18 %x2b0L\g
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number 6"%qv`.Fp
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The f-+.;`H)T
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at &va*IR
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The v ($L
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 SfDQ;1?
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, &z ksRX
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive hWxT !
control for Ca2+ induction. The data thus obtained was analyzed with the software Win HDj$"pS
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on ;Q90Y&{L=$
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 d pn3 (
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were gb_X?j%p7
harvested and fractionated as detailed above, and the S-100 fractions were assessed by UPO^V:.R4
immunoblotting for presence or absence of annexin I. 5B|,S1b
Mouse bone marrow transduction and transplantation. u\5g3BH
Retrovirus-mediated transduction of mouse bone marrow cells was done by published ?#ihJt,
methods49. Prestimulated low-density bone marrow cells were infected with high-titer 4?]ZV_BD
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated wT%"5:
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing ~,Mr0
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by A^vvST%7
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) J!<#Nc
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone O\JD, w
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis >]?Jrs
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of TU-c9"7M~
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was vnVZJ}]w\
confirmed by immunoblot analysis. Wx k;g
Determination of renal morphology xH@'H?
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an 19w_tSg
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, /x
O{
.dr
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner We\Y \*!v
for morphologic alterations, as previously detailed Ff&R0v
Patient population FdM<;}6T
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) ;x16shH
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per mCK],TOA:
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) c+wuC,
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. YPG,9iZ&f
The Mayo Institutional Review Board and the Research Ethical Board, University Health 6."PS4}:
Network, University of Toronto approved the study protocol. All patients gave written mDlCt_h
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or 9D%qXU
19 F6DxvyANr
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 *afejjW[
months were not included in the study. Patients with active infection, diabetes, or a ~R'BU=!;F
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), Vv2{^!aZ
medications, malignancies) were also excluded. ` %l&zwj>
Treatment dA|Lufy#
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of (;C$gnr.C
high-quality protein) diet was recommended and patients were encouraged to maintain -ywX5B
the same diet throughout the duration of the study. All patients received a similar T^d#hl.U
conservative treatment regimen that included loop diuretics to control edema, an |1lf(\T_
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. U{HyxZ|q<
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added J-b~4
when required to control systolic blood pressures to <135 mm Hg in >75% of the 2 aew6~
readings. Patients who after a minimum of 4 months of conservative therapy and 4v0dd p
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of
LgO i3
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, 3,%nkW
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine y9=t;qH@|
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given 1bT'u5
&
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count Av@&hD\
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count }!eF
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per Nz3zsP$
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a -hQ96S8
second course of rituximab treatment following the same protocol described above. i<'{Y
Follow-up $,}Qf0(S
In all patients, clinical and laboratory parameters including complete blood counts, u):X>??
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum qw9e)
`3$
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry 6{cybD`Ef&
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion #"=%b
e3
in the urine were assessed by performing two consecutive 24-h urine collections at each yW%&_s0
time point. Data were considered accurate when urinary creatinine excretion was xWd9%,mDNR
consistent with a complete 24 h collection. The mean of the two measurements was eL>K2Jxq
considered for the analysis. The presence of HACAs was evaluated at baseline and at 5Xp$yX =
months 3, 6, 9, and 12. m]bL)]Z
Method / Approach / Study/ Technique rdORNlK&
A discussion is presented of a problem-solving system ;5&k/CB1
To improve the efficiency of the method, the following approach may be applied. oc!biE`u
In order to an investigation was made to find the causes of the >:3xi{
Although large collections of rules and equations have been complied, none are generally *5ka.=Qs
accepted trID#DT~
20 P58\+9d_
This approach will be explained and discussed thoroughly in the body of the report. =g{_^^n
This can be accomplished by sV9{4T~#|
This algorithm to compute the total cost can be described step by step as follows: )_Z]=5Ds
The above preliminary analysis has provided important information FE$M[^1_
Various methods have been proposed for selecting an optimum... &xPOp$Sx~
These concepts have been applied to ;`X`c
On the basis of the concept mentioned above, jldcvW
This can be achieved by SL?%/$2g=O
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the fS;m+ D!j@
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, E9~&f^f
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced m?
