Statistical mechanics of a Feshbach coupled Bose-Fermi gas in an optical lattice

We consider an atomic Fermi gas confined in a uniform optical lattice potential, where the atoms can pair into molecules via a magnetic field controlled narrow Feshbach resonance. The phase diagram of the resulting atom-molecule mixture in chemical and thermal equilibrium is determined numerically in the absence of interactions under the constraint of particle conservation. In the limiting cases of vanishing or large lattice depth we derive simple analytical results for important thermodynamic quantities. One such quantity is the dissociation energy, defined as the detuning of the molecular energy spectrum with respect to the atomic one for which half of the atoms have been converted into dimers. Importantly we find that the dissociation energy has a non-monotonic dependence on lattice depth.Comment: 9 pages, 5 figure

Superfluid turbulence from quantum Kelvin wave to classical Kolmogorov cascades

A novel unitary quantum lattice gas algorithm is used to simulate quantum turbulence of a BEC described by the Gross-Pitaevskii equation on grids up to 5760^3. For the first time, an accurate power law scaling for the quantum Kelvin wave cascade is determined: k^{-3}. The incompressible kinetic energy spectrum exhibits very distinct power law spectra in 3 ranges of k-space: a classical Kolmogorov k^{-5/3} spectrum at scales much greater than the individual quantum vortex cores, and a quantum Kelvin wave cascade spectrum k^{-3} on scales of order the vortex cores. In the semiclassical regime between these two spectra there is a pronounced steeper spectral decay, with non-universal exponent. The Kelvin k^{-3} spectrum is very robust, even on small grids, while the Kolmogorov k^{-5/3} spectrum becomes more and more apparent as the grids increase from 2048^3 grids to 5760^3.Comment: 4 pages, 2 figure

Porcine Models of Pancreatic Cancer: Current Status and Future

The KRASG12D and TP53R172H mutations are the leading causes of pancreatic cancer, with the third deadliest cancer mortality rate. Majority of the pancreatic cancer research utilizes mouse models. Our lab is currently studying porcine as a suitable model to study pancreatic cancer due to the comparative anatomy and genomic similarities between humans and porcine. Our first approach to develop the porcine pancreatic cancer model was to orthotopically implant the transformed and mutated primary pig pancreatic epithelial cells into the pig pancreas. The second approach was using the Oncopig model with KRASG12D and TP53R172H genetic mutations. The mutated genes were expressed by injecting adenovirus with Cre recombinase to develop tumors. Hematoxylin and Eosin staining, immunohistochemistry, plasmid, and RNA isolation were used to study the porcine pancreas before and after the tumor induction. Results showed that humans and porcine have similar histological characteristics showing comprising islets, ducts, and acinar cells. For the orthotopic model, after two weeks of orthotopic implantation, there were signs of pancreatitis and some evidence of tumor-like cells, but not tumors. Some signs were the formation of acinar to ductal metaplasia, massive immune cell responses, and vimentin expression in the regions of desmoplasia. Our results showed that the Oncopigs did generate pancreatic tumors successfully and are currently being characterized for future use, and the orthotopic model showed promising results. However, implanted tumor cells will be given additional help to allow them to survive from host immune response by over-expressing PD-L1 on the implanted tumor cells surface.https://digitalcommons.unmc.edu/surp2022/1041/thumbnail.jp

Brachybacterium nesterenkovii isolated from a human blood culture-a first report

Brachybacterium is a genus of Gram-positive bacteria that rarely causes infections in humans. Here we report the case of an 8-month-old infant who presented with an acute febrile illness. During the diagnostic process, a blood culture was positive with Gram-positive cocci that were identified as Brachybacterium nesterenkovii by MALDI-TOF. As a result of the unclear clinical significance of this isolate and the continuous febrile state, a second blood culture was taken and returned B. nesterenkovii once more. To our knowledge this is the first time that B. nesterenkovii has been isolated from human blood cultures during the course of a systemic infection

Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy

We examined the brain injury and neurodevelopmental outcomes in a prospective cohort of 10 babies with mild encephalopathy who had early cessation of cooling therapy. All babies had MRI and spectroscopy within 2 weeks after birth and neurodevelopmental assessment at 2 years. Cooling was prematurely discontinued at a median age of 9 hours (IQR 5-13) due to rapid clinical improvement. Five (50%) had injury on MRI or spectroscopy, and two (20%) had an abnormal neurodevelopmental outcome at 2 years. Premature cessation of cooling therapy in babies with mild neonatal encephalopathy does not exclude residual brain injury and adverse long-term neurodevelopmental outcomes. This study refers to babies recruited into the MARBLE study (NCT01309711, pre-results stage)

Auditory assessment of patients with acute uncomplicated Plasmodium falciparum malaria treated with three-day mefloquine-artesunate on the north-western border of Thailand

<p>Abstract</p> <p>Background</p> <p>The use of artemisinin derivatives has increased exponentially with the deployment of artemisinin combination therapy (ACT) in all malarious areas. They are highly effective and are considered safe, but in animal studies artemisinin derivatives produce neurotoxicity targeting mainly the auditory and vestibular pathways. The debate remains as to whether artemisinin derivatives induce similar toxicity in humans.</p> <p>Methods</p> <p>This prospective study assessed the effects on auditory function of a standard 3-day oral dose of artesunate (4 mg/kg/day) combined with mefloquine (25 mg/kg) in patients with acute uncomplicated falciparum malaria treated at the Shoklo Malaria Research Unit, on the Thai-Burmese border. A complete auditory evaluation with tympanometry, audiometry and auditory brainstem responses (ABR) was performed before the first dose and seven days after initiation of the antimalarial treatment.</p> <p>Results</p> <p>Complete auditory tests at day 0 (D0) and day 7 (D7) were obtained for 93 patients. Hearing loss (threshold > 25 dB) on admission was common (57%) and associated with age only. No patient had a threshold change exceeding 10 dB between D0 and D7 at any tested frequency. No patient showed a shift in Wave III peak latency of more than 0.30 msec between baseline and D7.</p> <p>Conclusion</p> <p>Neither audiometric or the ABR tests showed clinical evidence of auditory toxicity seven days after receiving oral artesunate and mefloquine.</p

Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

Klebsiella spp. are frequently enriched in the gut microbiota of preterm neonates, and overgrowth is associated with necrotizing enterocolitis (NEC), nosocomial infections and late-onset sepsis. Little is known about the genomic and phenotypic characteristics of preterm-associated Klebsiella as previous studies have focussed on recovery of antimicrobial-resistant isolates or culture independent molecular analyses. The aim of this study was to better characterize preterm-associated Klebsiella populations using phenotypic and genotypic approaches. Faecal samples from a UK cohort of healthy and sick preterm neonates (n=109) were screened on MacConkey agar to isolate lactose positive Enterobacteriaceae. Whole-genome sequences were generated for Klebsiella spp., and virulence and antimicrobial resistance genes identified. Antibiotic susceptibility profiling, and in vitro macrophage and iron assays were undertaken for the Klebsiella strains. Metapangenome analyses with a manually curated genome dataset were undertaken to examine diversity of Klebsiella oxytoca and related bacteria in a publicly available shotgun metagenome dataset. Approximately one-tenth of faecal samples harboured Klebsiella spp. (Klebsiella pneumoniae, 7.3 %; Klebsiella quasipneumoniae, 0.9 %; Klebsiella grimontii, 2.8 %; Klebsiella michiganensis, 1.8 %). Isolates recovered from NEC- and sepsis-affected infants and those showing no signs of clinical infection (i.e. 'healthy') encoded multiple -lactamases. No difference was observed between isolates recovered from ‘healthy’ and sick infants with respect to in vitro siderophore production (all encoded enterobactin in their genomes). All K. pneumoniae, K. quasipneumoniae, K. grimontii and K. michiganensis faecal isolates tested were able to reside and persist in macrophages, indicating their immune evasion abilities. Metapangenome analyses of published metagenomic data confirmed our findings regarding the presence of K. michiganensis in the preterm gut. There is little difference in the phenotypic and genomic characteristics of Klebsiella isolates recovered from 'healthy' and sick infants. Identification of -lactamases in all isolates may prove problematic when defining treatment regimens for NEC or sepsis, and suggests ‘healthy’ preterm infants contribute to the resistome. Refined analyses with curated sequence databases are required when studying closely related species present in metagenomic data

Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic ischemic encephalopathy: a non-randomised cohort study

Objective To examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE). Design Non-randomised cohort study. Setting Eight tertiary neonatal units in the UK and the USA. Patients 47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth. Interventions Whole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours). Main outcome measures MRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years. Results The baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than non-cooled babies (p=0.02). Four (27%) non-cooled babies with mild HIE developed seizures after 6 hours of age, while none of the cooled babies developed seizures (p=0.008). Neurodevelopmental outcomes at 2 years were available in 40 (85%) of the babies. Adverse outcomes were seen in 2 (14.3%) non-cooled babies, and none of the cooled babies (p=0.09). Conclusions Therapeutic hypothermia may have a neuroprotective effect in babies with mild HIE, as demonstrated by improved MRS biomarkers and reduced white matter injury on MRI. This may warrant further evaluation in adequately powered randomised controlled trials

Transplantation of Skeletal Muscle-Derived Sca-1⁺/PW1⁺/Pax7⁻ Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction

We have previously shown that skeletal muscle-derived Sca-1⁺/PW1⁺/Pax7⁻ interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL/6 mice. 5 × 10⁵ eGFP-labelled PICs (MI + PICs; n = 7) or PBS (MI-PBS; n = 7) were injected intramyocardially into the border zone. Sham mice (n = 8) were not subjected to MI, or the transplantation of PICs or PBS. BrdU was administered via osmotic mini-pump for 14 days. Echocardiography was performed prior to surgery (baseline), and 1-, 3- and 6-weeks post-MI and PICs transplantation. Mice were sacrificed at 6 weeks post-MI + PICs transplantation, and heart sections were analysed for fibrosis, hypertrophy, engraftment, proliferation, and differentiation of PICs. A significant (\u1d631 < 0.05) improvement in ejection fraction (EF) and fractional shortening was observed in the MI-PICs group, compared to MI + PBS group at 6-weeks post MI + PICs transplantation. Infarct size/fibrosis of the left ventricle significantly (\u1d631 < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (\u1d631 < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 µM2 vs. 543.5 ± 26.6 µm2), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (\u1d631 < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 1.0%). PICs expressed and secreted pro-survival and reparative growth factors, supporting a paracrine effect of PICs during recovery/remodeling. Skeletal muscle-derived PICs show significant reparative potential, attenuating cardiac remodelling following transplantation into the infarcted myocardium. PICs can be easily sourced from skeletal muscle and therefore show promise as a potential cell candidate for supporting the reparative and regenerative effects of cell therapie

Identification of a conserved region of Plasmodium falciparum MSP3 targeted by biologically active antibodies to improve vaccine design

Merozoite surface protein 3 (MSP3) is a target of antibody-dependent cellular inhibition (ADCI), a protective mechanism against Plasmodium falciparum malaria. From the C-terminal half of the molecule, 6 overlapping peptides were chosen to characterize human immune responses. Each peptide defined at least 1 non-cross-reactive B cell epitope. Distinct patterns of antibody responses, by level and IgG subclass distribution, were observed in inhabitants of a malaria-endemic area. Antibodies affinity purified toward each peptide differed in their functional capacity to mediate parasite killing in ADCI assays: 3 of 6 overlapping peptides had a major inhibitory effect on parasite growth. This result was confirmed by the passive transfer of anti-MSP3 antibodies in vivo in a P. falciparum mouse model. T helper cell epitopes were identified in each peptide. Antigenicity and functional assays identified a 70-amino acid conserved domain of MSP3 as a target of biologically active antibodies to be included in future vaccine constructs based on MSP3