Efficacy of Combination of Immunotherapies in a Murine in a Murine Squamous Cell Carcinoma Model

Introduction: Head and neck squamous cell carcinomas (HNSCCs) are a type of neoplasm found in the epithelium of the oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx. Recent evidence has demonstrated that 70-90% of HNSCC are associated with Human Papillomavirus (HPV), particularly strain 16 producing oncogenic proteins E6/E7. Currently, HNSCCs are treated with surgery, chemotherapy, and radiation, however immunotherapy with immune checkpoint (PD-1) blocking agents promises to improve outcomes in HNSCC. Objective: This study examined the therapeutic effects of dual and triple combination immunotherapies in a mouse model of HPV-associated HNSCC. Methods: Treatment modalities included a tumor vaccine (attenuated Listeria monocytogenes based vaccine encoding HPV16 E6/E7 (AXAL)), an immune checkpoint inhibitor targeting PD1 (RMP1-14) and topical subtherapeutic radiation. Mice were injected subcutaneously with tumor cells expressing HPV16 E6/E7 (TC-1). When tumors were established, mice were vaccinated with AXAL (3 injections) either alone and/or with anti-PDi and/or with a single dose of radiation. Results: Partial responses were observed in some mice receiving dual combination therapies. Most mice treated with triple immunotherapy revealed complete tumor regression. Discussion: Combination immunotherapy is effective in the TC-1 HNSCC model system. The results obtained set the stage for investing immune mechanism underpinning treatment-associated tumor regression

Immunological assessment of plant-derived avian flu H5/HA1 variants.

Polypeptide variants of the HA1 antigenic domain of the H5N1 avian influenza virus hemagglutinin (HA) molecule were produced in plants using transient and stable expression systems and fused with His/c-myc tags or with mouse or human Fc antibody fragments. The resulting peptides were purified and used for intramuscular immunization of mice. While the recombinant HA1 variants induced a significant serum humoral immune response in the mice, none of the HA1 preparations induced virus-neutralizing antibodies. Fusion with the Fc fragment improved overall yield of the constructs and allowed purification requiring only a single step, but led to no detectable fusion-related enhancement of immunogenicity or quality of immune response

Autonomic Wireless Sensor Networks: A Systematic Literature Review

Autonomic computing (AC) is a promising approach to meet basic requirements in the design of wireless sensor networks (WSNs), and its principles can be applied to efficiently manage nodes operation and optimize network resources. Middleware for WSNs supports the implementation and basic operation of such networks. In this systematic literature review (SLR) we aim to provide an overview of existing WSN middleware systems that address autonomic properties. The main goal is to identify which development approaches of AC are used for designing WSN middleware system, which allow the self-management of WSN. Another goal is finding out which interactions and behavior can be automated in WSN components. We drew the following main conclusions from the SLR results: (i) the selected studies address WSN concerns according to the self-* properties of AC, namely, self-configuration, self-healing, self-optimization, and self-protection; (ii) the selected studies use different approaches for managing the dynamic behavior of middleware systems for WSN, such as policy-based reasoning, context-based reasoning, feedback control loops, mobile agents, model transformations, and code generation. Finally, we identified a lack of comprehensive system architecture designs that support the autonomy of sensor networking

Parámetros Electrocardiográficos en Terneros Holstein Criados en la Altura y a Nivel del Mar

The aim of the study was to compare the electrocardiographic parameters of clinically healthy Holstein calves raised in the high altitude (3827 m) and at sea level (175 m). Parameters under evaluation were rate, rhythm, size and morphology of the waves, segments and intervals and cardiac axis. The tests were performed in an upright position at an amplitude of 1 mV/cm and speed of 25 mm/sec, using the bipolar (I, II, III) and unipolar (AVL, AVR, and aVF) leads. The results showed that heart rate was 87.33 ± 9.77 and 127.40 ± 7.52 at high altitude and at sea level respectively. The heart rate at both locations were considered as regular normal sinus rhythm. The cardiac axis at high altitude was -120.1 ± 7.30° and at sea level was 63.7 ± 3.02°. It is concluded that there were statistical differences (p<0.05) in heart rate, size and morphology of the waves, intervals, segments and cardiac axis due to the physiological adaptation to the high altitudeEl propósito del estudio fue comparar los parámetros electrocardiográficos de terneros Holstein, clínicamente sanos, criados en la altura (3827 msnm) y a nivel del mar (175 msnm). Se evaluó la frecuencia, ritmo, tamaño y morfología de las ondas, segmentos e intervalos y el eje cardíaco. Los exámenes se realizaron en posición erguida, a una amplitud de 1 mV/cm y a velocidad de 25 mm/seg, utilizándose las derivaciones bipolares (I, II, III) y unipolares (avL, avR y avF). Los resultados reflejaron que la frecuencia cardíaca en la altura y a nivel del mar fue de 87.33 ± 9.77 y de 127.40 ± 7.52 latidos por minuto, respectivamente. El ritmo cardíaco en la altura y a nivel del mar tuvo como característica un ritmo regular sinusal normal. El eje cardíaco en la altura fue de -120.1 ± 7.30° y a nivel del mar de 63.7 ± 3.02°. Se concluye que existen diferencias estadísticas en frecuencia cardíaca, tamaño y morfología de las ondas, intervalos, segmentos y el eje cardíaco en los terneros de la altura y a nivel del mar (p<0.05), producto de la adaptación fisiológica a niveles altitudinales mayores

Monitoramento de parâmetros hidrossedimentológicos para valoração de serviços ambientais no âmbito do projeto: Produtores de Água e Floresta (Paf) sub-bacia do Rio Sacra Família.

