Effect of Seed Pellet Modification on Spiral Root Formation of Tobacco Seedlings

Tobacco seeds are often pelleted to facilitate precision seeding into float trays. Pelleting consists of the application of solid particles, such as clay, to seeds with a binder in a coating pan or tumbling drum to form spherically shaped dispersal units. One of the several advantages of pelleting is to provide seeds with a vastly enlarged bulk size to ensure proper placement of the seed at the surface of the growing medium

Recurrent network activity drives striatal synaptogenesis

Neural activity during development critically shapes postnatal wiring of the mammalian brain. This is best illustrated by the sensory systems, in which the patterned feed-forward excitation provided by sensory organs and experience drives the formation of mature topographic circuits capable of extracting specific features of sensory stimuli1,2. In contrast, little is known about the role of early activity in the development of the basal ganglia, a phylogenetically ancient group of nuclei fundamentally important for complex motor action and reward-based learning3,4. These nuclei lack direct sensory input and are only loosely topographically organized5,6, forming interlocking feed-forward and feed-back inhibitory circuits without laminar structure. Here we use transgenic mice and viral gene transfer methods to modulate neurotransmitter release and neuronal activity in vivo in the developing striatum. We find that the balance of activity among the two inhibitory and antagonist pathways in the striatum regulates excitatory innervation of the basal ganglia during development. These effects indicate that the propagation of activity through a multi-stage network regulates the wiring of the basal ganglia, revealing an important role of positive feedback in driving network maturation

Multiple Sclerosis Outcomes after Cancer Immunotherapy

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes. METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution. RESULTS: We identified 14 cases of MS with median age of presentation of 52 years. Indications for ICI included melanoma in 7 (36.36%) cases, non-small cell lung carcinoma in 2 (18.18%) cases, 1 case (9.09%) each of pleural mesothelioma, renal cell carcinoma, and colorectal cancer, and unreported in 2 (18.18%) cases. History of MS was confirmed in 8 (57.1%) cases. Median time to beginning of symptoms was 29 days with rapid disease progression; two patients died due to their relapse. Median time for symptom resolution was 8 weeks. Outcomes did not vary by comparing CTLA-4 and PD-1/PD-L1 inhibitors. CONCLUSIONS: Reported MS relapses after ICI are rare, but the adverse events described include rapid neurologic progression and death. Larger and prospective studies are warranted to assess disability and long-term outcomes and outweigh the risks of starting immunotherapy in patients with MS

The Influence of Specimen Thickness on the High Temperature Corrosion Behavior of CMSX-4 during Thermal-Cycling Exposure

CMSX-4 is a single-crystalline Ni-base superalloy designed to be used at very high temperatures and high mechanical loadings. Its excellent corrosion resistance is due to external alumina-scale formation, which however can become less protective under thermal-cycling conditions. The metallic substrate in combination with its superficial oxide scale has to be considered as a composite suffering high stresses. Factors like different coefficients of thermal expansion between oxide and substrate during temperature changes or growing stresses affect the integrity of the oxide scale. This must also be strongly influenced by the thickness of the oxide scale and the substrate as well as the ability to relief such stresses, e.g., by creep deformation. In order to quantify these effects, thin-walled specimens of different thickness (t = 100500 lm) were prepared. Discontinuous measurements of their mass changes were carried out under thermal-cycling conditions at a hot dwell temperature of 1100 C up to 300 thermal cycles. Thin-walled specimens revealed a much lower oxide-spallation rate compared to thick-walled specimens, while thinwalled specimens might show a premature depletion of scale-forming elements. In order to determine which of these competetive factor is more detrimental in terms of a component’s lifetime, the degradation by internal precipitation was studied using scanning electron microscopy (SEM) in combination with energy-dispersive X-ray spectroscopy (EDS). Additionally, a recently developed statistical spallation model was applied to experimental data [D. Poquillon and D. Monceau, Oxidation of Metals, 59, 409–431 (2003)]. The model describes the overall mass change by oxide scale spallation during thermal cycling exposure and is a useful simulation tool for oxide scale spallation processes accounting for variations in the specimen geometry. The evolution of the net-mass change vs. the number of thermal cycles seems to be strongly dependent on the sample thickness

Land Mollusks of Northeastern United States and Southeastern Canada

An illustrated key and description of the land snails and slugs of Northeastern United States and Southeastern CanadaOpe

Single-electron transport through the vortex core levels in clean superconductors

We develop a microscopic theory of single-electron transport in N-S-N hybrid structures in the presence of applied magnetic field introducing vortex lines in a superconductor layer. We show that vortex cores in a thick and clean superconducting layer are similar to mesoscopic conducting channels where the bound core states play the role of transverse modes. The transport through not very thick layers is governed by another mechanism, namely by resonance tunneling via vortex core levels. We apply our method to calculation of the thermal conductance along the magnetic field.Comment: 4 pages, 1 figur

