Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for synaptic stripping by cortical microglia

Recent studies have described significant demyelination and microglial activation in the cerebral cortex of brains from multiple sclerosis patients. To date, however, experimental models of cortical demyelination or cortical inflammation have not been extensively studied. In this report we describe focal cortical inflammation induced by stereotaxic injection of killed bacteria (BCG), followed 1 month later by subcutaneous injection of the same antigen, a protocol that overcomes the immune privilege of the cortex. Intracerebral BCG injection produced focal microglial activation at the injection site (termed acute lesion). Ten days after peripheral challenge (termed immune‐mediated lesion), larger areas and higher densities of activated microglia were found near the injection site. In both paradigms, activated microglia and/or their processes closely apposed neuronal perikarya and apical dendrites. In the immune‐mediated lesions, ∼45% of the axosomatic synapses was displaced by activated microglia. Upon activation, therefore, cortical microglial migrate to and strip synapses from neuronal perikarya. Since neuronal pathology was not a feature of either the acute or immune‐mediated lesion, synaptic stripping by activated microglia may have neuroprotective consequences. © 2006 Wiley‐Liss, Inc.
Enhanced AOMDV for energy conservation in hybrid ad hoc networks

Hybrid ad hoc networks are a combination of a fixed network, a base station or free standing mobile ad hoc network MANET. The energy conservation is a major issue in hybrid ad hoc network with limited battery life of mobile terminals. The lifetime of a network will be improved by suitably reducing the requirement of power for connections. This paper proposed a novel energy efficient ad hoc on-demand multipath distance vector EEAOMDV routing protocol that uses ad hoc on demand multipath distance vector AOMDV routing protocol as a basic routing strategy. The selected route satisfies quality of service in energy stable and the delay constraint on the application. The operation of EEAOMDV has three phases. In the first route discovery phase, the delay and energy constraints are built into the AOMDV route discovery mechanism. During link failure, the second phase is invoked to search for an energy stable alternate path locally. The third phase chooses the optimal path from available multiple paths from source to destination pair in the hybrid network. Simulation was performed to determine the packet delivery ratio, routing overhead, throughput, end-to-end delay and average energy consumption are experienced by varying nodes and pause time.
Enhancing Exemplar-Based Posteriors for Speech Recognition Tasks

Posteriors generated from exemplar-based sparse representation methods are often learned to minimize reconstruction error of the feature vectors. These posteriors are not learned through a discriminative process linked to the word error rate (WER) objective of a speech recognition task. In this paper, we explore modeling exemplar-based posteriors to address this issue. We ﬁrst explore posterior modeling by training a Neural Network using exemplar-based posteriors as inputs. This produces a new set of posteriors which have been learned to minimize a cross-entropy measure, and indirectly frame error rate. Second, we take the new NN posteriors and apply a tied mixture smoothing technique to these posteriors, making them more suited for a speech recognition task. On the TIMIT task, we show that using a NN model, we can improve the performance of our sparse representations by 1.3% absolute, achieving a PER of 19.0% by modeling SR posteriors with a NN. Furthermore, taking these NN posteriors and applying further smoothing techniques, we improve the PER to 18.7%, one of the best results reported in the literature on TIMIT.
Characteristics of children with microbiologically confirmed invasive bacterial infections in the emergency department

Background Determination of the characteristics of paediatric invasive bacterial infections (IBI) is essential for early identification of children requiring immediate antibiotic therapy. The main objective is to characterize the emergency presentation of the IBI among children aged younger than 14 years. Patients and methods A prospective registry-based cohort study including all patients aged younger than 14 years diagnosed with confirmed IBI (culture or genomic detection using the polymerase chain reaction) was carried out in a paediatric emergency department between 2008 and 2015. Severity criteria were as follows: death, sequelae or admission to the ICU. Results Of the 223 IBIs reported, 187 (83.9%) corresponded to previously healthy patients (median age=19 months) and 165 (74%) were well appearing. The most common diagnoses were occult bacteraemia [60 (26.9%)] and sepsis [56 (25.1%)]. The most frequent pathogens were Streptococcus pneumoniae [68 (30.5%)] and Neisseria meningitidis [42 (18.8%)]. Four (1.8) patients died (S. pneumoniae, 2) and eight (3.5%) had sequelae (S. pneumoniae, 5). The diagnoses and clinical characteristics of the children varied significantly depending on the isolated pathogen. Duration of fever less than 24 h, symptoms other than fever and not being well-appearing upon arrival to the emergency department were independent risk factors for greater severity (area under the receiver operating characteristics curve=0.805; 95% confidence interval: 0.741–0.868). Conclusion IBIs are commonly diagnosed in previously healthy and well-appearing young children. S. pneumoniae was responsible for the majority of deaths or sequelae. Short duration of fever, symptoms other than fever and not being stable on arrival are associated with greater severity.
Virus-Like Particles as Carriers for T-Cell Epitopes: Limited Inhibition of T-Cell Priming by Carrier-Specific Antibodies

