionless inverse viscosity $( N_f )$, Eötvös $( Eo )$ and Froude numbers $( U_m )$, the latter being based on the centreline liquid velocity, using a Galerkin finite-element method. A boundary-fitted domain is used to examine the dependence of the steady bubble shape on a wide range of $N_f$, $Eo$ and $U_m$. Our analysis of the bubble nose and bottom curvatures shows that the intervals $Eo = [ 20,30 )$ and $N_f=[60,80 )$ are the limits below which surface tension and viscosity, respectively, have a strong influence on the bubble shape. In the interval $Eo = (60,100 ]$, all bubble features studied are weakly dependent on surface tension. A linear stability analysis of the axisymmetric base states shows that there exist regions of $(N_f,Eo,U_m)$ space within which the bubble is unstable and assumes an asymmetric shape. To elucidate the mechanisms underlying the instability, an energy budget analysis is carried out which reveals that perturbation growth is driven by the bubble pressure for $Eo \geq 100$, and by the tangential interfacial stress for $Eo < 100$. Examples of the asymmetric bubble shapes and their associated flow fields are also provided near the onset of instability for a wide range of $N_f$, $Eo$ and $U_m$.
Answering Graph Pattern Queries using Compact Materialized Views

We address the problem of evaluating graph pattern queries involving reachability (edge-to-path mapping) and direct (edge-to-edge mapping) relationships under homomorphisms on data graphs using materialized graph pattern views. We propose an original approach for view materialization which materializes views as summary graphs, an approach that records, in a compact way, all the homomorphisms of the view to the data graph. In this context, we characterize view usability in terms of query edge coverage and provide necessary and sufficient conditions for answering queries using views. We design algorithms for deciding whether a query can be answered using a set of views, for generating the summary graph of a query from the view materializations, and for producing a minimal view set capable of answering a query. Our experimental evaluation demonstrates that our approach outperforms, by several orders of magnitude, a state-of-the-art approach which does not use materialized views, and substantially improves upon its scalability.
Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine

Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01B-adjuvanted RH5.1 malaria antigen — substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.
Regulation of metabolic health by dietary histidine in mice

Low protein (LP) diets are associated with a decreased risk of diabetes in humans, and a low protein diet promotes leanness and glycemic control in both rodents and humans. While the effects of a LP diet on glycemic control are mediated by reduced dietary levels of the branched- chain amino acids (BCAAs), we have observed that reducing dietary levels of the other six essential amino acids leads to changes in body composition. Here, we find that dietary histidine plays a key role in the response to a LP diet in male C57BL/6J mice. Specifically reducing dietary levels of histidine by 67% reduces weight gain of young, lean male mice, reducing both adipose and lean mass gain, without altering glucose metabolism. Specifically reducing dietary histidine rapidly reverses diet-induced obesity and hepatic steatosis in diet-induced obese male mice, increasing insulin sensitivity; this normalization of metabolic health was associated not with caloric restriction or increased activity, but with increased energy expenditure. We find that the effects of histidine restriction surprisingly does not require the energy balance hormone Fgf21. Histidine restriction started in mid-life promoted leanness and glucose tolerance in aged males but not females, but did not affect frailty or lifespan in either sex. Finally, we demonstrate that variation in dietary histidine levels helps to explain body mass index differences in humans. Overall, our findings demonstrate that dietary histidine is a key regulator of weight and body composition in male mice and in humans, and suggest that reducing dietary levels of histidine may be a highly translatable option for the treatment of obesity. Key Points Protein restriction (PR) promotes metabolic health in rodents and humans and extends rodent lifespan. Restriction of specific individual essential amino acids can recapitulate the benefits of PR. Reduced histidine promotes leanness and increased energy expenditure in mice. Reduced histidine does not extend the lifespan of mice when begun in mid-life. Dietary levels of histidine are positively associated with BMI in humans.
Of Seringueiros and Sambistas: Occupation Mappings in Historical Text

This work shows how shallow processing of available resources can help us improve the coverage of existing large-scale lexical resources like the OpenWordNet-PT, the Portuguese version of WordNet. Specifically, the work em-ploys the Brazilian Dictionary of Historical Biographies, a dictionary whose entries are short biographies of personalities of the History of Brazil since the 1930s, and the European multilingual classification of Skills, Competences and Occupations resource (ESCO), in order to extract professions and occupations and check how many of them are already present in OpenWordNet-PT. The work also allows interesting side-observations, for example on the quality of non-English NLP tools as well as within the socio-political scenery.
Rethinking the Interactivity of OS and Device Layers in Memory Management

In the big data era, a huge number of services has placed a fast-growing demand on the capacity of DRAM-based main memory. However, due to the high hardware cost and serious leakage power/energy consumption, the growth rate of DRAM capacity cannot meet the increased rate of the required main memory space when the energy or hardware cost is a critical concern. To tackle this issue, hybrid main-memory devices/modules have been proposed to replace the pure DRAM main memory with a hybrid main memory module that provides a large main memory space by integrating a small-sized DRAM and a large-sized non-volatile memory (NVM) into the same memory module. Although NVMs have high-density and low-cost features, they suffer from the low read/write performance and low endurance issue, compared to DRAM. Thus, inside the hybrid main-memory module, it also includes a memory management design to use DRAM as the cache of NVMs to enhance its performance and lifetime. However, it also introduces new design challenges in both the OS and the memory module. In this work, we rethink the interactivity of OS and hybrid main-memory module, and propose a cross-layer cache design that (1) utilizes the information from the operating system to optimize the hit ratio of the DRAM cache inside the memory module, and (2) takes advantage of the bulk-size (or block-based) read/write feature of NVM to minimize the time overhead on the data movement between DRAM and NVM. At the same time, this cross-layer cache design is very lightweight and only introduces limited runtime management overheads. A series of experiments was conducted to evaluate the effectiveness of the proposed cross-layer cache design. The results show that the proposed design could improve access performance for up to 88%, compared to the investigated well-known page replacement algorithms.
GNL3 is an evolutionarily conserved stem cell gene influencing cell proliferation, animal growth and regeneration in the hydrozoan Hydractinia

