18 "EftN5?/
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number :Eh'(
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The ]@xL=%
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at _
py2kjA6
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The J+<p+(^*v
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 q"aPJ0ni'
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, nx4P^PC
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive {^RG%
&S
control for Ca2+ induction. The data thus obtained was analyzed with the software Win @eQld\h'
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on 5A_4\YpDR
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 ?=|kC*$/G
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were /B HepD
}
harvested and fractionated as detailed above, and the S-100 fractions were assessed by f?0s &Xo
immunoblotting for presence or absence of annexin I. lg/sMF>z\f
Mouse bone marrow transduction and transplantation. A1JzW)B
Retrovirus-mediated transduction of mouse bone marrow cells was done by published sj
9D
methods49. Prestimulated low-density bone marrow cells were infected with high-titer x%XT2+
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated |"}4*V_ *
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing I5pp "*u
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by <lld*IH
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) <NQyP{p
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone E#h~V5Tf
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis 3&J&^O
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of Fd!iQ
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was H%.zXQ4}n
confirmed by immunoblot analysis. ^HFo3V
}h
Determination of renal morphology DPPS?~Pq
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an B82,.?
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, Oc-u=K,B
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner L[]^{ O
for morphologic alterations, as previously detailed 2NR7V*A
Patient population ta! V=U
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) U(3(ZqP
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per FU]4oKx
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) }vsO^4Sjc
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. s-5wbi.C
The Mayo Institutional Review Board and the Research Ethical Board, University Health :1BM=_WwI
Network, University of Toronto approved the study protocol. All patients gave written z+6QZQk
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or 5byeWH0n3
19 foyB{6q8
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 8|vld3;
months were not included in the study. Patients with active infection, diabetes, or a g =x"cs/[
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), V(I7*_ZFl
medications, malignancies) were also excluded. /yt7#!tm+
Treatment
,]U[W
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of n>T:2PQ3
high-quality protein) diet was recommended and patients were encouraged to maintain r+TK5|ke
the same diet throughout the duration of the study. All patients received a similar ;&7,73!
conservative treatment regimen that included loop diuretics to control edema, an Q(blW
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. () <`t}FQ
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added <hMtE/05B
when required to control systolic blood pressures to <135 mm Hg in >75% of the NJ>,'s
readings. Patients who after a minimum of 4 months of conservative therapy and :r^klJ(m
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of @jKDj]\
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, )8bFGX7|
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine 'FqEB]gu
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given fK);!Hh
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count 4y1
>
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count -3\7vpcdN
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per TIETj~+
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a >KKeV(Ur
second course of rituximab treatment following the same protocol described above. {Evcc+Eq
Follow-up
[Ek42%
In all patients, clinical and laboratory parameters including complete blood counts, :TlAL#
s&
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum Jxn3$
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry Nr%(2[$ =
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion ]L$4Py
in the urine were assessed by performing two consecutive 24-h urine collections at each JxnuGkE0[#
time point. Data were considered accurate when urinary creatinine excretion was T
G_bje
consistent with a complete 24 h collection. The mean of the two measurements was xM%`KP.8X
considered for the analysis. The presence of HACAs was evaluated at baseline and at /%5_~Jkr,
months 3, 6, 9, and 12. E*OG-r
Method / Approach / Study/ Technique YWSz84d
A discussion is presented of a problem-solving system &;Ed*OJ
To improve the efficiency of the method, the following approach may be applied. TR~|c|B
In order to an investigation was made to find the causes of the m$,cH>E
Although large collections of rules and equations have been complied, none are generally RZW$!tyI=
accepted r)OO&. P@j
20 [gpOuTW
This approach will be explained and discussed thoroughly in the body of the report. n>br,bQe
This can be accomplished by I
88Zrhw
This algorithm to compute the total cost can be described step by step as follows: T<f2\q8Uo=
The above preliminary analysis has provided important information xrfPZBLy
Various methods have been proposed for selecting an optimum... r|*:9|y{"/
These concepts have been applied to m5)EQE}gPp
On the basis of the concept mentioned above,
ZH_FA
This can be achieved by {,i=>%X*
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the C/CN
'
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, qx Wgt(Os
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced 3\7'm]
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 qe[
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada aF,jJ}On
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% jo<>Hc{g>
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections anK[P'Y
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin 'CS^2Z
complex. Sections were counterstained with hematoxylin and examined by light N )'8o}E
microscopy. ^OsA+Ea\
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay `@4 2jG}*
performed at Genentech Inc. that measures the antibody response to rituximab in human 4,j4E@?pG9
serum samples. Q.rB\8ea
In all patients, clinical and laboratory parameters including complete blood counts, FTbT9
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum |)28=Z|Z
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry \k|_&hG
and at months 1, 3, 6, 9, and 12. v;K{|zUdB
This fact suggests that a new concept 8o!
