Characterization of fundamental catalytic properties of MoS2/WS2 nanotubes and nanoclusters for desulfurization catalysis - a surface temperature study

The prior project consisted of two main project lines. First, characterization of novel nanomaterials for hydrodesulfurization (HDS) applications. Second, studying more traditional model systems for HDS such as vapor-deposited silica-supported Mo and MoSx clusters. In the first subproject, we studied WS2 and MoS2 fullerene-like nanoparticles as well as WS2 nanotubes. Thiophene (C4H4S) was used as the probe molecule. Interestingly, metallic and sulfur-like adsorption sites could be identified on the silica-supported fullerene-particles system. Similar structures are seen for the traditional system (vapor-deposited clusters). Thus, this may be a kinetics fingerprint feature of modern HDS model systems. In addition, kinetics data allowed characterization of the different adsorption sites for thiophene on and inside WS2 nanotube bundles. The latter is a unique feature of nanotubes that has not been reported before for any inorganic nanotube system; however, examples are known for carbon nanotubes, including prior work of the PI. Although HDS has been studied for decades, utilizing nanotubes as nanosized HDS reactors has never been tried before, as far as we know. This is of interest from a fundamental perspective. Unfortunately, the HDS activity of the nanocatalysts at ultra-high vacuum (UHV) conditions was close to the detection limit of our techniques. Therefore, we propose to run experiments at ambient pressure on related nanopowder samples as part of the renewal application utilizing a now-available GC (gas chromatograph) setup. In addition, Ni and Co doped nanocatalyts are proposed for study. These dopants will boost the catalytic activity. In the second subproject of the prior grant, we studied HDS-related chemistry on more traditional supported cluster catalysts. Mo clusters supported by physical vapor deposition (PVD) on silica have been characterized. Two reaction pathways are evident when adsorbing thiophene on Mo and MoSx clusters: molecular adsorption and dissociation. PVD Mo clusters turned out to be very reactive toward thiophene bond activation. Sulfur and carbon residuals form, which poison the catalyst and sulfide the Mo clusters. Sulfided silica-supported MoSx samples are not reactive toward thiophene bond activation. In addition to S and C deposits, H2, H2S, and small organic molecules were detected in the gas phase. Catalyst reactivation procedures, including O2 and atomic hydrogen treatments, have been tested. Cluster size effects have been seen: thiophene adsorbs molecularly with larger binding energies on smaller clusters. However, larger clusters have smaller activation energy for C4H4S bond activation than smaller clusters. The latter is consistent with early catalysis studies. Kinetics and dynamics parameters have been determined quantitatively. We spent a significant amount of time on upgrades of our equipment. A 2nd-hand refurbished X-ray photoelectron spectrometer (XPS) has been integrated into the existing molecular beam scattering system and is already operational (supported by the DoE supplemental grant available in October 2009). We also added a time of flight (TOF) system to the beam scattering apparatus and improved on the accessible impact energy range (new nozzle heater and gas mixing manifold) for the beam scattering experiments. In addition, a GC-based powder atmospheric flow reactor for studies on powder samples is now operational. Furthermore, a 2nd UHV kinetics system has been upgraded as well. In summary, mostly single crystal systems have so far been considered in basic science studies about HDS. Industrial catalysts, however, can be better approximated with the supported cluster systems that we studied in this project. Furthermore, an entirely new class of HDS systems, namely fullerene-like particles and inorganic nanotubes, has been included. Studying new materials and systems has the potential to impact science and technology. The systems investigated are closely related to energy and environmental-related surface science/catalysis. This prior project, conducted at NDSU by a small team, resulted in a total of 14 printed publications,1-5, 7-12, 14, 19, 20eight months before the end of the funding period. In addition, collaborators at national laboratories and abroad were part of the projects, as proposed. More specifically, projects about HDS on MoS2 and WS2 inorganic fullerene-like nanoparticles,1, 5 inorganic WS2 nanotubes,2 Mo and MoS2 vapor-deposited nanoclusters,3 modeling,19 reviews/book chapter,7, 11 and side projects8-10 have been conducted, as proposed, acknowledging solely (exception ref.7) funding from this grant. A list of publications and coworkers is given in sect. 6

Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.

Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31

Feasibility of a multidimensional home-based exercise programme for the elderly with structured support given by the general practitioner's surgery: Study protocol of a single arm trial preparing an RCT [ISRCTN58562962]

<p>Abstract</p> <p>Background</p> <p>Physical activity programmes can help to prevent functional decline in the elderly. Until now, such programmes use to target either on healthy community-dwelling seniors or on elderly living in special residences or care institutions. Sedentary or frail people, however, are difficult to reach when they live in their own homes. The general practitioner's (GP) practice offers a unique opportunity to acquire these people for participation in activity programmes. We conceptualised a multidimensional home-based exercise programme that shall be delivered to the target group through cooperation between GPs and exercise therapists. In order to prepare a randomised controlled trial (RCT), a feasibility study is being conducted.</p> <p>Methods</p> <p>The study is designed as a single arm interventional trial. We plan to recruit 90 patients aged 70 years and above through their GPs. The intervention lasts 12 weeks and consists of physical activity counselling, a home-exercise programme, and exercise consultations provided by an exercise therapist in the GP's practice and via telephone. The exercise programme consists of two main components: 1. a combination of home-exercises to improve strength, flexibility and balance, 2. walking for exercise to improve aerobic capacity. Primary outcome measures are: appraisal by GP, undesirable events, drop-outs, adherence. Secondary outcome measures are: effects (a. motor tests: timed-up-and-go, chair rising, grip strength, tandem stand, tandem walk, sit-and-reach; b. telephone interview: PRISCUS-Physical Activity Questionnaire, Short Form-8 Health Survey, three month recall of frequency of falls, Falls Efficacy Scale), appraisal by participant, exercise performance, focus group discussion. Data analyses will focus on: 1. decision-making concerning the conduction of a RCT, 2. estimation of the effects of the programme, detection of shortcomings and identification of subgroups with contrary results, 3. feedback to participants and to GPs.</p> <p>Conclusion</p> <p>A new cooperation between GPs and exercise therapists to approach community-dwelling seniors and to deliver a home-exercise programme is object of research with regard to feasibility and acceptance. In case of success, an RCT should examine the effects of the programme. A future implementation within primary medical care may take advantage from the flexibility of the programme.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN58562962.</p

Formation of the Food Vacuole in Plasmodium falciparum: A Potential Role for the 19 kDa Fragment of Merozoite Surface Protein 1 (MSP119)

Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) is synthesized during schizogony as a 195-kDa precursor that is processed into four fragments on the parasite surface. Following a second proteolytic cleavage during merozoite invasion of the red blood cell, most of the protein is shed from the surface except for the C-terminal 19-kDa fragment (MSP119), which is still attached to the merozoite via its GPI-anchor. We have examined the fate of MSP119 during the parasite's subsequent intracellular development using immunochemical analysis of metabolically labeled MSP119, fluorescence imaging, and immuno-electronmicroscopy. Our data show that MSP119 remains intact and persists to the end of the intracellular cycle. This protein is the first marker for the biogenesis of the food vacuole; it is rapidly endocytosed into small vacuoles in the ring stage, which coalesce to form the single food vacuole containing hemozoin, and persists into the discarded residual body. The food vacuole is marked by the presence of both MSP119 and the chloroquine resistance transporter (CRT) as components of the vacuolar membrane. Newly synthesized MSP1 is excluded from the vacuole. This behavior indicates that MSP119 does not simply follow a classical lysosome-like clearance pathway, instead, it may play a significant role in the biogenesis and function of the food vacuole throughout the intra-erythrocytic phase

A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses

New strategies are required to identify the most important targets of protective immunity in complex eukaryotic pathogens. Natural selection maintains allelic variation in some antigens of the malaria parasite Plasmodium falciparum (1–3). Analysis of allele frequency distributions could identify the loci under most intense selection (4–7). The merozoite surface protein 1 (Msp1) is the most-abundant surface component on the erythrocyte-invading stage of P. falciparum (8–10). Immunization with whole Msp1 has protected monkeys completely against homologous (11) and partially against non-homologous (12) parasite strains. The singlecopy msp1 gene, of about 5 kilobases, has highly divergent alleles (13) with stable frequencies in endemic populations (14,15). To identify the region of msp1 under strongest selection to maintain alleles within populations, we studied multiple intragenic sequence loci in populations in different regions of Africa and Southeast Asia. On both continents, the locus with the lowest inter-population variance in allele frequencies was block 2, indicating selection in this part of the gene. To test the hypothesis of immune selection, we undertook a large prospective longitudinal cohort study. This demonstrated that serum IgG antibodies against each of the two most frequent allelic types of block 2 of the protein were strongly associated with protection from P. falciparum malaria

Short and long term outcome of bilateral pallidal stimulation in chorea-acanthocytosis

BACKGROUND: Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS. METHODS: Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months). RESULTS: Motor severity, assessed by the Unified Huntington's Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥ 20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery. CONCLUSION: This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc