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Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat carlo M.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and Molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

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Antioxidant treatment for oligoasthenoteratozoospermia and varicocele:a DBPC trial to evaluate the impact of age and body mass index

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Asian Journal of Andrology 2024年第3期26卷 239-244页

作者： Gian Maria Busetto Bernarde F Rodrigues Ashraf Virmani Andrea Checchia Antonella Ninivaggi Anna Ricapito Giovanni Barbieri Piero Fischetti Ugo G Falagario Pasquale Annese Nicola d’Altilia Vito Mancini Matteo Ferro Felice Crocetto Angelo Porreca carlo Bettocchi Luigi Cormio Ashok Agarwal Giuseppe Carrieri University of Foggia Foggia 71122Italy Department of Urology and Renal Transplantation Policlinico of FoggiaFoggia 71122Italy Department of Urology Human Reproduction SectionFederal University of Sao PauloSao Paulo 05403-000Brazil Alfasigma Healthscience Utrecht 3528 BGThe Netherlands Urology Unit “G.Tatarella”HospitalCerignola 71042Italy Urology Unit European Institute of Oncology(IEO)IRCCSMilan 20142Italy University of Naples Federico II Naples80126Italy Department of Oncological Urology Veneto Institute of Oncology(IOV)IRCCSPadua 35039Italy Urology Unit “L.Bonomo”HospitalAndria 70031Italy Global Andrology Forum Moreland HillsOH 44022USA

Oxidative stress is one of the main mechanisms responsible for male *** conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the *** are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe *** reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive *** double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on *** concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this *** conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

关键词： aging antioxidants body mass index oligoasthenoteratozoospermia varicocele

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Herpes simplex keratitis:A brief clinical overview

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World Journal of Virology 2024年第1期13卷 5-32页

作者： Mutali Musa Ehimare Enaholo Gladness Aluyi-Osa George Nnamdi Atuanya Leopoldo Spadea carlo Salati Marco Zeppieri Department of Optometry University of BeninBenin 300283Nigeria Department of Ophthalmology Africa Eye Laser CentreKm 7Benin 300105Nigeria Department of Ophthalmology Centre for Sight AfricaNkpor 434101Nigeria Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy of Ophthalmology University Hospital of UdineUdine 33100Italy

The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal viral infection is caused by the herpes simplex virus(HSV),which can affect several tissues,including the *** significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the *** the initial infection,the HSV can establish a latent infection in the trigeminal ganglion,a nerve cluster near the *** virus may remain dormant for extended *** reactivation of the virus can occur,leading to recurrent episodes of *** triggering reactivation include stress,illness,immunosuppression,or *** episodes can manifest in different clinical patterns,ranging from mild epithelial involvement to more severe stromal or endothelial *** severity and frequency of recurrences vary among *** cases of HSK,especially those involving the stroma and leading to scarring,can result in vision impairment or even blindness in extreme *** cornea's clarity is crucial for good vision,and scarring can compromise this,potentially leading to visual *** management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via *** medications,such as oral Acyclovir or topical Ganciclovir,may be prescribed for *** immune response to the virus can contribute to corneal ***,caused by the body's attempt to control the infection,may inadvertently harm the corneal *** should be informed about triggers and advised on measures to minimize the risk of *** summary,the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintai

关键词： Herpes simplex virus Herpes simplex keratitis Acyclovir Neurotization Reactivation

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Minimally invasive surgical therapies(MISTs)for lower urinary tract symptoms(LUTS):promise or panacea?

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Asian Journal of Andrology 2024年第2期26卷 135-143页

