18 aSzI5J]/=
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number ,i2-
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The hsC T:1i
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at aZOn01v;!&
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The jm}CrqU
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 8dGsV5" *
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, sh<Q2X
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive i?x gV_q;
control for Ca2+ induction. The data thus obtained was analyzed with the software Win _olQ;{ U:
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on n5:uG'L\
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 ,2@o`R.27
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were NXW*{b
harvested and fractionated as detailed above, and the S-100 fractions were assessed by K d&/9<{>
immunoblotting for presence or absence of annexin I. n(:<pz
Mouse bone marrow transduction and transplantation. XkaREE
Retrovirus-mediated transduction of mouse bone marrow cells was done by published ]G/m,Zv*:
methods49. Prestimulated low-density bone marrow cells were infected with high-titer Q]ersA8 V>
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated ~tDYo)hH8
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing TEtmmp0OD
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by HW@wia
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) 70'OS:J=\
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone 19!?oeOU
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis =pH2V^<<#
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of ]Q^)9uE\D
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was \J'}CX*aQ
confirmed by immunoblot analysis. n]%-2`}(
Determination of renal morphology 2+1ybOwb
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an DT-VxF6
h
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, ejN/U{)jK'
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner JEUU~L;
for morphologic alterations, as previously detailed at uqo3
Patient population n`Q@<op
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) #M-!/E
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per a6{Zp{"Y
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) fdl.3~.C
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. ;ALWL~Xm
The Mayo Institutional Review Board and the Research Ethical Board, University Health f"6W ;b2L.
Network, University of Toronto approved the study protocol. All patients gave written 4fLRl-)
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or dNACE*g;q
19 @16GF!.
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 `TBXJ(Y
months were not included in the study. Patients with active infection, diabetes, or a )+.=z
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), Be6Yh~m
medications, malignancies) were also excluded. fi?4!h
Treatment yD+4YD
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of :i.@d?
high-quality protein) diet was recommended and patients were encouraged to maintain (< +A w7
the same diet throughout the duration of the study. All patients received a similar {npm9w<;
conservative treatment regimen that included loop diuretics to control edema, an bzr2Zj{4
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. "U\RN
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added qTJhYxm
when required to control systolic blood pressures to <135 mm Hg in >75% of the l5
9a3=q
readings. Patients who after a minimum of 4 months of conservative therapy and }c/p;<
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of ,`geOJn'
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, #Y7jNrxE
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine .a4,Lr#q.
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given 8t!jo.g
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count K43%9=sM
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count eHr0],
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per ,rMf;/[
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a ,,Qg"C
second course of rituximab treatment following the same protocol described above. oU\]#e^
Follow-up C19N
0=
In all patients, clinical and laboratory parameters including complete blood counts, P~a@{n*8
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum
#b ^6>
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry eoiz]L
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion yCQvo(V[F
in the urine were assessed by performing two consecutive 24-h urine collections at each o GuAF q
time point. Data were considered accurate when urinary creatinine excretion was mG[jR*JW
consistent with a complete 24 h collection. The mean of the two measurements was 7yE\,
considered for the analysis. The presence of HACAs was evaluated at baseline and at xJ>5 ol
months 3, 6, 9, and 12. gX"-3w
Method / Approach / Study/ Technique O#D{:H_dD>
A discussion is presented of a problem-solving system Ta\F~$M
To improve the efficiency of the method, the following approach may be applied. ;"M6}5dQ4
In order to an investigation was made to find the causes of the p{,#H/+J
Although large collections of rules and equations have been complied, none are generally w"{DL
N[Qw
accepted qSP&Fi
20 9"#C%~=+
This approach will be explained and discussed thoroughly in the body of the report. `,}7LfY
