Fabrication of the DESI corrector lenses

The Dark Energy Spectroscopic Instrument (DESI) is under construction to measure the expansion history of the Universe using the Baryon Acoustic Oscillation technique. The spectra of 35 million galaxies and quasars over 14000 square degrees will be measured during the life of the experiment. A new prime focus corrector for the KPNO Mayall telescope will deliver light to 5000 fiber optic positioners. The fibers in turn feed ten broad-band spectrographs. We describe the DESI corrector optics, a series of six fused silica and borosilicate lenses. The lens diameters range from 0.8 to 1.1 meters, and their weights 84 to 237 kg. Most lens surfaces are spherical, and two are challenging 10th-order polynomial aspheres. The lenses have been successfully polished and treated with an antireflection coating at multiple subcontractors, and are now being integrated into the DESI corrector barrel assembly at University College London. We describe the final performance of the lenses in terms of their various parameters, including surface figure, homogeneity, and others, and compare their final performance against the demanding DESI corrector requirements. Also we describe the reoptimization of the lens spacing in their corrector barrel after their final measurements are known. Finally we assess the performance of the corrector as a whole, compared to early budgeted estimates

The Canine Papillomavirus and Gamma HPV E7 Proteins Use an Alternative Domain to Bind and Destabilize the Retinoblastoma Protein

The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human cervical cells and the E7 protein can independently transform fibroblasts in vitro, primarily due to its ability to associate with and degrade the retinoblastoma tumor suppressor protein, pRb. The binding of E7 to pRb is mediated by a conserved Leu-X-Cys-X-Glu (LXCXE) motif in the conserved region 2 (CR2) of E7 and this domain is both necessary and sufficient for E7/pRb association. In the current study, we report that the E7 protein of the malignancy-associated canine papillomavirus type 2 encodes an E7 protein that has serine substituted for cysteine in the LXCXE motif. In HPV, this substitution in E7 abrogates pRb binding and degradation. However, despite variation at this critical site, the canine papillomavirus E7 protein still bound and degraded pRb. Even complete deletion of the LXSXE domain of canine E7 failed to interfere with binding to pRb in vitro and in vivo. Rather, the dominant binding site for pRb mapped to the C-terminal domain of canine E7. Finally, while the CR1 and CR2 domains of HPV E7 are sufficient for degradation of pRb, the C-terminal region of canine E7 was also required for pRb degradation. Screening of HPV genome sequences revealed that the LXSXE motif of the canine E7 protein was also present in the gamma HPVs and we demonstrate that the gamma HPV-4 E7 protein also binds pRb in a similar way. It appears, therefore, that the type 2 canine PV and gamma-type HPVs not only share similar properties with respect to tissue specificity and association with immunosuppression, but also the mechanism by which their E7 proteins interact with pRb

Ideal timing to transfer from an acute care hospital to an interdisciplinary inpatient rehabilitation program following a stroke: an exploratory study

BACKGROUND: Timely accessibility to organized inpatient stroke rehabilitation services may become compromised since the demand for rehabilitation services following stroke is rapidly growing with no promise of additional resources. This often leads to prolonged lengths of stays in acute care facilities for individuals surviving a stroke. It is believed that this delay spent in acute care facilities may inhibit the crucial motor recovery process taking place shortly after a stroke. It is important to document the ideal timing to initiate intensive inpatient stroke rehabilitation after the neurological event. Therefore, the objective of this study was to examine the specific influence of short, moderate and long onset-admission intervals (OAI) on rehabilitation outcomes across homogeneous subgroups of patients who were admitted to a standardized interdisciplinary inpatient stroke rehabilitation program. METHODS: A total of 418 patients discharged from the inpatient neurological rehabilitation program at the Montreal Rehabilitation Hospital Network after a first stroke (79% of all cases reviewed) were included in this retrospective study. After conducting a matching procedure across these patients based on the degree of disability, gender, and age, a total of 40 homogeneous triads (n = 120) were formed according to the three OAI subgroups: short (less than 20 days), moderate (between 20 and 40 days) or long (over 40 days; maximum of 70 days) OAI subgroups. The rehabilitation outcomes (admission and discharge Functional Independence Measure scores (FIM), absolute and relative FIM gain scores, rehabilitation length of stay, efficiency scores) were evaluated to test for differences between the three OAI subgroups. RESULTS: Analysis revealed that the three OAI subgroups were comparable for all rehabilitation outcomes studied. No statistical difference was found for admission (P = 0.305–0.972) and discharge (P = 0.083–0.367) FIM scores, absolute (P = 0.533–0.647) and relative (P = 0.496–0.812) FIM gain scores, rehabilitation length of stay (P = 0.096), and efficiency scores (P = 0.103–0.674). CONCLUSION: OAI does not seem to affect significantly inpatient stroke rehabilitation outcomes of patients referred from acute care facilities where rehabilitation services are rapidly initiated after the onset of the stroke and offered throughout their stay. However, other studies considering factors such as the type and intensity of the rehabilitation are required to support those results

