Key performance indicators and the mineral value chain integration

The exceptional advance of information technology and computer application to the mineral sector has allowed the automation of several processes of the mineral value chain. ERP systems (Enterprise Resource Planning) provided the platform for the efficient integration of all support activities of the mineral value chain. Despite all advances gathered with the application of computers, it was not possible to date, to effectively integrate the primary activities of the mineral value chain. The main reason for that are the uncertainties present in the productive process, which are intrinsic to the business, and the difficulty to quantify and qualify the benefits obtained with this integration due to the lack of a clear definition of the key performance indicators (KPIs). This work presents an analysis of the ERP systems application in Brazilian mining, identifies the KPIs of some of the most important Brazilian mining companies, and discusses the importance of mapping and measuring these indicators for the effective. management of the mining business.O rápido avanço da tecnologia da informação e da aplicação de computadores ao setor mineral permitiu a automatização de vários processos da cadeia de valor mineral. Os sistemas ERP (Enterprise Resource Planning) forneceram a plataforma para a integração eficiente de todas as atividades de suporte da mineração. Apesar do avanço\ud obtido com a aplicação dos computadores, não se conseguiu, até o presente momento, integrar, efetivamente, as atividades primárias da cadeia de valor mineral. A principal razão, para isso, são as incertezas existentes no processo produtivo, que são intrínsecas ao negócio, e a dificuldade de se quantificarem e qualificarem os benefícios advindos\ud de tal integração, isto por não existir uma definição clara dos indicadores-chave de desempenho (KPIs). Esse trabalho apresenta uma análise da aplicação de sistemas ERP, na mineração do Brasil, identifica os KPIs mais importantes utilizados em empresas de mineração e discute a importância de seu mapeamento e medição para a gestão efetiva do negócio “Mineração”

A Simple Transient Poiseuille-Based Approach to Mimic the Womersley Function and to Model Pulsatile Blood Flow

As it is known, the Womersley function models velocity as a function of radius and time. It has been widely used to simulate the pulsatile blood flow through circular ducts. In this context, the present study is focused on the introduction of a simple function as an approximation of theWomersley function in order to evaluate its accuracy. This approximation consists of a simple quadratic function, suitable to be implemented in most commercial and non-commercial computational fluid dynamics codes, without the aid of external mathematical libraries. The Womersley function and the new function have been implemented here as boundary conditions in OpenFOAM ESI software (v.1906). The discrepancy between the obtained results proved to be within 0.7%, which fully validates the calculation approach implemented here. This approach is valid when a simplified analysis of the system is pointed out, in which flow reversals are not contemplated

The TRPM1 channel in ON-bipolar cells is gated by both the α and the βî 3 subunits of the G-protein G o

Transmission from photoreceptors to ON bipolar cells in mammalian retina is mediated by a sign-inverting cascade. Upon binding glutamate, the metabotropic glutamate receptor mGluR6 activates the heterotrimeric G-protein Gα o β3γ 313, and this leads to closure of the TRPM1 channel (melastatin). TRPM1 is thought to be constitutively open, but the mechanism that leads to its closure is unclear. We investigated this question in mouse rod bipolar cells by dialyzing reagents that modify the activity of either Gα o or Gβγ 3 and then observing their effects on the basal holding current. After opening the TRPM1 channels with light, a constitutively active mutant of Gα o closed the channel, but wild-type Gα o did not. After closing the channels by dark adaptation, phosducin or inactive Gα o (both sequester Gβγ 3) opened the channel while the active mutant of Gα o did not. Co-immunoprecipitation showed that TRPM1 interacts with Gβ3 and with the active and inactive forms of Gα o. Furthermore, bioluminescent energy transfer assays indicated that while Gα o interacts with both the N-and the C-termini of TRPM1, Gβγ 3 interacts only with the N-terminus. Our physiological and biochemical results suggest that both Gα o and Gβγ 3 bind TRPM1 channels and cooperate to close them.Fil: Xu, Ying. Jinan University; China. Nantong University; ChinaFil: Orlandi, Cesare. The Scripps Research Institute; Estados UnidosFil: Cao, Yan. The Scripps Research Institute; Estados UnidosFil: Yang, Shengyan. Jinan University; ChinaFil: Choi, Chan-Il. Research Triangle Park; Estados UnidosFil: Pagadala, Vijayakanth. Research Triangle Park; Estados UnidosFil: Birnbaumer, Lutz. Research Triangle Park; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Martemyanov, Kirill A.. The Scripps Research Institute; Estados UnidosFil: Vardi, Noga. State University of Pennsylvania; Estados Unido

Cellular and Subcellular Localization of the RGS7/Gβ5/R7BP Complex in the Cerebellar Cortex

A member of regulator of G-protein signaling family, RGS7, is an essential modulator of signaling through GABAB receptors. RGS7 functions as a macromolecular complex with type 5 G protein β (Gβ5) and R7 binding protein (R7BP) to control the localization and function of the resultant heterotrimeric complexes. Here, we used co-immunoprecipitation, in situ hybridization, histoblot and immunohistochemical techniques at the light and electron microscopic level to advance understanding of RGS7-Gβ5-R7BP complexes in the central nervous system, focusing on distinct neuronal populations in the cerebellar cortex. Histoblot analysis showed that RGS7, Gβ5 and R7BP proteins were widely expressed in the brain, with mostly an overlapping pattern and showing a high expression level in the molecular layer of the cerebellar cortex. Co-immunoprecipitation experiments established that the RGS7/Gβ5 forms complexes with R7BP in the cerebellum. At the cellular level, RGS7 and R7BP mRNAs were expressed at the highest level in Purkinje cells (PCs) and Golgi cells, and at low levels in granule cells. Immunohistochemistry confirmed that labeling for RGS7, Gβ5 and R7BP were present in the three neuronal populations and concentrated in dendrites and spines. At the electron microscopic level, immunolabeling for RGS7, Gβ5 and R7BP proteins was found both at postsynaptic and presynaptic sites and showed similar distribution patterns. Immunoreactivity for the three proteins was mostly localized along the extrasynaptic plasma membrane of dendritic shafts and spines of PCs and to a lesser extent, in axon terminals (AT) establishing excitatory synapses. Quantitative analysis of immunogold particles for RGS7, Gβ5 and R7BP revealed that they are non-uniformly distributed along the surface of PCs, and show enrichment around excitatory synapses on dendritic spines. We further report that deletion of R7BP in mice reduced the targeting of both RGS7 and Gβ5 to the plasma membrane. Altogether, these data support the existence of macromolecular complexes composed of RGS7-Gβ5-R7BP in PCs. The location at post- and pre-synaptic sites in PCs spines-parallel fiber synapses suggests their involvement in the modulation of glutamatergic neurotransmission in the cerebellar cortex

A Randomized, Placebo-Controlled, Phase II Study of Tetomilast in Active Ulcerative Colitis

BACKGROUND & AIMS: Tetomilast (OPC-6535), a novel thiazole compound, inhibits phosphodiesterase-4 and proinflammatory functions of leukocytes including superoxide production and cytokine release. METHODS: One hundred eighty-six patients with mildly to moderately active ulcerative colitis (Disease Activity Index [DAI] 4-11 points) from 35 centers were randomized to receive an oral, once-daily dose of placebo or tetomilast 25 mg or 50 mg for 8 weeks. RESULTS: Percentages of patients reaching the primary end point (improvement as defined by reduction in DAI > or =3 at week 8) were not significantly different between placebo (35%) and either the 25 mg tetomilast (52%) or the 50 mg tetomilast (39%) groups (intent-to-treat population). Remission rates (DAI 0-1) were 7%, 16%, and 21%, respectively (not significant). Mean reduction in DAI at week 8 was greater in the 25-mg group than under placebo (2.8 +/- 0.4 vs 1.7 +/- 0.36, respectively, P = .041) and approached statistical significance in the 50-mg group (2.8 +/- 0.46, P = .056). A post hoc analysis focusing on patients with high activity scores (baseline DAI 7-11) suggested differences between tetomilast and placebo that will require further investigation. No significant safety concerns were raised. Main adverse effects included gastrointestinal problems (nausea, vomiting) and were preferentially seen in the 50-mg tetomilast group. CONCLUSIONS: This phase II trial of tetomilast in ulcerative colitis did not achieve statistical significance for the primary end point. Secondary end points indicate a potential clinical activity of tetomilast. The post hoc analysis suggests that further clinical development should focus on patients with objective parameters of inflammation

Two Different Therapeutic Approaches for SARS-CoV-2 in hiPSCs-Derived Lung Organoids

The global health emergency for SARS-CoV-2 (COVID-19) created an urgent need to develop new treatments and therapeutic drugs. In this study, we tested, for the first time on human cells, a new tetravalent neutralizing antibody (15033-7) targeting Spike protein and a synthetic peptide homologous to dipeptidyl peptidase-4 (DPP4) receptor on host cells. Both could represent powerful immunotherapeutic candidates for COVID-19 treatment. The infection begins in the proximal airways, namely the alveolar type 2 (AT2) cells of the distal lung, which express both ACE2 and DPP4 receptors. Thus, to evaluate the efficacy of both approaches, we developed three-dimensional (3D) complex lung organoid structures (hLORGs) derived from human-induced pluripotent stem cells (iPSCs) and resembling the in vivo organ. Afterward, hLORGs were infected by different SARS-CoV-2 S pseudovirus variants and treated by the Ab15033-7 or DPP4 peptide. Using both approaches, we observed a significant reduction of viral entry and a modulation of the expression of genes implicated in innate immunity and inflammatory response. These data demonstrate the efficacy of such approaches in strongly reducing the infection efficiency in vitro and, importantly, provide proof-of-principle evidence that hiPSC-derived hLORGs represent an ideal in vitro system for testing both therapeutic and preventive modalities against COVID-19