Cetuximab ameliorates suppressive phenotypes of myeloid antigen presenting cells in head and neck cancer patients

Background: Myeloid-derived suppressor cells (MDSC) and M2 monocytes/macrophages are two types of suppressive myeloid antigen presenting cells that have been shown to promote tumor progression and correlate with poor prognosis in cancer patients. Tumor antigen specific monoclonal antibodies (mAb) have emerged as important agents for cancer therapy. In addition to the direct inhibition of tumor growth, the Fc portions of the therapeutic mAbs, such as the IgG1 portion of the anti-epidermal growth factor receptor (EGFR) mAb cetuximab, might interact with the Fc-gamma receptors (FcγR) on myeloid cells and modulate their suppressive activity. Methods: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) on the UPCI 08-013 NCT01218048 trial were treated with single-agent cetuximab before surgery. Blood were collected pre- and post-cetuximab treatment to analyze frequency of monocytic MDSC (CD11b+CD14+HLA-DRlo/-), granulocytic MDSC (LIN-CD11b+CD15+) and CD11b+CD14+HLA-DRhi monocytes by flow cytometry. Besides, CD11b+CD14+HLA-DRhi monocytes were sorted for qPCR analysis of IL-10 and IL-12B transcripts. MDSC were generated in vitro with or without coated hIgG1 and tested for suppressive activity in mixed leukocyte reaction (MLR). Naïve monocytes from HNSCC patients co-cultured with tumor cell lines in the presence of cetuximab or hIgG1 were analyzed for M1/2 surface markers and cytokines. Results: We observed significantly increased monocytic MDSC in non-responders and decreased granulocytic MDSC in responders after cetuximab treatment. In addition, circulating CD11b+CD14+HLA-DRhi monocytes of cetuximab responders displayed attenuated M2 polarization, with decreased CD163+ expression and IL-10 transcripts after cetuximab treatment. This beneficial effect appeared to be FcγR dependent, since CD16 ligation reproduced the reversal of suppressive activity of MDSC in vitro. CD14+ naïve monocytes from the co-cultures of tumor cells, cetuximab and HNSCC patient PBMC or purified monocytes were skewed to an M1-like phenotype, with increased expression of HLA-DR, CD86 and production of IL-12 p70. Likewise, reduced M2 features (expression of CD163 and production of IL-10) were found after crosslinking CD16 on the surface of monocytes to cetuximab-coated tumor cells. Conclusion: Our studies demonstrate a novel function of cetuximab in ameliorating suppressive phenotypes of FcγR bearing myeloid cells in cancer patients, which is associated with better clinical outcome of cetuximab-treated patients. Clinical trial registry: # NCT01218048. Registered 7 October 2010

Conflict-free connection numbers of line graphs

A path in an edge-colored graph is called \emph{conflict-free} if it contains at least one color used on exactly one of its edges. An edge-colored graph $G$ is \emph{conflict-free connected} if for any two distinct vertices of $G$, there is a conflict-free path connecting them. For a connected graph $G$, the \emph{conflict-free connection number} of $G$, denoted by $cfc(G)$, is defined as the minimum number of colors that are required to make $G$ conflict-free connected. In this paper, we investigate the conflict-free connection numbers of connected claw-free graphs, especially line graphs. We first show that for an arbitrary connected graph $G$, there exists a positive integer $k$ such that $cfc(L^k(G))\leq 2$. Secondly, we get the exact value of the conflict-free connection number of a connected claw-free graph, especially a connected line graph. Thirdly, we prove that for an arbitrary connected graph $G$ and an arbitrary positive integer $k$, we always have $cfc(L^{k+1}(G))\leq cfc(L^k(G))$, with only the exception that $G$ is isomorphic to a star of order at least~$5$ and $k=1$. Finally, we obtain the exact values of $cfc(L^k(G))$, and use them as an efficient tool to get the smallest nonnegative integer $k_0$ such that $cfc(L^{k_0}(G))=2$.Comment: 11 page

Perception of Cantonese Parkinsonian speech

Abstract no. 1pSC18published_or_final_versio

Coherent oscillations and giant edge magnetoresistance in singly connected topological insulators

