Search

We study the singular nonlinear partial differential equation $ t\partial_tu = F(t, x, u, \partial_xu) $, where $ (t, x)\in\mathbb{R}\times\mathbb{R}^n $. Under some growth conditions on the coefficients of the partial Taylor expansion of $ F $, we construct the unique solution that is continuous in $ t $ and $ C^\infty $ in $ x $.

Neurodegenerative diseases called tauopathies, such as Alzheimer’s disease (AD), frontotemporal dementia, progressive supranuclear palsy, and Parkinson’s disease, among others, are characterized by the pathological processing and accumulation of tau protein. AD is the most prevalent neurodegenerative disease and is characterized by two lesions: neurofibrillary tangles (NFTs) and neuritic plaques. The presence of NFTs in the hippocampus and neocortex in early and advanced stages, respectively, correlates with the patient’s cognitive deterioration. So far, no drugs can prevent, decrease, or limit neuronal death due to abnormal pathological tau accumulation. Among potential non-pharmacological treatments, physical exercise has been shown to stimulate the development of stem cells (SCs) and may be useful in early stages. However, this does not prevent neuronal death from the massive accumulation of NFTs. In recent years, SCs therapies have emerged as a promising tool to repopulate areas involved in cognition in neurodegenerative diseases. Unfortunately, protocols for SCs therapy are still being developed and the mechanism of action of such therapy remains unclear. In this review, we show the advances and limitations of SCs therapy. Finally, we provide a critical analysis of its clinical use for AD.

Alzheimer's disease (AD) is clinically characterized by a progressive loss of cognitive functions and short-term memory. AD patients present two distinctive neuropathological lesions: neuritic plaques and neurofibrillary tangles (NFTs), constituted of beta-amyloid peptide (Aβ) and phosphorylated and truncated tau proteins. Aβ deposits around cerebral blood vessels (cerebral amyloid angiopathy, CAA) is a major contributor to vascular dysfunction in AD. Vascular amyloid deposits could be early events in AD due to dysfunction in the neurovascular unit (NVU) and the blood-brain barrier (BBB), deterioration of the gliovascular unit, and/or decrease of cerebral blood flow (CBF). These pathological events can lead to decreased Aβ clearance, facilitate a neuroinflammatory environment as well as synaptic dysfunction and, finally, lead to neurodegeneration. Here, we review the histopathological AD hallmarks and discuss the two-hit vascular hypothesis of AD, emphasizing the role of neurovascular dysfunction as an early factor that favors vascular Aβ aggregation and neurodegeneration. Addtionally, we emphasize that pericyte degeneration is a key and early element in AD that can trigger amyloid vascular accumulation and NVU/BBB dysfunction. Further research is required to better understand the early pathophysiological mechanisms associated with NVU alteration and CAA to generate early biomarkers and timely treatments for AD.

A search for a new Z^{'} gauge boson associated with (un)broken B-L symmetry in the keV-GeV mass range is carried out for the first time using the missing-energy technique in the NA64 experiment at the CERN SPS. From the analysis of the data with 3.22×10^{11} electrons on target collected during 2016-2021 runs, no signal events were found. This allows us to derive new constraints on the Z^{'}-e coupling strength, which, for the mass range 0.3≲m_{Z^{'}}≲100 MeV, are more stringent compared to those obtained from the neutrino-electron scattering data.

Autophagy is a highly conserved lysosomal degradation pathway active at basal levels in all cells. However, under stress conditions, such as a lack of nutrients or trophic factors, it works as a survival mechanism that allows the generation of metabolic precursors for the proper functioning of the cells until the nutrients are available. Neurons, as post-mitotic cells, depend largely on autophagy to maintain cell homeostasis to get rid of damaged and/or old organelles and misfolded or aggregated proteins. Therefore, the dysfunction of this process contributes to the pathologies of many human diseases. Furthermore, autophagy is highly active during differentiation and development. In this review, we describe the current knowledge of the different pathways, molecular mechanisms, factors that induce it, and the regulation of mammalian autophagy. We also discuss its relevant role in development and disease. Finally, here we summarize several investigations demonstrating that autophagic abnormalities have been considered the underlying reasons for many human diseases, including liver disease, cardiovascular, cerebrovascular diseases, neurodegenerative diseases, neoplastic diseases, cancers, and, more recently, infectious diseases, such as SARS-CoV-2 caused COVID-19 disease.