Capecitabine and Temozolomide in Neuroendocrine Tumor of Unknown Primary

Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North American Neuroendocrine Tumor Society estimates that the United States has more than 150,000 gastroenteropancreatic NET patients. About 10% of metastatic NETs can be unknown primary, and due to their rarity, dedicated treatment algorithms and regimens are not defined. Combination of capecitabine and temozolomide (CAPTEM) is one of the systemic treatments used in gastroenteropancreatic NETs. We explored clinical activity of CAPTEM in NET of unknown primary. Methods. Retrospective review of NET of unknown primary managed at the University of Kentucky over the past five years (2012–2016). Result. 56 patients with NET of unknown primary were identified; 12 patients were treated with CAPTEM. Median progression-free survival on CAPTEM in grade II and grade III NET of unknown primary was 10.8 and 7 months, respectively. Six patients showed reduction in metastatic tumor volume at three-month CT scan. Three patients had stable disease and three patients showed disease progression at the first surveillance scan. Common side-effects were as follows: four patients developed grade II thrombocytopenia, three patients developed grade I lymphocytopenia, and two patients developed hand foot syndrome (grades I and III). Six patients developed grade I fatigue. Conclusion. CAPTEM should be considered for grades I and II NET of unknown primary, especially in the case of visceral crisis or bulky disease

UCP2 Regulates the Glucagon Response to Fasting and Starvation

Glucagon is important for maintaining euglycemia during fasting/starvation, and abnormal glucagon secretion is associated with type 1 and type 2 diabetes; however, the mechanisms of hypoglycemia-induced glucagon secretion are poorly understood. We previously demonstrated that global deletion of mitochondrial uncoupling protein 2 (UCP2−/−) in mice impaired glucagon secretion from isolated islets. Therefore, UCP2 may contribute to the regulation of hypoglycemia-induced glucagon secretion, which is supported by our current finding that UCP2 expression is increased in nutrient-deprived murine and human islets. Further to this, we created α-cell–specific UCP2 knockout (UCP2AKO) mice, which we used to demonstrate that blood glucose recovery in response to hypoglycemia is impaired owing to attenuated glucagon secretion. UCP2-deleted α-cells have higher levels of intracellular reactive oxygen species (ROS) due to enhanced mitochondrial coupling, which translated into defective stimulus/secretion coupling. The effects of UCP2 deletion were mimicked by the UCP2 inhibitor genipin on both murine and human islets and also by application of exogenous ROS, confirming that changes in oxidative status and electrical activity directly reduce glucagon secretion. Therefore, α-cell UCP2 deletion perturbs the fasting/hypoglycemic glucagon response and shows that UCP2 is necessary for normal α-cell glucose sensing and the maintenance of euglycemia

PI3K/mTOR Dual Inhibitor PF-04691502 Is a Schedule-Dependent Radiosensitizer for Gastroenteropancreatic Neuroendocrine Tumors

Patients with advanced-stage gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor overall prognosis despite chemotherapy and radiotherapy (e.g., peptide receptor radionuclide therapy (PRRT)). Better treatment options are needed to improve disease regression and patient survival. The purpose of this study was to examine a new treatment strategy by combining PI3K/mTOR dual inhibition and radiotherapy. First, we assessed the efficacy of two PI3K/mTOR dual inhibitors, PF-04691502 and PKI-402, to inhibit pAkt and increase apoptosis in NET cell lines (BON and QGP-1) and patient-derived tumor spheroids as single agents or combined with radiotherapy (XRT). Treatment with PF-04691502 decreased pAkt (Ser473) expression for up to 72 h compared with the control; in contrast, decreased pAkt expression was noted for less than 24 h with PKI-402. Simultaneous treatment with PF-04691502 and XRT did not induce apoptosis in NET cells; however, the addition of PF-04691502 48 h after XRT significantly increased apoptosis compared to PF-04691502 or XRT treatment alone. Our results demonstrate that schedule-dependent administration of a PI3K/mTOR inhibitor, combined with XRT, can enhance cytotoxicity by promoting the radiosensitivity of NET cells. Moreover, our findings suggest that radiotherapy, in combination with timed PI3K/mTOR inhibition, may be a promising therapeutic regimen for patients with GEP-NET

Efficacy of ERL-4221 as an ovotoxin for feral pigs (\u3ci\u3eSus scrofa\u3c/i\u3e)

Context. The expansion of feral pig populations across the United States has increased the occurrence of damage and damage complaints.Newtechniques are needed to more effectively manage feral pig damage, including the development of fertility control agents. Aims. We aimed to assess the ovotoxic properties of ERL-4221 as a candidate fertility control agent for feral pigs. Methods. We conducted two palatability trials to determine ERL-4221 acceptance and one experimental trial with ERL- 4221 at the captive wildlife facility of Texas A&M University-Kingsville during 2008. Our experimental trial had three treatments, a control containing no ERL-4221, baits containing 16.0 mg ERL-4221 kg–1 bodyweight for 10 days, and baits containing 16.0 mg ERL-4221 kg–1 bodyweight for 20 days. Key results. Final body mass, total ovary mass, number of follicles and number of corpora lutea did not differ between treatments. Conclusions. We did not find it efficacious to orally deliver ERL-4221 to feral pigs to reduce fertility. Oral delivery is the most practical, cost-effective means of delivering fertility control agents to feral pigs and development of additional fertility control strategies are needed. Implications. Unless ovotoxic effects of ERL-4221 can be identified in feral pigs, along with a successful means of administration, other fertility control strategies may need to be explored, such as oocyte-secreted proteins that regulate follicular development