Lattice tilings of Hilbert spaces

We construct a bounded and symmetric convex body in $\ell_2(\Gamma)$ (forcertain cardinals $\Gamma$) whose translates yield a tiling of$\ell_2(\Gamma)$. This answers a question due to Fonf and Lindenstrauss. As aconsequence, we obtain the first example of an infinite-dimensional reflexiveBanach space that admits a tiling with balls (of radius $1$). Further, ourtiling has the property of being point-countable and lattice (in the sense thatthe set of translates forms a group). The same construction performed in$\ell_1(\Gamma)$ yields a point-$2$-finite lattice tiling by balls of radius$1$ for $\ell_1(\Gamma)$, which compares to a celebrated construction due toKlee. We also prove that lattice tilings by balls are never disjoint and, moregenerally, each tile intersects as many tiles as the cardinality of the tiling.Finally, we prove some results concerning discrete subgroups of normed spaces.By a simplification of the proof of our main result, we prove that everyinfinite-dimensional normed space contains a subgroup that is $1$-separated and$(1+\varepsilon)$-dense, for every $\varepsilon>0$; further, the subgroupadmits a set of generators of norm at most $2+\varepsilon$. This solves aproblem due to Swanepoel and yields a simpler proof of a result of Dilworth,Odell, Schlumprecht, and Zs\'ak. We also give an alternative elementary proofof Stepr\={a}ns' result that discrete subgroups of normed spaces are free.

Post-selection free time-bin entanglement on a thin-film lithium niobate photonic chip

Time-bin entanglement is the most commonly used form of entanglement forquantum communication protocols over fiber networks, due to the naturalresilience of this encoding scheme to thermal phase fluctuations in opticalfibers. Projective measurements on some bases in the time-bin encoding need,however, post-selection of the measured events, introducing a loophole in Belltests and requiring high temporal resolution. In this work, we demonstratechip-integrated receivers for time-bin entanglement certification including ahigh-speed optical switch to remove such post-selection loophole. The receiversare realized using thin-film lithium niobate and operate at a switchingfrequency of 5 GHz, enabling high secure key rates. We demonstrate a Bellinequality violation by more than 24 standard deviations without the need fortime resolution at the time-bin separation level.

Thermal Disorder‐Induced Strain and Carrier Localization Activate Reverse Halide Segregation

The reversal of halide ions is studied under various conditions. However, the underlying mechanism of heat‐induced reversal remains unclear. This work finds that dynamic disorder‐induced localization of self‐trapped polarons and thermal disorder‐induced strain (TDIS) can be co‐acting drivers of reverse segregation. Localization of polarons results in an order of magnitude decrease in excess carrier density (polaron population), causing a reduced impact of the light‐induced strain (LIS – responsible for segregation) on the perovskite framework. Meanwhile, exposing the lattice to TDIS exceeding the LIS can eliminate the photoexcitation‐induced strain gradient, as thermal fluctuations of the lattice can mask the LIS strain. Under continuous 0.1 W cm⁻ 2 illumination (upon segregation), the strain disorder is estimated to be 0.14%, while at 80 °C under dark conditions, the strain is 0.23%. However, in situ heating of the segregated film to 80 °C under continuous illumination (upon reversal) increases the total strain disorder to 0.25%, where TDIS is likely to have a dominant contribution. Therefore, the contribution of entropy to the system's free energy is likely to dominate, respectively. Various temperature‐dependent in situ measurements and simulations further support the results. These findings highlight the importance of strain homogenization for designing stable perovskites under real‐world operating conditions.

Diagnostic capabilities, clinical features, and longitudinal UBA1 clonal dynamics of a nationwide VEXAS cohort

VEXAS is a prototypic hemato‐inflammatory disease combining rheumatologic and hematologic disorders in a molecularly defined nosological entity. In this nationwide study, we aimed at screenshotting the current diagnostic capabilities and clinical‐genomic features of VEXAS, and tracked UBA1 longitudinal clonal dynamics upon different therapeutics, including allogeneic hematopoietic cell transplant. We leveraged a collaboration between the Italian Society of Experimental Hematology and of Rheumatology and disseminated a national survey to collect clinical and molecular patient information. Overall, 13/29 centers performed UBA1 genomic testing locally, including Sanger sequencing (46%), next‐generation sequencing (23%), droplet digital polymerase chain reaction (8%), or combination (23%). A total of 41 male patients were identified, majority (51%) with threonine substitutions at Met41 hotspot, followed by valine and leucine (27% and 8%). Median age at VEXAS diagnosis was 67 years. All patients displayed anemia (median hemoglobin 9.1 g/dL), with macrocytosis. Bone marrow vacuoles were observed in most cases (89%). The most common rheumatologic association was polychondritis (49%). A concomitant myelodysplastic neoplasm/syndrome (MDS) was diagnosed in 71% of patients ( n  = 28), chiefly exhibiting lower Revised International Prognostic Scoring System risk profiles. Karyotype was normal in all patients, except three MDS cases showing ‐Y, t(12;16)(q13;q24), and +8. The most frequently mutated gene was DNMT3A ( n  = 10), followed by TET2 ( n  = 3). At last follow‐up, five patients died and two patients progressed to acute leukemia. Longitudinal UBA1 clonal dynamics demonstrated mutational clearance following transplant. We collected a nationwide interdisciplinary VEXAS patient cohort, characterized by heterogeneous rheumatologic manifestations and treatments used. MDS was diagnosed in 71% of cases. Patients exhibited various longitudinal UBA1 clonal dynamics.

