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楼主  发表于: 2009-10-18   

医学SCI 论文经典句子

18 |Ax~zk;  
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number *_3+ DF  
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The a{,EX[~b  
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at VI[ikNpX  
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The A1>R8Zuhy  
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 X{<j%PdC  
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, eB^:+h#A_  
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive l^WFMeMD3a  
control for Ca2+ induction. The data thus obtained was analyzed with the software Win Ga"$_DyM  
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on 'C!b($Y  
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 R/A40i  
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were >/eQjp?:  
harvested and fractionated as detailed above, and the S-100 fractions were assessed by n<y!@p^X  
immunoblotting for presence or absence of annexin I. N@)tU;U3O  
Mouse bone marrow transduction and transplantation. '$UlJDZ  
Retrovirus-mediated transduction of mouse bone marrow cells was done by published +wgNuj0=*  
methods49. Prestimulated low-density bone marrow cells were infected with high-titer 1j9.Q;9  
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated CXb)k.L   
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing jx+%X\zokA  
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by r,EIOcz:  
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) q_ykB8Ensa  
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone Y*dzoN.sW  
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis /F5g@ X&  
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of 3;>|*(cO  
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was m("! M~1  
confirmed by immunoblot analysis. ZS4lb=)G  
Determination of renal morphology #,0%g 1  
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an tz6d }$   
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, +Y0Wiwr'  
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner (B}+uI{  
for morphologic alterations, as previously detailed 9pb4!=g*  
Patient population 2$jTj<.K  
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) "nf.kj:>  
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per o2He}t2o  
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) NgaX&m`  
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. AL>*Vj2h/n  
The Mayo Institutional Review Board and the Research Ethical Board, University Health A<C`JN}  
Network, University of Toronto approved the study protocol. All patients gave written X@*$3z#Z  
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or s"*zyLUUo  
19 3U!\5Nsby  
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 !i& ^H,  
months were not included in the study. Patients with active infection, diabetes, or a ek1Y aE  
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), >%h_ R:  
medications, malignancies) were also excluded. R+ lwOVX  
Treatment -n?}L#4%8  
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of Dt0S"`^=k  
high-quality protein) diet was recommended and patients were encouraged to maintain &B1d+.+  
the same diet throughout the duration of the study. All patients received a similar E5w. wx  
conservative treatment regimen that included loop diuretics to control edema, an kL 6f^MoL  
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. lX/6u E_%  
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added jhr{JApbJv  
when required to control systolic blood pressures to <135 mm Hg in >75% of the *z!!zRh3x  
readings. Patients who after a minimum of 4 months of conservative therapy and 8l-+ 4~mH  
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of (D]l/akP  
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, {}H5%W  
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine wXIsc;  
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given h?jy'>T?b2  
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count `c ~Va/Yi  
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count rlqn39  
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per *lRP ZN  
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a L ']EYK5  
second course of rituximab treatment following the same protocol described above.  uh*b[`e  
Follow-up Qctm" g|  
In all patients, clinical and laboratory parameters including complete blood counts, p:U9#(v)  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum Gnop  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry Xm`jD'G  
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion h~)oiT2v  
in the urine were assessed by performing two consecutive 24-h urine collections at each Kf2Ob 1  
time point. Data were considered accurate when urinary creatinine excretion was fEf ",{I  
consistent with a complete 24 h collection. The mean of the two measurements was p8o ~  
considered for the analysis. The presence of HACAs was evaluated at baseline and at %B5.zs]Of  
months 3, 6, 9, and 12. %p6"Sg*  
Method / Approach / Study/ Technique ,rVm81-2  
A discussion is presented of a problem-solving system Sr Z\]  
To improve the efficiency of the method, the following approach may be applied. c-.t8X,5(~  
In order to an investigation was made to find the causes of the Vui5ZK  
Although large collections of rules and equations have been complied, none are generally [ R1S+i  
accepted Tu2 BQ4\[  
20 ]BGWJA5  
This approach will be explained and discussed thoroughly in the body of the report. S^'?s fq  
This can be accomplished by dmI,+hHtL  
This algorithm to compute the total cost can be described step by step as follows: 0j\?zt?  
