text:
\section{Introduction}\label{sec:intro}

The Standard Model of particle physics is parametrized by several
dimensionless `fundamental constants', such as coupling constants and
mass ratios, whose values are not predicted by the Model itself.
Instead their values and, indeed, their constancy must be established
experimentally. If found to vary in time or space, understanding their
dynamics may require a more fundamental theory, perhaps one unifying
the four known physical interactions. One such parameter whose
constancy can be tested to high precision is the fine-structure
constant, $\alpha\equiv e^2/\hbar c$, characterising the strength of
electromagnetism. Earth-bound laboratory experiments, conducted over
several-year time-scales, which use ultra-stable lasers to compare
different atomic clocks based on different atoms/ions \citep[e.g.~Cs,
Hg$^+$, Al$^+$, Yb$^+$, Sr, Dy; e.g.][]{PrestageJ_95a}, have limited
the time-derivative of $\alpha$ to
$\dot{\alpha}/\alpha=(-1.6\pm2.3)\times10^{-17}{\rm \,yr}^{-1}$
\citep{RosenbandT_08a}

\begin{figure*}[t!]
\begin{center}
\includegraphics[width=0.70\textwidth]{SAIT_MURPHY_FIG1.eps}
\caption{\footnotesize Transitions used in MM analyses versus their
  rest-frame wavelength and their sensitivity to variations in
  $\alpha$. Note the very different signature of a varying $\alpha$ in
  absorption systems where only the Mg and Fe{\sc \,ii} transitions
  redwards of 2300\,\AA\ are detected and fitted, compared with the
  more complicated signature for systems containing a subset of the
  bluer transitions. Note that the relative strengths of the different
  transitions typically observed in quasar absorption systems is not
  portrayed here.}
\label{fig:shifts}
\end{center}
\end{figure*}

Important probes of variations over cosmological space- and
time-scales are narrow absorption lines imprinted on the spectra of
distant, background quasars by gas clouds associated with foreground
galaxies \citep{BahcallJ_67b}. In particular, electronic resonance
transitions from the ground states of metallic atoms and ions are
useful indicators of $\alpha$ variation for redshifts up to $\sim$4 --
when the universe was $\sim$10\,\% of its current age -- where the
transitions are easily accessed from ground-based optical telescopes.
The many-multiplet (MM) method \citep{DzubaV_99a,WebbJ_99a} utilises
the relative wavelength shifts expected from different transitions
from different multiplets of various atom/ions to measure $\alpha$
from quasar absorption spectra.  The velocity shift, $\Delta v_i$, of
transition $i$ due to a small relative variation in $\alpha$,
$\Delta\alpha/\alpha\ll 1$, is determined by the $q$-coefficient for
that transition,
\begin{equation}\label{eq:da1}
  \omega_{z,i} \equiv \omega_{0,i} + q_i\left[\left(\alpha_z/\alpha_0\right)^2-1\right]\,~{\rm or}
\end{equation}
\begin{equation}\label{eq:da2}
\frac{\Delta v_i}{c} \approx -2\frac{\Delta\alpha}{\alpha}\frac{q_i}{\omega_{0,i}}\,,
\end{equation}
where $\omega_{0,i}$ \& $\omega_{z,i}$ are the rest-frequencies in the
lab and at redshift $z$, $\alpha_0$ is the lab value of $\alpha$ and
$\alpha_z$ is the shifted value measured from an absorber at $z$. The
MM method is the comparison of measured velocity shifts from several
transitions (with different $q$-coefficients) to compute the best-fit
$\Delta\alpha/\alpha$. Figure \ref{fig:shifts} illustrates the
wavelength shifts experienced by the transitions typically utilized in
MM analyses.

Some evidence for $\alpha$-variation has emerged over the last decade
from quasar spectra observed with HIRES \citep{VogtS_94a} on the Keck
I 10-m telescope in Hawaii. The first tentative evidence in
\citet{WebbJ_99a} was subsequently strengthened with larger samples of
absorbers (\citealt{MurphyM_01a}; \citealt[hereafter
\citetalias{MurphyM_03a}]{MurphyM_03a}). MM analysis of 143 absorption
spectra, all from the Keck/HIRES instrument, currently indicate a
smaller $\alpha$ in the clouds at the fractional level
$\hbox{$\Delta\alpha/\alpha$}=(-0.57\pm0.11)\times10^{-5}$ over the redshift range
$0.2<\hbox{$z_{\rm abs}$}<4.2$ \citep[][hereafter
\citetalias{MurphyM_04a}]{MurphyM_04a}.

Obviously, confirmation of such a potentially fundamental result must
be made with many other telescopes and spectrographs. Similar MM
studies using the Ultraviolet and Visual Echelle Spectrograph on the
ESO Very Large Telescope in Chile are also beginning to yield
constraints on \hbox{$\Delta\alpha/\alpha$}, but none yet rule out (or confirm) the Keck/HIRES
results \citep{MurphyM_08a}. At the same time, further searches for
subtle systematic errors which, despite extensive searches
\citep[e.g.][]{MurphyM_01b}, have evaded detection so far, must be
considered in detail. Of particular importance are systematic errors
in the wavelength calibration of the quasar spectra, which is usually
established using exposures of a standard thorium-argon (ThAr)
hollow-cathode emission-line lamp taken immediately before and/or after
the quasar exposure. After the wavelength--pixel mapping is derived
from the ThAr exposure, that solution is simply applied to the quasar
exposure. Since the quasar and ThAr light illuminate the spectrograph
slit differently and, in general, take slightly different paths
through the spectrograph to the CCD, wavelength calibration errors may
ensue.

\citet{GriestK_09a} (hereafter \citetalias{GriestK_09a}) recently
observed a quasar absorption system using Keck/HIRES with an iodine
gas absorption cell for more direct wavelength calibration, thereby
allowing comparison with the ThAr wavelength scale. For
varying-$\alpha$ studies, the most important and robust result from
\citetalias{GriestK_09a} is the identification of distortions in the
ThAr wavelength scale across each echelle order (hereafter
`intra-order distortions'). See their figures 4 and 5. These may
result from differential and variable vignetting of quasar light
compared to ThAr light, where only the former enters HIRES from the
telescope, the optical axes of which differ slightly, causing the
quasar light path to rotate as the telescope tracks the quasar
(\citealt{SuzukiN_03a}; \citetalias{GriestK_09a}).
\citetalias{GriestK_09a} also discuss velocity offsets between the
ThAr and I$_2$ wavelength scales. If those results are robust, they
are less important for varying $\alpha$ studies because, as equation
(\ref{eq:da2}) makes clear, such velocity offsets will not directly
influence a \hbox{$\Delta\alpha/\alpha$}\ measurement\footnote{This is not strictly true when
  many quasar exposures are combined, as is generally the case for
  most of the Keck/HIRES sample. If different velocity shifts apply to
  the different exposures of the same quasar, and if the relative
  weights of the exposures vary with wavelength when forming the
  final, combined spectrum, then small relative velocity shifts will
  be measured between transitions at different wavelengths.
  Nevertheless, the effect on \hbox{$\Delta\alpha/\alpha$}\ of overall velocity shifts is of
  secondary importance to the intra-order distortions considered in
  detail here.}.

This paper aims to assess the impact these intra-order distortions may
have had on the Keck/HIRES results for varying $\alpha$. The following
section describes the general effect the distortions will have and
provides a crude calculation of their expected magnitude. Section
\ref{sec:calc} details a more refined calculation of the correction to
\hbox{$\Delta\alpha/\alpha$}\ for each absorber in the Keck/HIRES sample and Section
\ref{sec:res} discusses the results. In section \ref{sec:model} we
search for direct evidence for the need to apply the corrections and
consider the effect of model errors on our calculations. We conclude
in Section \ref{sec:conc}.

\section{The effect of intra-order wavelength distortions}\label{sec:distort}

The reason intra-order distortions are problematic for varying
$\alpha$ analyses is that they will produce velocity shifts {\it
  between} transitions. For an individual absorption system the
transitions will, in general, fall at different positions along
different echelle orders and will experience different velocity shifts
due to the wavelength calibration distortions. The
\citetalias{GriestK_09a} distortions generally cause blueward shifts
which increase towards the echelle order edges in either direction
from the center.  This pattern seems to be generally repeated on each
echelle order.  However, because the I$_2$ cell imprints absorption
lines on the quasar spectrum only over the wavelength range
$\sim$5000--6200\,\AA, no information about echelle orders outside
this range can be obtained. Nevertheless, it is clear that for two
absorbers at different redshifts, possibly with different transitions
detected and fitted, different spurious shifts in \hbox{$\Delta\alpha/\alpha$}\ will be caused
by the intra-order distortions. Indeed, in general, the effect on \hbox{$\Delta\alpha/\alpha$}\
will be random in sign and magnitude from absorber to absorber.