ABSTRACT Virus-like particles (VLPs) are able to induce cytotoxic T-cell responses in the absence of infection or replication. This makes VLPs promising candidates for the development of recombinant vaccines. However, VLPs are also potent inducers of B-cell responses, and it is generally assumed that such VLP-specific antibodies interfere with the induction of protective immune responses, a phenomenon summarized as carrier suppression. In this study, we investigated the impact of preexisting VLP-specific antibodies on the induction of specific cytotoxic T-cell and Th-cell responses in mice. The data show that VLP-specific antibodies did not measurably reduce antigen presentation in vitro or in vivo. Nevertheless, T-cell priming was slightly reduced by antigen-specific antibodies; however, the overall reduction was limited and vaccination with VLPs in the presence of VLP-specific antibodies still resulted in protective T-cell responses. Thus, carrier suppression is unlikely to be a limiting factor for VLP-based T-cell vaccines.
Potential distribution and conservation of the Colobosauroides carvalhoi Soares and Caramaschi , 1998 : a rare and endemic lizard of Northeast Brazil

Ecological niche modeling has contributed to the investigation of the geographical distribution and conservation of rare or little recorded species. Therefore, we studied the known and potential distributions of Colobosauroides carvalhoi Soares and Caramaschi 1998 and discuss the implications for its conservation. Data were obtained by manual collections made in quarterly samplings in three different regions, considering the regions with occurrence records and surrounding areas. The known distribution was determined by occurrence records and literature data, and potential distribution was estimated with an ecological niche model by the MaxEnt algorithm. Twenty-five specimens were collected exclusively in forest formations of Caatinga and Caatinga-Cerrado. Our data corroborated the relative rarity of C. carvalhoi and reflected the biogeographical history of the group, where it is restricted to forest formations with milder environmental conditions. The occurrence records indicated new records of C. carvalhoi, but the known distribution value is compatible with a restricted distribution. The ecological niche model estimated few areas with environmental suitability for the species and corroborated the restricted and relict distribution patterns. Finally, the known and potential distribution values were compatible with criteria for threatened species. These results suggest a worrisome scenario for C. carvalhoi conservation. However, the limited data about the species population do not allow the proper definition of its conservation status. Therefore, we suggest using potential distribution values with alternative criteria for redefining the conservation status of C. carvalhoi and the development of new studies that support a better assessment of its conservation aspects.
Endothelin ETA Receptor Blockade, by Activating ETB Receptors, Increases Vascular Permeability and Induces Exaggerated Fluid Retention

