18 ?hkOL$v<9}
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number m?<E >-bI
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The |SjRss:i+
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at I@9'd$YY
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The m:?"|.
]
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 edq,:
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, LO{Axf%
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive Wvr{
l
control for Ca2+ induction. The data thus obtained was analyzed with the software Win k[ro[E
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on TMj;NS
c3
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 gk%@& TB/
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were nlNk
harvested and fractionated as detailed above, and the S-100 fractions were assessed by Y!CUUWM
immunoblotting for presence or absence of annexin I. , [|aWT%9
Mouse bone marrow transduction and transplantation. V|_
h[hXE
Retrovirus-mediated transduction of mouse bone marrow cells was done by published ?FAI@4
methods49. Prestimulated low-density bone marrow cells were infected with high-titer h0rPMd(K
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated ^'V :T Y
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing ">oySo.B?
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by VIT|#
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) r\;fyeH
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone uX6yhaOp|
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis 2]5{Xmmo9
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of Ku75YFO,5
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was Cf2WBX$
confirmed by immunoblot analysis. C1k< P
Determination of renal morphology ?Afe}
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an n:
%4SZn
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, y QW7ng7D0
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner "o&8\KSs
for morphologic alterations, as previously detailed nF,F#V8l
Patient population Y_JQPup
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) l_^SU8i57
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per ec&/a2M
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) @Vre)OrN#
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. 6O7s^d&K
The Mayo Institutional Review Board and the Research Ethical Board, University Health zt(lV
Network, University of Toronto approved the study protocol. All patients gave written m4mE7Wn.3
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or SMEl'y
19 $DL}jH^S
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 UM oj9/-
months were not included in the study. Patients with active infection, diabetes, or a 3p%e_?
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), q/#e6;x
medications, malignancies) were also excluded. @J[@Pu O
Treatment p
F-Lz<V
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of v(1 [n]y
high-quality protein) diet was recommended and patients were encouraged to maintain 5Gz!Bf@!!
the same diet throughout the duration of the study. All patients received a similar J:Cr.K`
conservative treatment regimen that included loop diuretics to control edema, an _~<sb,W
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. PCviQ!X
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added d:%b
when required to control systolic blood pressures to <135 mm Hg in >75% of the ;TAj;Tf]H
readings. Patients who after a minimum of 4 months of conservative therapy and uo#1^`P
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of K10G+'H^
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, =zkN
63S
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine
Aa
~W,
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given cOV j
@z
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count $ev+0m_
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count ,aP6ct
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per W/Dd7G#IC
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a D=e*rrL7a
second course of rituximab treatment following the same protocol described above. }]x \ `}o
Follow-up )UzJ2Pa<+_
In all patients, clinical and laboratory parameters including complete blood counts, q$:1Xkl
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum i|eX X)$
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry Na0^csPm
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion R"B{IWQi
in the urine were assessed by performing two consecutive 24-h urine collections at each >?$2`I
time point. Data were considered accurate when urinary creatinine excretion was \+
se%O
consistent with a complete 24 h collection. The mean of the two measurements was
r h*F
considered for the analysis. The presence of HACAs was evaluated at baseline and at nBy-/BU&
months 3, 6, 9, and 12. >h7(kj:
Method / Approach / Study/ Technique |E8sw a
A discussion is presented of a problem-solving system .?Eb{W)^br
To improve the efficiency of the method, the following approach may be applied. ]A5F}wV4
In order to an investigation was made to find the causes of the S\GWMB!oF
Although large collections of rules and equations have been complied, none are generally (?z?/4>7<
accepted +Mo4g2W
20 I}`pY3
This approach will be explained and discussed thoroughly in the body of the report. 0L}`fYf
This can be accomplished by Kb; *"@LX
This algorithm to compute the total cost can be described step by step as follows: _^iY;&
The above preliminary analysis has provided important information X=QX9Ux?^
Various methods have been proposed for selecting an optimum... iOiFkka
These concepts have been applied to cv'8_3
On the basis of the concept mentioned above, g[} L
?
