Continuous Spin Representations of the Poincar\'e and Super-Poincar\'e Groups

We construct Wigner's continuous spin representations of the Poincar\'e algebra for massless particles in higher dimensions. The states are labeled both by the length of a space-like translation vector and the Dynkin indices of the {\it short little group} $SO(d-3)$, where $d$ is the space-time dimension. Continuous spin representations are in one-to-one correspondence with representations of the short little group. We also demonstrate how combinations of the bosonic and fermionic representations form supermultiplets of the super-Poincar\'e algebra. If the light-cone translations are nilpotent, these representations become finite dimensional, but contain zero or negative norm states, and their supersymmetry algebra contains a central charge in four dimensions.Comment: 19 page

Effect of Experimental Pain and Visual Feedback on the Accuracy and Precision of Knee Joint Position Sense

Objective: To investigate the effects of experimental pain and visual feedback on the accuracy and precision of knee joint position sense following a period of motor training. Methods: Forty healthy young subjects (age: 24.5 ± 3.6 years old) underwent an 8 day motor training. After the training, they were instructed to perform a knee reposition task before and after receiving an injection of either hypertonic (pain group) or isotonic (control group) saline into the infrapatellar fat pad of the left knee. The Visual Analog Scale (VAS) was recorded for both groups. In each condition, participants were instructed to extend their knee to three predetermined target positions (30°, 45°, and 60°) for 10 repetitions, both with visual feedback (VF) and without visual feedback (NVF). The accuracy and precision of the knee reposition task were measured before and after the injection. Accuracy was determined by calculating the mean difference between the target angle and the actual angle achieved, while precision was determined by calculating the standard deviation of all actual angles. Data were analyzed using two-way ANOVAs and independent-samples t-tests to compare the pain and control groups. Results: The VAS were 4.14 ± 2.48 for the pain group and 0.83 ± 0.89 for the control group. There was a significant decrease in knee accuracy after the injection of hypertonic saline compared to movements before the injection during VF (p=0.009). The pain group showed significantly worse knee accuracy compared to the control group in the relative change of performance during VF (p=0.015). Conclusions: This study demonstrates that experimental knee pain impairs the accuracy of joint position sense, even after a period of motor training. This could serve as a helpful cue for individuals with knee pain to pursue timely treatment, thereby reducing the risk of additional injury. Trial Registration: ClinicalTrials.gov identifier: NCT04146311.</p

The landscape of genetic aberrations in myxofibrosarcoma

Myxofibrosarcoma (MFS) is a rare subtype of sarcoma, whose genetic basis is poorly understood. We analyzed 69 MFS cases using whole-genome (WGS), whole-exome (WES) and/or targeted-sequencing (TS). Newly sequenced genomic data were combined with additional deposited 116 MFS samples. WGS identified a high number of structural variations (SVs) per tumor most frequently affecting the TP53 and RB1 loci, 40% of tumors showed a BRCAness-associated mutation signature, and evidence of chromothripsis was found in all cases. Most frequently mutated/copy number altered genes affected known disease drivers such as TP53 (56.2%), CDKN2A/B (29.7%), RB1 (27.0%), ATRX (19.5%) and HDLBP (18.9%). Several previously unappreciated genetic aberrations including MUC17, FLG and ZNF780A were identified in more than 20% of patients. Longitudinal analysis of paired diagnosis and relapse time points revealed a 1.2-fold mutation number increase accompanied with substantial changes in clonal composition over time. Our study highlights the genetic complexity underlying sarcomagenesis of MFS

A Rapid FACS-Based Strategy to Isolate Human Gene Knockin and Knockout Clones

Gene targeting protocols for mammalian cells remain inefficient and labor intensive. Here we describe FASTarget, a rapid, fluorescent cell sorting based strategy to isolate rare gene targeting events in human somatic cells. A fluorescent protein is used as a means for direct selection of targeted clones obviating the need for selection and outgrowth of drug resistant clones. Importantly, the use of a promoter-less, ATG-less construct greatly facilitates the recovery of correctly targeted cells. Using this method we report successful gene targeting in up to 94% of recovered human somatic cell clones. We create functional EYFP-tagged knockin clones in both transformed and non-transformed human somatic cell lines providing a valuable tool for mammalian cell biology. We further demonstrate the use of this technology to create gene knockouts. Using this generally applicable strategy we can recover gene targeted clones within approximately one month from DNA construct delivery to obtaining targeted monoclonal cell lines

Assessment and Management of Anti-insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome

Context: Insulin autoimmune syndrome (IAS), spontaneous hyperinsulinemic hypoglycemia due to insulin-binding autoantibodies, may be difficult to distinguish from tumoral or other forms of hyperinsulinemic hypoglycemia including surreptitious insulin administration. No standardized treatment regimen exists. Objectives: To evaluate an analytic approach to IAS and responses to different treatments. Design and Setting: Observational study in the UK Severe Insulin Resistance Service. Patients: 6 patients with hyperinsulinemic hypoglycemia and detectable circulating anti-insulin antibody (IA). Main outcome measures: Glycemia, plasma insulin and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), and IA were further characterized using radioligand binding studies. Results: All patients were diagnosed with IAS (5 IgG, 1 IgA) based on high insulin:C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. 1 patient was managed conservatively, 4 were treated with diazoxide without sustained benefit, and 4 were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis. Conclusions: IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin:C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response

Antagonistic Changes in Sensitivity to Antifungal Drugs by Mutations of an Important ABC Transporter Gene in a Fungal Pathogen

Fungal pathogens can be lethal, especially among immunocompromised populations, such as patients with AIDS and recipients of tissue transplantation or chemotherapy. Prolonged usage of antifungal reagents can lead to drug resistance and treatment failure. Understanding mechanisms that underlie drug resistance by pathogenic microorganisms is thus vital for dealing with this emerging issue. In this study, we show that dramatic sequence changes in PDR5, an ABC (ATP-binding cassette) efflux transporter protein gene in an opportunistic fungal pathogen, caused the organism to become hypersensitive to azole, a widely used antifungal drug. Surprisingly, the same mutations conferred growth advantages to the organism on polyenes, which are also commonly used antimycotics. Our results indicate that Pdr5p might be important for ergosterol homeostasis. The observed remarkable sequence divergence in the PDR5 gene in yeast strain YJM789 may represent an interesting case of adaptive loss of gene function with significant clinical implications

The Future Landscape of High-Redshift Galaxy Cluster Science

We describe the opportunities for galaxy cluster science in the high- redshift regime where massive, virialized halos first formed and where star formation and AGN activity peaked. New observing facilities from radio to X-ray wavelengths, combining high spatial/spectral resolution with large collecting areas, are poised to uncover this population.We describe the opportunities for galaxy cluster science in the high- redshift regime where massive, virialized halos first formed and where star formation and AGN activity peaked. New observing facilities from radio to X-ray wavelengths, combining high spatial/spectral resolution with large collecting areas, are poised to uncover this population