O recente histórico de crises hídricas cada vez mais recorrentes, tem deixado o governo dos principais centros urbanos do país em alerta, uma vez que a escassez de água coloca em xeque a manutenção de atividades industriais e agrícolas, assim como a garantia de abastecimento e geração de energia destinado à população em geral. Parte deste fenômeno atribui-se aos impactos resultantes da constante degradação ambiental e a imprevisibilidade das mudanças climáticas. Estratégias como o Pagamento por Serviços Ambientais (PSA), surgem da necessidade de reverter o quadro de degradação que chegamos, culminando na perda de importantes Serviços Ecossistêmicos (SEs) em muitos casos, dessa forma, vislumbra dotar de valor econômico as ações voltadas para conservação da natureza e seus atributos, geradas por produtores rurais por meio do princípio "protetor-recebedor". O monitoramento dos parâmetros hidrossedimentológicos pretende preencher uma lacuna na avaliação do impacto efetivo dos tratamentos testados pelo Projeto: Produtores de Águas e Florestas (PAF) sob o balanço hídrico em suas áreas de abrangência contempladas, uma vez que as metodologias de valoração até então adotadas não envolvem variáveis relacionadas à hidrologia das vertentes e a qualidade do solo, mas sim, exclusivamente de caráter vegetativo. A partir de instrumentação implementada na propriedade Sítio Vô Lisse, localizada no município de Mendes, o monitoramento vem sendo conduzido através de 4 parcelas de erosão de (22 m x 4 m) instaladas no terço superior de uma vertente, 16 Sensores de Matriz Granular distribuídos igualmente no interior de cada parcela nas profundidades de 5 – 15 cm e 15 – 25 cm e 2 pluviômetros instalados próximos a estação experimental

Monitoramento do escoamento superficial em um programa de pagamento por serviços ambientais hídrico.

Levando em consideração o atual cenário de degradação ambiental promovido principalmente pela ação antrópica sob o meio ambiente ao longo das últimas décadas, a elaboração de metodologias de valoração e conservação ambiental como os programas de Pagamento por Serviços Ambientais (PSA) surgem como resposta para conservação dos diferentes ecossistemas e garantia de seus serviços assim como seus recursos naturais. Nesse sentido, o presente estudo busca através do monitoramento do escoamento superficial e dos processos erosivos desencadeados pela ação da água, compreender o impacto destes sobre os solos, considerando-os importante variável para a resposta do balanço hídrico das bacias hidrográficas sob regime de programas de PSA hídrico. A metodologia utilizada no monitoramento consistiu na utilização de parcelas de erosão em conjunto de pluviômetros para leitura diária da chuva. Quatro parcelas de 22x4 metros cada uma com duas caixas de 1000 L anexadas foram instaladas em uma propriedade rural contemplada pelo Produtores de Água e Floresta (PAF), onde o estudo vem sendo conduzido. A partir dos primeiros resultados obtidos nessa fase inicial de monitoramento, foram observados 13 eventos de chuva onde o total mensurado foi de 174 mm e em apenas 4 destes eventos houve escoamento superficial assim como perda de sedimentos. Embora cada parcela tenha passado por diferentes tratamentos, o volume total escoado por elas desde o início do monitoramento foi de 6,54 mm, assim como o total de sedimentos foi de 44, 280 (g/m²)

Limits to the energy resolution of a single Air Cherenkov Telescope at low energies

The photon density on the ground is a fundamental quantity in all experiments based on Cherenkov light measurements, e.g. in the Imaging Air Cherenkov Telescopes (IACT). IACT's are commonly and successfully used in order to search and study Very High Energy (VHE) gamma-ray sources. Difficulties with separating primary photons from primary hadrons (mostly protons) in Cherenkov experiments become larger at lower energies. I have calculated longitudinal and lateral density distributions and their fluctuations at low energies basing on Monte Carlo simulations (for vertical gamma cascades and protonic showers) to check the influence of the detector parameters on the possible measurement. Relative density fluctuations are significantly higher in proton than in photon induced showers. Taking into account the limited detector field of view (FOV) implies the changes of these calculated distributions for both types of primary particles and causes an enlargement in relative fluctuations. Absorption due to Rayleigh and Mie scattering has an impact on mean values but does not change relative fluctuations. The total number of Cherenkov photons is more sensitive to the observation height in gamma cascades than in proton showers at low primary energies. The relative fluctuations of the density do not depend on the reflector size in the investigated size range (from 240 m^2 up to 960 m^2). This implies that a single telescope with a mirror area larger than that of the MAGIC telescope cannot achieve better energy resolution than estimated and presented in this paper. The correlations between longitudinal and lateral distributions are much more pronounced for primary gamma-ray than for primary proton showers.Comment: 21 pages, 11 figures, accepted for publication in Journal of Physics