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楼主  发表于: 2009-10-18   

医学SCI 论文经典句子

18 EJsb{$u  
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number ny0`~bl{p  
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The xC]/i(+bA  
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at G#>nOB  
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The  +yk>jx  
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 USY^ [@o[f  
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, Spb'jAKj'  
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive 6 kk(FVX  
control for Ca2+ induction. The data thus obtained was analyzed with the software Win "=)`*"rr  
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on n$8A"'.M  
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 ">7 bnOJ  
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were Cq=c'(cX  
harvested and fractionated as detailed above, and the S-100 fractions were assessed by OmW|\d PU  
immunoblotting for presence or absence of annexin I. wrWWXOZ 4  
Mouse bone marrow transduction and transplantation. 5 X rn]  
Retrovirus-mediated transduction of mouse bone marrow cells was done by published BC3I{Y |  
methods49. Prestimulated low-density bone marrow cells were infected with high-titer @W8RAS~  
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated &F)lvtt|  
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing -c. a7  
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by NB[b[1 Ch  
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) %NuS!v>  
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone Lgy}Gm8u5  
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis 5,A/6b  
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of ZCa?uzeo]  
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was gC?k6)p$N  
confirmed by immunoblot analysis. /PO5z7n0J  
Determination of renal morphology fz%u rbJR  
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an w%htY.-  
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, IP-mo!Y.  
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner z}Q54,9m  
for morphologic alterations, as previously detailed z7}@8F  
Patient population (URWi caB  
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) >n#Pq{7aF  
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per /.vB /{2  
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) cu |{cy-  
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. I~Ziq10  
The Mayo Institutional Review Board and the Research Ethical Board, University Health f>dWl$/_s  
Network, University of Toronto approved the study protocol. All patients gave written Rc @p!Xi  
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or 8^2Q ~{i  
19 =MA$xz3  
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 qXgg"k%A\  
months were not included in the study. Patients with active infection, diabetes, or a *?cE]U6;  
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), zl$'W=[rFs  
medications, malignancies) were also excluded. ftRf~5d2  
Treatment Y'wQ(6ok  
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of 3nMXfh/  
high-quality protein) diet was recommended and patients were encouraged to maintain !A qSG-  
the same diet throughout the duration of the study. All patients received a similar Bg {"{poy  
conservative treatment regimen that included loop diuretics to control edema, an Y<odXFIS  
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. #f d ;]  
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added .*+%-%CbP  
when required to control systolic blood pressures to <135 mm Hg in >75% of the Z$"E|nRN  
readings. Patients who after a minimum of 4 months of conservative therapy and eT0Y p  
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of Bu$Z+o  
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, (Rj'd>%c  
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine >NDI<9<'0}  
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given $}+t|`*q8]  
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count YBF|0A{[Y  
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count ;hzm&My  
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per -y]e`\+[  
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a 3HCH-?U5  
second course of rituximab treatment following the same protocol described above. $IUe](a{d  
Follow-up JlaT -j  
In all patients, clinical and laboratory parameters including complete blood counts, rW),xfo0  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum f i#p('8  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry 'z\$.L  
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion B\*"rSP\  
in the urine were assessed by performing two consecutive 24-h urine collections at each A*b>@>2  
time point. Data were considered accurate when urinary creatinine excretion was :^bjn3b  
consistent with a complete 24 h collection. The mean of the two measurements was dkUh[yo"H  
considered for the analysis. The presence of HACAs was evaluated at baseline and at jc0Trs{Jf  
months 3, 6, 9, and 12. Wy:xiP  
Method / Approach / Study/ Technique ;Gnk8lIsb  
A discussion is presented of a problem-solving system L@VIC|~E  
To improve the efficiency of the method, the following approach may be applied. <?h,;]U  
In order to an investigation was made to find the causes of the o%j[]P@4G  
Although large collections of rules and equations have been complied, none are generally w%'8bH!  
accepted pXap<T  
20 Tup2 ;\y  
This approach will be explained and discussed thoroughly in the body of the report. (Vz\02,K  
This can be accomplished by )Up'W   
This algorithm to compute the total cost can be described step by step as follows: <h"07.y  
The above preliminary analysis has provided important information :@oy5zib  
Various methods have been proposed for selecting an optimum... **KkPjAO?  
