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楼主  发表于: 2009-10-18   

医学SCI 论文经典句子

18 NoO>CjeFb  
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number <Q/^[  
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The m(q6Xe:Vc  
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at 3H%R`ha  
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The k^Zpb&`Hx  
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 O_K@\<;~  
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, \#1!qeF  
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive bxyEn'vNvQ  
control for Ca2+ induction. The data thus obtained was analyzed with the software Win Wv_5sPqLW  
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on >9a%"<(2#  
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 2FD[D `n]f  
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were 9Re605x Q6  
harvested and fractionated as detailed above, and the S-100 fractions were assessed by 6#T?g7\pyR  
immunoblotting for presence or absence of annexin I. ?=jmyDXH!  
Mouse bone marrow transduction and transplantation. +cvz  
Retrovirus-mediated transduction of mouse bone marrow cells was done by published |2CW!is  
methods49. Prestimulated low-density bone marrow cells were infected with high-titer aQCbR S6  
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated :>nk63V (  
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing Fly@"W4a  
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by _Jk-nZgn  
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) CEc& G  
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone UYW%% 5p?  
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis Vyj>&"28  
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of -kES]P?2  
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was $ 8_t.~q  
confirmed by immunoblot analysis. n]ar\f  
Determination of renal morphology ZgtW  
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an T=VVK6Lc:  
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, [Qy]henK  
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner JQ+4 SomK  
for morphologic alterations, as previously detailed ETH`.~ %  
Patient population A&$!s)8z  
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) s[nOB0  
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per Vt n$*ML  
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) (d^pYPr{  
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. 7Yk6C5C  
The Mayo Institutional Review Board and the Research Ethical Board, University Health s7FqE>#c0  
Network, University of Toronto approved the study protocol. All patients gave written %E1~I\n:F  
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or IZJV6clM  
19 Q ;m .m2  
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 WRVKh  
months were not included in the study. Patients with active infection, diabetes, or a L}>9@?;GW  
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), p*Q"<@n  
medications, malignancies) were also excluded. b\=0[kBQw  
Treatment EoQ.d|:g  
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of Pl1:d{"d  
high-quality protein) diet was recommended and patients were encouraged to maintain gQ?>%t]  
the same diet throughout the duration of the study. All patients received a similar q n=6>wP  
conservative treatment regimen that included loop diuretics to control edema, an O(&EnNm[2  
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. N:L<ySJ7  
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added WpTC,~-  
when required to control systolic blood pressures to <135 mm Hg in >75% of the . s? ''/(  
readings. Patients who after a minimum of 4 months of conservative therapy and aMv  
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of cB -XmX/  
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, Hd;>k$B  
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine +"' h?7'C  
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given Dm 'Q&  
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count j{p0yuZ)<  
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count OEB_LI'  
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per AqN(htGvx  
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a .YS[Md{  
second course of rituximab treatment following the same protocol described above. /x$jd )C  
Follow-up x!I7vs~~zW  
In all patients, clinical and laboratory parameters including complete blood counts, I9Z8]Q+2"  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum w' L;`k;Q  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry u;=("S{"0  
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion ^GRd;v=-@  
in the urine were assessed by performing two consecutive 24-h urine collections at each {Ziq~{W_  
time point. Data were considered accurate when urinary creatinine excretion was .Ta$@sPh}  
consistent with a complete 24 h collection. The mean of the two measurements was 4{fi=BA   
considered for the analysis. The presence of HACAs was evaluated at baseline and at VLQf uh;  
months 3, 6, 9, and 12. ^]aD LjD  
Method / Approach / Study/ Technique ?5/Sa  
A discussion is presented of a problem-solving system 2H]&3kM3X  
To improve the efficiency of the method, the following approach may be applied. Yt|{l  
In order to an investigation was made to find the causes of the `^_.E:f  
Although large collections of rules and equations have been complied, none are generally [k1N`K(M  
accepted c&'T By  
20 ->93.sge  
This approach will be explained and discussed thoroughly in the body of the report.  \f  
This can be accomplished by t3bN P K^  
This algorithm to compute the total cost can be described step by step as follows: $9hOWti  
The above preliminary analysis has provided important information "J[Crm  
Various methods have been proposed for selecting an optimum... (a)d7y.oo  
These concepts have been applied to RYvS,hf 6z  
On the basis of the concept mentioned above, ri\r%x  
This can be achieved by U)c,ZxE  
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the F;MFw2G  
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, iCw~4KG  
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced %Xp}d5-  
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 ,T1 t`  
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada wcV~z:&^5  
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% AZtZa'hbkQ  
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections Iy`Zh@"~  
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin dq|z;,`  
complex. Sections were counterstained with hematoxylin and examined by light v ?Y9z!M  
microscopy. mtJI#P  
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay w"A'uFXLc  
performed at Genentech Inc. that measures the antibody response to rituximab in human v( (fRX.`  
serum samples. IURi90Ir  
In all patients, clinical and laboratory parameters including complete blood counts, Af*^u|#  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum @gs Kb* ,  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry M [Ls:\1a  
and at months 1, 3, 6, 9, and 12. G~^Pkl3%T  
This fact suggests that a new concept 3pq&TYQU  
This was accomplished by taking ... =;c? 6{<1  
The preparatory stage is very time consuming process. 5H?`a7q N  
Test are performed for validity, completeness, and compatibility >dZ x+7  
There is little hope of achieving successful ... Po=)jkW  
There has been an increasing awareness of the potential of using most ..so far made have kqv>rA3  
not taken this approach, with the exception of j1<@ *W&b  
Only a few studies can be found. ^9"|tWf6O  
It is a very tedious process to go through `@=}5 9+|  
It is only when .. has been completed that .. may be effected 1 !OQxY}f  
The entire interpretation process is conducted in one's head. hIPDJ1a  
These approaches are sometimes very tedious. a<c %Xy/  
Several techniques can be used fl+ [(x<  
A polynomial parametric model can be written as [the following]/[follows]: {"'W!WT b  
A xx model is constructed/formulated using xx. Q_LPLmM  
A xx model represents an xx by its xx. 3}n=od=  
A process decision model captures the logic essential to ~D<o}ItRF  
From the equation above, xx is equal to the summation of xx times the ... Vx-H W;,  
21 w doA>a?q  
The validity of a xx model can be checked using Euler's formula. xzIs,i}U  
Given a model, one can mathematically determine whether ... or ... <k}>eGn  
Equations for xx need to be derived and implemented in the system. Z4bN|\I  
A number of heuristic rules have been developed for d/Fjs0pt  
Optimum .. techniques can be made more reliable by ... so that ~F>oNbJIv  
An algorithm based on the characteristic ... is used to determine 0O"GI33Mg  
Euler's formula states the following: e +4p__TmZ  
The completed model should agree with the formula. C[? itk!  
For manufacturing purposes, a detailed and precise model of the object is necessary C6CX{IA]  
Engineering design models are very well defined; therefore, Yca9G?^\v  
To keep the domain narrow enough to be implementable, yet wide enough to be useful. {HvR24#  
Point of View x-CY G?-x  
from an implementation standpoint, 6i%LM`8GEk  
From the point of view of this application, ~$!eB/6ty  
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). Fov/? :f$  
Information is the meaningful interpretation and correlation of some aggregation of data 1:q55!b  
in order to allow one to make decisions. noh3mi  
From a practical point of view, the computational aspects of an FLC require a B;hc|v{(  
simplification of the fuzzy control algorithm. q;tsA"l  
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, OQ W#BBet@  
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM uSM4:!8  
p.129] \*!g0C 8 o  
Statistical analysis a5L#c=  
Data were analyzed by one-way analysis of variance comparing the three conditions )|uPCZdLZ  
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If |C7GI[P  
significant F-statistic from analysis of variance existed, this test was followed by Dunnett JS}W4 N  
post hoc multiple comparison procedure with sham operation as the control group. For all u)R>ozER  
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as 3`IDm5  
statistically significant. >OZ+k(saL  
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney <MA!?7Z|  
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, H<X4R  
CA, USA). #}:VZ2Z  
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was ~9h6"0K!  