Endothelin (ET) receptor antagonists have been associated with fluid retention. It has been suggested that, of the two endothelin receptor subtypes, ETB receptors should not be blocked, because of their involvement in natriuresis and diuresis. Surprisingly, clinical data suggest that ETA-selective antagonists pose a greater risk of fluid overload than dual antagonists. The purpose of this study was to evaluate the contribution of each endothelin receptor to fluid retention and vascular permeability in rats. Sitaxentan and ambrisentan as ETA-selective antagonists and bosentan and macitentan as dual antagonists were used as representatives of each class, respectively. ETA-selective antagonism caused a dose-dependent hematocrit/hemoglobin decrease that was prevented by ETB-selective receptor antagonism. ETA-selective antagonism led to a significant blood pressure reduction, plasma volume expansion, and a greater increase in vascular permeability than dual antagonism. Isolated vessel experiments showed that ETA-selective antagonism increased vascular permeability via ETB receptor overstimulation. Acutely, ETA-selective but not dual antagonism activated sympathetic activity and increased plasma arginine vasopressin and aldosterone concentrations. The hematocrit/hemoglobin decrease induced by ETA-selective antagonism was reduced in Brattleboro rats and in Wistar rats treated with an arginine vasopressin receptor antagonist. Finally, the decrease in hematocrit/hemoglobin was larger in the venous than in the arterial side, suggesting fluid redistribution. In conclusion, by activating ETB receptors, endothelin receptor antagonists (particularly ETA-selective antagonists) favor edema formation by causing: 1) fluid retention resulting from arginine vasopressin and aldosterone activation secondary to vasodilation, and 2) increased vascular permeability. Plasma volume redistribution may explain the clinical observation of a hematocrit/hemoglobin decrease even in the absence of signs of fluid retention.
Surrogate Constraints Algorithm for Reliability Optimization Problems with Two Constraints

This paper presents an algorithm (called the N&M algorithm) for solving pure-integer separable nonlinear programming problems with two constraints. The N&M algorithm uses surrogate constraints and solves a given problem by effectively generating values of surrogate multiplier (i.e., surrogate problems) and solving the surrogate problems. Examples show that the N&M algorithm is superior to dynamic programming using the Lagrange multiplier in terms of number of iterations and narrowness of gap.
Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis

Lymph nodes (LNs) are at the center of adaptive immune responses. Various exogenous substances are transported into LNs and a series of immune responses ensue after recognition by antigen–specific lymphocytes. Although humanized mice have been used to reconstitute the human immune system, most lack LNs due to deficiency of the interleukin (IL)-2Rγ gene (cytokine common γ chain, γc). In this study, we established a transgenic strain, NOG-pRORγt-γc, in the NOD/shi-scid-IL-2Rγnull (NOG) background, in which the γc gene was expressed in a lymph-tissue inducer (LTi) lineage by the endogenous promoter of RORγt. In this strain, LN organogenesis was normalized and the number of human T cells substantially increased in the periphery after reconstitution of the human immune system by human hematopoietic stem cell transplantation. The distribution of human T cells differed between NOG-pRORγt-γc Tg and NOG-non Tg mice. About 40% of human T cells resided in LNs, primarily the mesenteric LNs. The LN-complemented humanized mice exhibited antigen-specific immunoglobulin G responses together and an increased number of IL-21+–producing CD4+ T cells in LNs. This novel mouse strain will facilitate recapitulation of human immune responses.
Membrane Association and Dimerization of a Cysteine-Rich, 16-Kilodalton Polypeptide Released from the C-Terminal Region of the Coronavirus Infectious Bronchitis Virus 1a Polyprotein

ABSTRACT More than 10 mature proteins processed from coronavirus gene 1-encoded polyproteins have been identified in virus-infected cells. Here, we report the identification of the most C-terminal cleavage product of the 1a polyprotein as a 16-kDa protein in infectious bronchitis virus-infected Vero cells. Indirect immunofluorescence demonstrated that the protein exhibits a distinct perinuclear punctate staining pattern, suggesting that it is associated with cellular membranes. Positive staining observed on nonpermeabilized cells indicates that the protein may get transported to the cell surface, but no secretion of the protein out of the cells was observed. Treatment of the membrane fraction prepared from cells expressing the 16-kDa protein with Triton X-100, a high pH, and a high concentration of salts showed that the protein may be tightly associated with intracellular membranes. Dual-labeling experiments demonstrated that the 16-kDa protein colocalized with the 5′-bromouridine 5′-triphosphate-labeled viral RNA, suggesting that it may be associated with the viral replication machinery. Sequence comparison of the 16-kDa protein with the equivalent products of other coronaviruses showed multiple conserved cysteine residues, and site-directed mutagenesis studies revealed that these conserved residues may contribute to dimerization of the 16-kDa protein. Furthermore, increased accumulation of the 16-kDa protein upon stimulation with epidermal growth factor was observed, providing preliminary evidence that the protein might be involved in the growth factor signaling pathway.
Differential species-specific ectoparasitic mite intensities in two intimately coexisting sibling bat species: resource-mediated host attractiveness or parasite specialization?