These concepts have been applied to wbImE;-Z  
On the basis of the concept mentioned above, gR#lRA/  
This can be achieved by jT:z#B%  
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the qPH=2k ,H  
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, qZ=%r u  
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced 5,~Ju>y*  
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 vQ_D% f4;  
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada azKiXr#_(  
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% @gM>Lxj  
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections ba`V`0p-(  
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin z]d2 rzV(_  
complex. Sections were counterstained with hematoxylin and examined by light /&jh10}H  
microscopy. x sN)a!  
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay rAwuWM@BIg  
performed at Genentech Inc. that measures the antibody response to rituximab in human Lbwc2Q,.-  
serum samples. ?ypX``3#s7  
In all patients, clinical and laboratory parameters including complete blood counts, -RK R. ,  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum X8uAwHa6F  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry GFX$vn-/F  
and at months 1, 3, 6, 9, and 12. PYhRP00}M  
This fact suggests that a new concept q y\Z2k  
This was accomplished by taking ... XhEJF !  
The preparatory stage is very time consuming process. MUjfqxTT  
Test are performed for validity, completeness, and compatibility *kM^l!<g  
There is little hope of achieving successful ... l'm\ *=3  
There has been an increasing awareness of the potential of using most ..so far made have _7=LSf,9  
not taken this approach, with the exception of 7AouiL 2-W  
Only a few studies can be found. L,7+26XV"B  
It is a very tedious process to go through mLb>*xt$b@  
It is only when .. has been completed that .. may be effected 29tih{ xx  
The entire interpretation process is conducted in one's head. &cuDGo.  
These approaches are sometimes very tedious. 40$- ]i  
Several techniques can be used =,w(D~ps  
A polynomial parametric model can be written as [the following]/[follows]: Wfp>BC  
A xx model is constructed/formulated using xx. + rN&@}Jt.  
A xx model represents an xx by its xx. .d;|iwl  
A process decision model captures the logic essential to )1iqM]~;B  
From the equation above, xx is equal to the summation of xx times the ... +Jl PQ~5  
21 /+JHnedK  
The validity of a xx model can be checked using Euler's formula. zkb[u"  
Given a model, one can mathematically determine whether ... or ... -POsbb>  
Equations for xx need to be derived and implemented in the system. 9?38/2kX4  
A number of heuristic rules have been developed for O]VHX![Y$  
Optimum .. techniques can be made more reliable by ... so that ^SvGSx i  
An algorithm based on the characteristic ... is used to determine G;he:Bf  
Euler's formula states the following: d3jzGJrU}  
The completed model should agree with the formula. \PL0-.t,  
For manufacturing purposes, a detailed and precise model of the object is necessary YS0^ !7u  
Engineering design models are very well defined; therefore, VxW>Xx G0  
To keep the domain narrow enough to be implementable, yet wide enough to be useful. 34c+70x7  
Point of View 9(pF!}1 %\  
from an implementation standpoint, (MzThGJK_  
From the point of view of this application, oZ\zi> Y,  
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). 1TlMB  
Information is the meaningful interpretation and correlation of some aggregation of data w[]\%`69}Z  
in order to allow one to make decisions. ZfVw33z  
From a practical point of view, the computational aspects of an FLC require a 7-("pp YX=  
simplification of the fuzzy control algorithm. <Gj]XAoe%  
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, &Pe[kCO]  
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM b ltZQI|  
p.129] siz:YRur  
Statistical analysis Nn{/_QG  
Data were analyzed by one-way analysis of variance comparing the three conditions '#u=w yp  
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If ;nw}x4Y[  
significant F-statistic from analysis of variance existed, this test was followed by Dunnett ZsN3 MbY  
post hoc multiple comparison procedure with sham operation as the control group. For all .(Tf$V  
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as `teaE7^Wm  
statistically significant. pGP$2  
