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楼主  发表于: 2009-10-18   

医学SCI 论文经典句子

18 Z$S0X $q}  
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number  9 'IDbe{  
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The sVP2$?  
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at to)Pl}9QkK  
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The kLbo |p"cT  
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 y|Y hDO  
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, K555z+,'e  
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive )`zfDio-1V  
control for Ca2+ induction. The data thus obtained was analyzed with the software Win ;o.,vQF*  
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on }:+P{  
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 ~PCS_  
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were / !A&z4;D  
harvested and fractionated as detailed above, and the S-100 fractions were assessed by kZS&q/6A*  
immunoblotting for presence or absence of annexin I. 2|LkCu)~,"  
Mouse bone marrow transduction and transplantation. t8-LPq  
Retrovirus-mediated transduction of mouse bone marrow cells was done by published JP 8v2) p  
methods49. Prestimulated low-density bone marrow cells were infected with high-titer i%9xt1 c_  
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated H/Ov8|  
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing xiQ;lE   
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by ~kPZh1n`  
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator)  [T#9#3  
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone pw1&WP&?3  
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis 1 *$-.  
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of uJ/ &!q<3  
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was WhR'MkfL  
confirmed by immunoblot analysis. PiwI.c  
Determination of renal morphology Q GDfX _  
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an .R {P%r  
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, FcZ)_m6m  
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner A+F@JpV  
for morphologic alterations, as previously detailed 9~WjCa*,&  
Patient population #me'1/z  
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) ?TVR{e:  
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per ;yg 9{"O  
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) 1\+d 5Q0  
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. !RwOU Ck  
The Mayo Institutional Review Board and the Research Ethical Board, University Health # :3~I  
Network, University of Toronto approved the study protocol. All patients gave written fQOh%i9n5  
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or Smlf9h &  
19 QAh6!<.;@  
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 FrryZe=  
months were not included in the study. Patients with active infection, diabetes, or a xu7Q^F#u  
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), O<?z\yBtS^  
medications, malignancies) were also excluded. ,BG L|5?3z  
Treatment Rc k k  
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of "kT?9&  
high-quality protein) diet was recommended and patients were encouraged to maintain z wJ Vi9sO  
the same diet throughout the duration of the study. All patients received a similar gnN"pa!&~  
conservative treatment regimen that included loop diuretics to control edema, an Z6xM(*vg  
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. Sx3R 2-!Z  
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added 1ti4 ZM  
when required to control systolic blood pressures to <135 mm Hg in >75% of the h\i>4^]X.  
readings. Patients who after a minimum of 4 months of conservative therapy and Lcpz(W ^  
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of  G(1y_t  
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions, 2{o eJ  
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine  rVo?I  
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given  9> k-";  
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count +Tw]u`  
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count !3'&_vmG$  
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per +kK6G#c  
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a k)l^ ; x-  
second course of rituximab treatment following the same protocol described above. Iq[Z5k(K  
Follow-up APA:K9jD  
In all patients, clinical and laboratory parameters including complete blood counts, R2[-Q"|Ra  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum  e ):rr*  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry otgU6S7F  
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion 06#40-   
in the urine were assessed by performing two consecutive 24-h urine collections at each fudIUG.  
time point. Data were considered accurate when urinary creatinine excretion was ?A4t &4  
consistent with a complete 24 h collection. The mean of the two measurements was 3M[b)At V.  
considered for the analysis. The presence of HACAs was evaluated at baseline and at Uj[E_4h  
months 3, 6, 9, and 12. AGdFJ>/  
Method / Approach / Study/ Technique &m>sGCZ  
A discussion is presented of a problem-solving system (7qdrAeP  
To improve the efficiency of the method, the following approach may be applied. jo_wBJKE  
In order to an investigation was made to find the causes of the C<.Ny,U  
Although large collections of rules and equations have been complied, none are generally ?Hd/!I&  
accepted NdW2OUxw"  
20 c= }#8d.  
This approach will be explained and discussed thoroughly in the body of the report. XJ`!d\WL/!  