The above preliminary analysis has provided important information V1 T?T9m  
Various methods have been proposed for selecting an optimum... Se/VOzzg  
These concepts have been applied to NKf][!bi  
On the basis of the concept mentioned above, i lk\&J~I  
This can be achieved by ?JO x9;`  
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the sN0S~}F+  
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, rM<|<6(L  
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced # le<R  
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 >ly`1t1  
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada {E`[ `Kf  
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% gjB36R  
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections <+@?V$&  
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin '7AlE!7%  
complex. Sections were counterstained with hematoxylin and examined by light PhL}V|W>  
microscopy. 17g\XC@ Cl  
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay &TYTeJ]  
performed at Genentech Inc. that measures the antibody response to rituximab in human B@g 0QgA  
serum samples. ^]:w5\DG  
In all patients, clinical and laboratory parameters including complete blood counts, `F5iZWW1  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum J%`-K"NB  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry  x~p8Mcv  
and at months 1, 3, 6, 9, and 12. G?$|aQ0j  
This fact suggests that a new concept |>o]+V  
This was accomplished by taking ... h?E[28QB  
The preparatory stage is very time consuming process. iIWz\FM  
Test are performed for validity, completeness, and compatibility :{@&5KQ8)  
There is little hope of achieving successful ... xL8r'gV@  
There has been an increasing awareness of the potential of using most ..so far made have Sc03vfmo"N  
not taken this approach, with the exception of V|GH4DT=  
Only a few studies can be found. qW*JB4`?a  
It is a very tedious process to go through LVNq@,s  
It is only when .. has been completed that .. may be effected S9/oBxGN  
The entire interpretation process is conducted in one's head. _GEt:=DAP#  
These approaches are sometimes very tedious. R gY-fc0  
Several techniques can be used xCU^4DO3p  
A polynomial parametric model can be written as [the following]/[follows]: ):"Z7~j=  
A xx model is constructed/formulated using xx. 4q sIJJ[.  
A xx model represents an xx by its xx. y+b4s Ff  
A process decision model captures the logic essential to _BGw)Z 6  
From the equation above, xx is equal to the summation of xx times the ... %Jy0?WN  
21 B-Bgk  
The validity of a xx model can be checked using Euler's formula. \Tq !(]o^  
Given a model, one can mathematically determine whether ... or ... )I7~ <$w  
Equations for xx need to be derived and implemented in the system. \Tf[% Kt x  
A number of heuristic rules have been developed for 6mcxp+lm|  
Optimum .. techniques can be made more reliable by ... so that o,o,(sII  
An algorithm based on the characteristic ... is used to determine hP1}Do  
Euler's formula states the following: )1 ]P4  
The completed model should agree with the formula. 6)<g%bH!  
For manufacturing purposes, a detailed and precise model of the object is necessary oU/CXz?H  
Engineering design models are very well defined; therefore, q\+khy,k  
To keep the domain narrow enough to be implementable, yet wide enough to be useful. <1")JDW  
Point of View 5f5 bhBZ<  
from an implementation standpoint, )qXl8HI  
From the point of view of this application, 80qSPitj  
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). mOiA}BGw  
Information is the meaningful interpretation and correlation of some aggregation of data h#_KO-#.[  
in order to allow one to make decisions. M0Eq 7:Ba  
From a practical point of view, the computational aspects of an FLC require a !~X[qT  
simplification of the fuzzy control algorithm. " S8JHHx  
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, yb 7  
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM #<_gY  
p.129] LjZvWts?  
