Altitudinal and seasonal variations of persistent organic pollutants in the Bolivian Andes Mountains

Polyurethane foam disk passive air samplers were deployed over four periods of approximately 3 months along an altitudinal gradient (1820, 2600, 4650, and 5200 masl) on the east side of the Andean mountain range in Bolivia. The purpose of the study was to assess the gas-phase concentration and the altitudinal and seasonal trends of organochlorine pesticides and polychlorinated biphenyls (PCBs). Target compounds that were regularly detected included alpha- and gamma-hexachlorocyclohexane (HCH), endosulfans, and select PCB congeners. Endosulfans and HCH concentrations increased with altitude. Enrichment factors (concentration at the highest altitude divided by concentration at the lowest altitude) ranged from 10 to 20 for HCHs and 3 to 10 for endosulfans. Air parcel back trajectory analysis indicated that, in general, the high-altitude sites were exposed to a larger airshed and hence susceptible to long-range atmospheric transport from more distant regions. Seasonal differences were also observed with SigmaHCH concentrations peaking during periods 2 and 3 (March-September 2005). Airsheds (derived from the analysis of back trajectories) for periods 2 and 3 were less oriented along the Andes range (mountain air) with greater input from coastal regions. Endosulfans peaked during periods 1 and 2 (February-June 2005) and also exhibited the highest air concentrations of the target compounds, reaching approximately 1500 pg/m3 at the two highest elevation sites. PCB air concentrations at all sites were generally typical of global background values (<12 pg/m3) and showed no increase with altitude. This is the first study to measure air concentrations of persistent organic pollutants (POPs) in Bolivia and one of only a few studies to investigate altitudinal gradients of POPs.     

Cooperating CoScheduling: A Coscheduling Proposal Aimed at Non-Dedicated Heterogeneous NOWs

Implicit coscheduling techniques applied to non-dedicated homogeneous Networks Of Workstations （NOWs） have shown they can perform well when many local users compete with a single parallel job. Implicit coscheduling deals with minimizing the communication waiting time of parallel processes by identifying the processes in need of coscheduling through gathering and analyzing implicit runtime information, basically communication events. Unfortunately, implicit coscheduling techniques do not guarantee the performance of local and parallel jobs, when the number of parallel jobs competing against each other is increased. Thus, a low efficiency use of the idle computational resources is achieved.
In order to solve these problems, a new technique, named Cooperating CoScheduling （CCS）, is presented in this work. Unlike traditional implicit coscheduling techniques, under CCS, each node takes its scheduling decisions from the occurrence of local events, basically communication, memory, Input/Output and CPU, together with foreign events received from cooperating nodes. This allows CCS to provide a social contract based on reserving a percentage of CPU and memory resources to ensure the progress of parallel jobs without disturbing the local users, while coscheduling of communicating tasks is ensured. Besides, the CCS algorithm uses status information from the cooperating nodes to balance the resources across the cluster when necessary. Experimental results in a non-dedicated heterogeneous NOW reveal that CCS allows the idle resources to be exploited efficiently, thus obtaining a satisfactory speedup and provoking an overhead that is imperceptible to the local user.     

Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function

Microcirculation homeostasis depends on several channels permeable to ions and/or small molecules that facilitate the regulation of the vasomotor tone, hyperpermeability, the blood–brain barrier, and the neurovascular coupling function. Connexin (Cxs) and Pannexin (Panxs) large-pore channel proteins are implicated in several aspects of vascular physiology. The permeation of ions (i.e., Ca²⁺) and key metabolites (ATP, prostaglandins, D-serine, etc.) through Cxs (i.e., gap junction channels or hemichannels) and Panxs proteins plays a vital role in intercellular communication and maintaining vascular homeostasis. Therefore, dysregulation or genetic pathologies associated with these channels promote deleterious tissue consequences. This review provides an overview of current knowledge concerning the physiological role of these large-pore molecule channels in microcirculation (arterioles, capillaries, venules) and in the neurovascular coupling function.     

miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (CCND1, EGFR, ENTPD5, HOXA10, IGF1R, MYC, and SNAI2) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA–miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA–miRNA regulation during disease progression.     

Extracellular Cysteines Are Critical to Form Functional Cx46 Hemichannels

Connexin (Cxs) hemichannels participate in several physiological and pathological processes, but the molecular mechanisms that control their gating remain elusive. We aimed at determining the role of extracellular cysteines (Cys) in the gating and function of Cx46 hemichannels. We studied Cx46 and mutated all of its extracellular Cys to alanine (Ala) (one at a time) and studied the effects of the Cys mutations on Cx46 expression, localization, and hemichannel activity. Wild-type Cx46 and Cys mutants were expressed at comparable levels, with similar cellular localization. However, functional experiments showed that hemichannels formed by the Cys mutants did not open either in response to membrane depolarization or removal of extracellular divalent cations. Molecular-dynamics simulations showed that Cys mutants may show a possible alteration in the electrostatic potential of the hemichannel pore and an altered disposition of important residues that could contribute to the selectivity and voltage dependency in the hemichannels. Replacement of extracellular Cys resulted in “permanently closed hemichannels”, which is congruent with the inhibition of the Cx46 hemichannel by lipid peroxides, through the oxidation of extracellular Cys. These results point to the modification of extracellular Cys as potential targets for the treatment of Cx46-hemichannel associated pathologies, such as cataracts and cancer, and may shed light into the gating mechanisms of other Cx hemichannels.     

