Arithmetic Spacetime Geometry from String Theory

An arithmetic framework to string compactification is described. The approach is exemplified by formulating a strategy that allows to construct geometric compactifications from exactly solvable theories at $c=3$. It is shown that the conformal field theoretic characters can be derived from the geometry of spacetime, and that the geometry is uniquely determined by the two-dimensional field theory on the world sheet. The modular forms that appear in these constructions admit complex multiplication, and allow an interpretation as generalized McKay-Thompson series associated to the Mathieu and Conway groups. This leads to a string motivated notion of arithmetic moonshine.Comment: 36 page

Evaluation of Bovine Myosin Heavy Chain Isoforms and Muscle Fiber Cross-Sectional Area on the Eating Quality of 11 Different Beef Muscles

Objective: The objective of this study was to investigate the contribution of muscle fiber type and size on the eating quality of 11 different beef muscles. Study Description: Eleven different beef muscles were utilized from two separate studies. In study 1, shoulder clod, flank, knuckle, mock tender, top sirloin butt, brisket, eye of round, and ribeye were collected from 10 U.S. Department of Agriculture choice carcasses (n = 80), and each muscle was fabricated into steaks at 2 days postmortem. In study 2, strip loin, tri-tip, and heel were collected from 10 USDA low choice carcasses (n = 30). Myofibrillar proteins were extracted and analyzed by immunoblot to determine muscle fiber type. Cross sectional area (CSA) and muscle fiber diameter were determined under the microscope. An average of 400 fibers per sample were analyzed to determine CSA and muscle fiber diameter. Pearson correlation analysis was conducted to determine the relationship between muscle fiber type, CSA, and diameter with the results for the eating quality of beef as determined by a trained panel that were reported in previous studies. Results: In study 1, there was a positive correlation between fiber type 1 and initial juiciness (r = 0.37; P \u3c 0.05), sustained juiciness (r = 0.39; P \u3c 0.05) and lipid flavor (r = 0.41; P \u3c 0.05). Conversely, there was a negative correlation between fiber type 2A and initial juiciness (r = -0.40; P \u3c 0.05) sustained juiciness (r = -0.42; P \u3c 0.05), and lipid flavor (r = -0.45; P \u3c 0.01). Both studies saw a negative correlation between muscle fiber CSA and diameter with connective tissue content (P \u3c 0.05), but positive correlations to overall tenderness (P \u3c 0.05). The Bottom Line: This study shows that muscles predominated by type 1 fibers will likely deliver a higher eating quality experience for consumers, while muscles with more glycolytic fibers 2A and 2X will deliver a less favorable eating experience for consumers. On the other hand, these data also demonstrated that larger muscle fiber CSA and diameter are not necessarily a negative eating quality marker as muscles with those characteristics had less connective tissue and had greater tenderness scores

Interpolated sequences and critical LL-values of modular forms

Recently, Zagier expressed an interpolated version of the Ap\'ery numbers for $\zeta(3)$ in terms of a critical $L$-value of a modular form of weight 4. We extend this evaluation in two directions. We first prove that interpolations of Zagier's six sporadic sequences are essentially critical $L$-values of modular forms of weight 3. We then establish an infinite family of evaluations between interpolations of leading coefficients of Brown's cellular integrals and critical $L$-values of modular forms of odd weight.Comment: 23 pages, to appear in Proceedings for the KMPB conference: Elliptic Integrals, Elliptic Functions and Modular Forms in Quantum Field Theor

Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease

Purpose It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with i) stable PCa post-primary or salvage RT (sPCa), ii) progressing PCa post-RT (pPCa), and iii) de novo metastatic PCa (mPCa). Experimental Design A cohort of 19 patients with diagnostic prostate biopsies (n=6 sPCa, n=5 pPCa, n=8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3’RNA sequencing (3’RNAseq) (n=19), nanoString analysis (n=12) and Illumina 850k methylation (n=8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes (DEGs) and methylated genomic regions (MGRs). Results 18 of 19 samples provided useable 3’RNAseq data. Principal Component Analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ∼600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p<0.0001) in an external cohort. Conclusions 3’RNAseq, nanoString and 850K-methylation analyses are each achievable from historical FFPE diagnostic pre-treatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation

Guidance for Remote Reporting of Digital Pathology Slides During Periods of Exceptional Service Pressure: An Emergency Response from the UK Royal College of Pathologists