Statistical analysis TVaD',5_V%  
Data were analyzed by one-way analysis of variance comparing the three conditions +7yirp~`K  
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If Xx.4K>j+j  
significant F-statistic from analysis of variance existed, this test was followed by Dunnett )8BGN'jyi  
post hoc multiple comparison procedure with sham operation as the control group. For all um/2.Sn>  
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as BGk>:Z`  
statistically significant. =m<; Jx5  
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney 9VqE:c /  
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, XwI~ 0  
CA, USA). 6??o(ziK$  
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was m8Wv46%  
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's /g|H?F0  
test, where appropriate. +ZuT\P&kR5  
Data are expressed as mean s.d., median and interquartile range, or frequencies, as :0G_n\  
appropriate. Variables who deviated from the normal distribution (positively skewed) $-HP5Kj(k-  
were log-transformed (log10) before the correlation study. t r)[6o#  
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test 4r'QP .h  
post hoc analysis of variance were used as indicated below, for the comparison of "6[a%f#Q  
22 B8XW+U  
morphological, immunohistological and functional parameters. Statistical significance 0F"W~OQ6  
was set at P<0.05. <>gX'te  
The primary efficacy parameter was defined as change in urinary protein excretion from  O=,[u?  
baseline (week 0) to 12 months after treatment. The 12-month changes were tested jkTh)Bm|'  
against zero using the paired t-test. Secondary end points included 6-month changes in 79DzrLu  
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular =r w60B  
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on |2i=oX(r|  
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. W^a-K  
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. HDmjt+3&n  
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 K;:_UJ>t  
Definition of remission status is according to the criteria established by Cattran et al.30 [uJfmrEH  
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a {;z{U;j  
>50% reduction in peak proteinuria and non-response as <50% reduction in peak Ri<7!Y?l  
proteinuria. Any patient reaching a CR or PR was considered a treatment success jTR>H bh  
The statistical significance of differences for the mean values of cytokine concentration 9.:]eL  
and T cell proliferation was determined with Student's t-test. Differences with a P value :.k1="H~@  
of less than 0.05 were considered significant. 3"*tP+H  
Statistical significance was determined by Student's t-test. Data with a P value of less ?S*Cvr+=4  
than 0.05 were considered significant. n7|8`? R^  
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P &["s/!O1R  
values less than 0.05 considered statistically significant. m1 tYDZ"i  
The significance of differences among groups was determined by Student's t-test and 6`c5\G+  
one-way analysis of variance (SigmaStat software; Jandel). kFRl+,bi~  
Comparisons s6DmZ^Y%  
As well, the pros and cons of these representations from a process planning point of view xJ$/#UdP  
will be discussed. %Tv2op  
The method of using xx to implement xx described by Zadeh (1973) appeared more <:n !qQS6  
suitable  &x":  
As discussed [in the previous section]/[preciously], 5[[ mS  
Relation s|`ZV^R  
We can not invert F' directly because it defines a many-to-one mapping. +HXR ))X  
The relationships appear very complicate qxQuXF>:#  
Lifting tasks involve complex and imprecise relationship between the task variables and n@JZ2K4  
the human operator's characteristics. hZ[(Ik]*Zd  
These methods are based on the relationship between ... and ... zao=}j?  
