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Neurological disorders are the top cause of global health loss, but drug development faces major challenges, primarily due to the blood-brain barrier (BBB). Other obstacles include gastrointestinal irritation, poor stability, rapid metabolism, imprecise targeting, and toxicity. Emerging drug-delivery strategies offer promising solutions. This review examines these challenges, explores innovative drug delivery strategies, and discusses their applications in neurological disorders.

Neurological disorders are the leading cause of global health loss and disability. However, the success rate of drug development in the nervous system is very low, mainly because of the blood-brain barrier (BBB). In addition, gastrointestinal irritation, low stability, rapid metabolism, imprecise targeting, and organ toxicity of drugs are also important constraints in the development and application of neurological drugs. Emerging technologies, such as nano-delivery technology, offer a number of strategies to address these challenges drugs face entering the central nervous system. This review systematically introduces the various challenges of existing drug development in neurological disorders and summarizes BBB regulation strategies, drug delivery strategies, and modes of administration. It's summarized that the challenges of BBB can be addressed with the help of strategies including physical stimulation and modification of nanocarriers, and drug delivery in the nervous system can be achieved with the help of passive and active nanocarriers and self-assembly. Moreover, drug delivery strategies in major neurological disorders are discussed in detail. Finally, the limitations of some drug delivery strategies are summarized and the future development direction is prospected, which can provide new ideas and technologies for the optimization of drug delivery for neurological disorders.

A fully integrated wearable sweat-sensing patch capable of real-time detection of three critical PD-related biomarkers: L-Dopa, ascorbic acid, and glucose is presented. The system integrates a biomimetic microfluidic module for sedentary sweat collection, an advanced electrochemical sensing platform for biomarker detection, on-site signal processing circuitry for data handling, and custom software for real-time data visualization.

Parkinson's disease (PD) is marked by a prolonged asymptomatic “window period” (several years). Early prediction and diagnosis during this window are crucial, as timely interventions can slow disease progression. In this study, a fully integrated wearable sweat-sensing patch capable of real-time detection of three key PD biomarkers: L-Dopa, ascorbic acid, and glucose is developed. The system includes a biomimetic microfluidic module for sedentary sweat collection, an advanced electrochemical sensing platform for biomarker analysis, on-site signal processing circuitry for data management, and custom software for real-time data visualization. A universal strategy is proposed to significantly extend the stability of oxidase enzymes without activity loss, achieved through the design of Cu-oxidase hybrid nanoflowers. The patch is successfully tested on dozens of volunteers (healthy and PD patients in various stages), demonstrating its capability to monitor biomarkers in real time, assess PD progression, and optimize medication management.

A co-additive strategy regulates perovskite crystallization, enabling CsPbBr3&Cs4PbBr6 dual-phase nanocrystals and nanoscale concave-convex morphology with polarity tuning via molecular doping. The resulting PeLEDs achieve record performance: 28.2% EQE, 4291 h T50 lifetime, 16.5 nm linewidth, and 92% Rec. 2020 gamut coverage, surpassing prior benchmarks in efficiency, stability, and color purity.

Metal halide perovskites hold great promise for display technologies owing to their excellent optoelectronic properties. Recent advances in perovskite light-emitting diodes (PeLEDs) have improved their efficiency, brightness, and operational stability, but simultaneously boosting these metrics remains challenging. Additionally, other critical metrics such as power consumption, color purity, and gamut have received little attention. Here, a co-additive approach is proposed to regulate the perovskite crystallization, enabling the synthesis of CsPbBr3&Cs4PbBr6 dual-phase nanocrystals (NCs) and the formation of nanoscale concave-convex morphology, as well as to change its semiconductor polarity by molecular doping. Due to the reduced defect density, balanced charge injection, and improved light extraction efficiency, the PeLEDs achieve a remarkable external quantum efficiency (EQE) of 28.2%, a high brightness of over 150000 cd m−2 and a T50 lifetime of 4291 h, along with an ultra-narrow spectral linewidth (16.5 nm), an ultra-low driving voltage (1.9 V), and a superior Rec. 2020 color gamut coverage (CGC) of 92%.