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney hx hs>eY  
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, Y@MFH>*  
CA, USA). d=/a{lP\  
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was ,B$e'KQ  
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's J<-2dvq  
test, where appropriate. 9&Ny;oy#6  
Data are expressed as mean s.d., median and interquartile range, or frequencies, as FB n . 4  
appropriate. Variables who deviated from the normal distribution (positively skewed) `! _mIh}  
were log-transformed (log10) before the correlation study. [-h=L Jf#  
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test v2}>/b)  
post hoc analysis of variance were used as indicated below, for the comparison of b ix}#M  
22 zfK3$|  
morphological, immunohistological and functional parameters. Statistical significance Y 016Xg5  
was set at P<0.05. 7-c3^5gn{  
The primary efficacy parameter was defined as change in urinary protein excretion from K!;>/3Y2-  
baseline (week 0) to 12 months after treatment. The 12-month changes were tested e@L?jBj8m  
against zero using the paired t-test. Secondary end points included 6-month changes in I=|}%WO#  
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular 0ae}! LO  
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on $ -M'  
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. -_fh=}.n+"  
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. bf$4Z: Y  
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 9FmX^t$T  
Definition of remission status is according to the criteria established by Cattran et al.30 >?ckBU9  
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a ,dSP%?vV  
>50% reduction in peak proteinuria and non-response as <50% reduction in peak 5db9C}0  
proteinuria. Any patient reaching a CR or PR was considered a treatment success )X5en=[)O  
The statistical significance of differences for the mean values of cytokine concentration kT4Oal+4  
and T cell proliferation was determined with Student's t-test. Differences with a P value YE1X*'4  
of less than 0.05 were considered significant. A9ru]|?  
Statistical significance was determined by Student's t-test. Data with a P value of less }yMA s  
than 0.05 were considered significant. ;p/$9b.0:  
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P jHBP:c  
values less than 0.05 considered statistically significant. 5/4q}U3  
The significance of differences among groups was determined by Student's t-test and AOR(1Qyo  
one-way analysis of variance (SigmaStat software; Jandel). jt4c*0z  
Comparisons w $z]Z-  
As well, the pros and cons of these representations from a process planning point of view D7OPFN 7`  
will be discussed. z*OQ4_  
The method of using xx to implement xx described by Zadeh (1973) appeared more ff.;6R\  
suitable 'I1^70bB  
As discussed [in the previous section]/[preciously], 0ZjinWkR[  
Relation 7~7_T#dTh  
We can not invert F' directly because it defines a many-to-one mapping. ^{ w]r5d  
The relationships appear very complicate H?W8_XiN  
Lifting tasks involve complex and imprecise relationship between the task variables and Uh8c!CA8:\  
the human operator's characteristics. ?(P3ZTk?.  
These methods are based on the relationship between ... and ... 3v7*@(y  
The fundamental concept of a fuzzy rating language is that we can establish a relationship ,]qTJ`J  
among terms such as high, medium, and low, and then modify these relationships. k\`~v$R3  
This article will thus mention the latter as well as the former. '}.Z' %;  
The former two bear a close relation to a fuzzy Cartesian product. xix: = a  
Importance euc|G Xs  
N)N\iad^  
23 MW$ X4<*KD  
The emphasis is on an implementation of a general approach to rule based decision Ww Bs_OMc  
making. hd)HJb-aR  
Consideration / Attention wYIlp  
Careful evaluation is necessary to ensure 380M &Guh  
Such a formulation does not change further considerations. E ) iEWc  
Considerable attention has been paid to p a)2TL/@  
Attention should be paid to an important finding of this investigation. ,/ bv3pE  
Caution should be exercised in this process to avoid ... _BP!{~&;  
Primary consideration is given to ... components, though others can be accommodated -U#e  
After ... has been defined by ..., a carefully analysis is carried out/performed to determine oe*Y(T\G  
A number of factors such as ...need to be taken into consideration before making the b6y/o48  
