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楼主  发表于: 2009-10-18   

医学SCI 论文经典句子

18 U.wgae].O;  
Jurkat cells cultured in calcium-free RPMI-1640 medium (Gibco BRL; number \f{C2d/6j  
22300-107) containing calcium-free 10% FBS were triggered by anti-Fas IgM. The bcj7.rh]'h  
treated cells were harvested at the indicated time points and incubated with Fluo-3-AM at YToRG7X#  
a final concentration of 1 micromolar for 30 min at 37°C (Scoltock et al., 2000). The Wgx lQXi-B  
labeled cells (50,000 cells per treatment) were then analyzed by exciting the cells at 488 H%])>  
nm and examining the fluorescence emission of Fluo 3 at 530 nm with a FACS Scan, <cepRjDn  
(Becton Dickinson). A one micromolar concentration of LPA was used as a positive ld2 \/9+n  
control for Ca2+ induction. The data thus obtained was analyzed with the software Win ,VHvQU  
MDI 2.8 and represented as contour plots.The effect of chelating intracellular calcium on KgKV(q=  
translocation of annexin I was studied by culturing Jurkat cells in the presence of 10 Iqo4INGIi  
micromolar BAPTA-AM, with or without the addition of anti-Fas IgM. Cells were C{Npipd}v  
harvested and fractionated as detailed above, and the S-100 fractions were assessed by (6JD<pBm  
immunoblotting for presence or absence of annexin I. [_H9l)  
Mouse bone marrow transduction and transplantation. TXy*-<#vR  
Retrovirus-mediated transduction of mouse bone marrow cells was done by published JQbI^ef_;  
methods49. Prestimulated low-density bone marrow cells were infected with high-titer v3aiX  
retrovirus supernatant on fibronectin-coated plates. Retrovirus supernatant was generated 1S_ KX.  
in the phoenix-gp cells with a mouse stem cell virus–based retroviral vector coexpressing #Q|$&b  
EGFP and HA–RhoH as described50. EGFP+ sorted cells were transplanted by fT'A{&h|U  
intravenous injection into the sublethally irradiated (300 rads with a 137Cs irradiator) /nC"'d(#  
Rag2-/- recipient mice. At 9 weeks after transplantation, thymus, peripheral blood, bone y8,es$  
marrow, spleen and lymph nodes from each recipient mouse were collected for analysis ^{Mx?]z  
of EGFP+ chimerism and hematopoietic lineage by flow cytometry. Expression of J/ rQ42d  
HA–RhoH and HA–RhoHF73F83 in EGFP+ sorted thymocytes of recipient mice was B;rq{ac!P]  
confirmed by immunoblot analysis. {O!fV<Vx 9  
Determination of renal morphology wV(_=LF  
Kidney slices were postfixed in buffered 2% OsO4, dehydrated, and embedded in an U;{VL!  
Araldite-EM bed 812 mixture. Large sections were cut perpendicular to the renal capsule, 4V[+6EV  
containing cortex, and medulla. Thin (1 m) sections were analyzed in a blinded manner ]Q)TqwYF  
for morphologic alterations, as previously detailed =8<SKY&\X  
Patient population | pJ.73  
Patients included in the study met the following criteria: (1) biopsy-proven IMN; (2) Lqz}h-Ei  
creatinine clearance 30 ml per min per 1.73 m2; and (3) persistent proteinuria >5 g per c.d*DM}W  
24 h despite treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) Ak4iG2  
reductase inhibitor, an ACEi, and/or ARB at maximal tolerated dose for at least 4 months. {zg}KiNDZd  
The Mayo Institutional Review Board and the Research Ethical Board, University Health beO*|  
Network, University of Toronto approved the study protocol. All patients gave written !q$IB?8   
informed consent. Patients who had been on treatment with prednisone, cyclosporine, or dyu~T{  
19 Aja'`Mu  
mycophenolic mofetil within the last 4 months or alkylating agents within the last 6 b/<n:*$   
months were not included in the study. Patients with active infection, diabetes, or a Ak|j J  
secondary cause of MN (for example, hepatitis B, systemic lupus erythematosus (SLE), VE{t]>*-u  
medications, malignancies) were also excluded. *y.KD4@{  
Treatment CQ13fu +|6  
At enrollment, a low-sodium (<4 g day-1) and low-protein (0.8 g per kg per day of 6B|IbQ^  
high-quality protein) diet was recommended and patients were encouraged to maintain MbjH\XRB  
the same diet throughout the duration of the study. All patients received a similar "z7.i{   
conservative treatment regimen that included loop diuretics to control edema, an ?1?m4i  