This can be achieved by }B0[S_mw
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the P(aBJ*((~
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, 9qap#A
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced LUQ.=:mBR
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 k4{!h?h
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada ZqclmCi
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% c=v016r\
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections 7Z>vQ f B
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin [4"(\r\
f
complex. Sections were counterstained with hematoxylin and examined by light mV}b
Q^*?Z
microscopy. \(Ma>E4PNU
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay ?mNB:-Q
performed at Genentech Inc. that measures the antibody response to rituximab in human JD*HG]
serum samples. {
j_-iF
In all patients, clinical and laboratory parameters including complete blood counts, T@1;Nbz]
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum .$\-{)
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry =%` s-[5b
and at months 1, 3, 6, 9, and 12. [8'?G5/n
This fact suggests that a new concept jf)cDj2
This was accomplished by taking ... ?NA$<0
The preparatory stage is very time consuming process. 7;Ze>"W>
Test are performed for validity, completeness, and compatibility L}
R"
1O
There is little hope of achieving successful ... `,AOxJ:$
There has been an increasing awareness of the potential of using most ..so far made have 5WI
bnV@
not taken this approach, with the exception of HS|Gz3~
Only a few studies can be found. 1gK|n
It is a very tedious process to go through OV{v6,>O
It is only when .. has been completed that .. may be effected dOv\]
The entire interpretation process is conducted in one's head. sqhMnDn[
These approaches are sometimes very tedious. Rxdj}xy
Several techniques can be used
KTYjC\\G
A polynomial parametric model can be written as [the following]/[follows]: U-DQ?OtmC@
A xx model is constructed/formulated using xx. bIm4s
A xx model represents an xx by its xx. XoD:gf
A process decision model captures the logic essential to xY?p(>(
From the equation above, xx is equal to the summation of xx times the ... 'A|c\sy
21 qG,h
1
The validity of a xx model can be checked using Euler's formula.
kb 74:
Given a model, one can mathematically determine whether ... or ... g@ J F
Equations for xx need to be derived and implemented in the system. ,q%X`F
rc
A number of heuristic rules have been developed for 8b0j rt
Optimum .. techniques can be made more reliable by ... so that !{*yWpZ:
An algorithm based on the characteristic ... is used to determine 9 ] N{8
Euler's formula states the following: 2{RRaUoRb
The completed model should agree with the formula. OybmyGHY
For manufacturing purposes, a detailed and precise model of the object is necessary ^+-
QY\N
j
Engineering design models are very well defined; therefore, O-[YU%K3?
To keep the domain narrow enough to be implementable, yet wide enough to be useful. GTOA>RB2
Point of View @5&57R3>
from an implementation standpoint, kYCm5g3u
From the point of view of this application, b)a5LFt|
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). BHp>(7,
Information is the meaningful interpretation and correlation of some aggregation of data KT<i%)t2
in order to allow one to make decisions. @[joM*U
From a practical point of view, the computational aspects of an FLC require a _*=4xmB.=
simplification of the fuzzy control algorithm. o_\vudXK
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, AHr^G
'
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM S7J.(;
82
p.129] Q0`@=5?-
Statistical analysis \_u{ EB'b
Data were analyzed by one-way analysis of variance comparing the three conditions 2.JrLBhN
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If _!|$ i
significant F-statistic from analysis of variance existed, this test was followed by Dunnett 2@T0QJ
post hoc multiple comparison procedure with sham operation as the control group. For all W|{!0w
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as /(||9\;
statistically significant. _s-X5xU
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney ^{J^o
Z'%~
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, %1cxZxGT
CA, USA). kLs{B
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was )s7 EhIP
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's ;[lLFI
test, where appropriate. o ;9H~E
Data are expressed as mean s.d., median and interquartile range, or frequencies, as 3#""`]
9H
appropriate. Variables who deviated from the normal distribution (positively skewed) ve a$G~[%6
were log-transformed (log10) before the correlation study. 7^)yo#i4
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test #WUN=u
post hoc analysis of variance were used as indicated below, for the comparison of
{a>JQW5=
22 ?3LV$S)U
morphological, immunohistological and functional parameters. Statistical significance Pvv7|AV
was set at P<0.05. 1mh7fZgn
The primary efficacy parameter was defined as change in urinary protein excretion from 7"eIZ
baseline (week 0) to 12 months after treatment. The 12-month changes were tested D}{]5R
against zero using the paired t-test. Secondary end points included 6-month changes in W }Ll)7(|T
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular bQ?Vh@j(M
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on t T
A
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. N>s3tGh
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. B'B0 e
`
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 #~rQ\A!4
Definition of remission status is according to the criteria established by Cattran et al.30 ,rY}IwMw
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a $Zi{1w
>50% reduction in peak proteinuria and non-response as <50% reduction in peak gpb
dK?
