Realization of an all-optical zero to π cross-phase modulation jump

We report on the experimental demonstration of an all-optical π cross-phase modulation jump. By performing a preselection, an optically induced unitary transformation, and then a postselection on the polarization degree of freedom, the phase of the output beam acquires either a zero or π phase shift (with no other possible values). The postselection results in optical loss in the output beam. An input state may be chosen near the resulting phase singularity, yielding a pi phase shift even for weak interaction strengths. The scheme is experimentally demonstrated using a coherently prepared dark state in a warm atomic cesium vapor

KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data

Kinase inhibitors as targeted therapies have played an important role in improving cancer outcomes. However, there are still considerable challenges, such as resistance, non-response, patient stratification, polypharmacology, and identifying combination therapy where understanding a tumor kinase activity profile could be transformative. Here, we develop a graph- and statistics-based algorithm, called KSTAR, to convert phosphoproteomic measurements of cells and tissues into a kinase activity score that is generalizable and useful for clinical pipelines, requiring no quantification of the phosphorylation sites. In this work, we demonstrate that KSTAR reliably captures expected kinase activity differences across different tissues and stimulation contexts, allows for the direct comparison of samples from independent experiments, and is robust across a wide range of dataset sizes. Finally, we apply KSTAR to clinical breast cancer phosphoproteomic data and find that there is potential for kinase activity inference from KSTAR to complement the current clinical diagnosis of HER2 status in breast cancer patients

Approximating Turaev-Viro 3-manifold invariants is universal for quantum computation

The Turaev-Viro invariants are scalar topological invariants of compact, orientable 3-manifolds. We give a quantum algorithm for additively approximating Turaev-Viro invariants of a manifold presented by a Heegaard splitting. The algorithm is motivated by the relationship between topological quantum computers and (2+1)-D topological quantum field theories. Its accuracy is shown to be nontrivial, as the same algorithm, after efficient classical preprocessing, can solve any problem efficiently decidable by a quantum computer. Thus approximating certain Turaev-Viro invariants of manifolds presented by Heegaard splittings is a universal problem for quantum computation. This establishes a novel relation between the task of distinguishing non-homeomorphic 3-manifolds and the power of a general quantum computer.Comment: 4 pages, 3 figure

Realization of an All-Optical Zero To Cross-Phase Modulation Jump

We report on the experimental demonstration of an all-optical π cross-phase modulation jump. By performing a preselection, an optically induced unitary transformation, and then a postselection on the polarization degree of freedom, the phase of the output beam acquires either a zero or π phase shift (with no other possible values). The postselection results in optical loss in the output beam. An input state may be chosen near the resulting phase singularity, yielding a π phase shift even for weak interaction strengths. The scheme is experimentally demonstrated using a coherently prepared dark state in a warm atomic cesium vapor

Transformation of alignment files improves performance of variant callers for long-read RNA sequencing data

Long-read RNA sequencing (lrRNA-seq) produces detailed information about full-length transcripts, including novel and sample-specific isoforms. Furthermore, there is an opportunity to call variants directly from lrRNA-seq data. However, most state-of-the-art variant callers have been developed for genomic DNA. Here, there are two objectives: first, we perform a mini-benchmark on GATK, DeepVariant, Clair3, and NanoCaller primarily on PacBio Iso-Seq, data, but also on Nanopore and Illumina RNA-seq data; second, we propose a pipeline to process spliced-alignment files, making them suitable for variant calling with DNA-based callers. With such manipulations, high calling performance can be achieved using DeepVariant on Iso-seq data

Delayed self-recognition in children with autism spectrum disorder.

This study aimed to investigate temporally extended self-awareness (awareness of one’s place in and continued existence through time) in autism spectrum disorder (ASD), using the delayed self-recognition (DSR) paradigm (Povinelli et al., Child Development 67:1540–1554, 1996). Relative to age and verbal ability matched comparison children, children with ASD showed unattenuated performance on the DSR task, despite showing significant impairments in theory-of-mind task performance, and a reduced propensity to use personal pronouns to refer to themselves. The results may indicate intact temporally extended self-awareness in ASD. However, it may be that the DSR task is not an unambiguous measure of temporally extended self-awareness and it can be passed through strategies which do not require the possession of a temporally extended self-concept

Outbreak of Marburg hemorrhagic fever among miners in Kamwenge and Ibanda Districts, Uganda, 2007

Marburg hemorrhagic fever was detected among 4 miners in Ibanda District, Uganda, from June through September, 2007. Infection was likely acquired through exposure to bats or bat secretions in a mine in Kamwenge District, Uganda, and possibly human-to-human transmission between some patients. We describe the epidemiologic investigation and the health education response

Attenuating Muscle Damage Biomarkers and Muscle Soreness After an Exercise-Induced Muscle Damage with Branched-Chain Amino Acid (BCAA) Supplementation:A Systematic Review and Meta-analysis with Meta-regression