Nucleostemin (NS) is a vertebrate gene preferentially expressed in stem and cancer cells, which acts to regulate cell cycle progression, genome stability, and ribosome biogenesis. NS and its paralogous gene, GNL3-like (GNL3L), arose in the vertebrate clade after a duplication event from their orthologous gene, G protein Nucleolar 3 (GNL3). Research on invertebrate GNL3, however, has been limited. To gain a greater understanding of the evolution and functions of the GNL3 gene, we have performed studies in the hydrozoan cnidarian Hydractinia symbiolongicarpus, a colonial hydroid that continuously generates pluripotent stem cells throughout its life cycle and presents impressive regenerative abilities. We show that Hydractinia GNL3 is expressed in stem and germline cells. The knockdown of GNL3 reduces the number of mitotic and S-phase cells in Hydractinia larvae of different ages. Genome editing of Hydractinia GNL3 via CRISPR/Cas9 resulted in colonies with reduced growth rates, polyps with impaired regeneration capabilities, gonadal morphological defects, and low sperm motility. Collectively, our study shows that GNL3 is an evolutionarily-conserved stem cell and germline marker involved in cell proliferation, animal growth, regeneration, and sexual reproduction in Hydractinia, and sheds new light into the evolution of GNL3 and of stem cell systems.
A comparison of different methods for handling measurements affected by medication use

In epidemiological research it is common to encounter measurements affected by medication use, such as blood pressure lowered by antihypertensive drugs. When one is interested in the relation between the variables not affected by medication, ignoring medication use can cause bias. Several methods have been proposed, but the problem is often ignored or handled with generic methods, such as excluding individuals on medication or adjusting for medication use in the analysis. This study aimed to investigate methods for handling measurements affected by medication use when one is interested in the relation between the unaffected variables and to provide guidance for how to optimally handle the problem. We focused on linear regression and distinguish between the situation where the affected measurement is an exposure, confounder or outcome. In the Netherlands Epidemiology of Obesity study and in several simulated settings, we compared generic and more advanced methods, such as substituting or adding a fixed value to the treated values, regression calibration, censored normal regression, Heckmans treatment model and multiple imputation methods. We found that often-used methods such as adjusting for medication use could result in substantial bias and that methods for handling medication use should be chosen cautiously.
Supporting Insertion in an Encrypted Multi-Maps with Volume Hiding using Trusted Execution Environment

There is a new type of threat to encrypted databases, called “vol-ume leakage,” which causes the volume of data associated with some keys in a multi-map to be leaked. To counter this threat, several methods for encrypting multi-maps to secure the volume of data they contain have been proposed. One such method supports the insertion of data into encrypted multi-maps. However, it suffers from inefficiency caused by its protocol, which stipulates that all data be sent from the server to the client to perturb the insertion position. For this reason, it is not practical for handling large amounts of data. To address this problem, we propose an improved method for encrypted multi-maps that supports data insertion. The proposed method exploits the trusted execution environment (TEE) supported by modern processors, e.g., Intel SGX, for executing perturbation. TEE is a secure area of a main processor that guarantees the confidentiality and integrity of the code and data inside it. Thus, we can secure the volume and insertion position in an encrypted multi-map without conducting costly perturbation on the client-side. We also overcome the challenge of the capacity of the TEE being typically limited and too small to accommodate the multi-map itself. Specifically, we divide the hash table of the multi-map into partitions so that they can be loaded into the TEE and apply perturbation within each partition. We provide a security analysis of the proposed method, w.r. t. the volume hiding and the insertion position hiding. Further, we provide the results of experiments conducted to evaluate the feasibility of potential applications in terms of the processing time and the amount of noise
Clinical evaluation of an automated, rapid mariPOC® antigen test in screening of symptomatics and asymptomatics for SARS‐CoV‐2 infection

A novel automated mariPOC SARS‐CoV‐2 antigen test was evaluated in a Health Care Center Laboratory among symptomatic and asymptomatic individuals seeking SARS‐CoV‐2 testing. According to the national testing strategy, reverse transcription polymerase chain reaction (RT‐PCR) was used as a reference method. A total of 962 subjects were included in this study, 4.8% (46/962) of their samples were SARS‐CoV‐2 RT‐PCR‐positive, and 87% (40/46) of these were from symptomatics. Among the symptomatics, the overall sensitivity of the mariPOC SARS‐CoV‐2 test was 82.5% (33/40), though the sensitivity increased to 97.1% (33/34) in samples with a Ct < 30. The mariPOC SARS‐CoV‐2 test detected two of six PCR‐positive samples among the asymptomatics, four cases that remained antigen test negative had Ct values between 28 and 36. The specificity of the mariPOC SARS‐CoV‐2 test was 100% (916/916). The evaluation showed that the mariPOC SARS‐CoV‐2 rapid antigen test is very sensitive and specific for the detection of individuals who most probably are contagious.