Multi-Institutional Audit of FLASH and Conventional Dosimetry With a 3D Printed Anatomically Realistic Mouse Phantom.

PURPOSE: We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3-dimensional (3D) printed mouse phantom. METHODS AND MATERIALS: A computed tomography (CT) scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.02 g/cm3) and polylactic acid (∼1.24 g/cm3) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid (∼0.64 g/cm3). Hounsfield units (HU), densities, and print-to-print stability of the phantoms were assessed. Three institutions were each provided a phantom and each institution performed 2 replicates of irradiations at selected anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film. RESULTS: Compared with the reference CT scan, CT scans of the phantom demonstrated mass density differences of 0.10 g/cm3 for bone, 0.12 g/cm3 for lung, and 0.03 g/cm3 for soft tissue regions. Differences in HU between phantoms were <10 HU for soft tissue and bone, with lung showing the most variation (54 HU), but with minimal effect on dose distribution (<0.5%). Mean differences between FLASH and CONV decreased from the first to the second replicate (4.3%-1.2%), and differences from the prescribed dose decreased for both CONV (3.6%-2.5%) and FLASH (6.4%-2.7%). Total dose accuracy suggests consistent pulse dose and pulse number, although these were not specifically assessed. Positioning variability was observed, likely due to the absence of robust positioning aids or image guidance. CONCLUSIONS: This study marks the first dosimetric audit for FLASH using a nonhomogeneous phantom, challenging conventional calibration practices reliant on homogeneous phantoms. The comparison protocol offers a framework for credentialing multi-institutional studies in FLASH preclinical research to enhance reproducibility of biologic findings.

Tracing the origin of SARS-CoV-2 omicron-like spike sequences detected in an urban sewershed: a targeted, longitudinal surveillance study of a cryptic wastewater lineage.

BACKGROUND: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such cryptic wastewater lineage by tracking and characterising its persistence and genomic evolution over time. METHODS: We first detected a cryptic lineage, WI-CL-001, in municipal wastewater in Wisconsin, USA, in January, 2022. To determine the source of WI-CL-001, we systematically sampled wastewater from targeted sub-sewershed lines and maintenance holes using compositing autosamplers. Viral concentrations in wastewater samples over time were measured by RT digital PCR. In addition to using metagenomic 12s rRNA sequencing to determine the virus's host species, we also sequenced SARS-CoV-2 spike receptor binding domains, and, where possible, whole viral genomes to identify and characterise the evolution of this lineage. FINDINGS: We traced WI-CL-001 to its source at a single commercial building. There we detected the cryptic lineage at concentrations as high as 2·7 × 109 genome copies per L. The majority of 12s rRNA sequences detected in wastewater leaving the identified source building were human. Additionally, we generated over 100 viral receptor binding domain and whole-genome sequences from wastewater samples containing the cryptic lineage collected over the 13 consecutive months this virus was detectable (January, 2022, to January, 2023). These sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in humans in Wisconsin at low levels from October, 2020, to February, 2021. Despite this, mutations in the spike gene and elsewhere resembled those subsequently found in omicron variants. INTERPRETATION: We propose that prolonged detection of WI-CL-001 in wastewater indicates persistent shedding of SARS-CoV-2 from a single human initially infected by an ancestral B.1.234 virus. The accumulation of convergent omicron-like mutations in WI-CL-001's ancestral B.1.234 genome probably reflects persistent infection and extensive within-host evolution. People who shed cryptic lineages could be an important source of highly divergent viruses that sporadically emerge and spread. FUNDING: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention, National Institute on Drug Abuse, and the Center for Research on Influenza Pathogenesis and Transmission.

Systematic review and bioinformatics analysis of plasma and serum extracellular vesicles proteome in type 2 diabetes.