This can be accomplished by ][y~(&=T  
This algorithm to compute the total cost can be described step by step as follows: AGe\PCn-  
The above preliminary analysis has provided important information 0;kp`hB  
Various methods have been proposed for selecting an optimum... 1%nE  
These concepts have been applied to J}9 I5O  
On the basis of the concept mentioned above, Ae0jfTv  
This can be achieved by n!r<\4I  
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the ;ss,x  
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, [a<u cJ  
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced m;S!E-W  
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 )\bA'LuFy  
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada a&Stdh  
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% D[7+xAwS  
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections (W~')A"hC'  
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin oM&}akPE  
complex. Sections were counterstained with hematoxylin and examined by light _dgS@n;6  
microscopy. +ti_?gfx  
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay H+oQ L(i|_  
performed at Genentech Inc. that measures the antibody response to rituximab in human 1gA9h-'w  
serum samples. :/c40:[  
In all patients, clinical and laboratory parameters including complete blood counts, ]Cfjs33H  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum a,GOS:?O5  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry [IF5Iv\b  
and at months 1, 3, 6, 9, and 12. g69^D  
This fact suggests that a new concept Md4hd#z  
This was accomplished by taking ... *kmD/J  
The preparatory stage is very time consuming process. H+ P&} 3  
Test are performed for validity, completeness, and compatibility ~]MACG:'  
There is little hope of achieving successful ... + [JvpDv%  
There has been an increasing awareness of the potential of using most ..so far made have l@ amAusE  
not taken this approach, with the exception of e ej:  
Only a few studies can be found. D#=$? {w  
It is a very tedious process to go through ^V1.Y  
It is only when .. has been completed that .. may be effected o =oXL2}  
The entire interpretation process is conducted in one's head. Y<4%4>a  
These approaches are sometimes very tedious. 8=GgTpO5  
Several techniques can be used tJ"8"T#6Vr  
A polynomial parametric model can be written as [the following]/[follows]: 88@" +2  
A xx model is constructed/formulated using xx. FZvh]ZX  
A xx model represents an xx by its xx. Y#VtZTcT  
A process decision model captures the logic essential to {Wi)/B}  
From the equation above, xx is equal to the summation of xx times the ... S%^*h{9u"  
21 'n>v}__&|  
The validity of a xx model can be checked using Euler's formula. 'ie+/O@G  
Given a model, one can mathematically determine whether ... or ... agbG)t0  
Equations for xx need to be derived and implemented in the system. b1*5#2rs.  
A number of heuristic rules have been developed for :t7M'BSm2z  
Optimum .. techniques can be made more reliable by ... so that 4x2 ;@Pd  
An algorithm based on the characteristic ... is used to determine T 5AoBUw  
Euler's formula states the following: 0SHF 8kek  
The completed model should agree with the formula. P^)J^{r  
For manufacturing purposes, a detailed and precise model of the object is necessary W$>AK_Y}  
Engineering design models are very well defined; therefore,  )S8fFV  
To keep the domain narrow enough to be implementable, yet wide enough to be useful. 1ti9FQ  
Point of View RT`jWWh*Lo  
from an implementation standpoint, ]c+HD*  
From the point of view of this application, |z+K]R8_  
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). Ag82tDL[u  
Information is the meaningful interpretation and correlation of some aggregation of data f4 [Bj{F  
in order to allow one to make decisions. RT~6#Caf  
From a practical point of view, the computational aspects of an FLC require a &gr)U3w  
simplification of the fuzzy control algorithm. # ~I.F4  
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, k-;A9!^h  
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM eyIbjgpV  
p.129] GGWdMGI/  
Statistical analysis a3Fe42G2c|  
Data were analyzed by one-way analysis of variance comparing the three conditions }#Q?\  
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If sT<XZLu  
significant F-statistic from analysis of variance existed, this test was followed by Dunnett ~stG2^"[  
post hoc multiple comparison procedure with sham operation as the control group. For all l2S 1?*  
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as 1M<;}hJ{/  
statistically significant. BMJsR0  
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney OngUZMgdb  
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, "?f_U/+D<  
CA, USA). 1oSU>I_i  
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was l.Yq4qW  
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's .1@8rVp7  
test, where appropriate. ,mY3oyu  
Data are expressed as mean s.d., median and interquartile range, or frequencies, as Vgg' 5o&.  
appropriate. Variables who deviated from the normal distribution (positively skewed) 7W7yjG3g  
were log-transformed (log10) before the correlation study. FDQP|,  
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test F=9 -po  
post hoc analysis of variance were used as indicated below, for the comparison of 7+c}D>/` :  
22 1(4 }rB3  
morphological, immunohistological and functional parameters. Statistical significance |j w{7\+  
was set at P<0.05. Pgh)+>ON  
The primary efficacy parameter was defined as change in urinary protein excretion from |-zefzD|  
baseline (week 0) to 12 months after treatment. The 12-month changes were tested yq]/r=e!k  
against zero using the paired t-test. Secondary end points included 6-month changes in 47yzI-1H+  
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular K[s!3.u  
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on $:!L38[7$  
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. AY)R2> fW%  
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. !IAd.<,  
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 u7G9 eN  
Definition of remission status is according to the criteria established by Cattran et al.30 +T*]!9%<`:  
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a "}ZUa~7  
>50% reduction in peak proteinuria and non-response as <50% reduction in peak QKt+Orz  
proteinuria. Any patient reaching a CR or PR was considered a treatment success C[2LP$6*/  
The statistical significance of differences for the mean values of cytokine concentration 34s>hm=0.  
and T cell proliferation was determined with Student's t-test. Differences with a P value yh{Wuz=T  
of less than 0.05 were considered significant. ^QbaMX  
Statistical significance was determined by Student's t-test. Data with a P value of less -xMM}r y  
than 0.05 were considered significant. *R8qnvE\()  
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P 1Uf8ef1,  
values less than 0.05 considered statistically significant. RAY.]:}jr  
The significance of differences among groups was determined by Student's t-test and oV,lEXz  
one-way analysis of variance (SigmaStat software; Jandel). ^h~oxZJw  
Comparisons C#@>osC  
As well, the pros and cons of these representations from a process planning point of view yaWHGre  
will be discussed. S/H!a:_5r  
The method of using xx to implement xx described by Zadeh (1973) appeared more .p?kAf`  
suitable /aX#j`PrH  
As discussed [in the previous section]/[preciously], e(~Y!:Q#O  
Relation 8iKupaaOX  
We can not invert F' directly because it defines a many-to-one mapping. +E8}5pDt  
The relationships appear very complicate ^ e4y:#Nu  
Lifting tasks involve complex and imprecise relationship between the task variables and t}A n:  
the human operator's characteristics. |C_sP,W  
These methods are based on the relationship between ... and ... VSQxlAGk@  
The fundamental concept of a fuzzy rating language is that we can establish a relationship  EWn\ ]f|  
among terms such as high, medium, and low, and then modify these relationships. -Ka0B={Z  
This article will thus mention the latter as well as the former. WlfS|/\%V^  
The former two bear a close relation to a fuzzy Cartesian product. 8j%hxAV$  
Importance \[F4ooe  
s\#eD0|  
23 -YfpfNt  
The emphasis is on an implementation of a general approach to rule based decision -4!i(^w[m/  
making. q)E J?-  
Consideration / Attention ;zZGV4Qc~  
Careful evaluation is necessary to ensure Ow7}&\;^-  
Such a formulation does not change further considerations. '@Q aeFm  
Considerable attention has been paid to IsjD-t  
Attention should be paid to an important finding of this investigation. Gkq<?q({t  
Caution should be exercised in this process to avoid ... jf'#2-   
Primary consideration is given to ... components, though others can be accommodated TRSR5D[  
After ... has been defined by ..., a carefully analysis is carried out/performed to determine 7<?~A6  
A number of factors such as ...need to be taken into consideration before making the g6=w MRt[  
appropriate decision. Q?\rwnW?U  
It should be noted that k2S6 SB  
It is important to point out that ... hc4W|Ofj  
These considerations have heightened interest in the possibility of providing ... QA3q9,C"  
We should stress the fundamental importance of the xx V/jEMJNks  
Results. s]p3dB#  
Advantages / Disadvantage -{A!zTw1w  
One of the major advantages of this new measure of xx is that it can be applied to the E'J|  p7  