The fundamental concept of a fuzzy rating language is that we can establish a relationship A_4.>g  
among terms such as high, medium, and low, and then modify these relationships. *el~sor;S  
This article will thus mention the latter as well as the former. ^pysoaZCT_  
The former two bear a close relation to a fuzzy Cartesian product. 6CV9ewr  
Importance 7'g{:dzS*3  
+_T`tmQ  
23 *U mWcFoF  
The emphasis is on an implementation of a general approach to rule based decision q`0wG3  
making. BN~g k~t_  
Consideration / Attention 8#{DBWU  
Careful evaluation is necessary to ensure Xl %ax!/  
Such a formulation does not change further considerations. fP KFU  
Considerable attention has been paid to 7C>5Xyy J  
Attention should be paid to an important finding of this investigation. u85  dG7  
Caution should be exercised in this process to avoid ... 6ec#3~ Y]  
Primary consideration is given to ... components, though others can be accommodated v,d bto0  
After ... has been defined by ..., a carefully analysis is carried out/performed to determine KNG7$icG  
A number of factors such as ...need to be taken into consideration before making the 61~7 L^882  
appropriate decision. ]ft}fU5C1  
It should be noted that YHOo6syk  
It is important to point out that ... 'Z8=y[l  
These considerations have heightened interest in the possibility of providing ... UbEK2&q/8  
We should stress the fundamental importance of the xx hd1aNaF-  
Results. +pY-- 5t  
Advantages / Disadvantage a{@gzB  
One of the major advantages of this new measure of xx is that it can be applied to the $]<wQH/?_  
experimental study of +GvPJI  
One advantage of using a .. is the ease of preparing it. #GuN.`__n,  
It has a very fast decision making process I&9Itn p$  
All the algorithms involve mostly logical operations. fZavZ\qU  
It can be easily and without additional cost implemented in a microprocessor;based cd(YH! 3  
environment. 1d 1 ~`B  
It can reduce the waste of designing from scratch. rHp2I6.0a  
The advantages of using a xx to represent xx are the following: 0fog/c#q(  
However, xx is not without its shortcomings. ;-^8lWt  
In most cases, the xxx shows an improvement over the existing xxx. KA? J:  
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. }u]7x:lh  
The "best case" results shows a savings of 6% to 9%. l.xKv$uOGR  
Most of the existing works based on xx approach can only recognize a xx . _P9*78  
Most of the above methods are computational expansive and limited to xx. Vr:`?V9Q2(  
Some other advantages of xx are the following: $'n?V=4  
The problem is the limitation of this method to a limited domain of parts. 9~{,Hj1xE  
It proved limited in application because it demanded precision in system modeling that ZkryoIQ%=  
was impossible in practice. ^#!\VGnL  
There are advantages to be gained in the structuring of costs and benefits, the use of xx, .dsB\ C  
The disadvantages of this method are also disadvantages of conventional xx approaches. j@R"AP}  
This combines the best features of both techniques CrB4%W:{  
24 TPn#cIPG  
Hopefully, this tool can be as the reference framework of for developing a xx platform, yRR[M@Y  
and helping the administration, marketing, and knowledge management activities in U%n>(!d  
virtual communities. jAdZS\?w  
Results !j /54,  
An improvement on the result shown above can be made by based on the data provided >P ~j@Lv  
Recent work has identified uann'ho?q  
Time-dependent changes of [r1dgwh8  
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase 1&RB=7.h  
and does not require ERK activation. =E62N7_`=  
Much of the current work on 48Jt1^  
Discussion of these theories is beyond the scope of this review &$ fyY:<\  
Based on the information contained in this @0V4$OoFl  
The result can be categorized into nine classes &crR nv ?  
The results are illustrated by an example urg^>n4V]  
The experimental results for each xx time are reported in Table 2. n#sK31;yb  
From the results obtained so far, it seem that X\kWJQ:  
Because of the inaccuracy of the ..., a conclusion cannot be drawn as S`Z[MNY  
Although much effort has been made to., this reality is far from completion. ipE|)Ns  
The results indicate that the total benefits are higher than the total costs. ;I*N%a TK  
Their results may then serve as guidelines for lower level models, less fuzzy and more ,/&|:PkS  
detailed. ?6UjD5NkX  
Conclusion yqH9*&KH{  
From the discussion, one may conclude that ... t t|P-p-  
The first indication that |;\pAZ2  
In summary, we have shown that RXw1HRR$V  
These results suggested that egAYJK-,!  
Our findings have shown that !<out4Mz"  
Our observations have provided P)Rq\1:  
This study reveals following five main findings: S$gLL kD1  
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in 7yjun|Lt}X  
the diabetic kidney. ^\[c][fo  
As mentioned above, VK!HuO9l  
Moreover, we demonstrate that, \58bz<u"  
A number of studies have elaborated a body of knowledge about hAs ReZ?  
There are findings to indicate that %`~+^{Wp  
On a descriptive level, there is agreement that for ` q`ah_  
One issue that became particularly evident from our study is ObJ-XNcNH  
Our data are in agreement with the findings and models presented by previous 3h$ E^"  
publications, in particular those of Jones et al eSHsE 3}h  
According to our observations, )!U@:x\K  
…was not evident from our data JTObyAoW  
25 u8t|!pMF8  
It could therefore be concluded that |!/+ T^u  
our data illustrate that l`uMtv/Wp  
All these different aspects, as listed above, lead to 2.N)N%@  
In fact, it has already been speculated that y4r?M8]"r  
It should be furthermore mentioned in this context that =>kg]  
To identify and verify the essential factors triggering developmental renin expression, it 6(x53 y__  
is of interest now to study the development of intrarenal renin expression in mice with Q v g_|~n  
defined gene mutations, using the results of this study as a reference system. L8H:, } 2  
In conclusion, using several approaches, we demonstrated that :I2,  
But we have not provided formal proof yet that We\i0zUU  
In summary, our results suggest that BsL+9lNue  
In conclusion, we identify oRJ !TAbD  
A better understanding of such regulatory systems may yield novel therapeutic X|/RV4x@Cq  
approaches to glomerular diseases. !* KQ2#e  
Preliminary results of short-term studies (2 weeks) indicate that ZJ~0o2xZ'  
However, we believe that iBtG@M  
However, despite our extensive measurements of these parameters, we found no q317~ z_nl  
relationship between response and initial proteinuria, time to B-cell recovery, the "5z@A/Z/  
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree I3b*sx$  
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be US=K}B=g  
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved ~kj96w4eAR  
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and /Oi(5?Jn  
that will also look for factors that may determine its efficacy in IMN. XA(.O|V Z  
It has become increasingly clear that )MLbE-@  
Form the above discussion, the conclusion can be reached that z@o6[g/*Q  
The conclusions drawn are also valid IW>~Y l?  
In conclusion to this, it becomes obvious that the problem of xx lies not only in... k Jw Pd;%  
We have attempted to introduce some concepts associated with a theory of tIV{uVM[|D  
Considerable more work, hopefully, will be done in this area lkly2|wA  
Employing the compositional rule of inference, the assessment of the xx compatibility in @GGQ13Cj(  
achieving prescribed xx projectiles in any level of the hierarchy is made possible. 1RX-`"^+  
This paper has presented a theoretical and experimental study of the xx process and xx aMxj{*v7  
concept. l_$>$d  
The experimental research results will hopefully serve as useful feedback information for <#;5)!gr{  
improvements for xx work. K" |~D0Qgo  
The scope of this contribution was to introduce a xx method. tCoE4Ed  
This has a tremendous impact on our understanding of -q[x"Ha%  
Significant progress has been made in advancing RNAi therapeutics in a remarkably 7cWeB5 e?O  
short period of time W`c$2KS?DO  
To date, little is known about… l:bbc!3  
Irrespective of the mechanisms and the molecules –which are still largely unknown – dZ8ldpf8  
involved in MSC functions, current data suggest that isy[RAP<  
To better understand .w _BA)  
26 GA` bWl  
Future Research (常用于conclustion 的结尾) D5({&.X[-  
Thus, first extension of the approach could be, "w0~f6o  
Further studies are needed to determine the importance of L[<Y6u>m!1  
Some improvements to the scheduling aspect of the model may be brought through (3Xs  
additional levels in the hierarchy for more detailed representation of the scheduling 1*$6u5.=F  
activity. |uz\XK  
It also unveiled new aspects of the role played by thyroid hormone in response to injury zBwqIJfM  
and tissue repair. (CH6Q]Wi_!  