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's NTs< ;ED  
test, where appropriate. <)?H98S  
Data are expressed as mean s.d., median and interquartile range, or frequencies, as 2s?j5 Sd  
appropriate. Variables who deviated from the normal distribution (positively skewed) 5(u7b  
were log-transformed (log10) before the correlation study. K)l{3\9l|  
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test Qn[4&nUD  
post hoc analysis of variance were used as indicated below, for the comparison of p Ic ;9  
22 o=q N+-N  
morphological, immunohistological and functional parameters. Statistical significance ;# {XNq<1  
was set at P<0.05. J j yQ  
The primary efficacy parameter was defined as change in urinary protein excretion from A9p$5jt7  
baseline (week 0) to 12 months after treatment. The 12-month changes were tested _o' jy^  
against zero using the paired t-test. Secondary end points included 6-month changes in Fl(+c0|kT  
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular j%]i#iqF  
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on aNv6 "  
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. !COaPrg  
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. \>23_d0  
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 nU[ROy5  
Definition of remission status is according to the criteria established by Cattran et al.30 1p+2*c  
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a $-5iwZ  
>50% reduction in peak proteinuria and non-response as <50% reduction in peak W%Br%VQJ  
proteinuria. Any patient reaching a CR or PR was considered a treatment success wvx N6  
The statistical significance of differences for the mean values of cytokine concentration vb5tyY0c  
and T cell proliferation was determined with Student's t-test. Differences with a P value v|t^th,  
of less than 0.05 were considered significant. Il~ph9{JH  
Statistical significance was determined by Student's t-test. Data with a P value of less 6LNm>O  
than 0.05 were considered significant. YOP=gvZq  
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P  W* `2lf  
values less than 0.05 considered statistically significant. SZ1+h TY7d  
The significance of differences among groups was determined by Student's t-test and 9p>3k&S  
one-way analysis of variance (SigmaStat software; Jandel). Z^>3}\_v  
Comparisons jW?.>(  
As well, the pros and cons of these representations from a process planning point of view ^[\F uSL  
will be discussed. Ax=Rb B"  
The method of using xx to implement xx described by Zadeh (1973) appeared more _9\ ayR>d  
suitable DH)@8)C  
As discussed [in the previous section]/[preciously], W O|2x0K  
Relation @xSS`&b  
We can not invert F' directly because it defines a many-to-one mapping. k2 k/v[60  
The relationships appear very complicate \qNj?;B  
Lifting tasks involve complex and imprecise relationship between the task variables and l')?w]|  
the human operator's characteristics. vxk1RL*Xu  
These methods are based on the relationship between ... and ... (!W:-|[K\  
The fundamental concept of a fuzzy rating language is that we can establish a relationship ,%v  
among terms such as high, medium, and low, and then modify these relationships. 9_5Fl,u z  
This article will thus mention the latter as well as the former. S=eY`,'#R  
The former two bear a close relation to a fuzzy Cartesian product. N/qr}- 3z  
Importance yZUB8erb.  