appropriate decision. "fTW2D74  
It should be noted that f7_EqS=(  
It is important to point out that ... 7_*k<W7|  
These considerations have heightened interest in the possibility of providing ... AYnk.H-v  
We should stress the fundamental importance of the xx r{pbUk  
Results. WMw^zq?hd@  
Advantages / Disadvantage y.PsC '  
One of the major advantages of this new measure of xx is that it can be applied to the #Z)8,N  
experimental study of 'W2B**}  
One advantage of using a .. is the ease of preparing it. 2Sg^SZFH+o  
It has a very fast decision making process v3 q.,I_  
All the algorithms involve mostly logical operations. }mx>3G{d  
It can be easily and without additional cost implemented in a microprocessor;based jf WZLb)  
environment. T4lE-g2%M  
It can reduce the waste of designing from scratch. e#/SFI0m  
The advantages of using a xx to represent xx are the following: jM%8h$&E  
However, xx is not without its shortcomings. zlhHSyK  
In most cases, the xxx shows an improvement over the existing xxx. 2iV/?.<Z&  
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. ]?3-;D.eG  
The "best case" results shows a savings of 6% to 9%. lc8zF5  
Most of the existing works based on xx approach can only recognize a xx . u>y/<9]q8  
Most of the above methods are computational expansive and limited to xx. S+* g  
Some other advantages of xx are the following: EjDr   
The problem is the limitation of this method to a limited domain of parts. 8[\ ~}Q6  
It proved limited in application because it demanded precision in system modeling that 4;D>s8dgG  
was impossible in practice. hqwDlapTt  
There are advantages to be gained in the structuring of costs and benefits, the use of xx, > %B7/l$  
The disadvantages of this method are also disadvantages of conventional xx approaches. p/WE[8U  
This combines the best features of both techniques oH>G3n|U^  
24 .jK,6't^  
Hopefully, this tool can be as the reference framework of for developing a xx platform, U3OXO 1  
and helping the administration, marketing, and knowledge management activities in 5kdh!qy[$,  
virtual communities. |:b!e  
Results ]rM HO  
An improvement on the result shown above can be made by based on the data provided $dkkgsw 7  
Recent work has identified s.j6" Q[W  
Time-dependent changes of /Ps5Og  
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase >yr1wVS  
and does not require ERK activation. </-aG[Fi  
Much of the current work on ]3&BLq  
Discussion of these theories is beyond the scope of this review ipH'}~=ID  
Based on the information contained in this e{E8_2d  
The result can be categorized into nine classes :/~TV   
The results are illustrated by an example \I+#M-V  
The experimental results for each xx time are reported in Table 2. W`gzMx  
From the results obtained so far, it seem that :=e"D;5  
Because of the inaccuracy of the ..., a conclusion cannot be drawn as G-Dc(QhU&  
Although much effort has been made to., this reality is far from completion. Dg'BlrwbR  
The results indicate that the total benefits are higher than the total costs. 9?.  
Their results may then serve as guidelines for lower level models, less fuzzy and more 5"mH6%d :8  
detailed. Y |'}VU  
Conclusion 0.z\YTZ9  
From the discussion, one may conclude that ... {2T;^+KE  
The first indication that R>y/Y<5=  
In summary, we have shown that vNSeNS@jxC  
These results suggested that |?<^4U8  
Our findings have shown that v&r\Z @%  
Our observations have provided fp?cb2'7  
This study reveals following five main findings: -W.bOr  
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in iCNJ%AZ H  
the diabetic kidney. `L7Cf&W\l8  
As mentioned above, SmCtwcB1  
Moreover, we demonstrate that, Tu&W7aoX5  
A number of studies have elaborated a body of knowledge about nXAGwU8a  
There are findings to indicate that Rg%Xy`gS  
On a descriptive level, there is agreement that for \W+Hzf] W#  
One issue that became particularly evident from our study is >gf,8flgj  
Our data are in agreement with the findings and models presented by previous q$7/X;A  
publications, in particular those of Jones et al gPcOm b  
According to our observations, X]c>clk ,  
…was not evident from our data ZDbzH=[  
25 f[Xsri  
It could therefore be concluded that iH>IV0 <  
our data illustrate that BY>]6SrP  
All these different aspects, as listed above, lead to VYnB&3 %DF  
In fact, it has already been speculated that cQrXrij;!  
