Financing Cleantech SME innovation: setting an agenda

The need for a clear research and policy agenda to assist early stage Cleantech financing has never been greater. These businesses may hold important keys to unlocking vital globally game changing technologies to tackle climate change. The paper provides an overview of recent academic literature and proposes a research agenda for early stage Cleantech SME finance. With growing interest in how to support innovations that tackle the climate emergency, there is a need for evidence that can assist the private sector, civil society organizations and policymakers in finding more effective ways to encourage impact investing and other finance for early stage Cleantech SMEs. This research agenda will therefore contribute to sustainability transitions in key sectors and the development of a sustainable low carbon economy

I-mode pedestal relaxation events at ASDEX Upgrade

The I-mode confinement regime can feature small edge temperature drops that can lead to an increase in the energy deposited onto the divertor targets. In this work, we show that these events are associated with a relaxation of both electron temperature and density edge profiles, with the largest drop found at the pedestal top position. The relative energy loss is about 1 %, and is thus lower than that of type-I ELMs for the same pedestal top collisionality. Stability analysis of edge profiles reveals that the operational points are far from the ideal peeling-ballooning boundary. Also, we show that these events appear close to the H-mode transition in the typical I-mode operational space in ASDEX Upgrade, and that no further enhancement of energy confinement is found when they occur. Moreover, scrape-off layer transport during these events is found to be very similar to type-I ELMs, with regard to timescales (≈ 800 µs), filament propagation, toroidally asymmetric energy effluxes at the midplane and asymmetry between inner and outer divertor deposited energy. In particular, the latter reveals that more energy reaches the outer divertor target. Lastly, first measurements of the divertor peak energy fluence are reported, and projections to ARC—a reactor that could potentially operate in I-mode—are drawn.EUROfusion Consortium Grant Agreement No. 63305

Specifying computer-supported collaboration scripts

Collaboration scripts are activity programs which aim to foster collaborative learning by structuring interaction between learners. Computer-supported collaboration scripts generally suffer from the problem of being restrained to a specific learning platform and learning context. A standardization of collaboration scripts first requires a specification of collaboration scripts that integrates multiple perspectives from computer science, education and psychology. So far, only few and limited attempts at such specifications have been made. This paper aims to consolidate and expand these approaches in light of recent findings and to propose a generic framework for the specification of collaboration scripts. The framework enables a description of collaboration scripts using a small number of components (participants, activities, roles, resources and groups) and mechanisms (task distribution, group formation and sequencing)

I-mode pedestal relaxation events at ASDEX Upgrade

The I-mode confinement regime can feature small edge temperature drops that can lead to an increase in the energy deposited onto the divertor targets. In this work, we show that these events are associated with a relaxation of both electron temperature and density edge profiles, with the largest drop found at the pedestal top position. Stability analysis of edge profiles reveals that the operational points are far from the ideal peeling-ballooning boundary. Also, we show that these events appear close to the H-mode transition in the typical I-mode operational space in ASDEX Upgrade, and that no further enhancement of energy confinement is found when they occur. Moreover, scrape-off layer transport during these events is found to be very similar to type-I ELMs, with regard to timescales ($\approx$ 800 $\mu$s), filament propagation, toroidally asymmetric energy effluxes at the midplane and asymmetry between inner and outer divertor deposited energy. In particular, the latter reveals that more energy reaches the outer divertor target. Lastly, first measurements of the divertor peak energy fluence are reported, and projections to ARC - a reactor designed to operate in I-mode - are drawn

Unusual Polymorphisms in Human Immunodeficiency Virus Type 1 Associated with Nonprogressive Infection

Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-Δ32, CCR2-64I, and SDF-1-3\u27A) which have been associated with slower disease progression. HIV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HIV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC). Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1- or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino-acid insertion in Vpu. The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases

Lymphocyte Subsets Show Different Response Patterns to In Vivo Bound Natalizumab—A Flow Cytometric Study on Patients with Multiple Sclerosis

Natalizumab is an effective monoclonal antibody therapy for the treatment of relapsing- remitting multiple sclerosis (RRMS) and interferes with immune cell migration into the central nervous system by blocking the α4 subunit of very-late activation antigen-4 (VLA-4). Although well tolerated and very effective, some patients still suffer from relapses in spite of natalizumab therapy or from unwanted side effects like progressive multifocal leukoencephalopathy (PML). In search of a routine-qualified biomarker on the effectiveness of natalizumab therapy we applied flow cytometry and analyzed natalizumab binding to α4 and α4 integrin surface levels on T-cells, B-cells, natural killer (NK) cells, and NKT cells from 26 RRMS patients under up to 72 weeks of therapy. Four-weekly infusions of natalizumab resulted in a significant and sustained increase of lymphocyte-bound natalizumab (p<0.001) which was paralleled by a significant decrease in detectability of the α4 integrin subunit on all lymphocyte subsets (p<0.001). We observed pronounced natalizumab accumulations on T and B cells at single measurements in all patients who reported clinical disease activity (n = 4). The natalizumab binding capacity of in vitro saturated lymphocytes collected during therapy was strongly diminished compared to treatment-naive cells indicating a therapy-induced reduction of α4. Summing up, this pilot study shows that flow cytometry is a useful method to monitor natalizumab binding to lymphocytes from RRMS patients under therapy. Investigating natalizumab binding provides an opportunity to evaluate the molecular level of effectiveness of natalizumab therapy in individual patients. In combination with natalizumab saturation experiments, it possibly even provides a means of studying the feasability of patient-tailored infusion intervals. A routine-qualified biomarker on the basis of individual natalizumab saturation on lymphocyte subsets might be an effective tool to improve treatment safety

Unexpected Diversity of Cellular Immune Responses against Nef and Vif in HIV-1-Infected Patients Who Spontaneously Control Viral Replication

Background: HIV-1-infected individuals who spontaneously control viral replication represent an example of successful containment of the AIDS virus. Understanding the anti-viral immune responses in these individuals may help in vaccine design. However, immune responses against HIV-1 are normally analyzed using HIV-1 consensus B 15-mers that overlap by 11 amino acids. Unfortunately, this method may underestimate the real breadth of the cellular immune responses against the autologous sequence of the infecting virus. Methodology and Principal Findings: Here we compared cellular immune responses against nef and vif-encoded consensus B 15-mer peptides to responses against HLA class I-predicted minimal optimal epitopes from consensus B and autologous sequences in six patients who have controlled HIV-1 replication. Interestingly, our analysis revealed that three of our patients had broader cellular immune responses against HLA class I-predicted minimal optimal epitopes from either autologous viruses or from the HIV-1 consensus B sequence, when compared to responses against the 15-mer HIV-1 type B consensus peptides. Conclusion and Significance: This suggests that the cellular immune responses against HIV-1 in controller patients may be broader than we had previously anticipated.National Institutes of Health (NIH)[R24 RR015371]Ministry of Health[914/BRA/3014-UNESCO]Sao Paulo City Health Department[2004-0.168.922-7]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/15856-9]Coordenacao de Aperfeicoamento de Pessoal de Ni-vel Superior (CAPES), Brazilian Ministry of Educatio