&AZr (>  
23 oizD: |  
The emphasis is on an implementation of a general approach to rule based decision "Z&{  
making. PG&@.KY  
Consideration / Attention T&w3IKb|}  
Careful evaluation is necessary to ensure H2E!A2\m  
Such a formulation does not change further considerations. &]16Hb~  
Considerable attention has been paid to W*}q;ub;  
Attention should be paid to an important finding of this investigation. $*9h\W-)`Q  
Caution should be exercised in this process to avoid ... jF_K*:gQ  
Primary consideration is given to ... components, though others can be accommodated )0yY|E \  
After ... has been defined by ..., a carefully analysis is carried out/performed to determine RUlM""@b  
A number of factors such as ...need to be taken into consideration before making the =5[}&W  
appropriate decision. kQsyvE  
It should be noted that ~Q0jz/#c  
It is important to point out that ... *&% kkbA  
These considerations have heightened interest in the possibility of providing ... 9"I/jd0B  
We should stress the fundamental importance of the xx vp[~%~1(  
Results. kzbgy)PK3  
Advantages / Disadvantage Pi40w+/  
One of the major advantages of this new measure of xx is that it can be applied to the 4%KNHeaN  
experimental study of Q/1 6D  
One advantage of using a .. is the ease of preparing it. A+iQH1C0h  
It has a very fast decision making process wHx1CXC  
All the algorithms involve mostly logical operations. Q|"{<2"]U0  
It can be easily and without additional cost implemented in a microprocessor;based DSM,dO'  
environment. cr27q6_  
It can reduce the waste of designing from scratch. =L 7scv%i  
The advantages of using a xx to represent xx are the following: KNic$:i  
However, xx is not without its shortcomings. : N>5{  
In most cases, the xxx shows an improvement over the existing xxx. TMhUo#`I|  
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. wbU pD(  
The "best case" results shows a savings of 6% to 9%. Hd U1gV>  
Most of the existing works based on xx approach can only recognize a xx . `2o/W]SSk  
Most of the above methods are computational expansive and limited to xx. bO>Mvf  
Some other advantages of xx are the following: j;=+5PY  
The problem is the limitation of this method to a limited domain of parts. 3G~ T_J&  
It proved limited in application because it demanded precision in system modeling that _W@q %L>  
was impossible in practice. Y`uL4)hR5  
There are advantages to be gained in the structuring of costs and benefits, the use of xx, vnw83a%3  
The disadvantages of this method are also disadvantages of conventional xx approaches. zb OEF  
This combines the best features of both techniques $-|`#|CBd  
24 <*i '  
Hopefully, this tool can be as the reference framework of for developing a xx platform, ^. &2-#i  
and helping the administration, marketing, and knowledge management activities in g7EJyA  
virtual communities. GO.mT/rB  
Results &y[Od{=  
An improvement on the result shown above can be made by based on the data provided Hq?-e?Nc  
Recent work has identified I: P/ ?-  
Time-dependent changes of ;[R{oW Nw  
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase jqPQ= X  
and does not require ERK activation. ZxlQyr`~a(  
Much of the current work on OxqK} %=Bw  
Discussion of these theories is beyond the scope of this review 8{Bcl5]<  
Based on the information contained in this p~Fc *g[!  
The result can be categorized into nine classes 3WZ]9v{k  
The results are illustrated by an example Wsyq  
The experimental results for each xx time are reported in Table 2. Z 7rVM   
From the results obtained so far, it seem that ~e~iCyW;S  
Because of the inaccuracy of the ..., a conclusion cannot be drawn as Kr3L~4>  
Although much effort has been made to., this reality is far from completion. H4ml0SS^  
The results indicate that the total benefits are higher than the total costs. v}XMFC !  
