Multiple bonding between atoms is immensely important to chemistry, biology, physics and their associated industries; multiple bonds are both ubiquitous in everyday products and extremely useful functionalities for effecting chemical transformations. While very common with the elements carbon, nitrogen and oxygen, multiple bonding is in comparison extremely rare with other elements. Multiple bonding between heavier elements of the main group of the periodic table becomes less favourable the heavier the element becomes. However, this does not explain the relative paucity of multiple bonding with boron, which is immediately to carbon's left on the periodic table. In particular, isolable, stable compounds containing multiple bonds between two boron atoms are extremely rare, and until 2007 only a handful of charged examples existed. A revolution in this field has recently been witnessed with the syntheses of the first neutral compounds with boron-boron double bonds, diborenes, and the first compounds with boron-boron triple bonds, diborynes. The first neutral diborenes were prepared in 2007, however, we have recently developed a number of rational, selective and more general routes to these compounds. The first diboryne compounds were prepared by our group in 2012. The significance of these two families of molecules is not only their unusual multiple bonding but also the extremely high electron density on the boron atoms, an unusual situation for an element that is known for its electron-poor character. This high electron density leads to strong boron-based nucleophilicity and extremely high reduction potentials – both highly novel phenomena. This proposal aims to: (A) comprehensively explore the syntheses of these unique compounds and the limits thereof, and to (B) exploit the unusual reactivity of these electron-rich boron molecules in synthesis, small-molecule activation and materials science.

IoT developers face a very fragmented landscape made of very different devices, from bare metal devices with few KB of RAM and limited or no security protection to devices equipped with powerful support for AI and with built-in hardware (HW) to implement Root of Trust (RoT) and Trusted Execution Environments (TEE). Such different devices coexist, and it is an open challenge to guarantee an acceptable level of security across the whole system to avoid “easy” entry points for attackers. The complexity is further exacerbated by the existence of many HW platforms, general purpose but also domain specific, each implementing proprietary instances of RoT and TEE that prevent or make it very difficult for applications and security services to interoperate. CROSSCON aims at addressing all these issues by designing a new open, flexible, highly portable and vendor independent IoT security stack that can run across a variety of different edge devices and multiple HW platforms to offer a consistent security baseline across an entire IoT system. A high-level assurance is guaranteed by the formal verification of the stack specifications. CROSSCON stack offers a unified set of trusted APIs to the layers above. It is modular and among all the security features it offers is possible to configure only the ones needed depending on the underlined HW and firmware. It leverages the security features already implemented in the layers below. In case such security features are missing, like in bare metal devices, the stack offers an entire TEE implementation suitable for such devices. As devices are getting more powerful and use cases more complex, there is the need to add new trusted services as building blocks to implement security at the higher levels, such as protection of the models given in input to ML engines embedded in HW or support for biometrics and template protections. CROSSCON provides the open specifications of the stack along with an open-source reference implementation.

Deregulated expression of MYC or one of its paralogues, MYCN and MYCL, maintains the growth of most human tumors. All current models explain the oncogenic potential of MYC proteins by their ability to form complexes with MAX that universally bind to active promoters and the ability of these complexes to induce a tumor-specific gene expression pattern. While MYC conforms to this model during unperturbed cell growth, we have discovered two paradigmatic situations in which MYC proteins undergo fundamental changes in their biochemical state, association with MAX and localization on chromatin: In response to pharmacological or physical disruption of transcription elongation, MYC moves away from active promoters to form large, spherical multimers that surround stalled replication forks. These multimers contain transcription termination factors and form a zone that shields stalled forks from RNA polymerase. Second, MYCN forms high molecular weight complexes during the S phase of the cell cycle that do not contain MAX and, like MYC multimers, contain termination factors. Their assembly depends on RNA that is normally degraded by the nuclear exosome, arguing that they too form in response to aberrant transcription. The switch between heterodimeric and multimeric states depends on non-proteolytic ubiquitylation of MYC, which alters protein-protein interactions that retain MYC at promoters. Our data show that MYC proteins exist in a hitherto unknown dynamic equilibrium between globally promoter-bound heterodimers and multimers that form locally in response to perturbed transcription. We aim to show that these dynamics enable tumor cells to cope with stress arising from deregulated transcription and are crucial for MYC´s oncogenic function. We expect that inhibiting MYC multimerization will maintain normal growth but block the ability of tumour cells to cope with deregulated transcription and is therefore a valid therapeutic strategy for targeting oncogenic functions of MYC

Access to a diverse spectrum of food resources ensures appropriate nutrition and is thus crucial for animal health and fitness. Bees obtain nearly all nutrients from flowers. Their population dynamics are therefore largely determined by the availability, composition and diversity of flowering plants. Alarmingly, many bee populations are in decline in contemporary landscapes, likely due to the loss of floral resource diversity and abundance and to a decrease in the nutritional quality of floral resources. However, the actual link between floral diversity and composition, the nutritional composition of floral resources and bee health is still unclear, particularly in wild bees, which are considered even less resilient to environmental changes than honeybees. In NutriB2, eleven scientists from seven different countries will combine their expertise in taxonomy, nutritional & chemical ecology, physiology, behavior, epidemiology, biostatistics and modeling to, in a synergistic effort, clarify the link between floral biodiversity, nutrition and bee health. We will further reveal critical nutrients and/or ratios and thus key plant species and compositions of plant species that cover the nutritional needs and support health of a large fraction of bee species. This knowledge is crucial for our understanding of how floral composition and diversity structure bee communities through nutritionally mediated health effects. It is also essential for designing and/or identifying and restoring habitats that support wild bee populations. Our results will be shared and processed with different stakeholders (i.e. seed companies, beekeeping and farmers’ organizations, regional to international conservation groups, schools with programs to actively promote bee diversity, other business representatives and policymakers) based on already established contacts and networks. Our aim is to determine feasible ways of a) restoring and/or maintaining semi-natural habitats with nutritionally highly valuable plant species and b) designing and implementing nutritionally balanced floral seed mixes. Nutritionally appropriate and diverse floral communities will not only benefit diverse bee species, but also others animals depending on plants as well as higher trophic levels. NutriB2 will therefore not only shed light on the mechanisms underlying the known positive correlation between floral biodiversity and bee health, but also enable us to design better strategies for conserving or restoring floral diversity for bees and thus mitigate the ongoing wild bee and biodiversity decline.