Background: Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated morbidity and mortality rates. The pathophysiological mechanisms underlying the onset and progression of this disease remain subjects of ongoing investigation. Recent evidence underscores the pivotal role of the intricate intercellular communication network, wherein cell-derived vesicles, commonly referred to as extracellular vesicles (EVs), emerge as dynamic regulators of diabetes-related complications. Given that the protein cargo carried by EVs is contingent upon the metabolic conditions of the originating cells, particular proteins may serve as informative indicators for the risk of activating or inhibiting signaling pathways crucial to the progression of T2D complications. Methods: In this study, we conducted a systematic review to analyze the published evidence on the proteome of EVs from the plasma or serum of patients with T2D, both with and without complications (PROSPERO: CRD42023431464). Results: Nine eligible articles were systematically identified from the databases, and the proteins featured in these articles underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We identified changes in the level of 426 proteins, with CST6, CD55, HBA1, S100A8, and S100A9 reported to have high levels, while FGL1 exhibited low levels. Conclusion: These proteins are implicated in pathophysiological mechanisms such as inflammation, complement, and platelet activation, suggesting their potential as risk markers for T2D development and progression. Further studies are required to explore this topic in greater detail.

Exploring Deep Learning for Estimating the Isoeffective Dose of FLASH Irradiation From Mouse Intestinal Histological Images.

PURPOSE: Ultrahigh-dose-rate (FLASH) irradiation has been reported to reduce normal tissue damage compared with conventional dose rate (CONV) irradiation without compromising tumor control. This proof-of-concept study aims to develop a deep learning (DL) approach to quantify the FLASH isoeffective dose (dose of CONV that would be required to produce the same effect as the given physical FLASH dose) with postirradiation mouse intestinal histology images. METHODS AND MATERIALS: Eighty-four healthy C57BL/6J female mice underwent 16 MeV electron CONV (0.12 Gy/s; n = 41) or FLASH (200 Gy/s; n = 43) single fraction whole abdominal irradiation. Physical dose ranged from 12 to 16 Gy for FLASH and 11 to 15 Gy for CONV in 1 Gy increments. Four days after irradiation, 9 jejunum cross-sections from each mouse were hematoxylin and eosin stained and digitized for histological analysis. CONV data set was randomly split into training (n = 33) and testing (n = 8) data sets. ResNet101-based DL models were retrained using the CONV training data set to estimate the dose based on histological features. The classical manual crypt counting (CC) approach was implemented for model comparison. Cross-section-wise mean squared error was computed to evaluate the dose estimation accuracy of both approaches. The validated DL model was applied to the FLASH data set to map the physical FLASH dose into the isoeffective dose. RESULTS: The DL model achieved a cross-section-wise mean squared error of 0.20 Gy2 on the CONV testing data set compared with 0.40 Gy2 of the CC approach. Isoeffective doses estimated by the DL model for FLASH doses of 12, 13, 14, 15, and 16 Gy were 12.19 ± 0.46, 12.54 ± 0.37, 12.69 ± 0.26, 12.84 ± 0.26, and 13.03 ± 0.28 Gy, respectively. CONCLUSIONS: Our proposed DL model achieved accurate CONV dose estimation. The DL model results indicate that in the physical dose range of 13 to 16 Gy, the biologic dose response of small intestinal tissue to FLASH irradiation is represented by a lower isoeffective dose compared with the physical dose. Our DL approach can be a tool for studying isoeffective doses of other radiation dose modifying interventions.

A severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nosocomial cluster with inter-facility spread: Lessons learned.

BACKGROUND: Despite infection control guidance, sporadic nosocomial coronavirus disease 2019 (COVID-19) outbreaks occur. We describe a complex severe acute respiratory coronavirus virus 2 (SARS-CoV-2) cluster with interfacility spread during the SARS-CoV-2 δ (delta) pandemic surge in the Midwest. SETTING: This study was conducted in (1) a hematology-oncology ward in a regional academic medical center and (2) a geographically distant acute rehabilitation hospital. METHODS: We conducted contact tracing for each COVID-19 case to identify healthcare exposures within 14 days prior to diagnosis. Liberal testing was performed for asymptomatic carriage for patients and staff. Whole-genome sequencing was conducted for all available clinical isolates from patients and healthcare workers (HCWs) to identify transmission clusters. RESULTS: In the immunosuppressed ward, 19 cases (4 patients, 15 HCWs) shared a genetically related SARS-CoV-2 isolate. Of these 4 patients, 3 died in the hospital or within 1 week of discharge. The suspected index case was a patient with new dyspnea, diagnosed during preprocedure screening. In the rehabilitation hospital, 20 cases (5 patients and 15 HCWs) positive for COVID-19, of whom 2 patients and 3 HCWs had an isolate genetically related to the above cluster. The suspected index case was a patient from the immune suppressed ward whose positive status was not detected at admission to the rehabilitation facility. Our response to this cluster included the following interventions in both settings: restricting visitors, restricting learners, restricting overflow admissions, enforcing strict compliance with escalated PPE, access to on-site free and frequent testing for staff, and testing all patients prior to hospital discharge and transfer to other facilities. CONCLUSIONS: Stringent infection control measures can prevent nosocomial COVID-19 transmission in healthcare facilities with high-risk patients during pandemic surges. These interventions were successful in ending these outbreaks.

Monocyte (THP-1) Response to Silver Nanoparticles Synthesized with Rumex hymenosepalus Root Extract.

The study, synthesis, and application of nanomaterials in medicine have grown exponentially in recent years. An example of this is the understanding of how nanomaterials activate or regulate the immune system, particularly macrophages. In this work, nanoparticles were synthesized using Rumex hymenosepalus as a reducing agent (AgRhNPs). According to thermogravimetric analysis, the metal content of nanoparticles is 55.5% by weight. The size of the particles ranges from 5-26 nm, with an average of 11 nm, and they possess an fcc crystalline structure. The presence of extract molecules on the nanomaterial was confirmed by UV-Vis and FTIR. It was found by UPLC-qTOF that the most abundant compounds in Rh extract are flavonols, flavones, isoflavones, chalcones, and anthocyanidins. The viability and apoptosis of the THP-1 cell line were evaluated for AgRhNPs, commercial nanoparticles (AgCNPs), and Rh extract. The results indicate a minimal cytotoxic and apoptotic effect at a concentration of 12.5 µg/mL for both nanoparticles and 25 µg/mL for Rh extract. The interaction of the THP-1 cell line and treatments was used to evaluate the polarization of monocyte subsets in conjunction with an evaluation of CCR2, Tie-2, and Arg-1 expression. The AgRhNPs nanoparticles and Rh extract neither exhibited cytotoxicity in the THP-1 monocyte cell line. Additionally, the treatments mentioned above exhibited anti-inflammatory effects by maintaining the classical monocyte phenotype CD14++CD16, reducing pro-inflammatory interleukin IL-6 production, and increasing IL-4 production.

Differences between the geometric phase and propagation phase: clarifying the boundedness problem.

We show white light interferometer experiments that clearly demonstrate the basic differences between geometric and propagation phases. These experimental results also suggest a way to answer the "boundedness problem" in geometric phase-whether geometric phase is unbounded (i.e., can take on any values without limit) or bounded (i.e., limited to values between -π and +π). We show why the answer to this question is not as easy as it seems, from both a theoretical and an experimental perspective, and explain how the answer depends on one's choice of phase convention. We also hope that the videos provided will be pedagogically useful for explaining geometric phase.

Metagenome-assembled genomes of two nitrifying microorganisms from the freshwater archaeal ammonia-oxidizing enrichment culture BO1.

Two metagenome-assembled genomes (MAGs) were recovered from the ammonia-oxidizing enrichment culture BO1 obtained from the sediment of the freshwater reservoir Lake Burr Oak, Ohio, USA. High quality MAGs were assembled for the archaeal ammonia oxidizer Nitrosarchaeum sp. BO1 and the canonical nitrite oxidizer Nitrospira sp. BO1.

Digestive glycosidases from cannonball jellyfish (Stomolophus sp. 2): identification and temporal-spatial variability.

Jellyfish are economically important organisms in diverse countries, carnivorous organisms that consume various prey (crustaceans, mollusks, bivalves, etc.) and dissolved carbohydrates in marine waters. This study was focused on detecting and quantifying the activity of digestive glycosidases from the cannonball jellyfish (Stomolophus sp. 2) to understand carbohydrate digestion and its temporal-spatial variation. Twenty-three jellyfish gastric pouches were collected in 2015 and 2016 in the Gulf of California in three localities (Las Guásimas, Hermosillo, and Caborca). Nine samples were in intra-localities from Las Guásimas. Chitinase (Ch), ß-glucosidase (ß-glu), and ß-N-acetylhexosaminidase (ß-NAHA) were detected in the gastric pouches. However, cellulase, exoglucanase, α-amylase, polygalacturonase, xylanase, and κ-carrageenase were undetected. Detected enzymes showed halotolerant glycolytic activity (i = 0-4 M NaCl), optimal pH, and temperature at 5.0 and 30-50 °C, respectively. At least five ß-glucosidase and two ß-N-acetylhexosaminidase were detected using zymograms; however, the number of proteins with chitinase activity is not precise. The annual variation of cannonball jellyfish digestive glycosidases from Las Guásimas between 2015-2016 does not show significant differences despite the difference in phytoplankton measured as chlorophyll α (1.9 and 3.4 mg/m3, respectively). In the inter-localities, the glycosidase activity was statistically different in all localities, except for ß-N-acetylhexosaminidase activity between Caborca and Hermosillo (3,009.08 ± 87.95 and 3,101.81 ± 281.11 mU/g of the gastric pouch, respectively), with chlorophyll α concentrations of 2.6, 3.4 mg/m3, respectively. For intra-localities, the glycosidase activity did not show significant differences, with a mean chlorophyll α of 1.3 ± 0.1 mg/m3. These results suggest that digestive glycosidases from Stomolophus sp. 2 can hydrolyze several carbohydrates that may belong to their prey or carbohydrates dissolved in marine waters, with salinity over ≥ 0.6 M NaCl and diverse temperature (4-80 °C) conditions. Also, chlorophyll α is related to glycosidase activity in both seasons and inter-localities, except for chitinase activity in an intra-locality (Las Guásimas).

Biochemical and hemostatic description of a thrombin-like enzyme TLBro from Bothrops roedingeri snake venom.

Objective: The current study's objective is to characterize a new throm-bin-like enzyme called TLBro that was obtained from Bothrops roedingeris snake from a biochemical and hemostatic perspective. Methodology: One chromatographic step was used to purify it, producing the serine protease TLBro. Molecular mass was estimated by SDS-PAGE to be between reduced and unreduced by 35 kDa. Tryptic peptide sequencing using Swiss Prot provided the complete amino acid sequence. Expasy.org by conducting a search that is limited to Crotalinae snake serine proteases and displaying a high degree of amino acid sequence. Results: Ser (182) is inhibited by phenylmethylsulfonyl fluoride (PMSF), and TLBro demonstrated the presence of Asp (88) residues. It also deduced the positions of His (43) and Ser (182) in the set of three coordinated amino acids in serine proteases. It was discovered that this substrate had high specificity for BANA, Michaelis-Menten behavior with KM 0 point85 mM and Vmax 1 point89 nmoles -NA/L/min, and high stability between temperatures (15 to 70°C) and pHs (2 point0 to 10 point0). According to doses and incubation times, TLBro degraded fibrin preferentially on the B-chain; additionally, its activities were significantly diminished after preincubation with divalent ions (Zn2 and Cd2). When incubated with PMSF, a particular serine protease inhibitor, enzymatic activities and platelet aggregation were inhibited. Conclusion: The findings revealed distinct structural and functional differences between the serine proteases, adding to the information and assisting in the improvement of the structure-function relationship.

Genome analysis of haloalkaline isolates from the soda saline crater lake of Isabel Island; comparative genomics and potential metabolic analysis within the genus Halomonas.

BACKGROUND: Isabel Island is a Mexican volcanic island primarily composed of basaltic stones. It features a maar known as Laguna Fragatas, which is classified as a meromictic thalassohaline lake. The constant deposition of guano in this maar results in increased levels of phosphorus, nitrogen, and carbon. The aim of this study was to utilize high-quality genomes from the genus Halomonas found in specialized databases as a reference for genome mining of moderately halophilic bacteria isolated from Laguna Fragatas. This research involved genomic comparisons employing phylogenetic, pangenomic, and metabolic-inference approaches. RESULTS: The Halomonas genus exhibited a large open pangenome, but several genes associated with salt metabolism and homeostatic regulation (ectABC and betABC), nitrogen intake through nitrate and nitrite transporters (nasA, and narGI), and phosphorus uptake (pstABCS) were shared among the Halomonas isolates. CONCLUSIONS: The isolated bacteria demonstrate consistent adaptation to high salt concentrations, and their nitrogen and phosphorus uptake mechanisms are highly optimized. This optimization is expected in an extremophile environment characterized by minimal disturbances or abrupt seasonal variations. The primary significance of this study lies in the dearth of genomic information available for this saline and low-disturbance environment. This makes it important for ecosystem conservation and enabling an exploration of its biotechnological potential. Additionally, the study presents the first two draft genomes of H. janggokensis.

