18 PWS5s^WM
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number oLt%i:, A
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The #ahe@|E'Y
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at OB
+QVYk"
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The [h0)V(1KR
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 |1m2h]];Q
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, stq%Eg?
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive ,'@t.XP
control for Ca2+ induction. The data thus obtained was analyzed with the software Win O?Qi
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on _TVKvRh
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 @[O|n)7
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were \WM"VT
harvested and fractionated as detailed above, and the S-100 fractions were assessed by ?b?YiK&yz
immunoblotting for presence or absence of annexin I. ]fU0;jzX
Mouse bone marrow transduction and transplantation. +QEiY~i
Retrovirus-mediated transduction of mouse bone marrow cells was done by published 69zMWuY
methods49. Prestimulated low-density bone marrow cells were infected with high-titer Ym9~/'%]
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated +wm%`N;v<
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing 1*OZu.NdK
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by 3:3>k
8
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) rf
=Wq_
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone l' Uj"9r,
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis LbnW(wr6:(
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of OsgjSJrf
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was )8V=!73
confirmed by immunoblot analysis. *NoixV1>
Determination of renal morphology XK/bE35%^!
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an 4X$|jGQ\
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, =dY!-#yg!
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner \T^ptj(0
for morphologic alterations, as previously detailed e^or qw/I
Patient population tIo
b
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) rWip[>^
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per *m[[>wE
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) u Qz!of%x
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. rch Kr w
The Mayo Institutional Review Board and the Research Ethical Board, University Health !OMl-:KUzE
Network, University of Toronto approved the study protocol. All patients gave written hWRr#030
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or {z
|+.D
19 &Yd6w}8
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 Nt7z
]F `
months were not included in the study. Patients with active infection, diabetes, or a gh.+}8=
"
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), `':G92}#
medications, malignancies) were also excluded. 3?<LWrhV3
Treatment O@`KGZEPY
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of 8Bx58$xRq
high-quality protein) diet was recommended and patients were encouraged to maintain > QG@P
the same diet throughout the duration of the study. All patients received a similar U i`#B
conservative treatment regimen that included loop diuretics to control edema, an * 5(%'3
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. \qtdbi|Y
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added m`Pk )c0
when required to control systolic blood pressures to <135 mm Hg in >75% of the H}gp`YW:4
readings. Patients who after a minimum of 4 months of conservative therapy and 6T%5<I*&3s
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of deC
i\n
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, Nu@dMG
<5
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine $Ao'
mT
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given ,n&Lp
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count XUTsW,WC
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count x pBQ(6Y
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per >O~
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a L)"CE].
second course of rituximab treatment following the same protocol described above. D_ XOYzN}
Follow-up Em(Okr,0
In all patients, clinical and laboratory parameters including complete blood counts, &!B4v<#, U
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum %<<JWo
B
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry %$67*pY'JH
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion EF'8-*
in the urine were assessed by performing two consecutive 24-h urine collections at each XT1P.
w[aA
time point. Data were considered accurate when urinary creatinine excretion was ^7YZ>^
consistent with a complete 24 h collection. The mean of the two measurements was (W?t'J^#
considered for the analysis. The presence of HACAs was evaluated at baseline and at NKl`IiGv
months 3, 6, 9, and 12. "G@(Cb*+T
Method / Approach / Study/ Technique FIx|4[&>S
A discussion is presented of a problem-solving system {+V ]@sz
To improve the efficiency of the method, the following approach may be applied. 2.'hr/.
