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楼主  发表于: 2009-10-18   

医学SCI 论文经典句子

18 4`i8m  
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number N`Q.u-'   
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The {3x>kRaKci  
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at sex\dg<  
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The  p?f\/  
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 ^:-GPr  
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, f(pq`v^-n  
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive >g<Y H'U{  
control for Ca2+ induction. The data thus obtained was analyzed with the software Win #B5,k|"/,M  
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on R KP, w %  
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 ~Fuq{e9`  
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were 5Rl\& G\  
harvested and fractionated as detailed above, and the S-100 fractions were assessed by aB6xRn9  
immunoblotting for presence or absence of annexin I. bq ED5;d'#  
Mouse bone marrow transduction and transplantation. d[_26.  
Retrovirus-mediated transduction of mouse bone marrow cells was done by published bvtpqI QZ  
methods49. Prestimulated low-density bone marrow cells were infected with high-titer KzVi:Hm  
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated 5VV}wR  
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing LH4A!a]  
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by Q7uJ9Y{X  
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) .j:,WF<"l5  
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone w1G(s$;C  
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis <}J !_$A  
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of fLe~X!#HF  
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was /u$'=!<b;  
confirmed by immunoblot analysis. Ow4_0l&  
Determination of renal morphology vR\E;V  
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an geR :FO;\  
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, i]c{(gd`  
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner ceG\Q2  
for morphologic alterations, as previously detailed Be|! S_Y P  
Patient population w80X~  
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2)  Lw\u{E@  
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per NIQ}A-b  
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) {}$rN@OM$  
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. @4;'>yr(  
The Mayo Institutional Review Board and the Research Ethical Board, University Health fo,0NxF9  
Network, University of Toronto approved the study protocol. All patients gave written y tY\&m  
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or ^# $IoW  
19 Tm`@ 5  
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 hA ){>B<;  
months were not included in the study. Patients with active infection, diabetes, or a b;VIR,2  
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), &MpLm&  
medications, malignancies) were also excluded. pl>b 6 |  
Treatment ~3 bV~H#~m  
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of b*Qd9  
high-quality protein) diet was recommended and patients were encouraged to maintain US)i"l7:H*  
the same diet throughout the duration of the study. All patients received a similar C[,h!  
conservative treatment regimen that included loop diuretics to control edema, an 1R}9k)JQ  
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. ]izHn;+  
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added #+o$Tg  
when required to control systolic blood pressures to <135 mm Hg in >75% of the 2;sTSGDG  
readings. Patients who after a minimum of 4 months of conservative therapy and $?F_Qsy{d  
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of Tp-W/YC  
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, n*9QSyJN]  
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine @2"uJ6o  
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given :WWHEZK  
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count jlb8<xIC]  
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count lai@,_<GV  
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per ~EmK ;[Z  
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a Q.$/I+&j  
second course of rituximab treatment following the same protocol described above. imADjBR]  
Follow-up s>L-0vG  
In all patients, clinical and laboratory parameters including complete blood counts, cWnEp';.  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum `}t5`:#k  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry \ 3E%6L  
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion k @fxs]Y_L  
in the urine were assessed by performing two consecutive 24-h urine collections at each ?6*\  M  
time point. Data were considered accurate when urinary creatinine excretion was }{:Jj/d p  
consistent with a complete 24 h collection. The mean of the two measurements was 0>m$e(Z  