It should be furthermore mentioned in this context that Kj/Lcx;bh  
To identify and verify the essential factors triggering developmental renin expression, it &/8B (0<  
is of interest now to study the development of intrarenal renin expression in mice with OXS.CFZM  
defined gene mutations, using the results of this study as a reference system. =4 NKXP~C  
In conclusion, using several approaches, we demonstrated that Qq3>Xv <  
But we have not provided formal proof yet that 5#mHWBGd7  
In summary, our results suggest that WXd#`f%  
In conclusion, we identify ;E0x#JUrw  
A better understanding of such regulatory systems may yield novel therapeutic J~)JsAXAI  
approaches to glomerular diseases. py$i{v%  
Preliminary results of short-term studies (2 weeks) indicate that EOXuc9> G  
However, we believe that }c=YiH,o  
However, despite our extensive measurements of these parameters, we found no =yZ6$ hK  
relationship between response and initial proteinuria, time to B-cell recovery, the .t.4y. 97  
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree zvwv7JtB  
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be jQ['f\R  
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved x LGMN)@r  
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and ]L?WC  
that will also look for factors that may determine its efficacy in IMN. 83F]d+n  
It has become increasingly clear that Ct]?  /  
Form the above discussion, the conclusion can be reached that m}t`43}QE  
The conclusions drawn are also valid @B9#Hrc  
In conclusion to this, it becomes obvious that the problem of xx lies not only in... O@>{%u  
We have attempted to introduce some concepts associated with a theory of A_+*b [P  
Considerable more work, hopefully, will be done in this area uzL|yxt  
Employing the compositional rule of inference, the assessment of the xx compatibility in }] . |7h  
achieving prescribed xx projectiles in any level of the hierarchy is made possible. AjINO}b  
This paper has presented a theoretical and experimental study of the xx process and xx 5Zl7crA[  
concept. zwK$ q=-:  
The experimental research results will hopefully serve as useful feedback information for c+jnQM'  
improvements for xx work. ._<gc;G  
The scope of this contribution was to introduce a xx method. GuQ#  
This has a tremendous impact on our understanding of iBCIJ!;  
Significant progress has been made in advancing RNAi therapeutics in a remarkably Jo9c|\4  
short period of time BXr._y, cr  
To date, little is known about… ]CgZt' h{  
Irrespective of the mechanisms and the molecules –which are still largely unknown – #J%Fi).^)  
involved in MSC functions, current data suggest that BF U#FE)s  
To better understand N~B'gJJDx  
26 + N!/>w]n  
Future Research (常用于conclustion 的结尾) o Hrx$>W]  
Thus, first extension of the approach could be, VqeW;8&*iv  
Further studies are needed to determine the importance of X($@E!|  
Some improvements to the scheduling aspect of the model may be brought through =[o/D0-Kn  
additional levels in the hierarchy for more detailed representation of the scheduling 62#8c~ dL  
activity. IO?6F@(  
It also unveiled new aspects of the role played by thyroid hormone in response to injury ni3A+Y0  
and tissue repair. 92L{be; SY  
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and a4N8zDS  
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of znd fIt^  
drug molecules. )X-TJ+d  
In the next few years it should become clear whether H/Ov8|  
It should be an exciting time for researchers seeking to harness this powerful endogenous j(\jYH>   
pathway to treat human disease. U+g<lgH1J  
Acknowledgement >HQ<KFA  
The authors are grateful to the insightful work provided by Mr. John W. Harney and all )UG<KcdI  
of the fellows and students that contributed with some of the studies discussed in this k'+Mc%pg4E  
article Toc="F`SW  
I would like to express my gratitude to all those who gave me the possibility to complete ,]-A~^|  
