Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors

Our previous studies showed that glioblastomas express increased urokinase-type plasminogen activator receptors (uPARs) in comparison to low-grade gliomas (Yamamoto et al., Cancer Res., 54, 5016-5020, 1994). To explore whether downregulation of uPAR inhibits tumor formation and invasiveness, a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5¢ end in an antisense orientation, resulting in a reduced number of uPA receptors. Co-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed to invade fetal rat brain aggregates. Intracerebral injection of SNB19-AS1 stable transfectants failed to form tumors and were negative for uPAR expression in nude mice. Thus uPAR appears in this model to be essential for tumorigenicity and invasion of glioblastomas in vivo.     

Incremental value of live/real time three‐dimensional transesophageal echocardiography in the assessment of ventricular septal rupture following acute myocardial infarction

Ventricular septal rupture is a serious complication following acute myocardial infarctions and is associated with a significant mortality rate. Classically, two‐dimensional transthoracic echocardiography has been used to diagnose this complication and visualize its location. Two‐dimensional transesophageal echocardiography has supplemented the transthoracic approach by providing more accurate assessment of the defect size and in guiding closure both percutaneously and intraoperatively. This modality, however, is limited to two‐dimensional views only, and a greater breadth of information is instead available through the use of three‐dimensional transesophageal echocardiography. We present a series of 11 patients in which live/real time three‐dimensional transesophageal echocardiography offered incremental benefits over two‐dimensional imaging alone.     

Anomalously weak solar convection

Convection in the solar interior is thought to comprise structures on a spectrum of scales. This conclusion emerges from phenomenological studies and numerical simulations, though neither covers the proper range of dynamical parameters of solar convection. Here, we analyze observations of the wavefield in the solar photosphere using techniques of time-distance helioseismology to image flows in the solar interior. We downsample and synthesize 900 billion wavefield observations to produce 3 billion cross-correlations, which we average and fit, measuring 5 million wave travel times. Using these travel times, we deduce the underlying flow systems and study their statistics to bound convective velocity magnitudes in the solar interior, as a function of depth and spherical-harmonic degree ℓ. Within the wavenumber band ℓ < 60, convective velocities are 20–100 times weaker than current theoretical estimates. This constraint suggests the prevalence of a different paradigm of turbulence from that predicted by existing models, prompting the question: what mechanism transports the heat flux of a solar luminosity outwards? Advection is dominated by Coriolis forces for wavenumbers ℓ < 60, with Rossby numbers smaller than approximately 10^-2 at r/R_⊙ = 0.96, suggesting that the Sun may be a much faster rotator than previously thought, and that large-scale convection may be quasi-geostrophic. The fact that isorotation contours in the Sun are not coaligned with the axis of rotation suggests the presence of a latitudinal entropy gradient.     

Percutaneous coronary interventions and cardiovascular outcomes for patients with chronic total occlusions

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Resident selection of Hand Surgery Fellowships: a survey of the 2011, 2012, and 2013 Hand Fellowship graduates

Background

We desired information from the recent, current, and future matched hand surgery fellows regarding their residency training, number of interviews, position matched, cost of interviewing, influences, opinions on future hand training models, and post-fellowship job information.

Methods

Institutional review board approval was obtained from our institution to submit an online survey. An email was sent to the coordinators of all US Hand Fellowships to be forwarded to their fellows with graduation years 2011, 2012, and 2013, as well as directly to the fellows if their email addresses were provided. Data on the application process, relative importance of program attributes, and opinions regarding optimal training of a hand surgeon were collected. Statistical analysis was performed with respect to the training background and graduation year of the respondent.

Results

The survey was completed by 137 hand surgery fellows. Seventy-one percent of the survey responders were from an orthopedic residency background, 20 % from plastic, and 7 % from general surgery. Forty-four percent of all of the respondents matched into their first choice. The type of operative cases performed by the current fellows was most often selected as very important when making their rank list. Seventy-seven percent of the respondents reflected their personal preference in fellowship model to be a 1-year fellowship program.

