Compression of an elastic roller between two rigid plates

A closed solution - exact within two-dimensional linear elastostatics - is deduced for the problem appropriate to the compression of an elastic circular cylinder between two smooth, flat and parallel, rigid plates. The boundary displacements obtained for the cylinder involve elliptic integrals, whereas its stress field is given in terms of elementary functions exclusively. The results found for the distribution of the contact pressure and for the width of the contact zone are compared with the corresponding predictions of Hertz's approximate theory, for which elementary corrections are determined by asymptotic means. Analogous corrections are established for a previously available approximate estimate of the diametral compression undergone by the roller, which remains indeterminate in the Hertz treatment of this two-dimensional contact problem

Load-Transfer and Load-Diffusion in Elastostatics

This paper summarizes a recent sequence of theoretical investigations of plane and spatial load-transfer problems in linear elastostatics. Whereas the two-dimensional problems dealt with here have a particular relevance to aircraft structures, those concerning the transfer of load between a bar and a three-dimensional elastic medium are primarily of interest in connection with civil engineering structures and have a bearing on the mechanics of fiber-reinforced materials. An attempt is made to assess the role of alternative mathematical models in the treatment of the physical problems under consideration, to sketch the essential features of the required analysis, and to discuss the principal results obtained

Three-Dimensional Stress Concentration Around a Cylindrical Hole in a Semi-Infinite Elastic Body

This paper contains a three-dimensional solution, exact within classical elastostatics, for the stresses and deformations arising in a half space with a semi-infinite transverse cylindrical hole, if the body -- at infinite distances from its cylindrical boundary -- is subjected to an arbitrary uniform plane field of stress that is parallel to the bounding plane. The solution presented is in integral form and is deduced with the aid of the Papkovich stress functions by means of an especially adapted, unconventional, integral-transform technique. Numerical results for the non-vanishing stresses along the boundary of the hole and for the normal displacement at the plane boundary, corresponding to several values of Poisson's ratio, are also included. These results exhibit in detail the three-dimensional stress boundary layer that emerges near the edges of the hole in the analogous problem for a plate of finite thickness, as the ratio of the plate-thickness to the diameter of the hole grows beyond bounds. The results obtained thus illustrate the limitations inherent 1n the two-dimensional plane-strain treatment of the spatial plane problem; in addition, they are relevant to failure considerations and are of interest 1n connection with experimental stress analysis

PTF11eon/SN2011dh: Discovery of a Type IIb Supernova From a Compact Progenitor in the Nearby Galaxy M51

On May 31, 2011 UT a supernova (SN) exploded in the nearby galaxy M51 (the Whirlpool Galaxy). We discovered this event using small telescopes equipped with CCD cameras, as well as by the Palomar Transient Factory (PTF) survey, and rapidly confirmed it to be a Type II supernova. Our early light curve and spectroscopy indicates that PTF11eon resulted from the explosion of a relatively compact progenitor star as evidenced by the rapid shock-breakout cooling seen in the light curve, the relatively low temperature in early-time spectra and the prompt appearance of low-ionization spectral features. The spectra of PTF11eon are dominated by H lines out to day 10 after explosion, but initial signs of He appear to be present. Assuming that He lines continue to develop in the near future, this SN is likely a member of the cIIb (compact IIb; Chevalier and Soderberg 2010) class, with progenitor radius larger than that of SN 2008ax and smaller than the eIIb (extended IIb) SN 1993J progenitor. Our data imply that the object identified in pre-explosion Hubble Space Telescope images at the SN location is possibly a companion to the progenitor or a blended source, and not the progenitor star itself, as its radius (~10^13 cm) would be highly inconsistent with constraints from our post-explosion photometric and spectroscopic data

FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression

Purpose: Rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression. We assessed rogaratinib efficacy and safety versus chemotherapy in patients with FGFR mRNA-positive advanced/metastatic UC previously treated with platinum chemotherapy. Methods: FORT-1 (ClinicalTrials.gov identifier: NCT03410693) was a phase II/III, randomized, open-label trial. Patients with FGFR1/3 mRNA-positive locally advanced or metastatic UC with ≥ 1 prior platinum-containing regimen were randomly assigned (1:1) to rogaratinib (800 mg orally twice daily, 3-week cycles; n = 87) or chemotherapy (docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2 intravenously once every 3 weeks; n = 88). The primary end point was overall survival, with objective response rate (ORR) analysis planned following phase II accrual. Because of comparable efficacy between treatments, enrollment was stopped before progression to phase III; a full interim analysis of phase II was completed. Results: ORRs were 20.7% (rogaratinib, 18/87; 95% CI, 12.7 to 30.7) and 19.3% (chemotherapy, 17/88; 95% CI, 11.7 to 29.1). Median overall survival was 8.3 months (95% CI, 6.5 to not estimable) and 9.8 months (95% CI, 6.8 to not estimable; hazard ratio, 1.11; 95% CI, 0.71 to 1.72; P = .67). Grade 3/4 events occurred in 37 (43.0%)/4 (4.7%) patients and 32 (39.0%)/15 (18.3%), respectively. No rogaratinib-related deaths occurred. Exploratory analysis of patients with FGFR3 DNA alterations showed ORRs of 52.4% (11/21; 95% CI, 29.8 to 74.3) for rogaratinib and 26.7% (4/15; 95% CI, 7.8 to 55.1) for chemotherapy. Conclusion: To our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response

