Global health landscape challenges triggered by COVID-19.

The COVID-19 pandemic highlighted the vulnerability of every aspect of the globalized world, including R&D. Potentially critical R&D areas have been neglected because of the lack of market-driven incentives. However, new initiatives are emerging to address the present crisis of COVID-19 and possibly future similar incidents that will threaten humanity. In this paper, the global health landscape of R&D is discussed in terms of research focus and funding, illustrating under-funding in communicable diseases with the exception of three major infections: HIV/AIDS, tuberculosis, and malaria. The initiatives triggered by the COVID-19 pandemic and the novel emphasis on "access" are discussed. Finally, the authors propose a new funding model to address R&D in the case of market failure, by forming alliance between government, industry, and international philanthropic organization (GHIT model), and define clear strategy of enhancing access as the way forward.

Pathway-specific feedforward circuits between thalamus and neocortex revealed by selective optical stimulation of axons.

Thalamocortical and corticothalamic pathways mediate bidirectional communication between the thalamus and neocortex. These pathways are entwined, making their study challenging. Here we used lentiviruses to express channelrhodopsin-2 (ChR2), a light-sensitive cation channel, in either thalamocortical or corticothalamic projection cells. Infection occurred only locally, but efferent axons and their terminals expressed ChR2 strongly, allowing selective optical activation of each pathway. Laser stimulation of ChR2-expressing thalamocortical axons/terminals evoked robust synaptic responses in cortical excitatory cells and fast-spiking (FS) inhibitory interneurons, but only weak responses in somatostatin-containing interneurons. Strong FS cell activation led to feedforward inhibition in all cortical neuron types, including FS cells. Corticothalamic stimulation excited thalamic relay cells and inhibitory neurons of the thalamic reticular nucleus (TRN). TRN activation triggered inhibition in relay cells but not in TRN neurons. Thus, a major difference between thalamocortical and corticothalamic processing was the extent to which feedforward inhibitory neurons were themselves engaged by feedforward inhibition.

A microelectrode array incorporating an optical waveguide device for stimulation and spatiotemporal electrical recording of neural activity.

Targeted neural excitation coupled with simultaneous multineuron recording is desirable both for studying the real-time dynamics of neural circuits and for prospective clinical treatment of neurological diseases. Optical stimulation of genetically targeted neurons expressing the light sensitive channel protein Channelrhodopsin (ChR2) has recently been reported as a means for millisecond temporal control of neuronal spiking activity with cell-type selectivity. This offers the prospect of enabling local (cellular level) stimulation and the concomitant monitoring of neural activity by extracellular electrophysiological methods, both in the vicinity of and distant to the stimulation site. We report here a novel dual-modality hybrid device which consists of a tapered coaxial optical waveguide ("optrode") directly integrated into a 100 element intra-cortical multi-electrode recording array. The dual-modality array device was used in ChR2 transfected mouse brain slices. Specifically, epileptiform events were reliably optically triggered by the optrode and their spatiotemporal patterns were simultaneously recorded by the multi-electrode array.

Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue.

Neural stimulation with high spatial and temporal precision is desirable both for studying the real-time dynamics of neural networks and for prospective clinical treatment of neurological diseases. Optical stimulation of genetically targeted neurons expressing the light sensitive channel protein Channelrhodopsin (ChR2) has recently been reported as a means for millisecond temporal control of neuronal spiking activities with cell-type selectivity. This offers the prospect of enabling local delivery of optical stimulation and the simultaneous monitoring of the neural activity by electrophysiological means, both in the vicinity of and distant to the stimulation site. We report here a novel dual-modality hybrid device, which consists of a tapered coaxial optical waveguide ('optrode') integrated into a 100 element intra-cortical multi-electrode recording array. We first demonstrate the dual optical delivery and electrical recording capability of the single optrode in in vitro preparations of mouse retina, photo-stimulating the native retinal photoreceptors while recording light-responsive activities from ganglion cells. The dual-modality array device was then used in ChR2 transfected mouse brain slices. Specifically, epileptiform events were reliably optically triggered by the optrode and their spatiotemporal patterns were simultaneously recorded by the multi-electrode array.

Large ordered arrays of single photon sources based on II-VI semiconductor colloidal quantum dot.

In this paper, we developed a novel and efficient method of deterministically organizing colloidal particles on structured surfaces over macroscopic areas. Our approach utilizes integrated solution-based processes of dielectric encapsulation and electrostatic-force-mediated self-assembly, which allow precisely controlled placement of sub-10nm sized particles at single particle resolution. As a specific demonstration, motivated by application to single photon sources, highly ordered 2D arrays of single II-VI semiconductor colloidal quantum dots (QDs) were created by this method. Individually, the QDs display triggered single photon emission at room temperature with characteristic photon antibunching statistics, suggesting a pathway to scalable quantum optical radiative systems.

Large enhancement of fluorescence efficiency from CdSe/ZnS quantum dots induced by resonant coupling to spatially controlled surface plasmons.

Nanoengineered fluorescent response is reported from semiconductor core-shell (CdSe/ZnS) quantum dots in proximity to the surface plasmon polariton field of periodic Ag nanoparticle arrays. Tuning the surface plasmon polariton resonance to the quantum dot exciton emission band results in an enhancement of up to approximately 50-fold in the overall fluorescence efficiency, in a design where each Ag nanoparticle is interconnected by a continuous Ag thin film. Propagating modes of surface plasmon resonances have a direct impact on the fluorescence enhancement.