An S-F group is directly grafted onto the SO2 group in the sulfone solvent, enabling rapid defluorination and decomposition of the solvent to form a robust SEI layer dominated by inorganics, thereby effectively isolating the LMA. The design ensures stable operation of Li-metal full cells from ambient to extreme conditions, offering a novel perspective for the molecular engineering of electrolytes tailored for Li-metal batteries.

Integrating Li metal anode (LMA) with a high-voltage NCM811 cathode is considered a pragmatic path in the pursuit of high-energy-density electrochemical energy storage systems. Yet, their practical application is still plagued by suboptimal cycling behavior. Numerous reports have already upgraded the cycle life of Li metal batteries (LMB) through anion-derived electrode-electrolyte interphase (EEI), but the adverse consequence brought by the inevitable decomposition of organic solvents is often underestimated. Here, a bipolar solvent molecule (1-Butanesulfonyl fluoride, BSF), is engineered by fusing an F-SO2 polar head for dissociating Li salts and contributing to the construction of EEI, along with a (CH2)4 nonpolar tail to lower molecular polarity and enhance wettability. Within the BSF-based electrolyte, FSI− anions and BSF coexist in the Li+ solvation shell, jointly contributing to the development of inorganic-rich EEI. Supported by robust interphases and expedited interfacial kinetics, the Li||NCM811 full cells (N/P = 1.05–1.8) exhibit favorable electrochemical performance over a wide temperature range from −40 to +55 °C. Furthermore, a 5.2 Ah Li metal pouch cell with a high cathode loading of 30 mg cm−2 and lean electrolyte (1.9 g Ah−1) delivers an energy density of 470 Wh kg−1 and achieves 100 stable cycles.

A lithium-free battery is designed by integrating a graphite|TiS2 pouch cell with a standard electrolyte modified by lithium trifluoromethanesulfinate (LiSO2CF3). Through electrochemical activation, the additive liberates Li ions without compromising structural stability or leaving detrimental residues. An unprecedented cycle life exceeding 14 000 cycles is achieved at a high current rate of 10C.

Energy storage batteries are pivotal for enabling reliable integration of renewable energy systems, yet further advancements in their longevity and rate performance remain imperative. Lithium (Li)-free cathode materials, while offering exceptional electrochemical stability, rate capability, and cost efficiency, face a critical limitation: the absence of active Li ions when paired with conventional graphite anodes. To address this challenge, a Li-free battery design is presented that integrates a graphite|TiS2 pouch cell architecture with a standard electrolyte modified by lithium trifluoromethanesulfinate (LiSO2CF3). This additive serves as an in situ Li-ion reservoir, electrochemically releasing Li ions during operation without generating deleterious residues or compromising structural integrity. The optimized cell achieves an unprecedented cycle life exceeding 14 000 cycles at a high current rate of 10C, alongside remarkable sustainability and cost-effectiveness. This work establishes a practical pathway for deploying long-lasting, fast-charging Li-free batteries in grid-scale energy storage applications.

This work designs a new DNA logical processing strategy based on cell surface-confined DNAzyme coordination for high-precision engineering and identification of cells. This strategy integrates the advantage of spatially-confined DNA-based reactions and allows for concurrently and logically analyzing multiple cell surface proteins, and demonstrates successful application even in tumor tissues from breast and lung cancer patients.

DNA logical processing, which employs DNA as a building block to perform logic operations, attracts considerable attention in biomedical applications. Herein, a new DNA logical processing strategy is explored for selective cell engineering and to develop a feasible technology for precise cell identification. Specifically, this cell identification technology accomplishes logical engineering through the employment of cell surface-confined DNAzyme coordination, which not only enables the labeling of versatile DNA probes at specific cells but also avoids false-positive outputs caused by the neighboring non-target cells. In proof-of-principle studies, this cell identification technology achieves precise magnetic isolation and electrochemical determination of specific cancer cells (i.e., stem cell-like subpopulations in breast cancer). When further applied to tumors taken from mouse models, this technology exhibits accuracy comparable to that of flow cytometry; however, it is simple to operate and offers superior recognition capabilities for revealing multiple biomarkers. More importantly, this cell identification technology can be successfully applied in tumor tissues from breast cancer and lung cancer patients, demonstrating satisfactory practicability. Therefore, this work may provide new insights for the precise identification of cells, especially cancer cells, and is expected to offer technical support for clinical diagnosis and related biomedical research.