This can be accomplished by Y"lEMY
This algorithm to compute the total cost can be described step by step as follows: BL&AZv/T
The above preliminary analysis has provided important information ].Yz
=:
Various methods have been proposed for selecting an optimum... {D[6=\F
These concepts have been applied to T +vo)9w
On the basis of the concept mentioned above, *H!BThf
t4
This can be achieved by b? o
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the Z"VP
<-
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, uE.BB#
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced wp@_4Iq1$
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 ah*{NR)
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada 'i%r
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% eN<L)a:J_
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections D^4nT,&8
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin Qa,=
complex. Sections were counterstained with hematoxylin and examined by light v \i"-KH
microscopy. +%YBa'Lk
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay V22z-$cb
performed at Genentech Inc. that measures the antibody response to rituximab in human !64Tx
serum samples. F
,472H
In all patients, clinical and laboratory parameters including complete blood counts, `rVru= zoy
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum e' M&Eh
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry ?=9'?K/~a
and at months 1, 3, 6, 9, and 12. Wu
0:X*>}p
This fact suggests that a new concept :\|A.#
U
This was accomplished by taking ... vS\ 2zwb}
The preparatory stage is very time consuming process. V~/G,3:0y%
Test are performed for validity, completeness, and compatibility I4"p]>Y"
There is little hope of achieving successful ... ?5EH/yV;
There has been an increasing awareness of the potential of using most ..so far made have *:yG)J 3F
not taken this approach, with the exception of %]Z4b;W[Y
Only a few studies can be found. kY$EK]s
It is a very tedious process to go through mi] WZlg$
It is only when .. has been completed that .. may be effected eMRH*MyD
The entire interpretation process is conducted in one's head. *U^Y@""a
These approaches are sometimes very tedious. tle`O)&uo
Several techniques can be used Qel)%|dOn
A polynomial parametric model can be written as [the following]/[follows]: Oin9lg-jR
A xx model is constructed/formulated using xx. !uGfS' Vl
A xx model represents an xx by its xx. nW)+-Wxq
A process decision model captures the logic essential to 6=;:[
From the equation above, xx is equal to the summation of xx times the ... hty'L61\z
21 z&gmaYwq
The validity of a xx model can be checked using Euler's formula. KdCrI@^
Given a model, one can mathematically determine whether ... or ... Y2DL%'K^
Equations for xx need to be derived and implemented in the system. SxYz)aF~
A number of heuristic rules have been developed for 'oIE:#b
Optimum .. techniques can be made more reliable by ... so that WRD
z*Zf
An algorithm based on the characteristic ... is used to determine 2uEI@B
Euler's formula states the following: WPRk>j
The completed model should agree with the formula. j~N*T XkC
For manufacturing purposes, a detailed and precise model of the object is necessary {P6Bfh7CZ
Engineering design models are very well defined; therefore, ]00 so`
To keep the domain narrow enough to be implementable, yet wide enough to be useful. E,m|E]WP
Point of View aLg,-@
from an implementation standpoint, 1;/SXJ s
From the point of view of this application, &
^$@LH3
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). c$ /.Xp
Information is the meaningful interpretation and correlation of some aggregation of data ,?yjsJd.
in order to allow one to make decisions.
\uTlwS
From a practical point of view, the computational aspects of an FLC require a }p?,J8=-
simplification of the fuzzy control algorithm. KRxJ2
The use of a hammer to insert screws, although partly effective, tends to distort, destroy,
!U?C
_
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM _AF$E"f@
p.129] vT#R>0@mi
Statistical analysis Tp-W/YC
Data were analyzed by one-way analysis of variance comparing the three conditions h~Ir
=JV
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If F2zo
!a8
significant F-statistic from analysis of variance existed, this test was followed by Dunnett B-LV/WJ_
post hoc multiple comparison procedure with sham operation as the control group. For all #Tc`W_-
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as L<dh\5#p9Y
statistically significant. }N9PV/a
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney pImq<Z
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, d1#lC*.Sg
CA, USA). >0SG]er@
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was \
3E%6L
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's ]foS.D,
test, where appropriate. B[mZQ&Gz`a
Data are expressed as mean s.d., median and interquartile range, or frequencies, as q>%.zc[x
appropriate. Variables who deviated from the normal distribution (positively skewed) :JBtqpo2
were log-transformed (log10) before the correlation study. nEUH; z
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test lrPIXIM
post hoc analysis of variance were used as indicated below, for the comparison of &iD&C>;pf
