MicroRNA fingerprints in juvenile myelomonocytic leukemia (JMML) identified miR-150-5p as a tumor suppressor and potential target for treatment

Juvenile myelomonocytic leukemia (JMML) is an aggressive leukemia of early childhood characterized by aberrant proliferation of myelomonocytic cells and hypersensitivity to GM-CSF stimulation. Mutually exclusive mutations in the RAS/ERK pathway genes such as PTPN11, NRAS, KRAS, CBL, or NF1 are found in ~90% of the cases. These mutations give rise to disease at least in part by activating STAT5 through phosphorylation and by promoting cell growth. MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression, which are often deregulated in leukemia. However, little is known about their role in JMML. Here, we report distinctive miR expression signatures associated with the molecular subgroups of JMML. Among the downregulated miRs in JMML, miR-150-5p was found to target STAT5b, a gene which is often over-activated in JMML, and contributes to the characteristic aberrant signaling of this disorder. Moreover, loss of miR-150-5p and upregulation of STAT5b expression were also identified in a murine model of JMML. Ectopic overexpression of miR-150-5p in mononuclear cells from three JMML patients significantly decreased cell proliferation. Altogether, our data indicate that miR expression is deregulated in JMML and may play a role in the pathogenesis of this disorder by modulating key effectors of cytokine receptor pathways

Transition Within a Hypervelocity Boundary Layer on a 5-Degree Half-Angle Cone in Air/CO_2 Mixtures

Laminar to turbulent transition on a smooth 5-degree half angle cone at zero angle of attack is investigated computationally and experimentally in hypervelocity flows of air, carbon dioxide, and a mixture of 50% air and carbon dioxide by mass. Transition N factors above 10 are observed for air flows. At comparable reservoir enthalpy and pressure, flows containing carbon dioxide are found to transition up to 30% further downstream on the cone than flows in pure air in terms of x-displacement, and up to 38% and 140%, respectively, in terms of the Reynolds numbers calculated at edge and reference conditions

Differential Interferometric Measurement of Instability at Two Points in a Hypervelocity Boundary Layer

The focused laser differential interferometer (FLDI) was used to investigate disturbances in a hypervelocity boundary layer on a sharp five degree half-angle cone. The T5 hypervelocity free-piston driven reflected-shock tunnel was used as the test facility; in such a facility the study of thermo-chemical/fluid-dynamic energy exchange is emphasized. Two sensitive FLDI probe volumes were aligned along a generator of the cone that recorded time-traces of density fluctuation at sufficient time resolution, spatial resolution, and signal to noise ratio, so that the boundary layer instability could be resolved. This arrangement of the FLDI allows for the interpretation of disturbances at two points and the correlation between them. The acoustic instability is detected with narrow-band peaks in the spectral response at a number of frequencies (500 kHz to 1.29 MHz). The data indicate that the instability driving the boundary layer to turbulence is acoustic in nature. Preliminary analysis indicates that there is not a significant difference between N2 and air acoustic boundary layer disturbance amplification factors for the representative cases presented. Computation of acoustic damping by thermo-chemical relaxation processes is presented for the same representative cases, and indicates that there is a negligible amount of absorption for both air and N_2 at the observed disturbance frequencies

Control of hypersonic turbulent skin friction by boundary-layer combustion of hydrogen

Shvab-Zeldovich coupling of flow variables has been used to extend Van Driest's theory of turbulent boundary-layer skin friction to include injection and combustion of hydrogen in the boundary layer. The resulting theory is used to make predictions of skin friction and heat transfer that are found to be consistent with experimental and numerical results. Using the theory to extrapolate to larger downstream distances at the same experimental conditions, it is found that the reduction in skin-friction drag with hydrogen mixing and combustion is three times that with mixing alone. In application to flow on a flat plate at mainstream velocities of 2, 4, and 6 knits, and Reynolds numbers from 3 X 10(6) to 1 x 10(8), injection and combustion of hydrogen yielded values of skin-friction drag that were less than one-half of the no-injection skin-friction drag, together with a net reduction in heat transfer when the combustion heat release in air was less than the stagnation enthalpy. The mass efficiency of hydrogen injection, as measured by effective specific impulse values, was approximately 2000 s

A Coordinated Effort to Manage Soybean Rust in North America: A Success Story in Soybean Disease Monitoring

Existing crop monitoring programs determine the incidence and distribution of plant diseases and pathogens and assess the damage caused within a crop production region. These programs have traditionally used observed or predicted disease and pathogen data and environmental information to prescribe management practices that minimize crop loss (3,69). Monitoring programs are especially important for crops with broad geographic distribution or for diseases that can cause rapid and great economic losses. Successful monitoring programs have been developed for several plant diseases, including downy mildew of cucurbits, Fusarium head blight of wheat, potato late blight, and rusts of cereal crops (13,36,51,80)

Transition Within a Hypervelocity Boundary Layer on a 5-Degree Half-Angle Cone in Air/CO_2 Mixtures

Laminar to turbulent transition on a smooth 5-degree half angle cone at zero angle of attack is investigated computationally and experimentally in hypervelocity flows of air, carbon dioxide, and a mixture of 50% air and carbon dioxide by mass. Transition N factors above 10 are observed for air flows. At comparable reservoir enthalpy and pressure, flows containing carbon dioxide are found to transition up to 30% further downstream on the cone than flows in pure air in terms of x-displacement, and up to 38% and 140%, respectively, in terms of the Reynolds numbers calculated at edge and reference conditions

Deferred imitation and declarative memory in domestic dogs

This study demonstrates for the first time deferred imitation of novel actions in dogs (Canis familiaris) with retention intervals of 1.5 min and memory of familiar actions with intervals ranging from 0.40 to 10 min. Eight dogs were trained using the 'Do as I do' method to match their own behaviour to actions displayed by a human demonstrator. They were then trained to wait for a short interval to elapse before they were allowed to show the previously demonstrated action. The dogs were then tested for memory of the demonstrated behaviour in various conditions, also with the so-called two-action procedure and in a control condition without demonstration. Dogs were typically able to reproduce familiar actions after intervals as long as 10 min, even if distracted by different activities during the retention interval and were able to match their behaviour to the demonstration of a novel action after a delay of 1 min. In the two-action procedure, dogs were typically able to imitate the novel demonstrated behaviour after retention intervals of 1.5 min. The ability to encode and recall an action after a delay implies that facilitative processes cannot exhaustively explain the observed behavioural similarity and that dogs' imitative abilities are rather based on an enduring mental representation of the demonstration. Furthermore, the ability to imitate a novel action after a delay without previous practice suggests presence of declarative memory in dogs. © 2013 Springer-Verlag Berlin Heidelberg

Differential Interferometric Measurement of Instability at Two Points in a Hypervelocity Boundary Layer

The focused laser differential interferometer (FLDI) was used to investigate disturbances in a hypervelocity boundary layer on a sharp five degree half-angle cone. The T5 hypervelocity free-piston driven reflected-shock tunnel was used as the test facility; in such a facility the study of thermo-chemical/fluid-dynamic energy exchange is emphasized. Two sensitive FLDI probe volumes were aligned along a generator of the cone that recorded time-traces of density fluctuation at sufficient time resolution, spatial resolution, and signal to noise ratio, so that the boundary layer instability could be resolved. This arrangement of the FLDI allows for the interpretation of disturbances at two points and the correlation between them. The acoustic instability is detected with narrow-band peaks in the spectral response at a number of frequencies (500 kHz to 1.29 MHz). The data indicate that the instability driving the boundary layer to turbulence is acoustic in nature. Preliminary analysis indicates that there is not a significant difference between N2 and air acoustic boundary layer disturbance amplification factors for the representative cases presented. Computation of acoustic damping by thermo-chemical relaxation processes is presented for the same representative cases, and indicates that there is a negligible amount of absorption for both air and N_2 at the observed disturbance frequencies

More mentoring needed? A cross-sectional study of mentoring programs for medical students in Germany

<p>Abstract</p> <p>Background</p> <p>Despite increasing recognition that mentoring is essential early in medical careers, little is known about the prevalence of mentoring programs for medical students. We conducted this study to survey all medical schools in Germany regarding the prevalence of mentoring programs for medical students as well as the characteristics, goals and effectiveness of these programs.</p> <p>Methods</p> <p>A definition of mentoring was established and program inclusion criteria were determined based on a review of the literature. The literature defined mentoring as a steady, long-lasting relationship designed to promote the mentee's overall development. We developed a questionnaire to assess key characteristics of mentoring programs: the advocated mentoring model, the number of participating mentees and mentors, funding and staff, and characteristics of mentees and mentors (e.g., level of training). In addition, the survey characterized the mentee-mentor relationship regarding the frequency of meetings, forms of communication, incentives for mentors, the mode of matching mentors and mentees, and results of program evaluations. Furthermore, participants were asked to characterize the aims of their programs. The questionnaire consisted of 34 questions total, in multiple-choice (17), numeric (7) and free-text (10) format. This questionnaire was sent to deans and medical education faculty in Germany between June and September 2009. For numeric answers, mean, median, and standard deviation were determined. For free-text items, responses were coded into categories using qualitative free text analysis.</p> <p>Results</p> <p>We received responses from all 36 medical schools in Germany. We found that 20 out of 36 medical schools in Germany offer 22 active mentoring programs with a median of 125 and a total of 5,843 medical students (6.9 - 7.4% of all German medical students) enrolled as mentees at the time of the survey. 14 out of 22 programs (63%) have been established within the last 2 years. Six programs (27%) offer mentoring in a one-on-one setting. 18 programs (82%) feature faculty physicians as mentors. Nine programs (41%) involve students as mentors in a peer-mentoring setting. The most commonly reported goals of the mentoring programs include: establishing the mentee's professional network (13 programs, 59%), enhancement of academic performance (11 programs, 50%) and counseling students in difficulties (10 programs, 45%).</p> <p>Conclusions</p> <p>Despite a clear upsurge of mentoring programs for German medical students over recent years, the overall availability of mentoring is still limited. The mentoring models and goals of the existing programs vary considerably. Outcome data from controlled studies are needed to compare the efficiency and effectiveness of different forms of mentoring for medical students.</p

Mirizzi syndrome type IV associated with cholecystocolic fistula: a very rare condition- report of a case

<p>Abstract</p> <p>Background</p> <p>Mirizzi syndrome is a rare complication of prolonged cholelithiasis with presence of large, impacted gallstone into the Hartman's pouch, causing chronic extrinsic compression of common bile duct (CBD). Fistula formation between the CBD and the gallbladder may represent an outcome of that condition. According to Mirizzi's classification and Csendes's subclassification, Mirizzi syndrome type IV represents the most uncommon type (4%).</p> <p>Spontaneous biliary-enteric fistulas have also been rarely reported (1.2–5%) in a large series of cholecystectomies. Cholecystocolic fistula is the most infrequent biliary enteric fistula, causing significant morbidity and representing a diagnostic challenge.</p> <p>Case presentation</p> <p>We describe a very rare, to our knowledge, combination of Mirizzi syndrome type IV and cholecystocolic fistula. A 52 year old male, presented to our clinic complaining of episodic diarrhea (monthly episodes lasting 16 days), high temperature (38°C–39°C), right upper quadrant pain without jaundice. The definitive diagnosis was made intraoperatively. Magnetic Resonance Imaging (MRI) and Endoscopic Retrograde Cholangiopancreatography (ERCP) demonstrated the presence of Mirizzi syndrome with cholecystocolic fistula formation. The patient was operated upon, and cholecystectomy, cholecystocolic fistula excision and Roux-en-Y biliary-enteric anastomosis were undertaken with excellent post-operative course.</p> <p>Conclusion</p> <p>Appropriate biliary tree imaging with ERCP and MRI/MRCP is essential for the diagnosis of Mirizzi syndrome and its complications. Cholecystectomy, fistula excision and biliary-enteric anastomosis with Roux-en-Y loop appears to be the most appropriate surgical intervention in order to avoid damage to Calot's triangle anatomic elements. Particularly in our case, ERCP was a valuable diagnostic tool that Mirizzi syndrome type IV and cholecystocolic fistula.</p