HMG-CoA reductase inhibitor, and an ACEi combined with an ARB if tolerated. pGUrYik4  
-Blockers and non-dihydropyridine calcium channel blockers, in that order, were added Tpkm\_  
when required to control systolic blood pressures to <135 mm Hg in >75% of the P>jlFm  
readings. Patients who after a minimum of 4 months of conservative therapy and Pm V:J9  
maximized Ang II blockade had proteinuria >5 g per 24 h received two i.v. infusions of d94Lc-kq^  
rituximab at a dose of 1000 mg on days 1 and 15. To minimize infusion reactions,  ,9  
patients were premedicated with acetaminophen (1000 mg) and diphenhydramine m<TKy_C`  
hydrochloride (50 mg) orally. In addition, methylprednisolone (100 mg, i.v.) was given Smg,1,=  
prior to the first rituximab infusion. B-cell depletion was defined as CD19+ count 9?@M Zh  
<5 cells per l at any time and B-cell recovery was defined as CD19+ cell count Z*x Q"+\  
>15 cells per l. Patients treated with rituximab, who at month 6 had proteinuria >3 g per '}]w=2Lf  
24 h and in whom CD19+ B-cell counts had increased to >15 cells per l, received a 2 ;U(r: ]  
second course of rituximab treatment following the same protocol described above. #t po@pJsE  
Follow-up F0]NtKaH  
In all patients, clinical and laboratory parameters including complete blood counts, 8^^Xr  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum )0~zL} )?  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry q>o1kTI  
and at months 1, 3, 6, 9, and 12. Creatinine clearance and protein and creatinine excretion XwE(&ZCf'b  
in the urine were assessed by performing two consecutive 24-h urine collections at each .$L'Jt2X  
time point. Data were considered accurate when urinary creatinine excretion was C.Y]PdYyj  
consistent with a complete 24 h collection. The mean of the two measurements was pma'C\b>  
considered for the analysis. The presence of HACAs was evaluated at baseline and at Ae;> @k/|=  
months 3, 6, 9, and 12. -Wb/3 X  
Method / Approach / Study/ Technique &X }GJLC3  
A discussion is presented of a problem-solving system edx-R-Dc-1  
To improve the efficiency of the method, the following approach may be applied. ` XE8[XY  
In order to an investigation was made to find the causes of the IlN9IF\9L  
Although large collections of rules and equations have been complied, none are generally 7%b?[}y4  
accepted /YKg.DA|  
20 rB}Iwp8  
This approach will be explained and discussed thoroughly in the body of the report. &-dyg+b3  
This can be accomplished by o $7:*jU  
This algorithm to compute the total cost can be described step by step as follows: S|CN)8Jsi  
The above preliminary analysis has provided important information +fBbW::R^  
Various methods have been proposed for selecting an optimum... |_x U{Pu  
These concepts have been applied to _lcx?IV  
On the basis of the concept mentioned above, VEj-%"\   
This can be achieved by yU<T_&M  
In addition, tissues were stained for infiltrating lymphocytes (CD20 and CD3), and the !VBl/ aU@  
amount of interstitial fibrosis was quantified by histomorphometry. Formalin-fixed, #;4<dDVy  
paraffin-embedded sections were cut onto coated glass slides. Following heat-induced >c %*:a  
antigen retrieval, sections were incubated at 20°C overnight with either anti-CD20 C^oj/} ^  
primary antibody or anti-CD3 primary antibody, both at 1:1000 dilution (Dako, Canada r {R879  
Inc, Mississauga, Ontario, Canada). After rinsing all sections, pretreatment with 3% b9`vYnLk  
hydrogen peroxide was performed to prevent endogenous peroxidase activation. Sections hA 1_zKZ  
were incubated with a secondary rabbit anti-mouse antibody linked with avidin–biotin U?]}K S;6  
complex. Sections were counterstained with hematoxylin and examined by light *f<+yF{=A  
microscopy. 4OX|pa  
The HACA assay is a proprietary bridging enzyme-linked immunosorbent assay 2aj9:S  
performed at Genentech Inc. that measures the antibody response to rituximab in human %?  87#|  
serum samples. +8p4\l$<`  
In all patients, clinical and laboratory parameters including complete blood counts, -(~OzRfYi  
electrolytes, serum albumin, B-cell flow cytometry for CD19+ B cells, serum b~oQhU??"  