experimental study of Y=#g_(4*  
One advantage of using a .. is the ease of preparing it. L*VO2YI  
It has a very fast decision making process (|PxR#{l<  
All the algorithms involve mostly logical operations. XNU[\I  
It can be easily and without additional cost implemented in a microprocessor;based >/DyR+?>4  
environment. K8l|qe  
It can reduce the waste of designing from scratch. )D:I@`*  
The advantages of using a xx to represent xx are the following: n0T'"i[  
However, xx is not without its shortcomings. coxMsDs  
In most cases, the xxx shows an improvement over the existing xxx. L##lXUl  
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. $Qv+*%c  
The "best case" results shows a savings of 6% to 9%. x_JCH7-  
Most of the existing works based on xx approach can only recognize a xx . pOCLyM9c  
Most of the above methods are computational expansive and limited to xx. I]]3=?Y  
Some other advantages of xx are the following: ;-d }\f ,  
The problem is the limitation of this method to a limited domain of parts. Ew=8"V`C  
It proved limited in application because it demanded precision in system modeling that OgiE lA.  
was impossible in practice. aIv>X@U}  
There are advantages to be gained in the structuring of costs and benefits, the use of xx, m q`EM OH  
The disadvantages of this method are also disadvantages of conventional xx approaches. l)glT]G3+  
This combines the best features of both techniques `5[d9z/6  
24 8"4&IX  
Hopefully, this tool can be as the reference framework of for developing a xx platform, ?= B$-)/  
and helping the administration, marketing, and knowledge management activities in gp:,DC?(  
virtual communities. -,Q !:  
Results 4+od N.  
An improvement on the result shown above can be made by based on the data provided krPwFp2[*  
Recent work has identified I_('Mr)  
Time-dependent changes of h&+dIk\[3  
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase |hjm^{!TpW  
and does not require ERK activation. fPf8hz>  
Much of the current work on Wc4F'}s  
Discussion of these theories is beyond the scope of this review ')w:`8Tl  
Based on the information contained in this J#7\R':}zl  
The result can be categorized into nine classes \f6SA{vR|  
The results are illustrated by an example \`\& G-\  
The experimental results for each xx time are reported in Table 2. 66*/"dBwm  
From the results obtained so far, it seem that PpD ?TAlA  
Because of the inaccuracy of the ..., a conclusion cannot be drawn as 0Zp) DM  
Although much effort has been made to., this reality is far from completion. ~6z<tyD^  
The results indicate that the total benefits are higher than the total costs. W3s>+yU  
Their results may then serve as guidelines for lower level models, less fuzzy and more @vdBA hXk  
detailed. &v7$*n27  
Conclusion _5(lp} s  
From the discussion, one may conclude that ... FUic7>  
The first indication that kw&,<V77~  
In summary, we have shown that M=$ qus  
These results suggested that 095:"Gv O  
Our findings have shown that S"ZH5O(  
Our observations have provided C?jk#T  
This study reveals following five main findings: <R)%K);  
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in fvn`$  
the diabetic kidney. 'thWo wE  
As mentioned above, q}[g/%  
Moreover, we demonstrate that, qRkY-0vB P  
A number of studies have elaborated a body of knowledge about x%Ph``XI  
There are findings to indicate that )[&'\SOO  
On a descriptive level, there is agreement that for 6%bZZTP`  
One issue that became particularly evident from our study is c5x2FM z  
Our data are in agreement with the findings and models presented by previous LT 7C>b  
publications, in particular those of Jones et al Bw _^"e8X  
According to our observations, 5VD(fW[OW]  
…was not evident from our data q1!45a  
25 <d89eV+  
It could therefore be concluded that {~J'J$hn8  
our data illustrate that -]$q8 Q(hM  
All these different aspects, as listed above, lead to  -D*,*L  
In fact, it has already been speculated that ctI=|K  
It should be furthermore mentioned in this context that jeb ]3i=pw  
To identify and verify the essential factors triggering developmental renin expression, it h9<*+T  
is of interest now to study the development of intrarenal renin expression in mice with g{|F<2rd[m  
defined gene mutations, using the results of this study as a reference system. qiEw[3Za]'  
In conclusion, using several approaches, we demonstrated that KrVP#|9%"  
But we have not provided formal proof yet that HRQ3v`P.  
