Geographic distribution and clinical description of leishmaniasis cases in Peru

Asymmetric acetylcholinesterase (AChE) is anchored to the basal lamina (BL) of cholinergic synapses via its collagenic tail, yet the complement of matrix receptors involved in its attachment remains unknown. The development of a novel overlay technique has allowed us to identify two Torpedo BL components that bind asymmetric AChE: a polypeptide of approximately 140 kDa and a doublet of 195-215 kDa. These were found to stain metachromatically with Coomassie blue R-250, were solubilized by acetic acid, and were sensitive to collagenase treatment. Upon sequence analysis, the 140 kDa polypeptide yielded a characteristic collagenous motif. Another AChE-binding BL constituent, identified by overlay, corresponded to a heparan sulfate proteoglycan. Lastly, we established that this proteoglycan, but not the collagenous proteins, interacted with at least one heparin binding domain of the collagenic tail of AChE. Our results indicate that at least two BL receptors are likely to exist for asymmetric AChE in Torpedo electric organ.     

Failure pressure evaluation of the containment building of a large dry nuclear power plant

The evaluation of the failure pressure of the containment building of a large dry PWR-W three loops nuclear power plant, based on computer numerical simulation, is described in this paper. The proposed method considers fully three-dimensional finite element models in order to take into account the effect of the most significant structural characteristics (presence of three buttresses, penetrations, additional reinforcement around the penetrations, etc.), the lack of symmetry of the forces generated by the prestressing system, as well as the nonlinear behaviour of the materials and the sensitivity of the results to uncertainties associated with several parameters. The computational model is completely described, including the constitutive equations for the concrete, the reinforcing steel and prestressing tendons, the spatial discretization—isoparametric elements including the reinforcement are used. The structural models and the analyses performed for their calibration are also described. The influence on the failure pressure of incorporating the foundation slab in the structural model, and the influence of the thermal effects, are discussed. One of the conclusions of the numerical study is that the failure process can be appropriately simulated by means of a structural model which does not include either the foundation slab or the thermal effects. Finally, results of a probabilistic simulation of the failure pressure are given.     

Optic neuropathy resembling normal-pressure glaucoma in a teenager with congenital macrodiscs

We report a unique case of a renal transplant patient with a long-term nonprogressive human immunodeficiency virus type-1 (HIV-1) infection and who is asymptomatic despite sustained immunosuppression. Renal function is normal, and HIV infection was probably acquired through blood transfusion before the transplant. Nonprogression may be due either to an effective immune control of HIV replication or to particular genetic aspects of the virus. Several virological investigations were carried out to verify if she is infected with an attenuated virus strain. Results show an unusual combination of high and stable CD4 count, ongoing viral replication and elevated viral loads. Attempts to isolate the virus from plasma were unsuccessful, but isolation was possible from peripheral blood mononuclear cells, and the virus was shown to be non-syncytium-inducing. Sequence analysis of the nef gene revealed no mutation. This exceptional lack of progression of HIV infection under immunosuppressive therapy requires further investigation.     

Auditory feedback in haptic collaborative interfaces

The combined effect of haptic and auditory feedback in shared interfaces on the cooperation between visually impaired and sighted persons is under-investigated. A central challenge for cooperating group members lies in obtaining a common understanding of the elements of the workspace and maintaining awareness of the other members' actions, as well as one's own, during the group work process. The aim of the experimental study presented here was to investigate if adding audio cues in a haptic and visual interface makes collaboration between a sighted and a blindfolded person more efficient. Results showed that task performance was significantly faster in the audio, haptic and visual feedback condition compared to the haptic and visual feedback condition. One special focus was also to study how participants utilize the auditory and haptic force feedback in order to obtain a common understanding of the workspace and to maintain an awareness of the group members' actions. Results from a qualitative analysis showed that the auditory and haptic feedback was used in a number of important ways to support the group members' action awareness and in the participants' grounding process.     

Reliability of portal frames with discrete design variables

Virtually all structural optimization based on system reliability was conducted considering continuous design variables. The solution of the reliability-based design problem is obtained by solving alternatively a reliability assessment problem and an optimal sizing program until the best reliability-based design occurs. The reliability assessment problem is formulated as a linearly constrained concave quadratic program. By introducing the concept of segmental members, the discrete optimum design is achieved based upon linear programming. Examples are solved by employing the proposed computational technique.Presented at NATO ASI Optimization of Large Structural Systems, Berchtesgaden, Germany, Sept. 23 – Oct. 4, 1991     

The Neurovascular Unit Dysfunction in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.     

Investigating T Cell Immunity in Cancer: Achievements and Prospects

T cells play a key role in tumour surveillance, both identifying and eliminating transformed cells. However, as tumours become established they form their own suppressive microenvironments capable of shutting down T cell function, and allowing tumours to persist and grow. To further understand the tumour microenvironment, including the interplay between different immune cells and their role in anti-tumour immune responses, a number of studies from mouse models to clinical trials have been performed. In this review, we examine mechanisms utilized by tumour cells to reduce their visibility to CD8⁺ Cytotoxic T lymphocytes (CTL), as well as therapeutic strategies trialled to overcome these tumour-evasion mechanisms. Next, we summarize recent advances in approaches to enhance CAR T cell activity and persistence over the past 10 years, including bispecific CAR T cell design and early evidence of efficacy. Lastly, we examine mechanisms of T cell infiltration and tumour regression, and discuss the strengths and weaknesses of different strategies to investigate T cell function in murine tumour models.     

Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10⁻⁵, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10⁻⁵, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10⁻⁵, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10⁻⁵, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10⁻⁵, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10⁻², p = 5.1 × 10⁻³, p = 1.2 × 10⁻², respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.