Background: Branched-chain amino acid (BCAA) supplementation is one of the most popular strategies used by the general population and athletes to reduce muscle soreness and accelerate the recovery process of muscle damage biomarkers after an intense exercise or training session. Objectives: This systematic review and meta-analysis investigated the effects of BCAA supplementation on muscle damage biomarkers and muscle soreness after exercise-induced muscle damage (EIMD). Methods: The systematic literature search for randomized controlled trials was conducted using seven databases, up to September 13th, 2022. The eligibility criteria for selecting studies were as follows: studies performed on healthy active participants, using BCAA at least once, controlled with a placebo or control group, performing resistance or endurance exercises, and followed up at least once post-EIMD. The methodological quality of the studies was assessed using the “SIGN RCT checklist”. Random-effects meta-analyses were processed to compute the standardized mean difference (Hedges’ g). Meta-regression analyses were completed with daily and total dosage and supplementation as continuous moderator variables. Results: Of the 18 studies included in this meta-analysis, 13 were of high quality and five were of acceptable quality. Our results revealed BCAA supplementation elicits a significant effect on reducing creatine kinase (CK) levels immediately (g = − 0.44; p = 0.006) and 72 h (g = − 0.99; p = 0.002), but not 24 h, 48 h, and 96 h post-EIMD. Additionally, a significant effect on delayed onset of muscle soreness (DOMS) was identified at 24 h (g = − 1.34; p < 0.001), 48 h (g = − 1.75; p < 0.001), 72 h (g = − 1.82; p < 0.001), and 96 h (g = − 0.82; p = 0.008), but not immediately post-EIMD. No significant effect was found on lactate dehydrogenase (LDH) levels at any time point. Meta-regression indicated higher daily and total dosages of BCAA, and longer supplementation periods were related to the largest beneficial effects on CK (total dosage and supplementation period) at 48 h, and on DOMS at 24 h (only daily dosage). Conclusion: The overall effects of BCAA supplementation could be considered useful for lowering CK and DOMS after EIMD, but not LDH. The longer supplementation period prior to the EIMD could be more effective for CK and DOMS reduction

Regulation of pH by Carbonic Anhydrase 9 Mediates Survival of Pancreatic Cancer Cells With Activated KRAS in Response to Hypoxia.

Background & Aims Most pancreatic ductal adenocarcinomas (PDACs) express an activated form of KRAS, become hypoxic and dysplastic, and are refractory to chemo and radiation therapies. To survive in the hypoxic environment, PDAC cells upregulate enzymes and transporters involved in pH regulation, including the extracellular facing carbonic anhydrase 9 (CA9). We evaluated the effect of blocking CA9, in combination with administration of gemcitabine, in mouse models of pancreatic cancer. Methods We knocked down expression of KRAS in human (PK-8 and PK-1) PDAC cells with small hairpin RNAs. Human and mouse (KrasG12D/Pdx1-Cre/Tp53/RosaYFP) PDAC cells were incubated with inhibitors of MEK (trametinib) or extracellular signal-regulated kinase (ERK), and some cells were cultured under hypoxic conditions. We measured levels and stability of the hypoxia-inducible factor 1 subunit alpha (HIF1A), endothelial PAS domain 1 protein (EPAS1, also called HIF2A), CA9, solute carrier family 16 member 4 (SLC16A4, also called MCT4), and SLC2A1 (also called GLUT1) by immunoblot analyses. We analyzed intracellular pH (pHi) and extracellular metabolic flux. We knocked down expression of CA9 in PDAC cells, or inhibited CA9 with SLC-0111, incubated them with gemcitabine, and assessed pHi, metabolic flux, and cytotoxicity under normoxic and hypoxic conditions. Cells were also injected into either immune-compromised or immune-competent mice and growth of xenograft tumors was assessed. Tumor fragments derived from patients with PDAC were surgically ligated to the pancreas of mice and the growth of tumors was assessed. We performed tissue microarray analyses of 205 human PDAC samples to measure levels of CA9 and associated expression of genes that regulate hypoxia with outcomes of patients using the Cancer Genome Atlas database. Results Under hypoxic conditions, PDAC cells had increased levels of HIF1A and HIF2A, upregulated expression of CA9, and activated glycolysis. Knockdown of KRAS in PDAC cells, or incubation with trametinib, reduced the posttranscriptional stabilization of HIF1A and HIF2A, upregulation of CA9, pHi, and glycolysis in response to hypoxia. CA9 was expressed by 66% of PDAC samples analyzed; high expression of genes associated with metabolic adaptation to hypoxia, including CA9, correlated with significantly reduced survival times of patients. Knockdown or pharmacologic inhibition of CA9 in PDAC cells significantly reduced pHi in cells under hypoxic conditions, decreased gemcitabine-induced glycolysis, and increased their sensitivity to gemcitabine. PDAC cells with knockdown of CA9 formed smaller xenograft tumors in mice, and injection of gemcitabine inhibited tumor growth and significantly increased survival times of mice. In mice with xenograft tumors grown from human PDAC cells, oral administration of SLC-0111 and injection of gemcitabine increased intratumor acidosis and increased cell death. These tumors, and tumors grown from PDAC patient-derived tumor fragments, grew more slowly than xenograft tumors in mice given control agents, resulting in longer survival times. In KrasG12D/Pdx1-Cre/Tp53/RosaYFP genetically modified mice, oral administration of SLC-0111 and injection of gemcitabine reduced numbers of B cells in tumors. Conclusions In response to hypoxia, PDAC cells that express activated KRAS increase expression of CA9, via stabilization of HIF1A and HIF2A, to regulate pH and glycolysis. Disruption of this pathway slows growth of PDAC xenograft tumors in mice and might be developed for treatment of pancreatic cancer