In summary, our results suggest that UAleGR`,  
In conclusion, we identify CK[w0VCT  
A better understanding of such regulatory systems may yield novel therapeutic dsJMhB_41U  
approaches to glomerular diseases. s{g^K#BoFi  
Preliminary results of short-term studies (2 weeks) indicate that 7]\_7L |>]  
However, we believe that ckDWY<@v  
However, despite our extensive measurements of these parameters, we found no :Vdo.uUa  
relationship between response and initial proteinuria, time to B-cell recovery, the }EJAC*W,  
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree O4`am:@  
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be d WKjVf  
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved +\s32o zg  
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and O+f'Ql  
that will also look for factors that may determine its efficacy in IMN. {3)^$F=T  
It has become increasingly clear that +K2p2Dw(k  
Form the above discussion, the conclusion can be reached that #_(t46  
The conclusions drawn are also valid "}|&eBH^<  
In conclusion to this, it becomes obvious that the problem of xx lies not only in... $3yzB9\a"  
We have attempted to introduce some concepts associated with a theory of G~. bi<(v  
Considerable more work, hopefully, will be done in this area P3e}G-Oz  
Employing the compositional rule of inference, the assessment of the xx compatibility in :`Sd5b>  
achieving prescribed xx projectiles in any level of the hierarchy is made possible. [B_(,/?  
This paper has presented a theoretical and experimental study of the xx process and xx Aq]*$s2\G  
concept. Xi  8rD"v  
The experimental research results will hopefully serve as useful feedback information for  0?80V'  
improvements for xx work. ,qUOPW ?=  
The scope of this contribution was to introduce a xx method. V#Pz `D  
This has a tremendous impact on our understanding of qA;!Pql`  
Significant progress has been made in advancing RNAi therapeutics in a remarkably -|cB7 P  
short period of time &sA@!  
To date, little is known about… Kk9eJ\  
Irrespective of the mechanisms and the molecules –which are still largely unknown – -~+Y0\%E  
involved in MSC functions, current data suggest that Y I?4e7Z+  
To better understand :c/](M  
26 b%_[\((  
Future Research (常用于conclustion 的结尾) 1)N~0)dO  
Thus, first extension of the approach could be, \L5h&  
Further studies are needed to determine the importance of <&m `)FJ  
Some improvements to the scheduling aspect of the model may be brought through +cf.In,{  
additional levels in the hierarchy for more detailed representation of the scheduling nq,P.~l  
activity. gZ 6Hj62D  
It also unveiled new aspects of the role played by thyroid hormone in response to injury }'c@E0"  
and tissue repair. y&(R1Y75  
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and $ 0Up.  
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of ,0fYB*jk  
drug molecules. 6i=Nk"d  
In the next few years it should become clear whether r$/.x6g//  
It should be an exciting time for researchers seeking to harness this powerful endogenous R2B 0?fu  
pathway to treat human disease. U66}nN9  
Acknowledgement 5#}wI~U;  
The authors are grateful to the insightful work provided by Mr. John W. Harney and all A6AIkKjzq  
of the fellows and students that contributed with some of the studies discussed in this >&DNxw  
article O ]Stf7]%;  
I would like to express my gratitude to all those who gave me the possibility to complete Z:kX9vw.  
