Experiences in Agile R&D Project Management for New Product Design and Development in the Automotive Industry

In the past 20 years technology has advanced at incredible speed. Product life cycle has decreased tremendously. Innovation in product and process has become essential for companies’ survival. Products are not longer simple, they integrate different and new technologies and therefore manufacturing process is evolving towards intelligent, virtual, sustainable and high performance factories. In spite of all these changes in manufacturing, R&D project management has not evolved at the same pace. The authors have approached a new way of conducting R&D projects that can integrate IT Agile Project Management and Innovation Management best practices. As a result the present paperformulates a methodology for agile new product and process development that can match the actual product cycle development requirements, shortening project life cycles but keeping space for innovation and creativity. The methodology has been applied in R&D projects for the automotive industry to develop new automated manufacturing cells for production lines. The experience allowed to identify the key processes with more risk during the project execution and helped us to gather information to keep improving the methodology.Postprint (published version

Application of time-controlled critical point in pressure reducing valves: a case study in North Spain

Potable water utilities are currently making great efforts to reduce leakage rates and assure long-term supply to the population due to the challenges of climate change, growing population and water shortage scenarios that have been on them over the last years. One of the most employed methods to reduce leakage includes the installation of pressurereducing valves along the water distribution network and the utilization of pressure management schemes. Pressure management includes different types of control models, which are applied according to the requirements of each site. The most advanced and sophisticated scheme is critical point control, which relies on a flow signal from a measuring device or online communication between the critical point and the valve. This paper proposes the utilization of a seasonal autoregressive integrated moving average, or the SARIMA model, to correlate pressure at the outlet of the valve and pressure on the critical point of the area supplied, aiming to set a fixed pressure in the critical point. The SARIMA model is developed according to historical data logged in the field and then validated. Later, the SARIMA model was tested on a real location in the village of Noja, Spain. The analysis of the field test results prove that the proposed model is feasible to be used since there is no significance difference between the target values set in the critical point and the real values measured in the field. The research proves that the SARIMA model can be used as an alternative for critical point control in water distribution networks when no flow signal is available or when communication between the critical point and the pressure reducing valve is not an option

Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections

Antimicrobial drugs applied topically offer several advantages. However, the widespread use of antibiotics has led to increasing antimicrobial resistance. One interesting approach in the drug discovery process is drug repurposing. Disulfiram, which was originally approved as an anti-alcoholism drug, offers an attractive alternative to treat topical multidrug resistance bacteria in skin human infections. This study aimed to evaluate the biopharmaceutical characteristics of the drug and the effects arising from its topical application in detail. Microdilution susceptibility testing showed antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes. Dermal absorption revealed no permeation in pig skin. The quantification of the drug retained in pig skin demonstrated concentrations in the stratum corneum and epidermis, enough to treat skin infections. Moreover, in vitro cytotoxicity and micro-array analyses were performed to better understand the mechanism of action and revealed the importance of the drug as a metal ion chelator. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic to treat superficial human skin infections

Partial Polarization in Interfered Plasmon Fields

We describe the polarization features for plasmon fields generated by the interference between two elemental surface plasmon modes, obtaining a set of Stokes parameters which allows establishing a parallelism with the traditional polarization model. With the analysis presented, we find the corresponding coherence matrix for plasmon fields incorporating to the plasmon optics the study of partial polarization effects

Influence of Femtosecond Laser Modification on Biomechanical and Biofunctional Behavior of Porous Titanium Substrates

Bone resorption and inadequate osseointegration are considered the main problems of titanium implants. In this investigation, the texture and surface roughness of porous titanium samples obtained by the space holder technique were modified with a femtosecond Yb-doped fiber laser. Different percentages of porosity (30, 40, 50, and 60 vol.%) and particle range size (100–200 and 355–500 μm) were compared with fully-dense samples obtained by conventional powder metallurgy. After femtosecond laser treatment the formation of a rough surface with micro-columns and micro-holes occurred for all the studied substrates. The surface was covered by ripples over the micro-metric structures. This work evaluates both the influence of the macro-pores inherent to the spacer particles, as well as the micro-columns and the texture generated with the laser, on the wettability of the surface, the cell behavior (adhesion and proliferation of osteoblasts), micro-hardness (instrumented micro-indentation test, P–h curves) and scratch resistance. The titanium sample with 30 vol.% and a pore range size of 100–200 μm was the best candidate for the replacement of small damaged cortical bone tissues, based on its better biomechanical (stiffness and yield strength) and biofunctional balance (bone in-growth and in vitro osseointegration).Ministerio de Ciencia e Innovación del Gobierno de España PID2019-109371GB-100Junta de Andalucía (Spain) PAIDI P20-0067

A CRISPR-Cas9-engineered mouse model for GPI anchor deficiency mirrors human phenotype and shows hippocampal synaptic dysfunctions

Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency. Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol anchor pathway show cognitive impairments, a motor delay and in many cases epilepsy. Thus far, the pathophysiology underlying the disease remains unclear and suitable rodent models that mirror human pathophysiology have not been available. We therefore generated a mouse model using CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, at a site that is also conserved in mice, Pigv:c.1022C>A (p.A341E). Reflecting the human pathology mutant Pigv(341E) mice showed deficits in motor coordination and cognitive impairment with poorer long-term spatial memory than wild-type mice, as well as alterations in sociability and sleep patterns. Furthermore, immunohistochemistry showed decreased synaptophysin-immunoreactivity and electrophysiology recordings demonstrated reduced hippocampal synaptic transmission in Pigv(341E) mice that may underlie impaired memory formation. To gain a deeper and broader molecular understanding of the consequences of glycosylphosphatidylinositol anchor deficiency, we performed single-cell RNA sequencing on acutely isolated hippocampal cells of Pigv(341E) and wild-type mice. We found that hippocampal cells from adult Pigv(341E) mice exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction of Abl1 transcripts in several cell clusters suggests a link to the signaling pathway of glycosylphosphatidylinositol-anchored ephrins. We also observed increased levels of Hdc that might affect histamine metabolism with consequences in circadian rhythm. In summary, we present here the first mouse model with a patient-specific hypomorphic mutation that mirrors the human phenotype and shows a hippocampal synaptic defect. This new mouse model will not only open the doors for further investigation into the pathophysiology of glycosylphosphatidylinositol biosynthesis deficiency in future studies, but will also deepen our understanding in the role of glycosylphosphatidylinositol-anchor related pathways in brain development

Revealing prevalent cancers by interrogating glycoproteins with sustainable immunoelectrochemical tools

Trabajo presentado en el 4th European Biosensor Symposium, celebrado en Aquisgrán (Alemania), del 27 al 30 de agosto de 2023Introduction. The worldwide incidence and death toll of colorectal and pancreatic cancers (CRC and PDAC) have increased considerably since 1990. For this reason, both early detection and regular follow-up are considered key factors in improving patient prognosis. In this sense, the determination of the total content of specific proteins and their aberrantly glycosylated fraction in oncologic processes could help to achieve the proposed goals. Results and Discussion. In this work, two simple but highly competitive electrochemical immunoplatforms for the determination of total and glycosylated post-translational modified haptoglobin (Hp) [1], and CA19-9 [2] (candidate biomarkers associated with colorectal and pancreatic cancer, respectively) are presented. As seen in Figure 1, these biotools are uplifted in the use of magnetic immunocaptors and another antibody or a lectin as detector elements lastly labeled with HRP, which enables subsequent amperometric detection. The presented bioplatforms exhibit attractive characteristics in terms of simplicity, affordability, and point-of-care application compared to the conventional available methodologies, highlighting low detection limits (0.07 and 0.46 ng mL¿1 for total and glycosylated Hp, respectively, and 1.5 U mL¿1 for CA19-9), and short assay times (< 2 h). The workability of these quantitative bioplatforms for the analysis of secretomes from cultured CRC cells with the distinct potential to metastasize (Hp) or serum samples from healthy and PDAC-diagnosed subjects (CA19-9) was assessed to definitely confirm full exploitation of all the above exposed enticing attributes. Conclusions. Our findings clearly revealed the unquestionable ability of these modern electrochemical immunoplatforms to discriminate between healthy and cancer-diagnosed subjects, as well as to assess disease progression, positioning these simple but effective methodologies as advanced electroanalytical tools with proven real biomedical applications, and the hope of aiding in the accurate diagnosis of prevalent and high mortality cancers

Preparation of a questionnaire to detect cases of hate violence in emergency rooms.

In the context of the SIVIVO project, the development of a tool to facilitate the detection, recording and description of cases of hate violence and its consequences on health was proposed. A two-round Delphi method was used with experts from clinical-care, public health, epidemiological, academic, administration and non-governmental organizations to assess the relevance of different items using a Likert scale, presenting the results with medians and coefficients of variation. The best evaluated questions, with scores equal to or greater than 4, and which make up the final version of the questionnaire are the relative socio-demographic characteristics of the victim, the injuries, description of the incident, the motivations perceived by the aggrieved person, possible evidence of hatred, the intention to denounce and the perception of the health personnel of the motive for the aggression. The piloting showed the adequacy of the questions that were finally selected. The systematic incorporation of this tool can help us to learn the magnitude and characteristics of hate violence and its impact on health. This information would allow the elaboration of prevention and intervention strategies aimed, specifically, at the sectors of the population most exposed to this type of violence.Acción Estratégica en Salud 2013: PI13/02267. Cofinanciado con fondos FEDER.S

Intra and Inter-Population Morphological Variation of Shape and Size of the Chilean Magnificent Beetle, Ceroglossus chilensis in the Baker River Basin, Chilean Patagonia

The alteration of habitat generates different degrees of stress in insects. It has been suggested that the degrees of phenotypic disturbances reflect the ability of an individual to overcome the effects of stress. The Baker River Basin in the Aysén Region, Chilean Patagonia has a very fragmented landscape, due to the destruction of the native forest and the use of land for agriculture and animal husbandry. This alteration should generate different degrees of disturbances in the insect communities, whose effects may be quantified by geometric morphometric tools. We analyzed morphological differences in 244 males and 133 females of the the Chilean magnificent beetle, Ceroglossus chilensis (Eschscholtz) (Coleoptera: Carabidae) collected in January, 2007, in mixed forests of Nothofagus dombeyi Mirbel (Ørsted) (Fagales: Nothofagaceae) and N. nitida Hofmus and in Second-growth forest of N. pumilio (Poepp. & Endl.) Krasser. Males were generally wider in the pronotum, while females had wider abdominal sternites. Although there were significant differences in shape and size between mature forests and second-growth forest, these were less significant among the sites within each type of vegetal formation. Individuals had more shape variations in the mature forest. We suggest that differences in shape are due at least in part to the isolation of the habitat. The differences found between sexes raises the question of how morphological variations and sexual dimorphism may be affected spatially by natural selection