In order to an investigation was made to find the causes of the <MoyL1=
Although large collections of rules and equations have been complied, none are generally (,b\"Q
accepted BDLJDyf B
20 L. 8`5<ITw
This approach will be explained and discussed thoroughly in the body of the report. Ok<,_yh
This can be accomplished by gZ8JfA_\R(
This algorithm to compute the total cost can be described step by step as follows: YKzfI9Y
The above preliminary analysis has provided important information 1'|gxYT
Various methods have been proposed for selecting an optimum... lv+:
`
These concepts have been applied to ay]l\d2!3
On the basis of the concept mentioned above, m[Mw2 F
This can be achieved by 4RfBXVS
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the t:b}Mo0
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, |Qn>K
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced 4gZ)9ya
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 Wl}J=
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada s\p 1EL(
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% uvJ&qd8M
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections $-]I?cWlQ
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin `q
Ryh}Ax"
complex. Sections were counterstained with hematoxylin and examined by light 8fktk?|
microscopy. 3#y`6e=5
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay u=Xpu,q
performed at Genentech Inc. that measures the antibody response to rituximab in human !Y&]Y
G
serum samples. rV} 5&N*c
In all patients, clinical and laboratory parameters including complete blood counts, | >'q%xK
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum t+\<i8
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry HMDuP2Y
and at months 1, 3, 6, 9, and 12. c'mg=jH
This fact suggests that a new concept 5sNN:m
This was accomplished by taking ... .1z=VLKF'
The preparatory stage is very time consuming process. WD! " $
Test are performed for validity, completeness, and compatibility c6AwO?x/
There is little hope of achieving successful ... W8r"dK
There has been an increasing awareness of the potential of using most ..so far made have G( BSe`f
not taken this approach, with the exception of /1$u|Gs
*
Only a few studies can be found. z, FPhbFn
It is a very tedious process to go through C](djkA$
It is only when .. has been completed that .. may be effected *`LrvE@t
The entire interpretation process is conducted in one's head. \v$zU
These approaches are sometimes very tedious. >[:qJ|i%
Several techniques can be used 'Gamb+[
A polynomial parametric model can be written as [the following]/[follows]: v`G}
sgn
A xx model is constructed/formulated using xx. sx]{N
A xx model represents an xx by its xx. J3e'?3w[
A process decision model captures the logic essential to Y88N*axDW.
From the equation above, xx is equal to the summation of xx times the ... ZkO2*;
21 f(5;Rf(
The validity of a xx model can be checked using Euler's formula. _+H $Pa}?
Given a model, one can mathematically determine whether ... or ... s^4wn:*$zd
Equations for xx need to be derived and implemented in the system. 0AF,} &$
A number of heuristic rules have been developed for A (p^Q
Optimum .. techniques can be made more reliable by ... so that C' {B
An algorithm based on the characteristic ... is used to determine j}`ku9S~
Euler's formula states the following: U<>@)0~7g!
The completed model should agree with the formula. B9$pG
For manufacturing purposes, a detailed and precise model of the object is necessary
HKJ^6|'
Engineering design models are very well defined; therefore, <:T/hm$
To keep the domain narrow enough to be implementable, yet wide enough to be useful. og~a*my3
Point of View :(.:bf
from an implementation standpoint, /m,i,NX07
From the point of view of this application, ;b. m X
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). MgN;[4|[h
Information is the meaningful interpretation and correlation of some aggregation of data *5?Qam3
in order to allow one to make decisions. p$= 3$I
From a practical point of view, the computational aspects of an FLC require a pGF;,h>
simplification of the fuzzy control algorithm. jTZi<
Y:bB
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, [
dUAb
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM
w5rtYTI
p.129] ?iEn~9WCS
Statistical analysis c&aqN\'4"
Data were analyzed by one-way analysis of variance comparing the three conditions i_+e&Bjd4j
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If <<Y]P+uU
significant F-statistic from analysis of variance existed, this test was followed by Dunnett |2=w":2#
post hoc multiple comparison procedure with sham operation as the control group. For all m^0 I3;
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as [u J<]
statistically significant. Zy{hYHQ