A simple illustrative estimate of the expected magnitude of the effect
on \hbox{$\Delta\alpha/\alpha$}\ in a typical Mg/Fe{\sc \,ii} absorber can be calculated as
follows. Consider two transitions which, depending on the redshift of
the absorber, fall at different positions along their echelle order.
If we model the intra-order distortions found by
\citetalias{GriestK_09a} as a simple saw-tooth pattern of peak-to-peak
amplitude $\Delta v_{\rm amp}=500\,\hbox{${\rm m\,s}^{-1}$}$ then the root-mean-square
(RMS) velocity difference between the two transitions, averaged over
redshift, will be $\Delta v_{\rm amp}/(2\!\sqrt{2})=177\,\hbox{${\rm m\,s}^{-1}$}$ if the
transitions have arbitrary wavelengths. If one transition is from Mg
and the other is from Fe{\sc \,ii}, with typical rest wavelengths
$\sim$2700\,\AA\ (i.e.~frequencies $\sim$37000\,cm$^{-1}$), then the
typical difference in $q$-coefficients will be $\sim$1250\,cm$^{-1}$.
The resulting effect on \hbox{$\Delta\alpha/\alpha$}\ then follows from equation
(\ref{eq:da2}): $\left|\hbox{$\Delta\alpha/\alpha$}_{\rm corr}\right|\sim0.87\times10^{-5}$. Adding more
transitions will reduce this effect approximately as $\sqrt{N}$. Thus,
with typically 4--6 transitions observed in a single absorber, the
spurious effect the intra-order distortions will have on its value of
\hbox{$\Delta\alpha/\alpha$}\ will be $\left|\hbox{$\Delta\alpha/\alpha$}_{\rm corr}\right|\sim0.4\times10^{-5}$.

Degradation in the accuracy of the wavelength solution near the order
edges was already considered a possibility in \citet{WebbJ_99a}. To
test the possible effect of this \citeauthor{WebbJ_99a} artificially
increased the 1-$\sigma$ error bar on \hbox{$\Delta\alpha/\alpha$}\ for absorption systems with
transitions falling near order edges, thereby down-weighting those
systems in the calculation of the weighted mean \hbox{$\Delta\alpha/\alpha$}\ for the entire
sample. The effect was found to be insignificant. However, a more
detailed calculation is clearly warranted given the additional
information about the particular form of the intra-order wavelength
distortions identified by \citetalias{GriestK_09a}; we carry this out
in the following section.

\section{Calculating the effect on the Keck/HIRES results}\label{sec:calc}

In principle, the best way to understand the effect of intra-order
distortions on the Keck/HIRES results would be to correct the
wavelength scale of each extracted quasar exposure individually and
then combine together exposures of the same quasar to again form the
1-dimensional spectrum. The $\chi^2$ minimization of the Voigt profile
fits to the absorbers could be run again on the new versions of the
combined spectra, producing new, corrected values of \hbox{$\Delta\alpha/\alpha$}. This,
clearly, would involve enormous effort and the results would still be
subject to possible errors in our model of the intra-order distortions
(hereafter `model errors'). We therefore take a cruder approach, but
one which still allows us to check our expectations that (a) the
correction to \hbox{$\Delta\alpha/\alpha$}\ should be random in sign and magnitude from
absorber to absorber and (b) that the typical correction will be of
order $\hbox{$\Delta\alpha/\alpha$}_{\rm corr}\approx0.4\times10^{-5}$ as calculated above
(Section \ref{sec:distort}).

We first assume an appropriate functional form to counter the
intra-order distortions of \citetalias{GriestK_09a}: a velocity shift
increasing from zero at the echelle order centre to $+$500\,\hbox{${\rm m\,s}^{-1}$}\
(i.e.~a redward shift) at the order edges linearly in wavelength
space. We consider a more complex model in Section \ref{sec:model} to
illustrate the likely size of model errors in our results.

For each absorption system in the Keck/HIRES sample, we must determine
where each transition falls with respect to the order edges to
estimate the velocity shifts between all the transitions due to the
intra-order distortions. This is complicated by the fact that most
quasar spectra used in the analysis were formed by combining extracted
spectra of many separate exposures. For each absorption system, we
derived the order positions for all relevant transitions from the
extracted, wavelength calibrated spectrum for each quasar exposure.
Thus, for each transition, $i$, an average velocity shift, $\Delta
v_i$, was determined assuming that all quasar exposures contributing
spectra of that transition did so with equal weight. While the
signal-to-noise ratio (\hbox{${\rm SNR}$}) did vary between exposures, this is a
good approximation for most absorbers.

From the velocity shifts between the transitions in a given absorber,
equation (\ref{eq:da2}) can be used to compute the corresponding
correction to the value of \hbox{$\Delta\alpha/\alpha$}. That is, $\hbox{$\Delta\alpha/\alpha$}_{\rm corr}$ is the slope
(up to a factor of $-2$) of a linear least-squares fit of the values
of $\Delta v_i/c$ versus $q_i/\omega_{0,i}$. We use values for the
laboratory frequencies, $\omega_0$, and $q$-coefficients from
\citetalias{MurphyM_03a} in these calculations. However, two
complications arise here. The first is that not all transitions have
spectra of the same \hbox{${\rm SNR}$}. This is easily remedied by weighting the
least squares fit with the squares of the \hbox{${\rm SNR}$}\ values measured from
the combined spectra in the continuum around each transition.

The second complication is that the {\it shape} of the absorption
profile of each transition, and the relative {\it strength} of its
constituent velocity components, also determine its relative
contribution to constraining \hbox{$\Delta\alpha/\alpha$}\ in a given absorber. For example, in
an absorber with many strong, marginally resolved velocity components,
a strong transition may appear very saturated. Thus, the centroids of
the velocity components are very weakly constrained, if at all. But if
several weaker transitions were also fitted, those velocity components
will be optically thin and their centroids will be strongly
constrained in the weak transitions. Thus, in this example, the strong
transition may not contribute much to the final constraint on \hbox{$\Delta\alpha/\alpha$}\ in
this absorber. Properly taking this into account is as `simple' as
re-running the $\chi^2$ minimization of the Voigt profile fits to the
absorption profiles after correcting the spectrum of each transition
$i$ by its corresponding velocity shift, $\Delta v_i$. However, we
have ignored this complication, thereby allowing a simpler, more
illustrative calculation. Nevertheless, we have tested the importance
of this simplification by re-running the $\chi^2$ minimization on
several absorption systems, at both low- and high-$z$, and find it to
be fairly unimportant in most cases.

\section{Results}\label{sec:res}

Our estimates of the corrections to \hbox{$\Delta\alpha/\alpha$}\ for each of the 143 absorbers
in the \citetalias{MurphyM_04a} Keck/HIRES sample, calculated using
the method described above, are given in Table \ref{tab:res}. These
corrections should be added to the original values of \hbox{$\Delta\alpha/\alpha$}, which are
also given in the table for convenience. The upper panel of
Fig.~\ref{fig:res} shows the corrections plotted versus the redshifts
of the absorbers. Immediately we notice that the sign and magnitude of
the corrections vary randomly from absorber to absorber. Indeed, the
mean correction, $(-0.05\pm0.05)\times10^{-5}$, is consistent with
zero, indicating that there is no strong influence on the average
value of \hbox{$\Delta\alpha/\alpha$}, as expected. The median magnitude of the corrections is
$0.37\times10^{-5}$, in line with expectations from the very crude
estimate made in Section \ref{sec:distort}. And while the assumptions
required to perform the calculation for each absorber, detailed in the
last section, are not unimportant, they should not significantly
affect these two main conclusions.

\begin{table*}
  \caption{\footnotesize Values of \hbox{$\Delta\alpha/\alpha$}\ and corrections for possible intra-order distortions of the wavelength scale. The first three columns specify the B1950 quasar name, the emission and absorption redshifts. The fourth column provides the transitions used to determine \hbox{$\Delta\alpha/\alpha$}\ in each absorber; each letter represents a transition and the key is provided in table 2 of \citetalias{MurphyM_03a}. The fifth column is the raw value of \hbox{$\Delta\alpha/\alpha$}\ together with the formal 1-$\sigma$ statistical error. The systematic error term, $\delta(\hbox{$\Delta\alpha/\alpha$})_{\rm sys}$, is non-zero only for ``high-contrast'' absorbers; see text for explanation. The seventh and eighth columns provide our estimate of the correction, $\hbox{$\Delta\alpha/\alpha$}_{\rm corr}$, for intra-order distortions, to be added to \hbox{$\Delta\alpha/\alpha$}, and the systematic error term, $\delta(\hbox{$\Delta\alpha/\alpha$})^{\rm corr}_{\rm sys}$, which was calculated in the same way as $\delta(\hbox{$\Delta\alpha/\alpha$})_{\rm sys}$ but using the corrected values of \hbox{$\Delta\alpha/\alpha$}. The final column specifies the observational sub-samples employed: A = ``Previous low-$z$ sample'' from \citetalias{MurphyM_03a}; B1 = ``Previous high-$z$ sample'' from \citetalias{MurphyM_03a}; B2 = The 15 absorbers added in \citetalias{MurphyM_04a}; C = ``New sample'' from \citetalias{MurphyM_03a}. Only a excerpt of the table is provided here; the complete table is available from the authors or http://astronomy.swin.edu.au/$\sim$mmurphy/pub.html\,.}\vspace{-2.5em}
\label{tab:res}
\footnotesize
\begin{center}
\begin{tabular}{lcccccccl}\hline
B1950 name   & \hbox{$z_{\rm em}$} & \hbox{$z_{\rm abs}$}   & Transitions  & \hbox{$\Delta\alpha/\alpha$}                        & $\delta(\hbox{$\Delta\alpha/\alpha$})_{\rm sys}$ & $\hbox{$\Delta\alpha/\alpha$}_{\rm corr}$ & $\delta(\hbox{$\Delta\alpha/\alpha$})^{\rm corr}_{\rm sys}$ & Sample \\
             &      &         &              & [$10^{-5}$]                & [$10^{-5}$]             & [$10^{-5}$]      & [$10^{-5}$]                        &        \\\hline
1634$+$7037  & 1.34 & 0.99010 & bcnpqr       & $\phantom{-}1.156\pm2.399$ & 0.000                   &  0.498           & 0.000                              & A      \\
0019$-$1522  & 4.53 & 3.4388  & ghl          & $\phantom{-}0.937\pm3.912$ & 0.000                   &  1.414           & 0.000                              & B1     \\
0100$+$1300  & 2.68 & 2.3095  & efgjklmvw    & $-3.949\pm1.370$           & 1.754                   &  0.063           & 1.707                              & B1     \\\hline
\end{tabular}
\end{center}
\normalsize
\end{table*}

