Personal neoantigen cancer vaccines: The momentum builds

Neoantigen-based cancer vaccines designed to target the unique immunogenic mutations arising in each patient’s tumor are breathing new life into a struggling approach. Data continue to demonstrate the importance of neoantigens in immune control of cancer. Despite manufacturing complexity, outstanding questions and desired further improvements, neoantigen vaccines are currently undergoing clinical evaluation

Field-temperature phase diagram and entropy landscape of CeAuSb2

We report a field-temperature phase diagram and an entropy map for the heavy-fermion compound CeAuSb2. CeAuSb2 orders antiferromagnetically below TN=6.6 K and has two metamagnetic transitions, at 2.8 and 5.6 T. The locations of the critical end points of the metamagnetic transitions, which may play a strong role in the putative quantum criticality of CeAuSb2 and related compounds, are identified. The entropy map reveals an apparent entropy balance with Fermi-liquid behavior, implying that above the Néel transition the Ce moments are incorporated into the Fermi liquid. High-field data showing that the magnetic behavior is remarkably anisotropic are also reported

Acceptability and usage patterns of an image analysis workstation.

Critical to the successful deployment and use ofnew computer systems is the acceptance of the system by the users, i.e., the clinicians. We describe a study which evaluated, in an experimental setting, the potential acceptability of an image analysis workstation for radiation therapy. The acceptability and usage patterns were measured using semistructured questionnaires and maintaining logs of user interactions. The results ofthe study showed that the radiation oncologists, who were the subjects for the study, perceived the workstation as acceptable. The results also suggested several areas for improvement of workstation that could increase its acceptance in the clinical setting

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Control of CD1d-restricted antigen presentation and inflammation by sphingomyelin.

Invariant natural killer T (iNKT) cells recognize activating self and microbial lipids presented by CD1d. CD1d can also bind non-activating lipids, such as sphingomyelin. We hypothesized that these serve as endogenous regulators and investigated humans and mice deficient in acid sphingomyelinase (ASM), an enzyme that degrades sphingomyelin. We show that ASM absence in mice leads to diminished CD1d-restricted antigen presentation and iNKT cell selection in the thymus, resulting in decreased iNKT cell levels and resistance to iNKT cell-mediated inflammatory conditions. Defective antigen presentation and decreased iNKT cells are also observed in ASM-deficient humans with Niemann-Pick disease, and ASM activity in healthy humans correlates with iNKT cell phenotype. Pharmacological ASM administration facilitates antigen presentation and restores the levels of iNKT cells in ASM-deficient mice. Together, these results demonstrate that control of non-agonistic CD1d-associated lipids is critical for iNKT cell development and function in vivo and represents a tight link between cellular sphingolipid metabolism and immunity

Transforming European Water Governance? Participation and River Basin Management under the EU Water Framework Directive in 13 Member States

The European Union (EU) Water Framework Directive (WFD) requires EU member states to produce and implement river basin management plans, which are to be designed and updated via participatory processes that inform, consult with, and actively involve all interested stakeholders. The assumption of the European Commission is that stakeholder participation, and institutional adaptation and procedural innovation to facilitate it, are essential to the effectiveness of river basin planning and, ultimately, the environmental impact of the Directive. We analyzed official documents and the WFD literature to compare implementation of the Directive in EU member states in the initial WFD planning phase (2000–2009). Examining the development of participatory approaches to river basin management planning, we consider the extent of transformation in EU water governance over the period. Employing a mixed quantitative and qualitative approach, we map the implementation “trajectories” of 13 member states, and then provide a detailed examination of shifts in river basin planning and participation in four member states (Germany, Sweden, Poland and France) to illustrate the diversity of institutional approaches observed. We identify a general tendency towards increased, yet circumscribed, stakeholder participation in river basin management in the member states examined, alongside clear continuities in terms of their respective pre-WFD institutional and procedural arrangements. Overall, the WFD has driven a highly uneven shift to river basin-level planning among the member states, and instigated a range of efforts to institutionalize stakeholder involvement—often through the establishment of advisory groups to bring organized stakeholders into the planning process

Nested inversion polymorphisms predispose chromosome 22q11.2 to meiotic rearrangements [RETRACTED]

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders