18 L~I<y;x
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number 4h:Oo
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The DtXXfp@;
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at _
CXKJ]m4
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The sjWhtd[fgG
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 `lN1u'(:
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, :4]&R9J>o
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive H6bomp"
control for Ca2+ induction. The data thus obtained was analyzed with the software Win `:i|y
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on |K aXek
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10
XRJ<1w:
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were "EWU:9\0
harvested and fractionated as detailed above, and the S-100 fractions were assessed by (<itE3P
immunoblotting for presence or absence of annexin I. \eI )(,A
Mouse bone marrow transduction and transplantation. <LzN/I aJ
Retrovirus-mediated transduction of mouse bone marrow cells was done by published 9]1-J5iO
methods49. Prestimulated low-density bone marrow cells were infected with high-titer e`<=&w
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated
AN$}%t"
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing }Jjq
] lW
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by x%vt$dy*8
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) ^^3
>R`
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone kx]f`b
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis ?n? Ep [D
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of Vnv<]D
zC
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was F 3,hx
confirmed by immunoblot analysis. goIn7ei92
Determination of renal morphology sJt&`k Z
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an 1,,o_e\nn3
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, TcO@q ]+S
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner
OHp 121
for morphologic alterations, as previously detailed fVb&=%e
Patient population y9Yh%M(
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) 1i2jYDB"
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per <y-KWWE
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) Y]B2-wt-
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. K
s8S^77
The Mayo Institutional Review Board and the Research Ethical Board, University Health HQQc<7c",
Network, University of Toronto approved the study protocol. All patients gave written pYceMZ$
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or \qNj?;B
19 2+sNt6B2
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 Z3~$"V*ZB{
months were not included in the study. Patients with active infection, diabetes, or a
Tx`;y|
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), sW3-JA]
medications, malignancies) were also excluded. [=S@lURzm@
Treatment qD7#q]
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of ) i.p[
high-quality protein) diet was recommended and patients were encouraged to maintain oizD:
|
the same diet throughout the duration of the study. All patients received a similar 6@ToPbj4
conservative treatment regimen that included loop diuretics to control edema, an pWO,yxr:
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. l?pZdAE
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added 2Z\6xb|u
when required to control systolic blood pressures to <135 mm Hg in >75% of the
O292JA
readings. Patients who after a minimum of 4 months of conservative therapy and TL1pv l
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of xzz[!yJjG
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, ,*
@m<{DX)
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine t
/EB
y"N#
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given 1Xu\Tm\Ux
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count tceQn
^|<
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count V[HHP_
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per a4 O
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a h<$V ry}
second course of rituximab treatment following the same protocol described above. bJx{mq
Follow-up .px*.e s
In all patients, clinical and laboratory parameters including complete blood counts, ]9l=geZd%;
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum "m3u}!`3
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry `Ft.Rwj2:m
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion iKv{)5
in the urine were assessed by performing two consecutive 24-h urine collections at each f)({;,q
time point. Data were considered accurate when urinary creatinine excretion was 4[ "$}O5
consistent with a complete 24 h collection. The mean of the two measurements was )^|zuYzN
considered for the analysis. The presence of HACAs was evaluated at baseline and at ]RML;]^
months 3, 6, 9, and 12. yLW iY~Fd
Method / Approach / Study/ Technique #?@k=e\
A discussion is presented of a problem-solving system L@_IGH
To improve the efficiency of the method, the following approach may be applied. lo,?mj%M
In order to an investigation was made to find the causes of the QNLkj`PL/
Although large collections of rules and equations have been complied, none are generally Gm}ecW
accepted ;4z6="<Y
20 g|9'Lk
This approach will be explained and discussed thoroughly in the body of the report. 2~<?E`+
This can be accomplished by $*Njvr7
This algorithm to compute the total cost can be described step by step as follows: ?}D@{%O3T
The above preliminary analysis has provided important information a<k x95
Various methods have been proposed for selecting an optimum... "]f0wLzh
These concepts have been applied to ~gNa<tg"1
On the basis of the concept mentioned above, O3bo3Cm$
This can be achieved by )(oRJu)y
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the "~:o#~F6
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, |2,u!{
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced x=pq-&9>B
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 _Jn-# du
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada aze}koNE
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% +!\$SOaR{
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections 2%y}El^+_
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin l ~kxt2&
complex. Sections were counterstained with hematoxylin and examined by light 494"-F 6
microscopy. `rzgC \
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay 9!6sf
GZ
performed at Genentech Inc. that measures the antibody response to rituximab in human WI/&r5rq
serum samples. w~wpm7
In all patients, clinical and laboratory parameters including complete blood counts, o(Yj[:+m
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum 59A@~;.F
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry B~K@o.%
and at months 1, 3, 6, 9, and 12. r8x<-u4
This fact suggests that a new concept %;$zR}
This was accomplished by taking ... MwMv[];I
The preparatory stage is very time consuming process. = s^KZV
Test are performed for validity, completeness, and compatibility 5]D"y Ay81
There is little hope of achieving successful ... SC/|o
There has been an increasing awareness of the potential of using most ..so far made have .21[3.bp/q
not taken this approach, with the exception of P/uk]5H^
Only a few studies can be found. F)rU*i7
It is a very tedious process to go through EF1aw2
It is only when .. has been completed that .. may be effected F*Lm=^:
The entire interpretation process is conducted in one's head. J<J_yRg2
These approaches are sometimes very tedious. gbF^m`A>%+
Several techniques can be used MD`1KC_m
A polynomial parametric model can be written as [the following]/[follows]: t<~$?tuZ
A xx model is constructed/formulated using xx. x
xMV2&,Jq
A xx model represents an xx by its xx. RE~:+.eB
A process decision model captures the logic essential to 2rK%fV53b
From the equation above, xx is equal to the summation of xx times the ... ';<gc5EK
21 W6cA@DN$#
The validity of a xx model can be checked using Euler's formula. L<8:1/d\
Given a model, one can mathematically determine whether ... or ... ;.Dm?J0
Equations for xx need to be derived and implemented in the system. QAs$fi}f]s
A number of heuristic rules have been developed for -n.ltgW@
Optimum .. techniques can be made more reliable by ... so that ;Oh abbj*
An algorithm based on the characteristic ... is used to determine ~{-zj
Euler's formula states the following: )qxZHV
The completed model should agree with the formula. 2|Of$oMc
For manufacturing purposes, a detailed and precise model of the object is necessary hRKAs
]^j
Engineering design models are very well defined; therefore, |/Q7 o1i
To keep the domain narrow enough to be implementable, yet wide enough to be useful.
v E4ce
Point of View j A/xe
from an implementation standpoint, Na6z1&wS
From the point of view of this application, %5) 1^
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). ,_ zivUU
Information is the meaningful interpretation and correlation of some aggregation of data k(<:
in order to allow one to make decisions. a!OS2Tz:
From a practical point of view, the computational aspects of an FLC require a wOfx7D
simplification of the fuzzy control algorithm. kX0hRX
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, '*`25BiQ
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM G{wIY" ~4
p.129] >a6{y
Statistical analysis |@Cx%aEKU
Data were analyzed by one-way analysis of variance comparing the three conditions osBwX.G'l
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If QJeL&mf
significant F-statistic from analysis of variance existed, this test was followed by Dunnett 8XS_I{}?
post hoc multiple comparison procedure with sham operation as the control group. For all tWT,U[
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as &?(<6v7
statistically significant. 5uo?