\begin{figure*}[t!]
\begin{center}
\includegraphics[width=0.8\textwidth]{SAIT_MURPHY_FIG2.eps}\vspace{-0.1em}
\caption{\footnotesize Corrections to \hbox{$\Delta\alpha/\alpha$}\ and corrected values of
  \hbox{$\Delta\alpha/\alpha$}\ versus absorption redshift and cosmological look-back time
  ($H_0=71\,\hbox{${\rm km\,s}^{-1}$}\,{\rm Mpc}^{-1}$, $\Omega_{{\rm m,}0}=0.27$,
  $\Omega_{\Lambda,0}=0.73$). {\it Top:} Estimated corrections to \hbox{$\Delta\alpha/\alpha$}\
  due to intra-order distortions. Note that their sign and magnitude
  vary randomly from absorber to absorber. The median magnitude of the
  corrections is $0.37\times10^{-5}$. {\it Middle:} The corrected
  values of \hbox{$\Delta\alpha/\alpha$}\ with their error bars representing the quadrature sum
  of the 1-$\sigma$ statistical and systematic errors. {\it Bottom}:
  Weighted mean values of \hbox{$\Delta\alpha/\alpha$}, with 1-$\sigma$ errors, in bins
  containing 13 absorbers each.}
\label{fig:res}
\end{center}
\end{figure*}

It is important to emphasise that the sub-samples of absorbers below
and above $\hbox{$z_{\rm abs}$}=1.8$ are qualitatively different. All the absorbers
at $\hbox{$z_{\rm abs}$}<1.8$ (`low-$z$') depend only on Mg and Fe{\sc \,ii}
transitions, whereas those at $\hbox{$z_{\rm abs}$}>1.8$ (`high-$z$') tend not to
include Mg and generally contain the wider variety of transitions,
with a mixture of $q$-coefficients, bluewards of $\lambda_{\rm
  rest}=2300$\,\AA\ in Fig.~\ref{fig:shifts}. As illustrated in
Fig.~\ref{fig:shifts}, the signature of a varying $\alpha$ for
Mg/Fe{\sc \,ii} absorbers is therefore very simple, while that for the
higher-$z$ systems is more complicated, strongly depending on which
transitions are detected and fitted. In this sense, absorbers with
only Mg/Fe{\sc \,ii} transitions fitted are more susceptible to simple
instrumental systematic errors which cause long-range, low-order
distortions of the wavelength scale and also astrophysical effects
which might shift velocity components of Fe{\sc \,ii} relative to
those of Mg. However, for the low-$z$ Mg/Fe{\sc \,ii} absorbers in the
Keck/HIRES sample, the scatter around the weighted mean \hbox{$\Delta\alpha/\alpha$}\ was
consistent with the individual error bars in \citetalias{MurphyM_03a}
and \citetalias{MurphyM_04a}. This remains true even after the
corrections for intra-order distortions are applied: $\chi^2=76.03$
around the weighted mean \hbox{$\Delta\alpha/\alpha$}\ for the 77 low-$z$ absorbers.

The same cannot be said of the high-$z$ absorbers: in
\citetalias{MurphyM_03a} and \citetalias{MurphyM_04a} we identified a
sub-sample of high-$z$ absorbers for which the scatter in \hbox{$\Delta\alpha/\alpha$}\
exceeded expectations based on the individual errors. In these 27
absorbers both very strong and very weak transitions were fitted
simultaneously -- i.e.~they are ``high-contrast'' absorbers -- making
the multi-component Voigt profile fitting process more difficult and
error-prone. These systems could be `under-fitted' -- too few velocity
components used to model each absorber -- and this may lead to
systematic errors in individual absorbers which are random in sign and
magnitude. We demonstrated the effect of under-fitting with simulated
spectra in \citet{MurphyM_08a}. Just as in \citetalias{MurphyM_03a}
and \citetalias{MurphyM_04a}, the average systematic error in the
sample of 27 high-contrast absorbers is that which, when added in
quadrature to the individual statistical errors, reduces $\chi^2$ per
degree of freedom, $\chi^2_\nu$, to unity around the weighted mean
\hbox{$\Delta\alpha/\alpha$}\ for those absorbers. The fact that we find a very similar
systematic error term using the corrected values of \hbox{$\Delta\alpha/\alpha$},
$1.71\times10^{-5}$, as found from the uncorrected values,
$1.75\times10^{-5}$, indicates that the extra scatter in \hbox{$\Delta\alpha/\alpha$}\ for
these absorbers does not arise from the intra-order distortions; our
postulate that it arises from the mixture of strong and weak
transitions fitted, and the resulting under-fitting, remains. These
systematic error components are shown for the high-contrast absorbers
in Table \ref{tab:res}.

The middle panel of Fig.~\ref{fig:res} shows the corrected values of
\hbox{$\Delta\alpha/\alpha$}\ with their 1-$\sigma$ statistical errors and systematic error
components added in quadrature. The lower panel shows a binned version
of these results, where the weighted mean \hbox{$\Delta\alpha/\alpha$}\ of the 13 absorbers in
each bin is shown with its 1-$\sigma$ error. As with the uncorrected
results in \citetalias[see][]{MurphyM_04a}, \hbox{$\Delta\alpha/\alpha$}\ is consistently
smaller $\alpha$ in the absorption systems compared to the current
laboratory value. Table \ref{tab:stats} quantifies this: the weighted
mean \hbox{$\Delta\alpha/\alpha$}\ for the full sample, $\hbox{$\Delta\alpha/\alpha$}=(-0.61\pm0.11)\times10^{-5}$,
differs only slightly from the uncorrected value from
\citetalias{MurphyM_04a}, $(-0.57\pm0.11)\times10^{-5}$, as expected.

\begin{table*}
  \caption{\footnotesize Basic statistics for the entire sample and redshift sub-samples. The second column gives the number of absorbers, $N_{\rm abs}$, in each sample. The statistics before any corrections for intra-order distortions are applied are in columns 3, 4 \& 5, while the remaining columns provide the same statistics after the \hbox{$\Delta\alpha/\alpha$}\ values are corrected. $\left<\hbox{$\Delta\alpha/\alpha$}\right>_{\rm w}$ is the weighted mean and $\left<\hbox{$\Delta\alpha/\alpha$}\right>$ is the unweighted mean.}\vspace{-2.5em}
\label{tab:stats}
\footnotesize
\begin{center}
\begin{tabular}{lcccccccc}\hline
               &               & \multicolumn{3}{c}{Before correction}                            & & \multicolumn{3}{c}{After correction}                            \\
Sample         & $N_{\rm abs}$ & $\left<\hbox{$\Delta\alpha/\alpha$}\right>_{\rm w}$ & $\left<\hbox{$\Delta\alpha/\alpha$}\right>$  & Median        & & $\left<\hbox{$\Delta\alpha/\alpha$}\right>_{\rm w}$ & $\left<\hbox{$\Delta\alpha/\alpha$}\right>$  & Median       \\
               &               & [$10^{-5}$]                & [$10^{-5}$]         & [$10^{-5}$]   & & [$10^{-5}$]                & [$10^{-5}$]         & [$10^{-5}$]  \\\hline
{\bf Fiducial} & {\bf 143}     & \boldmath{$-0.57\pm0.11$}        & \boldmath{$-0.53\pm0.19$} & \boldmath{$-0.42$}  & & \boldmath{$-0.61\pm0.11$}        & \boldmath{$-0.58\pm0.20$} & \boldmath{$-0.56$} \\
$\hbox{$z_{\rm abs}$}<1.8$    &  77           & $-0.54\pm0.12$             & $-0.61\pm0.22$      & $-0.39$       & & $-0.58\pm0.12$             & $-0.60\pm0.23$      & $-0.58$      \\
$\hbox{$z_{\rm abs}$}>1.8$    &  66           & $-0.74\pm0.27$             & $-0.45\pm0.34$      & $-0.43$       & & $-0.79\pm0.27$             & $-0.57\pm0.34$      & $-0.55$      \\\hline
\end{tabular}
\end{center}
\normalsize
\end{table*}

Table \ref{tab:stats} gives the statistics for the low- and high-$z$
sub-samples. It was shown in \citetalias{MurphyM_03a} that the low-
and high-$z$ samples respond, on average, in opposite ways to simple,
long-range distortions of the wavelength scale. Note that the weighted
means for the low- and high-$z$ absorbers are similar and both depart
significantly from zero, even after the corrections are applied. This
also quantifies the fact that the evidence for a varying $\alpha$ is
dominated by the low-$z$ absorbers, with the evidence at high-$z$
being at the $\approx$3-$\sigma$ level both before and after
correction. Still, as mentioned above, if long-range wavelength
calibration distortions remain in the data, the low- and high-$z$
samples' weighted mean \hbox{$\Delta\alpha/\alpha$}\ values should have opposite sign.  This is
an important internal consistency check that is only available when
one compares low-$z$ Mg/Fe{\sc \,ii} with higher-$z$ absorbers
constraining a greater diversity of transitions. Of course, we must
also recognise that absence of evidence for systematic errors capable
of explaining the consistency of the low- and high-$z$ \hbox{$\Delta\alpha/\alpha$}\ values is
not evidence for their absence.