作者： Gian Maria Busetto Andrea Checchia Marco Recchia Edoardo Tocci Ugo G Falagario Gennaro Annunziata Pasquale Annese Nicola d'Altilia Vito Mancini Matteo Ferro Felice Crocetto Octavian Sabin Tataru Luca Di Gianfrancesco Angelo Porreca Francesco Del Giudice Ettore De Berardinis carlo Bettocchi Luigi Cormio Giuseppe Carrieri University of Foggia Foggia 71122Italy Department of Urology and Renal Transplantation Policlinico of FoggiaFoggia 71122Italy Urology Unit "G.Tatarlla"HospitalCerignola 71042Italy Urology Unit European Institute of Oncology(IE0)IRCcSMilan 20141Italy University of Naples Federico Il Naples 80126Italy G.E.Palade University of Medicine PharmacyScienceand Technology of Targu MuresTargu Mures 540142Romania Department of Oncological Urology Veneto Institute of Oncology(IOv)IRccSPadua 35128Italy Department of Maternal-Infant and Urological Sciences Sapienza Rome UniversityRoma 00161Italy Urology Unit "L.Bonomo"HospitalAndria 76123Italy

The increasing importance of treatment of lower urinary tract symptoms(LUTS),while avoiding side effects and maintaining sexual function,has allowed for the development of minimally invasive surgical therapies(MiSTs).Recently,the European Association of Urology guidelines reported a paradigm shift from the management of benign prostatic hyperplasia(BPH)to the management of nonneurogenic male *** aim of the present review was to evaluate the efficacy and safety of the most commonly used MisTs:ablative techniques such as aquablation,prostatic artery embolization,water vapor energy,and transperineal prostate laser ablation,and nonablative techniques such as prostatic urethral lift and temporarily implanted nitinol device(iTIND).MiSTs are becoming a new promise,even if clinical trials with longer follow-up are still *** of them are still under investigation and,to date,only a few options have been given as a recommendation for *** cannot be considered as standard of care and are not suitable for all *** and disadvantages should be underlined,without forgetting our objective:treatment of LUTS and re-treatment avoidance.

关键词： aquablation iTIND prostatic artery embolization prostatic urethral lift transperineal prostate laser ablation water vapor energy

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New frontiers in retinal transplantation

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World Journal of Transplantation 2024年第4期14卷 67-77页

作者： Francesco Saverio Sorrentino Patrick Di Terlizzi Francesco De Rosa carlo Salati Leopoldo Spadea Caterina Gagliano Mutali Musa Marco Zeppieri Department of Surgical Sciences Unit of OphthalmologyOspedale MaggioreBologna 40100Italy Department of Oncology IRCCS Istituto Romagnolo per lo Studio dei Tumori“Dino Amadori”Meldola 47014Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy Department of Medicine and Surgery University of Enna"Kore"Enna 94100Italy Eye Clinic Catania University San Marco HospitalCatania 95121Italy Department of Optometry University of BeninBenin 300283Nigeria Department of Ophthalmology Centre for Sight AfricaNkporOnitsha 434112Nigeria

New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal *** or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal ***,the disruption of photoreceptors takes ***,even in advanced forms of retinal degeneration,a good percentage of the ganglion cells and the inner nuclear layer neurons remain *** phenomenon provides evidence for obtaining retinal circuitry through the transplantation of photoreceptors into the subretinal *** eye is regarded as an optimal organ for cell transplantation because of its immunological privilege and the relatively small number of cells collaborating to carry out visual *** eyeball's immunological privilege,characterized by the suppression of delayed-type hypersensitivity responses in ocular tissues,is responsible for the low rate of graft rejection in transplant *** main discoveries highlight the capacity of embryonic stem cells(ESCs)and induced pluripotent stem cells to regenerate damaged retinal *** progress has shown significant enhancements in transplant procedures and *** research also explores the ethical ramifications linked to the utilization of stem cells,emphasizing the ongoing issue surrounding *** analysis centers on recent breakthroughs,including the fabrication of three-dimensional retinal organoids and the innovation of scaffolding for cell ***,researchers are currently assessing the possibility of CRISPR and other advanced gene editing technologies to enhance the outcomes of retinal *** widespread use of universally recognized safe surgical and imaging methods enables retinal transplantation and monitoring of transplanted cell growth toward the correct ***,most therapy approaches

关键词： Retinal transplantation Retinal stem cell Human embryonic stem cells Pluripotent stem cells Retinal tissue transplant

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The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 71-76页