Preliminary Target Selection for the DESI Milky Way Survey (MWS)

The DESI Milky Way Survey (MWS) will observe $\ge$8 million stars between $16 < r < 19$ mag, supplemented by observations of brighter targets under poor observing conditions. The survey will permit an accurate determination of stellar kinematics and population gradients; characterize diffuse substructure in the thick disk and stellar halo; enable the discovery of extremely metal-poor stars and other rare stellar types; and improve constraints on the Galaxy's 3D dark matter distribution from halo star kinematics. MWS will also enable a detailed characterization of the stellar populations within 100 pc of the Sun, including a complete census of white dwarfs. The target catalog from the preliminary selection described here is public

Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustine but responded to temozolomide after re-operation to temozolomide. The primary tumour -derived BTL1 cells showed chromosomal imbalances typical of highly aggressive glioblastomas. Interestingly, BTL2 cells established from the first recurrence developed under therapy showed signs of enhanced chromosomal instability. In contrast, BTL3 cells from the second recurrence resembled a less aggressive subclone of the primary tumour. Although BTL2 cells exhibited a highly aggressive phenotype, BTL3 cells were characterised by reduced proliferative and migratory potential. Despite persistent methylation of the O6-methylguanine-DNA methyltransferase promoter, BTL3 cells exhibited the highest temozolomide sensitivity. A comparable situation was found in two out of five glioblastoma patients, both characterised by enhanced survival time, who also relapsed after surgery/chemotherapy with less aggressive recurrences. Taken together, our data suggest that pretreated glioblastoma patients may relapse with highly chemosensitive tumours confirming the feasibility of temozolomide treatment even in case of repeated recurrence

Coding “What” and “When” in the Archer Fish Retina

Traditionally, the information content of the neural response is quantified using statistics of the responses relative to stimulus onset time with the assumption that the brain uses onset time to infer stimulus identity. However, stimulus onset time must also be estimated by the brain, making the utility of such an approach questionable. How can stimulus onset be estimated from the neural responses with sufficient accuracy to ensure reliable stimulus identification? We address this question using the framework of colour coding by the archer fish retinal ganglion cell. We found that stimulus identity, “what”, can be estimated from the responses of best single cells with an accuracy comparable to that of the animal's psychophysical estimation. However, to extract this information, an accurate estimation of stimulus onset is essential. We show that stimulus onset time, “when”, can be estimated using a linear-nonlinear readout mechanism that requires the response of a population of 100 cells. Thus, stimulus onset time can be estimated using a relatively simple readout. However, large nerve cell populations are required to achieve sufficient accuracy

Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

The epidermal growth factor receptor (EGFR) family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%). After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004). This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour

An internal ribosome entry site in the 5′ untranslated region of epidermal growth factor receptor allows hypoxic expression

The expression of epidermal growth factor receptor (EGFR/ERBB1/HER1) is implicated in the progress of numerous cancers, a feature that has been exploited in the development of EGFR antibodies and EGFR tyrosine kinase inhibitors as anti-cancer drugs. However, EGFR also has important normal cellular functions, leading to serious side effects when EGFR is inhibited. One damaging characteristic of many oncogenes is the ability to be expressed in the hypoxic conditions associated with the tumour interior. It has previously been demonstrated that expression of EGFR is maintained in hypoxic conditions via an unknown mechanism of translational control, despite global translation rates generally being attenuated under hypoxic conditions. In this report, we demonstrate that the human EGFR 5′ untranslated region (UTR) sequence can initiate the expression of a downstream open reading frame via an internal ribosome entry site (IRES). We show that this effect is not due to either cryptic promoter activity or splicing events. We have investigated the requirement of the EGFR IRES for eukaryotic initiation factor 4A (eIF4A), which is an RNA helicase responsible for processing RNA secondary structure as part of translation initiation. Treatment with hippuristanol (a potent inhibitor of eIF4A) caused a decrease in EGFR 5′ UTR-driven reporter activity and also a reduction in EGFR protein level. Importantly, we show that expression of a reporter gene under the control of the EGFR IRES is maintained under hypoxic conditions despite a fall in global translation rates