Impact on physical function of the +AGIL Barcelona program in community-dwelling older adults with cognitive impairment: an interventional cohort study.

BACKGROUND: Older adults with cognitive impairment (CI) have higher multimorbidity and frailty prevalence, lower functional status and an increased likelihood to develop dementia, non-cognitive deficits, and adverse health-related events. +AGIL, a real-world program for frail older adults in a primary care area of Barcelona, is a pragmatic, multi-component and integrated intervention implemented since 2016. It includes physical activity, nutrition, sleep hygiene, revision and adequacy of pharmacological treatment, detection of undesired loneliness and screening for CI; to improve physical function in community-dwelling older adults. We aimed to assess the + AGIL longitudinal impact on physical function among community-dwelling frail older persons with CI. METHODS: An interventional cohort study included data from all the + AGIL consecutive participants from July 2016 until March 2020. Based on the comprehensive geriatric assessment, participants were offered a tailored multi-component community intervention, including a 10-week physical activity program led by an expert physical therapist. Physical performance was measured at baseline, three and six months follow-up. The pre-post impact on physical function was assessed by paired sample t-test for repeated samples. Linear mixed models were applied to analyze the + AGIL longitudinal impact. P-values < 0.05 were considered statistically significant. RESULTS: 194 participants were included (82 with CI, based on previous diagnosis or the Mini-COG screening tool), 68% women, mean age 81.6 (SD = 5.8) yo. Participants were mostly independent in Activities of Daily Living (mean Barthel = 92.4, SD = 11.1). The physical activity program showed high adherence (87.6% attended ≥ 75% sessions). At three months, there was a clinically and statistically significant improvement in the Short Physical Performance Battery (SPPB) and its subcomponents in the whole sample and after stratification for CI [CI group improvements: SPPB = 1.1 (SD = 1.8) points, gait speed (GS) = 0.05 (SD = 0.13) m/s, Chair stand test (CST)=-2.6 (SD = 11.4) s. Non-CI group improvements: SPPB = 1.6 (SD = 1.8) points, GS = 0.08 (SD = 0.13) m/s, CST=-6.4 (SD = 12.1) seg]. SPPB and gait speed remained stable at six months in the study sample and subgroups. CI had no significant impact on SPPB or GS improvements. CONCLUSION: Our results suggest that older adults with CI can benefit from a multidisciplinary integrated and comprehensive geriatric intervention to improve physical function, a component of frailty.

Human enteroids as a tool to study conventional and ultra-high dose rate radiation.

Radiation therapy, one of the most effective therapies to treat cancer, is highly toxic to healthy tissue. The delivery of radiation at ultra-high dose rates, FLASH radiation therapy (FLASH), has been shown to maintain therapeutic anti-tumor efficacy while sparing normal tissues compared to conventional dose rate irradiation (CONV). Though promising, these studies have been limited mainly to murine models. Here, we leveraged enteroids, three-dimensional cell clusters that mimic the intestine, to study human-specific tissue response to radiation. We observed enteroids have a greater colony growth potential following FLASH compared with CONV. In addition, the enteroids that reformed following FLASH more frequently exhibited proper intestinal polarity. While we did not observe differences in enteroid damage across groups, we did see distinct transcriptomic changes. Specifically, the FLASH enteroids upregulated the expression of genes associated with the WNT-family, cell-cell adhesion, and hypoxia response. These studies validate human enteroids as a model to investigate FLASH and provide further evidence supporting clinical study of this therapy. Insight Box Promising work has been done to demonstrate the potential of ultra-high dose rate radiation (FLASH) to ablate cancerous tissue, while preserving healthy tissue. While encouraging, these findings have been primarily observed using pre-clinical murine and traditional two-dimensional cell culture. This study validates the use of human enteroids as a tool to investigate human-specific tissue response to FLASH. Specifically, the work described demonstrates the ability of enteroids to recapitulate previous in vivo findings, while also providing a lens through which to probe cellular and molecular-level responses to FLASH. The human enteroids described herein offer a powerful model that can be used to probe the underlying mechanisms of FLASH in future studies.

Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom.