This was accomplished by taking ... ''$`
;?t>
The preparatory stage is very time consuming process. 'Y hA
Test are performed for validity, completeness, and compatibility U#8\#jo
There is little hope of achieving successful ... "B3iX@C
There has been an increasing awareness of the potential of using most ..so far made have K{,
W_^
not taken this approach, with the exception of JOA%Y;`<#
Only a few studies can be found. \%w7D6dEZ
It is a very tedious process to go through #rh0r`
It is only when .. has been completed that .. may be effected vs5
D:cZ}
The entire interpretation process is conducted in one's head. 6$W -?
These approaches are sometimes very tedious. tfi2y]{A
Several techniques can be used mJwv&E
A polynomial parametric model can be written as [the following]/[follows]: e7Yb=/F
A xx model is constructed/formulated using xx. ?whRlh
A xx model represents an xx by its xx. 2z.k)Qx!Z
A process decision model captures the logic essential to 0lLr[
From the equation above, xx is equal to the summation of xx times the ... 0z#l0-NdQ
21 2N6Pa(6
The validity of a xx model can be checked using Euler's formula. /V#MLPA
Given a model, one can mathematically determine whether ... or ... )OARO
Equations for xx need to be derived and implemented in the system. Jm{As*W>
A number of heuristic rules have been developed for N&R
'$w
Optimum .. techniques can be made more reliable by ... so that )a4E&D
An algorithm based on the characteristic ... is used to determine Z&~k]R0y
Euler's formula states the following: }M"-5K}
The completed model should agree with the formula. rXHHD#\oF
For manufacturing purposes, a detailed and precise model of the object is necessary S&4w`hdD>~
Engineering design models are very well defined; therefore, kw*Cr/'*
To keep the domain narrow enough to be implementable, yet wide enough to be useful. R7\{w(`K
Point of View kMwIuy
from an implementation standpoint, ~Mg8C9B?%3
From the point of view of this application, 'W<a54T?z
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). 44/0}v]
Information is the meaningful interpretation and correlation of some aggregation of data aT`02X
in order to allow one to make decisions. t<KEx^gb
From a practical point of view, the computational aspects of an FLC require a ^c;
skV&S
simplification of the fuzzy control algorithm. %k1q4qOG]^
The use of a hammer to insert screws, although partly effective, tends to distort, destroy,
|-c
ALQ
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM hc@;}a\Y
p.129] 6`$,-(J=
Statistical analysis OTy4"%
Data were analyzed by one-way analysis of variance comparing the three conditions *;\
K5
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If kBDe*K.V
significant F-statistic from analysis of variance existed, this test was followed by Dunnett ]0/~6f
post hoc multiple comparison procedure with sham operation as the control group. For all FZ}C;yUPD
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as ZT3jxwe
statistically significant. ' /@!"IXz
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney %]P@G^Bv
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, Jn^Wzn[q
CA, USA). `6l24_eKf
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was TF([yZO'
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's :,J86#S)
test, where appropriate. w~FO:/
Data are expressed as mean s.d., median and interquartile range, or frequencies, as .Q6{$Y%l
appropriate. Variables who deviated from the normal distribution (positively skewed) ZPG8q
were log-transformed (log10) before the correlation study. L>R!A3G1
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test JY,l#?lM{
post hoc analysis of variance were used as indicated below, for the comparison of @_tA"E
22 dT0z^SG
morphological, immunohistological and functional parameters. Statistical significance A_4\$NZ^
was set at P<0.05. oVj A$|
The primary efficacy parameter was defined as change in urinary protein excretion from Lu$:,^ C
baseline (week 0) to 12 months after treatment. The 12-month changes were tested n6-!@RYr
against zero using the paired t-test. Secondary end points included 6-month changes in oqm{<g?2
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular b ffml
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on Gm?"7R.
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. :-jP8X
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. E(K$|k_>
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 I{P$B-
Definition of remission status is according to the criteria established by Cattran et al.30
$AJy^`E^
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a looPO:bo^
>50% reduction in peak proteinuria and non-response as <50% reduction in peak 0O9
Lg}
proteinuria. Any patient reaching a CR or PR was considered a treatment success L[9+xK^g
The statistical significance of differences for the mean values of cytokine concentration 0i1?S6]d-
and T cell proliferation was determined with Student's t-test. Differences with a P value sC*E;7gT,
of less than 0.05 were considered significant. .dq.F#2B;
Statistical significance was determined by Student's t-test. Data with a P value of less MyR\_)P?
than 0.05 were considered significant. 7}HA_@[
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P tYxlM!
values less than 0.05 considered statistically significant. Y&:\s8C
The significance of differences among groups was determined by Student's t-test and Iw-6Z+ 94
one-way analysis of variance (SigmaStat software; Jandel). hD~/6bx
Comparisons ViC
76aJ
As well, the pros and cons of these representations from a process planning point of view UgBY
){<
will be discussed. 5Szo5
The method of using xx to implement xx described by Zadeh (1973) appeared more l~>rpG
suitable *h8XbBZH
As discussed [in the previous section]/[preciously], Y- 9j2.{
Relation Z|7I }i
We can not invert F' directly because it defines a many-to-one mapping. !{- 3:N7
The relationships appear very complicate .6]cu{K(
Lifting tasks involve complex and imprecise relationship between the task variables and ntUVhIE0
the human operator's characteristics. J-,X0v"
These methods are based on the relationship between ... and ... )FiU1E
The fundamental concept of a fuzzy rating language is that we can establish a relationship %JU23c*
among terms such as high, medium, and low, and then modify these relationships. 60
gn`s,,
This article will thus mention the latter as well as the former. 5 BG&r*U
The former two bear a close relation to a fuzzy Cartesian product. W;*vcbP
Importance ?9M+fi
) yD'h5)yu
23 E&=?\KM
The emphasis is on an implementation of a general approach to rule based decision G&B}jj
making. x{w ?X.Nt
Consideration / Attention $BN+SD!
Careful evaluation is necessary to ensure ;(Va_
Such a formulation does not change further considerations. W..>Ny;'3
Considerable attention has been paid to 2{qG
Attention should be paid to an important finding of this investigation. DxG'/5jQ[
Caution should be exercised in this process to avoid ... ijSYQ
Primary consideration is given to ... components, though others can be accommodated <GlV!y
After ... has been defined by ..., a carefully analysis is carried out/performed to determine ,l"2MXD
A number of factors such as ...need to be taken into consideration before making the ~H.