considered for the analysis. The presence of HACAs was evaluated at baseline and at T=w0T-[f  
months 3, 6, 9, and 12. [|$C2Dhw=  
Method / Approach / Study/ Technique >Ch2 Ep  
A discussion is presented of a problem-solving system dgQ<>+9]6  
To improve the efficiency of the method, the following approach may be applied. vZQraY nJ  
In order to an investigation was made to find the causes of the ,I|^d.[2  
Although large collections of rules and equations have been complied, none are generally .HTRvE`X  
accepted YO.ddy*59  
20 V,zFHXO  
This approach will be explained and discussed thoroughly in the body of the report. ?pQ0* O0  
This can be accomplished by PQi(Oc  
This algorithm to compute the total cost can be described step by step as follows: a-#$T)mmfj  
The above preliminary analysis has provided important information nCV 7(ldmH  
Various methods have been proposed for selecting an optimum... Q-iBK*-w  
These concepts have been applied to BQ,749^S  
On the basis of the concept mentioned above, &n?RKcH}d  
This can be achieved by "KCG']DF  
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the /^K-tz-R  
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, N:KM8PZ&~  
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced w$]wd`N}  
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 E i2M~/  
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada F1}d@^K 7d  
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% lP4s"8E`h  
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections `"V}Wq ?I  
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin T#e|{ZCbq  
complex. Sections were counterstained with hematoxylin and examined by light i u 0'[  
microscopy. Bs '=YK$  
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay [@pumH>   
performed at Genentech Inc. that measures the antibody response to rituximab in human 1TzwXX7  
serum samples. %b h: c5  
In all patients, clinical and laboratory parameters including complete blood counts, r0OP !u  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum .|P :n'  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry 0<<ATw$aQ  
and at months 1, 3, 6, 9, and 12. >Cc DG  
This fact suggests that a new concept EpT^r8I  
This was accomplished by taking ... re4z>O*  
The preparatory stage is very time consuming process. 3C;;z  
Test are performed for validity, completeness, and compatibility rNm_w>bq  
There is little hope of achieving successful ... ))X"bFP!3  
There has been an increasing awareness of the potential of using most ..so far made have "fN 6_*  
not taken this approach, with the exception of x*X{*?5@  
Only a few studies can be found. SpIiM u(  
It is a very tedious process to go through FLG{1dS  
It is only when .. has been completed that .. may be effected gL@]p  
The entire interpretation process is conducted in one's head. 9B>P Qbs  
These approaches are sometimes very tedious. "2tKh!?Q  
Several techniques can be used  zDxJK  
A polynomial parametric model can be written as [the following]/[follows]: 5]kv1nQ  
A xx model is constructed/formulated using xx. +T,0,^ *  
A xx model represents an xx by its xx. 3<1x>e2nT  
A process decision model captures the logic essential to ts,V+cEA  
From the equation above, xx is equal to the summation of xx times the ... m,5?|J=  
21 (b1e!gJpy  
The validity of a xx model can be checked using Euler's formula. c:B` <  
Given a model, one can mathematically determine whether ... or ... r0pwKRE~t  
Equations for xx need to be derived and implemented in the system. 4)XB3$<  
A number of heuristic rules have been developed for j(>xP*il  
Optimum .. techniques can be made more reliable by ... so that YPKB4p#  
An algorithm based on the characteristic ... is used to determine ,nV4%Aa  
Euler's formula states the following: z$ {[Z=  
The completed model should agree with the formula. %z~kHL  
For manufacturing purposes, a detailed and precise model of the object is necessary PH^Gjm  
Engineering design models are very well defined; therefore, e)XnS'  
To keep the domain narrow enough to be implementable, yet wide enough to be useful. 4#t-?5"  
Point of View Bob-qCBV  
from an implementation standpoint, 6 =G=4{q  
From the point of view of this application, >V\^oh)t]t  
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). 5e?<x>e  
Information is the meaningful interpretation and correlation of some aggregation of data 0fqycGSmU  
in order to allow one to make decisions. & Yx12B\  
From a practical point of view, the computational aspects of an FLC require a fILvEf4b  
simplification of the fuzzy control algorithm. $++O@C5  
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, W|s" ;EAM  
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM [ Q/kNK  
p.129] 1<*U:W $g  
Statistical analysis Io&HzQW^a  
Data were analyzed by one-way analysis of variance comparing the three conditions 7;&,L H  