proteinuria. Any patient reaching a CR or PR was considered a treatment success q|lP?-j
The statistical significance of differences for the mean values of cytokine concentration RXWdqaENx
and T cell proliferation was determined with Student's t-test. Differences with a P value /K,@{__JP
of less than 0.05 were considered significant. ,ueA'GZ
Statistical significance was determined by Student's t-test. Data with a P value of less H?=[9?1wI5
than 0.05 were considered significant. w(Mi?
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P #5{lOeN
values less than 0.05 considered statistically significant. tnXW7ej ^
The significance of differences among groups was determined by Student's t-test and m KKa0"
one-way analysis of variance (SigmaStat software; Jandel). 527u d^:
Comparisons 6il+hz2&lH
As well, the pros and cons of these representations from a process planning point of view ZE/Aj/7Qy
will be discussed. wxG*mOw
The method of using xx to implement xx described by Zadeh (1973) appeared more U|+`Eth8(
suitable 4l{La}Aj
As discussed [in the previous section]/[preciously], P6'0:M@5
Relation JS >"j d#
We can not invert F' directly because it defines a many-to-one mapping. &4p~i Z
The relationships appear very complicate %CrpUx
Lifting tasks involve complex and imprecise relationship between the task variables and XQ Si
the human operator's characteristics. X*r?@uK5
These methods are based on the relationship between ... and ... ]V"B`ip[2
The fundamental concept of a fuzzy rating language is that we can establish a relationship aTLr%D:Ka
among terms such as high, medium, and low, and then modify these relationships. FxX nX
This article will thus mention the latter as well as the former. U,`F2yD/!
The former two bear a close relation to a fuzzy Cartesian product. gqAN
-b'
Importance zL+M-2hV
)
M[Jy?b)
23 pWGIA6&v(
The emphasis is on an implementation of a general approach to rule based decision ][T>052v
making. .18MMzdN
Consideration / Attention #fF';Y7
Careful evaluation is necessary to ensure A6F/w
Such a formulation does not change further considerations. LkJ-M=y
Considerable attention has been paid to Z@#kivcpz
Attention should be paid to an important finding of this investigation. Y#Pg*C8>8
Caution should be exercised in this process to avoid ... Ar$Am
Primary consideration is given to ... components, though others can be accommodated ){i
9,u")
After ... has been defined by ..., a carefully analysis is carried out/performed to determine s !HOrhV
A number of factors such as ...need to be taken into consideration before making the eq36mIo
appropriate decision. hzy#%FaB
It should be noted that WNV}@
It is important to point out that ... &;%LTF@I,
These considerations have heightened interest in the possibility of providing ... )>^!X$`3
We should stress the fundamental importance of the xx ?xCWg.#l4V
Results. 1:q5h*
Advantages / Disadvantage k iY1
One of the major advantages of this new measure of xx is that it can be applied to the IaR D"oCH
experimental study of 6t`cY
One advantage of using a .. is the ease of preparing it. _2S(
*
It has a very fast decision making process b(:U]>
J
All the algorithms involve mostly logical operations. JE/Kf<
It can be easily and without additional cost implemented in a microprocessor;based 1ihdH1rg[
environment. ;Z{jol
It can reduce the waste of designing from scratch. rW0-XLbL5H
The advantages of using a xx to represent xx are the following: : ]~G9]R`
However, xx is not without its shortcomings. r/mKuGa]
In most cases, the xxx shows an improvement over the existing xxx. /gq
VXDY+`
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. >Y"Ru#Ju9
The "best case" results shows a savings of 6% to 9%. pK@8= +
Most of the existing works based on xx approach can only recognize a xx . jB%aHUF;
Most of the above methods are computational expansive and limited to xx. L+2<J,
Some other advantages of xx are the following: 6Y&`mgMF'
The problem is the limitation of this method to a limited domain of parts. ._US8
It proved limited in application because it demanded precision in system modeling that [$%O-_x
was impossible in practice.