Whether neuroinflammation leads to dopaminergic nigrostriatal system neurodegeneration is controversial. We addressed this issue by inducing acute neuroinflammation in the substantia nigra (SN) with a single local administration (5 µg/2 µL saline solution) of lipopolysaccharide (LPS). Neuroinflammatory variables were assessed from 48 h to 30 days after the injury by immunostaining for activated microglia (Iba-1 +), neurotoxic A1 astrocytes (C3 + and GFAP +), and active caspase-1. We also evaluated NLRP3 activation and Il-1β levels by western blot and mitochondrial complex I (CI) activity. Fever and sickness behavior was assessed for 24 h, and motor behavior deficits were followed up until day 30. On this day, we evaluated the cellular senescence marker β-galactosidase (β-Gal) in the SN and tyrosine hydroxylase (TH) in the SN and striatum. After LPS injection, Iba-1 (+), C3 (+), and S100A10 (+) cells were maximally present at 48 h and reached basal levels on day 30. NLRP3 activation occurred at 24 h and was followed by a rise of active caspase-1 (+), Il-1β, and decreased mitochondrial CI activity until 48 h. A significant loss of nigral TH (+) cells and striatal terminals was associated with motor deficits on day 30. The remaining TH (+) cells were β-Gal (+), suggesting senescent dopaminergic neurons. All the histopathological changes also appeared on the contralateral side. Our results show that unilaterally LPS-induced neuroinflammation can cause bilateral neurodegeneration of the nigrostriatal dopaminergic system and are relevant for understanding Parkinson’s disease (PD) neuropathology.

Alzheimer’s disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1–5% of the total number of cases. It is categorized as early onset (EOAD

Parkinson’s disease (PD) is the most common α-synucleinopathy worldwide. The pathognomonic hallmark of PD is the misfolding and propagation of the α-synuclein (α-syn) protein, observed in post-mortem histopathology. It has been hypothesized that α-synucleinopathy triggers oxidative stress, mitochondrial dysfunction, neuroinflammation, and synaptic dysfunction, leading to neurodegeneration. To this date, there are no disease-modifying drugs that generate neuroprotection against these neuropathological events and especially against α-synucleinopathy. Growing evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists confer neuroprotective effects in PD, however, whether they also confer an anti-α-synucleinopathy effect is unknown. Here we analyze the reported therapeutic effects of PPARs, specifically the gamma isoform (PPARγ), in preclinical PD animal models and clinical trials for PD, and we suggest possible anti-α-synucleinopathy mechanisms acting downstream from these receptors. Elucidating the neuroprotective mechanisms of PPARs through preclinical models that mimic PD as closely as possible will facilitate the execution of better clinical trials for disease-modifying drugs in PD.

Overexpression of neurotrophic factors in nigral dopamine neurons is a promising approach to reverse neurodegeneration of the nigrostriatal dopamine system, a hallmark in Parkinson’s disease. The human cerebral dopamine neurotrophic factor (hCDNF) has recently emerged as a strong candidate for Parkinson’s disease therapy. This study shows that hCDNF expression in dopamine neurons using the neurotensin-polyplex nanoparticle system reverses 6-hydroxydopamine-induced morphological, biochemical, and behavioral alterations. Three independent electron microscopy techniques showed that the neurotensin-polyplex nanoparticles containing the hCDNF gene, ranging in size from 20 to 150 nm, enabled the expression of a secretable hCDNF in vitro. Their injection in the substantia nigra compacta on day 21 after the 6-hydroxydopamine lesion resulted in detectable hCDNF in dopamine neurons, whose levels remained constant throughout the study in the substantia nigra compacta and striatum. Compared with the lesioned group, tyrosine hydroxylase-positive (TH+) nigral cell population and TH+ fiber density rose in the substantia nigra compacta and striatum after hCDNF transfection. An increase in βIII-tubulin and growth-associated protein 43 phospho-S41 (GAP43p) followed TH+ cell recovery, as well as dopamine and its catabolite levels. Partial reversal (80%) of drug-activated circling behavior and full recovery of spontaneous motor and non-motor behavior were achieved. Brain-derived neurotrophic factor recovery in dopamine neurons that also occurred suggests its participation in the neurotrophic effects. These findings support the potential of nanoparticle-mediated hCDNF gene delivery to develop a disease-modifying treatment against Parkinson’s disease. The Institutional Animal Care and Use Committee of Centro de Investigación y de Estudios Avanzados approved our experimental procedures for animal use (authorization No. 162-15) on June 9, 2019.

The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

The observation of beam spin asymmetries in two-pion production in semi-inclusive deep inelastic scattering off an unpolarized proton target is reported for the first time. The data presented here were taken in the fall of 2018 with the CLAS12 spectrometer using a 10.6 GeV longitudinally spin-polarized electron beam delivered by CEBAF at JLab. The measured asymmetries provide the first observation of a signal that can be used to extract the PDF $e(x)$ in a collinear framework and the helicity-dependent two-pion fragmentation function $G_1^\perp$.

