DNA-vaccination via tattooing induces stronger humoral and cellular immune responses than intramuscular delivery supported by molecular adjuvants

Tattooing is one of a number of DNA delivery methods which results in an efficient expression of an introduced gene in the epidermal and dermal layers of the skin. The tattoo procedure causes many minor mechanical injuries followed by hemorrhage, necrosis, inflammation and regeneration of the skin and thus non-specifically stimulates the immune system. DNA vaccines delivered by tattooing have been shown to induce higher specific humoral and cellular immune responses than intramuscularly injected DNA. In this study, we focused on the comparison of DNA immunization protocols using different routes of administrations of DNA (intradermal tattoo versus intramuscular injection) and molecular adjuvants (cardiotoxin pre-treatment or GM-CSF DNA co-delivery). For this comparison we used the major capsid protein L1 of human papillomavirus type 16 as a model antigen. L1-specific immune responses were detected after three and four immunizations with 50 μg plasmid DNA. Cardiotoxin pretreatment or GM-CSF DNA co-delivery substantially enhanced the efficacy of DNA vaccine delivered intramuscularly by needle injection but had virtually no effect on the intradermal tattoo vaccination. The promoting effect of both adjuvants was more pronounced after three rather than four immunizations. However, three DNA tattoo immunizations without any adjuvant induced significantly higher L1-specific humoral immune responses than three or even four intramuscular DNA injections supported by molecular adjuvants. Tattooing also elicited significantly higher L1-specific cellular immune responses than intramuscularly delivered DNA in combination with adjuvants. In addition, the lymphocytes of mice treated with the tattoo device proliferated more strongly after mitogen stimulation suggesting the presence of inflammatory responses after tattooing. The tattoo delivery of DNA is a cost-effective method that may be used in laboratory conditions when more rapid and more robust immune responses are required

Análisis, diseño y optimización de una red local con intervlans troncalizadas y seguridad de acceso mediante la aplicación de acls

En esta tesis diseñamos una red local con 3 VLANS, las cuales se comunican entre ellas de manera troncalizada, para este propósito empleamos un router que permite la comunicación entre ellas. Sobre nuestro diseño implementamos los 4 principales protocolos de enrutamiento que existen en la actualidad que son: RIP V1, RIP V2, IGRP, y, EIGRP, siendo estos dos últimos protocolos propietarios de la marca CISCO. Realizamos pruebas de conectividad entre los distintos dispositivos que conformaron nuestra red, aplicando cada uno de los protocolos de enrutamiento detallados en este resumen, escogimos el mejor en base a la escalabilidad y convergencia, sobre la configuración de los routers con el protocolo seleccionado se aplicaron ACLS a las interfases tanto físicas como virtuales de los routers, con lo cual comprobamos el correcto funcionamiento de las ACLS. También se efectuaron pruebas de redundancia aplicando Etherchannel, tecnología propietaria de CISCO, se simularon caídas de enlace, verificando de esta manera la continuidad de la conectividad de nuestra re

Integration of Arrival-Time Datasets for Consistent Quality Control: A Case Study of Amphibious Experiments along the Middle America Trench

We have integrated waveform and arrival-onset data collected in Costa Rica as part of the National Science Foundation (NSF)-sponsored Costa Rica Seismogenic Zone Experiment (CRSEIZE) and along central Costa Rica and Nicaragua as part of the German SFB 574 program. The five arrays, composed of different sensor types (one-and three-component land and ocean bottom seismometers and hydrophones), were archived using different software packages (Antelope and SEISAN) and were automatically and manually picked using various quality criteria resulting in a disparate set of pick weights. We evaluate pick quality using automated arrival detection and picking algorithm based on the wavelet transform and Akaike information criterion picker. The consistency of the arrival information over various scales provides a basis for assigning a quality to the analyst pick. Approximately 31% of P arrival times and 26% of S times have been classified as high-quality picks (quality 0-1). An additional 21% of P times and 27% of S arrivals are good quality (quality 2-3). The revised quality picks are mapped directly into new pick weights for inversion studies. We explore the effect of new weighting and removal of poor data by relocating hypocenters through a minimum 1D velocity model and conducting double-difference local earthquake tomography (LET). Analysis of the hypocenter relocation and seismic velocity tomography results suggest that using the improved quality determinations have a greater effect on improving sharpness in the velocity images than on the magnitude of hypocentral movement

Estrategias para mejor la calidad educativa con base en el análisis de la trayectoria académica en el área de ingeniería.