Their results may then serve as guidelines for lower level models, less fuzzy and more Q|q.~x<RQ  
detailed. Xp"ZK=r  
Conclusion MDGD*Qn~  
From the discussion, one may conclude that ... BUqe~E|I  
The first indication that i1e|UR-wl  
In summary, we have shown that  i1v0J->  
These results suggested that ~:~-AXaMT  
Our findings have shown that 4loG$l+a1  
Our observations have provided 'B ocMjRA  
This study reveals following five main findings: 0l=g$G \%  
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in G9J+D?'hH  
the diabetic kidney. x PoI+,  
As mentioned above, Z+! ._uA  
Moreover, we demonstrate that, sDA&U9;  
A number of studies have elaborated a body of knowledge about 4+qoq$F</  
There are findings to indicate that $a|C/s+}7>  
On a descriptive level, there is agreement that for b2]1Dfw  
One issue that became particularly evident from our study is {WfZE&B  
Our data are in agreement with the findings and models presented by previous N]f"+  
publications, in particular those of Jones et al / qp)n">  
According to our observations, 1 ;Bgtv$  
…was not evident from our data -8H0f- 1  
25 !cS A|C  
It could therefore be concluded that Q'xZ\t  
our data illustrate that -wJ/j~ +m+  
All these different aspects, as listed above, lead to &!7{2E\7C  
In fact, it has already been speculated that ?[{_*qh  
It should be furthermore mentioned in this context that zQvp<IUq  
To identify and verify the essential factors triggering developmental renin expression, it X.TsOoy  
is of interest now to study the development of intrarenal renin expression in mice with n HiE$Y  
defined gene mutations, using the results of this study as a reference system. x xMV2&,Jq  
In conclusion, using several approaches, we demonstrated that h:%L% Y9z  
But we have not provided formal proof yet that DLMM1 A  
In summary, our results suggest that ?}<4LK]  
In conclusion, we identify m^hi}Am1  
A better understanding of such regulatory systems may yield novel therapeutic L<8:1/d\  
approaches to glomerular diseases. 8bl&-F `  
Preliminary results of short-term studies (2 weeks) indicate that Lckb*/jV&  
However, we believe that i4"BN,NZ{  
However, despite our extensive measurements of these parameters, we found no aH@GhI^@  
relationship between response and initial proteinuria, time to B-cell recovery, the Hqsj5j2i  
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree T.m*LM  
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be eAvOT$  
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved }@VdtH  
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and 4@|"1D3  
that will also look for factors that may determine its efficacy in IMN. >;|~ z\8  
It has become increasingly clear that Z.:g8Xl-6  
Form the above discussion, the conclusion can be reached that 9/[1a_ r  
The conclusions drawn are also valid c -1Hxd YD  
In conclusion to this, it becomes obvious that the problem of xx lies not only in... II=(>G9v  
We have attempted to introduce some concepts associated with a theory of .aJ\^Fx  
Considerable more work, hopefully, will be done in this area Pr|:nJs  
Employing the compositional rule of inference, the assessment of the xx compatibility in /da5 "  
achieving prescribed xx projectiles in any level of the hierarchy is made possible. POZ5W)F(  
This paper has presented a theoretical and experimental study of the xx process and xx R 1CoS6  
concept. \J@i:J6x$1  
The experimental research results will hopefully serve as useful feedback information for Atdr|2  
improvements for xx work. >b6!*Lrhs  
The scope of this contribution was to introduce a xx method. SEf:u  
This has a tremendous impact on our understanding of {\HEUIa]w  
Significant progress has been made in advancing RNAi therapeutics in a remarkably w4 R!aWLd  
short period of time p_ H;|m9  
To date, little is known about… ! };OL Q  
Irrespective of the mechanisms and the molecules –which are still largely unknown – HLD8W8  
involved in MSC functions, current data suggest that e|6kgj3/  
To better understand (4;m*' X  
26 b#h}g>l  
Future Research (常用于conclustion 的结尾) 4V2}'/|[  
Thus, first extension of the approach could be, g>L4N.ZH_v  
Further studies are needed to determine the importance of huPAWlxT  
Some improvements to the scheduling aspect of the model may be brought through >v sy P  
additional levels in the hierarchy for more detailed representation of the scheduling Rw j4  
activity. {>x6SVF  
It also unveiled new aspects of the role played by thyroid hormone in response to injury ^`BiA'gPPC  
and tissue repair. wW. V>$q  
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and [ 2WJ];FJ  
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of ?%QWpKO7X  
drug molecules. iZ^tLnc  
In the next few years it should become clear whether c >8I M  