"{
appropriate decision. %zVv3p:
It should be noted that *m/u 3.\
It is important to point out that ... uZI:Kt#
These considerations have heightened interest in the possibility of providing ... a,\u|T:g
We should stress the fundamental importance of the xx 3
+9|7=d
Results. KPrxw }P
Advantages / Disadvantage $fG/gYvI\
One of the major advantages of this new measure of xx is that it can be applied to the ZPog)d@!
experimental study of
W u{nC
One advantage of using a .. is the ease of preparing it. AE~}^(G`
It has a very fast decision making process G7xjW6^T
All the algorithms involve mostly logical operations. "6h.6_bTw
It can be easily and without additional cost implemented in a microprocessor;based dRC+|^rSC
environment. $*> _0{<
It can reduce the waste of designing from scratch. x
$4'a~E
The advantages of using a xx to represent xx are the following: 3mpjSL
However, xx is not without its shortcomings. CK
x}.<_
In most cases, the xxx shows an improvement over the existing xxx. zh#uwT1u
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. *GnO&&m'B
The "best case" results shows a savings of 6% to 9%. KLB?GN?Pb
Most of the existing works based on xx approach can only recognize a xx . ]P5u:~U
Most of the above methods are computational expansive and limited to xx. YkbLf#2AE|
Some other advantages of xx are the following: o^J&c_U\3'
The problem is the limitation of this method to a limited domain of parts. "=O)2}
It proved limited in application because it demanded precision in system modeling that YzVLa,[
was impossible in practice. w=5qth7
There are advantages to be gained in the structuring of costs and benefits, the use of xx, =@ RVLml
The disadvantages of this method are also disadvantages of conventional xx approaches. s4*,ocyBP
This combines the best features of both techniques <taW6=
;c
24 ggWfk
Hopefully, this tool can be as the reference framework of for developing a xx platform, 4G2V{(@QiZ
and helping the administration, marketing, and knowledge management activities in A5\S0l$Q
virtual communities. %kT:"j(xW
Results :}-[%LSV
An improvement on the result shown above can be made by based on the data provided S{06bLXU"
Recent work has identified 4B
6Aw?
Time-dependent changes of 8X5XwFf}
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase ^TGHWCK!t
and does not require ERK activation. D\JYa@*?.h
Much of the current work on Xh
iC'.B_
Discussion of these theories is beyond the scope of this review *G4;
Based on the information contained in this ,v+SD\7|
The result can be categorized into nine classes {cFei3'q
The results are illustrated by an example -1:asM7
The experimental results for each xx time are reported in Table 2. Z:{
Z&HQC
From the results obtained so far, it seem that 195(Kr<5$
Because of the inaccuracy of the ..., a conclusion cannot be drawn as jEadVM9
Although much effort has been made to., this reality is far from completion. eAj}/2y"
The results indicate that the total benefits are higher than the total costs. uQlV zN.?
Their results may then serve as guidelines for lower level models, less fuzzy and more <|@9]>z
detailed. ,&$Y2+
Conclusion p#w,+)1!d
From the discussion, one may conclude that ... $A,=z
The first indication that Wil+"[Ge
In summary, we have shown that #"|Ey6
&
These results suggested that ~H.;pJ{ 8
Our findings have shown that 8I'?9rt2M
Our observations have provided 7%
tn+
This study reveals following five main findings: Nb6HM~
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in z{ 8!3>:E
the diabetic kidney. &1&*(oi]X
As mentioned above, b#F3,T__`Y
Moreover, we demonstrate that, ?s//a_nL*
A number of studies have elaborated a body of knowledge about Ez)Go6Q
There are findings to indicate that t9kgACo/M
On a descriptive level, there is agreement that for #S"=)BZ8L
One issue that became particularly evident from our study is V\_
&2',t
Our data are in agreement with the findings and models presented by previous l!b#v`
publications, in particular those of Jones et al nm)F tX|A
According to our observations, ("{'],>
…was not evident from our data SF6n06UZu
25 ms?h/*E<H
It could therefore be concluded that V\
|b#?KL
our data illustrate that 7-^d4P+|g
All these different aspects, as listed above, lead to w$p v
In fact, it has already been speculated that j/sZ:Q
It should be furthermore mentioned in this context that _jtBU
To identify and verify the essential factors triggering developmental renin expression, it z:w
7e0
is of interest now to study the development of intrarenal renin expression in mice with NTV0DkX
defined gene mutations, using the results of this study as a reference system. \t}!Dr+yN
In conclusion, using several approaches, we demonstrated that `18G
5R
But we have not provided formal proof yet that n@*NQ`(_
In summary, our results suggest that 5n_<)Ycj
In conclusion, we identify L"IdD5`7T
A better understanding of such regulatory systems may yield novel therapeutic [u<1DR
approaches to glomerular diseases. r!;NH3 *
Preliminary results of short-term studies (2 weeks) indicate that O:1YG$uKa
However, we believe that k'm!|
However, despite our extensive measurements of these parameters, we found no
wqw$6"~
relationship between response and initial proteinuria, time to B-cell recovery, the (mv8_~F0
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree lO:[^l?F
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be +~7@K{6q-
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved *dGW=aM#C
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and !fZxK
CsQ
that will also look for factors that may determine its efficacy in IMN. :=-h'<D
It has become increasingly clear that 0%v
p'v
Form the above discussion, the conclusion can be reached that w*
v%S
The conclusions drawn are also valid (}'0K?
In conclusion to this, it becomes obvious that the problem of xx lies not only in... B&"fPi
We have attempted to introduce some concepts associated with a theory of ucyxvhH^-
Considerable more work, hopefully, will be done in this area x6m21DW w
Employing the compositional rule of inference, the assessment of the xx compatibility in 0nBAO
achieving prescribed xx projectiles in any level of the hierarchy is made possible. euQd
This paper has presented a theoretical and experimental study of the xx process and xx )wmXicURC
concept. E:#VS~
The experimental research results will hopefully serve as useful feedback information for wF
}/7b54
improvements for xx work. w_6h
$"^x
The scope of this contribution was to introduce a xx method. ?k#-)inf)
This has a tremendous impact on our understanding of DT;Hr4Z8^"
Significant progress has been made in advancing RNAi therapeutics in a remarkably ._#|h5
short period of time UDhW Y.`'~
To date, little is known about… ?NJ\l5'
Irrespective of the mechanisms and the molecules –which are still largely unknown – ;4%^4<+3
involved in MSC functions, current data suggest that 7h,SX]4Q
To better understand gFJd8#6t
26 VcA87*pel
Future Research (常用于conclustion 的结尾) >$k_tC'"
Thus, first extension of the approach could be, 7\<#z|
Further studies are needed to determine the importance of 0Kq\ oMn
Some improvements to the scheduling aspect of the model may be brought through 5_#wOz0u$
additional levels in the hierarchy for more detailed representation of the scheduling ]=7}Y%6
activity. )FYz*:f>&
It also unveiled new aspects of the role played by thyroid hormone in response to injury X^7bOFWE
and tissue repair. [*Wq6n
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and vQ$ FMKz7
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of z1*8 5?