作者： Alessandro Fugazza Matteo Colombo Michel Kahaleh V.Raman Muthusamy Bick Benjamin Wim Laleman Carmelo Barbera carlo Fabbri Jose Nieto Abed Al-Lehibi Mohan Ramchandani Amy Tyberg Haroon Shahid Avik Sarkar Dean Ehrlich Stuart Shermand Cecilia Binda Marco Spadaccini Andrea Iannone Kareem Khalaf Nageshwar Reddy Andrea Anderloni Alessandro Repici Division of Gastroenterology and Digestive Endoscopy Humanitas Research Hospital-IRCCSVia Manzoni 5620089RozzanoMilanoItaly Gastroenterology Rutgers Robert Wood JohnsonNew BrunswickNew JerseyUSA Vatche and Tamar Manoukian Division of Digestive Diseases University of CaliforniaLos Angeles School of Medicine at UCLALos AngelesCaliforniaUSA Division of Digestive and Liver Disorders Indiana University School of MedicineIndianapolisINUSA Department of Gastroenterology and Hepatology University Hospitals LeuvenKU Leuven3000 LeuvenBelgium U.O.C.di Gastroenterologia ed Endoscopia Digestiva Ospedale Giuseppe MazziniASL TeramoItaly Gastroenterology and Digestive Endoscopy Unit Forlì-Cesena HospitalsAUSL RomagnaForlì-CesenaItaly Borland Groover Clinic JacksonvilleFloridaUSA Department of Gastroenterology and Hepatology King Fahad Medical CityRiyadhSaudi Arabia Asian Institute of Gastroenterology HyderabadIndia Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Department of Biomedical Sciences Humanitas UniversityVia Rita Levi Montalcini 420090Pieve EmanueleMilanItaly

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 ***: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

关键词： Single-operator cholangioscopy Single-use duodenoscope Endoscopic retrograde cholangiopancreatography Indeterminate biliary stricture Difficult biliary stones

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Fat management in upper blepharoplasty:Addition or subtraction blepharoplasties,how and when

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World Journal of Clinical Cases 2024年第16期12卷 2796-2802页

作者： Giovanni Miotti Jacopo Di Filippo Martina Grando carlo Salati Pier Camillo Parodi Leopoldo Spadea Caterina Gagliano Mutali Musa Marco Zeppieri Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Internal Medicine Azienda Sanitaria Friuli OccidentaleSan Vito al Tagliamento 33078Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy Department of Medicine and Surgery University of Enna"Kore"Enna 94100Italy Eye Clinic Catania University San Marco HospitalCatania 95121Italy Department of Optometry University of BeninBenin 3000283Nigeria Department of Ophthalmology Centre for Sight AfricaNkporOnitsha 434112Niger

BACKGROUND As one of the most common aesthetic surgical procedures carried out today,blepharoplasty should be in the repertoire of every plastic *** term blepharoplasty encompasses a wide range of techniques and options that must be tailored to the specific defect and patient one has to treat.A sound knowledge of the upper and lower eyelids’anatomy is essential for proper surgical *** have shifted towards more conservative methods(especially of the fat compartment)and sometimes in combination with augmentation techniques,helping to reach a rejuvenated *** To present an overview of the surgical techniques considered for upper lid blepharoplasty and fat pad management,in addition to information on how a surgeon may approach the best treatment for his patient based on current publications in *** We searched the literature published between 2013,to 2023 using Medline and Reference Citation *** database was searched using the keywords“upper blepharoplasty”AND“fat”.Papers without full text/abstracts and reviews were *** search strategy followed the *** American Society of Plastic Surgeons guidelines for Therapeutic Studies checklist was used to assess all *** authors individually reviewed each article and rated them for importance and relevance to the topic.A consensus was sought and the most relevant *** After the application of the selection criteria used in our review,13 publications were found to address upper lid blepharoplasty *** of these studies were reviews and three were retrospective *** publications were comparative studies and a further two were clinical *** The tendency of modern surgery is to be conservative,by removing adipose tissue only if strictly necessary and restoring the volume of the upper eyelid in a concept of beauty that espouses a"full"*** is no gold standard technique to achieve younger and enhanced eyelids

关键词： Blepharoplasty Fat pads Eye lid surgery Cosmetic aesthetic surgery Rejuvenation Plastic surgery