It should be an exciting time for researchers seeking to harness this powerful endogenous ?2RDd|#  
pathway to treat human disease. A s5*)o"&  
Acknowledgement PG51+#  
The authors are grateful to the insightful work provided by Mr. John W. Harney and all !Dc|g~km\  
of the fellows and students that contributed with some of the studies discussed in this @R c/ ^B:  
article j3W )  
I would like to express my gratitude to all those who gave me the possibility to complete -@I+IKz  
this thesis. J*!_kg)>J  
I want to thank the Department of Transport of the former Interim Government of -za+Wa`vH  
Namibia for giving me permission to commence this thesis in the first instance, to do the 80'!XKSP  
necessary research work and to use departmental data .=kXO{>  
This work was supported by NIH grants AI058695 and AI056900. We thank members of cs-wqxTX[$  
the laboratory and our collaborators for many useful suggestions. qcmf*Yl:v  
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. Y& ![2o.Q  
Duckman for graphics assistance and A. Capobianco for word processing assistance. uQ(C, f[6p  
Author contributions t7P[^f15[  
All authors were involved in experimental planning and data analysis and contributed to aSGZF w  
manuscript preparation. ],W/IDv  
Tables and Figures 'joc8o sS  
Figure 7-1 sketches these relationships. ]ChGi[B~9  
The graphical representation of these functions is shown in Figure 1. :`Z'vRj  
The xx may be depicted as in Figure 1. }hm "49,O  
Figure x shows the schematic diagram of the +";<Kd-  
Figure 1 though 2 provide a ... that q r<+@Q  
the architecture of this expert system for .... is illustrated in Figure 2. FD1Z}v!5IJ  
Figure 2 gives the outline of an ... system ,B'n0AO/'  
Table shows the F7"v}K]X  
27 # o;\5MOE%  
Time-dependent changes of #}lq2!f6  
as shown in Table 1 and 2 1y{@fg~..  
This concept is illustrated in Figure 2 Cqra\  
At the top of Table xx are shown two blocks of data. B/^1uPTZ71  
Each table or matrix has constructs xx through xx as row;headings, !A|ayYBb\  
xx through xx as column;headings. >hFg,5 _l3  
Time course of calculated renin immunoreactive tissue volumes during development of /ygC_,mx  
the mouse kidney. Data are single values per time point. They were derived from the kw$*o k  
kidneys shown in Figure 1. I7-6|J@#^  
Yellow color indicates 5;:964Et  
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then $j"TPkW{M  
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were O Bp&64  
analyzed by western blot using phospho-specific antibodies. V.?Oly  
ERK and PKB activation were measured by western blot using phospho-specific mW 4{*   
antibodies 2+'4m#@)  
The data are the means of three different experiments taking the number of untreated cells p(6!7t:  
(vehicle alone) as 100%. 6?uo6 I  
ERK and PKB activation were then analyzed by western blot with the corresponding *D:"I!Ho  
phospho-specific antibodies. To ensure equal amount of protein in each lane, western WvVf+| Km  
blots against total protein were performed for ERK and PKB. B.ar!*X  
The means of optical density (OD) values of the bands detected in western blots of three |\# 6?y[o  
different experiments are plotted, taking the maximal value of phosphorylation of ERK F8En )#  
and PKB as 100%. JZom#A. dt  
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with :WM[ [LOaC  
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then U oq t  
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence ;z3w#fNMv  
microscopy (lower panel). _ rIFwT1]  
The data are the means of three experiments performed on different days taking the iL\eMa  
number of cells at the onset of the experiment as 100%. n^+rxG6 L  
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction jC3)^E@:"  
(n=9 each). *0!IHr"fn  
*P<0.05 versus non-nephritic rats. )m4O7'2G  
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, \4FKZ>1+R  
positive control, M, molecular weight markers). Wti?J.Csc  
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. c.JMeh  
Data are means s.d. of four independent experiments. X{-[ E^X  
*P<0.05 versus 0.5 h. 5:6]ZFW  
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 18{" @<wIs  
mRNA as determined by real-time RT-PCR and normalized to vb1Gz]~)>  
glyceraldehyde-3-phosphate dehydrogenase mRNA. ^cz;UQX~}  
Cell number was counted in duplicate using a Malassez hemocytometer cUPC8k.1  
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with 6d%'>^`(o-  
MCDB media for 24 h, #P<0.05. <&Q(I+^  
28 _5l3e7YN  
The curves are adjusted for history of coronary artery disease, CRP, and progression to M>kk"tyM  
ESRD. A\S1{JrR  
Both models are independent of age, gender, baseline GFR and proteinuria, and other mok%TK  
clinical characteristics and traditional and nontraditional cardiovascular risk factors @ApX43U(  
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH -0R;C`(!  
