Random-field random surfaces

We study how the typical gradient and typical height of a random surface are modified by the addition of quenched disorder in the form of a random independent external field. The results provide quantitative estimates, sharp up to multiplicative constants, in the following cases. It is shown that for real-valued disordered random surfaces of the $\nabla \phi$ type with a uniformly convex interaction potential: (i) The gradient of the surface delocalizes in dimensions $1\le d\le 2$ and localizes in dimensions $d\ge3$. (ii) The surface delocalizes in dimensions $1\le d\le 4$ and localizes in dimensions $d\ge 5$. It is further shown that for the integer-valued disordered Gaussian free field: (i) The gradient of the surface delocalizes in dimensions $d=1,2$ and localizes in dimensions $d\ge3$. (ii) The surface delocalizes in dimensions $d=1,2$. (iii) The surface localizes in dimensions $d\ge 3$ at weak disorder strength. The behavior in dimensions $d\ge 3$ at strong disorder is left open. The proofs rely on several tools: explicit identities satisfied by the expectation of the random surface, the Efron--Stein concentration inequality, a coupling argument for Langevin dynamics (originally due to Funaki and Spohn) and the Nash--Aronson estimate.Comment: Revised version streamlines some of the proofs, improves the introduction and extends the discussion and open questions section; 45 page

Genetically Engineering Glycolysis in T Cells Increases Their Antitumor Function

BACKGROUND: T cells play a central role in the antitumor response. However, they often face numerous hurdles in the tumor microenvironment, including the scarcity of available essential metabolites such as glucose and amino acids. Moreover, cancer cells can monopolize these resources to thrive and proliferate by upregulating metabolite transporters and maintaining a high metabolic rate, thereby outcompeting T cells. METHODS: Herein, we sought to improve T-cell antitumor function in the tumor vicinity by enhancing their glycolytic capacity to better compete with tumor cells. To achieve this, we engineered human T cells to express a key glycolysis enzyme, phosphofructokinase, in conjunction with Glucose transporter 3, a glucose transporter. We co-expressed these, along with tumor-specific chimeric antigen or T-cell receptors. RESULTS: Engineered cells demonstrated an increased cytokine secretion and upregulation of T-cell activation markers compared with control cells. Moreover, they displayed superior glycolytic capacity, which translated into an improved in vivo therapeutic potential in a xenograft model of human tumors. CONCLUSION: In summary, these findings support the implementation of T-cell metabolic engineering to enhance the efficacy of cellular immunotherapies for cancer

High-throughput marker discovery in melon using a self-designed oligo microarray

<p>Abstract</p> <p>Background</p> <p>Genetic maps constitute the basis of breeding programs for many agricultural organisms. The creation of these maps is dependent on marker discovery. Melon, among other crops, is still lagging in genomic resources, limiting the ability to discover new markers in a high-throughput fashion. One of the methods used to search for molecular markers is DNA hybridization to microarrays. Microarray hybridization of DNA from different accessions can reveal differences between them--single-feature polymorphisms (SFPs). These SFPs can be used as markers for breeding purposes, or they can be converted to conventional markers by sequencing. This method has been utilized in a few different plants to discover genetic variation, using Affymetrix arrays that exist for only a few organisms. We applied this approach with some modifications for marker discovery in melon.</p> <p>Results</p> <p>Using a custom-designed oligonucleotide microarray based on a partial EST collection of melon, we discovered 6184 putative SFPs between the parents of our mapping population. Validation by sequencing of 245 SFPs from the two parents showed a sensitivity of around 79%. Most SFPs (81%) contained single-nucleotide polymorphisms. Testing the SFPs on another mapping population of melon confirmed that many of them are conserved.</p> <p>Conclusion</p> <p>Thousands of new SFPs that can be used for genetic mapping and molecular-assisted breeding in melon were discovered using a custom-designed oligo microarray. A portion of these SFPs are conserved and can be used in different breeding populations. Although improvement of the discovery rate is still needed, this approach is applicable to many agricultural systems with limited genomic resources.</p

The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

Objective To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system

What Insights Do Patients and Caregivers Have on Acute Kidney Injury and Posthospitalization Care? A Single-Centre Qualitative Study from Toronto, Canada

Objectives Hospitalisation with acute kidney injury (AKI) is associated with short-term and long-term adverse events, but patient and caregiver experiences with AKI are not well described. We sought to better understand patient and caregiver perspectives after a hospitalisation with AKI to inform discharge strategies that may improve outcomes for this high-risk population. Design Qualitative study with semistructured interviews. Setting Tertiary care hospital in Toronto, Ontario, Canada. Participants Adult patients (n=15) who survived a hospitalisation with Kidney Disease Improving Global Outcomes stage 2 or 3 AKI from May to December 2016. We also interviewed five patient caregivers. We required patients to have no previous evidence of severe chronic kidney disease (ie, prior receipt of dialysis, previous kidney transplantation or pre-existing estimated glomerular filtration rate (eGFR) under 30 mL/min/1.73 m2). Results We identified three over-arching themes: (1) prioritisation of conditions other than AKI, reflected by the importance placed on other comorbidities and the omission of AKI as part of the ongoing medical history; (2) variability in comprehension of the significance of AKI, represented by minimal knowledge of the causes and symptoms associated with AKI, along with misinformation on the kidneys’ ability to self-repair; and (3) anxiety from discharge planning and competing health demands, illustrated by complicated discharge plans involving multiple specialist appointments. Conclusions Patients and caregivers view AKI as a short-term and reversible condition, giving it little thought during the postdischarge period. As a result, reliance on patients and caregivers to report an episode of AKI to their outpatient physicians is unlikely to be successful. Patient-centred tools and decision aids are needed to bridge the gap between a hospitalisation with AKI and the safe transition to the outpatient setting