La calidad de las instituciones de educación superior (IES) depende de la pertinencia de los programas ofertados, lo cual se puede conocer mediante diversos indicadores de la trayectoria académica, como el rezago, la reprobación, la eficiencia terminal y la deserción. Estos permiten diagnosticar y determinar el impacto de la educación recibida por los alumnos, así como de la eficiencia de las instituciones (González, 1999), lo que en definitiva sirve para elaborar y aplicar alternativas que permitan fortalecer el funcionamiento de la universidad.El objetivo de esta investigación fue analizar algunos indicadores de la trayectoria académica de alumnos de ingeniería en Computación (ICO) e ingeniaría en Sistemas y Comunicaciones (ISC) (cohorte 2014-2019) del Centro Universitario UAEM Valle de México. Para ello, se desarrolló un trabajo de tipo no experimental, en el cual se tomaron en cuenta los siguientes indicadores: número de alumnos que concluyeron su plan de estudios, grado de avance, deserción escolar, reprobación, tipo de examen (ordinario, extraordinario y título) mediante el cual los alumnos aprueban cuando están cursando por segunda vez una materia y escuela de donde procedían los estudiantes de ambas ingenierías

The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal

BACKGROUND: Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr) on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse. RESULTS: Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr (-/-) mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide. CONCLUSION: Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance

DNA sequence analysis suggests that cytb-nd1 PCR-RFLP may not be applicable to sandfly species identification throughout the Mediterranean region

Molecular methods are increasingly used for both species identification of sandflies and assessment of their population structure. In general, they are based on DNA sequence analysis of targets previously amplified by PCR. However, this approach requires access to DNA sequence facilities, and in some circumstances, it is time-consuming. Though DNA sequencing provides the most reliable information, other downstream PCR applications are explored to assist in species identification. Thus, it has been recently proposed that the amplification of a DNA region encompassing partially both the cytochrome-B (cytb) and the NADH dehydrogenase 1 (nd1) genes followed by RFLP analysis with the restriction enzyme Ase I allows the rapid identification of the most prevalent species of phlebotomine sandflies in the Mediterranean region. In order to confirm the suitability of this method, we collected, processed, and molecularly analyzed a total of 155 sandflies belonging to four species including Phlebotomus ariasi, P. papatasi, P. perniciosus, and Sergentomyia minuta from different regions in Spain. This data set was completed with DNA sequences available at the GenBank for species prevalent in the Mediterranean basin and the Middle East. Additionally, DNA sequences from 13 different phlebotomine species (P. ariasi, P. balcanicus, P. caucasicus, P. chabaudi, P. chadlii, P. longicuspis, P. neglectus, P. papatasi, P. perfiliewi, P. perniciosus, P. riouxi, P. sergenti, and S. minuta), from 19 countries, were added to the data set. Overall, our molecular data revealed that this PCR-RFLP method does not provide a unique and specific profile for each phlebotomine species tested. Intraspecific variability and similar RFLP patterns were frequently observed among the species tested. Our data suggest that this method may not be applicable throughout the Mediterranean region as previously proposed. Other molecular approaches like DNA barcoding or phylogenetic analyses would allow a more precise molecular species identification.This work was supported in part by Instituto de Salud Carlos III (MPY-1248/12) grant and (PI14CIII/00016) funded by AESI. Ivonne Pamela Llanes-Acevedo was granted a student fellowship by COLCIENCIAS/COLFUTURO.S

Individual Profiling of Circulating Tumor Cell Composition and Therapeutic Outcome in Patients with Hepatocellular Carcinoma

AbstractBACKGROUND AND AIMS: Circulating tumor cells (CTCs) have been proposed as a monitoring tool in patients with solid tumors. So far, automated approaches are challenged by the cellular heterogeneity of CTC, especially the epithelial-mesenchymal transition. Recently, Yu and colleagues showed that shifts in these cell populations correlated with response and progression, respectively, to chemotherapy in patients with breast cancer. In this study, we assessed which non-hematopoietic cell types were identifiable in the peripheral blood of hepatocellular carcinoma (HCC) patients and whether their distribution during treatment courses is associated with clinical characteristics. METHODS: Subsequent to few enrichment steps, cell suspensions were spun onto glass slides and further characterized using multi-immunofluorescence staining. All non-hematopoietic cells were counted and individual cell profiles were analyzed per patient and treatment. RESULTS:We detected a remarkable variation of cells with epithelial, mesenchymal, liver-specific, and mixed characteristics and different size ranges. The distribution of these subgroups varied significantly between different patient groups and was associated with therapeutic outcome. Kaplan-Meier logrank test showed that a change in the ratio of epithelial to mesenchymal cells was associated with longer median time to progression (1 vs 15 months; P = .03; hazard ratio = 0.18; 95%confidence interval = 0.01-2.75). CONCLUSIONS: Our data suggest that different CTC populations are identifiable in peripheral blood of HCC patients and, for the first time in HCC, that these individual cell type profiles may have distinct clinical implications. The further characterization and analysis of patients in this ongoing study seems to be warranted