drug molecules. 7&qunK'
In the next few years it should become clear whether ]W]o6uo7
It should be an exciting time for researchers seeking to harness this powerful endogenous twq!@C
pathway to treat human disease. ,)[u<&
Acknowledgement k7'_
The authors are grateful to the insightful work provided by Mr. John W. Harney and all De6WC*trq
of the fellows and students that contributed with some of the studies discussed in this KQ9~\No]
article 1.6yi];6
I would like to express my gratitude to all those who gave me the possibility to complete [2"a~o\
this thesis. p HXslmrD
I want to thank the Department of Transport of the former Interim Government of cQ} ,q+GR~
Namibia for giving me permission to commence this thesis in the first instance, to do the `qbf_;\
necessary research work and to use departmental data s3Pr$h
This work was supported by NIH grants AI058695 and AI056900. We thank members of Gb4k5j
l
the laboratory and our collaborators for many useful suggestions. )v
!GiZ"7
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. E_[|ZrIO&*
Duckman for graphics assistance and A. Capobianco for word processing assistance. dDK4I3a
Author contributions |4^us|XY
All authors were involved in experimental planning and data analysis and contributed to 0K<y
}
manuscript preparation. c07'mgsU
Tables and Figures Uus%1hC%a
Figure 7-1 sketches these relationships. Up*1j:_O
The graphical representation of these functions is shown in Figure 1. I|8'#QX
The xx may be depicted as in Figure 1. '#LbIv4
Figure x shows the schematic diagram of the n;+CV~
Figure 1 though 2 provide a ... that E%8Op{zv_
the architecture of this expert system for .... is illustrated in Figure 2. $a.fQ<,\X
Figure 2 gives the outline of an ... system HI&N&a9C
Table shows the .$&mWytw=
27 s&&8~
)H
Time-dependent changes of v<CZ.-r\j
as shown in Table 1 and 2 3>asl54
This concept is illustrated in Figure 2 v%a)nv
At the top of Table xx are shown two blocks of data. *9Ta0e*
Each table or matrix has constructs xx through xx as row;headings, @pq2Z^SQ H
xx through xx as column;headings. mWEaUi)Zz
Time course of calculated renin immunoreactive tissue volumes during development of sT8(f=^)8F
the mouse kidney. Data are single values per time point. They were derived from the }9=X*'BO
kidneys shown in Figure 1. <5@VFRjc
Yellow color indicates W;L<zFFbU)
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then I
"Qf};n
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were ^V6cx2M
analyzed by western blot using phospho-specific antibodies. \EI<1B
ERK and PKB activation were measured by western blot using phospho-specific E3hql3=
antibodies 0SS,fs<w3
The data are the means of three different experiments taking the number of untreated cells :)JIKP%$\)
(vehicle alone) as 100%. J:D{5sE<|
ERK and PKB activation were then analyzed by western blot with the corresponding r{Lr
Q
phospho-specific antibodies. To ensure equal amount of protein in each lane, western z3Id8G&>
blots against total protein were performed for ERK and PKB. y-#{v.|L
The means of optical density (OD) values of the bands detected in western blots of three WzinEo{f
different experiments are plotted, taking the maximal value of phosphorylation of ERK !V.2~V[^M
and PKB as 100%. 9!XXuMWU<
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with r ,cz
yE/
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then ;D8175px;
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence 7=3'PfS
microscopy (lower panel). 3[{RH*nHD
The data are the means of three experiments performed on different days taking the 2.p?gRO
number of cells at the onset of the experiment as 100%. Z-U-n/6I
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction qX9x#92
(n=9 each). ^WF/gup\hS
*P<0.05 versus non-nephritic rats. 1
`& Yg(
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, wjzR 8g0bQ
positive control, M, molecular weight markers). n=F|bW
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. rbt/b0ET
Data are means s.d. of four independent experiments. (J6>]MZ#)
*P<0.05 versus 0.5 h. y1qJ
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 / biB*Z
mRNA as determined by real-time RT-PCR and normalized to Dve+ #H6N
glyceraldehyde-3-phosphate dehydrogenase mRNA. xfzGixA
Cell number was counted in duplicate using a Malassez hemocytometer [,a2A
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with O~*`YsL9
MCDB media for 24 h, #P<0.05. hU|TP3*
28 Pd8zdzf{
The curves are adjusted for history of coronary artery disease, CRP, and progression to dbsD\\,2%N
ESRD. Y=5}u&\
Both models are independent of age, gender, baseline GFR and proteinuria, and other |& Pa`=sp
clinical characteristics and traditional and nontraditional cardiovascular risk factors 4\Q
pS
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH 0ZAT;ea B
(n=99, P<0.0001, r2=0.190) c'}dsq\
Concentration of serum FGF23 concentration before starting and at the end of the 4-h rtn.^HF
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001,
NsN =0ff
Student's paired t-test). Yw6^(g8
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; elDt!9Pu
arrow=endothelial cell and CD=collecting duct @%b&(x^UD
Magnification: 1000. %~rXJrK
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