immunoglobulin (IgG, IgM, IgA) levels, and a lipid panel were evaluated at study entry aUZh_<@  
and at months 1, 3, 6, 9, and 12. gs/ i%O  
This fact suggests that a new concept dbVMG-z8  
This was accomplished by taking ... <?8 aM7W7  
The preparatory stage is very time consuming process. ' v)@K0P  
Test are performed for validity, completeness, and compatibility 9szUN;:ZZ  
There is little hope of achieving successful ... 2?c# #Izn  
There has been an increasing awareness of the potential of using most ..so far made have fGtYvl O-5  
not taken this approach, with the exception of T5<851rH  
Only a few studies can be found. ctk~}( 1#  
It is a very tedious process to go through ]wxjd l  
It is only when .. has been completed that .. may be effected v^0*{7N'  
The entire interpretation process is conducted in one's head. @yImR+^.7  
These approaches are sometimes very tedious. W[VbFsI&b  
Several techniques can be used fV(WUN+  
A polynomial parametric model can be written as [the following]/[follows]: #Ch*a.tI@  
A xx model is constructed/formulated using xx. Tf*DFyr  
A xx model represents an xx by its xx. zhdS6Gk+  
A process decision model captures the logic essential to (/ qOY  
From the equation above, xx is equal to the summation of xx times the ... |O';$a1S  
21 RW4,j&)  
The validity of a xx model can be checked using Euler's formula. WeiDg,]e$b  
Given a model, one can mathematically determine whether ... or ... '_~qAx@F#c  
Equations for xx need to be derived and implemented in the system. Hy~+|hLvh  
A number of heuristic rules have been developed for @{q:179w^  
Optimum .. techniques can be made more reliable by ... so that *,FU*zi  
An algorithm based on the characteristic ... is used to determine U_KCN09  
Euler's formula states the following: q@=3`yQ  
The completed model should agree with the formula. <p5?yF  
For manufacturing purposes, a detailed and precise model of the object is necessary ]8+ D  
Engineering design models are very well defined; therefore, "$k rK7Z  
To keep the domain narrow enough to be implementable, yet wide enough to be useful. r oM!%hb  
Point of View e.VQ!)>  
from an implementation standpoint, fNk0&M  
From the point of view of this application, 7!g"q\s  
From this point of view, Zadeh suggested an inference rule named xxx (CRI for short). ^61;0   
Information is the meaningful interpretation and correlation of some aggregation of data  SH6+'7  
in order to allow one to make decisions. 6PyW(i(bs  
From a practical point of view, the computational aspects of an FLC require a 2DNB?,uP,'  
simplification of the fuzzy control algorithm. lj /IN[U/  
The use of a hammer to insert screws, although partly effective, tends to distort, destroy, Y !%2vOt  
and generally defeat the purpose of using a screw [Kusiak AI Implications for CIM -2B3 xIZJ  
p.129] "F:V$,mJ  
Statistical analysis \7PC2IsT3  
Data were analyzed by one-way analysis of variance comparing the three conditions P%aNbMg  
(sham operation, ischemic AKI, and bilateral nephrectomy) at each time point. If 5t,X;  
significant F-statistic from analysis of variance existed, this test was followed by Dunnett jG`,k*eUrJ  
post hoc multiple comparison procedure with sham operation as the control group. For all &!F"3bD0  
other comparisons, Student's t-test was used. A P-value of <0.05 was considered as watTV\b  
statistically significant. k$|g) [RE  
Values are expressed as means s.e.m. and significance was evaluated by Mann–Whitney 9@8'*a{`m  
U test using GraphPad Prism, version 4.0 software (GraphPad Software Inc., San Diego, }5AA}=  
CA, USA). GuC 9h^[=M  
All values are expressed as means s.d. Statistical significance (defined as P<0.05) was EXsVZg"#  
evaluated using analysis of variance and Bonferroni t-tests, and the two-tailed Pearson's o@L2c3?c5  
test, where appropriate. _jb&=f8  
Data are expressed as mean s.d., median and interquartile range, or frequencies, as PJT$9f~3;.  