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney zQt)>Qx_
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, M?hPlo"_
CA, USA). DYC2bs>
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was gbh/`
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's 3,{;wJ
Z
test, where appropriate. ";jAH GbO
Data are expressed as mean s.d., median and interquartile range, or frequencies, as {ehYE ^%N
appropriate. Variables who deviated from the normal distribution (positively skewed) Qy=tkCN
were log-transformed (log10) before the correlation study. >yqEXx5{
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test 'd;aAG
post hoc analysis of variance were used as indicated below, for the comparison of rq1~%S
22 &9.3-E47*
morphological, immunohistological and functional parameters. Statistical significance }g%&}`%'
was set at P<0.05. P9Eh,j0_
The primary efficacy parameter was defined as change in urinary protein excretion from 7)Tix7:9S;
baseline (week 0) to 12 months after treatment. The 12-month changes were tested E)X_
against zero using the paired t-test. Secondary end points included 6-month changes in 2(e;pM2Dq
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular ,'l.u?SKyd
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on 36.mf_AM
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. S_VzmCi
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. ;;U&mhz`
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 P/]8+_K
Definition of remission status is according to the criteria established by Cattran et al.30 b+Vlq7Bc
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a Yx ;j
>50% reduction in peak proteinuria and non-response as <50% reduction in peak 7Bf4ojKt
proteinuria. Any patient reaching a CR or PR was considered a treatment success &qa16bz
The statistical significance of differences for the mean values of cytokine concentration WFS6N.Ap
and T cell proliferation was determined with Student's t-test. Differences with a P value |Z Cv>8?n
of less than 0.05 were considered significant.
"[Tr"nI
Statistical significance was determined by Student's t-test. Data with a P value of less fKua om9
than 0.05 were considered significant. W>P :EI1
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P b~8&P_
values less than 0.05 considered statistically significant. :b#5cMUe
The significance of differences among groups was determined by Student's t-test and *y>
|
one-way analysis of variance (SigmaStat software; Jandel). bs?4|#[K
Comparisons )%!X,
As well, the pros and cons of these representations from a process planning point of view $ WWi2cI;
will be discussed. sn@)L ~$V
The method of using xx to implement xx described by Zadeh (1973) appeared more -OfAl~ 4
suitable #KtV 4)(
As discussed [in the previous section]/[preciously], #`"B
YFV[E
Relation \nQEvcH
We can not invert F' directly because it defines a many-to-one mapping. Uf$IH!5;Z
The relationships appear very complicate m :]F&s
Lifting tasks involve complex and imprecise relationship between the task variables and Pp|pH|(n ,
the human operator's characteristics. y|wR)\
These methods are based on the relationship between ... and ...
"M]`>eixL
The fundamental concept of a fuzzy rating language is that we can establish a relationship $,Y?qn/
among terms such as high, medium, and low, and then modify these relationships. bHHR^*B
This article will thus mention the latter as well as the former. '9|R7
The former two bear a close relation to a fuzzy Cartesian product. e}L(tXZ
Importance
q0\$wI
) Z?w=-
23 @gJPMgF$F
The emphasis is on an implementation of a general approach to rule based decision An
!i
making. 0j{KZy
Consideration / Attention P`M1sON~
Careful evaluation is necessary to ensure u\UI6/
Such a formulation does not change further considerations. e?-LB
Considerable attention has been paid to N{zou?+
Attention should be paid to an important finding of this investigation. 5{8,+
Z
Caution should be exercised in this process to avoid ... !E\J`K0_e
Primary consideration is given to ... components, though others can be accommodated `3F/7$q_
After ... has been defined by ..., a carefully analysis is carried out/performed to determine * (<3 oIRS
A number of factors such as ...need to be taken into consideration before making the k8"[)lDc.
appropriate decision. &oiBMk`*
It should be noted that {pB9T3ry]
It is important to point out that ... 2VS#=i(B^
These considerations have heightened interest in the possibility of providing ... N&lKo}hk
We should stress the fundamental importance of the xx 2c<phmiK
Results. ^kpu9H
Advantages / Disadvantage 93#wU})
One of the major advantages of this new measure of xx is that it can be applied to the %|3UWN
experimental study of [p_C?hHO
One advantage of using a .. is the ease of preparing it. *CXVA&?