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If IcGX~zWr  
significant F-statistic from analysis of variance existed, this test was followed by Dunnett S.<4t *,  
post hoc multiple comparison procedure with sham operation as the control group. For all p(Osz7K  
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as $q .}eb0  
statistically significant. 9b@yDq3hQ  
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney aeAx0yE[p  
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, Tf? `_jL  
CA, USA). YBF$/W+=9|  
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was Htln <N  
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's DVJn;X^T:  
test, where appropriate. ZE~zs~z|  
Data are expressed as mean s.d., median and interquartile range, or frequencies, as gFT lP  
appropriate. Variables who deviated from the normal distribution (positively skewed) c& bms)Jwa  
were log-transformed (log10) before the correlation study. ]0j_yX   
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test Nd{U|k3pL  
post hoc analysis of variance were used as indicated below, for the comparison of Q;A\M  
22 %/5Wj_|p  
morphological, immunohistological and functional parameters. Statistical significance ='m%Iq7X  
was set at P<0.05. 8F@Sy,D  
The primary efficacy parameter was defined as change in urinary protein excretion from \j3dB tc  
baseline (week 0) to 12 months after treatment. The 12-month changes were tested ek0!~v<I  
against zero using the paired t-test. Secondary end points included 6-month changes in =;b3i1'U  
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular {8`$~c  
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on s f->8  
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. E-FR w  
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. |r36iUHZS  
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 Ym! e}`A\F  
Definition of remission status is according to the criteria established by Cattran et al.30 S6 a\KtVa  
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a Pnm$g; `P  
>50% reduction in peak proteinuria and non-response as <50% reduction in peak slUi)@b  
proteinuria. Any patient reaching a CR or PR was considered a treatment success )|^8`f  
The statistical significance of differences for the mean values of cytokine concentration u *rP 8GuS  
and T cell proliferation was determined with Student's t-test. Differences with a P value G9yK/g&q  
of less than 0.05 were considered significant. +@?'dw  
Statistical significance was determined by Student's t-test. Data with a P value of less ]sk=V.GGQ  
than 0.05 were considered significant. lw.[qP  
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P 5)eM0,:  
values less than 0.05 considered statistically significant. *X2PT(e[  
The significance of differences among groups was determined by Student's t-test and T,1qR: 58  
one-way analysis of variance (SigmaStat software; Jandel). ZH9Fs'c=  
Comparisons yb ?Pyq.D  
As well, the pros and cons of these representations from a process planning point of view RLB"}&SF]  
will be discussed. j-W$)c3X  
The method of using xx to implement xx described by Zadeh (1973) appeared more emK*g<]  
suitable 4n7Kz_!SVf  
As discussed [in the previous section]/[preciously], KvPCb%!ZP  
Relation iae NY;T  
We can not invert F' directly because it defines a many-to-one mapping. vk4 8&8  
The relationships appear very complicate #X?[")R  
Lifting tasks involve complex and imprecise relationship between the task variables and H>%AK''  
the human operator's characteristics. cK u[ 4D{  
These methods are based on the relationship between ... and ... (EY@{'.&  
The fundamental concept of a fuzzy rating language is that we can establish a relationship C9sU^ ]#F  
among terms such as high, medium, and low, and then modify these relationships. ?{J1Uw<  
This article will thus mention the latter as well as the former. `cXLa=B)9  
The former two bear a close relation to a fuzzy Cartesian product. >{tn2Fkg>  
Importance 4A6Y \ZXI  
A%Ka)UU+n  
23 f(D'qV T{  
The emphasis is on an implementation of a general approach to rule based decision QhJN/v  
making. 0't)-Pj+,  
Consideration / Attention  Jc ze.t  
Careful evaluation is necessary to ensure WF~BCP$OR  
Such a formulation does not change further considerations. Qr$ 7 U6p  
Considerable attention has been paid to KYm8|]'g  
Attention should be paid to an important finding of this investigation. yj4"eDg]  
Caution should be exercised in this process to avoid ... Ia}qDGqPp!  
Primary consideration is given to ... components, though others can be accommodated &'W7-Z\j-  
After ... has been defined by ..., a carefully analysis is carried out/performed to determine ~&D =;M/  
A number of factors such as ...need to be taken into consideration before making the {]]%0!n\  
appropriate decision. M1-tRF  
It should be noted that 5.{=Op!  