this thesis. /sa\Ze;E  
I want to thank the Department of Transport of the former Interim Government of nd xijqw  
Namibia for giving me permission to commence this thesis in the first instance, to do the $ 8WJ$73  
necessary research work and to use departmental data z<Y >phc  
This work was supported by NIH grants AI058695 and AI056900. We thank members of 99mo]1_  
the laboratory and our collaborators for many useful suggestions. ;=oGg%@aP  
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. *JmU",X  
Duckman for graphics assistance and A. Capobianco for word processing assistance. ?[~)D}] j  
Author contributions z;KUIWg  
All authors were involved in experimental planning and data analysis and contributed to @ZFU< e$!  
manuscript preparation. 7iM;X2=7}  
Tables and Figures O,A}p:Pgs  
Figure 7-1 sketches these relationships. mzoNXf:x  
The graphical representation of these functions is shown in Figure 1. ].,T Snb  
The xx may be depicted as in Figure 1. e)x;3r"j  
Figure x shows the schematic diagram of the 9X[}ik0  
Figure 1 though 2 provide a ... that 7IV:X _y  
the architecture of this expert system for .... is illustrated in Figure 2. twA2U7F  
Figure 2 gives the outline of an ... system G*$a81dAX  
Table shows the ?=lnYD j  
27 ~RS^O poa  
Time-dependent changes of Y =BXV7\  
as shown in Table 1 and 2 oL 69w1  
This concept is illustrated in Figure 2 %=O$@.%Zc  
At the top of Table xx are shown two blocks of data. _-.~>C  
Each table or matrix has constructs xx through xx as row;headings, >RMp`HxDf  
xx through xx as column;headings. )xMP  
Time course of calculated renin immunoreactive tissue volumes during development of Q, !b  
the mouse kidney. Data are single values per time point. They were derived from the v8L&F9 o  
kidneys shown in Figure 1. <(%cb.^c=N  
Yellow color indicates 0- 'f1 1S  
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then }nW)+  
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were s3LR6Z7;i  
analyzed by western blot using phospho-specific antibodies. G3G"SJ np  
ERK and PKB activation were measured by western blot using phospho-specific D(]])4  
antibodies A -dL_3  
The data are the means of three different experiments taking the number of untreated cells F ;m1I+;  
(vehicle alone) as 100%. %Jr6pmc  
ERK and PKB activation were then analyzed by western blot with the corresponding VK)K#!O8  
phospho-specific antibodies. To ensure equal amount of protein in each lane, western #^bkM)pc  
blots against total protein were performed for ERK and PKB. bh8IF,@a  
The means of optical density (OD) values of the bands detected in western blots of three w C0fPPeA  
different experiments are plotted, taking the maximal value of phosphorylation of ERK EPz$`#Sh"  
and PKB as 100%. _S(]/d(c  
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with ~!,Q<?  
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then wghz[q e  
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence tN 5brf  
microscopy (lower panel). ve #cz2Z  
The data are the means of three experiments performed on different days taking the QrP$5H{[E  
number of cells at the onset of the experiment as 100%. <9S?wju4W'  
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction I]`>m3SJ  
(n=9 each).  +McKyEa  
*P<0.05 versus non-nephritic rats. o%Lk6QA$  
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, qO<'_7TN[  
positive control, M, molecular weight markers). 27vLI~  
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. \kiCczW_  
Data are means s.d. of four independent experiments. 6/9h=-w&  
*P<0.05 versus 0.5 h. DlR&Lnv  
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 U4_ <  
mRNA as determined by real-time RT-PCR and normalized to -#b-@sD  
