Cognitive Energy Cost of Informed Decisions

Time irreversibility in neuronal dynamics has recently been demonstrated to correlate with various indicators of cognitive effort in living systems. Using Landauer's principle, which posits that time-irreversible information processing consumes energy, we establish a thermodynamically consistent measure of cognitive energy cost associated with belief dynamics. We utilize this concept to analyze a two-armed bandit game, a standard decision-making framework under uncertainty, considering exploitation, finite memory, and concurrent allocation to both game options or arms. Through exploitative, prediction-error-based belief dynamics, the decision maker incurs a cognitive energy cost. Initially, we observe the rise of dissipative structures in the steady state of the belief space due to time-reversal symmetry breaking at intermediate exploitative levels. To delve deeper into the belief dynamics, we liken it to the behavior of an active particle subjected to state-dependent noise. This analogy enables us to relate emergent risk aversion to standard thermophoresis, connecting two apparently unrelated concepts. Finally, we numerically compute the time irreversibility of belief dynamics in the steady state, revealing a strong correlation between elevated - yet optimized - cognitive energy cost and optimal decision-making outcomes. This correlation suggests a mechanism for the evolution of living systems towards maximally out-of-equilibrium structures

Neonatal Hyperbilirubinemia: <i>in vivo</i> Characterization of Mechanisms of Bilirubin Neurotoxicity and Pharmacological Treatments

Neonatal jaundice or hyperbilirubinemia is the result of alterations in the bilirubin metabolism. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced neurological dysfunction and, if untreated, eventually death by kernicterus. Severe hyperbilirubinemia results in the saturation of the bilirubin binding capacity of plasma albumin, with the consequent increase in the fraction of unconjugated bilirubin (UCB) not bound to albumin (free bilirubin, Bf) that, due to its lipophilicity, crosses the blood brain barrier accumulating in the brain and triggering the neuronal injury. In the developing central nervous system, a wide range of cellular functions are affected and the concerted disruption of their regulation results in cellular damage. Patients experiencing prolonged toxic bilirubin levels are characterized by a number of neurological deficits, such as abnormalities in motor, sensitive and cognitive functions. Despite intensive studies, several aspects of the mechanisms operating at the onset of the disease are still partially understood. To study severe neonatal hyperbilirubinemia and possible therapies, I took advantage of the Ugt1-/- mouse model previously generated in my laboratory. Homozygous mutant mice develop jaundice and accumulate bilirubin in the brain due to the lack of the Ugt1a1 enzyme. If untreated, mutant mice show neurological deficits leading to early neonatal lethality. The work performed in this Thesis explores three different aspects of bilirubin neurotoxicity: 1. The role of Bf in vivo by the administration of human serum albumin; 2. The events preceding death by a time-course analysis of mutant pups; 3. The investigation of the role of neuroinflammation by the administration of a neuroprotective and anti-inflammatory drug. The obtained results showed that increasing plasma bilirubin-binding capacity by albumin supplementation decreases bilirubin neurotoxicity. In fact, daily albumin administration avoided the accumulation of Bf in the brain by its mobilization from tissues to plasma, resulting in the complete rescue of bilirubin-induced brain impairment and lethality. Moreover, this study highlighted the reliability of Bf as the best marker to predict neurotoxicity risk. The time-course investigation of the events occurring in the cerebellum of Ugt1-/- pups leading to bilirubin-brain damage showed the prevalence of ER stress, oxidative stress and neuroinflammation at the onset of neonatal hyperbilirubinemia that, in turn, affected brain integrity by their concerted effect resulting in neurodegeneration. Finally, the administration of minocycline (MNC), an antibiotic with neuroprotective and anti-inflammatory properties, partially prevented lethality by hyperbilirubinemia and rescued animals by significantly reducing neurodegenerative and neuroinflammatory features that characterized the untreated Ugt1-/- mouse model. This study demonstrates the contribution of ER stress and inflammation in the onset of the disease, the relevance of these mechanisms during the attenuation of neurodegeneration by MNC administration, and that albumin supplementation is a potential therapeutic alternative to treat bilirubin neurotoxicity in acute cases in which prompt exchange transfusion is required

Redundancy in sensors, control and planning of a robotic system for space telerobotics

The analysis and development of a manipulator redundant in structure and sensor devices controlled by a distributed multiprocessor architecture are discussed. The goal has been the realization of a modular structure of the manipulator with evident aspects of flexibility and transportability. The distributed control structure, thanks to his modularity and flexibility could be integrated in the future into an operative structure aimed to space telerobotics. The architecture is applied to the 6 DOF manipulator Gilberto

Le Varietà di olive sarde suscettibili di trasformazione per olive da mensa: nota 2.: caratteristiche e attitudini della cv. « Sivigliana »

A research has been carried in the 1975 and 1977 on the « Sivigliana » cv. olives from Sassari, by control the technological and marketing characteristic and behaviour during the preparation of table olives by emploing the lacting fermentation. The results obtained have revealed the excellent charactcristics of size and the favorable ratio of pulpe/stone. Some reserve is expressed in relation to their sugar content. The processing test have confirmed that is possible to destine the « Sivigliana» cv. olives from Sassari at the trasformation for the table

Pengembangan Perangkat Pembelajaran Flipped Classroom Pada Materi Getaran Harmonis

The aims of this research are to determine the validity of the product by experts and practitioners as well as to describe the attractiveness, the easiness and the expediency of the product. Development models used in this research is the ADDIE model which consists of five stages: analysis, design, development, implementation, and evaluation. The stage at this research explains only at the stage of development. The results obtained from expert validation test with an average score of 3.60 with the qualifying products is very valid, practitioners test results obtained an average score of 3.28 with very valid qualifying, and one by one test results of the product showed that the product was very attractive, very easy to use, and helpful. Penelitian ini bertujuan untuk mengetahui validitas produk oleh ahli dan praktisi serta untuk mendeskripsikan kemenarikan, kemudahan, dan kemanfaatan dari produk pengembangan. Model pengembangan yang digunakan dalam penelitian ini adalah model ADDIE yang terdiri dari lima tahapan, yaitu analisis, desain, pengembangan, implementasi, dan evaluasi. Pada penelitian ini, tahapan yang dilakukan hanya sampai pada tahap pengembangan. Hasil penelitian yang diperoleh dari uji validasi ahli yaitu rata-rata skor produk 3,60 dengan kualifikasi sangat valid, hasil uji praktisi diperoleh rata-rata skor 3,28 dengan kualifikasi sangat valid, dan hasil uji 1-1 menunjukkan bahwa produk memiliki kualitas sangat menarik, sangat mudah digunakan, dan bermanfaat

Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia

Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free bilirubin, Bf). Human serum albumin (HSA) administration was suggested to increase plasma bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency. Albumin infusion increased plasma bilirubin-binding capacity, mobilizing bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of albumin administration in severe acute hyperbilirubinemia conditions to prevent or treat bilirubin neurotoxicity in situations in which exchange transfusion may be required.</p

A new laser device for ultra-rapid and sustainable aerosol sterilization

The current COVID-19 pandemic has highlighted the importance of aerosol-based transmission of human pathogens; this therefore calls for novel medical devices which are able to sterilize contaminated aerosols. Here we describe a new laser device able to sterilize droplets containing either viruses or bacteria. Using engineered viral particles, we determined the 10,600 nm wavelength as the most efficient and exploitable laser source to be manufactured in a commercial device. Given the lack of existing working models to reproduce a human aerosol containing living microbial particles, we developed a new system mimicking human droplet formation and preserving bacterial and viral viability. This evidenced the efficacy of 10,600 nm laser light to kill two aerosol transmitted human pathogens, Legionella pneumophila and SARS-CoV-2. The minimal exposure time of &lt;15 ms was required for the inactivation of over 99% pathogens in the aerosol; this is a key element in the design of a device that is safe and can be used in preventing inter-individual transmission. This represents a major advantage over existing devices, which mainly aim at either purifying incoming air by filters or sterilizing solid surfaces, which are not the major transmission routes for airborne communicable diseases

La Deumidificazione su piccola scala dei frutti di fico

Niedda longa fig fruits (Ficus carica L.) were dried by dehumidification. Fruits were divided in two different size groups, and dried for 120 h (A) or 96 h (B) in a room (8.5 m3), in which 30.5°C-32.0°C of temperature and 34-40% of relative humidity were held by a small dehumidifier (29 kg weight). The lots A and B reached respectively 79.3±0.88% and 69.6±4.74% of dry matter content, at the end of the process. Following drying, fruits were sprayed with a potassium sorbate solution, then film packaged in air or in modified atmosphere and transferred at 20 °C to simulate shelf life. Lot A fruits were the most similar for chemical composition to imported dried figs. However, neither lot A nor B substantially differed, after 3 months of shelf life, for external-total count of yeasts, moulds and bacteria from the purchased fruits. Thus, the combination between dehumidification and potassium-sorbate treatment may allow for safe dried figs to be obtained. Si riferisce su una prova di essiccazione per deumidificazione di frutti di fico (Ficus carica L.) della cv "Niedda longa". I frutti, separati in due lotti differenti per il peso, venivano essiccati per 120 h (A) o 96 h (B), con un deumidificatore, di 29 kg di peso, che manteneva i valori di temperatura e di umidità relativa di un ambiente di 8,5 m3, rispettivamente tra 30,5°-32,0°C e 34-40%. I lotti A e B rispettivamente, al termine dell'essiccazione, avevano un contenuto di sostanza secca del 79,3±0,88% e del 69,6±4,74%. Alla fine i frutti venivano trattati con potassio sorbato, confezionati anche in regime di atmosfera modificata e conservati per 3 mesi a 20°C. Il lotto A era il più simile, per composizione chimica, ai fichi secchi d'importazione. Comunque, per quanto riguarda le conte di lieviti, muffe e batteri epifitici, entrmabi i lotti non presentavano differenze degne di nota, rispetto ai fichi d'importazione. Sembra pertanto che l'abbinamento tra deumidificazione e trattamento con potassio sorbato permetta di produrre fichi essiccati stabili nel tempo

Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice

Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced encephalopathy and eventually death by kernicterus. Despite extensive studies, the molecular and cellular mechanisms of bilirubin toxicity are still poorly defined. To fill this gap, we investigated the molecular processes underlying neuronal injury in a mouse model of severe neonatal jaundice, which develops hyperbilirubinemia as a consequence of a null mutation in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia, neuronal cell death and die shortly after birth because of bilirubin neurotoxicity. To identify protein changes associated with bilirubin-induced cell death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild-type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant processes as important intracellular mechanisms altered during bilirubin-induced neurotoxicity. In particular, they revealed that down-representation of DJ-1, superoxide dismutase, peroxiredoxins 2 and 6 was associated with hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction in protein levels seems to result from post-translational mechanisms because we did not detect significant quantitative differences in the corresponding mRNAs. We also observed an increase in neuro-specific enolase 2 both in the cerebellum and in the serum of mutant mice, supporting its potential use as a biomarker of bilirubin-induced neurological damage. In conclusion, our data show that different protective mechanisms fail to contrast oxidative burst in bilirubin-affected brain regions, ultimately leading to neurodegeneration. \ua9 2015 Macmillan Publishers Limited All rights reserved

Detection of fish allergen by droplet digital PCR

Fish is one of fourteen allergens that must be highlighted on the label within the ingredients list. It should be noted that the European regulation, is very restrictive to allergens with zero tolerance. Therefore it is important to establish sensitive and specific methods for detecting fish allergen. Applicability to detect and quantify fish allergen by droplet digital polymerase chain reaction (ddPCR) has been evaluated in this work. Genomic DNA of three fish species belonging to the most common fish families were analyzed. PCR primers were designed to amplify a 166 bp region of the 18S rRNA gene. Comparative studies were performed to establish the optimal primer and probe concentrations.  Annealing temperature was determined by using thermal gradient. The results have shown good applicability of the optimized 18S rRNA gene-method to detect and quantify small amounts of the target in all samples analyzed. However, validation studies are needed in order to apply ddPCR technology for routine allergens analysis.