\section{Are the corrections warranted?}\label{sec:model}

We saw in the previous section that correcting the \hbox{$\Delta\alpha/\alpha$}\ values for
intra-order distortions of the kind found by \citetalias{GriestK_09a}
makes no difference to the overall conclusions, nor for some more
detailed aspects of the Keck/HIRES results. So, having calculated
reasonable estimates of the corrections, can we find evidence that
applying them really is warranted?

For example, if the corrections are important, we should expect the
distribution of \hbox{$\Delta\alpha/\alpha$}\ values around the mean to significantly narrow
after applying the corrections. We should also expect a significant
anti-correlation between the values of \hbox{$\Delta\alpha/\alpha$}\ and the corrections. We
find neither of these effects.

Table \ref{tab:stats} provides the mean \hbox{$\Delta\alpha/\alpha$}\ and its standard error --
i.e.~the RMS/$\sqrt{N_{\rm abs}}$ -- for the full sample and low- and
high-$z$ sub-samples. Only very small changes in the RMS are evident
in each case, indicating that the corrections do not remove a
significant amount of scatter in the \hbox{$\Delta\alpha/\alpha$}\ values. A small Monte Carlo
simulation can be used to gauge how much difference in the RMS we
should expect if the corrections were important. We generated random
absorber data-sets, with the same size, total errors and corrections
as the real Keck/HIRES sample. The corrected \hbox{$\Delta\alpha/\alpha$}\ values in each
realisation were set to $-0.6\times10^{-5}$ and then randomised,
according to the Gaussian errors for individual absorbers. The RMS of
this sample, and the same realisation with the corrections removed
from the \hbox{$\Delta\alpha/\alpha$}\ values, were compared. Differences in RMS values between
the corrected and uncorrected realizations of $>0.1$ and
$>0.2\times10^{-5}$ occurred 37 and 4\,\% of the time by chance alone.
Thus, the lack of RMS differences between our real corrected and
uncorrected samples cannot be used as evidence that the corrections
are not meaningful. But the Monte Carlo simulation does indicate that
the corrections are too small, in comparison to the total errors on
\hbox{$\Delta\alpha/\alpha$}\ in individual absorbers, to make a large difference to the sample
overall.

Similarly, the Spearman rank correlation and Kendall's $\tau$ tests
find insignificant anti-correlations between \hbox{$\Delta\alpha/\alpha$}\ and the corrections
for the full sample or sub-samples. Nor are absorbers with large \hbox{$\Delta\alpha/\alpha$}\
errors masking an underlying anti-correlation; using only absorbers
with total errors (quadrature sum of statistical and systematic
errors) less than $3\times10^{-5}$, gives similarly insignificant
results.  However, again a small Monte Carlo simulation confirms that,
effectively, this is not unexpected given the small size of the
corrections relative to the larger total errors on individual \hbox{$\Delta\alpha/\alpha$}\
values.

To summarise, while we do not find evidence that the corrections we
calculate need to be applied, it is their relative smallness in
general which precludes a clear test for this.  In essence, the formal
errors in the Keck/HIRES sample still dominate over the potential
systematic errors caused by the intra-order distortions identified by
\citetalias{GriestK_09a}.

However, an important assumption so far has been the particular form
of intra-order distortion we have used; the \citetalias{GriestK_09a}
results have been approximated with a simple saw-tooth pattern in
every echelle order. Because the \citetalias{GriestK_09a} analysis
relies on I$_2$-cell calibration, it can only probe the intra-order
distortions over the wavelength range $\sim$5000--6200\,\AA. Even over
that relatively short wavelength range, there is some evidence for a
slow decrease in the peak-to-peak amplitude of the saw-tooth pattern
in bluer orders. How this extrapolates to longer and shorter
wavelengths than 6200 and 5000\,\AA\ (respectively) is unknown. Thus,
model errors may well exist in our estimates of the corrections to the
Keck/HIRES \hbox{$\Delta\alpha/\alpha$}\ values above.

To test the importance of this, we can repeat the calculation of the
corrections using a somewhat different model of the intra-order
distortions: we fix $\Delta v_{\rm amp}$ to 500\,\hbox{${\rm m\,s}^{-1}$} at 5500\,\AA\ and
increase (decrease) it linearly with slope 0.55\,\hbox{${\rm m\,s}^{-1}$}\,\AA$^{-1}$ above
(below) 5500\,\AA\ and enforce a maximum (minimum) amplitude of
1000\,\hbox{${\rm m\,s}^{-1}$}\ (200\,\hbox{${\rm m\,s}^{-1}$}) at redder (bluer) wavelengths outside the range
covered by the I$_2$ cell calibration. The RMS difference between the
old and new corrections is $0.56\times10^{-5}$ and, with the new
corrections, the weighted mean becomes $(-0.62\pm0.11)\times10^{-5}$
over the whole sample and $(-0.61\pm0.12)\times10^{-5}$
[$(-0.66\pm0.27)\times10^{-5}$] at low$-z$ [high-$z$]. Comparison with
the values in Table \ref{tab:stats} reveals that the model errors in
this case are very small. Of course, this model is not very different
to our original, simpler one. For example, it may be that the
intra-order distortions have a completely different shape, phase
and/or amplitude for different quasar observations. This possibility
must be explored with future observations.

\section{Conclusions}\label{sec:conc}

Exploring systematic effects which may explain the Keck/HIRES evidence
for a varying $\alpha$ is clearly an important problem. However,
various properties of the Keck/HIRES results make the task difficult;
the consistency between the average \hbox{$\Delta\alpha/\alpha$}\ values in the low-$z$
Mg/Fe{\sc \,ii} and the more diverse high-$z$ systems being an
important one. We have demonstrated here that if we model the
intra-order distortions identified by \citetalias{GriestK_09a} in a
simple way, and extrapolate the model to all echelle orders (not just
those within the I$_2$-cell calibration range) the effect on the
overall evidence for varying $\alpha$ is very small. As expected, the
distortions affect individual values of \hbox{$\Delta\alpha/\alpha$}\ randomly in sign and
magnitude, because the differing redshifts place the transitions at
varying positions with respect to echelle order edges where the
distortions are worst. Indeed, the effect for a typical absorber is to
shift \hbox{$\Delta\alpha/\alpha$}\ by $0.4\times10^{-5}$ which, compared to the median error
on \hbox{$\Delta\alpha/\alpha$}, $\sim$$1.9\times10^{-5}$, is too small for us even to find
direct evidence of the need to apply the corrections we calculate.

Despite the above conclusions, it is important to emphasise that we do
not yet fully understand the origin of the intra-order distortions
identified by \citetalias{GriestK_09a}, how they depend on various
observational parameters (e.g.~telescope pointing direction,
temperature, time etc.) and therefore how they may differently affect
spectra of different quasars in the Keck/HIRES sample. Indeed,
\citetalias{GriestK_09a} show that separate exposures taken through
the I$_2$ cell seem to have somewhat different intra-order distortion
patterns. And while we have made a simple attempt to address this
problem of model errors, it is not enough to completely rule out
intra-order distortions as an important systematic error for the
Keck/HIRES results. If future Keck/HIRES observations allow much
smaller statistical errors on \hbox{$\Delta\alpha/\alpha$}\ in individual absorbers or small
samples, intra-order distortions like those identified by
\citetalias{GriestK_09a} must either be eliminated or carefully
modelled.

\begin{acknowledgements}
  We thank K.~Griest and J.~B.~Whitmore for discussions. MTM thanks
  the Australian Research Council for a QEII Research Fellowship
  (DP0877998).
\end{acknowledgements}