\#vw$
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 (hD X4;4
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada *@b~f&Lx6
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% `Gy>tD.#V-
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections Z_eqM4{
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin 1Ud
t9$~T
complex. Sections were counterstained with hematoxylin and examined by light i]hR7g<
microscopy. [4V|UvKz
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay ijR-?nrR
performed at Genentech Inc. that measures the antibody response to rituximab in human HbJadOK
serum samples. D9@<#2-
In all patients, clinical and laboratory parameters including complete blood counts, P~b%;*m}8
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum RN cI]oJ
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry A_X^k|)T
and at months 1, 3, 6, 9, and 12. O(c4iWm
This fact suggests that a new concept cSH tl<UY
This was accomplished by taking ... A-@-?AR
The preparatory stage is very time consuming process. 6w .iEb
Test are performed for validity, completeness, and compatibility 2yVGEp^
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There has been an increasing awareness of the potential of using most ..so far made have *I;Mp
not taken this approach, with the exception of v~W6yjp
Only a few studies can be found. @/ovdf{
It is a very tedious process to go through QtO[g
It is only when .. has been completed that .. may be effected B=nx8s
The entire interpretation process is conducted in one's head. s3f
GX|;
These approaches are sometimes very tedious. %Tm'aY"
Several techniques can be used .jG.90
A polynomial parametric model can be written as [the following]/[follows]: "p_[A
A xx model is constructed/formulated using xx. E Zu
A xx model represents an xx by its xx. s
$=B~l
A process decision model captures the logic essential to v*T@<]f3j
From the equation above, xx is equal to the summation of xx times the ... 0$dY;,Q .
21 T=)L5 Vuq<
The validity of a xx model can be checked using Euler's formula. 5tbiNm^X
Given a model, one can mathematically determine whether ... or ...
)F9V=PJE
Equations for xx need to be derived and implemented in the system. M. UUA?d<'
A number of heuristic rules have been developed for {UjIxV(J
Optimum .. techniques can be made more reliable by ... so that Q0oDl8~
An algorithm based on the characteristic ... is used to determine 'XjHB!!hU
Euler's formula states the following: I[
YfF
The completed model should agree with the formula. {N8rZ [Oo
For manufacturing purposes, a detailed and precise model of the object is necessary #on fac- 3
Engineering design models are very well defined; therefore, ^SES')x
To keep the domain narrow enough to be implementable, yet wide enough to be useful. <H(AS'
Point of View Pp" )hFx
from an implementation standpoint, SZ1pf#w!
From the point of view of this application, 4?6'~G$k
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). L``mF(R^
Information is the meaningful interpretation and correlation of some aggregation of data ? F:C!_
in order to allow one to make decisions. MDXQj5s^
From a practical point of view, the computational aspects of an FLC require a NhaeAD
$e
simplification of the fuzzy control algorithm. 9hi(P*%q
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, >Sl:Z ,g;
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM y#SD-#I-
p.129] N,'qMoNf
Statistical analysis X(
[n>w
Data were analyzed by one-way analysis of variance comparing the three conditions T"jDq1C/,E
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If 5nlyb,"^g
significant F-statistic from analysis of variance existed, this test was followed by Dunnett vt7C
post hoc multiple comparison procedure with sham operation as the control group. For all x[<#mt
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as >WG91b<Xq
statistically significant. o]k]pNO
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney 6O?S r,
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego,
jfhDi6N
CA, USA). olW`.3f
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was =cX"gI
[
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's dtXJ<1:
test, where appropriate. E.*OA y
Data are expressed as mean s.d., median and interquartile range, or frequencies, as :'Kx?Es
appropriate. Variables who deviated from the normal distribution (positively skewed) ;-w PXXR
were log-transformed (log10) before the correlation study. B~?Q. <M
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test !c' ;L'
post hoc analysis of variance were used as indicated below, for the comparison of h1d0{
22 JHOBg{Wg
morphological, immunohistological and functional parameters. Statistical significance V)?g4M3}
was set at P<0.05. Ya{1/AaM
The primary efficacy parameter was defined as change in urinary protein excretion from FO3*[O
baseline (week 0) to 12 months after treatment. The 12-month changes were tested ^qy-el
against zero using the paired t-test. Secondary end points included 6-month changes in c7N9X 3A
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular Dy'l]vN$
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on t|,Ex 7
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. q.Mck9R7
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d.
K8we*
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 h2*&>Mc
Definition of remission status is according to the criteria established by Cattran et al.30 lt"*y.%@b
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a smS0Rk
>50% reduction in peak proteinuria and non-response as <50% reduction in peak nlnJJM&J$
proteinuria. Any patient reaching a CR or PR was considered a treatment success YA8~O5
The statistical significance of differences for the mean values of cytokine concentration a-hGpYJJG
and T cell proliferation was determined with Student's t-test. Differences with a P value *a.*Ha
of less than 0.05 were considered significant. 2C&%UZim;P
Statistical significance was determined by Student's t-test. Data with a P value of less q{(&:~M
than 0.05 were considered significant. b
DvbM
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P xz'd5 re%
values less than 0.05 considered statistically significant. `v
er "s;
The significance of differences among groups was determined by Student's t-test and |
Ylk`<
one-way analysis of variance (SigmaStat software; Jandel). <
us{4%
Comparisons
k"c_x*f
As well, the pros and cons of these representations from a process planning point of view znRhQ+8;!
will be discussed. m$g^On
The method of using xx to implement xx described by Zadeh (1973) appeared more -qF| Y
f
suitable #+\G-
=-
As discussed [in the previous section]/[preciously], x=)$sD-3
Relation [J
Xrj{
We can not invert F' directly because it defines a many-to-one mapping. z w9r0bG
The relationships appear very complicate i|GC 'XD@
Lifting tasks involve complex and imprecise relationship between the task variables and s9>!^MzBK
the human operator's characteristics. }IL@j A
These methods are based on the relationship between ... and ... s,x]zG"
The fundamental concept of a fuzzy rating language is that we can establish a relationship 1L7,x @w
among terms such as high, medium, and low, and then modify these relationships. ?YO%]mTP
This article will thus mention the latter as well as the former. QeoDq
The former two bear a close relation to a fuzzy Cartesian product. rJ>8|K[kt
Importance f_8~b0`
) {VG6m
Hw
23 1\uS~R R
The emphasis is on an implementation of a general approach to rule based decision Viw3 /K
making. *Q?HaG|S
Consideration / Attention I5]zOKlVR
Careful evaluation is necessary to ensure e`^j_VnEH
Such a formulation does not change further considerations. (n\
cs$
Considerable attention has been paid to vCM'n
kXY
Attention should be paid to an important finding of this investigation. /_\4(vvf
Caution should be exercised in this process to avoid ... R0[Gfq9M=
Primary consideration is given to ... components, though others can be accommodated 3]acfCacC
After ... has been defined by ..., a carefully analysis is carried out/performed to determine p
WH u[Fu
A number of factors such as ...need to be taken into consideration before making the mf#oa~_
appropriate decision. C'ZU .Y
It should be noted that G)Y!aX
It is important to point out that ... :nI.Qa'"H
These considerations have heightened interest in the possibility of providing ... F<[8!^l(z
We should stress the fundamental importance of the xx >\ W" 3.