It has a very fast decision making process %5H>tG`]
All the algorithms involve mostly logical operations. sQe>LNp,G
It can be easily and without additional cost implemented in a microprocessor;based :YZMRJL
environment. 5bKn6O)K
It can reduce the waste of designing from scratch. qT L@N9
The advantages of using a xx to represent xx are the following: Z?-l-sK
However, xx is not without its shortcomings. W1J7$
In most cases, the xxx shows an improvement over the existing xxx. wA}+E)x/C
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. %@
FTg$
The "best case" results shows a savings of 6% to 9%. bx<7@
Most of the existing works based on xx approach can only recognize a xx . #VEHyz 6P
Most of the above methods are computational expansive and limited to xx. Wc$1Re{z
Some other advantages of xx are the following: Wz7jB6AWA
The problem is the limitation of this method to a limited domain of parts. ;=6~,k)
It proved limited in application because it demanded precision in system modeling that up7]Yy;o=
was impossible in practice. !(Y23w*
There are advantages to be gained in the structuring of costs and benefits, the use of xx, cv["Ps#;`W
The disadvantages of this method are also disadvantages of conventional xx approaches. 6(}8[i:
This combines the best features of both techniques gI^*O@Q4{b
24 5A6d]
Hopefully, this tool can be as the reference framework of for developing a xx platform, (v8jVbg
and helping the administration, marketing, and knowledge management activities in pemb2HQ'4j
virtual communities. 3B|o
Results eg-,;X#
An improvement on the result shown above can be made by based on the data provided
sD*8:Hl
Recent work has identified 7PZ0
Time-dependent changes of Khxl'qj
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase ?8n`4yO0
and does not require ERK activation. MDS;qZx=
Much of the current work on ,r{\aW@
Discussion of these theories is beyond the scope of this review VZ;ASA?;
Based on the information contained in this R1FBH:Iu
The result can be categorized into nine classes y!Q&;xO+!
The results are illustrated by an example $aX}i4F
The experimental results for each xx time are reported in Table 2. [=-?n6
From the results obtained so far, it seem that ?*
a:f"vQ
Because of the inaccuracy of the ..., a conclusion cannot be drawn as 0Q=4{*:?
Although much effort has been made to., this reality is far from completion. ]v3 9ag_hu
The results indicate that the total benefits are higher than the total costs. #!KbqRt
Their results may then serve as guidelines for lower level models, less fuzzy and more |b52JF
",
detailed. -1~bWRYq
Conclusion o
@r+Y
From the discussion, one may conclude that ... rm NqS+t
The first indication that 1+PLj[;jJ:
In summary, we have shown that %^g BDlR^
These results suggested that ` IiAtS
Our findings have shown that *?K3jy{
Our observations have provided YsXP$y]g-
This study reveals following five main findings: o jzO?z
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in yK<%AV@v
the diabetic kidney. 6)kF!/J
As mentioned above, oBQr6-nZ
Moreover, we demonstrate that, JGp~A#H&
A number of studies have elaborated a body of knowledge about c-!rJHL`
There are findings to indicate that J.mEOo!>
On a descriptive level, there is agreement that for !MNUp(:
One issue that became particularly evident from our study is k`6T% [D]
Our data are in agreement with the findings and models presented by previous l~wx8
,?G
publications, in particular those of Jones et al
eP$0TDZ
According to our observations, agN`)
F!