(n=99, P<0.0001, r2=0.190) {24Y1ohK  
Concentration of serum FGF23 concentration before starting and at the end of the 4-h hJIF!eoI  
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, YnLwBJ2i  
Student's paired t-test). V {H/>>k7  
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; #'?gMVSk  
arrow=endothelial cell and CD=collecting duct Y#[>j4<T  
Magnification: 1000.  sM0o,l(5  
A table of .. is developed and significant recommendations are made. Y\pRk6,  
CONJUGATION v *UJ4r  
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additionally, again, also, and then, as can be easily understood, besides, equally important, YR$ )yl  
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broadly speaking JMa[Ulz  
To Indicate Cause and Effect v7kR]HU[y  
accordingly, as a result, consequently, for this reason, hence, in short, otherwise, then, S7 _^E  
therefore, thus, truly fvUD' sx  
To indicate Comparison ^%<t^sE  
in a like manner, likewise, similarly , alternatively /Wqx@#  
To Indicate Concession O alBr?^  
after all, although this may be true, at the same time, even though, even so , I admit, QoVRZ$!p  
naturally, of course iH#b"h{w  
To Indicate Contrast EE<^q?[3^  
and yet, at the same time, but, for all that, however, yet, in fact, in contrast, in the real life, qauZ-Qoc9  
in spite of, nevertheless, notwithstanding, normally, on the contrary, on the other hand, :?}U Z#  
still, traditionally, rather, unfortunately, _P]!J~$5  
To Indicate Time Relationships xO<$xx  
after a short time, afterwards, as indicated earlier, as long as, as soon as, at last, at length, .}V&*-ep  
at the moment, at that time, at the same time, before, earlier, currently, immediately, in Q4&|^RLLG  
the meantime, in recent years, lately, later, meanwhile, often, of late, presently, recently, $)fybn Y  
soon, shortly, since, thereupon, temporarily, therefore, until, when, while %j=xLV\  
29 ~SW_jiKM  
To Indicate Special Features or Examples %%w/;o!c  
for example, for instance, incidentally, indeed, in fact, in other words, in particular, in (DW[#2\.  
practice, specifically, that is, to illustrate, in this respect, theoretically, as mentioned 22<T.c  
before / above $j\UD8Hj'-  
To Indicate Summary 5"]t{-PD  
in brief, in conclusion, in short, in summary, on the whole, to conclude JvZNr?_w%  
, in general, to summarize, to sum up, as a result, ultimately, 08!pLE  
VERB PHASE FrXh\4C  
build a .. model [AZN a  
have been described to /<Doe SDJ|  
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we detected _(q|W3  
build up the key link Nm 0kMq|h  
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began a new era in ... 'kD~tpZ  
can be regarded as / achieved / used to/for / found / obtained through O-M4NKl] 6  
can result in osJ;"B36  
carries out ... tasks $=? CW(  
production information in order to simultaneously |Q'l&Gt6  
contains all information necessary to describe 4}~zVT0'~  
do not make use of production information 2{!^"iW  
deals with }- Jw"|^W  
end with failure mkCv  f  
fetch the information from the model directly kW#{[,7r  
has great potential / yet to be resolved / spurred the development of / e6n^l $'  
been recognized as 6[h 3pb/m  
site component / cable of / currently implemented for / demonstrated by an example / OOEmXb]8  
finally reached / made equal to / equivalent to / more suitable to / oriented to / M. Fu>Xi  
interpreted as / pointed out / potentially of great benefit in the complex task of / shown :>Gm&w (n  
in / used to effectively guide the search *j,5TO-j  
makes use of aqjS5!qh  
was significantly higher as compared to 0YsC@r47wL  
To assess disease-specific alterations, we measured 2Et7o/\<  
To specifically assess the relationship between iB Ld*B|#K  
make up J^@0Ff;=5^  
To determine if 2VOdI  
This statistically significant difference still 2EubMG  
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Our results are consistent with our recent data that suggest that X*2M Nx^K~  
30 MorR&K  
contribute to XD5z+/F<"0  
meets the needs of real life production,/ the current demands placed upon it &v+8RY^F=  
must be justified 0kI.d X)  
point out 6]dK,  
play an important role Kc=&jCn  
relates to goi5I(yn^  
rely on DWep5$ >&K  
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satisfy the needs N(v<*jn  
determine the total requirements for the ... ?d1H]f<M  
uses ... as a key to search for... >dol  
without relying on m'$]lf;*  
will be available/ performed/ overlooked NZ/>nNs  
NOUN PHASE s@C@q(i6  
a basic technical function of  F>,kKR-  
a significant reduction of ir<HC 'D[  
drug variability d#.9!m~.  