Results. 9EEHLx"
Advantages / Disadvantage _PF><ODX2
One of the major advantages of this new measure of xx is that it can be applied to the -84Z8
?_
experimental study of ZfU_4Pl->
One advantage of using a .. is the ease of preparing it. 43Q&<r$[T
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All the algorithms involve mostly logical operations. $1e@3mzM
It can be easily and without additional cost implemented in a microprocessor;based 15COwc*k
environment. Rjf|
It can reduce the waste of designing from scratch. PA E)3
The advantages of using a xx to represent xx are the following: MEu-lM7v
However, xx is not without its shortcomings. 3;A1[E6K
In most cases, the xxx shows an improvement over the existing xxx. jVDNThm+
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. Po5}Vh
The "best case" results shows a savings of 6% to 9%. GCrN:+E0FJ
Most of the existing works based on xx approach can only recognize a xx . (H$eXW7
Most of the above methods are computational expansive and limited to xx. m +gVGK
Some other advantages of xx are the following: $jHL8r\e7
The problem is the limitation of this method to a limited domain of parts. Xe5J
It proved limited in application because it demanded precision in system modeling that *G9;
d0
was impossible in practice. .D :v0Zm}m
There are advantages to be gained in the structuring of costs and benefits, the use of xx, .}tL:^'~o
The disadvantages of this method are also disadvantages of conventional xx approaches. ;j$84o{
This combines the best features of both techniques V#=N?p
24 9DIG K\
Hopefully, this tool can be as the reference framework of for developing a xx platform, txi
m|)
and helping the administration, marketing, and knowledge management activities in (nBsf1l
virtual communities. w(vf>L6(
Results Qwb@3{
An improvement on the result shown above can be made by based on the data provided h.67]U7m
Recent work has identified 9(m^^
Time-dependent changes of zIQ\_>
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase ]Y3ALQr!
and does not require ERK activation. e@6}?q;
Much of the current work on blLX ncyD
Discussion of these theories is beyond the scope of this review Qc6323/"
Based on the information contained in this Cu0 /TeEM
The result can be categorized into nine classes A0'Yfuie
The results are illustrated by an example Z!*Wn`d-k
The experimental results for each xx time are reported in Table 2. ^D!UF(H
From the results obtained so far, it seem that 0n5N-b?G-@
Because of the inaccuracy of the ..., a conclusion cannot be drawn as GLEGyT?~
Although much effort has been made to., this reality is far from completion. $PNR?
The results indicate that the total benefits are higher than the total costs. d=q2Or
Their results may then serve as guidelines for lower level models, less fuzzy and more !W8$-iq
detailed. [~$9n_O94
Conclusion J.~$^-&!
From the discussion, one may conclude that ... v\Q${6kEtx
The first indication that kGCd!$fsk
In summary, we have shown that 2LXy$[)7
These results suggested that mhh8<BI
Our findings have shown that /I="+
Our observations have provided xqIt?v2c
This study reveals following five main findings: !5pnl0D K*
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in CmM K\R.
the diabetic kidney. u PjJ>
v
As mentioned above, 2}t2k>
Moreover, we demonstrate that, W,}C*8{+
A number of studies have elaborated a body of knowledge about ~p^6
There are findings to indicate that /z`LB
On a descriptive level, there is agreement that for nCJ)=P.d
One issue that became particularly evident from our study is Yaht<Hy
Our data are in agreement with the findings and models presented by previous "\Z.YZUa\
publications, in particular those of Jones et al Z_Hc":4i
According to our observations, t*~V]
wZ
…was not evident from our data pvD\E
25 G)G5eXXX
It could therefore be concluded that <Zl}u:(w
our data illustrate that .sgP3Ah
All these different aspects, as listed above, lead to ^,qi`Tk
In fact, it has already been speculated that w/#k.YE
It should be furthermore mentioned in this context that 3
a_~18W
To identify and verify the essential factors triggering developmental renin expression, it l`4hWs\I
is of interest now to study the development of intrarenal renin expression in mice with Qk*`9
defined gene mutations, using the results of this study as a reference system. y}Oc^Fc
In conclusion, using several approaches, we demonstrated that $OldHe[p
But we have not provided formal proof yet that jTH,GF
In summary, our results suggest that R<I)}<g(A3
In conclusion, we identify JmjqA Dex
A better understanding of such regulatory systems may yield novel therapeutic Y92wL}
approaches to glomerular diseases.
^"STM'Zh
Preliminary results of short-term studies (2 weeks) indicate that e3oHe1"hP
However, we believe that qwM71
B!r
However, despite our extensive measurements of these parameters, we found no =dSH8C"
relationship between response and initial proteinuria, time to B-cell recovery, the U@T"teGBA
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree Fuq ;4UcbL
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be >Z r f}H
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved *")Req
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and 0A9llE
that will also look for factors that may determine its efficacy in IMN. ?5-Y'(r
It has become increasingly clear that f9ux+XQk9
Form the above discussion, the conclusion can be reached that G'<:O(Imu
The conclusions drawn are also valid *oZ]k`-!8
In conclusion to this, it becomes obvious that the problem of xx lies not only in... +?
y ', Ir
We have attempted to introduce some concepts associated with a theory of 2t
7':X
Considerable more work, hopefully, will be done in this area q(xr5iuP_
Employing the compositional rule of inference, the assessment of the xx compatibility in a4aM.o
achieving prescribed xx projectiles in any level of the hierarchy is made possible. In13crr4!
This paper has presented a theoretical and experimental study of the xx process and xx 2[}
O:
concept. ;GQCq@)-
The experimental research results will hopefully serve as useful feedback information for 7W[+e&
improvements for xx work. v
*icoj
The scope of this contribution was to introduce a xx method. lEAf\T7
This has a tremendous impact on our understanding of 7]sRHX0o%
Significant progress has been made in advancing RNAi therapeutics in a remarkably pNUe|b+P
short period of time p.@kv
To date, little is known about… =1#obB
Irrespective of the mechanisms and the molecules –which are still largely unknown – D*=.;Rq
involved in MSC functions, current data suggest that 'k'"+
To better understand J(>T&G;
26 ^k J>4
Future Research (常用于conclustion 的结尾) 'Nkd *
Thus, first extension of the approach could be, !#y_vz9
Further studies are needed to determine the importance of x&p.-Fi
Some improvements to the scheduling aspect of the model may be brought through 8yC
t(ms
additional levels in the hierarchy for more detailed representation of the scheduling MoZ8A6e?B
activity. Uc%kyTBm1
It also unveiled new aspects of the role played by thyroid hormone in response to injury x`:c0y9uG
and tissue repair. LA]UIM@
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and ^V}c8 P|
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of \X2r?
drug molecules. B@j2^Dr~!
In the next few years it should become clear whether sEymwpm9
It should be an exciting time for researchers seeking to harness this powerful endogenous gp+aUK~o
pathway to treat human disease. 2WK c;?
Acknowledgement HT:V;?"
The authors are grateful to the insightful work provided by Mr. John W. Harney and all Y(RB@+67
of the fellows and students that contributed with some of the studies discussed in this KwHlpW*
article "IHFme@^
I would like to express my gratitude to all those who gave me the possibility to complete 5pU/X.lc
this thesis. _]v@Dq VP
I want to thank the Department of Transport of the former Interim Government of ;I9g;}
Namibia for giving me permission to commence this thesis in the first instance, to do the }U'VVPh_
necessary research work and to use departmental data }
fa
This work was supported by NIH grants AI058695 and AI056900. We thank members of &
gF9VY
the laboratory and our collaborators for many useful suggestions. '=0l{hv@
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. F'-,Ksn
Duckman for graphics assistance and A. Capobianco for word processing assistance. 704_ehrlE
Author contributions _lDNYpv
All authors were involved in experimental planning and data analysis and contributed to Kzx`
E>,z'
manuscript preparation. G<-<>)zO!