Objective To evaluate the long‐term safety of rituximab in an observational cohort of patients with rheumatoid arthritis (RA) who had an inadequate response to ≥1 anti–tumor necrosis factor therapy in the US (SUNSTONE [Study of the Safety of Rituxan in Patients With Rheumatoid Arthritis After an Inadequate Response to Previous Anti‐TNF Therapy] registry). Methods In this prospective, observational cohort study, patients received rituximab according to their physician's standard practice and were evaluated at standard‐of‐care follow‐up visits at least every 6 months. The primary outcome was the incidence of protocol‐defined significant infections. Secondary outcomes included serious adverse events potentially associated with rituximab, cardiovascular or thrombotic events, seizures, deaths, and pregnancies. Post hoc analyses assessed outcomes by concomitant medication use. Results Overall, 989 patients (safety‐evaluable population) received ≥1 dose of rituximab, with a total follow‐up of 3,844 patient‐years (mean duration 3.9 years). In total, 341 significant infections occurred in 197 patients (19.9%). The incidence rates (95% confidence intervals [95% CIs]) for significant infections, cardiovascular or thrombotic events, and seizures were 8.87 (95% CI 7.98–9.86), 1.95 (95% CI 1.56–2.45), and 0.18 (95% CI 0.09–0.38) per 100 patient‐years, respectively. The incidence of significant infections did not increase with time or with cumulative rituximab exposure. During the study, 64 patients died (crude mortality rate 1.66 per 100 patient‐years [95% CI 1.30–2.13]). The most common causes of death were infections (n = 19), malignancy (n = 14), and cardiovascular events (n = 13). Eight pregnancies were reported in 7 patients. Conclusion In patients with RA treated with rituximab for up to 5 years, the rates of significant infections were stable over time and higher in patients who received long‐term systemic steroid treatment.

BackgroundNonlinear associations in rheumatoid arthritis (RA) prevalence and sociodemographic indices suggest social determinants of health affect RA.1 RA screening tools have lower sensitivity and specificity for Hispanic/Latinx individuals compared with white individuals (77% vs 85% sensitivity and 45% vs 87% specificity).2 Hispanic/Latinx people also present to physicians later and with more severe RA.3 There is little research in this population to explain these differences or how they can be addressed. Because it is known the Hispanic/Latinx population has lower English-language proficiency, we hypothesized this is in part because of the lack of validated Spanish-language educational materials and research tools for RA.ObjectivesTo validate a Spanish-language patient-provider questionnaire (PPQ) for Hispanic/Latinx patients with RA that had previously been validated as concordant for primary care visits in Sweden.4To understand if rheumatologist and patient assessments for Hispanic/Latinx people with RA are concordant when using a Spanish-language digital PPQ.To determine if a Spanish-language rheumatologist-completed PPQ could be a proxy for patient impressions in a prospective clinical study.MethodsA Spanish-language PPQ for RA was created by translating 9 of 13 questions previously validated in the Swedish study,4 and adding a question about treating to target specific to RA. The survey was made available on tablet devices in 4 rheumatology clinics in the U.S. and Puerto Rico. Clinic staff obtained patient consent and gathered demographic information to generate a unique confidential identifier code for each visit, which was inputted into surveys on tablet devices. After the visit ended the patient and rheumatologist were each given the PPQ coded for that visit to complete independently of one another. The PPQs were submitted electronically to a secure database in which the visit code was the only identifier recorded.ResultsAcross 114 clinical visits, 96.75% of possible answers were recorded and were almost invariably positive with scores of 5 (strongly agree; 88%), 4 (agree; 12%), or 3 (neither agree nor disagree; 0.09%). Physicians responded with 4 (agree) more often than patients (18% vs 6% of responses). Responses from both patient and physician were available for (96.64%) of answered questions. Within these paired answers, 80.67% were concordant (same answer from both patient and physician). Physicians answered 4 when patients answered 5 in 76.5% of discordant responses (different ratings from patient and physician). Most physician ratings of 4 came from 1 of the 4 physicians involved and only 12.5% of patients were responsible for 75% of the patient responses of 4.ConclusionHispanic/Latinx patients with RA and their rheumatologist rated their communication, goal setting, and relationships extremely positively, making it difficult to evaluate true concordance and not possible to use rheumatologist-completed PPQs as proxy for patient assessments. Notably, ratings were substantially different from what is typically seen on Likert scales, which normally skew positively but with a normal distribution. This finding may reflect social determinants of health or cultural differences such as a social-desirability bias toward positive statements about physician-patient interactions. Heterogeneity within the participants is also a plausible explanation, considering that a distinct subset of respondents account for almost all responses below the 5 rating. Further research is needed to identify best practices for measuring treatment to target and patient-rheumatologist interactions in the Hispanic/Latinx population with RA.References[1]Safiri S, et al. Ann Rheum Dis. 2019;78(11):1463-71. doi:10.1136/annrheumdis-2019-215920[2]Potter J, et al. J Rheumatol. 2008;35(8):1545-9. PMID: 18597406[3]Riad M, et al. J Clin Rheumatol. 2019. doi:10.1097/RHU.0000000000001085[4]Ahlén GC, et al. Fam Pract. 2007;24(5):498503. doi.org/10.1093/fampra/cmm043AcknowledgementsWe wish to acknowledge the important contributions of our HOPE CAPE RA participants, including the patients and providers and Anne Sydor, PhD for her invaluable advice and help throughout the project.This project was funded by the Bristol Myers Squibb Foundation.Disclosure of InterestsDaniel Hernandez Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Julio Bravo Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Juan Jose Maya Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Oscar Soto-Raíces Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Angel Tapia Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, Guillermo Valenzuela Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation, W. Benjamin Nowell Grant/research support from: This research was supported by the Bristol Myers Squibb Foundation, Shilpa Venkatachalam Grant/research support from: This project is supported by the Bristol Myers Squibb Foundation

