A Reevaluation of the Vestibulo-Ocular Reflex: New Ideas of its Purpose, Properties, Neural Substrate, and Disorders

Conventional views of the Vestibulo-Ocular Reflex (VOR) have emphasized testing with caloric stimuli and by passively rotating patients at low frequencies in a chair. The properties of the VOR tested under these conditions differ from the performance of this reflex during the natural function for which it evolved-locomotion. Only the VOR (and not visually mediated eye movements) can cope with the high-frequency angular and linear perturbations of the head that occur during locomotion; this is achieved by generating eye movements at short latency (less than 16 msec). Interpretation of vestibular testing is enhanced by the realization that, although the di- and trisynaptic components of the VOR are essential for this short-latency response, the overall accuracy and plasticity of the VOR depend upon a distributed, parallel network of neurons involving the vestibular nuclei. Neurons in this network variously encode inputs from the labyrinthine semicircular canals and otoliths, as well as from the visual and somatosensory systems. The central vestibular pathways branch to contact vestibular cortex (for perception) and the spinal cord (for control of posture). Thus, the vestibular nuclei basically coordinate the stabilization of gaze and posture, and contribute to the perception of verticality and self-motion. Consequently, brainstem disorders that disrupt the VOR cause not just only nystagmus, but also instability of posture (eg, increased fore-aft sway in patients with downbeat nystagmus) and disturbance of spatial orientation (eg, tilt of the subjective visual vertical in Wallenberg's syndrome)

Impact of the JOBS Act and crowdfunding on the commercial real estate market

Thesis (S.M. in Real Estate Development)--Massachusetts Institute of Technology, Program in Real Estate Development in Conjunction with the Center for Real Estate, 2013.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 145-152).This thesis systematically evaluates how rapid developments in the nascent crowdfunding industry, combined with recent regulatory changes, will impact the commercial real estate markets. The phenomenon of crowdfunding, defined as raising numerous small amounts of capital from a large number of people, or the crowd, has been accelerated by the recent passage of the Jumpstart Our Businesses Start-up Act (JOBS Act). The JOBS Act legalizes and facilitates the sale of securities used to crowdfund equity and debt investments, giving rise to a proliferation of new crowdfund entrants in various business sectors, including the commercial real estate arena. This thesis first gives a detailed analysis of the JOBS Act legislation and how it alters the current regulatory and business landscape. The focus then turns to the commercial real estate markets, tracing the evolution of commercial real estate as an institutional asset class and the influence large, institutional investors such as pension funds and real estate investment trusts exert on this market. The authors also examine the impact on the average investor and conclude that these large institutional investors have bifurcated the market, leaving the average investor unable to gain exposure to "hard" commercial real estate assets. The authors then link the research to crowdfunding, first with a chapter on the emerging and dynamic crowdfund industry in general, and then on specific commercial real estate crowdfunding sites, also discussing sites related to this sector. The authors strengthen this primary research with field investigations, conducting interviews with real estate developers, investors, and securities lawyers specializing in regulatory law. They concurrently surveyed 138 well-vetted real estate professionals (the MIT Center for Real Estate alumni). The thesis then projects the size of the potential dollar value of the commercial real estate crowdfund market based on existing value and turnover in the commercial real estate markets. The final chapter imagines what this market will look like in 2015; concluding that crowdfunding will have a profound effect on the commercial real estate market.by John R. McDonald and Bonnie L. Burgett.S.M.in Real Estate Developmen

Muscimol inactivation caudal to the interstitial nucleus of Cajal induces hemi-seesaw nystagmus