22 M`7lYw\Or!
morphological, immunohistological and functional parameters. Statistical significance k_1;YOBF
was set at P<0.05. maSVq G
The primary efficacy parameter was defined as change in urinary protein excretion from xGOmvn^lQ
baseline (week 0) to 12 months after treatment. The 12-month changes were tested
9Pvv6WyKy
against zero using the paired t-test. Secondary end points included 6-month changes in Md9y:)P@Y
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular $2]>{g
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on OGH,
K'l
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. :V6t5I'_
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. L09r|g4Z
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 v!DU ewz
Definition of remission status is according to the criteria established by Cattran et al.30 >C{8}Lg-.
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a 6%9 kc+
9
>50% reduction in peak proteinuria and non-response as <50% reduction in peak c8zok `\P_
proteinuria. Any patient reaching a CR or PR was considered a treatment success 5%K|dYv^^
The statistical significance of differences for the mean values of cytokine concentration ]T40VGJ:h
and T cell proliferation was determined with Student's t-test. Differences with a P value `S3)uV]I
of less than 0.05 were considered significant. x!7!)]h
Statistical significance was determined by Student's t-test. Data with a P value of less <RbsQ^U
than 0.05 were considered significant. Gf!c
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P _9=cxwi<w
values less than 0.05 considered statistically significant. 0X
C3O 8q
The significance of differences among groups was determined by Student's t-test and '"hSX=
one-way analysis of variance (SigmaStat software; Jandel). Fo0s<YlS-
Comparisons 39pA:3iTd
As well, the pros and cons of these representations from a process planning point of view =|fB":vk
will be discussed. JCB3 BZg7&
The method of using xx to implement xx described by Zadeh (1973) appeared more #N"QTD|i
suitable LF{8hC[
As discussed [in the previous section]/[preciously], Hkf]=kPy*
Relation fU.z_T[@
We can not invert F' directly because it defines a many-to-one mapping. s gZlk9x!Q
The relationships appear very complicate ts,V+cEA
Lifting tasks involve complex and imprecise relationship between the task variables and fCX8s(|F
the human operator's characteristics. puh-\Q/P
These methods are based on the relationship between ... and ... <a+@4d;
The fundamental concept of a fuzzy rating language is that we can establish a relationship (7$BF~s:,
among terms such as high, medium, and low, and then modify these relationships. ^8dCFw.rU
This article will thus mention the latter as well as the former. 0q]0+o*%
The former two bear a close relation to a fuzzy Cartesian product. \0e`sOS`L
Importance D'% O<.m
) e;|$nw-
23 oDt{;S8|]
The emphasis is on an implementation of a general approach to rule based decision 8WKY 4nkj
making. wL>;_KdU`
Consideration / Attention j^hLn>
Careful evaluation is necessary to ensure 8NJT:6Q7l
Such a formulation does not change further considerations. =NNxe"Kd;U
Considerable attention has been paid to U: )Gc
Attention should be paid to an important finding of this investigation. zW)Wt.svP
Caution should be exercised in this process to avoid ... /f AAQ7
Primary consideration is given to ... components, though others can be accommodated >Ml5QO$*.q
After ... has been defined by ..., a carefully analysis is carried out/performed to determine {9^p3Q+:P
A number of factors such as ...need to be taken into consideration before making the 2n-kJl`: O
appropriate decision.
H4sc7-
It should be noted that q1ZZ T"'
It is important to point out that ... $~
%h4
These considerations have heightened interest in the possibility of providing ... 1083p9Uh
We should stress the fundamental importance of the xx Hk(=_[S
Results. g=,}j]tl
Advantages / Disadvantage :-$8u;!M
One of the major advantages of this new measure of xx is that it can be applied to the GJs~aRiz
experimental study of JO90TP
$
One advantage of using a .. is the ease of preparing it. @7V~CNB
+
It has a very fast decision making process KD H<T4#x
All the algorithms involve mostly logical operations. =q`T|9v
It can be easily and without additional cost implemented in a microprocessor;based )}t't"
environment.