{Z(kzJwN
There are advantages to be gained in the structuring of costs and benefits, the use of xx, RD0=\!w *5
The disadvantages of this method are also disadvantages of conventional xx approaches. 58o'Q
This combines the best features of both techniques 4S3uzy%
24 n]fMl:77
Hopefully, this tool can be as the reference framework of for developing a xx platform, =/MA`>
and helping the administration, marketing, and knowledge management activities in &-hXk!A
virtual communities. Vo8gLX]a
Results X6SWcJtSw
An improvement on the result shown above can be made by based on the data provided :2(U3~3:
Recent work has identified `(o:;<&3
Time-dependent changes of HGlQZwf
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase oZ,_ G,b^
and does not require ERK activation. G#nZ%qQ:I
Much of the current work on 'j(F=9)
Discussion of these theories is beyond the scope of this review )4e?-?bK!
Based on the information contained in this XsbYWJdds
The result can be categorized into nine classes =C 7 WQ
The results are illustrated by an example FDC
c?>,o
The experimental results for each xx time are reported in Table 2. &r)[6a$fW
From the results obtained so far, it seem that iqr/MB,W
Because of the inaccuracy of the ..., a conclusion cannot be drawn as
Bvsxn5z+:
Although much effort has been made to., this reality is far from completion. )J{.z
The results indicate that the total benefits are higher than the total costs. Xli$4 uL
Their results may then serve as guidelines for lower level models, less fuzzy and more ]+A%37
detailed. p(Ux]_s%
Conclusion 7]H
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From the discussion, one may conclude that ... E.eUd4XG
The first indication that W.CbNou
In summary, we have shown that h0a|R4J
These results suggested that z}w7X6&e
Our findings have shown that qs Wy
<yL+
Our observations have provided <NWq03:&
This study reveals following five main findings: Hg5:>?Lw@
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in Z@,[a
the diabetic kidney. ,0a\Ka{^
As mentioned above, Kv9Z.DY
Moreover, we demonstrate that, V:h7}T95
A number of studies have elaborated a body of knowledge about LyH1tF
There are findings to indicate that ;2 P
On a descriptive level, there is agreement that for {$g3R@f^~
One issue that became particularly evident from our study is D$N;Qb
Our data are in agreement with the findings and models presented by previous o$Ju\(Y$<+
publications, in particular those of Jones et al `I.pwst8i-
According to our observations, rCUGaf~
…was not evident from our data jn(%v]
25 %Ai' 6
It could therefore be concluded that YPW
UncV
our data illustrate that X|-[i hp;
All these different aspects, as listed above, lead to h4#'@%
In fact, it has already been speculated that ocu,qL)W
It should be furthermore mentioned in this context that B"8jEYT5
To identify and verify the essential factors triggering developmental renin expression, it k/(]1QnW
is of interest now to study the development of intrarenal renin expression in mice with #q4uS~
defined gene mutations, using the results of this study as a reference system. Xv3pKf-K
In conclusion, using several approaches, we demonstrated that Wy%FF\D.Y
But we have not provided formal proof yet that h+ud[atk.