It is important to point out that ... %"Um8`]FVg  
These considerations have heightened interest in the possibility of providing ... Twa(RjB<  
We should stress the fundamental importance of the xx KqntOo} y)  
Results. ?5nEmG|kO  
Advantages / Disadvantage 0q"4\#4l  
One of the major advantages of this new measure of xx is that it can be applied to the ZL<X* l2  
experimental study of F,~BhKkbV  
One advantage of using a .. is the ease of preparing it. L.'61ZU  
It has a very fast decision making process VtLRl0/  
All the algorithms involve mostly logical operations. -#f.}H'  
It can be easily and without additional cost implemented in a microprocessor;based erEB4q+ #O  
environment.  (yP1}?  
It can reduce the waste of designing from scratch. <?7qI85OT  
The advantages of using a xx to represent xx are the following: I~n4}}9M  
However, xx is not without its shortcomings. gdf0  
In most cases, the xxx shows an improvement over the existing xxx. zni9  
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. ]Wkgpfd56  
The "best case" results shows a savings of 6% to 9%. yk?bz  
Most of the existing works based on xx approach can only recognize a xx . >JE+j=  
Most of the above methods are computational expansive and limited to xx. {UP[iw$~  
Some other advantages of xx are the following: vEg%ivj3  
The problem is the limitation of this method to a limited domain of parts. X|{ Tljn  
It proved limited in application because it demanded precision in system modeling that rah"\f2  
was impossible in practice. 59)w+AW  
There are advantages to be gained in the structuring of costs and benefits, the use of xx, 3Y38l P:>h  
The disadvantages of this method are also disadvantages of conventional xx approaches. O ^~IY/[  
This combines the best features of both techniques c46-8z$  
24 V>QyiB  
Hopefully, this tool can be as the reference framework of for developing a xx platform, #8et91qw  
and helping the administration, marketing, and knowledge management activities in _rYW|*cIF  
virtual communities. > IaG a!4  
Results BQ Pmo1B  
An improvement on the result shown above can be made by based on the data provided \09A"fs{  
Recent work has identified Yg.[R] UC  
Time-dependent changes of $t%IJT  
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase {`SMxDevc}  
and does not require ERK activation. Jd7chIK  
Much of the current work on 6m?<"y8]  
Discussion of these theories is beyond the scope of this review {V>F69IU  
Based on the information contained in this DehjV6t  
The result can be categorized into nine classes _\\Al v.  
The results are illustrated by an example {BJ>x:2  
The experimental results for each xx time are reported in Table 2. q3#[6!  
From the results obtained so far, it seem that P0}B&B/a:  
Because of the inaccuracy of the ..., a conclusion cannot be drawn as i5TGK#3o  
Although much effort has been made to., this reality is far from completion. o~XK*f=(  
The results indicate that the total benefits are higher than the total costs. L-`V ^{R]  
Their results may then serve as guidelines for lower level models, less fuzzy and more gNW+Dq|X%  
detailed. < ?B3^z$  
Conclusion +ytP5K7  
From the discussion, one may conclude that ... qj _0 td$  
The first indication that }MOXJb @  
In summary, we have shown that o_Zs0/  
These results suggested that KE,.Evyu=  
Our findings have shown that f%EHzm/V  
Our observations have provided ~!Sd|e:4  
This study reveals following five main findings: K[iAN;QCe%  
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in } iKjef#J  
the diabetic kidney. 7<WUj K|  
As mentioned above, i FZGfar?  
