3,539 research outputs found
Unusual formations of the free electromagnetic field in vacuum
It is shown that there are exact solutions of the free Maxwell equations
(FME) in vacuum allowing an existence of stable spherical formations of the
free magnetic field and ring-like formations of the free electric field. It is
detected that a form of these spheres and rings does not change with time in
vacuum. It is shown that these convergent solutions are the result of an
interference of some divergent solutions of FME. One can surmise that these
electromagnetic formations correspond to Kapitsa's hypothesis about
interference origin and a structure of fireball.Comment: Revtex-file, without figures. To get lournal-pdf-copy with figures
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Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent of HER-2/neu Expression
Double transgenic mice overespressing the transforming rat HER-2/neu oncogene and the mutated p53, with both deminant-negative and a gain-of-function properties, display early aggressive and metastasizing parotid tumors. Multiple acinar and ductal hyperplasia foci overexpressing the HER-2/neu gene product are evident at wk 5 and progress to poorly differentiated carcinoma by wk 7. Mice die before wk 18 with invasive carcinomas and multiple metastases that no longer express HER-2/neu. A combination of repeated electroporations of plasmids coding for the extracellular and transmembrane domains of the rat HER-2/neu receptor with systemic IL-12 administrations started when the parotids that present diffuse hyperplasia protected all female and 50% of the male mice until the close of the experiment at wk 40. This combined treatment began when multifocal in situ - carcinomas that were already present cured 33% of the females and 25 % of the males. The most prominent immunologic features associated with the antitumor protection were the production of high titers of anti-HER-2/neu Abs and the nonappearance of cell-mediated cytotoxic reactivity. In conclusion, anti-HER-2/neu vaccination combined with systemic IL-12 control parotid carcinomas as far as p53 mutation makes their growth independent of HER-2/neu expression
LAG-3 enables DNA vaccination to persistently prevent mammary carcinogenesis in HER-2/neu transgenic BALB/c mice
Within 33 weeks of life, all 10 mammary glands of virgin BALB/c mice transgenic for the transforming rat HER-2/neu oncogene under the mammary tumor virus promoter (BALB-neuT mice) progress from atypical hyperplasia to invasive palpable carcinoma. Repeated DNA vaccination with plasmids coding for the extracellular and transmembrane domain of the protein product of rat HER-2/neu (r-p185neu) delayed tumor onset and reduced tumor multiplicity, but this protection eventually declined, and few mice were tumor free at 1 year of age. Association of plasmid vaccination with administration of soluble mouse LAG-3 (lymphocyte activation gene-3/CD223) generated by fusing the extracellular domain of murine LAG-3 to a murine IgG2a Fc portion (mLAG-3Ig) elicited a stronger and sustained protection that kept 70% of 1-year-old mice tumor free. Moreover, this combined vaccination, which was performed when multiple in situ carcinomas were already evident, extended disease-free survival and reduced carcinoma multiplicity. Inhibition of carcinogenesis was associated with markedly reduced epithelial cell proliferation and r-p185neu expression, whereas the few remaining hyperplastic foci were heavily infiltrated by reactive leukocytes. A stronger and enduring r-p185neu-specific cytotoxicity, a sustained release of IFN-γ and interleukin 4, and a marked expansion of both CD8+/CD11b+/CD28+ effector and CD8+/CD11b+/CD28- memory effector T-cell populations were induced in immunized mice. This combined vaccination also elicited a quicker and higher antibody response to r-p185neu, as well as an early antibody isotype switch. These data suggest that the appropriate costimulation provided by mLAG-3Ig enables DNA vaccination to establish an effective protection, probably by enhancing cross-presentation of the DNA coded antigen
Cure of mammary carcinomas in Her-2 transgenic mice through sequential stimulation of innate (neoadjuvant interleukin-12) and adaptive (DNA vaccine electroporation) immunity.