Tables and Figures ]D&U}n
Figure 7-1 sketches these relationships. v|M
T^.
The graphical representation of these functions is shown in Figure 1. ix hF,F
The xx may be depicted as in Figure 1. klAvi%^jE
Figure x shows the schematic diagram of the ;X;(7
Figure 1 though 2 provide a ... that $>7T s>8
the architecture of this expert system for .... is illustrated in Figure 2. G8zbb
Figure 2 gives the outline of an ... system -'F27])
Table shows the R$p(5>#\5
27 Zoy)2E{
Time-dependent changes of 6L;
]5)#
as shown in Table 1 and 2 AhkDLm+
This concept is illustrated in Figure 2 @?jtB
At the top of Table xx are shown two blocks of data. .C.b5x!
Each table or matrix has constructs xx through xx as row;headings, qRR%aJ/
xx through xx as column;headings. A2ufET
Time course of calculated renin immunoreactive tissue volumes during development of $Dd-2p
the mouse kidney. Data are single values per time point. They were derived from the Dlpmm2
kidneys shown in Figure 1. i&8|@CACb
Yellow color indicates +$Y*1{hyOo
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then 9Z }<H/q
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were W/3sJc9
analyzed by western blot using phospho-specific antibodies. *VmX.
ERK and PKB activation were measured by western blot using phospho-specific MsBm0r`a
antibodies D.-G!0
!
The data are the means of three different experiments taking the number of untreated cells ( et W4p
(vehicle alone) as 100%. in5e *
ERK and PKB activation were then analyzed by western blot with the corresponding xXc>YTK'
phospho-specific antibodies. To ensure equal amount of protein in each lane, western 7#W]Qj
blots against total protein were performed for ERK and PKB. }n
"5r(*^@
The means of optical density (OD) values of the bands detected in western blots of three <f`n[QD2z
different experiments are plotted, taking the maximal value of phosphorylation of ERK OR*JWW[]
and PKB as 100%. }O>4XFj
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with =3
6fS/Gb
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then ;c>"gW8
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence z9g ++]rkJ
microscopy (lower panel). 3tCTPZy
The data are the means of three experiments performed on different days taking the <i4]qO(0u
number of cells at the onset of the experiment as 100%. IC5QH<.$C
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction NJ+$3n om
(n=9 each). 4I$Y"|_e
*P<0.05 versus non-nephritic rats. j}tM0Ug.U
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, 8nu!5 3
positive control, M, molecular weight markers). FwlDP
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. [k>{q+MWK
Data are means s.d. of four independent experiments. AT+l%%
*P<0.05 versus 0.5 h. uS,?oS
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 ?d3FR!
mRNA as determined by real-time RT-PCR and normalized to YPGzI]\
glyceraldehyde-3-phosphate dehydrogenase mRNA. i+qg*o$
Cell number was counted in duplicate using a Malassez hemocytometer l"A/6r!Dp
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with #h^nvRmON
MCDB media for 24 h, #P<0.05. gm2|`^Xq$
28 =.;ib6M
The curves are adjusted for history of coronary artery disease, CRP, and progression to Wz=&
0>Mm_
ESRD. Qw5(5W[L
Both models are independent of age, gender, baseline GFR and proteinuria, and other 6WQN!H8+^
clinical characteristics and traditional and nontraditional cardiovascular risk factors :d9GkC
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH ,hu@V\SKv
(n=99, P<0.0001, r2=0.190) =WUL%MfW
Concentration of serum FGF23 concentration before starting and at the end of the 4-h i a!!jK
}
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, "i(f+N,)
Student's paired t-test). D{Nd2G
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; ]o]`X$n
arrow=endothelial cell and CD=collecting duct iB(?}SaAZ
Magnification: 1000. "hI"4xSg
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