Incorporation of low molecular weight liquid crystals (LC) into liquid crystal elastomers (LCE) leads to a significant increase in their stiffness and output work density. Such remarkable stiffening is attributed to nanoscale phase-separation and the formation of induced-smectic domains in polydomain and monodomain LC-LCEs, respectively.

Liquid crystal elastomers (LCEs) are promising building blocks for soft robots, given their large, programmable, reversible, and stimuli-responsive shape change. Enhancing LCEs’ stiffness and toughness has been a longstanding desire previously explored by reinforcing them with fillers, crystalline microdomains, and interpenetrating polymer networks. While promising, these methods adversely affect molecular order and thermal strain. Here, a significant enhancement of the stiffness of LCEs is reported by loading them with low molecular weight liquid crystals (LMWLCs) without sacrificing thermal strain and molecular order. While pristine LCEs rapidly transition to a soft elastic plateau when strained from poly- to monodomain, LC-loaded samples (LC-LCEs) first experience a pronounced linear elasticity, followed by a soft elastic plateau at higher stresses. Further thermomechanical and X-ray analysis confirm the emergence of an additional mesophase in polydomain LC-LCEs, which evolves to short-range smectic (cybotactic) during the poly- to monodomain transition. Monodomain LC-LCEs show between 6.5- and 9.0-fold stiffness enhancement with improved molecular order and thermal strain. Their work densities are more than double that of pristine LCEs, with active thermal stroke of up to 25% under loads of over 2000 times their weight. Such remarkable behaviors are attributed to the interplay between post-polymerization phase separation of LCs and their strain-enhanced smectic ordering. The results suggest that LMWLC inclusion can be a simple yet robust method to significantly improve the mechanical properties of LCEs.

A survivin peptide-CpG nanovaccine, SPOD-NV, is designed for GBM immunotherapy. Using a strategic sequential administration through intranasal and intravenous routes, it capitalizes on the advantages of both methods exhibiting enhanced accumulation in tumors, NALT, CLNs and spleen. Combined with anti-CTLA-4 therapy, it effectively activates local and systemic T-cell and humoral responses, achieving 43% complete remission and long-lasting immune memory in orthotopic GBM models.

Peptide vaccines hold great promise for treatment of glioblastoma (GBM), though their efficacy remains suboptimal due to factors such as immunosuppressive tumor microenvironment, poor accessibility to tumor site and inadequate activation of antigen-presenting cells. Here, this work reports on survivin peptide-CpG oligodeoxynucleotide (ODN) nanovaccines (SPOD-NV), which feature antigen peptides strategically displayed on polymersomes with CpG ODN encapsulated as an immunostimulatory adjuvant. Sequential administration via intranasal and intravenous routes elicits robust immune response against murine GBM. These results demonstrate that SPOD-NV significantly enhances mucosa penetration and markedly improves dendritic cell uptake and activation. Notably, the intranasal administration of SPOD-NV to orthotopic murine GL261 tumor models reveals marked accumulation in cervical lymph nodes and tumors, likely facilitated by lymphatic transport from nasal mucosa and pathways via olfactory bulb and trigeminal nerve, bypassing the blood-brain barrier. Interestingly, the therapeutic strategy, comprising three intranasal and two intravenous administrations of SPOD-NV in combination with anti-CTLA-4 antibody, results in substantial tumor inhibition, achieving a 43% complete regression rate, in line with the stimulation of robust and long-lasting local and systemic anti-GBM immune responses. These intranasal-intravenous administration strategy of peptide-CpG nanovaccines provides a potential curative therapy for brain tumors, paving the way for further developments in GBM immunotherapy.

A covalent grafting strategy is proposed to fabricate a lamellar COP network COP@G, which is achieved by edge-functionalizing COP with aromatic primary amine groups, followed by diazotization reactions and covalent attachment of graphene dispersions. COP@G demonstrates an order-of-magnitude enhancement in maximum power density compared to van der Waals-assembled COP-carbon composites in proton-exchange-membrane fuel cell device.

Covalent organic polymers (COPs) have emerged as promising oxygen reduction reaction (ORR) catalysts due to their structural tunability and well-defined active sites. However, their practical application is hindered by inherent electrical conductivity and restricted active site accessibility in bulk configurations. While van der Waals-assembled COP-carbon composites enhance conductivity, persistent stacking, and weak interfaces still impede electron/mass transport during ORR. Herein, a covalent grafting strategy is proposed to fabricate a lamellar COP network COP@G, which is achieved by edge-functionalizing COP with aromatic primary amine groups, followed by diazotization reactions and covalent attachment of graphene dispersions. The resulting hybrid exhibits significantly improved active site accessibility and a tenfold increase in conductivity compared to pristine COP. As a result, in 0.1 M HClO4, COP@G delivers an exceptional acidic ORR performance, with a record half-wave potential of 801 mV, surpassing van der Waals-assembled COP-G by 194 mV. When integrated into proton-exchange-membrane fuel cell (PEMFC) cathodes, COP@G demonstrates an order-of-magnitude enhancement in maximum power density compared to conventional COP-carbon composites.

NeoNectins are de novo-designed miniproteins that selectively bind and stabilize the extended open form of integrin α5β1. When grafted onto biomaterials including hydrogel and titanium, they promote cell attachment and spreading in vitro and promoting tissue integration and bone growth in animal models, demonstrating broad potential for regenerative medicine and biomaterials.

Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins can have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin (FN) and RGD peptides in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed FN- and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.

In this research, 3D/2D or 3D/quasi-2D perovskite heterojunctions with tunable energy levels and uniform n-values are developed. The well-refined heterogeneous structure effectively mitigates the non-radiative recombination losses and facilitates carrier extraction at the WBG perovskite/C60 interface. As a result, the optimized WBG PSCs and all-perovskite tandem solar cells exhibit improved performance and stability.

Wide-bandgap (WBG) perovskite sub-cells in all-perovskite tandem solar cells (AP-TSCs) suffer from severe open-circuit voltage loss and poor light stability. The formation of 3D/2D or 3D/quasi-2D perovskite heterojunctions can effectively passivate interface defects and optimize energy level alignments at the 3D perovskite/C60 interface, thereby enhancing both the efficiency and stability of perovskite solar cells. Herein, a combined evaporation/solution technique is employed to construct Dion-Jacobson (DJ) 2D or quasi-2D perovskites with uniform-phase distribution on wide-bandgap 3D perovskite substrates. By tuning the n values of the DJ phase perovskites, well-refined WBG 3D/2D or quasi-2D perovskite heterostructures are achieved, which exhibit tunable energy levels and mitigate the non-radiative recombination losses at the WBG 3D perovskite/C60 interface. The devices with the WBG (1.78 eV) 3D/quasi-2D n = 3 perovskite heterostructures achieve the champion power conversion efficiency (PCE) of 20.71% (certified 20.53%). When combined with narrow-bandgap (NBG) perovskite sub-cells, the fabricated 2-terminal AP-TSCs achieve a PCE of 28.99% (certified 28.81%). The tandem device maintains 80% of its initial PCE after 501 h of operation at maximum power point.

Directly evolved biovesicles are developed as biological clock-modulated nanovaccines (Clock-NVs) to augment circadian gene expression in tumors, enhance mitochondrial metabolism and antigen processing in dendritic cells for amplified antitumor immune responses, and potentiate the antitumor efficiency of anti-PD-L1 and adoptive T cells in multiple cancer mice models.