We conducted a multi-institutional audit of dosimetric variability between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3D-printed mouse phantom. A CT scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene ($~1.02 g/cm^3$) and polylactic acid ($~1.24 g/cm^3$) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid ($~0.64 g/cm^3$). Hounsfield units (HU) and densities were compared with the reference CT scan of the live mouse. Print-to-print reproducibility of the phantom was assessed. Three institutions were each provided a phantom, and each institution performed two replicates of irradiations at selected mouse anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film. Compared to the reference CT scan, CT scans of the phantom demonstrated mass density differences of $0.10 g/cm^3$ for bone, $0.12 g/cm^3$ for lung, and $0.03 g/cm^3$ for soft tissue regions. Between phantoms, the difference in HU for soft tissue and bone was <10 HU from print to print. Lung exhibited the most variation (54 HU) but minimally affected dose distribution (<0.5% dose differences between phantoms). The mean difference between FLASH and CONV from the first replicate to the second decreased from 4.3% to 1.2%, and the mean difference from the prescribed dose decreased from 3.6% to 2.5% for CONV and 6.4% to 2.7% for FLASH. The framework presented here is promising for credentialing of multi-institutional studies of FLASH preclinical research to maximize the reproducibility of biological findings.

FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates.

BACKGROUND AND PURPOSE: The impact of radiotherapy (RT) at ultra high vs conventional dose rate (FLASH vs CONV) on the generation and repair of DNA double strand breaks (DSBs) is an important question that remains to be investigated. Here, we tested the hypothesis as to whether FLASH-RT generates decreased chromosomal translocations compared to CONV-RT. MATERIALS AND METHODS: We used two FLASH validated electron beams and high-throughput rejoin and genome-wide translocation sequencing (HTGTS-JoinT-seq), employing S. aureus and S. pyogenes Cas9 "bait" DNA double strand breaks (DSBs) in HEK239T cells, to measure differences in bait-proximal repair and their genome-wide translocations to "prey" DSBs generated after various irradiation doses, dose rates and oxygen tensions (normoxic, 21% O2; physiological, 4% O2; hypoxic, 2% and 0.5% O2). Electron irradiation was delivered using a FLASH capable Varian Trilogy and the eRT6/Oriatron at CONV (0.08-0.13 Gy/s) and FLASH (1x102-5x106 Gy/s) dose rates. Related experiments using clonogenic survival and γH2AX foci in the 293T and the U87 glioblastoma lines were also performed to discern FLASH-RT vs CONV-RT DSB effects. RESULTS: Normoxic and physioxic irradiation of HEK293T cells increased translocations at the cost of decreasing bait-proximal repair but were indistinguishable between CONV-RT and FLASH-RT. Although no apparent increase in chromosome translocations was observed with hypoxia-induced apoptosis, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal significant differences in the level of translocations nor in their junction structures. Furthermore, RT dose rate modality on U87 cells did not change γH2AX foci numbers at 1- and 24-hours post-irradiation nor did this affect 293T clonogenic survival. CONCLUSION: Irrespective of oxygen tension, FLASH-RT produces translocations and junction structures at levels and proportions that are indistinguishable from CONV-RT.

In-Situ Modification of Nanofiltration Membranes Using Carbon Nanotubes for Water Treatment.

Modification of thin-film composite (TFC) nanofiltration (NF) membranes to increase permeability and improve separation performance remains a significant challenge for water scarcity. This study aimed to enhance the permeability and selectivity of two commercial polyamide (PA) NF membranes, NF90 and NF270, by modifying them with carbon nanotubes (CNTs) using microwave (MW)-assisted in-situ growth. The conducting polymer, polypyrrole (Ppy), and a ferrocene catalyst were used to facilitate the growth process. Chemical and morphological analyses confirmed that the surface of both membranes was modified. The NF270-Ppy-CNT membrane was selected for ion rejection testing due to its superior permeability compared to the NF90-Ppy-CNT. The modified NF270 membrane showed a 14% increase in ion rejection while maintaining constant water permeability. The results demonstrated that it is feasible to attach CNTs to a polymeric surface without compromising its functional properties. The Spliegler-Kedem model was employed to model the rejection and permeate flux of NF270-Ppy-CNT and NF270 membranes, which indicated that diffusive transport contributes to the modification to increase NaCl rejection. The present study provides a promising approach for modifying membranes by in-situ CNT growth to improve their performance in water treatment applications, such as desalination.

Efficient line shape estimation by ghost spectroscopy.