Hemi-seesaw nystagmus (hemi-SSN) is a jerk-waveform nystagmus with conjugate torsional and disjunctive vertical components. Halmagyi et al. in Brain 117(Pt 4):789–803 (1994), reported hemi-SSN in patients with unilateral lesions in the vicinity of the Interstitial Nucleus of Cajal (INC) and suggested that an imbalance in projections from the vestibular nuclei to the INC was the source of the nystagmus. However, this hypothesis was called into question by Helmchen et al. in Exp Brain Res 119(4):436–452 (1998), who inactivated INC in monkeys with muscimol (a GABAA agonist) and induced failure of vertical gaze-holding (neural integrator) function but not hemi-SSN. We injected 0.1–0.2 ?l of 2% muscimol into the supraoculomotor area, 1–2 mm dorso-lateral to the right oculomotor nucleus and caudal to the right INC. A total of seven injections in two juvenile rhesus monkeys were performed. Hemi-SSN was noted within 5–10 min after injection for six of the injections. Around the time the hemi-SSN began, a small skew deviation also developed. However, there was no limitation of horizontal or vertical eye movements, suggesting that the nearby oculomotor nucleus was not initially compromised. Limitations in eye movement range developed about ½–1 h following the injections. Clinical signs that were observed after the animal was released to his cage included a moderate to marked head tilt toward the left (contralesional) side, consistent with an ocular tilt reaction. We conclude that hemi-SSN can be caused by lesions just caudal to the INC, whereas lesions of the INC itself cause down-beat nystagmus and vertical gaze-holding failure, as demonstrated by Helmchen et al. Combined deficits may be encountered with lesions that involve several midbrain structures

Automated, high accuracy classification of Parkinsonian disorders: a pattern recognition approach

Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and idiopathic Parkinson’s disease (IPD) can be clinically indistinguishable, especially in the early stages, despite distinct patterns of molecular pathology. Structural neuroimaging holds promise for providing objective biomarkers for discriminating these diseases at the single subject level but all studies to date have reported incomplete separation of disease groups. In this study, we employed multi-class pattern recognition to assess the value of anatomical patterns derived from a widely available structural neuroimaging sequence for automated classification of these disorders. To achieve this, 17 patients with PSP, 14 with IPD and 19 with MSA were scanned using structural MRI along with 19 healthy controls (HCs). An advanced probabilistic pattern recognition approach was employed to evaluate the diagnostic value of several pre-defined anatomical patterns for discriminating the disorders, including: (i) a subcortical motor network; (ii) each of its component regions and (iii) the whole brain. All disease groups could be discriminated simultaneously with high accuracy using the subcortical motor network. The region providing the most accurate predictions overall was the midbrain/brainstem, which discriminated all disease groups from one another and from HCs. The subcortical network also produced more accurate predictions than the whole brain and all of its constituent regions. PSP was accurately predicted from the midbrain/brainstem, cerebellum and all basal ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from the midbrain/brainstem only. This study demonstrates that automated analysis of structural MRI can accurately predict diagnosis in individual patients with Parkinsonian disorders, and identifies distinct patterns of regional atrophy particularly useful for this process

The thrombopoietin receptor, c-Mpl, is a selective surface marker for human hematopoietic stem cells