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and aIQC[ry  
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of   )*6  
drug molecules. t6`(9o@}  
In the next few years it should become clear whether AZ^>osr  
It should be an exciting time for researchers seeking to harness this powerful endogenous AS:k&t  
pathway to treat human disease. n[qnrk*3 %  
Acknowledgement -|s% 5p|  
The authors are grateful to the insightful work provided by Mr. John W. Harney and all z.\\m;s  
of the fellows and students that contributed with some of the studies discussed in this \ *BRFUAc  
article [+CFQf>  
I would like to express my gratitude to all those who gave me the possibility to complete bA$ElKT  
this thesis. ;"e55|d9I  
I want to thank the Department of Transport of the former Interim Government of |0>rojMq  
Namibia for giving me permission to commence this thesis in the first instance, to do the nGK=Nf.5  
necessary research work and to use departmental data ._;It198f  
This work was supported by NIH grants AI058695 and AI056900. We thank members of $AvaOI.l  
the laboratory and our collaborators for many useful suggestions. Y#-c<o}f  
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. Au/'|%2#(  
Duckman for graphics assistance and A. Capobianco for word processing assistance. nehk8+eV_  
Author contributions mI:D  
All authors were involved in experimental planning and data analysis and contributed to E5|GP  
manuscript preparation. )@y'$)5s  
Tables and Figures *!Gb_!98  
Figure 7-1 sketches these relationships. Rf>V]R  
The graphical representation of these functions is shown in Figure 1. ts@ e ,  
The xx may be depicted as in Figure 1. <; Td8O89_  
Figure x shows the schematic diagram of the 6 !fq658  
Figure 1 though 2 provide a ... that j\Fbi3H  
the architecture of this expert system for .... is illustrated in Figure 2. B=X_c5  
Figure 2 gives the outline of an ... system 9WQ'"wy AQ  
Table shows the YY7dw:>e/  
27 ygQAA!&']  
Time-dependent changes of 4IM&#_6  
as shown in Table 1 and 2  %\B?X;(  
This concept is illustrated in Figure 2 G&M)n*o  
At the top of Table xx are shown two blocks of data.  Spo[JQ%6  
Each table or matrix has constructs xx through xx as row;headings, 4`r-*Lx  
xx through xx as column;headings. {cw+kY]m4-  
Time course of calculated renin immunoreactive tissue volumes during development of ,d=Dicaz  
the mouse kidney. Data are single values per time point. They were derived from the T0\[": A  
kidneys shown in Figure 1. &mA{_|>  
Yellow color indicates N$ 2Iz  
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then MpIP)bdq7  
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were lx82:_  
analyzed by western blot using phospho-specific antibodies. g^\>hjNX  
ERK and PKB activation were measured by western blot using phospho-specific 3}.OSt'=  
antibodies n0^3F1Z  
The data are the means of three different experiments taking the number of untreated cells G#'G9/Tm  
(vehicle alone) as 100%. _9iF`Q  
ERK and PKB activation were then analyzed by western blot with the corresponding +gb"} cN  
phospho-specific antibodies. To ensure equal amount of protein in each lane, western S8]YS@@D   
blots against total protein were performed for ERK and PKB. "+4r4  
The means of optical density (OD) values of the bands detected in western blots of three cn_*,\}  
different experiments are plotted, taking the maximal value of phosphorylation of ERK l W Lj==  
and PKB as 100%. k~$}&O  
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with DJRr  
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then \&Oc}]  
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence *eUxarI  
microscopy (lower panel). jouT9~[L'  
The data are the means of three experiments performed on different days taking the Vjr}"K$Y  
number of cells at the onset of the experiment as 100%. i$'#7U  
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction 88atj+N]  
(n=9 each). 0a v2w5>af  
*P<0.05 versus non-nephritic rats. e= _7Q.cn  
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, y@]:7  
positive control, M, molecular weight markers). v;R+{K87  
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. 5' 3H$%dC  
Data are means s.d. of four independent experiments. 0J9Ub   
*P<0.05 versus 0.5 h. L>2gx$f  
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 aw'o=/a8  
mRNA as determined by real-time RT-PCR and normalized to Csx??T_>r  
glyceraldehyde-3-phosphate dehydrogenase mRNA. %@[ ~s,6<  
Cell number was counted in duplicate using a Malassez hemocytometer ltG|#(  
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with 1?ST*b  
MCDB media for 24 h, #P<0.05. }kb6;4>c  
28 >]l7AZ:,  
The curves are adjusted for history of coronary artery disease, CRP, and progression to Vb8{OD3PK  
ESRD. hc5iIJ]  
Both models are independent of age, gender, baseline GFR and proteinuria, and other ;!/g`*?  
