Early transconjunctival needling revision with 5-fluorouracil versus medical treatment in encapsulated blebs: a 12-month prospective study

OBJECTIVE: To compare the efficacy of transconjunctival needling revision with 5-fluorouracil versus medical treatment in glaucomatous eyes with uncontrolled intraocular pressure due to encapsulated bleb after trabeculectomy. METHODS: Prospective, randomized, interventional study. A total of 40 eyes in 39 patients with elevated intraocular pressure and encapsulated blebs diagnosed at a maximum five months after primary trabeculectomy with mitomycin C were included. The eyes were randomized to either transconjunctival needling revision with 5- fluorouracil or medical treatment (hypotensive eyedrops). A maximum of two transconjunctival needling revisions per patient was allowed in the needling arm. All patients underwent follow-up for 12 months. Successful treatment was defined as an intraocular pressure ≤ 18 mmHg and a 20% reduction from baseline at the final follow-up. Clinicaltrial.gov: NCT01887223. RESULTS: Mean intraocular pressure at the final 12-month follow-up was lower in the transconjunctival needling revision group compared to the medical treatment group. Similar numbers of eyes reached the criteria for treatment success in both the transconjunctival needling revision group and the medical treatment group. CONCLUSIONS: Despite similar success rates in eyes randomized to transconjunctival needling revision with 5-fluorouracil compared to eyes receiving medical treatment, there was a significantly lower mean intraocular pressure at 12 months after transconjunctival needling revision

Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation.

Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) where aberrant signaling downstream of this receptor contributes to tumor growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. We previously reported that EGFRvIII is expressed in up to 40% of HNSCC tumors where it is associated with increased proliferation, tumor growth and chemoresistance to antitumor drugs including the EGFR-targeting monoclonal antibody cetuximab. Cetuximab was FDA-approved in 2006 for HNSCC but has not been shown to prevent invasion or metastasis. This study was undertaken to evaluate the mechanisms of EGFRvIII-mediated cell motility and invasion in HNSCC. We found that EGFRvIII induced HNSCC cell migration and invasion in conjunction with increased signal transducer and activator of transcription 3 (STAT3) activation, which was not abrogated by cetuximab treatment. Further investigation showed that EGF-induced expression of the STAT3 target gene HIF1-α, was abolished by cetuximab in HNSCC cells expressing wild-type EGFR under hypoxic conditions, but not in EGFRvIII-expressing HNSCC cells. These results suggest that EGFRvIII mediates HNSCC cell migration and invasion by increased STAT3 activation and induction of HIF1-α, which contribute to cetuximab resistance in EGFRvIII-expressing HNSCC tumors

Upon the existence of short-time approximations of any polynomial order for the computation of density matrices by path integral methods

In this article, I provide significant mathematical evidence in support of the existence of short-time approximations of any polynomial order for the computation of density matrices of physical systems described by arbitrarily smooth and bounded from below potentials. While for Theorem 2, which is ``experimental'', I only provide a ``physicist's'' proof, I believe the present development is mathematically sound. As a verification, I explicitly construct two short-time approximations to the density matrix having convergence orders 3 and 4, respectively. Furthermore, in the Appendix, I derive the convergence constant for the trapezoidal Trotter path integral technique. The convergence orders and constants are then verified by numerical simulations. While the two short-time approximations constructed are of sure interest to physicists and chemists involved in Monte Carlo path integral simulations, the present article is also aimed at the mathematical community, who might find the results interesting and worth exploring. I conclude the paper by discussing the implications of the present findings with respect to the solvability of the dynamical sign problem appearing in real-time Feynman path integral simulations.Comment: 19 pages, 4 figures; the discrete short-time approximations are now treated as independent from their continuous version; new examples of discrete short-time approximations of order three and four are given; a new appendix containing a short review on Brownian motion has been added; also, some additional explanations are provided here and there; this is the last version; to appear in Phys. Rev.