The quark structure of the f2(1270) meson has, for many years, been assumed to be a pure quark-antiquark (qq¯) resonance with quantum numbers JPC=2++. Recently, it was proposed that the f2(1270) is a molecular state made from the attractive interaction of two ρ mesons. Such a state would be expected to decay strongly to final states with charged pions due to the dominant decay ρ→π+π-, whereas decay to two neutral pions would likely be suppressed. Here, we measure for the first time the reaction γp→π0π0p, using the CEBAF Large Acceptance Spectrometer detector at Jefferson Lab for incident beam energies between 3.6 and 5.4 GeV. Differential cross sections, dσ/dt, for f2(1270) photoproduction are extracted with good precision due to low backgrounds and are compared to theoretical calculations.

We report a measurement of the π − photoproduction beam asymmetry for the reaction → γ p → π − Δ + + using data from the GlueX experiment in the photon beam energy range 8.2–8.8 GeV. The asymmetry Σ is measured as a function of four-momentum transfer t to the Δ + + and compared to phenomenological models. We find that Σ varies as a function of t : negative at smaller values and positive at higher values of | t | . The reaction can be described theoretically by t -channel particle exchange requiring pseudoscalar, vector, and tensor intermediaries. In particular, this reaction requires charge exchange, allowing us to probe pion exchange and the significance of higher-order corrections to one-pion exchange at low momentum transfer. Constraining production mechanisms of conventional mesons may aid in the search for and study of unconventional mesons. This is the first measurement of the process at this energy.

Physical review letters 126(6), 062002 (2021). doi:10.1103/PhysRevLett.126.062002, Published by APS, College Park, Md.

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD.

Photoproduction cross sections are reported for the reaction $\gamma p\to p\eta$ using energy-tagged photons and the CLAS spectrometer at Jefferson Laboratory. The $\eta$ mesons are detected in their dominant charged decay mode, $\eta\to \pi^+\pi^-\pi^0$, and results on differential cross sections are presented for incident photon energies between 1.2 and 4.7 GeV. These new $\eta$ photoproduction data are consistent with earlier CLAS results but extend the energy range beyond the nucleon resonance region into the Regge regime. The normalized angular distributions are compared with the experimental results from several other experiments, and with predictions of $\eta$ MAID\,2018 and the latest solution of the Bonn-Gatchina coupled-channel analysis. Differential cross sections $d\sigma/dt$ are presented for incident photon energies $E_\gamma > 2.9$ GeV ($W > 2.5$ GeV), and compared with predictions which are based on Regge trajectories exchange in the $t$-channel (Regge models). The data confirm the expected dominance of $\rho$, $\omega$ vector-meson exchange in an analysis by the Joint Physics Analysis Center.

We present the first measurement of the exclusive reaction $\gamma p \rightarrow a_2(1320)^0 \, p$ in the photon energy range $3.5$-$5.5$ GeV and four-momentum transfer squared $0.2

We report measurements of the photon beam asymmetry Σ for the reaction γp→K+Σ0 (1193) using the GlueX spectrometer in Hall D at Jefferson Lab. Data were collected by using a linearly polarized photon beam in the energy range of 8.2–8.8 GeV incident on a liquid hydrogen target. The beam asymmetry Σ was measured as a function of the Mandelstam variable t , and a single value of Σ was extracted for events produced in the u channel. These are the first exclusive measurements of the photon beam asymmetry Σ for the reaction in this energy range. For the t channel, the measured beam asymmetry is close to unity over the t range studied, − t = ( 0.1 – 1.4 ) ( GeV / c ) 2 , with an average value of Σ = 1.00 ± 0.05 . This agrees with theoretical models that describe the reaction via the natural-parity exchange of the K ∗ (892) Regge trajectory. A value of Σ = 0.41 ± 0.09 is obtained for the u channel integrated up to − u = 2.0 ( GeV / c ) 2 .