glyceraldehyde-3-phosphate dehydrogenase mRNA. gFvFd:"uZ  
Cell number was counted in duplicate using a Malassez hemocytometer hnM|=[wM  
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with #ZIV>(Q\H  
MCDB media for 24 h, #P<0.05. }TRr*] P<%  
28 AAsl )  
The curves are adjusted for history of coronary artery disease, CRP, and progression to :y 'D] ,_  
ESRD. lC6#EU;  
Both models are independent of age, gender, baseline GFR and proteinuria, and other c7IgndVAV  
clinical characteristics and traditional and nontraditional cardiovascular risk factors BNg\;2r  
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH y^zVb\"4  
(n=99, P<0.0001, r2=0.190) {"e/3  
Concentration of serum FGF23 concentration before starting and at the end of the 4-h :Qu!0tY  
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, MUNeGqv  
Student's paired t-test). 0-g,C=L  
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; r{kV*^\E  
arrow=endothelial cell and CD=collecting duct =[`wyQe`_  
Magnification: 1000. j2#Vdw|j  
A table of .. is developed and significant recommendations are made. G`w,$:,  
CONJUGATION &I?1(t~hT  
To Indicate Addition 'E0{zk  
additionally, again, also, and then, as can be easily understood, besides, equally important, >}<:5gZtA  
especially, finally, for the same reason, first, further, furthermore, in addition, last, tF&%7(EU3  
likewise, moreover, next, second, third, too, evidently, obviously, roughly speaking, X8b o?0  
broadly speaking F& H~JJ  
To Indicate Cause and Effect Np|i Xwl1  
accordingly, as a result, consequently, for this reason, hence, in short, otherwise, then, pZGs o  
therefore, thus, truly b_Ba0h=  
To indicate Comparison )TyL3Z\>(  
in a like manner, likewise, similarly , alternatively ~srmlBi6  
To Indicate Concession WLNkO^zb  
after all, although this may be true, at the same time, even though, even so , I admit, Bi kCjP[b  
naturally, of course 9A3Q&@,  
To Indicate Contrast h+.^8fPR   
and yet, at the same time, but, for all that, however, yet, in fact, in contrast, in the real life, C(iA G  
in spite of, nevertheless, notwithstanding, normally, on the contrary, on the other hand, r9s1\7]x  
still, traditionally, rather, unfortunately, 4_t aCK  
To Indicate Time Relationships zK:/ 1  
after a short time, afterwards, as indicated earlier, as long as, as soon as, at last, at length, gNLjk4H,S[  
at the moment, at that time, at the same time, before, earlier, currently, immediately, in j@kBCzX  
the meantime, in recent years, lately, later, meanwhile, often, of late, presently, recently, 9S6vU7W  
soon, shortly, since, thereupon, temporarily, therefore, until, when, while Os@ofnC  
29 wqE ]o= k  
To Indicate Special Features or Examples )CdglPK  
for example, for instance, incidentally, indeed, in fact, in other words, in particular, in MQ\:/]a  
practice, specifically, that is, to illustrate, in this respect, theoretically, as mentioned _vU,avw  
before / above ,fET.s^|U  
To Indicate Summary _7$j>xX  
in brief, in conclusion, in short, in summary, on the whole, to conclude yo (&~r  
, in general, to summarize, to sum up, as a result, ultimately, @ [ :sP  
VERB PHASE Cn28&$:J  
build a .. model O%c6vp7  
have been described to =/dW5qy;*+  
To assess the functional role of y62;&{?m  
we detected 5QS d$J  
build up the key link V!},a@>p  
Although a number of studies have identified predictors of "_#%W oo  
began a new era in ... 0^[ " &K/  
can be regarded as / achieved / used to/for / found / obtained through T5-4Q  
can result in L9r 3jz  
carries out ... tasks $(zJ  
production information in order to simultaneously j*xens$ )  
contains all information necessary to describe  6f1;4Jfp  
do not make use of production information g_n=vO('X  
deals with j./bVmd.  