X>P|-n#
It can reduce the waste of designing from scratch. gx?r8
The advantages of using a xx to represent xx are the following: n
\f]?B(
However, xx is not without its shortcomings. DH.UJ+
In most cases, the xxx shows an improvement over the existing xxx. jIVD i~Ld
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. '
2O
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The "best case" results shows a savings of 6% to 9%. aq
l8Or1[
Most of the existing works based on xx approach can only recognize a xx . dM P'Vnfj
Most of the above methods are computational expansive and limited to xx. %~gI+0HK
Some other advantages of xx are the following: m8e()8lZ3
The problem is the limitation of this method to a limited domain of parts. Im@OAR4,R
It proved limited in application because it demanded precision in system modeling that ,sL%Ykr
was impossible in practice. KB(W'M_D\
There are advantages to be gained in the structuring of costs and benefits, the use of xx, ~(kqq#=s
The disadvantages of this method are also disadvantages of conventional xx approaches. 7v)p\#-
This combines the best features of both techniques v+W'0ymbnV
24 }2Euz.0
Hopefully, this tool can be as the reference framework of for developing a xx platform, ;l
ZKgi8`
and helping the administration, marketing, and knowledge management activities in 1gbFl/i6T
virtual communities. T,1qR:58
Results %Uz\P|6PO
An improvement on the result shown above can be made by based on the data provided zqXF`MAB=
Recent work has identified j-W$)c3X
Time-dependent changes of G[yzi
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase C49\'1\6
and does not require ERK activation. ;p`to"6IFD
Much of the current work on PQ[?zNrSV
Discussion of these theories is beyond the scope of this review H>%AK''
Based on the information contained in this (EY@{'.&
The result can be categorized into nine classes Uq#2~0n>
The results are illustrated by an example `+n#CWZ"Y
The experimental results for each xx time are reported in Table 2. xz!0BG
From the results obtained so far, it seem that e72Fz#<q
Because of the inaccuracy of the ..., a conclusion cannot be drawn as $`3yImv+w
Although much effort has been made to., this reality is far from completion. 6GunEYK!N8
The results indicate that the total benefits are higher than the total costs. 5tbCx!tL
Their results may then serve as guidelines for lower level models, less fuzzy and more K-TsSW$}
detailed. ojnO69v
Conclusion
YFm%W@
From the discussion, one may conclude that ... GuR^L@+ -.
The first indication that I
p{R'HG/
In summary, we have shown that kiM:( =5
These results suggested that aH1CX<3)~
Our findings have shown that )\u%XFPhS
Our observations have provided MygAmV&
This study reveals following five main findings: Y
bJg{Sb
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in 5eff3qrH{
the diabetic kidney. qBBCnT
As mentioned above, m*_X PY
Moreover, we demonstrate that, #b[bgxm
A number of studies have elaborated a body of knowledge about JGHj(0j
There are findings to indicate that Mn
,hmIz
On a descriptive level, there is agreement that for J "I,]
One issue that became particularly evident from our study is `r1}:`.m,
Our data are in agreement with the findings and models presented by previous (%L/|F_
publications, in particular those of Jones et al Vhv'
Z\
According to our observations, EX_j|/&tZ
…was not evident from our data DK?aFSf\
25 9k;,WU(K<
It could therefore be concluded that %.=}v7&<z
our data illustrate that t~ {O)tt
All these different aspects, as listed above, lead to $}su'EIo
In fact, it has already been speculated that &'fER-
It should be furthermore mentioned in this context that 0V3dc+t)O
To identify and verify the essential factors triggering developmental renin expression, it tNFw1&
is of interest now to study the development of intrarenal renin expression in mice with q{&c?l*2
defined gene mutations, using the results of this study as a reference system. .*`^dt
In conclusion, using several approaches, we demonstrated that bss2<mqlH
But we have not provided formal proof yet that X?t;uZI^
In summary, our results suggest that f\oW<2k]~
In conclusion, we identify 6,YoP|@0
A better understanding of such regulatory systems may yield novel therapeutic 2p, U ^h
approaches to glomerular diseases. SWzqCF
Preliminary results of short-term studies (2 weeks) indicate that @Pcgm"H<
However, we believe that .;
7V]B1o
However, despite our extensive measurements of these parameters, we found no m?Y-1!E0
relationship between response and initial proteinuria, time to B-cell recovery, the =,zB|sjn
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree AI3x,rk#
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be $[A^8[//
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved ZX&e,X~V
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and 2z
!05]B%
that will also look for factors that may determine its efficacy in IMN. QP\:wi
It has become increasingly clear that ?rOj?