KSX%
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney pJnT \~o
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, 8Uv2
p{ <#
CA, USA). {c(@u6l28
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was ,b b/
$
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's
PG51+#
test, where appropriate. X-lB1uq^
Data are expressed as mean s.d., median and interquartile range, or frequencies, as Fj_
6jsDb
appropriate. Variables who deviated from the normal distribution (positively skewed) %oee x1`=
were log-transformed (log10) before the correlation study. u0o}rA
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test ;?q>F3n
post hoc analysis of variance were used as indicated below, for the comparison of t9U-c5bR
22 ?W27
h
morphological, immunohistological and functional parameters. Statistical significance D
,U#z
was set at P<0.05. uQ(C,
f[6p
The primary efficacy parameter was defined as change in urinary protein excretion from Y<ZaW{%
baseline (week 0) to 12 months after treatment. The 12-month changes were tested 8@)4)+e
against zero using the paired t-test. Secondary end points included 6-month changes in ]Yw/}GKB
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular _aaQ1A`p
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on lihV! 1
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. mw!EDJ;'
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d.
BH<jnQ
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 K(:
_52rt
Definition of remission status is according to the criteria established by Cattran et al.30 r8wip\[
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a fZ6-ap,u
>50% reduction in peak proteinuria and non-response as <50% reduction in peak yGs:3KI
proteinuria. Any patient reaching a CR or PR was considered a treatment success =qNZ7>Qw
The statistical significance of differences for the mean values of cytokine concentration {L#+v~d^'n
and T cell proliferation was determined with Student's t-test. Differences with a P value
L7rEMq
of less than 0.05 were considered significant. qt.Y6s:r_
Statistical significance was determined by Student's t-test. Data with a P value of less |bM?Q$>~
than 0.05 were considered significant. ssUm1F\
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P xE"QX
N
values less than 0.05 considered statistically significant. },& =r= B
The significance of differences among groups was determined by Student's t-test and 713)D4y}
one-way analysis of variance (SigmaStat software; Jandel). fnJ!~b*qo
Comparisons "3H?_!A9
As well, the pros and cons of these representations from a process planning point of view *B0
7-
will be discussed. ?E|be
)
The method of using xx to implement xx described by Zadeh (1973) appeared more ^;DbIo\6H
suitable {[tx^b
As discussed [in the previous section]/[preciously], rE5q
BEh
Relation [}1+=Ub
We can not invert F' directly because it defines a many-to-one mapping. i4g99Kvl
The relationships appear very complicate e
N Y?
Lifting tasks involve complex and imprecise relationship between the task variables and H]a@"gO
the human operator's characteristics. x/]]~@:
These methods are based on the relationship between ... and ... 1^R:[L4R`
The fundamental concept of a fuzzy rating language is that we can establish a relationship JQdeI+
among terms such as high, medium, and low, and then modify these relationships. _N2tf/C&=
This article will thus mention the latter as well as the former. W9A
[Z
The former two bear a close relation to a fuzzy Cartesian product. |.;LI=CT
Importance W%&'EJ)62
) 'du{ky
23
(Tbw@BFk
The emphasis is on an implementation of a general approach to rule based decision 18{" @<wIs
making. idLC
q^jnJ
Consideration / Attention D$$,T.'u
Careful evaluation is necessary to ensure 6d%'>^`(o-
Such a formulation does not change further considerations. :f|X$>
b
Considerable attention has been paid to %^VQw!
Attention should be paid to an important finding of this investigation. fD:>cje
Caution should be exercised in this process to avoid ... Or9`E(
Primary consideration is given to ... components, though others can be accommodated @2eV^eO9
After ... has been defined by ..., a carefully analysis is carried out/performed to determine \Tii
S
A number of factors such as ...need to be taken into consideration before making the #Emz9qTsce
appropriate decision. rh%-va9
It should be noted that `E4OgO
It is important to point out that ... <xpHlLc
These considerations have heightened interest in the possibility of providing ... g-cC&)0Q
We should stress the fundamental importance of the xx }M+2 ,#l
Results. v?S~
=$.
