18 26c,hPIeXY
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number JO4rU-
n
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The oCBZ9PGkK
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at ;_.%S *W\
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The R).?lnS
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 M>pcG.6V
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, l@x/{0
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive XNwZSW
control for Ca2+ induction. The data thus obtained was analyzed with the software Win ]*8K4n G
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on 9Ytf7NpR
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 H5f>Q0jq
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were Hoaf3
`n
harvested and fractionated as detailed above, and the S-100 fractions were assessed by o<*H!oyP\
immunoblotting for presence or absence of annexin I. H1]An'qz,
Mouse bone marrow transduction and transplantation. ZgN )sVJ
Retrovirus-mediated transduction of mouse bone marrow cells was done by published nQ*9|v4
methods49. Prestimulated low-density bone marrow cells were infected with high-titer <<zYF.9L]
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated XY[uyR4Z
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing >a@c5
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by xwZcO
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) a9CY,+z5B
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone [
7W@/qqv
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis ^f:oKKaAW;
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of (x{6N^J.t
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was ggr\nY
confirmed by immunoblot analysis. <,%qt_
!
Determination of renal morphology lg)jc3
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an R<}n?f\#JZ
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, .w/_Om4T*b
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner Zrtyai{8l
for morphologic alterations, as previously detailed <r_L-
Patient population Q+
r4
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) t(-`==.R
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per 8+ P)V4}
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) _e%jM[
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. ~J}{'l1{yf
The Mayo Institutional Review Board and the Research Ethical Board, University Health Q`nsL)J
Network, University of Toronto approved the study protocol. All patients gave written Xx~ za{p
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or %?gh;? GD
19 3jMHe~.E<
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 YK[PC]w
months were not included in the study. Patients with active infection, diabetes, or a PNwXZ/N%
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), GCn^+`.h1t
medications, malignancies) were also excluded. 1]wx Ru
Treatment pIKQx5;
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of XG]ltSOy
high-quality protein) diet was recommended and patients were encouraged to maintain Bnju_)U5)
the same diet throughout the duration of the study. All patients received a similar 6%/@b`vZ
conservative treatment regimen that included loop diuretics to control edema, an F!FXZht$P
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. 0'Kbh$LU
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added Q;m:o8Q5
when required to control systolic blood pressures to <135 mm Hg in >75% of the &/K:zWk3mx
readings. Patients who after a minimum of 4 months of conservative therapy and XUf]gQu3=
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of MdzG2uZT
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, }pP<+U
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine 4CR.=
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given 9,h'c
f`F
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count RQzcsO
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count *XRAM.
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per >heFdKq1
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a i
*W9 4
second course of rituximab treatment following the same protocol described above. ich\`j[i
Follow-up _wa1R+`_
In all patients, clinical and laboratory parameters including complete blood counts, 4wLp
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum Tvd=EO
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry R)s@2S
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion yQkj4v{
in the urine were assessed by performing two consecutive 24-h urine collections at each %G~f>
time point. Data were considered accurate when urinary creatinine excretion was dW3 q
consistent with a complete 24 h collection. The mean of the two measurements was zLQplw`#
considered for the analysis. The presence of HACAs was evaluated at baseline and at Ol8ma`}Nq3
months 3, 6, 9, and 12. P
I gbeP
Method / Approach / Study/ Technique tvH{[e$
A discussion is presented of a problem-solving system ~(2G7x)
To improve the efficiency of the method, the following approach may be applied. `mU'{
In order to an investigation was made to find the causes of the G813NoS o
Although large collections of rules and equations have been complied, none are generally <mE)&7C
accepted p4k*vuu>
20 ulM6R/V:?
This approach will be explained and discussed thoroughly in the body of the report. V
#!ftu#c?
This can be accomplished by
Vj^<V|=
This algorithm to compute the total cost can be described step by step as follows: ocwh*t)<k
The above preliminary analysis has provided important information Y|bCbaF
Various methods have been proposed for selecting an optimum... S<Zb>9pl
These concepts have been applied to !(=bH"P
On the basis of the concept mentioned above, v#EXlpS
This can be achieved by :cv_G;?
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the E}S)uI,gn
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, &M$s@FUY
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced ve.rpF\
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 o,a3J:j]
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada ]$)J/L(p/]
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% Q>y2C8rnJ/
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections }a= &o6=
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin m
S[Vl6
complex. Sections were counterstained with hematoxylin and examined by light sMh3IL9(*
microscopy. a}l^+
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay ?A7&SdJaO
performed at Genentech Inc. that measures the antibody response to rituximab in human D.G+*h@ g
serum samples. /M>8ad
In all patients, clinical and laboratory parameters including complete blood counts, &E.ckWf
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum Yrp
WGK520
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry 6AgevyVG
and at months 1, 3, 6, 9, and 12. Qn>0s
This fact suggests that a new concept {4"!~W
This was accomplished by taking ... j*"V!d
The preparatory stage is very time consuming process. eaQ)r?M
Test are performed for validity, completeness, and compatibility o@[yF<
There is little hope of achieving successful ... 9I*zgM!F
There has been an increasing awareness of the potential of using most ..so far made have 3P C'P2
not taken this approach, with the exception of wPTXRq%
Only a few studies can be found. T
'p
X)ZH
It is a very tedious process to go through w|?<
;+
It is only when .. has been completed that .. may be effected R.Xh&@f`
The entire interpretation process is conducted in one's head. 9J%
~?k
These approaches are sometimes very tedious. ?.#?h>MS{s
Several techniques can be used d*ch.((-
A polynomial parametric model can be written as [the following]/[follows]: Q/ rOIHiI
A xx model is constructed/formulated using xx. 0?525^
A xx model represents an xx by its xx. E/@w6uIK[
A process decision model captures the logic essential to \O
9j+L"
From the equation above, xx is equal to the summation of xx times the ... R%iyNK,
21 1wpT"5B
The validity of a xx model can be checked using Euler's formula. ?qwTOi
Given a model, one can mathematically determine whether ... or ... mZsftby}
Equations for xx need to be derived and implemented in the system. BE/#=$wPjM
A number of heuristic rules have been developed for n@[&SgZq
Optimum .. techniques can be made more reliable by ... so that q6'3-@%
An algorithm based on the characteristic ... is used to determine WT$m*I
Euler's formula states the following: YnC7e2
The completed model should agree with the formula. mB&nN+MV
For manufacturing purposes, a detailed and precise model of the object is necessary ^Nl)ocHv!
Engineering design models are very well defined; therefore, qB-9&X
To keep the domain narrow enough to be implementable, yet wide enough to be useful. L<bZVocOb_
Point of View NQzpgf|h
from an implementation standpoint, ?r"][<
From the point of view of this application, "TB4w2?=
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). ],vUW#6$N
Information is the meaningful interpretation and correlation of some aggregation of data >}{'{
Z
&
in order to allow one to make decisions. !<\"XxK+l
From a practical point of view, the computational aspects of an FLC require a !l!^`c
simplification of the fuzzy control algorithm. -#srn1A>
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, 9 ![oJ3
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM ~7aBli=
p.129] UO(B>Abp
Statistical analysis
5|2v6W!e
Data were analyzed by one-way analysis of variance comparing the three conditions OU+oS,
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If -'&4No
significant F-statistic from analysis of variance existed, this test was followed by Dunnett G!},jO*"
post hoc multiple comparison procedure with sham operation as the control group. For all z[:UPPbW
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as yIC.JmD*
statistically significant. P~nI6/r1
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney sX
m8KV
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, M,1Yce%+}
CA, USA). <4s$$Uw}6%
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was h*2Q0GRX
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's g0t$1cUR
test, where appropriate. .&d]7@!qy
Data are expressed as mean s.d., median and interquartile range, or frequencies, as "-JJ6Bk
appropriate. Variables who deviated from the normal distribution (positively skewed) 3f9J!B`n
were log-transformed (log10) before the correlation study. \F=w~
$)
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test F*QZVg+<*X
post hoc analysis of variance were used as indicated below, for the comparison of -DDH)VO
22 D&_Ir>"\
morphological, immunohistological and functional parameters. Statistical significance Qj(q)!Ku
was set at P<0.05. dA-ik
The primary efficacy parameter was defined as change in urinary protein excretion from J \U}U'qP
baseline (week 0) to 12 months after treatment. The 12-month changes were tested <(x[Qp/5P
against zero using the paired t-test. Secondary end points included 6-month changes in +T:F :X`
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular #I[tsly}
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on lVY`^pw?
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. D-*`b&i48
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. !J
")TP=
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 Gy0zh|me
Definition of remission status is according to the criteria established by Cattran et al.30 q:N"mp<%
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a 4eapR|#T
>50% reduction in peak proteinuria and non-response as <50% reduction in peak K FV&Dt}<
proteinuria. Any patient reaching a CR or PR was considered a treatment success INrl^P*
The statistical significance of differences for the mean values of cytokine concentration W 0^.Dx
and T cell proliferation was determined with Student's t-test. Differences with a P value nokk!v /
of less than 0.05 were considered significant. bnBnE[y<'
Statistical significance was determined by Student's t-test. Data with a P value of less "3CQ0
than 0.05 were considered significant. nTO,d$!Kp
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P oLVy?M%{P
values less than 0.05 considered statistically significant. s,>_kxuX
The significance of differences among groups was determined by Student's t-test and u
'-4hU
one-way analysis of variance (SigmaStat software; Jandel). @8X)hpHf
Comparisons Cv{>|g#
As well, the pros and cons of these representations from a process planning point of view :-HVK^$%
will be discussed. B3
[;}8u>
The method of using xx to implement xx described by Zadeh (1973) appeared more M\zM-B
suitable v^2q\A-?
As discussed [in the previous section]/[preciously], 1HY
rJb,d
Relation ;&4}hPq
We can not invert F' directly because it defines a many-to-one mapping. d`9%:2qE
The relationships appear very complicate 9[}L=n
Lifting tasks involve complex and imprecise relationship between the task variables and 7Pspx'u
the human operator's characteristics. _j t>%v4}4
These methods are based on the relationship between ... and ... V+My]9ki
The fundamental concept of a fuzzy rating language is that we can establish a relationship !v(j#N< m
among terms such as high, medium, and low, and then modify these relationships. 4'JuK{/ A7
This article will thus mention the latter as well as the former. b
'p0T1K(
The former two bear a close relation to a fuzzy Cartesian product. 2(V;OWY(@
Importance %9ef
[,WT
) ^hPREbD+f
23 S*,DX~vig
The emphasis is on an implementation of a general approach to rule based decision /KDKA)
making. (ZR+(+i,
Consideration / Attention Z_vIGH|1
Careful evaluation is necessary to ensure ]6)^+(zU
Such a formulation does not change further considerations. Tjba@^T
Considerable attention has been paid to Zd$a}~4~
Attention should be paid to an important finding of this investigation. feg
Caution should be exercised in this process to avoid ... =+24jHs
Primary consideration is given to ... components, though others can be accommodated Q/'jwyj_
After ... has been defined by ..., a carefully analysis is carried out/performed to determine M*ZR+pq,
A number of factors such as ...need to be taken into consideration before making the c^ $_
epc*
appropriate decision. )BI6nU
It should be noted that z7B>7}i-
It is important to point out that ... WE;QEA /
These considerations have heightened interest in the possibility of providing ... 8nCw1
We should stress the fundamental importance of the xx zJC!M
eN
Results. f|U;4{k
Advantages / Disadvantage )IN!CmpN
One of the major advantages of this new measure of xx is that it can be applied to the
GQ=Zp3[
experimental study of 7K"{}:
One advantage of using a .. is the ease of preparing it. @ol}~&"
It has a very fast decision making process P`ZzrN
All the algorithms involve mostly logical operations. \VQv
"wid
It can be easily and without additional cost implemented in a microprocessor;based z$#q'
+$
environment. NXwthc3
It can reduce the waste of designing from scratch. tOUpK20q.@
The advantages of using a xx to represent xx are the following: m
ab921-n
However, xx is not without its shortcomings. 'OrGt_U
In most cases, the xxx shows an improvement over the existing xxx. (i..7B:
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. QT\||0V~p
The "best case" results shows a savings of 6% to 9%. BQ8vg8e]B
Most of the existing works based on xx approach can only recognize a xx . HpbSf1VvAf
Most of the above methods are computational expansive and limited to xx. l', +l{\Z
Some other advantages of xx are the following: 1f3c3PJ
The problem is the limitation of this method to a limited domain of parts. S($8_u$U
It proved limited in application because it demanded precision in system modeling that <Zb~tYp
was impossible in practice. S10"yhn(-t
There are advantages to be gained in the structuring of costs and benefits, the use of xx, )P13AfK
The disadvantages of this method are also disadvantages of conventional xx approaches. %XF>k)
This combines the best features of both techniques G_ -8*.
24 0^lCZ,uq;
Hopefully, this tool can be as the reference framework of for developing a xx platform, Dx
M$4
and helping the administration, marketing, and knowledge management activities in sej$$m R
virtual communities. (5rfeSA^
Results + *xi&|%
An improvement on the result shown above can be made by based on the data provided nYFM^56>_
Recent work has identified }}?,({T|n
Time-dependent changes of M6nQ17\{
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase _^%DfMP3i\
and does not require ERK activation. $@Bd}35 J
Much of the current work on ]z77hcjB1
Discussion of these theories is beyond the scope of this review &~Hx!]uc
Based on the information contained in this ^-^ii3G`
The result can be categorized into nine classes C0K0c6A(4
The results are illustrated by an example J@}PBHK+
The experimental results for each xx time are reported in Table 2. f>CJ1;][{
From the results obtained so far, it seem that {D$5M/$
Because of the inaccuracy of the ..., a conclusion cannot be drawn as <jAn~=Uq[,
Although much effort has been made to., this reality is far from completion. m[}@\y
The results indicate that the total benefits are higher than the total costs. `R!%k]$
Their results may then serve as guidelines for lower level models, less fuzzy and more *)Us
detailed. cM_!_8o
Conclusion _LSp \{Z
From the discussion, one may conclude that ... xNd p]u
The first indication that B&+)s5hh
In summary, we have shown that ,;
@vVm'}
These results suggested that &cp
`? k
Our findings have shown that *'cyFu$
Our observations have provided E[ttamU
This study reveals following five main findings: koa-sy )#L
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in =5;t
B
the diabetic kidney. Qv
WvS9]
As mentioned above, *djVOC
Moreover, we demonstrate that, G]n_RP$G
A number of studies have elaborated a body of knowledge about tbXl5x0
There are findings to indicate that 9C
a }+
On a descriptive level, there is agreement that for xj[v$HP
One issue that became particularly evident from our study is 9$#@Oe8*
Our data are in agreement with the findings and models presented by previous %x-`Y[
publications, in particular those of Jones et al 34,'smH i%
According to our observations, b]4\$ rW7
…was not evident from our data u]*f^/6Q
25 L0)w~F
?m
It could therefore be concluded that fuU
3?SG
our data illustrate that < V*/1{
All these different aspects, as listed above, lead to ^;sE)L6
In fact, it has already been speculated that xpJ=yxO
It should be furthermore mentioned in this context that H]}mg='kI
To identify and verify the essential factors triggering developmental renin expression, it =h70!) Z5
is of interest now to study the development of intrarenal renin expression in mice with QM'|k6
defined gene mutations, using the results of this study as a reference system. AqAL)`#K
In conclusion, using several approaches, we demonstrated that ?
q_%
But we have not provided formal proof yet that UX'q64F!
In summary, our results suggest that H)h$@14xu
In conclusion, we identify qe5;Pq !G
A better understanding of such regulatory systems may yield novel therapeutic IF cre
approaches to glomerular diseases. t`Rbn{
Preliminary results of short-term studies (2 weeks) indicate that qu\U^F
However, we believe that 1En:QQ4/
However, despite our extensive measurements of these parameters, we found no I
Z|EPzS
relationship between response and initial proteinuria, time to B-cell recovery, the ^u2x26].
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree #iQF)x| D
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be F1S0C>N?5
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved 1gnLKf c
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and dlA0&;}z
that will also look for factors that may determine its efficacy in IMN. _f~$iY
It has become increasingly clear that },{sJ0To
Form the above discussion, the conclusion can be reached that +s6v!({Z
The conclusions drawn are also valid 2r!-
zEV
In conclusion to this, it becomes obvious that the problem of xx lies not only in... hE
E1i
We have attempted to introduce some concepts associated with a theory of ?,]eN&`
Considerable more work, hopefully, will be done in this area A9KPU:
Employing the compositional rule of inference, the assessment of the xx compatibility in )W6l/
achieving prescribed xx projectiles in any level of the hierarchy is made possible. K"[\)&WBG
This paper has presented a theoretical and experimental study of the xx process and xx Fn0|v66
concept. ?LJiFG]^m
The experimental research results will hopefully serve as useful feedback information for ;n.h !wmJ}
improvements for xx work. g<ov` bF
The scope of this contribution was to introduce a xx method. ~Q#!oh'i
This has a tremendous impact on our understanding of .2U3_1dX
Significant progress has been made in advancing RNAi therapeutics in a remarkably '(SivD
short period of time `\P1Ff@z0
To date, little is known about… "Ec9.#U/
Irrespective of the mechanisms and the molecules –which are still largely unknown – ]rSg,Q>E
involved in MSC functions, current data suggest that (.i wD&
To better understand &EYoviFp
26 t3g+>U_m
Future Research (常用于conclustion 的结尾) x3(
->?)D
Thus, first extension of the approach could be, cL!A,+S[_
Further studies are needed to determine the importance of E!.&y4
Some improvements to the scheduling aspect of the model may be brought through "Bwmq9Jq
additional levels in the hierarchy for more detailed representation of the scheduling H |7XfM
activity. 4<vi@,s
It also unveiled new aspects of the role played by thyroid hormone in response to injury FA\U4l-
and tissue repair. ;;m;f^]}
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and Q, "8Ty
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of 8^D1u`
drug molecules. *z#du*f[
In the next few years it should become clear whether X h}D_c
It should be an exciting time for researchers seeking to harness this powerful endogenous 7
, _b
pathway to treat human disease. WbBd<^Q
Acknowledgement eMdf[eS
The authors are grateful to the insightful work provided by Mr. John W. Harney and all eX lJ=S}
of the fellows and students that contributed with some of the studies discussed in this gHkHAOe/
article QSn18V>{
I would like to express my gratitude to all those who gave me the possibility to complete 9:GP~oI j
this thesis. 4e;$+!dlV
I want to thank the Department of Transport of the former Interim Government of 4eG\>#5
Namibia for giving me permission to commence this thesis in the first instance, to do the GD'Z"rhI
necessary research work and to use departmental data EaHJl
This work was supported by NIH grants AI058695 and AI056900. We thank members of r:g_mMvB
the laboratory and our collaborators for many useful suggestions. S0gxVd
(
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. nT+ZSr
Duckman for graphics assistance and A. Capobianco for word processing assistance. om9'A=ZU
Author contributions _Gaem"k|
All authors were involved in experimental planning and data analysis and contributed to >;bym)
manuscript preparation. sWMln:=
Tables and Figures fH?A.JP=a
Figure 7-1 sketches these relationships. ;+|Z5+7!6
The graphical representation of these functions is shown in Figure 1.
MxT&@pq
The xx may be depicted as in Figure 1. VCiq'LOR,<
Figure x shows the schematic diagram of the C984Ee
Figure 1 though 2 provide a ... that
sf[|8}(
the architecture of this expert system for .... is illustrated in Figure 2. Y'bz>@1(
Figure 2 gives the outline of an ... system zJl;|E".
Table shows the L6i|5 P
27 S:`Gi>D
Time-dependent changes of |HYST`
as shown in Table 1 and 2 FE^/us7r
This concept is illustrated in Figure 2 U{bv|vF
At the top of Table xx are shown two blocks of data. <?}pCX/O
Each table or matrix has constructs xx through xx as row;headings, a~a:mM>p
xx through xx as column;headings. 'UxI-Lt
Time course of calculated renin immunoreactive tissue volumes during development of 5/i/.
0?n
the mouse kidney. Data are single values per time point. They were derived from the ]h'
38W
kidneys shown in Figure 1. DO~[VK%|
Yellow color indicates 2yZ~j_AF[
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then S;gy:n!t
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were DR3om;Uk
analyzed by western blot using phospho-specific antibodies. wbcip8<t
ERK and PKB activation were measured by western blot using phospho-specific -64;P9:A>
antibodies 3`{;E{
The data are the means of three different experiments taking the number of untreated cells vE8'B^h1
(vehicle alone) as 100%. Y3FFi M[s~
ERK and PKB activation were then analyzed by western blot with the corresponding #>\SK
phospho-specific antibodies. To ensure equal amount of protein in each lane, western S{8-XiL,
blots against total protein were performed for ERK and PKB. +v5f-CBu
The means of optical density (OD) values of the bands detected in western blots of three RMpiwO^
different experiments are plotted, taking the maximal value of phosphorylation of ERK QRKP;aYt
and PKB as 100%. }fkdv6mz
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with &8Vh3QLEx
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then HWB\}jcA6u
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence
oQV3
microscopy (lower panel). $kHXt]fU
The data are the means of three experiments performed on different days taking the qNHI$r'
number of cells at the onset of the experiment as 100%. .E+O,@?<
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction ')yYpWO
(n=9 each). ~}d\sQF.
*P<0.05 versus non-nephritic rats. J(!=Dno
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, bx{njo1Mr
positive control, M, molecular weight markers). v?6*n>R
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. }Rh%bf7,
Data are means s.d. of four independent experiments. 8au Gz
,"
*P<0.05 versus 0.5 h. %g5#q64
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 AY
<L8
mRNA as determined by real-time RT-PCR and normalized to RFFbS{U*
glyceraldehyde-3-phosphate dehydrogenase mRNA. ^q/$a2<4
Cell number was counted in duplicate using a Malassez hemocytometer uqI'e_&=&5
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with {g`!2"
MCDB media for 24 h, #P<0.05. ik)u/r DW
28 Yq
WNp
The curves are adjusted for history of coronary artery disease, CRP, and progression to L
aA<`
ESRD. s?S e]?i
Both models are independent of age, gender, baseline GFR and proteinuria, and other <o3I<ci6
clinical characteristics and traditional and nontraditional cardiovascular risk factors N TDmOS\,
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH 3kUb
cm
(n=99, P<0.0001, r2=0.190) _7';1 D
Concentration of serum FGF23 concentration before starting and at the end of the 4-h \}k R'l
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, .mqMzV
Student's paired t-test). ''q;yKpaz
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; X6$Cd]MN
arrow=endothelial cell and CD=collecting duct }aa]1X(u
Magnification: 1000. R)$]r>YZF
A table of .. is developed and significant recommendations are made. TC'S
DDX
CONJUGATION aQY.96yo
To Indicate Addition L8'4d'N+>
additionally, again, also, and then, as can be easily understood, besides, equally important, @gf <%>
especially, finally, for the same reason, first, further, furthermore, in addition, last, 0LzS #J+
likewise, moreover, next, second, third, too, evidently, obviously, roughly speaking, ^qBm%R(
broadly speaking K%/\XnCY
To Indicate Cause and Effect F g):>];<9
accordingly, as a result, consequently, for this reason, hence, in short, otherwise, then, Yc~l Yz+b
therefore, thus, truly *0L3#. i
To indicate Comparison fU%Ys9:wU
in a like manner, likewise, similarly , alternatively QZ7W:%r(4
To Indicate Concession Zs3xoIW7Ai
after all, although this may be true, at the same time, even though, even so , I admit, =u
0a/2u|
naturally, of course @V1FBw9S!@
To Indicate Contrast uX{g4#eG
and yet, at the same time, but, for all that, however, yet, in fact, in contrast, in the real life, ]w]BKpU=
in spite of, nevertheless, notwithstanding, normally, on the contrary, on the other hand, _(io8zqe{j
still, traditionally, rather, unfortunately, R\5fl[
To Indicate Time Relationships G\k&sF
after a short time, afterwards, as indicated earlier, as long as, as soon as, at last, at length, o@j!J I&
at the moment, at that time, at the same time, before, earlier, currently, immediately, in 7T!t*sSO'
the meantime, in recent years, lately, later, meanwhile, often, of late, presently, recently, #_3-(H5u
soon, shortly, since, thereupon, temporarily, therefore, until, when, while VB8eGMo
29 k`[>Bk%b
To Indicate Special Features or Examples &A/b9GW^-
for example, for instance, incidentally, indeed, in fact, in other words, in particular, in HJ"sK5Q
practice, specifically, that is, to illustrate, in this respect, theoretically, as mentioned AOL=;z9c#
before / above &n83
>Q
To Indicate Summary )M[FPJP}
in brief, in conclusion, in short, in summary, on the whole, to conclude zI(uexxPqd
, in general, to summarize, to sum up, as a result, ultimately, @RoU
VERB PHASE $SFreyI;Uf
build a .. model km
lb,P
have been described to X
)
=
-a
To assess the functional role of 7+[L6q/K
we detected /9P7;1?