Moreover, we demonstrate that, P+f}r^4}  
A number of studies have elaborated a body of knowledge about [j/|)cj  
There are findings to indicate that [;ZCq!)>  
On a descriptive level, there is agreement that for [w<_Wj  
One issue that became particularly evident from our study is W<)nC_$  
Our data are in agreement with the findings and models presented by previous _<f%== I'  
publications, in particular those of Jones et al y%vAEQ2j=  
According to our observations, O W.CU=XU  
…was not evident from our data Fb1<Ic#  
25 ;MGm,F,o  
It could therefore be concluded that 'sZGLgT;m  
our data illustrate that +#wVe  
All these different aspects, as listed above, lead to XFoSGqD  
In fact, it has already been speculated that 424iFc[  
It should be furthermore mentioned in this context that T&[6  
To identify and verify the essential factors triggering developmental renin expression, it C<teZz8/w  
is of interest now to study the development of intrarenal renin expression in mice with 4RDY_HgF6  
defined gene mutations, using the results of this study as a reference system. &Y1h=,KR9  
In conclusion, using several approaches, we demonstrated that g8E5"jpXx3  
But we have not provided formal proof yet that fLs>|Rh  
In summary, our results suggest that ZhCd**  
In conclusion, we identify qnya cI  
A better understanding of such regulatory systems may yield novel therapeutic 873 bg|^hs  
approaches to glomerular diseases. %|x9C,0p#  
Preliminary results of short-term studies (2 weeks) indicate that [?N,3  
However, we believe that YSxr(\~j   
However, despite our extensive measurements of these parameters, we found no c*\i%I#f2  
relationship between response and initial proteinuria, time to B-cell recovery, the #tg\ bb  
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree 8Y8bFWuc  
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be >k\p%{P  
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved L44|/~  
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and HdlO Ga6C  
that will also look for factors that may determine its efficacy in IMN. <LH6my  
It has become increasingly clear that vbJdhaf  
Form the above discussion, the conclusion can be reached that Hc8^w6S1@  
The conclusions drawn are also valid VXZYRr3F  
In conclusion to this, it becomes obvious that the problem of xx lies not only in... 4P?`< K'  
We have attempted to introduce some concepts associated with a theory of 1E!.E=Y ?M  
Considerable more work, hopefully, will be done in this area #*9 | \  
Employing the compositional rule of inference, the assessment of the xx compatibility in mI<sf?.  
achieving prescribed xx projectiles in any level of the hierarchy is made possible. ';\norx;  
This paper has presented a theoretical and experimental study of the xx process and xx whe%o  
concept. H/`@6, j  
The experimental research results will hopefully serve as useful feedback information for 0?t;3 z$n  
improvements for xx work. bbS,pid1  
The scope of this contribution was to introduce a xx method. #l+Rs3T:  
This has a tremendous impact on our understanding of 2sgp$r  
Significant progress has been made in advancing RNAi therapeutics in a remarkably ;uc3_J]  
short period of time /+B6oE>8  
To date, little is known about… f uU"  
Irrespective of the mechanisms and the molecules –which are still largely unknown – /m>SEo\{C  
involved in MSC functions, current data suggest that D&K9!z"]  
To better understand %OHWGac"i  
26 N!<l~[rc  
Future Research (常用于conclustion 的结尾) uj\&-9gEi  
Thus, first extension of the approach could be, *qL'WrB1  
Further studies are needed to determine the importance of q},,[t  
Some improvements to the scheduling aspect of the model may be brought through :{S@KsPqE  
additional levels in the hierarchy for more detailed representation of the scheduling JgHYuLB  
activity. EJz!#f~  
It also unveiled new aspects of the role played by thyroid hormone in response to injury LZG(T$dI  
and tissue repair. b^<7a&  
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and Nf* .r  
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of ;H8`^;  
drug molecules. Wn=I[K&&  
In the next few years it should become clear whether ldU ><xc2  
It should be an exciting time for researchers seeking to harness this powerful endogenous ]X7_ji(l,  
pathway to treat human disease. Jk`l{N  
Acknowledgement W:j9KhvT  
The authors are grateful to the insightful work provided by Mr. John W. Harney and all bM_fuy55Op  
of the fellows and students that contributed with some of the studies discussed in this &\5bo=5V  