BACKGROUND: Thrombopoietin (TPO), the primary cytokine regulating megakaryocyte proliferation and differentiation, exerts significant influence on other hematopoietic lineages as well, including erythroid, granulocytic and lymphoid lineages. We previously demonstrated that the receptor for TPO, c-mpl, is expressed by a subset of human adult bone marrow hematopoietic stem/progenitor cells (HSC/PC) that are enriched for long-term multilineage repopulating ability in the SCID-hu Bone in vivo model of human hematopoiesis. METHODS: Here, we employ flow cytometry and an anti-c-mpl monoclonal antibody to comprehensively define the surface expression pattern of c-mpl in four differentiation stages of human CD34(+ )HSC/PC (I: CD34(+)38(--), II: CD34(+)38(dim), III: CD34(+)38(+), IV: CD34(dim)38(+)) for the major sources of human HSC: fetal liver (FL), umbilical cord blood (UCB), adult bone marrow (ABM), and cytokine-mobilized peripheral blood stem cells (mPBSC). We use a surrogate in vivo model of human thymopoiesis, SCID-hu Thy/Liv, to compare the capacity of c-mpl(+ )vs. c-mpl(-- )CD34(+)38(--/dim )HSC/PC for thymocyte reconstitution. RESULTS: For all tissue sources, the percentage of c-mpl(+ )cells was significantly highest in stage I HSC/PC (FL 72 ± 10%, UCB 67 ± 19%, ABM 82 ± 16%, mPBSC 71 ± 15%), and decreased significantly through stages II, III, and IV ((FL 3 ± 3%, UCB 8 ± 13%, ABM 0.6 ± 0.6%, mPBSC 0.2 ± 0.1%) [ANOVA: P < 0.0001]. The relative median fluorescence intensity of c-mpl expression was similarly highest in stage I, decreasing through stage IV [ANOVA: P < 0.0001]. No significant differences between tissue sources were observed for either % c-mpl(+ )cells [P = 0.89] or intensity of c-mpl expression [P = 0.21]. Primary Thy/Liv grafts injected with CD34(+)38(--/dim)c-mpl(+ )cells showed slightly higher levels of donor HLA(+ )thymocyte reconstitution vs. CD34(+)38(--/dim)c-mpl(--)-injected grafts and non-injected controls (c-mpl(+ )vs. c-mpl(--): CD2(+ )6.8 ± 4.5% vs. 2.8 ± 3.3%, CD4(+)8(-- )54 ± 35% vs. 31 ± 29%, CD4(--)8(+ )29 ± 19% vs. 18 ± 14%). CONCLUSION: These findings support the hypothesis that the TPO receptor, c-mpl, participates in the regulation of primitive human HSC from mid-fetal through adult life. This study extends our previous work documenting human B-lineage, myeloid and CD34(+ )cell repopulation by c-mpl(+ )progenitors to show that c-mpl(+ )HSC/PC are also capable of significant T-lineage reconstitution in vivo. These results suggest that c-mpl merits consideration as a selective surface marker for the identification and isolation of human HSC in both basic research and clinical settings

SIMULTANEOUS OBSERVATIONS OF GIANT PULSES FROM THE CRAB PULSAR, WITH THE MURCHISON WIDEFIELD ARRAY AND PARKES RADIO TELESCOPE: IMPLICATIONS FOR THE GIANT PULSE EMISSION MECHANISM

We report on observations of giant pulses from the Crab pulsar performed simultaneously with the Parkes radio telescope and the incoherent combination of the Murchison Widefield Array (MWA) antenna tiles. The observations were performed over a duration of approximately one hour at a center frequency of 1382 MHz with 340 MHz bandwidth at Parkes, and at a center frequency of 193 MHz with 15 MHz bandwidth at the MWA. Our analysis has led to the detection of 55 giant pulses at the MWA and 2075 at Parkes above a threshold of 3.5σ and 6.5σ, respectively. We detected 51% of the MWA giant pulses at the Parkes radio telescope, with spectral indices in the range of -3.6 > α > -4.9 (S[subscript v] ∝ v[superscript α]). We present a Monte Carlo analysis supporting the conjecture that the giant pulse emission in the Crab is intrinsically broadband, the less than 100% correlation being due to the relative sensitivities of the two instruments and the width of the spectral index distribution. Our observations are consistent with the hypothesis that the spectral index of giant pulses is drawn from normal distribution of standard deviation 0.6, but with a mean that displays an evolution with frequency from −3.00 at 1382 MHz, to −2.85 at 192 MHz

Effect of Temperature on Plant Resistance to Arthropod Pests

Temperature has a strong influence on the development, survival, and fecundity of herbivorous arthropods, and it plays a key role in regulating the growth and development of their host plants. In addition, temperature affects the production of plant secondary chemicals as well as structural characteristics used for defense against herbivores. Thus, temperature has potentially important implications for host plant resistance. Because temperature directly impacts arthropod pests, both positively and negatively, distinguishing direct effects from indirect effects mediated through host plants poses a challenge for researchers and practitioners. A more comprehensive understanding of how temperature affects plant resistance specifically, and arthropod pests in general, would lead to better predictions of pest populations, and more effective use of plant resistance as a management tactic. Therefore, the goals of this paper are to 1) review and update knowledge about temperature effects on plant resistance, 2) evaluate alternative experimental approaches for separating direct from plant-mediated indirect effects of temperature on pests, including benefits and limitations of each approach, and 3) offer recommendations for future research