…was not evident from our data p
mcy(<
25 gd-4hR
It could therefore be concluded that d {a^
our data illustrate that T+zZOI
All these different aspects, as listed above, lead to 5zX;/n~
In fact, it has already been speculated that z,
[4BM
It should be furthermore mentioned in this context that 0~Ot
To identify and verify the essential factors triggering developmental renin expression, it Zh]d&Xeq
is of interest now to study the development of intrarenal renin expression in mice with (X@JlAfB
defined gene mutations, using the results of this study as a reference system. |S|0'C*
In conclusion, using several approaches, we demonstrated that eyy{z;D8r
But we have not provided formal proof yet that 7OG=LF*V-
In summary, our results suggest that Z!60n{T79c
In conclusion, we identify >nkd U
A better understanding of such regulatory systems may yield novel therapeutic K?,eIZ{.S
approaches to glomerular diseases. i)g=Lew
Preliminary results of short-term studies (2 weeks) indicate that |\%[e@u
However, we believe that +^YXqOXU
However, despite our extensive measurements of these parameters, we found no tbF>"?FY/
relationship between response and initial proteinuria, time to B-cell recovery, the R:P'QM
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree #"fBF/Q
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be ;ajCnSmR
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved vF0#]
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and jt?4raNW
that will also look for factors that may determine its efficacy in IMN. XYhN;U}Z
It has become increasingly clear that ^&buX_nlO
Form the above discussion, the conclusion can be reached that I3]-$
The conclusions drawn are also valid F0W4B
In conclusion to this, it becomes obvious that the problem of xx lies not only in... h`X)sC+
We have attempted to introduce some concepts associated with a theory of "i_I<?aGB
Considerable more work, hopefully, will be done in this area 3
HOJCgit
Employing the compositional rule of inference, the assessment of the xx compatibility in Q;W[$yvW
achieving prescribed xx projectiles in any level of the hierarchy is made possible. losm<
This paper has presented a theoretical and experimental study of the xx process and xx [74HUw>
concept. >UvLeS2h:y
The experimental research results will hopefully serve as useful feedback information for !|;^
improvements for xx work. 'g.9
goQ
The scope of this contribution was to introduce a xx method. ~sT/t1Rp
This has a tremendous impact on our understanding of GTL gj'B
Significant progress has been made in advancing RNAi therapeutics in a remarkably 6x|"1
G{
short period of time f#mBMd
j
To date, little is known about… I.BsKB
Irrespective of the mechanisms and the molecules –which are still largely unknown – \^a(B{
involved in MSC functions, current data suggest that IZ+kw
.6e
To better understand 3<.]+ukm
26
uyBmGS2
Future Research (常用于conclustion 的结尾) gv)F`uRWA
Thus, first extension of the approach could be, yN}upYxp
Further studies are needed to determine the importance of "!43,!<
Some improvements to the scheduling aspect of the model may be brought through ,p2BB"^_i
additional levels in the hierarchy for more detailed representation of the scheduling "c5C0 pK0
activity. -(*<2Hy4
It also unveiled new aspects of the role played by thyroid hormone in response to injury uG<VQ2LM
and tissue repair. >Y,3EI\
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and GVS-_KP\
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of XfY~q~f8
drug molecules. pkTg.70wU
In the next few years it should become clear whether )Dn~e#
It should be an exciting time for researchers seeking to harness this powerful endogenous Gt;@.jY&
pathway to treat human disease. 2y6@:VxSh
Acknowledgement >!u@>
The authors are grateful to the insightful work provided by Mr. John W. Harney and all *;^!FBT
of the fellows and students that contributed with some of the studies discussed in this >JdA,i}1
article ~9#x/EG/
I would like to express my gratitude to all those who gave me the possibility to complete F:$Dz?F0v
this thesis. u=j|']hp#&
I want to thank the Department of Transport of the former Interim Government of QG{).|pm
Namibia for giving me permission to commence this thesis in the first instance, to do the -anLp8G*
necessary research work and to use departmental data Vj
Z_L_U}
This work was supported by NIH grants AI058695 and AI056900. We thank members of $7Sbz&)y3
the laboratory and our collaborators for many useful suggestions. @q=l H
*=
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. s=)0y$
Duckman for graphics assistance and A. Capobianco for word processing assistance. PT2b^PP
Author contributions a2:Tu
All authors were involved in experimental planning and data analysis and contributed to $^&SEz
manuscript preparation. *7L*:g
Tables and Figures Rg:3}T`~n
Figure 7-1 sketches these relationships. WW.\5kBl8
The graphical representation of these functions is shown in Figure 1. M~&|-Hm
The xx may be depicted as in Figure 1. ]>utLi5dX
Figure x shows the schematic diagram of the x.>E7
+
Figure 1 though 2 provide a ... that K?l1Gj
the architecture of this expert system for .... is illustrated in Figure 2. R=D\VIu,Z
Figure 2 gives the outline of an ... system [\9WqHs
Table shows the >.R6\>N%
27 H>AzxhX[n
Time-dependent changes of ?$O5w*
as shown in Table 1 and 2 ++KY+j.^
This concept is illustrated in Figure 2 +MQvq\%tG
At the top of Table xx are shown two blocks of data. dEXHd@"H
Each table or matrix has constructs xx through xx as row;headings, Z_%}pe39B
xx through xx as column;headings.