A topological insulator has a pair of extended states at the edge in the bulk insulating regime. We study a geometry in which such edge states will manifest themselves in a qualitative manner through periodic oscillations in the magnetoconductance of a singly connected sample coupled to leads through narrow point contacts. Detailed calculations identify the parameters for which these oscillations are expected to be the strongest, and also show their robustness to disorder. Such oscillations can be used as a spectroscopic tool of the edge states. A large change in the device resistance at small B, termed giant edge magnetoresistance, can have potential for application. © 2009 The American Physical Society.published_or_final_versio

An experimental study of exhaled substance exposure between two standing manikins

Conference Theme: Airborne Infection Control - Ventilation, IAQ & EnergyTransmission of the exhaled substances from one person to another in indoor environment is influenced by many individual factors. The impacts of these factors for two face-to-face standing persons are investigated by evaluating the exposure of the substances in a room ventilated by displacement. Experiments employing two breathing thermal manikins are conducted in a full-scale test room. The geometry of the test room is 4.2 m (length) × 3.6 m (width) × 2.6 m (height). The distance between two manikins is 0.8 m, which is regarded as a common distance between two persons ...postprin

Bott periodicity and stable quantum classes

We use Bott periodicity to relate previously defined quantum classes to certain "exotic Chern classes" on $BU$. This provides an interesting computational and theoretical framework for some Gromov-Witten invariants connected with cohomological field theories. This framework has applications to study of higher dimensional, Hamiltonian rigidity aspects of Hofer geometry of $\mathbb{CP} ^{n}$, one of which we discuss here.Comment: prepublication versio

Gaggle on the Gavel: Designing an Interactive Website to Create a Community of Lawyers

Law is behind other industries and professions in its implementation of technolo-gy that could make the practice of law and the delivery of legal services more ef-fective and satisfying. Although there has been considerable development in le-gal technology over the past few years, research identified the need for an interac-tive LinkedIn-style online community for lawyers to communicate other lawyers. Such a community would be particularly beneficial for solo practitioners, lawyers in small firms and lawyers in rural communities and would also provide a con-venient way to connect with lawyers for referrals and recommendations, for spe-cialized expertise and to develop contacts in different geographic locations. Ten-tatively titled Gaggle on the Gavel is an attempt to create such a community that would gather a number of attractive features and functionality under one umbrella and be compliant with the rules of professional conduct with respect to client con-fidentiality, security, advertising and solicitation. A system has been designed, prototyped and revised based on feedback from a focus group of lawyers

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

Pathological behaviour of the scalar graviton in Ho\v{r}ava-Lifshitz gravity

We confirm the recent claims that, in the infrared limit of Ho\v{r}ava-Lifshitz gravity, the scalar graviton becomes a ghost if the sound speed squared is positive on the flat de Sitter and Minkowski background. In order to avoid the ghost and tame the instability, the sound speed squared should be negative and very small, which means that the flow parameter $\lambda$ should be very close to its General Relativity (GR) value. We calculate the cubic interactions for the scalar graviton which are shown to have a similar structure with those of the curvature perturbation in k-inflation models. The higher order interactions become increasing important for a smaller sound speed squared, that is, when the theory approaches GR. This invalidates any linearized analysis and any predictability is lost in this limit as quantum corrections are not controllable. This pathological behaviour of the scalar graviton casts doubt on the validity of the projectable version of the theory.Comment: 7 pages, references added; v3: Typos corrected, minor changes to text and precise determination of the strong coupling scale. Replaced to match published version

Shear waves induced by moving needle in MR Elastography

Magnetic Resonance Elastography (MRE) is a phase contrast-based method for observing shear wave propagation in a material to determine its stiffness. The objective of this study was to determine whether shear waves suitable for MRE can be induced using a moving acupuncture needle. Tissue-simulating bovine gel phantom and a 0.4mm diameter acupuncture needle were used in the experiment. The results showed that observable shear waves could be induced in the gel phantom by cyclic needle motion. The observed wavelength varied with excitation frequency, as expected. Generating shear waves using moving needles may be a useful tool to study the basic mechanism of acupuncture with MRE. Further study will be conducted to observe the wave motion in inhomogeneous media and acupuncture-induced effects in invivo studies.published_or_final_versio