Purpose: Whereas neoadjuvant therapy is emerging as
a treatment option in early primary breast cancer, no data
are available on the use of antiangiogenic and immunomodulatory
agents in a neoadjuvant setting. In a model of
Her-2 spontaneous mammary cancer, we investigated the
efficacy of neoadjuvant interleukin 12 (IL-12) followed by
‘‘immune-surgery’’ of the residual tumor.
Experimental Design: Female BALB/c mice transgenic
for the rat Her-2 oncogene inexorably develop invasive
carcinomas in all their mammary glands by the 23rd week of
age. Mice with multifocal in situ carcinomas received four
weekly i.p. injections of 100 ng IL-12 followed by a 3-week
rest. This course was given four times. A few mice
additionally received DNA plasmids encoding portions of
the Her-2 receptor electroporated through transcutaneous
electric pulses.
Results: The protection elicited by IL-12 in combination
with two DNA vaccine electroporations kept 63% of
mice tumor-free. Complete protection of all 1-year-old mice
was achieved when IL-12-treated mice received four
vaccine electroporations. Pathologic findings, in vitro tests,
and the results from immunization of both IFN-; andimmunoglobulin gene knockout transgenic mice and of
adoptive transfer experiments all show that IL-12 augments
the B- and T-cell response elicited by vaccination and
slightly decreases the number of regulatory T cells. In
addition, IL-12 strongly inhibits tumor angiogenesis.
Conclusions: In Her-2 transgenic mice, IL-12 impairs
tumor progression and triggers innate immunity so markedly
that DNA vaccination becomes effective at late points in time
when it is ineffective on its own
Characterization of the AP-1 μ1A and μ1B adaptins in zebrafish (Danio rerio)
Protein transport between the trans-Golgi network and endosomes is mediated by transport vesicles formed by the adaptor-protein complex AP-1, consisting of the adaptins γ1, β1, μ1, σ1. Mammalia express μ1A ubiquitously and isoform μ1B in polarized epithelia. Mouse γ1 or μ1A 'knock out's revealed that AP-1 is indispensable for embryonic development. We isolated μ1A and μ1B from Danio rerio. Analysis of μ1A and μ1B expression revealed tissue-specific expression for either one during embryogenesis and in adult tissues in contrast to their expression in mammalia. μ1B transcript was detected in organs of endodermal derivation and "knock-down" experiments gave rise to embryos defective in formation of intestine, liver, and pronephric ducts. Development ceased at 7-8 dpf. μ1B is not expressed in murine liver, indicating loss of μ1B expression and establishment of alternative sorting mechanisms during mammalian development
The effects of organizational culture on salesperson customer orientation
В статье исследуются теоретические основы изучаемых вопросов, а также факторы воздействия концепции, ориентированной на клиента. Изучается роль организационной культуры на предприятии; удовлетворение от работы и обязательства работника по отношению к организации и выполнение продавцами их должностных обязанностей. Выдвигаются гипотезы, касающиеся связи организационной культуры и концепции, ориентированной на клиента. Рассматриваются данные тестирования выдвинутых гипотез на базе двух организаций, занимающихся предоставлением услуг; предлагаются результаты проведенного исследовани
High resolution spatial distribution for the hexactinellid sponges Asconema setubalense and Pheronema carpenteri in the Central Cantabrian Sea
In the present work we focus on the distribution of two species of sponges. One of
these is Asconema setubalense, a sponge found in rocky substrate that was sampled
with a photogrammetric vehicle through georeferenced images. The other is Pheronema
carpenteri, which inhabits soft bottoms and was sampled by beam trawl. For the spatial
distribution modeling of both sponges, the geomorphological variables of depth, slope,
broad and fine scale bathymetric position index (BPI), aspect, and types of bottoms
were used, all with a resolution of 32 m. Additionally, layers of silicates and currents near
the bottom were extracted from Copernicus Marine Environment Monitoring Service
(CMEMS), with a resolution of 4 and 9 km, respectively. Due to the low resolution
of the layers, it was considered necessary to validate their use by model comparison,
where those that included these variables turned out to be more explanatory than the
others. The models were developed in a complex continental break of the Central
Cantabrian Sea, which comprises several submarine canyons and a seamount (Le
Danois Bank). On the one hand, a very high resolution (32 m) spatial distribution model
based on A. setubalense presence was developed using the MaxEnt maximum entropy
model. On the other, depending on the availability of density data, generalized additive
models (GAMs) were developed for P. carpenteri distribution, although in this case the
sampler only allowed a maximum resolution of almost 1 Km. For the A. setubalense,
the variables that best explained their distribution were ground types and depth, and
for P. carpenteri, silicates, slope, northness, and eastward seawater velocity. The final
model scores obtained were an AUC of 0.98 for the MaxEnt model, and an R squared
of 0.87 for the GAM model.Postprin
In-situ growth rate assessment of hexactinellid sponge Asconema setubalense using 3D photogrammetric reconstruction
We describe the first application of a non-invasive and novel approach to estimate the
growth rate of Asconema setubalense (Porifera, Hexactinellida) through the use of 3D
photogrammetric methodology. Structure-from-Motion techniques (SfM) were applied
to videos acquired with the Politolana ROTV in the El Cachucho Marine Protected Area
(MPA) (Cantabrian Sea) on three different dates (2014, 2017, and 2019) over six years.
With these data, a multi-temporal study was conducted within the framework of MPA
monitoring. A complete 3D reconstruction of the deep-sea floor was achieved with
Pix4D Mapper Pro software for each date. Having 3D point clouds of the study area
enabled a series of measurements that were impossible to obtain in 2D images. In
3D space, the sizes (height, diameter, cup-perimeter, and cup-surface area) of several
A. setubalense specimens were measured each year. The annual growth rates recorded
ranged from zero (“no growth”) for a large size specimen, to an average of 2.2 cm
year�����1 in cup-diameter, and 2.5 cm year�����1 in height for developing specimens. Von
Bertalanffy growth parameters were estimated. Taking into account the size indicators
used in this study and based on the von Bertalanffy growth model, this sponge reaches
95% maximum size at 98 years of age. During the MPA monitoring program, a high
number of specimens disappeared. This raised suspicions of a phenomenon affecting
the survival of this species in the area. This type of image-based methodology does
not cause damage or alterations to benthic communities and should be employed in
vulnerable ecosystem studies and MPA monitoring.
Keywords: underwater photogrammetry, Asconema setubalense, Marine ProtectedPostprin
Community composition and habitat characterization of a rock sponge aggregation (Porifera, Corallistidae) in the Cantabrian Sea.
Deep-sea sponge-dominated communities are complex habitats considered hotspots
of biodiversity and ecosystem functioning. They are classified as Vulnerable Marine
Ecosystem and are listed as threatened or declining as a result of anthropogenic
activities. Yet, studies into the distribution, community structure and composition of
these habitats are scarce, hampering the development of appropriate management
measures to ensure their conservation. In this study we describe a diverse benthic
community, dominated by a lithistid sponge, found in two geomorphological features
of important conservation status —Le Danois Bank and El Corbiro Canyon— of the
Cantabrian Sea. Based on the analyses of visual transects using a photogrammetric
towed vehicle and samples collected by rock dredge, we characterize the habitat and
the associated community in detail. This deep-sea sponge aggregation was found on
bedrock. It is dominated by one lithistid sponge, Neoschrammeniella aff. bowerbankii
(0.2 ind./m2) and further composed of various sponge species as well as of other benthic
invertebrates such as cnidarians, bryozoans and crustaceans. Using a non-invasive
methodology (SfM – Structure from Motion) and empirical relationships of individuals
size and biomass/volume obtained in laboratory for N. aff. bowerbankii, we were able
to estimate a total biomass of 41 kg and volume of 39 l of this species in the surveyed
area. This approach allows a fine tune methodology for estimating biomass and volume
by image-based-observed area avoiding destructive techniques for this species.Postprin
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