Classical Propagation of Strings across a Big Crunch/Big Bang Singularity

One of the simplest time-dependent solutions of M theory consists of nine-dimensional Euclidean space times 1+1-dimensional compactified Milne space-time. With a further modding out by Z_2, the space-time represents two orbifold planes which collide and re-emerge, a process proposed as an explanation of the hot big bang. When the two planes are near, the light states of the theory consist of winding M2-branes, describing fundamental strings in a particular ten-dimensional background. They suffer no blue-shift as the M theory dimension collapses, and their equations of motion are regular across the transition from big crunch to big bang. In this paper, we study the classical evolution of fundamental strings across the singularity in some detail. We also develop a simple semi-classical approximation to the quantum evolution which allows one to compute the quantum production of excitations on the string and implement it in a simplified example.Comment: 38 pages, 19 figure

Molecular manipulation and new antimicrobial identification in Acanthamoeba spp

Date on title page is date of submission (November 2021). Date of award is 2022.Acanthamoeba spp. are causative agents of a painful and severe sight-threatening corneal infection that can lead to blindness known as Acanthamoeba keratitis and a subacute disease in the brain which is usually fatal known as granulomatous amoebic encephalitis. Over the last few years, there has been a notorious increase in the number of infections due to Acanthamoeba spp. Poor diagnosis, problems of side effects, toxicity of the current drug treatment and the lack of gene editing tools as potential future therapy contribute to a high mortality rate. Strathclyde Minor Groove Binders (S-MGBs), compounds that bind to the minor groove of the DNA that designed and synthesised at University of Strathclyde were evaluated as potential alternative inhibitors against Acanthamoeba infections. Through cell viability microplate alamarBlue assays 42 S-MGBs were screened from which S-MGB 235 showed the most potent inhibitory effect with IC50 in the nanomolar range against five Acanthamoeba isolates after 24 h and 96 h incubation. Confocal microscopy of trophozoites labelled with fluorescent S-MGB 363 (analogue of S-MGB235) showed this compound in the nucleus, nucleolus and distributed over the granuloplasm causing cell lysis, supporting the potent effect observed in vitro by S-MGB 235. Furthermore, conditions were standardised to establish Galleria mellonella larvae as a new in vivo infection model for A. castellanii Neff infections to assess the efficacy and toxicity of voriconazole, miltefosine and S-MGB 235. Voriconazole and miltefosine did not protect larvae from trophozoite infection, however S-MGB 235 significantly protected larvae when compared with the negative control. It was attempted to establish a CRISPR-Cas9 system for gene editing in Acanthamoeba. The plasmids pBRFPT7NeoCas9 and pBRFPT7PhleoCas9 (containing genes for the red fluorescent protein, T7 RNA polymerase, Cas9 along with the neomycin and phleomycin resistance genes, respectively, were constructed and transfected into A. castellanii Neff trophozoites using Xfect. Expression of RFP was confirmed by fluorescence microscopy and fluorescence-activated cell sorting.Acanthamoeba spp. are causative agents of a painful and severe sight-threatening corneal infection that can lead to blindness known as Acanthamoeba keratitis and a subacute disease in the brain which is usually fatal known as granulomatous amoebic encephalitis. Over the last few years, there has been a notorious increase in the number of infections due to Acanthamoeba spp. Poor diagnosis, problems of side effects, toxicity of the current drug treatment and the lack of gene editing tools as potential future therapy contribute to a high mortality rate. Strathclyde Minor Groove Binders (S-MGBs), compounds that bind to the minor groove of the DNA that designed and synthesised at University of Strathclyde were evaluated as potential alternative inhibitors against Acanthamoeba infections. Through cell viability microplate alamarBlue assays 42 S-MGBs were screened from which S-MGB 235 showed the most potent inhibitory effect with IC50 in the nanomolar range against five Acanthamoeba isolates after 24 h and 96 h incubation. Confocal microscopy of trophozoites labelled with fluorescent S-MGB 363 (analogue of S-MGB235) showed this compound in the nucleus, nucleolus and distributed over the granuloplasm causing cell lysis, supporting the potent effect observed in vitro by S-MGB 235. Furthermore, conditions were standardised to establish Galleria mellonella larvae as a new in vivo infection model for A. castellanii Neff infections to assess the efficacy and toxicity of voriconazole, miltefosine and S-MGB 235. Voriconazole and miltefosine did not protect larvae from trophozoite infection, however S-MGB 235 significantly protected larvae when compared with the negative control. It was attempted to establish a CRISPR-Cas9 system for gene editing in Acanthamoeba. The plasmids pBRFPT7NeoCas9 and pBRFPT7PhleoCas9 (containing genes for the red fluorescent protein, T7 RNA polymerase, Cas9 along with the neomycin and phleomycin resistance genes, respectively, were constructed and transfected into A. castellanii Neff trophozoites using Xfect. Expression of RFP was confirmed by fluorescence microscopy and fluorescence-activated cell sorting

Comment on “Bilaterian Burrows and Grazing Behavior at >585 Million Years Ago”

Pecoits et al. (Reports, 29 June 2012, p. 1693) describe bilaterian trace fossils and assign them an Ediacaran age based on the age of a granite interpreted as intrusive. We argue that the granite is not intrusive but in fact represents the basement of the sedimentary succession. Moreover, we show that identical trace fossils occur in nearby Carboniferous-Permian glacigenic rocks.Fil: Gaucher, Claudio. Universidad de la República; UruguayFil: Poire, Daniel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Bossi, Jorge. Universidad de la República; UruguayFil: Bettucci Sanchez, Leda. Universidad de la República; UruguayFil: Beri, Angeles. Universidad de la República; Urugua

Expansion of the geographic range of Cyatta abscondita Sosa-Calvo et al., 2013 (Hymenoptera: Formicidae)

The presence of the recently described fungus-farming ant genus and species Cyatta abscondita is reported in the northwestern region of Misiones Province in Argentina. A single worker of C. abscondita was collected in a pitfall trap in a mature plantation of Pinus taeda in the Atlantic Forest biome. This finding expands the distribution of the genus and species, extending it farther south in the Neotropics.Fil: Ramos, Carolina Samanta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Santoandre, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Sanchez, Federico Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Zurita, Gustavo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Universidad Nacional de Misiones. Instituto de Biología Subtropical; ArgentinaFil: Filloy, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Survey of Cutaneous Leishmaniasis in Mexico: Leishmania Species, Clinical Expressions and Risk Factors

Leishmaniasis is caused by Leishmania sp., which is transmitted to human beings and reservoirs by phlebotomine sand flies, with worldwide prevalence of approximately 12 million cases with population at risk of approximately 350 million. Cutaneous leishmaniasis (CL) is the most widespread form, causing localized skin lesions (LCL), mucocutaneous leishmaniasis (MCL), or nodular lesions in diffused cutaneous leishmaniasis (DCL). American CL includes LCL and DCL caused by Leishmania mexicana complex and MCL caused by the Leishmania braziliensis complex. In Mexico, CL is distributed in three endemic areas, Gulf of Mexico, Pacific of Mexico, and Central Mexico. In order to monitor clinical outcome and adequately target treatment as well as epidemiologic studies, diagnostic kinetoplast DNA (kDNA), polymerase chain reaction (PCR), Southern and dot blotting, and ITS1 PCR-RFLP of Leishmania DNA were evaluated in samples and Leishmania isolates from patients with cutaneous ulcers from several endemic areas. In Mexico, LCL can be caused by the L. mexicana, L. braziliensis, or both complexes. DCL is caused by L. (L.) mexicana or Leishmania (L.) amazonensis and visceral leishmaniasis (VL) by Leishmania (L.) chagasi and L. (L.) mexicana in immunocompromised patients. The geographic range in which CL is endemic has increased due to urbanization, new settlements, and ecological, social, and educative conditions, which favors its permanence and transmission

Multitarget activities of Müller Glial Cells and low-density Lipoprotein Receptor-Related Protein 1 in proliferative retinopathies

Müller glial cells (MGCs), the main glial component of the retina, play an active role in retinal homeostasis during development and pathological processes. They strongly monitor retinal environment and, in response to retinal imbalance, activate neuroprotective mechanisms mainly characterized by the increase of glial fibrillary acidic protein (GFAP). Under these circumstances, if homeostasis is not reestablished, the retina can be severely injured and GFAP contributes to neuronal degeneration, as they occur in several proliferative retinopathies such as diabetic retinopathy, sickle cell retinopathy and retinopathy of prematurity. In addition, MGCs have an active participation in inflammatory responses releasing proinflammatory mediators and metalloproteinases to the extracellular space and vitreous cavity. MGCs are also involved in the retinal neovascularization and matrix extracellular remodeling during the proliferative stage of retinopathies. Interestingly, low-density lipoprotein receptor-related protein 1 (LRP1) and its ligand α2-macroglobulin (α2M) are highly expressed in MGCs and they have been established to participate in multiple cellular and molecular activities with relevance in retinopathies. However, the exact mechanism of regulation of retinal LRP1 in MGCs is still unclear. Thus, the active participation of MGCs and LRP1 in these diseases, strongly supports the potential interest of them for the design of novel therapeutic approaches. In this review, we discuss the role of LRP1 in the multiple MGCs activities involved in the development and progression of proliferative retinopathies, identifying opportunities in the field that beg further research in this topic area. Summary Statement MGCs and LRP1 are active players in injured retinas, participating in key features such as gliosis and neurotoxicity, neovascularization, inflammation, and glucose control homeostasis during the progression of ischemic diseases, such as proliferative retinopathies.Fil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

EL CENTRALIDAD COMO UN ARQUETIPO SOCIAL DE LA CIUDAD

La centralidad ligada al crecimiento de las ciudades se traduce en un arquetipo social y urbano. En su origen los centros contribuyeron de manera significativa al desarrollo de la vida comunitaria. Los grandes imperios convirtieron a la centralidad en un mecanismo de control y sometimiento social. Una excesiva centralidad producirá tarde o temprano una severa crisis sistémica. El reto de la nueva centralidad radica en recuperar el sentido democrático de los núcleos urbanos.La centralidad ligada al crecimiento de las ciudades se traduce en un arquetipo social y urbano. En su origen los centros contribuyeron de manera significativa al desarrollo de la vida comunitaria. Los grandes imperios convirtieron a la centralidad en un mecanismo de control y sometimiento social. Una excesiva centralidad producirá tarde o temprano una severa crisis sistémica. El reto de la nueva centralidad radica en recuperar el sentido democrático de los núcleos urbanos

Slow Modulation of Ongoing Discharge in the Auditory Cortex during an Interval-Discrimination Task

In this study, we recorded single unit activity from rat auditory cortex while the animals performed an interval-discrimination task. The animals had to decide whether two auditory stimuli were separated by either 150 or 300 ms, and go to the left or right nose poke accordingly. Spontaneous firing in between auditory responses was compared in the attentive versus non-attentive brain states. We describe the firing rate modulation detected during intervals while there was no auditory stimulation. Nearly 18% of neurons (n = 14) showed a prominent neuronal discharge during the interstimulus interval, in the form of an upward or downward ramp towards the second auditory stimulus. These patterns of spontaneous activity were often modulated in the attentive versus passive trials. Modulation of the spontaneous firing rate during the task was observed not only between auditory stimuli, but also in the interval preceding the stimulus. These slow modulatory components could be locally generated or the result of a top-down influence originated in higher associative association areas. Such a neuronal discharge may be related to the computation of the interval time and contribute to the perception of the auditory stimulus

Analysis of the Fracture of Reinforced Concrete Flat Elements Subjected to Explosions. Experimental Procedure and Numerical Validation

Many of the material models most frequently used for the numerical simulation of the behavior of concrete when subjected to high strain rates have been originally developed for the simulation of ballistic impact. Therefore, they are plasticity-based models in which the compressive behavior is modeled in a complex way, while their tensile failure criterion is of a rather simpler nature. As concrete elements usually fail in tensión when subjected to blast loading, available concrete material models for high strain rates may not represent accurately their real behavior. In this research work an experimental program of reinforced concrete fíat elements subjected to blast load is presented. Altogether four detonation tests are conducted, in which 12 slabs of two different concrete types are subjected to the same blast load. The results of the experimental program are then used for the development and adjustment of numerical tools needed in the modeling of concrete elements subjected to blast

IGF-1 Regulates the extracellular level of active MMP-2 and promotes Müller glial cell motility

In ischemic proliferative retinopathies, Müller glial cells (MGCs) acquire migratory abilities. However, the mechanisms that regulate this migration remain poorly understood. In addition, proliferative disorders associated with enhanced activities of matrix metalloproteinases (MMPs) also involve insulin-like growth factor (IGF)-1 participation. Therefore, the main interest of this work was to investigate the IGF-1 effect on the extracellular proteolytic activity in MGCs.Methods: Cell culture supernatants and cell lysates of the human MGC line MIO-M1 stimulated with IGF-1 were analyzed for MMP-2 by zymographic and Western blot analysis. The MGCs´ motility was evaluated by scratch wound assay. The MMP-2, β1-integrin, and focal adhesions were detected by confocal microscopy. The localization of active MMPs and actin cytoskeleton were evaluated by in situ zymography.Results: The IGF-1 induced the activation of canonical signaling pathways through the IGF-1R phosphorylation. Culture supernatants showed a relative decrease in the active form of MMP-2, correlating with an increased accumulation of MMP-2 protein in the MGCs´ lysate. The IGF-1 effect on MMP-2 was abolished by an IGF-1R blocking antibody, αIR3, as well as by the PI3-kinase inhibitor, LY294002. The IGF-1 increased the migratory capacity of MGCs, which was blocked by the GM6001 MMP inhibitor, LY294002 and αIR3. Finally, IGF-1 induced the intracellular distribution of MMP-2 toward cellular protrusions and the partial colocalization with β1-integrin and phospo-focal adhesion kinase signals. Gelatinase activity was concentrated along F-actin filaments.Conclusions: Taken together, these data indicate that IGF-1, through its receptor activation, regulates MGCs´ motility by a mechanism that involves the MMP-2 and PI3K signaling pathway.Fil: Lorenc, Valeria Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Jaldín Fincati, Javier Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Luna Pinto, Jose Domingo. Departamento de Vítreo-retina, Centro Privado de Ojos R; ArgentinaFil: Chiabrando, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Sanchez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin