Postoperative irradiation after implant placement: A pilot study for prosthetic reconstruction

published_or_final_versio

Antibody Engineering Using Phage Display with a Coiled-Coil Heterodimeric Fv Antibody Fragment

A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to VH and VL for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of VH frameworks and VH-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering

Scalar-mediated ttˉt\bar t forward-backward asymmetry

A large forward-backward asymmetry in $t\bar t$ production, for large invariant mass of the $t\bar t$ system, has been recently observed by the CDF collaboration. Among the scalar mediated mechanisms that can explain such a large asymmetry, only the t-channel exchange of a color-singlet weak-doublet scalar is consistent with both differential and integrated $t\bar t$ cross section measurements. Constraints from flavor changing processes dictate a very specific structure for the Yukawa couplings of such a new scalar. No sizable deviation in the differential or integrated $t\bar t$ production cross section is expected at the LHC.Comment: 22 pages, 1 figure and 2 tables. v2: Corrected Eqs.(50,51,74), adapted Fig.1, Tab.1 and relevant discussions. Extended discussion of top decay and single to

The gene-reduction effect of chromosomal losses detected in gastric cancers

<p>Abstract</p> <p>Background</p> <p>The level of loss of heterozygosity (LOH) that reduces a gene dose and exerts a cell-adverse effect is known to be a parameter for the genetic staging of gastric cancers. This study investigated if the cell-adverse effect induced with the gene reduction was a rate-limiting factor for the LOH events in two distinct histologic types of gastric cancers, the diffuse- and intestinal-types.</p> <p>Methods</p> <p>The pathologic specimens obtained from 145 gastric cancer patients were examined for the level of LOH using 40 microsatellite markers on eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).</p> <p>Results</p> <p>Most of the cancer-associated chromosomes were found to belong to the gene-poor chromosomes and to contain a few stomach-specific genes that were highly expressed. A baseline-level LOH involving one or no chromosome was frequent in diffuse-type gastric cancers. The chromosome 17 containing a relatively high density of genes was commonly lost in intestinal-type cancers but not in diffuse-type cancers. A high-level LOH involving four or more chromosomes tended to be frequent in the gastric cancers with intestinal and mixed differentiation. Disease relapse was common for gastric cancers with high-level LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and for the baseline-level LOH cases through the non-hematogenous route (67%).</p> <p>Conclusions</p> <p>The cell-adverse effect of gene reduction is more tolerated in intestinal-type gastric cancers than in diffuse-type cancers, and the loss of high-dose genes is associated with hematogenous metastasis.</p

Suppression of ABCE1-mediated mRNA translation limits N-MYC-driven cancer progression

The ability of the N-MYC transcription factor to drive cancer progression is well demonstrated in neuroblastoma, the most common extracranial pediatric solid tumor, where MYCN amplification heralds a poor prognosis, with only 11% of high-risk patients surviving past 5 years. However, decades of attempts of direct inhibition of N-MYC or its paralogues has led to the conclusion that this protein is “undruggable.” Therefore, targeting pathways upregulated by N-MYC signaling presents an alternative therapeutic approach. Here, we show that MYCN-amplified neuroblastomas are characterized by elevated rates of protein synthesis and that high expression of ABCE1, a translation factor directly upregulated by N-MYC, is itself a strong predictor of poor clinical outcome. Despite the potent ability of N-MYC in heightening protein synthesis and malignant characteristics in cancer cells, suppression of ABCE1 alone selectively negated this effect, returning the rate of translation to baseline levels and significantly reducing the growth, motility, and invasiveness of MYCN-amplified neuroblastoma cells and patient-derived xenograft tumors in vivo. The growth of nonmalignant cells or MYCN-nonamplified neuroblastoma cells remained unaffected by reduced ABCE1, supporting a therapeutic window associated with targeting ABCE1. Neuroblastoma cells with c-MYC overexpression also required ABCE1 to maintain cell proliferation and translation. Taken together, ABCE1-mediated translation constitutes a critical process in the progression of N-MYC-driven and c-MYC-driven cancers that warrants investigations into methods of its therapeutic inhibition

Syntaxin 16 is a master recruitment factor for cytokinesis

Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively. However, it is not clear how either of these complexes is targeted to the midbody and whether their delivery is coordinated. The trafficking of membrane vesicles between different intracellular organelles involves the formation of soluble N-ethylmalei­mide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane traffic is known to play an important role in cytokinesis, the contribution and identity of intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment of both recycling endosome–associated Exocyst and ESCRT machinery during late telophase, and therefore that these two distinct facets of cytokinesis are inextricably linked

Top pair Asymmetries at Hadron colliders with general Z′Z' couplings

Recently it has been shown that measurement of charge asymmetry of top pair production at LHC excludes any flavor violating $Z'$ vector gauge boson that could explain Tevatron forward-backward asymmetry (FBA). We consider the general form of a $Z'$ gauge boson including left-handed, right-handed vector and tensor couplings to examine FBA and charge asymmetry. To evaluate top pair asymmetries at Tevatron and LHC, we consider $B^0_q$ mixing constraints on flavor changing $Z'$ couplings and show that this model still explain forward-backward asymmetry at Tevatron and charge asymmetry can not exclude it in part of parameters space.Comment: 18 pages, 7 figure

Plasticity and dystonia: a hypothesis shrouded in variability.

Studying plasticity mechanisms with Professor John Rothwell was a shared highlight of our careers. In this article, we discuss non-invasive brain stimulation techniques which aim to induce and quantify plasticity, the mechanisms and nature of their inherent variability and use such observations to review the idea that excessive and abnormal plasticity is a pathophysiological substrate of dystonia. We have tried to define the tone of our review by a couple of Professor John Rothwell's many inspiring characteristics; his endless curiosity to refine knowledge and disease models by scientific exploration and his wise yet humble readiness to revise scientific doctrines when the evidence is supportive. We conclude that high variability of response to non-invasive brain stimulation plasticity protocols significantly clouds the interpretation of historical findings in dystonia research. There is an opportunity to wipe the slate clean of assumptions and armed with an informative literature in health, re-evaluate whether excessive plasticity has a causal role in the pathophysiology of dystonia

LHC diphoton Higgs signal and top quark forward-backward asymmetry in quasi-inert Higgs doublet model

In the quasi-inert Higgs doublet model, we study the LHC diphoton rate for a standard model-like Higgs boson and the top quark forward-backward asymmetry at Tevatron. Taking into account the constraints from the vacuum stability, unitarity, electroweak precision tests, flavor physics and the related experimental data of top quark, we find that compared with the standard model prediction, the diphoton rate of Higgs boson at LHC can be enhanced due to the light charged Higgs contributions, while the measurement of the top quark forward-backward asymmetry at Tevatron can be explained to within $1\sigma$ due to the non-standard model neutral Higgs bosons contributions. Finally, the correlations between the two observables are discussed.Comment: 14 pages, 5 figues. Version to appear in JHEP, some references adde