The Geometry of Null Surfaces in Minkowski Space

This paper investigates the geometric properties of null surfaces in the Minkowski space M2;1. Invariants of these surfaces are found using Cartan\u27s method of moving frames. This leads to a complete classi cation of null surfaces. Examples of these surfaces are then given

Thumb Trauma: Bennett Fractures, Rolando Fractures, and Ulnar Collateral Ligament Injuries

Injuries to the thumb are predominated by fractures of the proximal phalanx, ligamentous injuries about the metacarpophalangeal joint, and metacarpal base fractures. This article will attempt to summarize recent advancements within the realm of thumb trauma, with particular attention to Bennett fractures, Rolando fractures, and ulnar collateral ligament injuries. (J Hand Surg 2009;34A:945-952. Copyright © 2009 T HE THUMB PROVIDES up to 40% of hand function. Total disability of the thumb is devastating and equilibrates to a loss of 22% of bodily function. 1 The thumb's uniqueness and versatility in man is primarily due to the position of the thumb axis. The thumb axis is based at the trapeziometacarpal (TM) joint and is pronated and flexed approximately 80°with respect to the other hand metacarpals. This position enables circumduction, which permits opposition and prehension; however this position also exposes the thumb to unique injury. INCIDENCE Recently, Stanton and colleagues examined the incidence of fractures within the tubular bones of the hand. Thumb fractures were found to occur most commonly in children and the elderly. In children (age 0 -16 years), 22% of all tubular bone hand fractures occurred somewhere within the first ray. In retirement age individuals (age Ͼ65 years), 20% of hand fractures occurred in the thumb, whereas only 12% of fractures in young adults (age 17-40 years) were found to occur in the thumb ray. First-ray fractures were half as common in the 17-to 40-year age group when compared with that for the elderly or the pediatric groups. In addition, in the elderly population, the thumb was the most common tubular bone fractured with fracture patterns tending to be oblique and intra-articular. RADIOGRAPHIC EVALUATION In addition to careful physical exam, radiographic imaging is an essential part of a complete evaluation after thumb trauma. Because the thumb sits out of plane from the rest of the hand and fingers, special radiographic views are necessary for appropriate evaluation. A true anteroposterior view of the thumb can be obtained with the Robert's view, which requires that the hand be hyperpronated so that the dorsum of the thumb lies against the radiographic plate. To obtain a true lateral of the TM joint, the palm of the hand must be placed flat on the cassette with the hand pronated 15°to 35°; the beam is then directed 15°distal to proximal. This imaging technique is referred to as the Bett's view of the thumb. This image allows one to evaluate the TM joint and the 3 additional articulations of the trapezium: the trapezoid, the scaphoid, and index metacarpal. Both views are helpful when evaluating fracture displacement and joint congruency. PHALANGEAL FRACTURES The management of extra-articular thumb phalangeal fractures differs from that of finger phalangeal fractures in that some angular displacement or malunion is ac

Bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1) alter connexin 43 phosphorylation in MC3T3-E1 Cells

BACKGROUND: Bone morphogenetic proteins (BMPs) and transforming growth factor-βs (TGF-βs) are important regulators of bone repair and regeneration. BMP-2 and TGF-β1 have been shown to inhibit gap junctional intercellular communication (GJIC) in MC3T3-E1 cells. Connexin 43 (Cx43) has been shown to mediate GJIC in osteoblasts and it is the predominant gap junctional protein expressed in these murine osteoblast-like cells. We examined the expression, phosphorylation, and subcellular localization of Cx43 after treatment with BMP-2 or TGF-β1 to investigate a possible mechanism for the inhibition of GJIC. RESULTS: Northern blot analysis revealed no detectable change in the expression of Cx43 mRNA. Western blot analysis demonstrated no significant change in the expression of total Cx43 protein. However, significantly higher ratios of unphosphorylated vs. phosphorylated forms of Cx43 were detected after BMP-2 or TGF-β1 treatment. Immunofluorescence and cell protein fractionation revealed no detectable change in the localization of Cx43 between the cytosol and plasma membrane. CONCLUSIONS: BMP-2 and TGF-β1 do not alter expression of Cx43 at the mRNA or protein level. BMP-2 and TGF-β1 may inhibit GJIC by decreasing the phosphorylated form of Cx43 in MC3T3-E1 cells

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment