Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation.

It has been shown that γδ T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of γδ T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third-leading cause of death by cancer in women, is unknown. Here, we investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16 oncoproteins. Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vγ5 <sup>+</sup> γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6 <sup>+</sup> γδ <sup>low</sup> CCR2 <sup>+</sup> CCR6 <sup>-</sup> ) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A <sup>+</sup> γδ T cells could only be observed at the cancer stage (SCC), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16 oncoproteins induce a reorganization of the local epithelial-associated γδ T-cell subpopulations, thereby promoting angiogenesis and cancer development

Rural veterinarian's perception and practices in terms of biosecurity across three European countries

The implementation of biosecurity measures in the animal health and production context is quite broad and aims at limiting the risk of introduction and spread of diseases. Veterinarians play a major role in biosecurity as key informants on the subject for cattle holders, key players in terms of disease prevention/control and eradication programs, as well as key risk factor in terms of disease dissemination. Many biosecurity studies have highlighted professional visitors such as veterinary practitioners as representing a high-risk factor in terms of disease introduction in animal facilities but, to date, very few studies have focused on the implementation level of biosecurity measures by veterinarians. An online survey was implemented in three European countries (Belgium, France and Spain) to assess the behaviour of rural veterinarians towards biosecurity, as well as their implementation level of the biosecurity measures. A descriptive analysis of data and a scoring system were applied to assess the implementation level of measures. The influence of different factors on the implementation level of biosecurity measures was investigated through a negative binomial regression model. The study identified different strengths, weaknesses, possible constraints and solutions in terms of veterinary perspectives. Veterinarians are considered as key informants by the farmers and could therefore play a more active role in terms of guidance and improvement of biosecurity at farm level. Based on the survey outcomes, two factors seemed to influence significantly the implementation level of measures: the country where he/she practices and the veterinarian's perception level of biosecurity. The biosecurity stages with the lowest application level, therefore representing the biggest threats, were bio-exclusion (increasing the risk of disease introduction) and biocontainment (increasing the risk of inter-herd transmission).info:eu-repo/semantics/acceptedVersio

Intra-arterial hepatic fotemustine for the treatment of liver metastases from uveal melanoma: experience in 101 patients

Background: Exclusive liver metastases occur in up to 40% of patients with uveal melanoma associated with a median survival of 2-7 months. Single agent response rates with commonly available chemotherapy are below 10%. We have investigated the use of fotemustine via direct intra-arterial hepatic (i.a.h.) administration in patients with uveal melanoma metastases. Patients and methods: A total of 101 patients from seven centers were treated with i.a.h. fotemustine, administered intra-arterially weekly for a 4-week induction period, and then as a maintenance treatment every 3 weeks until disease progression, unacceptable toxicity or patient refusal. Results: A median of eight fotemustine infusions per patient were delivered (range 1-26). Catheter related complications occurred in 23% of patients; however, this required treatment discontinuation in only 10% of the patients. The overall response rate was 36% with a median overall survival of 15 months and a 2-year survival rate of 29%. LDH, time between diagnosis and treatment start and gender were significant predictors of survival. Conclusions: Locoregional treatment with fotemustine is well tolerated and seems to improve outcome of this poor prognosis patient population. Median survival rates are among the longest reported and one-third of the patients are still alive at 2 year

Acute tubulo-interstitial nephritis leading to acute renal failure following multiple hornet stings

BACKGROUND: Hornet stings are generally associated with local and occasionally anaphylactic reactions. Rarely systemic complications like acute renal failure can occur following multiple stings. Renal failure is usually due to development of acute tubular necrosis as a result of intravascular haemolysis, rhabdomyolysis or shock. Rarely it can be following development of acute tubulo-interstitial nephritis. CASE PRESENTATION: We describe a young male, who was stung on face, head, shoulders and upper limbs by multiple hornets (Vespa orientalis). He developed acute renal failure as a result of acute tubulo-interstitial nephritis and responded to steroids. CONCLUSION: Rare causes of acute renal failure like tubulo-interstitial nephritis should be considered in a patient with persistent oliguria and azotemia following multiple hornet stings. Renal biopsy should be undertaken early, as institution of steroid therapy may help in recovery of renal functio

Feshbach projection-operator formalism to resonance scattering on Bargmann-type potentials

The projection-operator formalism of Feshbach is applied to resonance scattering in a single-channel case. The method is based on the division of the full function space into two segments, internal (localized) and external (infinitely extended). The spectroscopic information on the resonances is obtained from the non-Hermitian effective Hamilton operator $H_{\rm eff}$ appearing in the internal part due to the coupling to the external part. As well known, additional so-called cut-off poles of the $S$-matrix appear, generally, due to the truncation of the potential. We study the question of spurious $S$ matrix poles in the framework of the Feshbach formalism. The numerical analysis is performed for exactly solvable potentials with a finite number of resonance states. These potentials represent a generalization of Bargmann-type potentials to accept resonance states. Our calculations demonstrate that the poles of the $S$ matrix obtained by using the Feshbach projection-operator formalism coincide with both the complex energies of the physical resonances and the cut-off poles of the $S$-matrix.Comment: 12 pages, 9 figure

Evaluation of Phage Display Discovered Peptides as Ligands for Prostate-Specific Membrane Antigen (PSMA)

The aim of this study was to identify potential ligands of PSMA suitable for further development as novel PSMA-targeted peptides using phage display technology. The human PSMA protein was immobilized as a target followed by incubation with a 15-mer phage display random peptide library. After one round of prescreening and two rounds of screening, high-stringency screening at the third round of panning was performed to identify the highest affinity binders. Phages which had a specific binding activity to PSMA in human prostate cancer cells were isolated and the DNA corresponding to the 15-mers were sequenced to provide three consensus sequences: GDHSPFT, SHFSVGS and EVPRLSLLAVFL as well as other sequences that did not display consensus. Two of the peptide sequences deduced from DNA sequencing of binding phages, SHSFSVGSGDHSPFT and GRFLTGGTGRLLRIS were labeled with 5-carboxyfluorescein and shown to bind and co-internalize with PSMA on human prostate cancer cells by fluorescence microscopy. The high stringency requirements yielded peptides with affinities KD∼1 μM or greater which are suitable starting points for affinity maturation. While these values were less than anticipated, the high stringency did yield peptide sequences that apparently bound to different surfaces on PSMA. These peptide sequences could be the basis for further development of peptides for prostate cancer tumor imaging and therapy. © 2013 Shen et al

Response of the Great Barrier Reef to sea level and environmental changes over the past 30,000 years

Previous drilling through submerged fossil coral reefs has greatly improved our understanding of the general pattern of sea-level change since the Last Glacial Maximum, however, how reefs responded to these changes remains uncertain. Here we document the evolution of the Great Barrier Reef (GBR), the world\u27s largest reef system, to major, abrupt environmental changes over the past 30 thousand years based on comprehensive sedimentological, biological and geochronological records from fossil reef cores. We show that reefs migrated seaward as sea level fell to its lowest level during the most recent glaciation (~20.5-20.7 thousand years ago (ka)), then landward as the shelf flooded and ocean temperatures increased during the subsequent deglacial period (~20-10 ka). Growth was interrupted by five reef-death events caused by subaerial exposure or sea-level rise outpacing reef growth. Around 10 ka, the reef drowned as the sea level continued to rise, flooding more of the shelf and causing a higher sediment flux. The GBR\u27s capacity for rapid lateral migration at rates of 0.2-1.5 m yr−1 (and the ability to recruit locally) suggest that, as an ecosystem, the GBR has been more resilient to past sea-level and temperature fluctuations than previously thought, but it has been highly sensitive to increased sediment input over centennial-millennial timescales

Probabilistic Interpretation of Resonant States

We provide probabilistic interpretation of resonant states. This we do by showing that the integral of the modulus square of resonance wave functions (i.e., the conventional norm) over a properly expanding spatial domain is independent of time, and therefore leads to probability conservation. This is in contrast with the conventional employment of a bi-orthogonal basis that precludes probabilistic interpretation, since wave functions of resonant states diverge exponentially in space. On the other hand, resonant states decay exponentially in time, because momentum leaks out of the central scattering area. This momentum leakage is also the reason for the spatial exponential divergence of resonant state. It is by combining the opposite temporal and spatial behaviors of resonant states that we arrive at our probabilistic interpretation of these states. The physical need to normalize resonant wave functions over an expanding spatial domain arises because particles leak out of the region which contains the potential range and escape to infinity, and one has to include them in the total count of particle number.Comment: 11 pages, 5 figures, to appear in Pramana Journal of Physics as an article in the proceedings of Homi Bhabha Centenary Conference on Non-Hermitian Hamiltonians in Quantum Physics PHHQP VIII; this version are with added references as well as some rewording after reviewer's suggestion

Design Considerations for Tumor-Targeted Nanoparticles

Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale1. Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge2. Here, we show that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5–10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys.National Science Foundation (U.S.) (NSF-0070319)National Institutes of Health (U.S.) (NIH GM68762)National Institutes of Health (U.S.) (NIH grant no. R33-EB-000673)National Institutes of Health (U.S.) ( NIH grant no. R01-CA-115296)National Institutes of Health (U.S.) (MIT-Harvard NanoMedical Consortium (1U54-CA119349, a Center of Cancer Nanotechnology Excellence))Bank of AmericaMedical Foundation, inc. (Charles A. King Trust Postdoctoral Research Fellowship Program)cance

Unitarity and Interfering Resonances in pipi Scattering and in Pion Production piN->pipiN

Additivity of Breit-Wigner phases has been proposed to describe interfering resonances in partial waves in $\pi\pi$ scattering. This assumption leads to an expression for partial wave amplitudes that involves products of Breit-Wigner amplitudes. We show that this expression is equivalent to a coherent sum of Breit-Wigner amplitudes with specific complex coefficients which depend on the resonance parameters of all contributing resonances. We use analyticity of $\pi\pi$ partial wave amplitudes to show that they must have the form of a coherent sum of Breit-Wigner amplitudes with complex coefficients and a complex coherent background. The assumption of additivity of Breit-Wigner phases restricts the partial waves to analytical functions with very specific form of residues of Breit-Wigner poles. We argue that the general form provided by the analyticity is more appropriate in fits to data to determine resonance parameters. The partial wave unitarity can be imposed using the modern methods of constrained optimization. We discuss unitarity and the production amplitudes in $\pi N\to\pi\pi N$ and use analyticity in the dipion mass variable to justify the common practice of writing the production amplitudes as a coherent sum of Breit-Wigner amplitudes with free complex coefficients and a complex coherent background in fits to mass spectra with interfering resonances.Comment: 31 page