Capsid structure of dsRNA fungal viruses

Most fungal, double-stranded (ds) RNA viruses lack an extracellular life cycle stage and are transmitted by cytoplasmic interchange. dsRNA mycovirus capsids are based on a 120-subunit T = 1 capsid, with a dimer as the asymmetric unit. These capsids, which remain structurally undisturbed throughout the viral cycle, nevertheless, are dynamic particles involved in the organization of the viral genome and the viral polymerase necessary for RNA synthesis. The atomic structure of the T = 1 capsids of four mycoviruses was resolved: the L-A virus of Saccharomyces cerevisiae (ScV-L-A), Penicillium chrysogenum virus (PcV), Penicillium stoloniferum virus F (PsV-F), and Rosellinia necatrix quadrivirus 1 (RnQV1). These capsids show structural variations of the same framework, with 60 asymmetric or symmetric homodimers for ScV-L-A and PsV-F, respectively, monomers with a duplicated similar domain for PcV, and heterodimers of two different proteins for RnQV1. Mycovirus capsid proteins (CP) share a conserved α-helical domain, although the latter may carry different peptides inserted at preferential hotspots. Insertions in the CP outer surface are likely associated with enzymatic activities. Within the capsid, fungal dsRNA viruses show a low degree of genome compaction compared to reoviruses, and contain one to two copies of the RNA-polymerase complex per virion

Constitutive cytoplasmic localization of p21Waf1/Cip1 affects the apoptotic process in monocytic leukaemia

In the present study, we analysed the expression and localization of p21Waf1/Cip1 in normal and malignant haematopoietic cells. We demonstrate that in normal monocytic cells, protein kinase C (PKC)-induced p21 gene activation, which is nuclear factor-κB (NF-κB) independent, results in predominantly cytoplasmic localized p21 protein. In acute monocytic leukaemia (M4, M5), monocytic blasts (N=12) show constitutive cytoplasmic p21 expression in 75% of the cases, while in myeloid leukaemic blasts (N=10), low nuclear and cytoplasmic localization of p21 could be detected, which is also PKC dependent. Constitutive p21 expression in monocytic leukaemia might have important antiapoptotic functions. This is supported by the finding that in U937 cells overexpressing p21, VP16-induced apoptosis is significantly reduced (20.0±0.9 vs 55.8±3.8%, P<0.01, N=5), reflected by a reduced phosphorylation of p38 and JNK. Similarly, AML blasts with high cytoplasmic p21 were less sensitive to VP16-induced apoptosis as compared to AML cases with low or undetectable p21 expression (42.25 vs 12.3%, P<0.01). Moreover, complex formation between p21 and ASK1 could be demonstrated in AML cells, by means of coimmunoprecipitation. In summary, these results indicate that p21 has an antiapoptotic role in monocytic leukaemia, and that p21 expression is regulated in a PKC-dependent and NF-κB independent manner.

Palladium-Catalyzed Carbonyl Allylation Reactions Using Tin Chloride: A Mini-Review

The treatment of allylic alcohols as synthons of carbanions for carbonyl allylation reactions in the presence of a Pd-SnCl2 system has been one of the most interesting and most useful developments demonstrated by Yoshiro Masuyama and co-workers in the field of organic synthesis. The reaction makes use of palladium as an effective catalyst and tin (II) chloride as a low-valent reducing agent which also effectively transforms the allylic group to a nucleophilic group. The organic, as well as organometallic, chemistry of how the transformations occur and how the metals take part in the reaction is of great interest. These could help allow for better optimization of reagents and solvents, for better control of the extent of reaction or yield of desired product, and for possible applications in other reaction systems. This review will focus primarily on the work of Yoshiro Masuyama and various co-workers on carbonyl allylation reactions making use of a Pd-SnCl2 system or substitutes thereof

Li\u27l Daniel: One Year in a Relocation Center

Anniversary commemoration booklet following a cartoon character named Li\u27l Daniel through a full year of shenanigans at the Rohwer Relocation Center in Rohwer, Arkansashttps://scholarlycommons.pacific.edu/jacoby-nisei/1087/thumbnail.jp