\bibliographystyle{aa}

redpajama_set_name: RedPajamaArXiv


text:
Ebeneezer Scrooge Might Have Been Based On These Real People (Cool Weird Awesome 907)
Cool Weird Awesome, Podcasts
Charles Dickens' "A Christmas Carol" was first published today in 1843. The character of Ebeneezer Scrooge is said to be based on a real life person, though which person it was that inspired the story depends on who's telling the story.
By Brady Carlson|2022-12-19T10:48:17-05:00December 19, 2022|Categories: Cool Weird Awesome, Podcasts|Tags: A Christmas Carol, books, Charles Dickens, Ebeneezer Scrooge|
Meet Some Of The Oldest Books Ever Found (Cool Weird Awesome 843)
Today is National Read A Book Day, which reminds us of an article from HowStuffWorks that tries to answer a complicated question: "What is the oldest book in the world?"
By Brady Carlson|2022-09-06T07:59:34-04:00September 6, 2022|Categories: Cool Weird Awesome, Podcasts|Tags: books, gourds, Ithaca NY|
A Sprained Ankle Helped Bring Pippi Longstocking To The World (Cool Weird Awesome 742)
Today in 1944, Astrid Lindgren of Stockholm, Sweden fell on ice and sprained her ankle. While stuck in bed, she decided to write down some stories she'd been telling her daughter, stories that would lead to one of the most popular children's book series of all time.
By Brady Carlson|2022-03-28T09:16:18-04:00March 28, 2022|Categories: Cool Weird Awesome, Podcasts|Tags: Astrid Lindgren, books, children's books, running, ultramarathon|
Winnie the Pooh Is Named For A Zoo Bear And A Swan (Cool Weird Awesome 697)
Today in 1882 author A.A. Milne was born. His most famous character, Winnie the Pooh, was named partly for a real bear who lived at the London Zoo. And yes, the real Winnie had a sweet tooth as well.
By Brady Carlson|2022-01-18T07:04:22-05:00January 18, 2022|Categories: Cool Weird Awesome, Podcasts|Tags: bears, book history, books, mathematics, Winnie the Pooh|
The Chicago Cubs Once Had A "College of Coaches" Instead of a Manager (Cool Weird Awesome 693)
Today in 1961, the Chicago Cubs announced they wouldn't hire a manager for the new season, and would instead use a rotating "College" of coaches. You can probably guess how well that worked out.
By Brady Carlson|2022-01-12T06:49:54-05:00January 12, 2022|Categories: Cool Weird Awesome, Podcasts|Tags: baseball, books, clocks, Sports, sports history|
A Robot Seacraft Is Exploring The Ocean For A Few Years (Cool Weird Awesome 659)
It's called the Intrepid Benthic Rover II, and its five year (or more) mission is to explore the deep ocean, most of the time by itself. Plus: in a new book artist Marina Luz paints the covers of books where people are trying to describe a book when they can't remember the title.
By Brady Carlson|2021-11-18T07:04:22-05:00November 18, 2021|Categories: Cool Weird Awesome, Podcasts|Tags: books, oceans, robots, science|
Donald J. Sobol's Encyclopedia Brown Books Taught Young Readers To Solve Mysteries (Cool Weird Awesome 626)
Today's the birthday of a mystery author known to millions of kids, Donald J Sobol. He wrote the Encyclopedia Brown series, about a 10 year old detective who solved cases because he knew, as his nickname suggested, all sorts of unusual and obscure facts in the era way before the internet. Plus: it's National Taco Day, and here's the story of one of the largest tacos ever made.
By Brady Carlson|2021-10-04T09:14:12-04:00October 4, 2021|Categories: Cool Weird Awesome, Podcasts|Tags: authors, books, children's books, Encyclopedia Brown, tacos, world records|
There's A New Way To Recycle The Materials We Need For High-Tech Batteries (Cool Weird Awesome 521)
As automakers move toward all-electric vehicles, we're going to need a lot more batteries, only there are difficulties in getting some of the key elements. A startup called Nth cycle may have a way to help. Plus: meet a young reader who really knows how to multitask.
By Brady Carlson|2021-04-16T12:05:13-04:00April 16, 2021|Categories: Cool Weird Awesome, Podcasts|Tags: batteries, books, recycling|
Fuel Cells Are Strong To The Finish, When They're Powered By Spinach (Cool Weird Awesome 418)
Fuel cells need a catalyst for an important reaction, and a team at American University has found that spinach may be the best raw material for a catalyst we've found yet. Plus: ever wanted to smell like old books? A new scent can help make it happen!
By Brady Carlson|2021-06-28T11:51:44-04:00November 12, 2020|Categories: Cool Weird Awesome, Podcasts|Tags: alternative energy, books, fuel cells, perfume, spinach|
Never Skip The Dedication Page Of A Book, They Can Get Wild (Cool Weird Awesome 410)
If you're taking part in National Novel Writing Month, then here's a tip: don't forget the dedication page. They can be full of surprises, as we discovered in quite a few books. Plus: meet the prehistoric pelagornithid, probably the largest flying bird ever, with a 20 foot wingspan and teeth.
By Brady Carlson|2020-11-02T08:56:37-05:00November 2, 2020|Categories: Cool Weird Awesome, Podcasts|Tags: archaeology, birds, books|

redpajama_set_name: RedPajamaCommonCrawl


text:
Cape Breton Voices | Give cities bigger role in immigration, N.B. advocate tells MPs
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Give cities bigger role in immigration, N.B. advocate tells MPs
12 Feb Give cities bigger role in immigration, N.B. advocate tells MPs
Posted at 17:12h in Immigration	by	Cape Breton Voices 0 Comments
CBC News | Philip Drost | June 15, 2017.
Alex LeBlanc of the New Brunswick Multicultural Council calls for municipal nominee program
Municipalities need more power to make decisions about immigration, the head of the New Brunswick Multicultural Council told a Commons committee on Wednesday.
"Where immigration is controlled at a federal level, integration happens at a local level," Alex LeBlanc, the executive director of the council, said in a presentation to the standing committee on citizenship and immigration.
"Really, it's our cities, it's our communities that are the brokers for inclusion."
He proposed a municipal nominee program, similar to the provincial nominee program, which allows skilled workers and business people chosen from around the world to get into a faster track toward settling into a province that needs them in the workforce.
Calls for pilot municipal project
"Give cities the responsibility of selecting people, in partnership with employers, and then give cities a greater role in the integration and retention process," said LeBlanc, who was asked to speak to the committee about immigration to Atlantic Canada.
Using the provincial program, New Brunswick has brought in 625 immigrants a year to answer certain workforce needs, "and this program has dramatically increased the traffic to New Brunswick," LeBlanc said.
But LeBlanc wants a municipal program to complement the provincial one, and he recommended running a pilot project in New Brunswick.
"We could use the same structure that we have in place now with the provincial nominee program, but perhaps receive an additional allocation from the federal government which is earmarked to pilot a municipal approach," he said.
"Then it will be up to the cities to allocate any kind of resource staff time to do some of this work."
Municipalities interested
Edmundston Mayor Cyrille Simard supports a pilot program to get municipalities more involved in bringing immigrants to their communities. (CBC)
LeBlanc said if nothing is done, the population problem in New Brunswick won't go away.
"We represent 6.6 per cent per cent of the population in the country, and yet 3.1 per cent of immigrants that are coming to Canada are coming to our region," said LeBlanc.
He's already talked to people in municipalities across New Brunswick and been able to gather interest.
Edmundston Mayor Cyrille Simard agreed with the idea to increase the role of the municipalities.
Local input would help
"If a pilot project would be set up in the province or in Atlantic Canada, I'm pretty sure it would be welcome by most of municipalities who are already looking to the immigration file to get their demographics in a better way," Simard said.
New 'social' lab focuses on retaining and attracting immigrants in N.B.
N.B. employers have jobs they can't fill — so they're looking south for job-seekers
New Brunswick is Canada's only province with a shrinking population
He said that if the pilot program worked in conjunction with the current provincial nominee program, it would be a benefit to communities.
"It's just a matter of adding more input on a local level in order to fit the profiles of the prospective immigrants in a better way," said Simard.
OPINION: CBRM governance in the year ahead
Top Executives Kick Off Joint Initiative to Grow Women-Owned Businesses
LETTER: The baby, bathwater and downtown Sydney
LETTER: CBRM council should find way to make Cape Breton Centre for Arts, Culture and Innovation project happen
Joanne Pyke and Sarah Pyke: Capitalizing on well-being


