System-agnostic prediction of pharmaceutical excipient miscibility via computing-as-a-service and experimental validation.

We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C.

Kinetics of Water-Induced Amorphous Phase Separation in Amorphous Solid Dispersions via Raman Mapping.

The poor bioavailability of an active pharmaceutical ingredient (API) can be enhanced by dissolving it in a polymeric matrix. This formulation strategy is commonly known as amorphous solid dispersion (ASD). API crystallization and/or amorphous phase separation can be detrimental to the bioavailability.

Poly(vinyl alcohol) freeze casts with nano-additives as potential thermal insulators.

Freeze-casting consists of freezing a liquid suspension (aqueous or other), followed by sublimation of the solidified state to the gas state under reduced pressure, and subsequent sintering of the remaining scaffold to consolidate and densify the struts and walls. The structure is very porous with the pores being a replica of the solvent crystals. The technique is rather versatile and the use of a liquid solvent (water most of the time) as a pore forming agent is a strong asset.

Explaining the Release Mechanism of Ritonavir/PVPVA Amorphous Solid Dispersions.

In amorphous solid dispersions (ASDs), an active pharmaceutical ingredient (API) is dissolved on a molecular level in a polymeric matrix. The API is expected to be released from the ASD upon dissolution in aqueous media. However, a series of earlier works observed a drastic collapse of the API release for ASDs with high drug loads (DLs) compared to those with low DLs.

A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development.

Several literature publications have described the potential application of active pharmaceutical ingredient (API)-polymer phase diagrams to identify appropriate temperature ranges for processing amorphous solid dispersion (ASD) formulations via the hot-melt extrusion (HME) technique. However, systematic investigations and reliable applications of the phase diagram as a risk assessment tool for HME are non-existent. Accordingly, within AbbVie, an HME risk classification system (HCS) based on API-polymer phase diagrams has been developed as a material-sparing tool for the early risk assessment of especially high melting temperature APIs, which are typically considered unsuitable for HME.

Probing Photoinduced Two-Body Loss of Ultracold Nonreactive Bosonic ^{23}Na^{87}Rb and ^{23}Na^{39}K Molecules.

We probe photoinduced loss for chemically stable bosonic ^{23}Na^{87}Rb and ^{23}Na^{39}K molecules in chopped optical dipole traps, where the molecules spend a significant time in the dark. We expect the effective two-body decay to be significantly suppressed due to the small expected complex lifetimes of about 13 and 6  μs for ^{23}Na^{87}Rb and ^{23}Na^{39}K, respectively. However, instead we do not observe any suppression of the two-body loss in parameter ranges where large loss suppressions are expected.

STEER: 3D Printed Guide for Nerve Regrowth Control and Neural Interface in Non-Human Primate Model.

Objective: Peripheral neural interface (PNI) with a stable integration of synthetic elements with neural tissue is key for successfulneuro-prosthetic applications. An inevitable phenomenon of reactive fibrosis is a primary hurdle for long term functionality of PNIs. This proof-of-concept study aimed to fabricate and test a novel, stable PNI that harnesses fibro-axonal outgrowth at the nerve end and includes fibrosis in the design.

Ultracold Gas of Bosonic ^{23}Na^{39}K Ground-State Molecules.

We report the creation of ultracold bosonic dipolar ^{23}Na^{39}K molecules in their absolute rovibrational ground state. Starting from weakly bound molecules immersed in an ultracold atomic mixture, we coherently transfer the dimers to the rovibrational ground state using an adiabatic Raman passage. We analyze the two-body decay in a pure molecular sample and in molecule-atom mixtures and find an unexpectedly low two-body decay coefficient for collisions between molecules and ^{39}K atoms in a selected hyperfine state.

An adaptable two-lens high-resolution objective for single-site resolved imaging of atoms in optical lattices.

In this paper, we present a high-resolution, simple, and versatile imaging system for single-site resolved imaging of atoms in optical lattices. The system, which relies on an adaptable infinite conjugate two-lens design, has a numerical aperture of 0.52, which can in the ideal case be further extended to 0.

Novel molecular evidence of population structure in Anopheles (Kerteszia) bellator from Brazilian Atlantic Forest.

Anopheles bellator is a primary malaria vector in the Atlantic Forest. Partial sequences of timeless and Clock genes were used to assess the genetic differentiation of five Brazilian populations, which showed strong population structure (e.g.

Agglomeration-Free Preparation of Modified Silica Nanoparticles for Emulsion Polymerization-A Well Scalable Process.

To prepare modified silica nanospheres for emulsion polymerization, a new agglomeration-free change of dispersion media has been developed. Nanosized silica spheres were synthesized by the Stöber method and directly modified with a silane coupling agent. To prepare these particles for subsequent polymerization, the dispersion medium was changed in a two-step process from ethanol to water without agglomeration of the particles.

