Review conclusions by Ernst and Canter regarding spinal manipulation refuted

In the April 2006 issue of the Journal of Royal Society of Medicine, Ernst and Canter authored a review of the most recent systematic reviews on the effectiveness of spinal manipulation for any condition. The authors concluded that, except for back pain, spinal manipulation is not an effective intervention for any condition and, because of potential side effects, cannot be recommended for use at all in clinical practice. Based on a critical appraisal of their review, the authors of this commentary seriously challenge the conclusions by Ernst and Canter, who did not adhere to standard systematic review methodology, thus threatening the validity of their conclusions. There was no systematic assessment of the literature pertaining to the hazards of manipulation, including comparison to other therapies. Hence, their claim that the risks of manipulation outweigh the benefits, and thus spinal manipulation cannot be recommended as treatment for any condition, was not supported by the data analyzed. Their conclusions are misleading and not based on evidence that allow discrediting of a large body of professionals using spinal manipulation

Filtering Techniques to Improve Trace-Cache Efficiency

The trace cache is becoming an important building block of modern, wide-issue, processors. So far, trace cache related research has been focused on increasing fetch bandwidth. Trace-caches have been shown to effectively increase the number of “useful ” instructions that can be fetched into the machine, thus enabling more instructions to be executed each cycle. However, trace cache has another important benefit that got less attention in recent research: especially for variable length ISA, such as Intel’s IA-32 architecture (X86), reducing instruction decoding power is particularly attractive. Keeping the instruction traces in decoded format, implies the decoding power is only paid upon the build of a trace, thus reducing the overall power consumption of th

Selecting long atomic traces for high coverage

This paper performs a comprehensive investigation of dynamic selection for long atomic traces. It introduces a classification of trace selection methods and discusses existing and novel dynamic selection approaches – including loop unrolling, procedure inlining and incremental merging of traces based on dynamic bias. The paper empirically analyzes a number of selection schemes in an idealized framework. Observations based on the SPEC-CPU2000 benchmarks show that: (a) selection based on dynamic bias is necessary to achieve the best performance across all benchmarks, (b) the best selection scheme is benchmark and maximum trace-length specific, (c) simple selection, based on program structure information only, is sufficient to achieve the best performance for several benchmarks. Consequently, two alternatives for the trace selection mechanism are established: (a) a “best performance ” approach relying on complex dynamic criteria; (b) a “value ” approach that provides the best performance (and potentially the best power consumption) based on simpler static criteria. Another emerging alternative advocates adaptive based mechanisms to adjust selection criteria

abs_maxc_annotated

Source data for Fig. 4b, CFP part. The fields are described in the attached README file

abs_maxy_annotated

Source data for Fig. 4b, YFP part

Control of Relative Timing and Stoichiometry by a Master Regulator

<div><p>Developmental processes in cells require a series of complex steps. Often only a single master regulator activates genes in these different steps. This poses several challenges: some targets need to be ordered temporally, while co-functional targets may need to be synchronized in both time and expression level. Here we study in single cells the dynamic activation patterns of early meiosis genes in budding yeast, targets of the meiosis master regulator Ime1. We quantify the individual roles of the promoter and protein levels in expression pattern control, as well as the roles of individual promoter elements. We find a consistent expression pattern difference between a non-cofunctional pair of genes, and a highly synchronized activation of a co-functional pair. We show that dynamic control leading to these patterns is distributed between promoter, gene and external regions. Through specific reciprocal changes to the promoters of pairs of genes, we show that different genes can use different promoter elements to reach near identical activation patterns.</p></div

stat_files.tar

Quantitative data for each of the experiments represented in Fig1 - Fig4 and FigS3. For each experiment, the data is generated by an image analysis pipeline run over the YFP,CFP and DIC image series, and presented in a matlab object, whose fields are described in the attached README file

Contributions of ORF, promoter and external regions to timing and maximal protein levels.

<p>(a) T₅₀ values along a path from RRR to DDD alleles, where each step compares two alleles that differ in one region (ORF, promoter or external). The dominant contribution to timing difference comes from the ORF level (RRR→RRD). (b) A summary of comparative experiments between pairs of the 6 alleles and the Mei5 (MMM) allele. For each allele, the maximal protein level is plotted against its T₅₀ relative to the other alleles (where RRR was placed at t = 0). Both maximal level and relative timing were averaged over multiple pairwise experiments.</p

Effects of single binding site changes on absolute levels, timing or variability of stoichiometry.

<p>(a) A scheme of the promoters of Rec8, Dmc1 and Mei5. Gray bars denote the predicted +1 and -1 nucleosome locations. (b,c) Relative abundance over time in single cells of the pRec8-YFP, pRec8-CFP (b) and pRec8-YFP, pRec8(-MBF_bs)-CFP (c) promoter fusion strains. (d, e) Relative stoichiometry over time in single cells of the pMei5-YFP, pMei5-CFP (d) or pMei5-YFP, pMei5(-UME6_bs)-CFP (e) strains. (f) A summary of the motif change experiments (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127339#pone.0127339.s003" target="_blank">S3 Fig</a>). For each comparative experiment the mean and standard deviation of ΔT₅₀ and of <i>log(YFP/CFP)</i> in the terminal time point are shown. Removal of MBF binding site decreases pRec8 activity uniformly, with no significant effect on activation timing. Removal (or addition) of a second Ume6 binding site from pMei5 (or pDmc1) also affects mostly the absolute level.</p