Advantages / Disadvantage tUR9ti
One of the major advantages of this new measure of xx is that it can be applied to the TA~YCj$
experimental study of KE
k]<b=
One advantage of using a .. is the ease of preparing it. HGJfj*JH
It has a very fast decision making process nL[zXl
All the algorithms involve mostly logical operations. hExw} c
It can be easily and without additional cost implemented in a microprocessor;based 2*<'=*zaQ
environment. $*Z Zh
It can reduce the waste of designing from scratch. >*"6zR2 o
The advantages of using a xx to represent xx are the following: vKCgtk
However, xx is not without its shortcomings. buv*qPO
In most cases, the xxx shows an improvement over the existing xxx. O*d4zBT
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. /e0cx:.w
The "best case" results shows a savings of 6% to 9%. 0-9.u`)#yu
Most of the existing works based on xx approach can only recognize a xx . <P"4Mk7`s
Most of the above methods are computational expansive and limited to xx. G L> u3K
Some other advantages of xx are the following: hDf|9}/UQd
The problem is the limitation of this method to a limited domain of parts. m
<cvx3e
It proved limited in application because it demanded precision in system modeling that ydyGPZt
was impossible in practice. 7wU$P
There are advantages to be gained in the structuring of costs and benefits, the use of xx, (
^ Q:zU
The disadvantages of this method are also disadvantages of conventional xx approaches. W"@FRWcd
This combines the best features of both techniques 3Q@HP;<
24 h6Vm;{~
Hopefully, this tool can be as the reference framework of for developing a xx platform, t#0/_tD
and helping the administration, marketing, and knowledge management activities in ]-D;t~
virtual communities. +[DL]e]@U
Results P2+Z^J`Y>
An improvement on the result shown above can be made by based on the data provided +cw;a]o^>
Recent work has identified onuhNn_=>
Time-dependent changes of j3W)5ZX
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase BK_x5mGu3
and does not require ERK activation. (v\Cv)OS
Much of the current work on w;;.bz m
Discussion of these theories is beyond the scope of this review ?Q< o-o;B
Based on the information contained in this J)w58/`?t
The result can be categorized into nine classes k]n=7vw;
The results are illustrated by an example 6tE<`"P!
The experimental results for each xx time are reported in Table 2. mv1_vF:
From the results obtained so far, it seem that *Q<%(JJ
Because of the inaccuracy of the ..., a conclusion cannot be drawn as zk[%YG&
Although much effort has been made to., this reality is far from completion. S=^a''bg
The results indicate that the total benefits are higher than the total costs. P8JN
m"C
Their results may then serve as guidelines for lower level models, less fuzzy and more *S).@j\{W
detailed. bBQ1~ R
Conclusion JZ[~3swR
From the discussion, one may conclude that ... n=vW oU9
The first indication that V}l>p?
In summary, we have shown that $lj1924?^
These results suggested that fz`+j
-u
Our findings have shown that =H_|007C
Our observations have provided %bnDxCj"
This study reveals following five main findings: MorR&K
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in tQy@d_a=y
the diabetic kidney. P`'Nv
As mentioned above, 6g*B=d(j
Moreover, we demonstrate that, djeax
A number of studies have elaborated a body of knowledge about a*d>WN.;U
There are findings to indicate that (hefpqpi
On a descriptive level, there is agreement that for A f@IsCOJ
One issue that became particularly evident from our study is @Z.s:FV[
Our data are in agreement with the findings and models presented by previous iHo2=Cz
publications, in particular those of Jones et al Oo<^~d2=
According to our observations, '&5A*X]d
…was not evident from our data L&F0^
25 ?]}1FP
It could therefore be concluded that 9l?#ZuGXp
our data illustrate that />(e.)f
All these different aspects, as listed above, lead to qZlb?b"
In fact, it has already been speculated that &
ZgB b
It should be furthermore mentioned in this context that mh>)N"
To identify and verify the essential factors triggering developmental renin expression, it n83,MV?-