It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico.Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs.1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year.The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and 90% without regular scientific production.Es fundamental que los médicos residentes de ortopedia (traumatología) sean altamente competentes en todos los aspectos, considerando el equilibrio entre la oferta, demanda, necesidad y contexto. Es primordial identificar la capacidad y calidad instalada para su formación en México.Estudio observacional, transversal, muestreo no probabilístico-conglomerados, en dos fases. El instrumento tiene ocho dominios, 57 variables y 4,867 ítems. Sesenta profesores de postgrado de 20 estados, 50 sedes hospitalarias, 22 programas universitarios.1,038 años de experiencia (inteligencia colectiva), 17 años de experiencia/profesor (01 a 50 años). Se identificó: patología aguda 30 (2 a 90%), patología crónica 30 (5 a 96%), pacientes 15 años, 10 (3 a 30%), pacientes entre 15 y 65 años, 47 (2 a 78%), pacientes 65 años, 20 (2 a 60%), número de camas/sede 20 (2 a 510), número de consultorios 3 (1 a 48), el número de procedimientos quirúrgicos/sede al año a nivel nacional fue de 960 (50 a 24,650). La media nacional por médico residente es de 362 cirugías/año con 1,450 momentos quirúrgicos/año.Las necesidades y recursos para la formación de médicos especialistas en ortopedia/traumatología son en alto grado heterogéneos, por lo cual se debería adaptar a las necesidades epidemiológicas de la región de influencia, en un ámbito de transición epidemiológica. Sesenta y dos punto dos por ciento expresó no tener o tener deficiente infraestructura académica y científica en su sede, más de 50% sin rotación al extranjero y 90% sin producción científica regular.

The exclusive electroproduction process ep→e′p′π0 was measured in the range of photon virtualities Q2=0.4–1.0GeV2 and the invariant mass range of the pπ0 system of W=1.1–1.8 GeV. These kinematics are covered in exclusive π0 electroproduction off the proton with nearly complete angular coverage in the pπ0 center-of-mass system and with high statistical accuracy. Nearly 36 000 cross-section points were measured, and the structure functions σT+eσL,σLT, and σTT, were extracted via fitting the ϕπ0 dependence of the cross section. A Legendre polynomial expansion analysis demonstrates the sensitivity of our data to high-lying N* and Δ* resonances with M>1.6 GeV. As part of a broad effort to determine the electrocouplings of the N* and Δ* resonances using both single- and double-pion electroproduction, this dataset is crucial for the reliable extraction of the high-lying resonance electrocouplings from the combined isospin analysis of the Nπ and π+π−p channels.

We report on the measurement of the beam asymmetry Σ for the reactions → γ p → p η and → γ p → p η ′ from the GlueX experiment using an 8.2–8.8-GeV linearly polarized tagged photon beam incident on a liquid hydrogen target in Hall D at Jefferson Laboratory. These measurements are made as a function of momentum transfer − t with significantly higher statistical precision than our earlier η measurements and are the first measurements of η ′ in this energy range. We compare the results to theoretical predictions based on t -channel quasiparticle exchange. We also compare the ratio of Σ η to Σ η ′ to these models as this ratio is predicted to be sensitive to the amount of s ¯ s exchange in the production. We find that photoproduction of both η and η ′ is dominated by natural parity exchange with little dependence on − t .

High-momentum configurations of nucleon pairs at short-distance are probed using measurements of the $^{12}$C$(e,e'p)$ and $^{12}$C$(e,e'pN)$ reactions (where $N$ is either $n$ or $p$), at high-$Q^2$ and $x_B>1.1$. The data span a missing-momentum range of 300--1000 MeV/c and are predominantly sensitive to the transition region of the strong nuclear interaction from a Tensor to Scalar interaction. The data are well reproduced by theoretical calculations using the Generalized Contact Formalism with both chiral and phenomenological nucleon-nucleon ($NN$) interaction models. This agreement suggests that the measured high missing-momentum protons up to $1000$ MeV/c predominantly belong to short-ranged correlated (SRC) pairs. The measured $^{12}$C$(e,e'pN)$ / $^{12}$C$(e,e'p)$ and $^{12}$C$(e,e'pp)$ / $^{12}$C$(e,e'pn)$ cross-section ratios are consistent with a decrease in the fraction of proton-neutron SRC pairs and increase in the fraction of proton-proton SRC pairs with increasing missing momentum. This confirms the transition from an isospin-dependent tensor $NN$ interaction at $\sim 400$ MeV/c to an isospin-independent scalar interaction at high-momentum around $\sim 800$ MeV/c as predicted by theoretical calculation., Accepted for publication in Physics Letters B. 7 pages, 3 figures, and online supplementary materials

This paper presents a study carried out to first assess the impact of the Panama Canal expansion (PCE) on selected Caribbean ports, and thereafter, to examine how the ports can adapt in order to seize new opportunities created by the expansion. An applied case of long-term dynamic planning and flexibility in engineering design is presented for a new port terminal in Barranquilla, Colombia. Furthermore, this paper presents the results of a stochastic method for quantifying opportunities from containerized traffic using dynamic forecasting, real options analysis, and Monte Carlo simulation, within the framework and spirit of adaptive port planning under uncertainty.