Probing the Conformational States of Thimet Oligopeptidase in Solution

Thimet oligopeptidase (TOP) is a metallopeptidase involved in the metabolism of oligopeptides inside and outside cells of various tissues. It has been proposed that substrate or inhibitor binding in the TOP active site induces a large hinge-bending movement leading to a closed structure, in which the bound ligand is enclosed. The main goal of the present work was to study this conformational change, and fluorescence techniques were used. Four active TOP mutants were created, each equipped with a single-Trp residue (fluorescence donor) and a p-nitro-phenylalanine (pNF) residue as fluorescence acceptor at opposite sides of the active site. pNF was biosynthetically incorporated with high efficiency using the amber codon suppression technology. Inhibitor binding induced shorter Donor-Acceptor (D-A) distances in all mutants, supporting the view that a hinge-like movement is operative in TOP. The activity of TOP is known to be dependent on the ionic strength of the assay buffer and D-A distances were measured at different ionic strengths. Interestingly, a correlation between the D-A distance and the catalytic activity of TOP was observed: the highest activities corresponded to the shortest D-A distances. In this study for the first time the hinge-bending motion of a metallopeptidase in solution could be studied, yielding insight about the position of the equilibrium between the open and closed conformation. This information will contribute to a more detailed understanding of the mode of action of these enzymes, including therapeutic targets like neurolysin and angiotensin-converting enzyme 2 (ACE2).     

Distributed text search using suffix arrays

Text search is a classical problem in Computer Science, with many data-intensive applications. For this problem, suffix arrays are among the most widely known and used data structures, enabling fast searches for phrases, terms, substrings and regular expressions in large texts. Potential application domains for these operations include large-scale search services, such as Web search engines, where it is necessary to efficiently process intensive-traffic streams of on-line queries. This paper proposes strategies to enable such services by means of suffix arrays. We introduce techniques for deploying suffix arrays on clusters of distributed-memory processors and then study the processing of multiple queries on the distributed data structure. Even though the cost of individual search operations in sequential (non-distributed) suffix arrays is low in practice, the problem of processing multiple queries on distributed-memory systems, so that hardware resources are used efficiently, is relevant to services aimed at achieving high query throughput at low operational costs. Our theoretical and experimental performance studies show that our proposals are suitable solutions for building efficient and scalable on-line search services based on suffix arrays.     

P2P OLAP: Data model,implementation and case study

It is a common situation nowadays that business groups own different companies that operate in an autonomous way. Nevertheless, these companies must be requested to provide the headquarters with summarized information for decision-making. An architecture for cooperative interchange of decision-making information seems to be a natural solution for this problem. We propose the use of a peer-to-peer (P2P) architecture for addressing the problem of processing OLAP data in a distributed environment, in a way that all companies involved can maintain full autonomy over the use of its own data resources. In a scenario like this, data exchange between peers occurs when one of them, in the role of a local peer, receives a query and, for answering it, requests data available in other nodes, denoted acquaintances. No global schema is assumed to exist for any data under this computing paradigm. Henceforth, data provided by an acquaintance of a local peer must be adapted, in a manner that answers to queries posed by local peer users conform the view those users have of their data. Because multidimensional data normally consist of a collection of views of aggregated data, a careful translation process is needed in this case, in order to transform any summary concept that appears in a peer acquaintance into a summary concept meaningful to the requesting peer. We first present a model for multidimensional data distributed in a P2P network, and a query rewriting technique, that allows a local peer to propagate OLAP queries among its acquaintances, obtaining a meaningful and correct answer. Mappings are performed using a novel technique called revise and map, based on belief revision concepts. Revising a dimension instance allows to produce consistent aggregations when an OLAP query is answered at more than one node. We then describe an implementation of a P2P system for answering OLAP queries over a network of data warehouses. We apply our proposal to a real-world case study of an insurance group. Finally, we report the results of an experimental evaluation of our implementation, and discuss the issues that must be accounted for in this setting.     

Spatial Control of Substitutional Dopants in Hexagonal Monolayer WS2: The Effect of Edge Termination

The ability to control the density and spatial distribution of substitutional dopants in semiconductors is crucial for achieving desired physicochemical properties. Substitutional doping with adjustable doping levels has been previously demonstrated in 2D transition metal dichalcogenides (TMDs); however, the spatial control of dopant distribution remains an open field. In this work, edge termination is demonstrated as an important characteristic of 2D TMD monocrystals that affects the distribution of substitutional dopants. Particularly, in chemical vapor deposition (CVD)-grown monolayer WS₂, it is found that a higher density of transition metal dopants is always incorporated in sulfur-terminated domains when compared to tungsten-terminated domains. Two representative examples demonstrate this spatial distribution control, including hexagonal iron- and vanadium-doped WS₂ monolayers. Density functional theory (DFT) calculations are further performed, indicating that the edge-dependent dopant distribution is due to a strong binding of tungsten atoms at tungsten-zigzag edges, resulting in the formation of open sites at sulfur-zigzag edges that enable preferential dopant incorporation. Based on these results, it is envisioned that edge termination in crystalline TMD monolayers can be utilized as a novel and effective knob for engineering the spatial distribution of substitutional dopants, leading to in-plane hetero-/multi-junctions that display fascinating electronic, optoelectronic, and magnetic properties.