PENGEMBANGAN BAHAN AJAR UNTUK PELATIHAN DAN PENDAMPINGAN PROGRAM IbM KOMUNITAS IBU BELAJAR MATEMATIKA

Penelitian ini merupakan salah satu tahapan dari program pengabdian masyarakat yangdilaksanakan oleh kelompok dosen dan mahasiswa jurusan Matematika UNPAR.Program ini berupa pelatihan dan pendampingan bagi komunitas ibu untuk belajarMatematika. Merujuk pada hasil PISA (Programme for International Student Assessment)tahun 2009 bahwa kemampuan siswa Indonesia pada umumnya buruk dalammenyelesaikan masalah Matematika. Kebanyakan siswa berpandangan bahwaMatematika sulit untuk dipelajari dan kurangnya dukungan orang tua untuk membantusiswa belajar. Berdasarkan kondisi tersebut, kami merancang program untuk membantupihak sekolah untuk memberdayakan para Ibu siswa supaya mereka dapat membantuputra-putrinya untuk belajar Matematika. Tujuan tersebut dapat dicapai bila terjalinkerjasama yang harmonis dan berkesinambungan antara tiga pihak yaitu: sekolah-­‐orangtua-­‐siswa. Bentuk program adalah pendampingan dan pelatihan kepada para ibu sambilmenunggu putra-putri mereka mengikuti kegiatan belajar di sekolah. Tujuan penelitian iniadalah menyiapkan buku ajar Matematika untuk pelatihan dan pendampingan. Langkahpenelitian yang telah dilaksanakan adalah survei kebutuhan, menyusun kerangka danmembuat draf modul, uji validitas dari pakar, revisi, dan modul final. Hasil penelitianberupa bahan ajar yang terdiri dari 40 topik-topik esensial dalam Kurikulum Matematikasekolah dasar. Struktur bahan ajar untuk setiap topik dimulai dengan konsep, contoh soal,latihan, pembahasan, dan kunci jawaban. Buku ajar tersebut siap digunakan untukprogram tersebut

Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries

COVID-19 vaccine; Adverse drug reaction; MyocarditisVacuna contra el COVID-19; Reacció adversa a fàrmacs; MiocarditisVacuna contra el COVID-19; Reacción adversa a medicamentos; MiocarditisBackground: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39–49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed.The project received support from the European Medicines Agency (EMA/2018/23/PE)

Genetic Modifiers of Age at Onset in Carriers of the G206A Mutation in PSEN1 With Familial Alzheimer Disease Among Caribbean Hispanics

IMPORTANCE The present study identified potential genetic modifiers that may delay or accelerate age at onset of familial Alzheimer disease (AD) by examining age at onset in PSEN1 mutation carrier families, and further investigation of these modifiers may provide insight into the pathobiology of AD and potential therapeutic measures. DESIGN, SETTING, AND PARTICIPANTS Using a subset of Caribbean Hispanic families that carry the PSEN1 p.G206A mutation, we performed a 2-stage genome study. The mutation carrier families from an ongoing genetic study served as a discovery set, and the cohort of those with LOAD served as a confirmation set. To identify candidate loci, we performed linkage analysis using 5 p.G206A carrier families (n = 56), and we also performed whole-exome association analysis using 31 p.G206A carriers from 26 families. To confirm the genetic modifiers identified from the p.G206A carrier families, we analyzed the GWAS data for 2888 elderly individuals with LOAD. All study participants were Caribbean Hispanics. RESULTS Linkage analysis of AD identified the strongest linkage support at 4q35 (LOD [logarithm of odds] score, 3.69), and the GWAS of age at onset identified variants on 1p13.1, 2q13, 4q25, and 17p11. In the confirmation stage, genewise analysis identified SNX25, PDLIM3, and 3 SH3 domain genes (SORBS2, SH3RF3, and NPHP1) to be significantly associated with LOAD. Subsequent allelic association analysis confirmed SNX25, PDLIM3, and SORBS2 as genetic modifiers of age at onset of EOAD and LOAD and provided modest support for SH3RF3 and NPHP1. CONCLUSIONS AND RELEVANCE Our 2-stage analysis revealed that SNX25, PDLIM3, and SORBS2 may serve as genetic modifiers of age at onset in both EOAD and LOAD