article 5>e<|@2 X  
I would like to express my gratitude to all those who gave me the possibility to complete L`O7-'`  
this thesis. s/>0gu]A8  
I want to thank the Department of Transport of the former Interim Government of >}0H5Q8@  
Namibia for giving me permission to commence this thesis in the first instance, to do the {@x-T  
necessary research work and to use departmental data sGiK S,.K  
This work was supported by NIH grants AI058695 and AI056900. We thank members of tqB6:p-%  
the laboratory and our collaborators for many useful suggestions. Q>\DM'{:4  
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. wr:-n   
Duckman for graphics assistance and A. Capobianco for word processing assistance. 2Z"\%ZD  
Author contributions }43qpJe8U  
All authors were involved in experimental planning and data analysis and contributed to (VCJn<@@  
manuscript preparation. ]<%NX $9\  
Tables and Figures +#UawYLJ  
Figure 7-1 sketches these relationships. !)J$f _88D  
The graphical representation of these functions is shown in Figure 1. 2}.~ 6EU/  
The xx may be depicted as in Figure 1. - ?  i  
Figure x shows the schematic diagram of the |XQ\c.A  
Figure 1 though 2 provide a ... that g38 MF  
the architecture of this expert system for .... is illustrated in Figure 2. siV]NI ':|  
Figure 2 gives the outline of an ... system PF)s>  
Table shows the ?< Ma4yl</  
27 d[H`Fe6h  
Time-dependent changes of L&|^y8  
as shown in Table 1 and 2 G_k_qP^:  
This concept is illustrated in Figure 2 vQoZk,  
At the top of Table xx are shown two blocks of data. o~xGE6A*"  
Each table or matrix has constructs xx through xx as row;headings, #?>p l.  
xx through xx as column;headings. )T slI  
Time course of calculated renin immunoreactive tissue volumes during development of 5VVU%STP  
the mouse kidney. Data are single values per time point. They were derived from the I&&;a.  
kidneys shown in Figure 1. B1Z;  
Yellow color indicates NQOf\.#g  
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then NJ$Qm.S  
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were Kb/qM}jS  
analyzed by western blot using phospho-specific antibodies. #>z!ns  
ERK and PKB activation were measured by western blot using phospho-specific I34 1s0  
antibodies \ZSqZDq  
The data are the means of three different experiments taking the number of untreated cells r'*#i>PkQD  
(vehicle alone) as 100%. eG dFupfz  
ERK and PKB activation were then analyzed by western blot with the corresponding B" ]a8}u  
phospho-specific antibodies. To ensure equal amount of protein in each lane, western p7.~k1h  
blots against total protein were performed for ERK and PKB. ,a0RI<D  
The means of optical density (OD) values of the bands detected in western blots of three cw_B^f8^  
different experiments are plotted, taking the maximal value of phosphorylation of ERK *^Z -4  
and PKB as 100%. w H`GzB"  
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with kH[thR k}  
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then  T#Z#YMk  
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence +R 8dy  
microscopy (lower panel). <#./q LSR  
The data are the means of three experiments performed on different days taking the , s,AkH  
number of cells at the onset of the experiment as 100%. Ub wmn!~  
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction  \5HVX/  
(n=9 each). |B2>}Y/  
*P<0.05 versus non-nephritic rats. 5m>f1`4JS  
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, |k: FNu]C  
positive control, M, molecular weight markers). ?uF3Q)rCk  
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. o RmA\R*  
Data are means s.d. of four independent experiments. lvR>%I0`*  
*P<0.05 versus 0.5 h. +N|t:8qaf  
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 "DecS:\  
mRNA as determined by real-time RT-PCR and normalized to m9ky?A,  
glyceraldehyde-3-phosphate dehydrogenase mRNA. 4`?WdCW8  
Cell number was counted in duplicate using a Malassez hemocytometer Ou|kb61zg  
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with r;"Qu  
MCDB media for 24 h, #P<0.05. qM d4awB R  
28 ?nM]eUAP  
The curves are adjusted for history of coronary artery disease, CRP, and progression to IL%P\Zs  
ESRD. - G=doP0  
Both models are independent of age, gender, baseline GFR and proteinuria, and other Jg6@)<n  
clinical characteristics and traditional and nontraditional cardiovascular risk factors J(,{ -d-E  
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH :M@#.  