Parkinson's disease (PD) is a progressive neuropathology characterized by motor and non-motor alterations. β-sitosterol β-d-glucoside (BSSG) is a neurotoxin whose prolonged oral administration in rats has been proposed as a new PD model. Herein, we demonstrate that a single, unilateral, and intranigral administration of BSSG also elicits bilateral sensorimotor alterations in the rat. Six behavioral tests evaluated the effect of different concentrations of BSSG (3, 6, 9, and 12 μg/μL DMSO) from 15 to 120 days after administration. The first behavioral alterations, which appeared on day 15, were unbalanced and uncoordinated gaits and a decrease in the sensorimotor cortex activity, as evidenced by the beam-walking and the vibrissae tests, respectively. After 30 days, the corridor test revealed hyposmia and a decreased locomotor activity in the open field. The last alteration was a depressive-like behavior, as shown by the forced swim test on days 60 and 120. According to the cylinder test, no locomotor asymmetry was observed over time with any BSSG concentrations tested. Also, a mesencephalic TH(+) cell loss (p 0.05) was shown on day 30 when compared with the mock condition, and such a loss was even higher on day 120. At this time, the presence of pathological α-synuclein aggregates in the mesencephalon was documented. Our results show that the stereotaxic intranigral administration of BSSG reproduces some characteristics of oral administration, such as the progression of behavioral alterations, dopaminergic neurons loss, and the presence of Lewy body-like synuclein aggregations, in less time and resources.

First measurements of double-polarization observables in ω photoproduction off the proton are presented using transverse target polarization and data from the CEBAF Large Acceptance Spectrometer (CLAS) FROST experiment at Jefferson Lab. The beam-target asymmetry F has been measured using circularly polarized, tagged photons in the energy range 1200-2700 MeV, and the beam-target asymmetries H and P have been measured using linearly polarized, tagged photons in the energy range 1200-2000 MeV. These measurements significantly increase the database on polarization observables. The results are included in two partial-wave analyses and reveal significant contributions from several nucleon (N^{*}) resonances. In particular, contributions from new N^{*} resonances listed in the Review of Particle Properties are observed, which aid in reaching the goal of mapping out the nucleon resonance spectrum.

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.

The COMASA S.A. power plant is located near Temuco and burns a high amount of residual biomass produced in the Araucanía region. However, the main problem associated with this plant is the transportation and disposal of fly ash (9 tons per week), a residue generated during the combustion of Boiler I. Currently, fly ashes from Boiler I are transported more than 200 km south, increasing transportation and final disposal costs. In this study, the development of a mortar based on fly ash from the combustion of biomass from COMASA S.A. was analysed at a pre-feasibility level. The experimental procedure consisted of (i) the physicochemical characterization of biomass fly ash, (ii) obtaining different test specimens (mortars) via the addition of different proportions of fly ash (10-35%) to cement, and (iii) obtaining the best specimen by analysing the requirements of mortars for construction purposes (Chilean Standard NCh 1037). The test specimens were subjected to determination of apparent density, compression resistance, water absorption capacity and moisture content. The laboratory results showed that the mortar obtained with the addition of 20% of fly ash has similar physical characteristics to mortars used for building blocks, proving capable of resisting up to 20 MPa. To analyse the viability of the production of construction blocks based on best specimen, market, technical and economic-financial studies were carried out, considering the reuse of at least 60% of the fly ash generated per year. The study concluded that the project was viable, evidencing the potential use of this residue for the manufacture of low-cost blocks, while minimizing the cost associated with residue handling.

The barrel calorimeter is part of the new spectrometer installed in Hall D at Jefferson Lab for the GlueX experiment. The calorimeter was installed in 2013, commissioned in 2014 and has been operating routinely since early 2015. The detector configuration, associated Monte Carlo simulations, calibration and operational performance are described herein. The calorimeter records the time and energy deposited by charged and neutral particles created by a multi-GeV photon beam. It is constructed as a lead and scintillating-fiber calorimeter and read out with 3840 large-area silicon photomultiplier arrays. Particles impinge on the detector over a wide range of angles, from normal incidence at 90 degrees down to 11.5 degrees, which defines a geometry that is fairly unique among calorimeters. The response of the calorimeter has been measured during a running experiment and performs as expected for electromagnetic showers below 2.5 GeV. We characterize the performance of the BCAL using the energy resolution integrated over typical angular distributions for $\pi^0$ and $\eta$ production of $\sigma_E/E$=5.2\%/$\sqrt{E(\rm{GeV})} \oplus$ 3.6\% and a timing resolution of $\sigma$\,=\,150\,ps at 1\,GeV., Comment: 46 pages, 33 figures

We report measurements of the photon beam asymmetry Σ for the reactions γ - p→pπ0 and γ - p→pη from the GlueX experiment using a 9 GeV linearly polarized, tagged photon beam incident on a liquid hydrogen target in Jefferson Lab's Hall D. The asymmetries, measured as a function of the proton momentum transfer, possess greater precision than previous π0 measurements and are the first η measurements in this energy regime. The results are compared with theoretical predictions based on t-channel, quasiparticle exchange and constrain the axial-vector component of the neutral meson production mechanism in these models.