clinical characteristics and traditional and nontraditional cardiovascular risk factors -D,kL  
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH e!O:z   
(n=99, P<0.0001, r2=0.190) 1ba* U~OEg  
Concentration of serum FGF23 concentration before starting and at the end of the 4-h $8Y|& P  
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, X0gWTs  
Student's paired t-test). '9q:gFO  
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; BZWGXzOFh  
arrow=endothelial cell and CD=collecting duct GF awmN Z  
Magnification: 1000. +h? z7ZY^  
A table of .. is developed and significant recommendations are made. iQ_^MzA  
CONJUGATION wDS(zG   
To Indicate Addition Q?TXM1Bp  
additionally, again, also, and then, as can be easily understood, besides, equally important, Nc[V kJ]  
especially, finally, for the same reason, first, further, furthermore, in addition, last, /2e,,)4g  
likewise, moreover, next, second, third, too, evidently, obviously, roughly speaking, s~MCt|a  
broadly speaking tR% &.,2  
To Indicate Cause and Effect Luu.p<   
accordingly, as a result, consequently, for this reason, hence, in short, otherwise, then, Pi:=0,"XOp  
therefore, thus, truly =5Auk 5&  
To indicate Comparison GjvTYg~  
in a like manner, likewise, similarly , alternatively  #mcU);s  
To Indicate Concession fE/|U|5L[  
after all, although this may be true, at the same time, even though, even so , I admit, 4Z<  
naturally, of course VyL|d^'f_  
To Indicate Contrast -$m?ShDd  
and yet, at the same time, but, for all that, however, yet, in fact, in contrast, in the real life, Q.Ljz Z  
in spite of, nevertheless, notwithstanding, normally, on the contrary, on the other hand, -S%)2(f^  
still, traditionally, rather, unfortunately, z@n77 9i  
To Indicate Time Relationships @ s@67\  
after a short time, afterwards, as indicated earlier, as long as, as soon as, at last, at length, !4l\*L  
at the moment, at that time, at the same time, before, earlier, currently, immediately, in LQrm/)4bF5  
the meantime, in recent years, lately, later, meanwhile, often, of late, presently, recently, }8cX0mZ1j  
soon, shortly, since, thereupon, temporarily, therefore, until, when, while SQd`xbIuL  
29 nmrYBw>  
To Indicate Special Features or Examples ] /{987  
for example, for instance, incidentally, indeed, in fact, in other words, in particular, in _{5t/^w&!  
practice, specifically, that is, to illustrate, in this respect, theoretically, as mentioned  kwd)5J  
before / above 8^Ov.$rP  
To Indicate Summary `F<[\@\d5  
in brief, in conclusion, in short, in summary, on the whole, to conclude Ew kZzVuX  
, in general, to summarize, to sum up, as a result, ultimately, IN%04~= H  
VERB PHASE {? dW-  
build a .. model MjHjL~Tg  
have been described to @.fyOyOC  
To assess the functional role of YQ+Kl[ec  
we detected KVrK:W--p  
build up the key link q;V1fogqI)  
Although a number of studies have identified predictors of nBVknyMFNF  
began a new era in ... CF`fn6  
can be regarded as / achieved / used to/for / found / obtained through mxRe2<W  
can result in %Jpb&CEY  
carries out ... tasks Nh[{ B{k  
production information in order to simultaneously RO"*&o'K'  
contains all information necessary to describe A<& :-Zz  
do not make use of production information ?Ze3t5Ll  
deals with ^<e"OV  
end with failure fV;&)7d&  
fetch the information from the model directly pw7_j;}l  
has great potential / yet to be resolved / spurred the development of / kPVP+}cA  
been recognized as 2,>q(M6,EA  
site component / cable of / currently implemented for / demonstrated by an example / Hf/2KYZ  
finally reached / made equal to / equivalent to / more suitable to / oriented to / 8bX\^&N  
interpreted as / pointed out / potentially of great benefit in the complex task of / shown N[$(y} !s  
in / used to effectively guide the search pr-{/6j6  
makes use of ] 05Q4  
was significantly higher as compared to e;=G|E  
To assess disease-specific alterations, we measured , "zS  pN  
To specifically assess the relationship between  *ihg'  
make up WPE@yI(  
To determine if MjI}fs<   
This statistically significant difference still l!ye\  
They positively correlated with &- +&`h|s  
Present IBVP4&}x$  
Our results are consistent with our recent data that suggest that e?G*q)l  
30 ji( S ?^  
contribute to @D"1}CW  
meets the needs of real life production,/ the current demands placed upon it /$rS0@p  
must be justified "0L@cOy G  
point out &V( LeSI  
play an important role N13 <!QQ  
relates to q0y?$XS  
rely on y&__ 2t^u  
We performed ==(M vu`  
satisfy the needs `T9<}&=!  