this thesis. =k22f`8ew  
I want to thank the Department of Transport of the former Interim Government of d!]_n|B@9  
Namibia for giving me permission to commence this thesis in the first instance, to do the QOY M/1U  
necessary research work and to use departmental data k/V:QdD Sb  
This work was supported by NIH grants AI058695 and AI056900. We thank members of Md,KW#  
the laboratory and our collaborators for many useful suggestions.  dz Z75  
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. j /=4f�  
Duckman for graphics assistance and A. Capobianco for word processing assistance. Se- n#  
Author contributions ]pP [0 S  
All authors were involved in experimental planning and data analysis and contributed to RP4P"m(   
manuscript preparation. 'w5g s}1D  
Tables and Figures o>Jr6: D(  
Figure 7-1 sketches these relationships. LdM9k(  
The graphical representation of these functions is shown in Figure 1. g}=opw6z  
The xx may be depicted as in Figure 1. :=K <2  
Figure x shows the schematic diagram of the t!,GI&  
Figure 1 though 2 provide a ... that KcQe1mT!+  
the architecture of this expert system for .... is illustrated in Figure 2. jVtRn.qh  
Figure 2 gives the outline of an ... system fer~NlX  
Table shows the $pg1Av7l  
27 ZeyA bo  
Time-dependent changes of 0'9z XJ"  
as shown in Table 1 and 2 P@z,[,sy"$  
This concept is illustrated in Figure 2 RIO4`,  
At the top of Table xx are shown two blocks of data. ,[{)4J$MV  
Each table or matrix has constructs xx through xx as row;headings, C{8d^SCA"  
xx through xx as column;headings. h#>%\Pvt;  
Time course of calculated renin immunoreactive tissue volumes during development of .oNs8._:  
the mouse kidney. Data are single values per time point. They were derived from the ZOK,P  
kidneys shown in Figure 1. eQRY xx{  
Yellow color indicates >$yqx1=jW  
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then k7gm)}RKcu  
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were e5 ?;{H  
analyzed by western blot using phospho-specific antibodies. /M1 /  
ERK and PKB activation were measured by western blot using phospho-specific _K?{DnTb  
antibodies `]8z]PD  
The data are the means of three different experiments taking the number of untreated cells 0;kp`hB  
(vehicle alone) as 100%. w<ol$2&B  
ERK and PKB activation were then analyzed by western blot with the corresponding Z7X_U` Q  
phospho-specific antibodies. To ensure equal amount of protein in each lane, western 5IPZ;  
blots against total protein were performed for ERK and PKB. v{Rj,O u  
The means of optical density (OD) values of the bands detected in western blots of three xSQ:#o=8G  
different experiments are plotted, taking the maximal value of phosphorylation of ERK {F/0pvP9  
and PKB as 100%. h}k/okG  
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with a}Dx"zl;  
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then )NoNgU\7!  
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence oM&}akPE  
microscopy (lower panel). f8T6(cA  
The data are the means of three experiments performed on different days taking the atW=xn  
number of cells at the onset of the experiment as 100%. (^:0g.~c  
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction GI~JIXHTQ  
(n=9 each). +ld]P}  
*P<0.05 versus non-nephritic rats. [O"9OW'2!B  
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, <}G*/ z?/  
positive control, M, molecular weight markers). ig Q,ZY1  
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. V__|NVoOm  
Data are means s.d. of four independent experiments. N-0kB vo  
*P<0.05 versus 0.5 h. y@#JzfY?Hr  
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 (R.l{(A  
mRNA as determined by real-time RT-PCR and normalized to |XDbf3^6  
glyceraldehyde-3-phosphate dehydrogenase mRNA. N)kZ2|oD  
Cell number was counted in duplicate using a Malassez hemocytometer F9Hxqa#1T  
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with /IO<TF(X  
MCDB media for 24 h, #P<0.05. [ T6MaP?  