The circadian rhythm, as a crucial endogenous biological oscillator, often undergoes disruptions, thus fostering severe immunosuppression within tumors. Here, this work develops directly evolved biovesicles as biological clock-modulated nanovaccines (Clock-NVs) to augment circadian clock gene expression and enhance cancer immunotherapy. These biovesicles act as bioreactors, transforming an unfavorable factor, ROS, into a beneficial circadian clock enhancer, oxygen. By targeting HIF-1α-BMAL1 axis, Clock-NVs restore the disrupted circadian rhythm within tumors. Upregulation of the core clock gene, BMAL1, initiates tumor cell death, enhances mitochondrial metabolism and antigen processing in dendritic cells to amplify antitumor immune responses. Clock-NVs effectively inhibit tumor growth, diminish metastasis, and demonstrate robust antitumor activity in a model of chemotherapy-resistant senescent tumors. Notably, Clock-NVs combined with adoptive T cell-based therapies achieve a 60% regression of primary tumors, while their use with anti-PD-L1 results in 100% inhibition of tumor recurrence. This strategy introduces nanovaccines designed to enhance temporal immunotherapy by precisely restoring the suppressed rhythm gene expression within tumors.

Assigning unforgeable “fingerprints” to manufactured goods is a key strategy to fight global counterfeiting. Optical physical unclonable functions (PUFs) are chemically generated random patterns of optically active materials serving as unique authenticators. Here, recent advances in optical PUF devices are presented for anticounterfeiting via an overview of available optical taggants and compatible fabrication techniques.

Physical unclonable functions (PUFs) are artificial “fingerprints” provided by physical devices to authenticate manufactured goods. Their inherent unclonable nature positions them as one of the most promising tools to tackle global counterfeiting challenges. Leveraging the large parameter space in solution chemistry, chemically generated PUFs can achieve excellent device performance. Particularly, optically active materials have become valuable security inks thanks to their versatile, non-invasive, and non-destructive readouts, and PUF devices generated from stochastic nano-/micro-patterns of optical inks hold great potential. This review highlights recent advances in the design of optical PUF devices. A range of resonant and non-resonant optical materials used as security taggants are presented and their incorporation in state-of-the-art PUF devices is examined using non-deterministic fabrication techniques. By outlining design criteria, challenges, and opportunities, a roadmap is provided for developing next-generation PUFs using established and emerging optical probes and help advance security and reliability in anticounterfeiting technologies.

The long-period radio transients are a newly-discovered class of Galactic radio sources that produce pulsed emission lasting tens of seconds to several minutes, repeating on timescales of tens of minutes to hours. Such cadence is unprecedented, and there is currently no clear emission mechanism or progenitor that can explain the observations, which include complex polarisation behaviour, pulse microstructure, and activity windows that range from hours to decades.

Could they be ultra-long period magnetars, and connected to the phenomenon of Fast Radio Bursts? Could they be white dwarf pulsars, defying the expectations of the magnetic field evolution of these stellar remnants? In this talk I will describe the ten discoveries made so far, informative simulations of their evolution, the potential physical explanations, and the prospects for detecting more of these sources in ongoing and upcoming radio surveys, that will help uncover their true nature.

• Speaker: Prof. Natasha Hurley-Walker (Curtin University)
• Thursday 12 June 2025, 11:15-12:00
• Venue: Martin Ryle Seminar Room, Kavli Institute.
• Series: Hills Coffee Talks; organiser: Charles Walker.

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Abstract not available

• Speaker: James Jackson
• Friday 13 June 2025, 16:00-17:00
• Venue: Tea Room, Old House.
• Series: Bullard Laboratories Tea Time Talks; organiser: David Al-Attar.

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• Speaker: Antonio Pellegrino, Department of Mechanical Engineering, University of Bath
• Thursday 06 November 2025, 15:00-16:00
• Venue: Seminar Room West, Room A0.015, Ray Dolby Centre, Cavendish Laboratory.
• Series: Physics and Chemistry of Solids Group; organiser: Stephen Walley.

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We introduce MultiBLiMP, a massively multilingual benchmark of linguistic minimal pairs, covering 101 languages, 6 linguistic phenomena and containing more than 120.000 minimal pairs. Our minimal pairs are created using a fully automated pipeline, leveraging the large-scale linguistic resources of Universal Dependencies and UniMorph. MultiBLiMP evaluates linguistic abilities of LLMs at an unprecedented multilingual scale, and highlights the shortcomings of the current state-of-the-art in modelling low-resource languages.