build up the key link $mf6!p4
Although a number of studies have identified predictors of m<cv3dbZo
began a new era in ... +>a(9r|:
can be regarded as / achieved / used to/for / found / obtained through NJoHrhC='
can result in |
ObA=[j
carries out ... tasks MfFmJ7>Bg
production information in order to simultaneously %JA^b5''
contains all information necessary to describe z! k
do not make use of production information Yc5)
^v
deals with DC$> 5FDv
end with failure "zFTPL"
fetch the information from the model directly 5g9K|-
has great potential / yet to be resolved / spurred the development of / Di$++T8"
been recognized as f=4q]y#& X
site component / cable of / currently implemented for / demonstrated by an example / Zjc
0R
finally reached / made equal to / equivalent to / more suitable to / oriented to / "QtkNy%E
interpreted as / pointed out / potentially of great benefit in the complex task of / shown -b
)~
in / used to effectively guide the search s
cd}{Y
makes use of f~p[izt
was significantly higher as compared to @_;vE(!5
To assess disease-specific alterations, we measured 7#26Smv
To specifically assess the relationship between de"+ABR
make up uH)v\Js
To determine if hN;$'%^
This statistically significant difference still Jy]}'eE?pr
They positively correlated with XJ7mvLM;
Present DpL|aRdbK
Our results are consistent with our recent data that suggest that M_;hfpJZ
30 >>h0(G|
contribute to gvxOo#8]
meets the needs of real life production,/ the current demands placed upon it c 9zMI
must be justified 'd< 1;Ayw
point out =l}XKl->
play an important role $-mwr,i
relates to mH4Jl1S&
rely on 'c/Z
W
We performed QPz3IK%
satisfy the needs hr GfA
determine the total requirements for the ... 9Jf.Ls
uses ... as a key to search for... "3uPK$
without relying on Lq5Eu$;r
will be available/ performed/ overlooked T_4y;mf!@O
NOUN PHASE 9$N~OZ;-*x
a basic technical function of ,Je9]XT
a significant reduction of (>gHfC>(lq
drug variability }!5+G:JAh
a critical need rY(h }z
negatively correlated with >^+c s^jCM
a key / principle feature of !"
7ip9a
a substantial impact on 4.i< `'
an intensive review was conducted A>Oi9%OY:
The analysis of the correlations by dW2Lvnh!>/
an increasing need for expanding the application of .... xrCb29{
an important component / function / aspect / issue "_36W
X
each rule is numbered in sequence SXm Hn.?
each of these involves HPeN0=7>
for this calculation, it is necessary to define tGh!5EZ6`
in the physical environment / integration of BJI"DrF
in the reality of situations where … hS 7o=G[
many aspects of xO` O$ie
most past efforts have been spent on ... dQH9NsV7g
common sense to a well studied and documented technical field. XCU>b[Cj,
sources of additional information on ... are listed w%Tjn^ d
systematic and rationally structured format
6.
6g9
the basis on which a range of ...operations can be established is shown sas:5iB5
THE basic philosophy / principles of / key element / general hypothesis / candidate list )M(-EDL>Qk
of / concept of ... has attracted wide interest / function is concerned with / heart / SLMnEtyTS
impact / nature / role / task of / kernel functions mtg3}etA
the number of parts needed to 0]^ke:(#
the above statement means that {Kkut?5
the output data is passed to ;wvhe;!
31 VygiR|f-
the proposed method / underlying principle ('7qJkV
the recommendations made in this report, if implemented, should BK16~Wl
this information resides in @z1Yj"^Pm
this process is composed of ... different ... operation v*k}{M
along with the use of Pn[R.u(l
concerning general aspects of F7~T=X)1
due to @z!|HLD+
for later use in generating..., pN
^^U[
in turn, Xitsbf=Gg
it can be claimed/concluded that J$X{4
it demonstrates the decisions required of 0j)D[K
it also provides information to .. 6!GO{2d"
it becomes essential to y6*9, CF
let ... be the probability that 2,,t+8"`
once... is written, it is compiled into...
|wFfVDp
suppose it is observed that qz
.{[l
this is because g~i%*u,Y<
this results in a |6d0,muN
upon completion of the ... analysis, U94Tp A6
when the knowledge is of mathematics or quantum physics, it will also be /)Pf ]
recorded in books and papers );zLy?n
selection of rules for using the tools, for generating operation plans, wNX2*
is another matter of preference, since practice varies greatly. X!vBD
for the sake of convenience 1>BY:xZr
correct decision to be reach np#RBy
keeping the number of rules to a minimum. cU^Z=B
a good process plan will result exhibiting several characteristics: p*_^JU(<p
practical solutions )_\ZUem
because of rather small job lot sizes tXgsWG?v[H
Backward reasoning can be used to answer the question "should milling tool be select" XsVp7zk\
different level of knowledge in the realm of process planning