MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

PTP1B regulates Eph receptor function and trafficking

Changes in protein tyrosine phosphatase 1B expression affect duration and amplitude of EphA3 phosphorylation and cell surface concentration

A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates

<p>Abstract</p> <p>Background</p> <p>The purpose of this article is to present a relatively easy to understand cancer model where transformation occurs when the first cell, among many at risk within a colon, accumulates a set of driver mutations. The analysis of this model yields a simple algebraic equation, which takes as inputs the number of stem cells, mutation and division rates, and the number of driver mutations, and makes predictions about cancer epidemiology.</p> <p>Methods</p> <p>The equation [<it>p </it>= 1 - (1 - (1 - (1 - <it>u</it>)^<it>d</it>)^<it>k</it>)^{<it>Nm </it>}] calculates the probability of cancer (<it>p</it>) and contains five parameters: the number of divisions (<it>d</it>), the number of stem cells (<it>N </it>× <it>m</it>), the number of critical rate-limiting pathway driver mutations (<it>k</it>), and the mutation rate (<it>u</it>). In this model progression to cancer "starts" at conception and mutations accumulate with cell division. Transformation occurs when a critical number of rate-limiting pathway mutations first accumulates within a single stem cell.</p> <p>Results</p> <p>When applied to several colorectal cancer data sets, parameter values consistent with crypt stem cell biology and normal mutation rates were able to match the increase in cancer with aging, and the mutation frequencies found in cancer genomes. The equation can help explain how cancer risks may vary with age, height, germline mutations, and aspirin use. APC mutations may shorten pathways to cancer by effectively increasing the numbers of stem cells at risk.</p> <p>Conclusions</p> <p>The equation illustrates that age-related increases in cancer frequencies may result from relatively normal division and mutation rates. Although this equation does not encompass all of the known complexity of cancer, it may be useful, especially in a teaching setting, to help illustrate relationships between small and large cancer features.</p

CA8 Mutations Cause a Novel Syndrome Characterized by Ataxia and Mild Mental Retardation with Predisposition to Quadrupedal Gait

We describe a consanguineous Iraqi family in which affected siblings had mild mental retardation and congenital ataxia characterized by quadrupedal gait. Genome-wide linkage analysis identified a 5.8 Mb interval on chromosome 8q with shared homozygosity among the affected persons. Sequencing of genes contained in the interval revealed a homozygous mutation, S100P, in carbonic anhydrase related protein 8 (CA8), which is highly expressed in cerebellar Purkinje cells and influences inositol triphosphate (ITP) binding to its receptor ITPR1 on the endoplasmatic reticulum and thereby modulates calcium signaling. We demonstrate that the mutation S100P is associated with proteasome-mediated degradation, and thus presumably represents a null mutation comparable to the Ca8 mutation underlying the previously described waddles mouse, which exhibits ataxia and appendicular dystonia. CA8 thus represents the third locus that has been associated with quadrupedal gait in humans, in addition to the VLDLR locus and a locus at chromosome 17p. Our findings underline the importance of ITP-mediated signaling in cerebellar function and provide suggestive evidence that congenital ataxia paired with cerebral dysfunction may, together with unknown contextual factors during development, predispose to quadrupedal gait in humans

Information and Arena: The Dual Function of the News Media for Political Elites

Abstract: How do individual politicians use the news media to reach their political goals? This study addresses the question by proposing an actor-centered, functional approach. We distinguish 2 essential functions (and subfunctions) the mass media have for political elites. The media are a source of information; politicians depend on it for pure information and they can profit from the momentum generated by media information. The media also are an arena elites need access to in order to promote themselves and their issues. These 2 functions offer certain politicians a structural advantage over others and, hence, are relevant for the power struggle among political elites. A systematic functional account enables comparisons of the role of the media across politicians and political systems

Inre antenn knappast en enkel match

Mobiltelefonen har gått igenom en enorm teknisk utveckling de senaste åren. För antennens del har det inneburit en rad förändringar och denna artikel försöker beskriva några av de nya utmaningar som antennspecialisterna idag ställs inför. Antennen är numera ofta inbyggd i telefonen och täcker fler band på högre frekvenser och som inbyggd har den betydligt sämre förutsättningar än tidigare att fungera lika bra. Slutsatsen är att det idag är lättare mekaniskt, men betydligt svårare elektriskt, att konstruera en mobiltelefonantenn

Köln E52 – Radioraritet med rörande varmt mottagande

Den kanske allra bästa radiomottagaren under andra världskriget heter Köln E52, figur 1, och konstruerades och byggdes av Telefunken. Den har med åren blivit en raritet eftersom kriget, tillsammans med tidens tand, reducerat antalet mottagare betydlig. Det var därför med stor glädje och förvåning som en sådan apparat nyligen återupptäcktes på Lunds Tekniska Högskola (LTH)

Low-impedance transmitter antenna for multi-antenna WCDMA handsets

The possibility of building compact, low-ohmic antennas suitable for mobile handsets is investigated. An F-antenna is built with a self-impedance of 10 Ω instead of the commonly used 50 Ω. Low impedance is chosen to minimize voltages in circuits prior to the antenna, in this case an adaptive matching network designed in CMOS or a similar process. To optimize this adaptive matching network, the antenna structure is two-fold: one antenna for transmission and one for reception. A resulting benefit is increased isolation between transmitter and receiver, as shown for a typical case. The 10 Ω antenna has an average efficiency of over 70% and an omnidirectional pattern; isolation increases by distance and reaches about 10dB at 4 c

Reconfigurable Impedance Matching Networks for Radio Receivers

Mobile phones become smaller but include more advanced functions for every new generation. This paradox is possible since reduced transistor size and increased integration of digital building blocks free space for new functions. Unfortunately, not all components are easily integrated or scaled, such as the antenna, since its performance is dependent on the size. Shrinking mobile phone size results in increased impedance mismatch, as the available antenna volume and the length of the ground plane are reduced. As a consequence, the performance of the whole mobile phone transceiver is degraded, since the noise increases and the output power decreases with increased mismatch. In this work, study of reconfigurable matching networks, and their improvement of receiver and transmitter performance with mismatched antennas, has been performed. In the general introduction, the matching network is introduced as an Impedance Tuning Unit (ITU) and the behaviour from the fundamental building blocks to system aspects are studied. Also, interaction with other building blocks in the receiver chain, such as low noise amplifier, mixer, and filter, is investigated. It is shown that noise performance and power transfer are improved by introducing an ITU, which has the ability to change its matching configuration. It is also shown that it is possible to realize an ITU for receivers in CMOS. Paper I and II examine antenna design and aspects such as shielding and coupling. Paper III is a parameter study of a switched capacitor. In paper IV, V, and VI ITU topologies are simulated and measured for 0.35 um and 0.13 um and for 2.4 to 2.5 GHz and 470 to 702 MHz. The results are presented together with system aspects relevant for receivers