is of interest now to study the development of intrarenal renin expression in mice with :tY;K2wDM
defined gene mutations, using the results of this study as a reference system. N<$U:!Z
In conclusion, using several approaches, we demonstrated that ;"=a-$vm
But we have not provided formal proof yet that 2E^zQ>;01
In summary, our results suggest that DQ^yqBVgQ
In conclusion, we identify 4f
<%<Z
A better understanding of such regulatory systems may yield novel therapeutic 5An|#^]
approaches to glomerular diseases. CRvUD.D
Preliminary results of short-term studies (2 weeks) indicate that w+bQpIPM
However, we believe that x|G#oG)_
However, despite our extensive measurements of these parameters, we found no s8.O L_e
relationship between response and initial proteinuria, time to B-cell recovery, the Af5O;v\
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree dL'hC#!h
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be wxpE5v+f|
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved L,0HX
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and
.Ya]N+r*
that will also look for factors that may determine its efficacy in IMN. O.e^?ysp/
It has become increasingly clear that MCU{@\?Xf
Form the above discussion, the conclusion can be reached that &*RJh'o|N(
The conclusions drawn are also valid @yPa9Ug(V
In conclusion to this, it becomes obvious that the problem of xx lies not only in... v:(_-8:F
We have attempted to introduce some concepts associated with a theory of HJ]\VP9Zb
Considerable more work, hopefully, will be done in this area Qfr%BQV
Employing the compositional rule of inference, the assessment of the xx compatibility in 0l !%}E
achieving prescribed xx projectiles in any level of the hierarchy is made possible.
'n%Ac&kk
This paper has presented a theoretical and experimental study of the xx process and xx \2)a.2mAz
concept. 'h_PJ%
The experimental research results will hopefully serve as useful feedback information for bvz
eU
n
improvements for xx work. C72?vAc,F
The scope of this contribution was to introduce a xx method. /~V.qisZ
This has a tremendous impact on our understanding of y-O#
+{7
Significant progress has been made in advancing RNAi therapeutics in a remarkably (nfra,'
short period of time SC)4u l%
To date, little is known about… |rkj$s,
Irrespective of the mechanisms and the molecules –which are still largely unknown – I^sWf3'db
involved in MSC functions, current data suggest that Z W`
Ur>
To better understand EL$"MT}p
26 G=a.Wff
Future Research (常用于conclustion 的结尾) o-2FGM`*VB
Thus, first extension of the approach could be, bs$x%CR
Further studies are needed to determine the importance of [,)yc/{*
Some improvements to the scheduling aspect of the model may be brought through
IE!fNuR4
additional levels in the hierarchy for more detailed representation of the scheduling &hWLG<IE
activity. [?VYxX@
It also unveiled new aspects of the role played by thyroid hormone in response to injury [vb>5EhL!
and tissue repair.
p%
ESp&
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and Bi2be$nV
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of +hL+3`TD#H
drug molecules. CLU !/J$!
In the next few years it should become clear whether c0jdZ#H
It should be an exciting time for researchers seeking to harness this powerful endogenous 6r"uDV #0
pathway to treat human disease. -]c5**O}
Acknowledgement YgiwtZ5FY
The authors are grateful to the insightful work provided by Mr. John W. Harney and all s.+2[R1HF
of the fellows and students that contributed with some of the studies discussed in this ^~}|X%q3
article D ODo
!
I would like to express my gratitude to all those who gave me the possibility to complete &RP!9{F<
this thesis. xMJF1O?3
I want to thank the Department of Transport of the former Interim Government of Dgh|,LqUB
Namibia for giving me permission to commence this thesis in the first instance, to do the .E:[\H"
necessary research work and to use departmental data ^Cb7R/R3
This work was supported by NIH grants AI058695 and AI056900. We thank members of $,"{g
<*k;
the laboratory and our collaborators for many useful suggestions. SvC|"-[mJ
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M.