28 ru#CywK{{;  
The curves are adjusted for history of coronary artery disease, CRP, and progression to ,&q Q[i  
ESRD. aANzL  
Both models are independent of age, gender, baseline GFR and proteinuria, and other KE_GC ;bQ  
clinical characteristics and traditional and nontraditional cardiovascular risk factors h{Zd, 9H  
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH |EjMpRNE  
(n=99, P<0.0001, r2=0.190) p%]ZG,  
Concentration of serum FGF23 concentration before starting and at the end of the 4-h UWPzRk#s"  
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, DOa%|H'P  
Student's paired t-test). *;0Ods+IcY  
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; <0M 2qt8  
arrow=endothelial cell and CD=collecting duct px~:'U  
Magnification: 1000. ro8c-[ V  
A table of .. is developed and significant recommendations are made. rF:l+I]  
CONJUGATION : 6|nXL  
To Indicate Addition }%lk$g';  
additionally, again, also, and then, as can be easily understood, besides, equally important, j}F;Bfq!  
especially, finally, for the same reason, first, further, furthermore, in addition, last, 8_h:_7e  
likewise, moreover, next, second, third, too, evidently, obviously, roughly speaking, D:DtP6  
broadly speaking 8oxYgj&~X  
To Indicate Cause and Effect U3rpmml  
accordingly, as a result, consequently, for this reason, hence, in short, otherwise, then, 032P R;]  
therefore, thus, truly Q!`   
To indicate Comparison yE=tuHv(0  
in a like manner, likewise, similarly , alternatively u7G9 eN  
To Indicate Concession RuBL_Vi  
after all, although this may be true, at the same time, even though, even so , I admit, Bm:N@w g  
naturally, of course {I p)%uR  
To Indicate Contrast hY} .2  
and yet, at the same time, but, for all that, however, yet, in fact, in contrast, in the real life, Ew$-,KC[  
in spite of, nevertheless, notwithstanding, normally, on the contrary, on the other hand, nX\Q{R2  
still, traditionally, rather, unfortunately, dePI&z:  
To Indicate Time Relationships @ (I)]Ca%O  
after a short time, afterwards, as indicated earlier, as long as, as soon as, at last, at length, }&qr"z4  
at the moment, at that time, at the same time, before, earlier, currently, immediately, in 3lG=.yD  
the meantime, in recent years, lately, later, meanwhile, often, of late, presently, recently, y _A7CG"^  
soon, shortly, since, thereupon, temporarily, therefore, until, when, while rwCjNky!  
29 ly)L%hG  
To Indicate Special Features or Examples <F#/wU^9  
for example, for instance, incidentally, indeed, in fact, in other words, in particular, in e,rCutA)  
practice, specifically, that is, to illustrate, in this respect, theoretically, as mentioned lgei<\6~n5  
before / above s\dhQZw3  
To Indicate Summary gW_^GrKpI  
in brief, in conclusion, in short, in summary, on the whole, to conclude & GM&,  
, in general, to summarize, to sum up, as a result, ultimately, "F8A:tR  
VERB PHASE L7 f'  
build a .. model xfqW~&  
have been described to Fm,} sP"Qx  
To assess the functional role of Kk t9M\  
we detected Tx!c }  
build up the key link '.&z y#  
Although a number of studies have identified predictors of *[?DnF+  
began a new era in ... =|G l  
can be regarded as / achieved / used to/for / found / obtained through {2,OK=XM|  
can result in \hcb~>=C  
carries out ... tasks 'G-zJcU  
production information in order to simultaneously sG~5O\,E  
contains all information necessary to describe L8zY?v(bG  
do not make use of production information L>qLl_.  