Conclusions

The field of hand surgery is unique in that it has residents from multiple training backgrounds who all apply to one fellowship. The current fellowship model allows for diversity of training and the possibility of obtaining a second fellowship if desired.     

Chance in agrammatic sentence comprehension: What does it really mean? Evidence from eye movements of German agrammatic aphasic patients

Background: In addition to the canonical subject-verb-object (SVO) word order, German also allows for non-canonical order (OVS), and the case-marking system supports thematic role interpretation. Previous eye-tracking studies (Kamide et al., 2003 Kamide, Y., Scheepers, C. and Altmann, G. M. 2003. Integration of syntactic and semantic information in predictive processing: Cross-linguistic evidence from German and English. Journal of Psycholinguistics Research, 32: 37–54. doi: 10.1023/A:1021933015362 [Google Scholar]; Knoeferle, 2007 Knoeferle, P. 2007. “Comparing the time-course of processing initially ambiguous and unambiguous German SVO/OVS sentences in depicted events”. In Eye movement research. A window on mind and brain, Edited by: van Gompel, R., Fischer, M., Murray, W. and Hill, R. 517–531. Oxford, , UK/Amsterdam: Elsevier.  [Google Scholar]) have shown that unambiguous case information in non-canonical sentences is processed incrementally. For individuals with agrammatic aphasia, comprehension of non-canonical sentences is at chance level (Burchert et al., 2003 Burchert, F., De Bleser, R. and Sonntag, K. 2003. Does morphology make the difference? Agrammatic sentence comprehension in German. Brain and Language, 87: 323–342. doi: 10.1016/S0093-934X(03)00132-9[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). The trace deletion hypothesis (Grodzinsky 1995 Grodzinsky, Y. 1995. A restrictive theory of agrammatic comprehension. Brain and Language, 50: 27–51. doi: 10.1006/brln.1995.1039[Crossref], [PubMed], [Web of Science ®] , [Google Scholar], 2000 Grodzinsky, Y. 2000. The neurology of syntax: Language use without Broca's area. Behavioral and Brain Sciences, 23: 1–71. doi: 10.1017/S0140525X00002399[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) claims that this is due to structural impairments in syntactic representations, which force the individual with aphasia (IWA) to apply a guessing strategy. However, recent studies investigating online sentence processing in aphasia (Caplan et al., 2007 Caplan, D., Waters, G., DeDe, G., Michaud, J. and Reddy, A. 2007. A study of syntactic processing in aphasia I: Behavioral (psycholinguistic) aspects. Brain and Language, 101: 103–150. doi: 10.1016/j.bandl.2006.06.225[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Dickey et al., 2007 Dickey, M. W., Choy, J. J. and Thompson, C. K. 2007. Real-time comprehension of Wh-movement in aphasia: Evidence from eyetracking while listening. Brain and Language, 100: 1–22. doi: 10.1016/j.bandl.2006.06.004[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) found that divergences exist in IWAs' sentence-processing routines depending on whether they comprehended non-canonical sentences correctly or not, pointing rather to a processing deficit explanation.

Aims: The aim of the current study was to investigate agrammatic IWAs' online and offline sentence comprehension simultaneously in order to reveal what online sentence-processing strategies they rely on and how these differ from controls' processing routines. We further asked whether IWAs' offline chance performance for non-canonical sentences does indeed result from guessing.

Methods & Procedures: We used the visual-world paradigm and measured eye movements (as an index of online sentence processing) of controls (N?=?8) and individuals with aphasia (N?=?7) during a sentence–picture matching task. Additional offline measures were accuracy and reaction times.

Outcomes & Results: While the offline accuracy results corresponded to the pattern predicted by the TDH, IWAs' eye movements revealed systematic differences depending on the response accuracy.

Conclusions: These findings constitute evidence against attributing IWAs' chance performance for non-canonical structures to mere guessing. Instead, our results support processing deficit explanations and characterise the agrammatic parser as deterministic and inefficient: it is slowed down, affected by intermittent deficiencies in performing syntactic operations, and fails to compute reanalysis even when one is detected.