In summary, our results suggest that inip/&P?V
In conclusion, we identify [Q+k2J_h
A better understanding of such regulatory systems may yield novel therapeutic G[1\5dK*uR
approaches to glomerular diseases. NBHpM}1xtU
Preliminary results of short-term studies (2 weeks) indicate that AJm$(3?/D
However, we believe that =r*Ykd;W|E
However, despite our extensive measurements of these parameters, we found no LT"H-fTgs
relationship between response and initial proteinuria, time to B-cell recovery, the s&Y"a,|Z
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree <Se9aD
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be [q Uv|l1
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved X'-Yz7J?o
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and 4hODpIF
that will also look for factors that may determine its efficacy in IMN. 2j}DI"|h
It has become increasingly clear that n}
j6gN! O
Form the above discussion, the conclusion can be reached that a{.q/Tbt
The conclusions drawn are also valid P:t .Nr"
In conclusion to this, it becomes obvious that the problem of xx lies not only in... %4f.<gz~r|
We have attempted to introduce some concepts associated with a theory of QeG9CS)E}j
Considerable more work, hopefully, will be done in this area PO?_i>mA
Employing the compositional rule of inference, the assessment of the xx compatibility in (
6Od
achieving prescribed xx projectiles in any level of the hierarchy is made possible. Z Cjw)To(
This paper has presented a theoretical and experimental study of the xx process and xx //_H_ue$
concept. 3TH?7wi
The experimental research results will hopefully serve as useful feedback information for o$buoGSPc
improvements for xx work. |PlNVd2
The scope of this contribution was to introduce a xx method. kQ}n~Hn
This has a tremendous impact on our understanding of dWPQp*f2
Significant progress has been made in advancing RNAi therapeutics in a remarkably Z sTtSM\Ac
short period of time (rd
[tc
To date, little is known about… 8v4 o+wP
Irrespective of the mechanisms and the molecules –which are still largely unknown – =I'3C']Z W
involved in MSC functions, current data suggest that ^w.hI5ua)
To better understand +
7^p d9F.
26 Ch_rV+
Future Research (常用于conclustion 的结尾) [YfoQ1
Thus, first extension of the approach could be, iU;e!\A
Further studies are needed to determine the importance of akxNT_
Some improvements to the scheduling aspect of the model may be brought through fq]PKLW'
additional levels in the hierarchy for more detailed representation of the scheduling S@FO&o 0
activity. \A"o[A2v
It also unveiled new aspects of the role played by thyroid hormone in response to injury >sfg`4
and tissue repair. 15\m.Ix
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and S3E,0%yo+)
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of t>I.1AS
drug molecules. &0Yg
:{k$
In the next few years it should become clear whether 8Ojqm#/f
It should be an exciting time for researchers seeking to harness this powerful endogenous 8AuBs;i
pathway to treat human disease. aa`(2%(:
Acknowledgement QO/0VB42
The authors are grateful to the insightful work provided by Mr. John W. Harney and all ["Ltqgx
of the fellows and students that contributed with some of the studies discussed in this G^~[|a4`
article -
{cHp
I would like to express my gratitude to all those who gave me the possibility to complete O?JJE8~']
this thesis. -n|bi cP
I want to thank the Department of Transport of the former Interim Government of elOeXYO0
Namibia for giving me permission to commence this thesis in the first instance, to do the `p\=NP!n
necessary research work and to use departmental data J:L+q}A
This work was supported by NIH grants AI058695 and AI056900. We thank members of HTJ2D@h
the laboratory and our collaborators for many useful suggestions. 5i!Q55Yv=,
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. _FY&XL=
Duckman for graphics assistance and A. Capobianco for word processing assistance. k$w~JO!s
Author contributions +I3jI <