BCR::ABL1 digital PCR for treatment‐free remission prediction in chronic myeloid leukemia patients: An individual participant data meta‐analysis

Handgrip strength of young athletes differs based on the type of sport played and age

Objective Handgrip strength may differ depending on the type of sport played during the developmental period. Youth sports in which athletes hold equipment in their hands may be the most effective for improving handgrip strength. This study aimed to examine the age at which differences in handgrip strength appear by comparing sports that involve gripping (kendo) with those that do not involve gripping (soccer) in young athletes. Methods Two hundred and twenty‐two male athletes (115 kendo and 107 soccer) between 6 and 15 years old participated in this study. Handgrip strength was measured using a dynamometer, and the average value of both hands was used for analysis. Sports experience was determined when they started practicing each sport. Handgrip strength was compared between sports. Statistical moderation was used to determine if the relationship between sport and handgrip strength depended upon the age of the athlete. Results Kendo athletes had significantly higher handgrip strength than soccer athletes (4.77 kg [95% CI: 2.34, 7.19]) in the overall sample. We found that the relationship between sport and handgrip strength depended upon the age of the child (sport*age t = −3.6, p  = .004). Using the Johnson‐Neyman procedure, we found statistically significant differences between sports from 8.48 years and older. Conclusions Our results suggest that the type of sport played, that is, whether or not an athlete plays with sports equipment in their hands, may influence the development of handgrip strength during the period of growth, and these sports may contribute to a higher level of handgrip strength in adulthood.

Tracking handgrip strength in Kendo athletes from university to middle and older adulthood

Abstract Objective This study aimed to compare the current handgrip strength (HGS) of Kendo athletes with their HGS when they were in university (up to 50 years). Methods Eighty male graduates who were Kendo club members during their university days performed anthropometric and HGS measurements, and these HGS were compared with those measured during their university days (mean age of 19.5 years old). Results There was no evidence of a statistical difference in HGS between the current measurement and the measurement taken during university [−0.64 (−1.9, 0.67) kg, p  = .336]. There was, however, evidence that the difference in HGS depended upon the current age of the individual ( t  = −6.43, p  < .001). When probing the interaction, there were statistical differences between the ages of 24.6 and 38.2 years and between the ages of 47.4 and 69.9 years. Strength increased across time in the younger participants and decreased for those who were older. Between the ages of 38.9 and 46.1 years, there was no evidence of a statistical difference indicating a maintenance of strength. Conclusion The HGS of Kendo club graduates, which they acquired during their formative years, continued to increase even after they graduated from university and entered their 30s. However, their HGS decreased from age 50, even though they practiced Kendo.

Sex Differences in Strength During Development: Implications for Inclusivity and Fairness in Sport

ABSTRACT Objectives Males, on average, are bigger and stronger than females. Hormonal differences during puberty are one reason given for this performance advantage. However, not all evidence supports that thesis. Our aim was to further this discussion by measuring early life changes between sexes (when hormones would be similar) in components of muscle function. Methods Fifty‐one children (29 boys, 22 girls) completed this study. Forearm muscle size and strength were assessed three times with each time point being separated by approximately a year (2021–2023). Results There was no sex*time interaction for handgrip strength ( p  = 0.637). There was, however, a time ( p  < 0.001) and sex ( p  < 0.001) effect. Strength increased each year and boys were stronger than girls (difference of 1.5 [95% 0.7, 2.3] kg). There was no sex*time interaction for ulnar muscle thickness ( p  = 0.714) but there was a time ( p  < 0.001) effect. Muscle size increased each year but there was no evidence of a sex effect ( p  = 0.12; difference of 0.81 [95% −0.21, 1.8] mm). A strong positive within‐participant correlation between muscle size and strength ( r  = 0.803 95% CI: [0.72, 0.86], p  < 0.0001) was found across time. Conclusion Muscle size and strength increased together but this increase did not differ based on sex and boys were stronger than girls. Future work is needed to determine the reason for this difference in maximal strength. Any effect was seemingly present at the initial measurement (at the age of 4 years), since muscle size and strength did not change differently between boys and girls over time.