"8|y
Duckman for graphics assistance and A. Capobianco for word processing assistance. A3ad9?LR[R
Author contributions a*JM2^,HO
All authors were involved in experimental planning and data analysis and contributed to r
*]0PQ{?
manuscript preparation. iK{q_f\"
Tables and Figures :/fG %e
Figure 7-1 sketches these relationships. fU^B
3S6X
The graphical representation of these functions is shown in Figure 1. O-B~~$g
The xx may be depicted as in Figure 1. ,GEMc a,`
Figure x shows the schematic diagram of the {H s""/sb
Figure 1 though 2 provide a ... that ]4SnOSV?S
the architecture of this expert system for .... is illustrated in Figure 2. {V%ZOdg9
Figure 2 gives the outline of an ... system ;AKtbS;H
Table shows the q]q(zUtU
27 +:1ay
^YI
Time-dependent changes of )l*H$8
as shown in Table 1 and 2 @OAX#iQl
This concept is illustrated in Figure 2 cAC2Xq
At the top of Table xx are shown two blocks of data. ?cdSZ'49[
Each table or matrix has constructs xx through xx as row;headings, vai.",b=n6
xx through xx as column;headings. 6~GaFmW=
Time course of calculated renin immunoreactive tissue volumes during development of %lNWaA
the mouse kidney. Data are single values per time point. They were derived from the w=\Lw+X
kidneys shown in Figure 1. \lHi=}0
Yellow color indicates Pa2HFy2
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then vgOmcf%;
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were :xZ/c\
analyzed by western blot using phospho-specific antibodies. 'dM &~LSQ
ERK and PKB activation were measured by western blot using phospho-specific A$ %5l
antibodies @va{&i`%A7
The data are the means of three different experiments taking the number of untreated cells Mo
&Ia6^
(vehicle alone) as 100%. \*6%o0c
ERK and PKB activation were then analyzed by western blot with the corresponding "-XL Y_
phospho-specific antibodies. To ensure equal amount of protein in each lane, western cRz7.9-<
blots against total protein were performed for ERK and PKB. x(3E#7>1
The means of optical density (OD) values of the bands detected in western blots of three i\2MphS
different experiments are plotted, taking the maximal value of phosphorylation of ERK 2N)=fBF%-
and PKB as 100%. %^^2
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with "m})~va
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then +^<CJNDL9
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence \l_
RyMi
microscopy (lower panel). ;3Fgy8T
The data are the means of three experiments performed on different days taking the h0Acpd2
number of cells at the onset of the experiment as 100%. eOy{]<l3
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction 9cFFQM
|o
(n=9 each). * kgbcU f8
*P<0.05 versus non-nephritic rats. 65N;PH59D
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, -,q&Zm
positive control, M, molecular weight markers). C2AP
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. Ia)wlA02S
Data are means s.d. of four independent experiments. G9 z Q{E
*P<0.05 versus 0.5 h. =r+u!~%@''
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 W>dS@;E
mRNA as determined by real-time RT-PCR and normalized to ~zRUJ2hD!
glyceraldehyde-3-phosphate dehydrogenase mRNA. ho#]?Z#
Cell number was counted in duplicate using a Malassez hemocytometer Ha$|9li`
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with ^o !K0t*
MCDB media for 24 h, #P<0.05. V;=SncUb
28 ma~WJ0LM\
The curves are adjusted for history of coronary artery disease, CRP, and progression to J\_tigd
ESRD. vb9G_Pfz
Both models are independent of age, gender, baseline GFR and proteinuria, and other _zJY1cr
clinical characteristics and traditional and nontraditional cardiovascular risk factors +
R])u5c'
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH PQ@(p%
(n=99, P<0.0001, r2=0.190) mY(~94{d
Concentration of serum FGF23 concentration before starting and at the end of the 4-h .pu]21m
=
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, GUmOK=D >
Student's paired t-test). oQ8W0`bZa
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; n1DD+@
arrow=endothelial cell and CD=collecting duct L\nWhmwl
Magnification: 1000. }_3<Q\j
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