(n=99, P<0.0001, r2=0.190) gjB(Pwx  
Concentration of serum FGF23 concentration before starting and at the end of the 4-h 87R$Y> V  
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, [3v&j_  
Student's paired t-test). h0-CTPQ7A  
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; 6MQyr2c  
arrow=endothelial cell and CD=collecting duct C]krJse@  
Magnification: 1000. [-nPHm ZV[  
A table of .. is developed and significant recommendations are made. }x"8v&3CM_  
CONJUGATION <t,lq  
To Indicate Addition Gr~J-#a3~D  
additionally, again, also, and then, as can be easily understood, besides, equally important, Co:Rg@i(F  
especially, finally, for the same reason, first, further, furthermore, in addition, last, \Bl`;uXb  
likewise, moreover, next, second, third, too, evidently, obviously, roughly speaking, wHs4~"EY9  
broadly speaking "iuNYM5 P  
To Indicate Cause and Effect `OWwqLoeA  
accordingly, as a result, consequently, for this reason, hence, in short, otherwise, then, + $Lc'G+:  
therefore, thus, truly JiX-t\V~  
To indicate Comparison xp]_>WGq  
in a like manner, likewise, similarly , alternatively >oyZD^gj  
To Indicate Concession %p^`,b}  
after all, although this may be true, at the same time, even though, even so , I admit, }`_x%]EJ  
naturally, of course Yi|Nd;  
To Indicate Contrast [:l=>yJ{(  
and yet, at the same time, but, for all that, however, yet, in fact, in contrast, in the real life, dMa6hI{k  
in spite of, nevertheless, notwithstanding, normally, on the contrary, on the other hand, 7"Q;Yi2(  
still, traditionally, rather, unfortunately, YDGW]T]i ?  
To Indicate Time Relationships P5Pb2|\*  
after a short time, afterwards, as indicated earlier, as long as, as soon as, at last, at length, ^dKtUH/78G  
at the moment, at that time, at the same time, before, earlier, currently, immediately, in wU&vkb)k  
the meantime, in recent years, lately, later, meanwhile, often, of late, presently, recently, knRs{1}Pw{  
soon, shortly, since, thereupon, temporarily, therefore, until, when, while x,QXOh\a  
29 cTdX'5  
To Indicate Special Features or Examples {br6*  
for example, for instance, incidentally, indeed, in fact, in other words, in particular, in R(#ZaFuo[  
practice, specifically, that is, to illustrate, in this respect, theoretically, as mentioned \C"hL(4-  
before / above Pq3|O Z  
To Indicate Summary OTWp,$YA=  
in brief, in conclusion, in short, in summary, on the whole, to conclude +.66Ky`|[  
, in general, to summarize, to sum up, as a result, ultimately, qyR}|<F8*  
VERB PHASE _kUtj(re  
build a .. model 1raq;^e9  
have been described to Eu$hC]w  
To assess the functional role of ; r95i1a'  
we detected |) CfO4  
build up the key link M)sAMfuUw  
Although a number of studies have identified predictors of \y+@mJWa  
began a new era in ... a}'dIDj  
can be regarded as / achieved / used to/for / found / obtained through >4nQ&b.u  
can result in b}Xh|0`b+  
carries out ... tasks 3NN )ql  
production information in order to simultaneously G)&S%R!i\N  
contains all information necessary to describe vg*~t3{L  
do not make use of production information @$5= 4HA  
deals with 6K5mMu#4  
end with failure Dh)(?"^9A  
fetch the information from the model directly h<bCm`qj  
has great potential / yet to be resolved / spurred the development of / yMJ(Sf  
been recognized as -BEd7@?A  
site component / cable of / currently implemented for / demonstrated by an example / SL?YU(a  
finally reached / made equal to / equivalent to / more suitable to / oriented to / E*d UJ.>  
interpreted as / pointed out / potentially of great benefit in the complex task of / shown &M6Zsmo  
in / used to effectively guide the search 3|4<SMm  
makes use of 96<0=   
was significantly higher as compared to YZ6" s-  
To assess disease-specific alterations, we measured q5\iQ2f{WV  
To specifically assess the relationship between &A~hM[-  
make up $Ao' mT  
To determine if TVAa/_y2`  
This statistically significant difference still XUTsW,WC  
They positively correlated with @]dv   
Present | cL,$G  
Our results are consistent with our recent data that suggest that bmO(tQS$5  
30 DSK?7F$_oE  
contribute to mEyIbMci  
meets the needs of real life production,/ the current demands placed upon it u=7 #_ZC9L  
must be justified #?'@?0<6  
point out ; KT/;I  
play an important role JV?d/[u,  
relates to >tm4Rg~y  
rely on w|61dB  
We performed EF'8-*  
satisfy the needs \4>& zb4  
determine the total requirements for the ... I!T=$Um  
uses ... as a key to search for... cJzkA^T9  
without relying on DC0O N`  
will be available/ performed/ overlooked ~bz$]o-<  
NOUN PHASE uo bQ S!  