appropriate. Variables who deviated from the normal distribution (positively skewed) jx} 7/  
were log-transformed (log10) before the correlation study. N;a'`l  
Data are represented as means s.e.m. Student's t-test and multiple comparisons with t-test 1)3'Y2N*  
post hoc analysis of variance were used as indicated below, for the comparison of EE*|#  
22 u2OrH3E4E3  
morphological, immunohistological and functional parameters. Statistical significance klMpiy  
was set at P<0.05. 7m%[$X`  
The primary efficacy parameter was defined as change in urinary protein excretion from N8DouD q  
baseline (week 0) to 12 months after treatment. The 12-month changes were tested }~p%e2<  
against zero using the paired t-test. Secondary end points included 6-month changes in Z_a@,k:+[  
protein; the number with PR or CR at 6 or 12 months; and changes in glomerular CM6! 1 7  
filtration rate (GFR), serum albumin, and lipid profiles. Study sample size was based on \t%iUZ$  
the desire to have 80% power to detect a drop in urinary protein of at least 2.0 g day-1. lavy?tFer  
Assuming a two-sided hypothesis test performed at a significance level of 0.05 and an s.d. 2.^CIJc  
of urinary protein change of 2.5 g, it was determined that 15 patients were required.2 do9~#F  
Definition of remission status is according to the criteria established by Cattran et al.30 j{johV+`8  
CR was defined as proteinuria <0.3 g per 24 h, PR as proteinuria 3 g per 24 h, and a E@6gTx*  
>50% reduction in peak proteinuria and non-response as <50% reduction in peak Xpv<v[a  
proteinuria. Any patient reaching a CR or PR was considered a treatment success C$$Zwgy  
The statistical significance of differences for the mean values of cytokine concentration ^y%8_r&  
and T cell proliferation was determined with Student's t-test. Differences with a P value ?]aVRmL  
of less than 0.05 were considered significant. 76] Z~^Y  
Statistical significance was determined by Student's t-test. Data with a P value of less Z78i7k}  
than 0.05 were considered significant. S(^YTb7  
In vitro and in vivo experiments were analyzed by the two-tailed Student's t-test, with P _yF@k~ h  
values less than 0.05 considered statistically significant. 66sgs16k  
The significance of differences among groups was determined by Student's t-test and  @' %XdH  
one-way analysis of variance (SigmaStat software; Jandel). OH@gwC  
Comparisons JG&E"j#q  
As well, the pros and cons of these representations from a process planning point of view =[[I<[BZq  
will be discussed. LE~vSm^#  
The method of using xx to implement xx described by Zadeh (1973) appeared more +>AVxV=A#  
suitable E2z=U  
As discussed [in the previous section]/[preciously], .:4*HB  
Relation }eI9me@Aa  
We can not invert F' directly because it defines a many-to-one mapping. MiKq|  
The relationships appear very complicate Z0O0Q=e\Y  
Lifting tasks involve complex and imprecise relationship between the task variables and 8kr$w$=q  
the human operator's characteristics. Z-pZyDz  
These methods are based on the relationship between ... and ... ttH Rc!  
The fundamental concept of a fuzzy rating language is that we can establish a relationship XMykUr e|  
among terms such as high, medium, and low, and then modify these relationships. MtgY `p  
This article will thus mention the latter as well as the former. keKsLrd  
The former two bear a close relation to a fuzzy Cartesian product. T,Q7 YI  
Importance %Wm)  
m*h O@M  
23 TEGg)\+D>  
The emphasis is on an implementation of a general approach to rule based decision j~=<O<P  
making. u-bgk(u  
Consideration / Attention {j<?+o5A  
Careful evaluation is necessary to ensure Xk:3w,  
Such a formulation does not change further considerations. @Jlsx0i}}  
Considerable attention has been paid to s0h0Ep ED  
Attention should be paid to an important finding of this investigation. !c0x^,iE  
Caution should be exercised in this process to avoid ... o)CW7Y#?,  
Primary consideration is given to ... components, though others can be accommodated Nv=%R  
After ... has been defined by ..., a carefully analysis is carried out/performed to determine zxd<Cq>d  
A number of factors such as ...need to be taken into consideration before making the hh.`Yu L  
appropriate decision. 1-<?EOYaE  
It should be noted that :; La V  
It is important to point out that ... dDA&\BuS  
These considerations have heightened interest in the possibility of providing ... j.V7`x  
We should stress the fundamental importance of the xx 3.=o}!  