J9
Form the above discussion, the conclusion can be reached that (!fx5&F
The conclusions drawn are also valid 'sZGLgT;m
In conclusion to this, it becomes obvious that the problem of xx lies not only in... H,TApF89A
We have attempted to introduce some concepts associated with a theory of 1f+A_k/@
Considerable more work, hopefully, will be done in this area kkZ}&OXS;
Employing the compositional rule of inference, the assessment of the xx compatibility in ~9o@1TO:v
achieving prescribed xx projectiles in any level of the hierarchy is made possible. gnZ
#86sO
This paper has presented a theoretical and experimental study of the xx process and xx =LLpJ+
concept. Vq0X:<9
The experimental research results will hopefully serve as useful feedback information for 1p~ORQ
improvements for xx work. v\bWQs1
The scope of this contribution was to introduce a xx method. O-7)"
This has a tremendous impact on our understanding of i
Ehc<
Significant progress has been made in advancing RNAi therapeutics in a remarkably 1d+Kn Jy
short period of time &iu]M=Yb
To date, little is known about… L44|/~
Irrespective of the mechanisms and the molecules –which are still largely unknown – \3ydNgl
involved in MSC functions, current data suggest that i?d545. u
To better understand xKBi".wA
26 bx2<WdLyT
Future Research (常用于conclustion 的结尾) 6?5dGYAX<
Thus, first extension of the approach could be, lFf>z}eLy
Further studies are needed to determine the importance of {9;-5@b
Some improvements to the scheduling aspect of the model may be brought through whe%o
additional levels in the hierarchy for more detailed representation of the scheduling A-m IWTa
activity. %w>3Fwj`z
It also unveiled new aspects of the role played by thyroid hormone in response to injury o1\N)
%
and tissue repair. xX<T5Ls
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and Muq~p~m}
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of :''Swi<H
drug molecules. +68age;dM
In the next few years it should become clear whether %OHWGac"i
It should be an exciting time for researchers seeking to harness this powerful endogenous x ]}'H
pathway to treat human disease. IC"ktv bHz
Acknowledgement qp*~|
The authors are grateful to the insightful work provided by Mr. John W. Harney and all h
8M_Uk
of the fellows and students that contributed with some of the studies discussed in this Ivcy=W=Jk
article R$IsP,Uw
I would like to express my gratitude to all those who gave me the possibility to complete 0H%zkJ>Q
this thesis. [V8^}s}tF
I want to thank the Department of Transport of the former Interim Government of Nk%$;Si
Namibia for giving me permission to commence this thesis in the first instance, to do the (7,Q4T
necessary research work and to use departmental data
Jk`l{N
This work was supported by NIH grants AI058695 and AI056900. We thank members of v`'Iew }
the laboratory and our collaborators for many useful suggestions. Je"XIhBr
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. FncP,F$8
Duckman for graphics assistance and A. Capobianco for word processing assistance. W:WRG8(F
Author contributions s/>0gu]A8
All authors were involved in experimental planning and data analysis and contributed to >}0H5Q8@
manuscript preparation. /18fpH|
Tables and Figures Z3Ww@&bU