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Uveal melanoma:Recent advances in immunotherapy

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World Journal of Clinical Oncology 2024年第1期15卷 23-31页

作者： Francesco Saverio Sorrentino Francesco De Rosa Patrick Di Terlizzi Giacomo Toneatto Andrea Gabai Lucia Finocchio carlo Salati Leopoldo Spadea Marco Zeppieri Department of Surgical Sciences Unit of OphthalmologyOspedale MaggioreBologna 40100Italy Department of Oncology IRCCS Istituto Romagnolo per lo Studio dei Tumori“Dino Amadori”Meldola 47014Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I“Sapienza”University of RomeRome 00142Italy

Uveal melanoma(UM)is the most common primary intraocular cancer in *** incidence in Europe and the United States is 6-7 per million population per *** most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 *** date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor *** standard therapeutic approaches for its prevention or treatment have been *** application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular *** is due to UM’s distinct genetics,natural history,and complex interaction with the immune *** cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or *** a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being *** this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

关键词： Uveal melanoma Immunotherapy Ocular oncology Tumor Metastatic disease Genetic mutations

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Physical insights into trapping effects on vertical GaN-on-Si trench MOSFETs from TCAD

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Journal of Semiconductors 2024年第3期45卷 45-52页

作者： NicolòZagni Manuel Fregolent Andrea Del Fiol Davide Favero Francesco Bergamin Giovanni Verzellesi carlo De Santi Gaudenzio Meneghesso Enrico Zanoni Christian Huber Matteo Meneghini Paolo Pavan Department of Engineering“Enzo Ferrari” University of Modena and Reggio EmiliaModena 41125Italy Department of Information Engineering University of PadovaPadova 35131Italy Department of Sciences and Methods for Engineering(DISMI) University of Modena and Reggio EmiliaReggio Emilia 42122Italy EN&TECH Center University of Modena and Reggio EmiliaReggio Emilia 42122Italy Advanced Technologies and Micro Systems Department Robert Bosch GmbHRenningen 71272Germany

Vertical GaN power MOSFET is a novel technology that offers great potential for power switching *** still in an early development phase,vertical GaN devices are yet to be fully optimized and require careful studies to foster their *** this work,we report on the physical insights into device performance improvements obtained during the development of vertical GaN-on-Si trench MOSFETs(TMOS’s)provided by TCAD simulations,enhancing the dependability of the adopted process optimization ***,two different TMOS devices are compared in terms of transfer-curve hysteresis(H)and subthreshold slope(SS),showing a≈75%H reduction along with a≈30%SS *** allow attributing the achieved improvements to a decrease in the border and interface traps,respectively.A sensitivity analysis is also carried out,allowing to quantify the additional trap density reduction required to minimize both figures of merit.

关键词： vertical GaN trench MOSFET SiO_(2) interface traps border traps hysteresis BTI

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Thermal and Electrical Modelling of a CPV/T System Varying Its Configuration

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Journal of Thermal Science 2019年第1期28卷 123-132页

作者： RENNO carlo Department of Industrial Engineering University of Salerno

In this paper, the main aim is the performances modelling from the electrical and thermal point of view of a concentrating photovoltaic and thermal(CPV/T) system in order to evaluate the primary energy and economic savings respect to a traditional system, when the same energy loads are satisfied. This study is realized by both varying the CPV/T system configuration and considering two different users. In particular, the point-focus(PF), and linear focus(LF) configurations of the CPV/T system are considered in order to match the residential user and hotel energy loads. The CPV/T system is sized adopting as input data: the Direct Normal Irradiance(DNI) modelled by an artificial neural network and the users' energy demands. In these hypotheses, the performances of the PF and LF systems are evaluated and then compared for the two users located in Southern Italy, in terms of electrical and thermal energy production, cells number, space occupied, energy and economic savings and CO2 emissions avoided. Finally, the PF system shows a lower simple pay-back and a higher primary energy saving, while the space occupied by a LF system results to be lower respect to the PF configuration.

关键词： CPV/T system point-focus configuration linear focus configuration thermal analysis electrical analysis primary energy saving economic analysis

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