deals with P{!r<N  
end with failure Zg@NMT  
fetch the information from the model directly ZxRD+`  
has great potential / yet to be resolved / spurred the development of / LOkNDmj  
been recognized as _=.f+1W  
site component / cable of / currently implemented for / demonstrated by an example / M8,W|eTM  
finally reached / made equal to / equivalent to / more suitable to / oriented to / p6yC1\U!o  
interpreted as / pointed out / potentially of great benefit in the complex task of / shown 6BJPQdqSl  
in / used to effectively guide the search TuBl9 p'6  
makes use of [kyF|3k~  
was significantly higher as compared to ,4-)  e  
To assess disease-specific alterations, we measured SY` U]-h  
To specifically assess the relationship between 1r?<1vh:z  
make up !`k{Ga  
To determine if %r0yBK2uOp  
This statistically significant difference still `5[d9z/6  
They positively correlated with lEBt<  
Present gc 14 %  
Our results are consistent with our recent data that suggest that %&+j(?9  
30 y#:_K(A" k  
contribute to I_('Mr)  
meets the needs of real life production,/ the current demands placed upon it Ji_3*(  
must be justified kzG m D i  
point out n jveZav  
play an important role )oJn@82C|  
relates to sv0) sL  
rely on CA)DQYp{  
We performed wfQ 6J0  
satisfy the needs 3%Z:B8:<y  
determine the total requirements for the ... { as#lHn  
uses ... as a key to search for... a9C8Q l  
without relying on !rzbm&@  
will be available/ performed/ overlooked 5F{NPKa Q  
NOUN PHASE `LU[+F8<  
a basic technical function of tLXwszR0r  
a significant reduction of 3-z; pk  
drug variability XdX1GH*C  
a critical need 'thWo wE  
negatively correlated with qRkY-0vB P  
a key / principle feature of C7#ji"t  
a substantial impact on #@s[!4)_I  
an intensive review was conducted #=mLQSiQ  
The analysis of the correlations by Y5nj _xQJL  
an increasing need for expanding the application of .... )Qe<XJH!  
an important component / function / aspect / issue dU`kJ,=Z  
each rule is numbered in sequence 28,Hd!{  
each of these involves LpCJfQ  
for this calculation, it is necessary to define cu{c:z~  
in the physical environment / integration of En01LrC?  
in the reality of situations where … j#:IG/)GL  
many aspects of qiEw[3Za]'  
most past efforts have been spent on ... r<< ]41  
common sense to a well studied and documented technical field. 8EbJ5wu/%S  
sources of additional information on ... are listed CK[w0VCT  
systematic and rationally structured format ^j~CYzmt  
the basis on which a range of ...operations can be established is shown R( 2,1f=d  
THE basic philosophy / principles of / key element / general hypothesis / candidate list d\c?sYLv  
of / concept of ... has attracted wide interest / function is concerned with / heart / 73C7g< Mx  
impact / nature / role / task of / kernel functions ENoGV;WG  
the number of parts needed to 3[_zz ;Y*d  
the above statement means that 6gr?#D -F  
the output data is passed to MBp,! _Q6  
31 O@9<7@h+Nl  
the proposed method / underlying principle 4hl`~&yDf  
the recommendations made in this report, if implemented, should ,F;<Y9]  
this information resides in P3e}G-Oz  
this process is composed of ... different ... operation s?j||  
along with the use of E]MyP=g$  
concerning general aspects of aG*Mj;J  
due to ;o#wK>pk%M  
for later use in generating..., <>l!  
in turn, AQ<2 "s  
it can be claimed/concluded that gH u!~l  
it demonstrates the decisions required of EJByYk   
it also provides information to .. -dO9y=?t  
it becomes essential to h*lU&8)m\  
let ... be the probability that zNh$d;(O$^  
once... is written, it is compiled into... +Rq7m]  
suppose it is observed that $ T2 n^yz  
this is because w+Oo-AGNH  
this results in a N*{>8iFo4  
upon completion of the ... analysis, L=v"5)m2R  
when the knowledge is of mathematics or quantum physics, it will also be {0J (=\u  
recorded in books and papers _[p@V_my  
selection of rules for using the tools, for generating operation plans, B,NHy C1i  
is another matter of preference, since practice varies greatly. /OsTZ"*.2/  
for the sake of convenience  gU%R9  
correct decision to be reach ?S0gazZm  
keeping the number of rules to a minimum. $?Yw{%W  
a good process plan will result exhibiting several characteristics: # fkOm Y7X  
practical solutions ATq-&1hs  
because of rather small job lot sizes ufc_m 4PN  
Backward reasoning can be used to answer the question "should milling tool be select" L\/YS;Y  
different level of knowledge in the realm of process planning
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