determine the total requirements for the ... 3F}d,aB A  
uses ... as a key to search for... 9/s- |jD  
without relying on 6}ax~wYct  
will be available/ performed/ overlooked `%ymg8^  
NOUN PHASE iCx'`^HnP  
a basic technical function of n6o}$]H  
a significant reduction of 1<R \V  
drug variability SwP h-6  
a critical need m d C. FO-  
negatively correlated with &P {%C5?{  
a key / principle feature of @pko zE-  
a substantial impact on \O/=g6w|t}  
an intensive review was conducted Hh@mIusj  
The analysis of the correlations by 2=3iA09px  
an increasing need for expanding the application of .... 2dI:],7  
an important component / function / aspect / issue 3 S5QqAm  
each rule is numbered in sequence E{Q^ZSV3B  
each of these involves cA Lu  
for this calculation, it is necessary to define Aqm0|GlJ  
in the physical environment / integration of Y.C*|p#  
in the reality of situations where … o4Ba l^=[  
many aspects of |F=^Cu,  
most past efforts have been spent on ... g{a0,B/j  
common sense to a well studied and documented technical field. igQyn|  
sources of additional information on ... are listed #e0+;kBh  
systematic and rationally structured format }gn0bCJy  
the basis on which a range of ...operations can be established is shown +<|w|c  
THE basic philosophy / principles of / key element / general hypothesis / candidate list FJ[(dGKeE  
of / concept of ... has attracted wide interest / function is concerned with / heart / \4&g 5vE  
impact / nature / role / task of / kernel functions e'?(`yW>  
the number of parts needed to #QB`'2)vw  
the above statement means that ~>EVI=?  
the output data is passed to w])Sz*J  
31 oc?VAF  
the proposed method / underlying principle { p/m+m  
the recommendations made in this report, if implemented, should qjFgy)qV  
this information resides in lV 1|\~?4  
this process is composed of ... different ... operation Tv KX8m"  
along with the use of !`WuLhB`  
concerning general aspects of ~+g5?y  
due to AX)zSrXn  
for later use in generating..., $OO[C={v[  
in turn, yqU++;6  
it can be claimed/concluded that v$cD!`+k  
it demonstrates the decisions required of 68SM br  
it also provides information to .. K$Ph$P@   
it becomes essential to e'`oisJU?q  
let ... be the probability that ^/+sl-6/F  
once... is written, it is compiled into... 8+ u8piG  
suppose it is observed that M Q6Y^,B  
this is because anvj{1  
this results in a x\%eg w  
upon completion of the ... analysis, cm]]9z_<  
when the knowledge is of mathematics or quantum physics, it will also be NR*SEbUU*  
recorded in books and papers EDo (  
selection of rules for using the tools, for generating operation plans, Rc 4EF HL  
is another matter of preference, since practice varies greatly. --9mTqx  
for the sake of convenience w.8~A,5}Dh  
correct decision to be reach g|P hNo  
keeping the number of rules to a minimum. d}ZH Y[  
a good process plan will result exhibiting several characteristics: +6=!ve}  
practical solutions gy{ a+Wbc*  
because of rather small job lot sizes _a&|,ajy >  
Backward reasoning can be used to answer the question "should milling tool be select" e0L;V@R  
different level of knowledge in the realm of process planning
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