Summary 1 The mechanisms underlying host choice strategies by parasites remain poorly understood. We address two main questions: (i) do parasites prefer vulnerable or well-fed hosts, and (ii) to what extent is a parasite species specialized towards a given host species? 2 To answer these questions, we investigated, both in the field and in the lab, a host–parasite system comprising one ectoparasitic mite (Spinturnix myoti) and its major hosts, two sibling species of bats (Myotis myotis and M. blythii), which coexist intimately in colonial nursery roosts. We exploited the close physical associations between host species in colonial roosts as well as naturally occurring annual variation in food abundance to investigate the relationships between parasite intensities and (i) host species and (ii) individual nutritional status. 3 Although horizontal transmission of parasites was facilitated by the intimate aggregation of bats within their colonial clusters, we found significant interspecific differences in degree of infestation throughout the 6 years of the study, with M. myotis always more heavily parasitized than M. blythii. This pattern was replicated in a laboratory experiment in which any species-specific resistance induced by exploitation of different trophic niches in nature was removed. 4 Within both host species, S. myoti showed a clear preference for individuals with higher nutritional status. In years with high resource abundance, both bat hosts harboured more parasites than in low-resource years, although the relative difference in parasite burden across species was maintained. This pattern of host choice was also replicated in the laboratory. When offered a choice, parasites always colonized better-fed individuals. 5 These results show first that host specialization in our study system occurred. Second, immediate parasite choice clearly operated towards the selection of hosts in good nutritional state.
A novel Depleted Monolithic Active Pixel Sensor for future High Energy Physics Detectors

El Gran Colisionador de Hadrones (LHC) tiene previsto aumentar su luminosidad hasta siete veces su valor actual con el objetivo de ampliar su actual programa de fisica. Esta mejora se conoce con el nombre de High Luminosity LHC (HL-LHC) y esta prevista para el ano 2024-2026. El actual Inner Detector (ID) del detector de ALTAS sera completamente reemplazado por uno nuevo para ajustarse a los rigurosos requisitos que impone el HL-LHC. Nuevos detectores de pixeles estan siendo investigados para su utilizacion en todo el ID cuando el HL-LHC entre en operacion. La utilizacion de sensores de pixeles tipo monolitico dentro del ID de ATLAS supondria una nueva era para los detectores de pixeles en fisica de altas energias debido a sus muchas ventajas con respecto a las tecnologias que se usan actualmente. Las principales ventajas son: mejor resolucion espacial, menor densidad, mayor rendimiento, y menor coste. En este contexto, un nuevo tipo de sensor monolitico conocido como Depleted Monolithic Active Pixel Sensor on silicon-on-insulator ha sido investigado en esta tesis. El capitulo 1 describe el LHC, el experimento ATLAS, y las mejoras previstas para el HL-LHC. Este capitulo tambien describe los requerimientos y desafios del futuro Inner Detector, al ser el subdetector mas cercano al punto de interaccion. El capitulo 2 describe la base de los detectores de particulas en fisica de altas energias. Este capitulo abarca la interaccion de particulas con la materia, los conceptos basicos para la construccion de un detector de pixeles, y la resolucion de momento transverso, vertice, y parametro de impacto de un detector. El capitulo 3 describe los danos que la radiacion produce en detectores de silicio, tanto en la electronica como en el sensor, cuyo impacto es crucial en el rendimiento de los detectores especialmente para experimentos en el HL-LHC. El capitulo 4 revisa la evolucion y tendencias en detectores de pixeles, abarcando desde los ya bien establecidos pixel hibridos, hasta los CMOS pixeles. La seccion dedicada a los CMOS pixeles describe los diferentes tipos que se estan considerando en ATLAS: High resistivity CMOS, high voltage CMOS, y monoliticos CMOS-on-SOI. Este ultimo compone el nucleo de estudio de esta tesis y es descrito en detalle. Los siguientes capitulos detallan el programa de caracterizacion y medidas realizado en el contexto de esta tesis. El capitulo 5 se centra en la caracterizacion del dano creado por la radiacion en la electronica hasta las dosis esperadas en el ID de ATLAS durante su operacion en el HL-LHC. Las propiedades del detector, como son las corrientes de fuga, el cociente entre senal y ruido, la coleccion de carga y la profundidad de deplecion, son descritas en el capitulo 6. El Capitulo 7 describe la caracterizacion de sensores monoliticos CMOS-on-SOI en un haz de piones, donde la coleccion de carga, el reparto de carga entre pixeles, la resolucion espacial, y la eficiencia son discutidas. Este trabajo concluye con un resumen, con vistas al futuro de las tecnologias monoliticas CMOS-on-SOI en la fisica de altas energias.
Tumoral non‐amyloidotic monoclonal immunoglobulin light chain deposits (‘aggregoma’): presenting feature of B‐cell dyscrasia in three cases with immunohistochemical and biochemical analyses