• Speaker: Jaap Jumelet (University of Groningen)
• Friday 13 June 2025, 12:00-13:00
• Venue: ONLINE ONLY. Here is the Zoom link: https://cam-ac-uk.zoom.us/j/4751389294?pwd=Z2ZOSDk0eG1wZldVWG1GVVhrTzFIZz09.
• Series: NLIP Seminar Series; organiser: Suchir Salhan.

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Neutrino oscillations have the potential to answer some of the highest priority open questions in particle physics, such as why is there a matter-antimatter asymmetry in the universe, and where does the flavour structure of the standard model come from. T2K and NOvA individually have the world’s leading single-experiment precision on several of the parameters of the PMNS neutrino oscillation model. Combining the data from these two experiments not only increases their statistical power, but allows degeneracies present in the individual data sets to be lifted. This talk will describe the results of the first combination of these two data sets.

• Speaker: Patrick Dunne: Imperial College London
• Tuesday 10 June 2025, 11:00-12:00
• Venue: Seminar Room -- RDC D2.002 .
• Series: Cavendish HEP Seminars; organiser: Dr Paul Swallow.

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In this talk I will present an efficient algorithm for a central problem in quadratic Fourier analysis, and which can be seen as a quadratic generalisation of the celebrated Goildreich-Levin algorithm. More precisely, given a bounded function f on the Boolean hypercube {0, 1}n and any ε > 0, our algorithm returns a quadratic polynomial q: {0, 1}n → {0, 1} so that the correlation of f with the function (−1)q is within an additive ε of the maximum possible correlation with a quadratic phase function. This algorithm runs in O(n3) time and makes O(n2 log n) queries to f. As a corollary, we obtain an algorithmic inverse theorem for the order-3 Gowers norm with polynomial guarantees.

Our algorithm is obtained using ideas from recent work on quantum learning theory. Its construction significantly deviates from previous approaches based on algorithmic proofs of the inverse theorem for order-3 Gowers norms (and in particular does not rely on the recent resolution of the polynomial Freiman-Ruzsa conjecture).

Based on joint work with Jop Briët.

Please note that this talk will exceptionally take place in MR14 .

• Speaker: Davi de Castro Silva (University of Cambridge)
• Wednesday 11 June 2025, 13:30-15:00
• Venue: MR14, CMS.
• Series: Discrete Analysis Seminar; organiser: Julia Wolf.

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In this talk I hope to show how I applied what I learned at the IEEF in my career as a consulting engineer. Of particular utility to me has been the idea of breaking a complex engineering problem into small tractable pieces. I am obliged to briefly introduce my company, Itasca International, and the type of work we do. I will show three examples: Potash is a water soluble rock made of potassium salts, it is economically important because its use as a fertilizer. In North America, potash is solution mined by circulating water that dissolves the rock. This is a rich problem that involves chemistry, fluid flow, heat transfer, and geomechanics. I will demonstrate some models that are used to help design solution mines, forecast production, and diagnose operational problems. Explosives are an inexpensive means to break and move rock for civil purposes like tunneling, road cut development, and open pit mine excavation. Rock blasting is a complex set of processes that span several orders of magnitude in time-scale, length-scale, and stress magnitude. I will describe some simple mathematical and numerical models that have helped understand blasting. Onshore wind energy is rapidly growing in the United States, partially as a consequence of the Inflation Reduction Act of 2022. During construction, the world’s largest mobile cranes are used to lift the nacelle and blades of turbines. There have been several high profile cases of these large cranes tipping over and being destroyed during construction. It is 2025, so every talk has to have something about machine learning now: I will describe the technical problem of soil bearing capacity failure and show how machine learning, via the concept of a surrogate model, has helped make wind turbine installation faster, safer, and less expensive.

Bio: Jason Furtney was a student at the IEEF from 2002 to 2006 after studying Geology at Edinburgh University. Since leaving the institute, Jason has been working as a consulting engineer for Itasca International, a geomechanics consulting and software company in Minneapolis, Minnesota.

• Speaker: Jason Furtney, Itasca International
• Thursday 03 July 2025, 11:30-12:30
• Venue: Open Plan Area, Institute for Energy and Environmental Flows, Madingley Rise CB3 0EZ.
• Series: Institute for Energy and Environmental Flows (IEEF); organiser: Catherine Pearson.

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