The novel Hamamatsu Multi Pixel Photon Counter Array S12045(X) is an array of 16 individual MPPCs (3×3 mm2) (further in the paper MPPC array channel) each with 3600 G-APD (Geiger-mode Avalanche Photodiodes) pixels (50×50 [ μ m 2 ]). Each MPPC in the array works with its individual reverse bias voltage mode (around 70 V). The paper summarizes the characterization process of MPPC arrays used in GlueX experiment (Hall D, Jefferson Lab). We studied the main features of each MPPC array channel for 2800 MPPC arrays at different temperatures. Two measurement stations were built to extract gain, breakdown voltage, photo detection efficiency (PDE), optical crosstalk and dark rate for each MPPC array channel. The hardware and the data analysis are described, which includes new analytical expressions to obtain the mean number of photo-electrons and optical crosstalk. The dynamical behavior of characterization parameters is presented as well.

Yeasts used in fermentation processes are subject to different stress conditions, including low pH, high initial substrate concentration, accumulation of toxic compounds (e.g. ethanol), and temperature fluctuations. The fermentation of mescal is conducted under variable environmental conditions throughout the year. One of the most important environmental factors is temperature, as autumn and winter fermentations occur at low temperatures, but fermentation temperatures are much higher in summertime. The aim of this work was to compare the response of Saccharomyces cerevisiae strains isolated from agave fermentations to different stress conditions and two different medium culture one mimicking mezcal production, using agave must and other synthetic must development for analysis in wine industry. The strains isolated from agave were compared with a commercial strain used in wine elaboration, which exhibits good tolerance to the different stresses found in industrial fermentations. All strains grew in the presence of glucose and fructose irrespective of the sugar concentration, and low pH did not affect the formation of colonies. Differences in growth were observed among the strains at low temperature and high concentrations of ethanol. Only 28% of the tested strains exhibited good tolerance to high ethanol concentrations, a desirable trait for avoiding stuck fermentations. The strain ITD00185 was able to grow in alcoholic stress condition, consuming sugar and producing ethanol in agave must. This strain shows tolerance to the different stress conditions and may be a useful starter culture for agave fermentation, the potential of the native strains to be used to improve other industrial fermentation processes that involve low temperatures and high ethanol yields. Key words: Ethanol, tolerance, Mescal, native strains.

EFECTO DE LAS HORMONAS OXITOCINA Y PROSTAGLANDINA F2a DURANTE LA INSEMINACIÓN ARTIFICIAL SOBRE LA EFICIENCIA REPRODUCTIVA EN CERDAS

Denitrification was studied in anoxic batch cultures of a simulated fish processing wastewater at 37 r C and pH 7.5, using a denitrifying enrichment culture from fishery wastewater. Different initial nitrate to biomass ratios (So/Xo) were used: nitrate and biomass varied from 7.5 to 94.7 mg NO3-N l−1, and from 20 to 4300 mg volatile suspended solids l−1, respectively. The specific maximum denitrification rate (r m) and the cell yield (Y X / S) depended on the So/Xo ratio under anoxic conditions: r m increased from 1.2 to 1584 mg NO3-N g−1 VSS h−1 and Y X / S decreased from 42 to 0.03 mg VSS mg−1 NO3-N when So/Xo varied from 5.5 ⋅ 10− 3 to 9.3 mg NO3-N/mg VSS. Nomenclature CNO3 − N nitrate concentration, mg NO3-N l−1 K S saturation constant, mg NO3-N l−1 r m specific maximum denitrification rate, mg NO3-N g−1 VSS h−1 So initial substrate concentration, mg l−1 t time, h TOC total organic carbon VSS volatile suspended solids x biomass concentration, g VSS l−1 Xo initial biomass concentration, g VSS l−1 Y X/S substrate to biomass cell yield, mg VSS/mg N Greek symbols: μm maximum specific growth rate of the anoxic microbial population, 1 h−1