h]Zc&&+8{
Time course of calculated renin immunoreactive tissue volumes during development of `1%SXP1
the mouse kidney. Data are single values per time point. They were derived from the o3H+.u$
kidneys shown in Figure 1. _/[n/"gn
Yellow color indicates 1B3,lYBM
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then .js4)$W^
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were W7NHr5RC
analyzed by western blot using phospho-specific antibodies. =q|fe%#
ERK and PKB activation were measured by western blot using phospho-specific Q^Ln`zMe
antibodies `w S
g/
The data are the means of three different experiments taking the number of untreated cells }iy`Ko+B"b
(vehicle alone) as 100%. !DnG)4#
ERK and PKB activation were then analyzed by western blot with the corresponding *8p\.za1
phospho-specific antibodies. To ensure equal amount of protein in each lane, western VGcl)fIqw?
blots against total protein were performed for ERK and PKB. ^v3+w"2
The means of optical density (OD) values of the bands detected in western blots of three FH8?W|
G
different experiments are plotted, taking the maximal value of phosphorylation of ERK b*Ipg8n+
and PKB as 100%. "xdJ9Z-B
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with [ hj|8)
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then Cu({%Gy+
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence KGUpXMd^Z
microscopy (lower panel). rOY^w9!
The data are the means of three experiments performed on different days taking the )<.S3
number of cells at the onset of the experiment as 100%. +2oZB]GPL
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction v%3)wD
(n=9 each). d$r JW m5H
*P<0.05 versus non-nephritic rats. G%YD2<V
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, 17D167\X
positive control, M, molecular weight markers). !W$3p'8Tu
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. 9r1pdG_C@
Data are means s.d. of four independent experiments. c%~'[W04\
*P<0.05 versus 0.5 h. 3|:uIoR{
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 n 2#uH
mRNA as determined by real-time RT-PCR and normalized to jZv8X5i
glyceraldehyde-3-phosphate dehydrogenase mRNA. 8Z3+S)6
Cell number was counted in duplicate using a Malassez hemocytometer |[34<tIN
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with GWE`'V
MCDB media for 24 h, #P<0.05. 4d]
28 Tjs-+$P+
The curves are adjusted for history of coronary artery disease, CRP, and progression to PLLlo~Bb
ESRD. flLmZ1"
Both models are independent of age, gender, baseline GFR and proteinuria, and other Y_/Kd7,\~
clinical characteristics and traditional and nontraditional cardiovascular risk factors 6C]!>i}U
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH Xkv>@7ec
(n=99, P<0.0001, r2=0.190) ]Vwky]d
Concentration of serum FGF23 concentration before starting and at the end of the 4-h %\b5)p
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, #-lk=>
Student's paired t-test). T[Gz
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; oub4/0tN,~
arrow=endothelial cell and CD=collecting duct coLn};W2
Magnification: 1000. wG{obsL.!
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