Results of the Australian geodetic VLBI experiment

The 250-2500 km baseline vectors between radio telescopes located at Tidbinbilla (DSS43) near Canberra, Parkes, Fleurs (X3) near Sydney, Hobart and Alice Springs were determined from radio interferometric observations of extragalactic sources. The observations were made during two 24-hour sessions on 26 April and 3 May 1982, and one 12-hour night-time session on 28 April 1982. The 275 km Tidbinbilla - Parkes baseline was measured with an accuracy of plus or minus 6 cm. The remaining baselines were measured with accuracies ranging from 15 cm to 6 m. The higher accuracies were achieved for the better instrumented sites of Tidbinbilla, Parkes and Fleurs. The data reduction technique and results of the experiment are discussed

Generalizability of Trial Results to Elderly Medicare Patients With Advanced Solid Tumors (Alliance 70802)

In the United States, patients who enroll in chemotherapy trials seldom reflect the attributes of the general population with cancer, as they are often younger, more functional, and have less comorbidity. We compared survival following three chemotherapy regimens according to the setting in which care was delivered (ie, clinical trial vs usual care) to determine the generalizability of clinical trial results to unselected elderly Medicare patients

Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

Selective Optical Control of Synaptic Transmission in the Subcortical Visual Pathway by Activation of Viral Vector-Expressed Halorhodopsin

The superficial layer of the superior colliculus (sSC) receives visual inputs via two different pathways: from the retina and the primary visual cortex. However, the functional significance of each input for the operation of the sSC circuit remains to be identified. As a first step toward understanding the functional role of each of these inputs, we developed an optogenetic method to specifically suppress the synaptic transmission in the retino-tectal pathway. We introduced enhanced halorhodopsin (eNpHR), a yellow light-sensitive, membrane-targeting chloride pump, into mouse retinal ganglion cells (RGCs) by intravitreously injecting an adeno-associated virus serotype-2 vector carrying the CMV-eNpHR-EYFP construct. Several weeks after the injection, whole-cell recordings made from sSC neurons in slice preparations revealed that yellow laser illumination of the eNpHR-expressing retino-tectal axons, putatively synapsing onto the recorded cells, effectively inhibited EPSCs evoked by electrical stimulation of the optic nerve layer. We also showed that sSC spike activities elicited by visual stimulation were significantly reduced by laser illumination of the sSC in anesthetized mice. These results indicate that photo-activation of eNpHR expressed in RGC axons enables selective blockade of retino-tectal synaptic transmission. The method established here can most likely be applied to a variety of brain regions for studying the function of individual inputs to these regions

Nanotools for Neuroscience and Brain Activity Mapping

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function

Generation of tissue-specific transgenic birds with lentiviral vectors

Birds are of great interest for a variety of research purposes, and effective methods for manipulating the avian genome would greatly accelerate progress in fields that rely on birds as model systems for biological research, such as developmental biology and behavioral neurobiology. Here, we describe a simple and effective method for producing transgenic birds. We used lentiviral vectors to produce transgenic quails that express GFP driven by the human synapsin gene I promoter. Expression of GFP was specific to neurons and consistent across multiple generations. Expression was sufficient to allow visualization of individual axons and dendrites of neurons in vivo by intrinsic GFP fluorescence. Tissue-specific transgene expression at high levels provides a powerful tool for biological research and opens new avenues for genetic manipulation in birds

Treatment Outcomes of Different Prognostic Groups of Patients on Cancer and Leukemia Group B Trial 39801: Induction Chemotherapy Followed by Chemoradiotherapy Compared with Chemoradiotherapy Alone for Unresectable Stage III Non-small Cell Lung Cancer

BackgroundIn Cancer and Leukemia Group B 39801, we evaluated whether induction chemotherapy before concurrent chemoradiotherapy would result in improved survival and demonstrated no significant benefit from the addition of induction chemotherapy. The primary objective of this analysis was to dichotomize patients into prognostic groups using factors predictive of survival and to investigate whether induction chemotherapy was beneficial in either prognostic group.Patients and MethodsA Cox proportional hazard model was used to assess the impact on survival of the following factors: (≥70 versus <70 years), gender, race, stage (IIIB versus IIIA), hemoglobin (hgb) (<13 versus ≥13 g/dl), performance status (PS) (1 versus 0), weight loss (≥5% versus <5%), treatment arm, and the interaction between weight loss and hgb.ResultsFactors predictive of decreased survival were weight loss ≥5%, age ≥70 years, PS of 1, and hgb <13 g/dl (p < 0.05). Patients were classified as having ≥2 poor prognostic factors (n = 165) or ≤1 factor (n = 166). The hazard ratio (HR) for overall survival for the patients with ≥2 versus patients with ≤1 was 1.88 [95% confidence interval (CI), 1.49–2.37; p = <0.0001]; median survival times observed were 9 (95% CI, 8–11) and 18 (95% CI, 16–24) months, respectively. There was no significant difference in survival between treatment arms in patients with ≥2 factors (HR = 0.86, 95% CI, 0.63–1.17; p = 0.34) or ≤1 factor (HR = 0.97, 95% CI, 0.70–1.35; p = 0.87).ConclusionsThere is no evidence that induction chemotherapy is beneficial in either prognostic group