Analysis of a Model Biological Switch

A model mechanism proposed by Murray [Phil. Traps. Roy. Soc. London B, 295 (1981), pp. 473–496] for generating wing patterns and eyespots on butterflies and moths is based on a morphogen (S) activated biological switch for a gene product (g). We analyse one of the resulting partial differential equation systems, namely S_t = DΔS - kS, g_t = k_tS + αg (g-k_2) (g_c-g ), where D,k,k_1 ,k_2 ,g_c > k_2 and α are positive constants. We determine analytically the size of the spatial domain where g → g_c as t → ∞ after an influx of S at the origin. This gives the size of the eyespot in terms of the mechanism parameters. The analytical problem is a nontrivial singular perturbation expansion which we discuss in detail

‘C’était moi mais ce n’était pas moi’: portrayal of the disabled body in Catherine Breillat’s Abus de faiblesse (2013)

Writer/director Catherine Breillat’s most recent film, Abus de faiblesse (2013), explores an important moment of bodily transition: the change from able to disabled body. This semi-autobiographic film follows the story of film director Maud (Breillat’s alter ego), who forms a destructive relationship with a conman, Vilko, after she suffers a disabling stroke. This film shows consistency with Breillat’s previous work in its exploration of the constructed nature of the female body onscreen. In the past the filmmaker has portrayed moments of trauma and transition (such as childbirth, loss of virginity or rape) to subvert processes of objectification. The article argues that Abus de faiblesse challenges and subverts representation of the post-menopausal and disabled body onscreen. The film interrogates binary oppositions such as able/disabled and independence/dependency to challenge representations of the disabled body as ‘other’. With reference to scholarly work on disability and the ageing female body, the article suggests that Maud’s sadomasochistic relationship with Vilko is driven by a quest to retain her subjectivity after her stroke. The article demonstrates that the film dissects the feared and the unknown territory of the ageing female body

Stationary solutions of driven fourth- and sixth-order Cahn-Hilliard type equations

New types of stationary solutions of a one-dimensional driven sixth-order Cahn-Hilliard type equation that arises as a model for epitaxially growing nano-structures such as quantum dots, are derived by an extension of the method of matched asymptotic expansions that retains exponentially small terms. This method yields analytical expressions for far-field behavior as well as the widths of the humps of these spatially non-monotone solutions in the limit of small driving force strength which is the deposition rate in case of epitaxial growth. These solutions extend the family of the monotone kink and antikink solutions. The hump spacing is related to solutions of the Lambert $W$ function. Using phase space analysis for the corresponding fifth-order dynamical system, we use a numerical technique that enables the efficient and accurate tracking of the solution branches, where the asymptotic solutions are used as initial input. Additionally, our approach is first demonstrated for the related but simpler driven fourth-order Cahn-Hilliard equation, also known as the convective Cahn-Hilliard equation

The return of the four- and five-dimensional preons

We prove the existence of 3/4-BPS preons in four- and five-dimensional gauged supergravities by explicitly constructing them as smooth quotients of the AdS_4 and AdS_5 maximally supersymmetric backgrounds, respectively. This result illustrates how the spacetime topology resurrects a fraction of supersymmetry previously ruled out by the local analysis of the Killing spinor equations.Comment: 10 pages (a minor imprecision has been corrected

Standard and Embedded Solitons in Nematic Optical Fibers

A model for a non-Kerr cylindrical nematic fiber is presented. We use the multiple scales method to show the possibility of constructing different kinds of wavepackets of transverse magnetic (TM) modes propagating through the fiber. This procedure allows us to generate different hierarchies of nonlinear partial differential equations (PDEs) which describe the propagation of optical pulses along the fiber. We go beyond the usual weakly nonlinear limit of a Kerr medium and derive an extended Nonlinear Schrodinger equation (eNLS) with a third order derivative nonlinearity, governing the dynamics for the amplitude of the wavepacket. In this derivation the dispersion, self-focussing and diffraction in the nematic are taken into account. Although the resulting nonlinear $PDE$ may be reduced to the modified Korteweg de Vries equation (mKdV), it also has additional complex solutions which include two-parameter families of bright and dark complex solitons. We show analytically that under certain conditions, the bright solitons are actually double embedded solitons. We explain why these solitons do not radiate at all, even though their wavenumbers are contained in the linear spectrum of the system. Finally, we close the paper by making comments on the advantages as well as the limitations of our approach, and on further generalizations of the model and method presented.Comment: "Physical Review E, in press

DNA copy number changes in young gastric cancer patients with special reference to chromosome 19

Only a few cytogenetic and genetic studies have been performed in gastric cancer patients in young age groups. In the present study we used the comparative genomic hybridisation (CGH) method to characterise frequent DNA copy number changes in 22 gastric cancer patients of 45 years or younger and three gastric cancer cell lines established from patients younger than 45 years. Analysis of DNA copy number changes revealed frequent DNA copy number increases at chromosomes 17q (52%), 19q (68%) and 20q (64%). To confirm the CGH results and to characterise the amplicon region on the most frequently amplified chromosome, chromosome 19, we carried out fluorescence in situ hybridisation (FISH) analysis and Southern blot analysis. Fluorescence in situ hybridisation with the bacterial artificial chromosome (BAC) clone mapped to 19q12 indicated a copy number increase in all eight tumour specimens studied. Southern blot analysis of six tumour specimens and three tumour cell lines, with five probes mapped to the 19q12-13.2 region, suggested cyclin E to be one of the candidate target genes in the 19q region for gastric cancer tumorigenesis. Cyclin E protein overexpression was verified in tumours with amplification on chromosome 19. Further studies are required to investigate the biological and clinical significance of 19q amplicon and cyclin E upregulation in gastric cancer of young patient

Pharmacological interventions enhance virus-free generation of TRAC-replaced CAR T cells

Chimeric Antigen Receptor (CAR) redirected T-cells are potent therapeutic options against hematological malignancies. The current dominant manufacturing approach for CAR T cells depends on retroviral transduction. With the advent of gene editing, insertion of a CD19-CAR into the T cell receptor (TCR) alpha constant (TRAC) locus using adeno-associated viruses for gene transfer was demonstrated, and these CD19-CAR T-cells showed improved functionality over their retrovirally transduced counterparts. However, clinical-grade production of viruses is complex and associated with extensive costs. Here, we optimized a virus-free genome editing method for efficient CAR insertion into the TRAC locus of primary human T-cells via nuclease-assisted homology-directed repair (HDR) using CRISPR-Cas and double-stranded template DNA (dsDNA). We evaluated DNA-sensor inhibition and HDR enhancement as two pharmacological interventions to improve cell viability and relative CAR knock-in rates, respectively. While the toxicity of transfected dsDNA was not fully prevented, the combination of both interventions significantly increased CAR knock-in rates and CAR T-cell yield. Resulting TRAC-replaced CD19-CAR T-cells showed antigen-specific cytotoxicity and cytokine production in vitro and slowed leukemia progression in a xenograft mouse model. Amplicon-sequencing did not reveal significant indel formation at potential off-target sites with or without exposure to DNA-repair modulating small molecules. With TRAC-integrated CAR+ T-cell frequencies exceeding 50%, this study opens new perspectives to exploit pharmacological interventions to improve non-viral gene editing in T-cells