Pathology departments must rise to new staffing challenges caused by the coronavirus disease-19 pandemic and may need to work more flexibly for the foreseeable future. In light of this, many pathologists and departments are considering the merits of remote or home reporting of digital cases. While some individuals have experience of this, little work has been done to determine optimum conditions for home reporting, including technical and training considerations. In this publication produced in response to the pandemic, we provide information regarding risk assessment of home reporting of digital slides, summarize available information on specifications for home reporting computing equipment, and share access to a novel point-of-use quality assurance tool for assessing the suitability of home reporting screens for digital slide diagnosis. We hope this study provides a useful starting point and some practical guidance in a difficult time. This study forms the basis of the guidance issued by the Royal College of Pathologists, available at: https://www.rcpath.org/uploads/assets/626ead77-d7dd-42e1-949988e43dc84c97/RCPath-guidance-for-remote-digital-pathology.pdf

Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus

The predictability of virus–host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape

Vinorelbine alternating oral and intravenous plus epirubicin in first-line therapy of metastatic breast cancer: results of a multicentre phase II study

The combination of intravenous (i.v.) vinorelbine and epirubicin is highly active in the treatment of metastatic breast cancer (MBC). In an effort to improve patient convenience, we investigated a regimen alternating i.v. and oral vinorelbine in combination with epirubicin as first-line chemotherapy of patients with MBC. In all, 49 patients with MBC received, as first-line treatment, a combination regimen consisting of i.v. vinorelbine 25 mg m−2 plus epirubicin 90 mg m−2 given on day 1, and oral vinorelbine 60 mg m−2 on day 8 (or day 15 if neutrophils <1500 mm−3) every 3 weeks, in an open-label, multicentre phase II study. Treatment was to be repeated for a maximum of six cycles. The study population had a median age of 55 years, half of the patients had received prior adjuvant chemotherapy and 86% presented a visceral involvement. In all, 25 responses were documented and validated by an independent panel review, yielding response rates of 51% (95% CI: 36–66) in the 49 enrolled patients and 54.5% (95% CI: 39–70) in the 44 evaluable patients. Median durations of progression-free survival and survival were 8 and 20 months, respectively. Neutropenia was the main dose-limiting toxicity, but complications were uncommon, four patients having experienced febrile neutropenia and six having developed neutropenic infection. Other frequently reported adverse events included stomatitis, nausea and vomiting, which were rarely severe. No toxic death was reported. Among patients who received six cycles, global score of quality of life remained stable. This regimen alternating oral and i.v. vinorelbine in combination with epirubicin is effective and safe. Oral vinorelbine on day 8 offers greater convenience to the patient, and decreases the need for i.v. injection and reduces time spent in hospital. Therefore, oral vinorelbine is a convenient alternative to the i.v. form in combination regimens commonly used to treat MBC

Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning

OBJECTIVE Complex phenotypes captured on histological slides represent the biological processes at play in individual cancers, but the link to underlying molecular classification has not been clarified or systematised. In colorectal cancer (CRC), histological grading is a poor predictor of disease progression, and consensus molecular subtypes (CMSs) cannot be distinguished without gene expression profiling. We hypothesise that image analysis is a cost-effective tool to associate complex features of tissue organisation with molecular and outcome data and to resolve unclassifiable or heterogeneous cases. In this study, we present an image-based approach to predict CRC CMS from standard H&E sections using deep learning. DESIGN Training and evaluation of a neural network were performed using a total of n=1206 tissue sections with comprehensive multi-omic data from three independent datasets (training on FOCUS trial, n=278 patients; test on rectal cancer biopsies, GRAMPIAN cohort, n=144 patients; and The Cancer Genome Atlas (TCGA), n=430 patients). Ground truth CMS calls were ascertained by matching random forest and single sample predictions from CMS classifier. RESULTS Image-based CMS (imCMS) accurately classified slides in unseen datasets from TCGA (n=431 slides, AUC)=0.84) and rectal cancer biopsies (n=265 slides, AUC=0.85). imCMS spatially resolved intratumoural heterogeneity and provided secondary calls correlating with bioinformatic prediction from molecular data. imCMS classified samples previously unclassifiable by RNA expression profiling, reproduced the expected correlations with genomic and epigenetic alterations and showed similar prognostic associations as transcriptomic CMS. CONCLUSION This study shows that a prediction of RNA expression classifiers can be made from H&E images, opening the door to simple, cheap and reliable biological stratification within routine workflows