Diversification of T Cell Responses to Carboxy-terminal Determinants within the 65-kD Heat-shock Protein Is Involved in Regulation of Autoimmune Arthritis

The T cell response to the 65-kD mycobacterial heat-shock protein (Bhsp65) has been implicated in the pathogenesis of autoimmune arthritis. Adjuvant arthritis (AA) induced in the Lewis rat (RT-1l) by injection of Mycobacterium tuberculosis serves as an experimental model for human rheumatoid arthritis (RA). However, the immunological basis of regulation of acute AA, or of susceptibility/resistance to AA is not known. We have defined the specificity of the proliferative T cell responses to Bhsp65 during the course of AA in the Lewis rat. During the early phase of the disease (6–9 d after onset of AA), Lewis rats raised T cell responses to many determinants within Bhsp65, spread throughout the molecule. Importantly, in the late phase of the disease (8–10 wk after onset of AA), there was evidence for diversification of the T cell responses toward Bhsp65 carboxy-terminal determinants (BCTD) (namely, 417–431, 441–455, 465–479, 513–527, and 521–535). Moreover, arthritic rats in the late phase of AA also raised vigorous T cell responses to those carboxy-terminal determinants within self(rat) hsp65 (Rhsp65) that correspond in position to the above BCTD. These results suggest that the observed diversification is possibly triggered in vivo by induction of self(Rhsp65)-reactive T cells. Interestingly, another strain of rat, the Wistar Kyoto (WKY/NHsd) rat (RT-1l), with the same major histocompatibility complex class II molecules as the Lewis rat, was found to be resistant to AA. In WKY rats, vigorous responses to the BCTD, to which the Lewis rat responded only in the late phase of AA, were observed very early, 10 d after injection of M. tuberculosis. Strikingly, pretreatment with the peptides comprising the set of BCTD, but not its amino-terminal determinants, provided significant protection to naive Lewis rats from subsequent induction of AA. Thus, T cell responses to the BCTD are involved in regulating inflammatory arthritis in the Lewis rat and in conferring resistance to AA in the WKY rat. These results have important implications in understanding the pathogenesis of RA and in devising new immunotherapeutic strategies for this disease

Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies

Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella Pathogenicity Island, and acquisition of individual loci, adaptation by gene loss in the more recently emerged tularensis, holarctica, and mediasiatica subspecies occurred and was distinct from evolutionary events that differentiated these subspecies, and the novicida subspecies, from a common ancestor. Our findings are applicable to future studies focused on variations in Francisella subspecies pathogenesis, and of broader interest to studies of genomic pathoadaptation in bacteria

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

On the Diffusion of an Axial Load from an Infinite Cylindrical Bar Embedded in an Elastic Medium

his investigation is concerned with the decay of the resultant axial force in an infinite cylindrical elastic bar that is completely bonded to an all around infinite elastic medium of distinct mechanical properties. The bar is subjected to an axial loading confined to, and uniformly distributed over, one of its cross-sections. First, a solution to this problem, exact within classical three-dimensional elastostatics, is obtained for the special case of a circular cylindrical bar. Next, an approximative solution scheme applicable to a cross-section of arbitrary shape is developed. This scheme is subsequently used to deduce an approximate solution for the bar of circular cross-section. The exact and the approximate solution appropriate to the circular bar are compared with each other, particular attention being given to their asymptotic behavior near the load and at large distances from the applied loading. The present work is preliminary to an approximate treatment of the physically more important problem pertaining to The diffusion of load from a transverse tension-bar that is immersed to a finite depth in an elastic halfspace. In addition, the results established here are of interest in connection with the study of fiber-reinforced materials

Discontinuous deformation gradients near the tip of a crack in finite anti-plane shear: an example

This investigation aims at the elastostatic field near the edges (tips) of a plane crack of finite width in an all-round infinite body, which — at infinity — is subjected to a state of simple shear parallel to the crack edges. The analysis is carried out within the fully nonlinear equilibrium theory of homogeneous and isotropic, incompressible elastic solids. Further, the particular constitutive law employed here gives rise to a loss of ellipticity of the governing displacement equation of equilibrium in the presence of sufficiently severe anti-plane shear deformations. The study reported in this paper is asymptotic in the sense that the actual crack is replaced by a semi-infinite one, while the far field is required to match the elastostatic field predicted near the crack tips by the linearized theory for a crack of finite width. The ensuing global boundary-value problem thus characterizes the local state of affairs in the vicinity of a crack-tip, provided the amount of shear applied at infinity is suitably small. An explicit exact solution to this problem, which is deduced with the aid of the hodograph method, exhibits finite shear stresses at the tips of the crack, but involves two symmetrically located lines of displacement-gradient and stress discontinuity issuing from each crack-tip