Summary. Tumoral monoclonal immunoglobulin (Ig) light chain non‐fibrillar deposits (‘aggregomas’), which can be considered analogous to solitary light chain amyloidomas, are a rare presenting feature of B‐cell dyscrasias. It is not certain if they are truly localized or if in reality they represent an initial expression of a silent systemic non‐amyloid light chain deposition disease (LCDD). This report describes three patients, two of whom presented with cervical masses and the third with a solitary lung nodule, each comprising granular aggregates of monoclonal kappa light chain. Extracted deposits from the lymph node of one patient were shown by N‐terminal amino acid sequence analysis to belong to the variable‐region kappa I (Vκ I) light chain subgroup, the first reported κ‐LCDD protein encoded by the L9 gene and the first report of an expressed protein related to this gene. Extracted deposits from the lung nodule of the second patient belonged to the Vκ IV light chain subgroup encoded by the B3 germ line gene. The N‐terminal amino acid sequences of the light chains from the aggregomas were compared with the related germ line sequences and to the N‐terminal amino acid sequences of the nine other known κ‐LCDD light chains reported thus far from patients with systemic LCDD.
Phosphorylation of mammalian CDC6 by Cyclin A/CDK2 regulates its subcellular localization

Cyclin‐dependent kinases (CDKs) are essential for regulating key transitions in the cell cycle, including initiation of DNA replication, mitosis and prevention of re‐replication. Here we demonstrate that mammalian CDC6, an essential regulator of initiation of DNA replication, is phosphorylated by CDKs. CDC6 interacts specifically with the active Cyclin A/CDK2 complex in vitro and in vivo, but not with Cyclin E or Cyclin B kinase complexes. The cyclin binding domain of CDC6 was mapped to an N‐terminal Cy‐motif that is similar to the cyclin binding regions in p21WAF1/SDI1 and E2F‐1. The in vivo phosphorylation of CDC6 was dependent on three N‐terminal CDK consensus sites, and the phosphorylation of these sites was shown to regulate the subcellular localization of CDC6. Consistent with this notion, we found that the subcellular localization of CDC6 is cell cycle regulated. In G1, CDC6 is nuclear and it relocalizes to the cytoplasm when Cyclin A/CDK2 is activated. In agreement with CDC6 phosphorylation being specifically mediated by Cyclin A/CDK2, we show that ectopic expression of Cyclin A, but not of Cyclin E, leads to rapid relocalization of CDC6 from the nucleus to the cytoplasm. Based on our data we suggest that the phosphorylation of CDC6 by Cyclin A/CDK2 is a negative regulatory event that could be implicated in preventing re‐replication during S phase and G2.
Micro Helicopter-airplane system: Trajectory tracking and attitude control

This paper focuses on the regulation and trajectory tracking for a Micro Coaxial Rocket Helicopter (MCR UAV) and a mini aircraft. The former has the characteristic of performing hover and forward flight while the latter is considered as an external air transporter for the MCR UAV. For control purposes, the helicopter stabilization is based on the Backsteeping procedure, and a PD controller is implemented in the aircraft in order to execute semi-autonomous flight. The avionics for these aerial vehicles consists of an embedded computer, low-cost sensors and homemade modules (Signal Conditioning Circuits, Analog Filters) and the flight control algorithm is implemented in the embedded system. Simulation and experimental results show an effective performance of the developed system during the flight.