Flexor tendons in the hand are commonly injured, leading to impaired hand function. However, the scar-tissue healing response is not well characterized. A murine model of flexor tendon healing is demonstrated here. This model can enhance overall understanding of the healing process and assess therapeutic approaches to improve healing.
Ackerman, J. E., Loiselle, A. E. Murine Flexor Tendon Injury and Repair Surgery. J. Vis. Exp. (115), e54433, doi:10.3791/54433 (2016).
Tendon connects skeletal muscle and bone, facilitating movement of nearly the entire body. In the hand, flexor tendons (FTs) enable flexion of the fingers and general hand function. Injuries to the FTs are common, and satisfactory healing is often impaired due to excess scar tissue and adhesions between the tendon and surrounding tissue. However, little is known about the molecular and cellular components of FT repair. To that end, a murine model of FT repair that recapitulates many aspects of healing in humans, including impaired range of motion and decreased mechanical properties, has been developed and previously described. Here an in-depth demonstration of this surgical procedure is provided, involving transection and subsequent repair of the flexor digitorum longus (FDL) tendon in the murine hind paw. This technique can be used to conduct lineage analysis of different cell types, assess the effects of gene gain or loss-of-function, and to test the efficacy of pharmacological interventions in the healing process. However, there are two primary limitations to this model: i) the FDL tendon in the mid-portion of the murine hind paw, where the transection and repair occur, is not surrounded by a synovial sheath. Therefore this model does not account for the potential contribution of the sheath to the scar formation process. ii) To protect the integrity of the repair site, the FT is released at the myotendinous junction, decreasing the mechanical forces of the tendon, likely contributing to increased scar formation. Isolation of sufficient cells from the granulation tissue of the FT during the healing process for flow cytometric analysis has proved challenging; cytology centrifugation to concentrate these cells is an alternate method used, and allows for generation of cell preparations on which immunofluorescent labeling can be performed. With this method, quantification of cells or proteins of interest during FT healing becomes possible.
Flexor tendons in the hand work in concert with the flexor muscles of the forearm and digital sheaths to enable flexion of the digits and grasping function of the hand. Flexor tendons run along the palmar aspect of the hand; this relatively superficial location often results in injuries to the flexor tendons during trauma to the hand. Tendons heal through a scar tissue response rather than regeneration of normal tendon tissue 1. While this scar tissue provides continuity to the tendon, function is dramatically decreased relative to healthy tendon. Tendon-scar tissue composites are characterized by impaired mechanical properties 1, rendering the repaired tendons more likely to rupture. In addition, scar tissue lacks the organization of the native tendon collagen fiber structure, resulting in an increase in tendon size and bulk. Given the anatomic constraints of the tendon-sheath unit, even a modest increase in tendon size can drastically reduce the gliding function of the tendon, and therefore digit range of motion and hand function.
Prior to the 1960's injuries to the flexor tendons, particularly those in Zone II of the hand, were not routinely repaired due to the severe complications in healing that arose with these repairs 2. This area of the hand was referred to as 'no man's land' 3. However, improvements in surgical techniques, suture patterns and physical therapy rehabilitation protocols have dramatically improved outcomes of flexor tendon repairs 2. Despite these advances, up to 40% of repairs result in sufficient adhesion formation to impede hand function 4. Therefore, a biological approach is required to improve healing. Unfortunately, very little is known about the tendon healing process at the cellular and molecular level. Thus, the goal was to develop a murine model that could be used to improve the fundamental understanding of the cellular and molecular components of flexor tendon healing and the scar formation response, as a means to identify novel therapeutic targets to improve healing.
Larger animal models have been instrumental in furthering understanding of the flexor tendon healing process. Canine and rabbit studies have demonstrated both the intrinsic and extrinsic healing ability of flexor tendons 5,6, the importance of early controlled passive motion in minimizing adhesion formation relative to immobilization 7, as well as the effects of different suture patterns on the healing process 8,9. In addition, the canine model has been useful in testing translational tissue-engineering approaches to improve healing 10. However, there are several important advantages in using a murine model relative to a large animal model, including the relative cost, availability of murine specific reagents, and the ease of generating global knock-outs or tissue-specific deletion/overexpression constructs. Moreover, the functional similarities between human and mice with respect to flexor tendons 11 indicate the potential utility in developing a murine model.
Development of a murine model of flexor tendon transection and repair mimics many aspects of clinical healing, including the formation of abundant scar tissue and impaired mechanical properties. The model described here is not a true recapitulation of clinical practice due to transection of the FDL at the myotendinous junction in order to protect the repair site. Furthermore, this model does not account for the contribution of synovial sheath cells to the healing response, as there is no synovial sheath covering the mid-portion of the tendon where the repair occurs. Despite these limitations, this model has the advantage of generating range of motion-limiting adhesions, which has yet to be demonstrated in murine models that more closely approximate the clinical scenario. This model has been used to assess knock-out mouse models 12,13, and to test different pharmacological approaches to improve healing 14-17. Histological analyses of this model, using immunohistochemistry and in situ hybridization, can provide important insights in to the localization of key genes and proteins during healing. However, histology provides only a cross-sectional spatial analysis and does not permit quantification throughout the entire tissue. Flow cytometry represents a more quantitative approach, but only a very limited number of cells can be isolated from the healing tendon tissue in the mouse model, and this number is further decreased during fixation, permeabilization, and washing steps. Taking this in to account, flow cytometry becomes an unfeasible approach due to the number of animals that would be required. An alternative method is necessary to preserve the majority of this small cell population in order to further characterize the healing milieu. The method used to accomplish this, shown here, involves concentration of the isolated cells via cytology centrifugation onto a glass slide, followed by immunocytochemistry. In the present study EdU (5-ethynyl-2'deoxyuridine, a thymidine analog) incorporation and subsequent labeling was used to determine the relative proliferative state of cells at the healing site. This approach can be applied to test the efficacy of pharmacological treatments on cell proliferation, gene knock-out or overexpression, or to identify and quantify different cell populations.
The University Committee on Animal Research at the University of Rochester approved all animal experiments. Ten-12 week old female C57BL/6J mice were used.
Autoclave surgical instruments to sterilize, wear sterile gloves throughout, and maintain a sterile operating field.
Anesthetize the mouse via intraperitoneal injection (i.p.) with a volume of ketamine (80 mg/kg) and xylazine (10 mg/kg) corresponding to body weight. Confirm depth of sedation via absence of toe-pinch reflex.
Administer pre-emptive analgesia (buprenorphine, 0.05-0.1 mg/kg) via subcutaneous injection. Apply ophthalmic ointment to prevent eyes from drying out.
Prepare the surgical site by clipping the fur on the entire hind limb. Sterilize the skin by scrubbing sequentially with povidone iodine, followed by 70% ethanol, and again with povidone iodine.
Find the flexor digitorum longus (FDL) tendon, seen superficially in the medial aspect of the calf. Using a scalpel, make a small 0.5-1 cm incision in the skin with micro-scissors to expose the tendon.
Use forceps to separate the FDL tendon from surrounding tissue and trace it up to the myotendinous junction. Cut the tendon at this junction with spring scissors to release it, taking care to avoid the posterior tibial artery.
Close the skin with 5-0 nylon sutures.
Note: The FDL transection and repair (steps 2.4) should be performed using a stereomicroscope.
Make a 3 mm incision over the posterolateral aspect of the hind paw using spring micro-scissors. Gently retract the surrounding soft tissue and muscle with forceps, making sure to minimize tissue damage, and identify the FDL tendon.
Gently raise the FDL tendon and completely transect it using micro-scissors. Suture the ends of the FDL tendon together in a modified Kessler pattern with 8-0 sutures, avoiding drying of the tendon by periodically wetting it with saline.
Replace soft tissue and muscle over the tendon, then close the incision with 5-0 nylon sutures.
Place mice on a slide warmer set to 37 °C, to maintain body temperature until recovered from anesthesia.
Monitor mice post-operatively for signs of impairment or infection including increased vocalizing and ruffled fur. Inject buprenorphine (50 µl/mouse) as analgesic every 12 hr until mice no longer show signs of pain or distress.
Allow mice to heal for a period of 10 days post-surgery before continuing to the next steps.
Note: Cells can be harvested at any time-point post-surgery. Here, 10 days are chosen for these representative experiments given the relatively high cellularity of the tissue at this time.
Prepare EdU (5-ethynyl-2'deoxyuridine) solution (10 mg/ml in sterile Phosphate buffered saline [PBS] + 1% Dimethyl Sulfoxide [DMSO] to increase solubility).
Inject mice with 100 µl EdU (50 mg/kg) via i.p. injection 24 hr prior to sacrifice.
Prepare 3 mg/ml collagenase I in PBS.
Euthanize mouse via carbon dioxide asphyxiation at a flow rate of no more than 3 L/min, and perform cervical dislocation as a secondary measure.
Locate the repaired tendon using step 2.4 above, and isolate tendon tissue by cutting about 2 mm on either side of the injury site with micro-scissors.
Mince tissue with scalpel in a petri dish with 1 ml of 3 mg/ml collagenase, then pass mixture through an 18 G needle several times to break up the tissue. Collect mixture into a 1.5 ml centrifuge tube.
Digest tendon tissue for 1 hour at 37 °C with shaking.
Spin tissue down (300 x g for 5 min), aspirate collagenase, then resuspend cells/tissue with 500 µl 3% bovine serum albumin (BSA) in PBS by pipetting up and down several times.
Filter cell suspension through a 70 µm cell strainer to remove debris and large pieces of tendon, and set aside in a 37 °C incubator.
Place tendon tissue into another 1.5 ml centrifuge tube, and refresh with 1 ml collagenase solution, pipetting up and down to mix.
Incubate tissue another hour at 37 °C with shaking.
Spin down digested tendon tissue (300 x g for 5 min), then resuspend in 500 µl 3% BSA in PBS by pipetting up and down several times.
Filter cell suspension through a 70 µm cell strainer, combine with suspension isolated in 4.3.3, then count cells with a hemocytometer.
Wash cells once more with 3% BSA in PBS, then resuspend to 3-6 x 104/100 µl.
Attach a cytology funnel to a positively charged slide and lock into the slide carrier. Insert the entire apparatus into a cytology centrifuge and add 100 µl cell suspension to the funnel. Centrifuge at 300 x g for 5 min to disperse the cells on to the slide.
Note: All incubation steps should be performed in the dark to limit photobleaching of fluorophores.
Circle cells with a hydrophobic barrier pen to minimize solution needed for following steps, then immediately fix with 150 µl 3% paraformaldehyde in PBS 15 min at room temperature (RT).
Wash twice for 5 min with 150 µl 3% BSA in PBS.
Permeabilize cells with 0.5% Triton-X 100 in PBS 20 min at RT.
Repeat wash step as in 5.1.1.
Prepare EdU reaction cocktail according to kit instructions not more than 30 min before use.
Add 150 µl cocktail to each slide, incubate 30 min at RT.
Incubate with 150 µl nuclear counterstain Hoechst33342 diluted 1:2,000 in PBS 30 min at RT.
Wash twice for 5 min with 150 µl 1x PBS.
Add 1-2 drops anti-fade mounting medium to cells, then slowly lower coverslip to prevent bubbles.
Allow mounting medium to cure overnight in the dark at RT.
Use clear nail polish to seal the coverslip to the slide.
Image slides at 40X magnification using a fluorescent microscope equipped with excitation/emission filters capable of detecting DAPI (Hoeschst33342), and Texas Red (Alexa Fluor 594).
The flexor digitorum longus (FDL) muscle, located in the calf, acts to flex the digits of the mouse hind paw via the flexor tendon (outlined in blue in Figure 1A, and shown histologically in Figure 2A), which runs proximally from the myotendinous junction and terminates in the distal phalanges. In this model of flexor tendon healing, the FDL tendon is transected and repaired at the mid-foot, proximal to the bifurcation in to the digits of the hind paw (red arrows, Figure 1A). To prevent rupture of the repair, which would preclude experimental analysis, the tendon (and adjacent muscle) is cut, or released, at the myotendinous junction (yellow arrow in Figure 1B, release shown in Figure 1C). While this step is not representative of the clinical scenario, it is critical to protect the repair by decreasing strain on the injury site. Figure 2D is a histological example of a ruptured flexor tendon repair, compared to a successful repair shown in Figure 2C. In the latter, the granulation tissue displays greatly increased cellularity as compared to the uninjured tendon (Figure 2B), and this cell population can then be analyzed further via cytology centrifugation onto a slide followed by immunocytochemistry. Figure 3 outlines the experimental procedure used to evaluate the proliferative state of the cells collected from healing tendons 10 days post-repair via EdU incorporation into newly synthesized DNA. EdU labeling therefore shows only those cells that actively proliferated during the 24 hr period following the EdU pulse in live mice, as seen in Figure 4. A quantitative assessment of proliferation in the granulation tissue of the healing tendon can then be determined by point-counting of the entire cell preparation. In this way, a baseline of proliferation can be established at each time point, and any changes due to genetic or pharmacological interventions may be assessed.
Figure 1:. Murine Hind Paw Anatomy and Identification of the Flexor Digitorum Longus Tendon. The flexor digitorum longus (FDL) flexes the digits in the mouse hind paw and runs along the palmar aspect of the hind paw (FDL outlined in blue) where it bifurcates into the digits (red arrows) (Figure 1A). Proximally, the FDL tendon runs through the tarsal tunnel (black arrow), into the calf, ending at the myotendinous junction (yellow arrow) (Figure 1B). The release of the tendon at the myotendinous junction to prevent rupture is shown in Figure 1C. Please click here to view a larger version of this figure.
Figure 2: Representative Histological Images of Un-injured, Normal Healing and Ruptured Flexor Tendon Repairs. The anatomy of the FDL tendon in the murine hind paw is shown in Figure 2A. Scale bar represents 1 mm. In Figures 2B-D, the tendon is magnified at 8X to compare uninjured tendon tissue (Figure 2B) to an intact and ruptured repair (Figures 2C & 2D, respectively). Whole hind paw samples were fixed in neutral buffered formalin, embedded in paraffin, cut in to 3 µm sections, and stained with Alcian Blue/Hematoxylin/Orange G as previously described 13. Native tendon is outlined in blue, tendon/granulation tissue composite is outlined in green, and black arrows indicate sutures. Scale bars represent 200 µm. Please click here to view a larger version of this figure.
Figure 3: Experimental Procedure to Perform EdU Click-it Chemistry on Cell Preparations. On day 10 post-surgery healing FDL tendons were dissected from mouse hind paws. The tendons were minced then digested for two hours in collagenase I to dissociate the cells. The cell suspension was strained to remove debris, and ~6 x 104 cells were spun into a monolayer on positively charged glass slides using a cytology centrifuge. The cells were circled with a hydrophobic barrier pen and then fixed immediately with paraformaldehyde. After permeabilization with Triton X-100, the cells were treated with an EdU detection cocktail, and a click chemistry reaction bound Alexa Fluor 594 to incorporated EdU. Hoechst 33342 was used as a nuclear stain, and the cells were analyzed at 10-40X with a fluorescent microscope. Please click here to view a larger version of this figure.
Figure 4: Immunocytochemistry Analysis of Cycling EdU-labeled Cells During Flexor Tendon Healing. Healing FDL tendons were harvested from the hind paws of mice 10 days post-surgery and digested with collagenase to obtain a cell suspension. Centrifugation was used to disperse these cells into a monolayer on slides, followed by immunocytochemistry to image EdU incorporation. Figure 4A and Figure 4B are images taken at 10X and 40X respectively of the cells following immunocytochemical analysis. Nuclear stain Hoechst 33342 is blue, and cells that have incorporated EdU are dotted with red. Scale bars represent 50 µm. Please click here to view a larger version of this figure.
The surgical procedure for a murine model of complete transection and repair of the flexor digitorum longus tendon is presented in this study. In addition a novel application of concentrating small cell populations with cytology centrifuge is demonstrated, allowing for quantitative immunocytochemical analysis of the cellular environment during flexor tendon healing. This model of flexor tendon repair demonstrates a reproducible healing response, which can be used to assess changes in the healing process using knockout models or with pharmacological intervention. Following surgery, an inflammatory reaction begins within 24 hr, during which cells are recruited to the injury site and a callus of fibrous tissue begins to form. A proliferative phase follows at about day four, involving greatly increased cellularity and abundant deposition of disorganized extracellular matrix at the repair site, leading to adhesion formation between 14-21 days. Tissue remodeling continues through day 35, at which time continuity and organization of the flexor tendon is restored, and cellularity is reduced 18.
Currently, there are several murine models of flexor tendon repair in addition to the one presented here. Tsubone et al., have described an in vitro model of flexor tendon healing 19. While this model can assess changes in gene expression over time, it cannot account for the recruitment of extrinsic cells or changes in the inflammatory/cytokine milieu that occurs in vivo. In vivo, two models of partial transection have been developed using either incisional or excisional defects 20,21. More recently, Wong et al., characterized a Zone II model of flexor tendon injury in a murine model 22. This is an important development, as it allows the contribution of synovial sheath-derived cells to the healing process to be defined. However, no quantifiable changes in gliding function have been described using this model. Each model has its own benefits and limitations that must be considered, including technical ease, clinical relevance and anatomy. A main limitation of the model described here is that the healing tendon may rupture prior to evaluation, rendering it unusable for further analysis. Harvesting sufficient cells is made unfeasible under these circumstances, and any histochemical analysis is not viable, as a ruptured tendon does not follow the standard healing process described above. Releasing the FDL tendon proximally to decrease strain on the healing tendon is therefore a critical step for prevention, despite the fact that it is not clinically relevant. Conducting the surgery unilaterally also lowers the rate of rupture. Another limitation is the inability to track the contribution of peri-tendinous sheath cells, as the synovial sheath does not surround the segment of FDL tendon that is injured in this model.
An important function of this flexor tendon repair model is that it allows evaluation of the cells at the healing site. Immunofluorescence/immunohistochemistry (IHC) is a common biological technique that can be used to characterize these cells. While IHC is uniquely suited for determination of spatial information, it is largely a qualitative method. Changes in tissue or cell composition throughout the depth of the tissue can be missed, and quantification of populations is difficult. Flow cytometry represents an ideal approach to define, quantify and potentially isolate cell populations during healing. However, isolation and digestion of healing tendon tissue from this model yields very low cell numbers for flow cytometric analysis (1-2 x 105 on average from each mouse), and fixation/permeabilization steps for detection of intracellular markers reduces this number further. Using cytology centrifugation to concentrate the isolated cells, followed by immunocytochemistry, provides a way to characterize these small cell populations. A significant advantage of this technique is that there is no need to pool samples together to obtain enough cells; therefore each mouse represents an individual sample for analysis. An important consideration in generating these cell preparations is maintaining consistency in the tissue harvested for analysis. Surrounding muscle and fascia may adhere to the granulation tissue and must be carefully dissected away. Since this method involves minimal processing of the cells prior to fixation on slides, it retains a majority of isolated cells for further analysis. In this way, nearly the entire population of cells making up the adhesion tissue at the repair site can be quantitatively assessed via immunocytochemistry. In the present study, EdU incorporation by proliferating cells is used to demonstrate the application of this cytology technique, however, it can also be used for more complex and in-depth characterization of the heterogeneous cell populations involved in flexor tendon healing. Future applications of this technique may lead to more in depth characterization of the cell populations involved in tendon healing, as it allows for determining co-localization of cellular markers in the cells associated with the granulation tissue in healing tendon.
This work was partially supported by the American Society for Surgery of the Hand Pilot Award and NIH/NIAMS 1K01AR068386-01 (to AEL) and NIAMS/NIH P30AR061307.
Lin, T. Biomechanics of tendon inury and repair. J Biomech. 37, 865-877 (2004).
Strickland, J. W. Development of flexor tendon surgery: twenty-five years of progress. J Hand Surg [Am]. 25, 214-235 (2000).
Bunnell, S. Repair of tendons in the fingers and description of two new instruments. Surg Gynecol Obstet. 26, 103-110 (1918).
Aydin, A., et al. Single-stage flexor tendoplasty in the treatment of flexor tendon injuries. Acta Orthop Traumatol Turc. 38, 54-59 (2004).
Gelberman, R. H., Steinberg, D., Amiel, D., Akeson, W. Fibroblast chemotaxis after tendon repair. J Hand Surg Am. 16, 686-693 (1991).
Lundborg, G., Rank, F. Experimental intrinsic healing of flexor tendons based upon synovial fluid nutrition. J Hand Surg Am. 3, 21-31 (1978).
Aoki, M., Kubota, H., Pruitt, D. L., Manske, P. R. Biomechanical and histologic characteristics of canine flexor tendon repair using early postoperative mobilization. J Hand Surg Am. 22, 107-114 (1997).
Kim, H. M., et al. Technical and biological modifications for enhanced flexor tendon repair. J Hand Surg Am. 35, 1031-1037 (2010).
Aoki, M., Manske, P. R., Pruitt, D. L., Kubota, H., Larson, B. J. Work of flexion after flexor tendon repair according to the placement of sutures. Clin Orthop Relat Res. 205-210 (1995).
Zhao, C., et al. Award for Outstanding Orthopaedic Research: Engineering flexor tendon repair with lubricant, cells, and cytokines in a canine model. Clin Orthop Relat Res. 472, 2569-2578 (2014).
Wong, J., Bennett, W., Ferguson, M. W., McGrouther, D. A. Microscopic and histological examination of the mouse hindpaw digit and flexor tendon arrangement with 3D reconstruction. J Anat. 209, 533-545 (2006).
Katzel, E. B., et al. Impact of Smad3 loss of function on scarring and adhesion formation during tendon healing. J. Orthop. Res. 29, 684-693 (2011).
Loiselle, A. E., et al. Bone marrow-derived matrix metalloproteinase-9 is associated with fibrous adhesion formation after murine flexor tendon injury. PloS one. 7, e40602 (2012).
Lee, D. J., et al. Parathyroid hormone 1-34 enhances extracellular matrix deposition and organization during flexor tendon repair. J Orthop Res. 33, 17-24 (2015).
Geary, M. B., et al. Systemic EP4 Inhibition Increases Adhesion Formation in a Murine Model of Flexor Tendon Repair. PloS one. 10, e0136351 (2015).
Loiselle, A. E., et al. Development of antisense oligonucleotide (ASO) technology against Tgf-beta signaling to prevent scarring during flexor tendon repair. J Orthop Res. 33, 859-866 (2015).
Orner, C. A., Geary, M. B., Hammert, W. C., O'Keefe, R. J., Loiselle, A. E. Low-dose and short-duration Matrix Metalloproteinase 9 Inhibition does not affect adhesion formation during murine flexor tendon healing. Plast Reconstr Surg. (2016).
Loiselle, A. E., et al. Remodeling of murine intrasynovial tendon adhesions following injury: MMP and neotendon gene expression. J Orthop Res. 27, 833-840 (2009).
Tsubone, T., et al. Effect of TGF-beta inducible early gene deficiency on flexor tendon healing. J Orthop Res. 24, 569-575 (2006).
Beason, D. P., Kuntz, A. F., Hsu, J. E., Miller, K. S., Soslowsky, L. J. Development and evaluation of multiple tendon injury models in the mouse. J Biomech. 45, 1550-1553 (2012).
David, M. A., et al. Tendon repair is compromised in a high fat diet-induced mouse model of obesity and type 2 diabetes. PloS one. 9, e91234 (2014).
Wong, J. K., et al. The cellular biology of flexor tendon adhesion formation: an old problem in a new paradigm. Am J Pathol. 175, 1938-1951 (2009).