A Highly Selective 3D Spiked Ultraflexible Neural (SUN) Interface for Decoding Peripheral Nerve Sensory Information.

Artificial sensors on the skin are proposed as a way to capture information that can be used in intracortical microstimulation or peripheral intraneural stimulation to restore sensory feedback to persons with tetraplegia. However, the ability of these artificial sensors to replicate the density and complexity of the natural mechanoreceptors is limited. One relatively unexplored approach is to make use of the signals from surviving tactile and proprioceptive receptors in existing limbs by recording from their transmitting axons within the primary sensory nerves.

Mechanisms underlying vestibulo-cerebellar motor learning in mice depend on movement direction.

Key Points: Directionality, inherent to movements, has behavioural and neuronal correlates. Direction of vestibular stimulation determines motor learning efficiency. Vestibulo-ocular reflex gain-increase correlates with Purkinje cell simple spike potentiation.

Tactile Stimulation Evokes Long-Lasting Potentiation of Purkinje Cell Discharge In Vivo.

In the cerebellar network, a precise relationship between plasticity and neuronal discharge has been predicted. However, the potential generation of persistent changes in Purkinje cell (PC) spike discharge as a consequence of plasticity following natural stimulation patterns has not been clearly determined. Here, we show that facial tactile stimuli organized in theta-patterns can induce stereotyped N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA-A) receptor-dependent changes in PCs and molecular layer interneurons (MLIs) firing: invariably, all PCs showed a long-lasting increase (Spike-Related Potentiation or SR-P) and MLIs a long-lasting decrease (Spike-Related Suppression or SR-S) in baseline activity and spike response probability.

Differential Purkinje cell simple spike activity and pausing behavior related to cerebellar modules.

The massive computational capacity of the cerebellar cortex is conveyed by Purkinje cells onto cerebellar and vestibular nuclei neurons through their GABAergic, inhibitory output. This implies that pauses in Purkinje cell simple spike activity are potentially instrumental in cerebellar information processing, but their occurrence and extent are still heavily debated. The cerebellar cortex, although often treated as such, is not homogeneous.

Climbing fiber input shapes reciprocity of Purkinje cell firing.

The cerebellum fine-tunes motor activity via its Purkinje cell output. Purkinje cells produce two different types of spikes, complex spikes and simple spikes, which often show reciprocal activity: a periodical increase in complex spikes is associated with a decrease in simple spikes, and vice versa. This reciprocal firing is thought to be essential for coordinated motor behavior, yet how it is accomplished is debated.

New Zealand National Acute Stroke Services Audit: acute stroke care delivery in New Zealand.

Aims: To audit the care of a consecutive group of acute stroke patients admitted to all District Health Boards (DHBs) in New Zealand.

Methods: A clinical audit involving a review of up to 40 consecutive stroke patients treated and discharged from each DHB between 1st of June 2008 and 31st of December 2008.

Results: The clinical care of 832 patients [400 men; median age 77 (interquartile range 67-84) years] admitted to 20 of 21 DHBs was audited.

New Zealand National Acute Stroke Services Audit 2009: organisation of acute stroke services in New Zealand.

Aims: To characterise the nature of acute stroke services provided by District Health Boards (DHBs) in New Zealand.

Methods: An audit of all 21 DHBs was carried out in 2009 via an online survey examining the structural and process elements of acute stroke service provision. A clinical audit involving a retrospective review of consecutive admitted stroke patients is reported separately.

Two-dimensional receptive fields of midbrain lateral line units in the goldfish, Carassius auratus.

We determined the receptive fields of midbrain lateral line units in goldfish, Carassius auratus, with a 50 Hz vibrating sphere placed at various azimuths and elevations alongside the fish and studied how responses were affected by different directions of sphere vibration. The receptive fields of toral lateral line units, in contrast to those of primary afferent nerve fibers, did not represent the pressure gradient pattern generated by a vibrating sphere. Thus, unlike primary afferents, single toral lateral line units did not code for source location in their spatial discharge patterns.

National beef tenderness survey - 2006: Assessment of Warner-Bratzler shear and sensory panel ratings for beef from US retail and foodservice establishments.

Beef from retail and foodservice establishments in 11 US cities was evaluated using Warner-Bratzler shear (WBS) and consumer evaluation panels. Postmortem aging times ranged from 3 to 83d for retail and 7 to 136d for foodservice with mean aging times of 22.6d and 30.

Retail cutting characteristics for US Choice and US Select beef subprimals.

US Choice (Ch) and US Select (Se) beef subprimals from the rib, chuck, plate, loin, and round were obtained to conduct retail cutting tests. Subprimals were merchandised into bone-in or boneless retail cuts and associated components by experienced retail meat merchandisers. These Se subprimals had less (P<0.