Polarised target for Drell-Yan experiment in COMPASS at CERN, part I

In the polarised Drell-Yan experiment at the COMPASS facility in CERN pion beam with momentum of 190 GeV/c and intensity about $10^8$ pions/s interacted with transversely polarised NH$_3$ target. Muon pairs produced in Drel-Yan process were detected. The measurement was done in 2015 as the 1st ever polarised Drell-Yan fixed target experiment. The hydrogen nuclei in the solid-state NH$_3$ were polarised by dynamic nuclear polarisation in 2.5 T field of large-acceptance superconducting magnet. Large helium dilution cryostat was used to cool the target down below 100 mK. Polarisation of hydrogen nuclei reached during the data taking was about 80 %. Two oppositely polarised target cells, each 55 cm long and 4 cm in diameter were used. Overview of COMPASS facility and the polarised target with emphasis on the dilution cryostat and magnet is given. Results of the polarisation measurement in the Drell-Yan run and overviews of the target material, cell and dynamic nuclear polarisation system are given in the part II.Comment: 4 pages, 2 figures, Proceedings of the 22nd International Spin Symposium, Urbana-Champaign, Illinois, USA, 25-30 September 201

The sign problem in Monte Carlo simulations of frustrated quantum spin systems

We discuss the sign problem arising in Monte Carlo simulations of frustrated quantum spin systems. We show that for a class of ``semi-frustrated'' systems (Heisenberg models with ferromagnetic couplings $J_z(r) < 0$ along the $z$-axis and antiferromagnetic couplings $J_{xy}(r)=-J_z(r)$ in the $xy$-plane, for arbitrary distances $r$) the sign problem present for algorithms operating in the $z$-basis can be solved within a recent ``operator-loop'' formulation of the stochastic series expansion method (a cluster algorithm for sampling the diagonal matrix elements of the power series expansion of ${\rm exp}(-\beta H)$ to all orders). The solution relies on identification of operator-loops which change the configuration sign when updated (``merons'') and is similar to the meron-cluster algorithm recently proposed by Chandrasekharan and Wiese for solving the sign problem for a class of fermion models (Phys. Rev. Lett. {\bf 83}, 3116 (1999)). Some important expectation values, e.g., the internal energy, can be evaluated in the subspace with no merons, where the weight function is positive definite. Calculations of other expectation values require sampling of configurations with only a small number of merons (typically zero or two), with an accompanying sign problem which is not serious. We also discuss problems which arise in applying the meron concept to more general quantum spin models with frustrated interactions.Comment: 13 pages, 16 figure

Refractive change following pseudophakic vitrectomy: a retrospective review

Background To assess the occurrence and magnitude of refractive change in pseudophakic eyes undergoing 20 gauge pars plana vitrectomy without scleral buckling and to investigate possible aetiological factors. Methods Retrospective case note review of 87 pseudophakic eyes undergoing 20 gauge pars plana vitrectomy for a variety of vitreo-retinal conditions over a three-year period. Anterior chamber depth (ACD) was measured before and after vitrectomy surgery in 32 eyes. Forty-three pseudophakic fellow eyes were used as controls. Results Eighty-seven eyes (84 patients) were included in the study. Mean spherical equivalent refraction prior to vitrectomy was -0.20 dioptres, which changed to a mean of -0.65 dioptres postoperatively (standard deviation of refractive change 0.59, range-2.13 to 0.75 dioptres) (p < 0.001). Sixty-one of the 87(70%) eyes experienced a myopic shift and 45(52%) eyes had a myopic shift of -0.5 dioptres or more. Mean fellow eye refraction was -0.19 dioptres preoperatively and -0.17 dioptres postoperatively (p = 0.14)(n = 37) Mean ACD preoperatively was 3.29 mm and postoperatively 3.27 mm (p = 0.53) (n = 32) and there was no significant change in ACD with tamponade use. Regression analysis revealed no statistically significant association between changes in anterior chamber depth, as well as a wide variety of other pre-, intra and postoperative factors examined, and the refractive change observed. Conclusion Significant refractive changes occur in some pseudophakic patients undergoing 20 g pars plana vitrectomy. The mean change observed was a small myopic shift but the range was large. The aetiology of the refractive change is uncertain