text:
Social Security scammer targets woman with phony call
By Nick Natario
Don't fall for this Social Security scam
HOUSTON, Texas (KTRK) -- A Houston woman thought someone bought a house and a car, and took money from the bank in her name, but Social Security officials warned it's all part of a scam.
Christine Waldon said she thought her world was crumbling down.
"I was shocked, because there's no way I could touch $60,000 right now," Waldon said.
Last week, Waldon received a phone call from someone claiming to be from the Social Security Administration. The caller said her identity was stolen, and someone bought a house, a car and took out money from banks in her name.
"I thought it was really real, because I spoke to these people more than twice," Waldon said. "I was thinking they were helping me and they're going to get to the bottom of it."
When we called the person, the number didn't work. That's when ABC13 called the Social Security Administration. A spokesperson for the Social Security Administration said this scam is impacting people across the country. It's so bad, the agency just released public service announcements.
"To come find out, they're not helping me," Waldon said. "They are actually helping to scam me. It's hard they would do that to me."
The agency said a real employee won't tell you your number has been suspended. They also won't demand payment, or ask for your credit card number over the phone. The Better Business Bureau also sent out similar warnings. The BBB said it's never a bad idea to monitor your identity.
"One of the things to do is to check your credit reports at least once a year. You can do that for free at annualcreditreport.com," BBB spokesperson, Leah Napoliello said. "If you see someone is opening lines of credit in your name, taking out loans, that sort of thing, that's a red flag right there that your identity has been stolen."
To protect people's identities, the Social Security Administration created a website to report this fraud. Waldon said she plans to report it, and hopes her story helps others.
"This can happen to me, but it doesn't need to happen to somebody else," Waldon said.
The agency said you can either report the scam to its website, or call 800-269-0271.
Follow Nick Natario on Facebook and Twitter.
houstoncrimebetter business bureausocial securityscamidentity theftconsumer concerns
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text:
Dubai Pearl ist der Name einer Wolkenkratzer-Baustelle in Dubai, die zurzeit aufgelassen ist.

Der Bau der Hochhausgruppe auf dem fast 500 Meter Durchmesser zählenden Rondellgrundstück vor Palm Jumeirah begann im Jahr 2008 und sollte bis 2018 in Phasen abgeschlossen werden. Das Gebäudeensemble sollte eine Höhe von 300 Metern erreichen.

Besonders beeindrucken sollte das Bauwerk aber nicht durch seine Höhe, sondern durch seine gewaltigen Proportionen. Es soll aus vier Türmen bestehen, die oben und unten miteinander verbunden sein werden. Das äußerst kompakte Gebäude wird 73 Etagen haben und dabei eine Nutzfläche von 1,8 Millionen Quadratmetern bieten. Das entspricht der Nutzfläche von 18 mittelgroßen Wolkenkratzern mit jeweils 100.000 Quadratmetern. Das Gebäude wird aufgrund seiner Dimension weitaus mehr Nutzfläche bieten als Wolkenkratzer vergleichbarer Höhe. Die Fassade soll zur optischen Kaschierung mit blau schimmerndem Glas verkleidet werden. Dubai Pearl wird eine in sich geschlossene Enklave für einige zehntausend Menschen bilden und u. a. Wohnungen, Büros, sieben Hotels, ein Theater mit 1800 Plätzen, Entertainment, Einzelhandel und Gastronomie beherbergen.

Seiner Funktion nach wird Dubai Pearl mit dem etwas niedrigeren Rockefeller Center in New York City vergleichbar sein. Die aus Abu Dhabi kommende Al Fahim Group finanziert das Bauprojekt.

Der Bau des Hochhauskomplexes ist aus unbekannten Gründen gestoppt worden. Einige der acht Kräne auf der Baustelle wurden abmontiert.

Siehe auch
 Liste der höchsten Gebäude in Dubai
 Liste der höchsten Wohngebäude der Welt
 Liste der höchsten Gebäude im Nahen Osten

Weblinks

 It's rise and shine for Dubai Pearl, Gulfnews.com

Hochhaus in Dubai
Bauwerk der Postmoderne in den Vereinigten Arabischen Emiraten
Wohngebäude in den Vereinigten Arabischen Emiraten
Hochhaus in Asien

redpajama_set_name: RedPajamaWikipedia


* Add `UTIME_NOW` and `UTIME_OMIT`.  It is a matter of taking the BSD values, add the `#define`s to the proper header, and implement the support in `*_S_file_utimes` functions.
* Add a [[futex kernel trap|microkernel/mach/gnumach/interface#futex]] to GNU Mach.
* Add a relatime option to ext2fs.
* Run it: `qemu-kvm -m 512 -no-kvm-irqchip -drive cache=writeback,index=0,media=disk,file=debian-hurd.img` # …irq… is a currently necessary fix due to some changes in Linux. Optionally use `--curses` to keep your keyboard layout. If need be modprobe kvm_amd, kvm intel and kvm to get kvm support (which is much, much faster). See also: [kvm FAQ](http://www.linux-kvm.org/page/FAQ).