Evaluation of the functional activity in synaptic genes related to polygenic risk for Alzheimer’s disease using a Massively Parallel Reporter Assay

Abstract Background Synaptic degeneration is a primary neuropathological factor associated with cognitive decline in Alzheimer’s disease (AD). In 2021, we generated a synaptic Polygenic Risk Score (PRS) that comprised only 8 variants within 6 synaptic genes ( APOE , PICALM , BIN1 , PTK2B , DLG2 and MINK1 ) that predicted AD with 72% accuracy in two neuropathological cohorts. This supports the hypothesis that genetic variants that regulate an individual’s vulnerability to AD‐related synapse degeneration could be used to identify individuals at‐risk for AD prior to the appearance of clinical symptoms. The aim of this study was to determine whether the constituent variants of the linkage disequilibrium (LD) blocks represented by the PRS have regulatory activity in vitro . Method We cloned an oligonucleotide library of 137 putative regulatory variants each represented by 5 barcodes per allele into pMPRA1 vector. Then we transfected the plasmids into HEK293 cells (n = 5). We extracted DNA and RNA from the cells and sequenced on an Illumina MiSeq. Using the mpra package in R, we normalized the tag counts to a common size of 10 million reads and computed paired log ratios of RNA/DNA counts for each barcode. We used weighted linear models to test for differential activity of the minor versus the major allele of each SNP using the mpralm function, adjusting for multiple testing using the Benjamini‐Hochberg method. Result We acquired approximately 15 million reads of DNA and RNA from 5 independent experiments. We found that 35 out of the 137 SNPs tested had differential activity between alleles (adj. p <0.05, Figure 1A). Three of the SNPs that showed regulatory activity were included in the PRS ( BIN1 : rs17014923 and rs35114168; DLG2 : rs286043) and the remaining 32 are captured on LD blocks within the synaptic PRS. Conclusion All LD captured by the synaptic PRS contain SNPs that impact on regulatory activity, thus supporting a potential mechanism by which changes in the expression of these specific loci that encode synaptic proteins could lead to a modified cumulative risk for AD. Further studies to determine the precise mechanism involved in this regulatory activity at the synapse could guide future therapeutic strategies for AD.

Synapse‐enriched miRNA expression in Alzheimer’s disease cortex tissue

Abstract Background Synapse degeneration is one of the earliest changes in Alzheimer’s disease (AD) and is the major neuropathologic correlate of cognitive impairment. The aim of this study was to characterize microRNA (miRNA) dysregulation at AD synapses post‐mortem brain tissue and explore the specificity for AD. Method We prepared synaptosomes (SYN) by serial ultracentrifugation of 10 AD (mean age = 77.4±13.3) and 10 control (CN; mean age = 72.3±18.8) temporal cortex samples over a sucrose gradient and saved the homogenates (H). We extracted and quantified miRNA from SYN and H fractions by TaqMan Advanced miRNA Assay‐Openarray system. We calculated deltaCt and performed linear regression to identify differentially expressed (DE) miRNA across AD and CN SYN, adjusting for multiple testing using Benjamini‐Hochberg method (α<0.05). We identified gene targets of the DE miRNA using two predictive databases (TargetScan and miRDB) and performed pathway analysis using the Panther database. We selected miRNA candidates that are DE in AD synapses and performed a follow‐up study in 4 different brain regions of 10 CN (mean age = 80.7±12.9), 10 AD (mean age = 77.4±13.3) and 10 non‐AD tauopathy (mean age = 70.6±6.4) cases to determine the regional distribution and the AD specificity. Result Synapse fractions were isolated demonstrating a 3.2‐fold enrichment in the synaptic protein VAMP‐2 (p<0.001) compared to homogenates. We detected 411 miRNA in H and 432 in SYN of the total in the panel with 89% overlap between AD and CN in SYN. Three miRNA from the same family (miR‐132‐3p, miR‐132‐5p and miR‐212‐3p) were under‐expressed and 2 miRNA (miR‐181a‐3p and miR‐1260a) were over‐expressed in AD compared to CN SYN. The gene targets of these miRNA were overrepresented in pathways regulating synaptic and mitochondrial function. In addition, targets of miR‐132 also were overrepresented in pathways related to tau pathology, Aβ production, interleukin production, apoptosis and oxidative stress. We will describe the regional distribution in AD brains post‐mortem and the specificity of the changes to AD by comparing to non‐pathological controls and non‐AD tauopathies. Conclusion miRNA that are dysregulated in AD synapses target genes that are involved in pathways related to AD pathogenesis. Future studies will focus on the use of these miRNA as therapeutic targets.