end with failure &S|laq H  
fetch the information from the model directly 5@Py`  
has great potential / yet to be resolved / spurred the development of / ~s5Sk#.z5  
been recognized as cJ[n<hTv  
site component / cable of / currently implemented for / demonstrated by an example / **s:H'Mw_  
finally reached / made equal to / equivalent to / more suitable to / oriented to / },f7I^s|  
interpreted as / pointed out / potentially of great benefit in the complex task of / shown 4G`YZZQ  
in / used to effectively guide the search zcZr )Oh  
makes use of /VJ@`]jhDf  
was significantly higher as compared to BAKfs/N  
To assess disease-specific alterations, we measured &12aI |u^<  
To specifically assess the relationship between hF2 G{{8A  
make up {'r*Jb0  
To determine if sPZa|AKHb  
This statistically significant difference still Gu_s:cgB9F  
They positively correlated with :nXB w%0x  
Present S3oU7*OZ  
Our results are consistent with our recent data that suggest that T:}Ed_m}q  
30 xHL{3^  
contribute to =8J\;h  
meets the needs of real life production,/ the current demands placed upon it igo7F@_,  
must be justified iu1iO;q  
point out twN(]w}Ps|  
play an important role MBwp{ET!p  
relates to XSD7~X/:  
rely on f'.yM*  
We performed }3i@5ctQ  
satisfy the needs :8 )4:4$^  
determine the total requirements for the ... @'U4-x  
uses ... as a key to search for... }=L >u>cP  
without relying on '%~zu]f'  
will be available/ performed/ overlooked |LjCtm)@+  
NOUN PHASE --/  .  
a basic technical function of >H%8~ Oek  
a significant reduction of nh8h?&q|  
drug variability 6zI?K4o  
a critical need UHg^F4>4  
negatively correlated with Wx-{F  
a key / principle feature of n/ 8fv~zU  
a substantial impact on hQ\]vp7V  
an intensive review was conducted ^KhFBed   
The analysis of the correlations by {:dE_tqo  
an increasing need for expanding the application of .... b"Ulc}$/&  
an important component / function / aspect / issue ov+qYBuFw  
each rule is numbered in sequence }i[jJb`bY  
each of these involves MdKZH\z/  
for this calculation, it is necessary to define D\TL6"wo  
in the physical environment / integration of z/T ZOFaM  
in the reality of situations where … ae<KUThm .  
many aspects of  OkQSqL  
most past efforts have been spent on ... `2Z=Lp  
common sense to a well studied and documented technical field. }1>a71  
sources of additional information on ... are listed \\T I4A^#  
systematic and rationally structured format OGVhb>LO1  
the basis on which a range of ...operations can be established is shown L%<1C \k  
THE basic philosophy / principles of / key element / general hypothesis / candidate list J'7Oxjlg  
of / concept of ... has attracted wide interest / function is concerned with / heart / MaEh8*  
impact / nature / role / task of / kernel functions WGO=@jkf  
the number of parts needed to :[rx|9M6  
the above statement means that < FJ#Hy+  
the output data is passed to vS0P] AUo  
31 oT_,k}LIX  
the proposed method / underlying principle J>'o,"D  
the recommendations made in this report, if implemented, should RWoiV10  
this information resides in UxW>hbzr&V  
this process is composed of ... different ... operation 8O7JuR  
along with the use of EbW7Av  
concerning general aspects of |fA[s7)  
due to Rl)/[T   
for later use in generating..., E8nqEx Q  
in turn, W t8 RC  
it can be claimed/concluded that <ya3|ycnS  
it demonstrates the decisions required of S38D cWIw  
it also provides information to .. %d>K tf  
it becomes essential to Qh*|mW  
let ... be the probability that mrJQB  I+  
once... is written, it is compiled into... m}XI?[!s  
suppose it is observed that _ 9k^Hd[L$  
this is because YgDgd \  
this results in a S)~h|&A(  
upon completion of the ... analysis, ^GbyAYEp  
when the knowledge is of mathematics or quantum physics, it will also be X23TS`  
recorded in books and papers 2"mO"2d%  
selection of rules for using the tools, for generating operation plans, & =frt3  
is another matter of preference, since practice varies greatly. \Lc pl-;?  
for the sake of convenience !Khsx  
correct decision to be reach  =HSE  
keeping the number of rules to a minimum. ('gjf l  
a good process plan will result exhibiting several characteristics: J#D!J8KP7  
practical solutions 8U8"k  
because of rather small job lot sizes 9 ROKueP  
Backward reasoning can be used to answer the question "should milling tool be select" H7{ 6t(0j  
different level of knowledge in the realm of process planning
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