a basic technical function of a I 1tG  
a significant reduction of fpJ%{z2  
drug variability eu'~(_2  
a critical need <MoyL1=  
negatively correlated with -K/c~'%'*  
a key / principle feature of B_>r|^Vh  
a substantial impact on QWE\Ud.q  
an intensive review was conducted PW\me7iCz  
The analysis of the correlations by -B#K}xL|x  
an increasing need for expanding the application of .... m$7C{Mr'  
an important component / function / aspect / issue MeV*]*   
each rule is numbered in sequence H~bbkql  
each of these involves ,P=.x%  
for this calculation, it is necessary to define 35L\  
in the physical environment / integration of a*uG^~ ).  
in the reality of situations where … Y(gai?  
many aspects of eKf5orN  
most past efforts have been spent on ... KY?ujeF  
common sense to a well studied and documented technical field. )a9C3-8Y'  
sources of additional information on ... are listed t#w,G  
systematic and rationally structured format bz.sWBugR  
the basis on which a range of ...operations can be established is shown 1 hD(l6tG@  
THE basic philosophy / principles of / key element / general hypothesis / candidate list z m]R76  
of / concept of ... has attracted wide interest / function is concerned with / heart / 3#y`6e=5  
impact / nature / role / task of / kernel functions w| ahb  
the number of parts needed to ! Y&]Y G  
the above statement means that rV} 5&N*c  
the output data is passed to |>'q%xK  
31 t+\<i8  
the proposed method / underlying principle |;&I$'i  
the recommendations made in this report, if implemented, should h6n!"z8H  
this information resides in F{c8{?:  
this process is composed of ... different ... operation ;aD?BD__Z  
along with the use of Pq@ -`sw  
concerning general aspects of gtT&97tT<  
due to \U##b~Z,g  
for later use in generating..., v6Wz:|G/u  
in turn, Yq4nmr4  
it can be claimed/concluded that b"nkF\P@Fj  
it demonstrates the decisions required of wQ[!~>A  
it also provides information to .. Mpco8b-b  
it becomes essential to l/"!}wF  
let ... be the probability that %~kE,^  
once... is written, it is compiled into... ^bfU>02Q6p  
suppose it is observed that y&bZai8WlE  
this is because 1$`|$V1  
this results in a Jd',v  
upon completion of the ... analysis, ii>^]iT  
when the knowledge is of mathematics or quantum physics, it will also be .v+  W>  
recorded in books and papers k8@bQ"#b  
selection of rules for using the tools, for generating operation plans, h7@%}<%  
is another matter of preference, since practice varies greatly. f.bwA x  
for the sake of convenience g3^:)$m  
correct decision to be reach Y3s8@0b3  
keeping the number of rules to a minimum. b5I 8jPj4c  
a good process plan will result exhibiting several characteristics: _8-T?j**   
practical solutions PgHmOs  
because of rather small job lot sizes O*!f%}  
Backward reasoning can be used to answer the question "should milling tool be select" ~)[ pL(4  
different level of knowledge in the realm of process planning
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