a critical need o'@VDGS`  
negatively correlated with 2HBYReQ  
a key / principle feature of Bry\"V"'g  
a substantial impact on IiV:bHUE}0  
an intensive review was conducted ]R/VE"-  
The analysis of the correlations by H d6g0  
an increasing need for expanding the application of .... >Liv].  
an important component / function / aspect / issue ^1M:wX r  
each rule is numbered in sequence a_/\.  
each of these involves >h/J{T(P>h  
for this calculation, it is necessary to define \w{x- }  
in the physical environment / integration of QT/ TZ:  
in the reality of situations where … 0n+Wv @/  
many aspects of 8 M3Q8&  
most past efforts have been spent on ... RuDn1h#u{  
common sense to a well studied and documented technical field. LbDhPG`u  
sources of additional information on ... are listed zlIXia5  
systematic and rationally structured format VL"!.^'c  
the basis on which a range of ...operations can be established is shown TOV531   
THE basic philosophy / principles of / key element / general hypothesis / candidate list |*"uj  
of / concept of ... has attracted wide interest / function is concerned with / heart / Q@hx +aM  
impact / nature / role / task of / kernel functions a9qB8/Gg[  
the number of parts needed to YbF}(iM  
the above statement means that MCU{@ \?Xf  
the output data is passed to *yOpMxE  
31 u^SXg dj  
the proposed method / underlying principle wy"^a45h  
the recommendations made in this report, if implemented, should 703=.xj  
this information resides in O`U&0lKi'  
this process is composed of ... different ... operation Mh>H 5l.1i  
along with the use of $+)2CXQe5  
concerning general aspects of D`PnY&ffT  
due to RekTWIspT/  
for later use in generating..., S#dkJu]]#  
in turn, Urur/_]-%  
it can be claimed/concluded that v;AMx-_WH  
it demonstrates the decisions required of IZY q  
it also provides information to .. 'm9f:iTr  
it becomes essential to C#[YDcp4  
let ... be the probability that fg"@qE-;  
once... is written, it is compiled into... V*xT5TljS-  
suppose it is observed that 0{g@j{Lbz  
this is because f~-81ctu  
this results in a ~>zml1aJ6  
upon completion of the ... analysis, 2f ]CnD0$  
when the knowledge is of mathematics or quantum physics, it will also be 2j8^Z  
recorded in books and papers gBz$RfyF  
selection of rules for using the tools, for generating operation plans, #k5WTcE  
is another matter of preference, since practice varies greatly. L {(\k$>'  
for the sake of convenience @=q,,t$r  
correct decision to be reach X~t]qT  
keeping the number of rules to a minimum. q 1a}o%  
a good process plan will result exhibiting several characteristics: I`w1IIY?m  
practical solutions de]r 9$ D  
because of rather small job lot sizes 7q?u`3l  
Backward reasoning can be used to answer the question "should milling tool be select" @sv==|h  
different level of knowledge in the realm of process planning
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