All authors were involved in experimental planning and data analysis and contributed to b(H{i}{]
manuscript preparation. ti\
${C3
Tables and Figures gg'1q3OjM
Figure 7-1 sketches these relationships. yB b%#GW
The graphical representation of these functions is shown in Figure 1. v= 55{
The xx may be depicted as in Figure 1. ?+yr7_f3*
Figure x shows the schematic diagram of the d7OygDb <
Figure 1 though 2 provide a ... that F "@% 7xy
the architecture of this expert system for .... is illustrated in Figure 2. e~o!Qm
Figure 2 gives the outline of an ... system Jh26!%<Bl
Table shows the diq}\'f
27 {f/qI`
Time-dependent changes of 9BCW2@Kp
as shown in Table 1 and 2 bjZJP\6
This concept is illustrated in Figure 2 +HK4sA2;
At the top of Table xx are shown two blocks of data. =
tv70d'
Each table or matrix has constructs xx through xx as row;headings, ~f/|bcep
xx through xx as column;headings. `zd,^.i5~
Time course of calculated renin immunoreactive tissue volumes during development of `+7F H
the mouse kidney. Data are single values per time point. They were derived from the z+"tAVB[i
kidneys shown in Figure 1. &qv~)ZM$
Yellow color indicates }V?m
=y [
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then th?+TNb^
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were zp:
dArh0
analyzed by western blot using phospho-specific antibodies. -^_m(@A<~
ERK and PKB activation were measured by western blot using phospho-specific =u.@W98, K
antibodies B}e/MlX3M
The data are the means of three different experiments taking the number of untreated cells |{(<A4W
(vehicle alone) as 100%. xL}i9ozZ
ERK and PKB activation were then analyzed by western blot with the corresponding |;ztK[(
phospho-specific antibodies. To ensure equal amount of protein in each lane, western ]vrZGX
a+
blots against total protein were performed for ERK and PKB. ClG%zE&i
The means of optical density (OD) values of the bands detected in western blots of three
L9GLjRp-
different experiments are plotted, taking the maximal value of phosphorylation of ERK F%OP,>zl
and PKB as 100%. L2}\Ah"[
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with ?
SFBUX(p
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then AdX))xgl
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence 4TtC~#D:
microscopy (lower panel). N*Y[[N(
The data are the means of three experiments performed on different days taking the +m=b
"g
number of cells at the onset of the experiment as 100%. qu=~\t1[6
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction Tz
@<hE
(n=9 each). 1d^~KBfv
*P<0.05 versus non-nephritic rats. "LBMpgpU
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, XlppA3JON|
positive control, M, molecular weight markers). v%tjZ5x
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. >xWS>
Data are means s.d. of four independent experiments. eG=d)`.JaV
*P<0.05 versus 0.5 h. `<XS5h
h=
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 xIdb9hm<
mRNA as determined by real-time RT-PCR and normalized to QiCia#_
glyceraldehyde-3-phosphate dehydrogenase mRNA. u[a-9^&g
Cell number was counted in duplicate using a Malassez hemocytometer eI8o#4nT
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with aDS:82GMQ
MCDB media for 24 h, #P<0.05. ~OD6K`s3
28 35h|?eN_m!
The curves are adjusted for history of coronary artery disease, CRP, and progression to b(Y
ESRD. ?QP>rm
Both models are independent of age, gender, baseline GFR and proteinuria, and other [P2>KQ\
clinical characteristics and traditional and nontraditional cardiovascular risk factors B`SX3,3
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH x[A|@\
Z
(n=99, P<0.0001, r2=0.190) oodA&0{)d
Concentration of serum FGF23 concentration before starting and at the end of the 4-h KOixFn1
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, <bcf"0A
Student's paired t-test). _Sj
j|j
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; =!Ik5LiD
arrow=endothelial cell and CD=collecting duct wgz]R
Magnification: 1000. v.ZUYa|
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