Recovering the original spectral line shapes from data obtained by instruments with extended transmission profiles is a basic tenet in spectroscopy. By using the moments of the measured lines as basic variables, we turn the problem into a linear inversion. However, when only a finite number of these moments are relevant, the rest of them act as nuisance parameters. These can be taken into account with a semiparametric model, which allows us to establish the ultimate bounds on the precision attainable in the estimation of the moments of interest. We experimentally confirm these limits with a simple ghost spectroscopy demonstration.

Deciphering Pancharatnam's discovery of geometric phase: retrospective.

While Pancharatnam discovered the geometric phase in 1956, his work was not widely recognized until its endorsement by Berry in 1987, after which it received wide appreciation. However, because Pancharatnam's paper is unusually difficult to follow, his work has often been misinterpreted as referring to an evolution of states of polarization, just as Berry's work focused on a cycle of states, even though this consideration does not appear in Pancharatnam's work. We walk the reader through Pancharatnam's original derivation and show how Pancharatnam's approach connects to recent work in geometric phase. It is our hope to make this widely cited classic paper more accessible and better understood.

A comprehensive approach to how hospital effluents lead to oxidative stress and shift the gene expression in target organs of Danio rerio.

Hospital effluents represent a threat to the environment owing to the content of toxic substances capable of altering the structure and function of ecosystems. Despite the available information about the impact of hospital effluents on aquatic organisms, the molecular mechanism underlying this process has received little or no attention. The present study aimed to evaluate the oxidative stress and gene expression induced by different proportions (2 %, 2.5 %, 3 % and 3.5 %) of hospital effluent treated by hospital wastewater treatment plant (HWWTP) in liver, gut, and gills of Danio rerio at different exposure times. Significant increases in the levels of protein carbonylation content (PCC), hydroperoxides content (HPC), lipoperoxidation level (LPX) and superoxide dismutase (SOD) and catalase (CAT) activity were observed in most of the organs evaluated at the four proportions tested with respect to the control group (p < 0.05). It was found that at longer exposure times there is a lower response in SOD activity, suggesting catalytic depletion due to the oxidative environment at the intracellular level. The lack of complementarity between SOD and mRNA activity patterns indicates that the activity itself is subordinated to post-transcriptional processes. Upregulation of transcripts related to antioxidant processes (sod, cat, nrf2), detoxification (cyp1a1) and apoptosis (bax, casp6, and casp9) was observed in response to oxidative imbalance. On the other hand, the metataxonomic approach allowed the characterization of pathogenic bacterial genera such as Legionella, Pseudomonas, Clostridium XI, Parachlamydia and Mycobacterium present in the hospital effluent. Our findings indicate that although hospital effluent was treated by HWWTP, it caused oxidative stress damage and disrupted gene expression by decreasing the antioxidant response in Danio rerio.

Treatment of tequila distillation volatile residues by electrochemical oxidation using titanium electrodes.

Tequila production occurs in Mexico's designated area of origin, principally in the Jalisco State. Its residues are a challenge in treatment and tracking due to a lack of technology, non-economic treatments available, low environmental consciousness and incipient control from authorities. In 2021, average production was close to 1.5 million tequila litres per day with an estimated residue yield of 10-12 litres of stillage (tequila vinasses) per tequila litre produced, including volatile fractions. This research aims to reduce organic matter by electrooxidation (EO) from 5 distillation volatile residual effluents (two-stage still distillation) from three tequila distilleries, first and second-stage heads and heads and tails and second-stage non-evaporated fraction. Round 3 mm titanium (grade-1) electrodes (one anode and one cathode) were used, with fixed voltage to a value of 30 VDC at 0, 3, 6, 9 and 12 h with 75 experiments. Gas chromatography was used to analyse methanol, ethanol, acetaldehyde, ethyl acetate, n-propanol, sec-butanol, iso-butanol, n-butanol, iso-amyl, n-amyl, and ethyl lactate content. Treatment shows positive results, reducing organic matter content in all effluents in a Chemical Oxygen Demand COD range of 580-1880 mg/L.h, particularly useful in the second-stage non-evaporated fraction for water recovery.HIGHLIGHTSResidual effluent treatment is beneficial to environmental and resource sustainability.Process without adding materials achieving cleaner treated effluents.Process aimed as the final step to recover water.This process could help the Tequila industry to reach a higher sustainability level by reducing water usage and untreated residues.