Mexico has long based its strength on the exploitation of its offshore fields to become one of the largest oil producers in the world. Although still yielding most of its production today, those mature fields have entered a downward trend for the past few years, with a gradual decline of their hydrocarbon output. This trend coincided with an increase in work over operations, most of them involving matrix acidizing interventions in carbonate formations for damage removal and stimulation purposes. Matrix stimulation of offshore Mexico fields presents several challenges, starting with the very nature of the carbonate rocks composing the reservoirs, whose properties can greatly vary within a short distance. In addition, the well conditions are also at times not well understood, with perforated intervals heterogeneously producing, and the increasing occurrence of water production. Finally, due to the location offshore, time-efficiency and operational simplicity became important workover requirements that have a direct impact on the chosen stimulation procedure, often achieved using a simple bullheading sequence, which unfortunately leaves the much needed control of zonal coverage out of the equation. This paper presents a carbonate acidizing workflow and interpretation method that have been developed and successfully implemented in offshore Mexico over the past couple of years. This technique constitutes the cornerstone to assessing and controlling matrix acidizing treatment coverage while it is pumped, in real-time, to ensure optimum treatment performance and maximum return on costs. The workflow relies on the use of a fiber-optic line enclosed inside a coiled tubing (CT) string to acquire distributed temperature sensing data, which are analyzed and translated into a zonal coverage profile using a fast interpretation algorithm. This information then allows stimulation engineers to determine the best strategy for the subsequent well stimulation treatment, including fluid volumes and placement sequence. As the case studies presented in this study will show, there is a lot to gain from this improved methodology. In particular, they show that the long-standing blind bullheading practice results in some shortcomings that may be detrimental to truly unlocking the full potential of those offshore fields.

A retrospective evaluation of the clinical and radiographic results of the Harris-Galante acetabular cups was performed in 112 patients with 127 total hip arthroplasties. Patients with 14 hips had died, and patients with 20 hips were lost to follow-up. A total of 82 patients with 93 hips was available for follow-up. There were 67 men and 45 women. The mean follow-up was 87 months (range, 48–113 months). There were a total of 9 revisions: 2 for recurrent dislocations, 1 for a loose cup, and 6 for wear and osteolysis. Radiographic evaluation demonstrated that 22 (24%) hips had periacetabular osteolysis, and 16 of these 22 (73%) were associated with the screws. Twenty-two hips (23%) demonstrated osteolytic lesions around the femoral stem. Mean femoral head displacement was of 1.00 mm (range, 0.40–4.5 mm) with a rate of 0.16 mm/yr (range, 0.05–0.44 mm/yr). The Harris-Galante socket has maintained a low implant failure rate at intermediate term, even in these young patients. As follow-up increases, wear of the polyethylene and periprosthetic osteolysis may become growing concerns.

To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA).RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences.Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0).The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients.Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.

The human evolutionary model is an intelligent global optimization method conceived to perform single and multiple objective optimization, this general method is still in development, especially the multi objective (MO) part is being improved. The single objective (SO) part has demonstrated that outperforms several algorithms that are in the state of the art, for example differential evolution (DE), particle swarm optimizer, and others, we called this part single objective intelligent evolutionary algorithm (SO-IEA). The SO-IEA uses mediative fuzzy logic (MFL) for handling doubtful and contradictory information from experts to calculate the appropriated amount of individuals to create and/or to eliminate. MFL is an extension of traditional fuzzy logic and includes intuitionistic fuzzy logic (IFL) in the Atanassov sense. In this work, we are presenting the algorithm's architecture, experimental results, and a graphical interface that will help to handle the required parameters to use the SO-IEA.

Heap leaching is an effective and widely used method of recovering metals from low-grade ores. However, the heap leaching technique has not yet been used in other biotechnological processes such as bioremediation. This work describes biostimulation of the native microbial consortium as a novel application of the heap leaching technique to bioremediate mining soils contaminated with hydrocarbons. Microorganisms present in the polluted soil were isolated in a liquid mineral solution using diesel fuel as the sole energy and carbon source. Biodegradation activity was evaluated and two genera, Flavobacterium and Aspergillus , were identified as the primary microorganisms that degraded hydrocarbons in the polluted soil. In order to simulate the heap leaching process on a laboratory scale, using both columns and piles, the contaminated soil was mixed with different sand concentrations and was agglomerated before it was used. Three flow rates, of the mineral solution, were evaluated. Of the rates tested, biodegradation was most efficient at a flow rate of 200 ml h −1 . The heap leaching technique demonstrated good efficiency in the column and pile, with a 2% soil–sand mixture lowering the TPH concentration from 61,000 to 1800 mg kg −1 (98.5%) in 15 d.

The neurovascular bundle anatomy in the upper arm displays changing relationships of nerve and vascular structures along short segments. Fibrous tissues segregate these elements into enclosed compartments allowing for specific patterns of injury. We report a patient with a iatrogenic brachial artery injury in this region who featured combined median and MAC neuropathies, which were consistent with complete axonotmesis on neurophysiological assessment. Increased intracompartmental pressure may have led to nerve injury either thorough an ischemic mechanism or to focal compression. Recognition of this unusual pattern of nerve damage is important, since injury can be accurately localized to the midportion of the neurovascular compartment in the upper arm.