Results. "CFU$~  
Advantages / Disadvantage |y?W#xb  
One of the major advantages of this new measure of xx is that it can be applied to the >{rD3X"d  
experimental study of }Py Z{yS  
One advantage of using a .. is the ease of preparing it. bQu@.'O!k  
It has a very fast decision making process ws,VO*4  
All the algorithms involve mostly logical operations. =;?Maexp3$  
It can be easily and without additional cost implemented in a microprocessor;based 4]%MrSjS  
environment. ! ;Ctz'wz  
It can reduce the waste of designing from scratch. nv: VX{%  
The advantages of using a xx to represent xx are the following: ,pdf$) XB  
However, xx is not without its shortcomings. C3K")BO!  
In most cases, the xxx shows an improvement over the existing xxx. nfE4rIE4  
Compared to the existing xx, the impacts of the xx are generally reduced by 5% to 9%. \YsLVOv%:d  
The "best case" results shows a savings of 6% to 9%. 'W~6-c9y  
Most of the existing works based on xx approach can only recognize a xx .  LD}<|  
Most of the above methods are computational expansive and limited to xx. V?jot<|$  
Some other advantages of xx are the following: D}nRH@<`  
The problem is the limitation of this method to a limited domain of parts.  ;W@  
It proved limited in application because it demanded precision in system modeling that .wQM_RZJ  
was impossible in practice. 1?".R]<{2T  
There are advantages to be gained in the structuring of costs and benefits, the use of xx, NHaqT@:  
The disadvantages of this method are also disadvantages of conventional xx approaches. y,$zSPJCi  
This combines the best features of both techniques 7KV0g1GQ  
24 OH`|aqN  
Hopefully, this tool can be as the reference framework of for developing a xx platform, 5 r&n  
and helping the administration, marketing, and knowledge management activities in $HFimU,V=0  
virtual communities. =XZd _v  
Results PO]c&}/  
An improvement on the result shown above can be made by based on the data provided w(!COu  
Recent work has identified _4X3g%nXl  
Time-dependent changes of R9^R G-x  
Cyclosporine-induced cell death is triggered by a non-classical phosphoinositide 3-kinase `SG8w_  
and does not require ERK activation. T7ICXpe@  
Much of the current work on <P pW.1w  
Discussion of these theories is beyond the scope of this review ^7V{nT@H3  
Based on the information contained in this O|Y~^:ny  
The result can be categorized into nine classes YC =:W  
The results are illustrated by an example t@3y9U$  
The experimental results for each xx time are reported in Table 2.  [?moS!  
From the results obtained so far, it seem that ,2`FSL%J  
Because of the inaccuracy of the ..., a conclusion cannot be drawn as ;.&k zzvJ  
Although much effort has been made to., this reality is far from completion. 'XW9+jj)/  
The results indicate that the total benefits are higher than the total costs. ,*d<hBGbh  
Their results may then serve as guidelines for lower level models, less fuzzy and more tY!GJusd  
detailed. _REAzxe S  
Conclusion th`pf   
From the discussion, one may conclude that ... L<[%tvV  
The first indication that ,HtX D~N  
In summary, we have shown that V~"-\@  
These results suggested that 0^ >b=a  
Our findings have shown that 8Ao pI3  
Our observations have provided 9 y{R_  
This study reveals following five main findings: NM0s*s42  
To our knowledge, this is the first immunohistochemical report of both PIM and HIFs in H_d^Xk QZ  
the diabetic kidney. :fA|J!^b[  
As mentioned above, ';KWHk8C  
Moreover, we demonstrate that, [K""6D  
A number of studies have elaborated a body of knowledge about v^3s?V D  
There are findings to indicate that i2l/y,UX  
On a descriptive level, there is agreement that for kV@?Oj.&I,  
One issue that became particularly evident from our study is Mew,g:m:  
Our data are in agreement with the findings and models presented by previous g+3_ $qIQ+  
publications, in particular those of Jones et al =2e{T J/  
According to our observations, UT_kw}1 o  
…was not evident from our data : 22)` ;0  
25 P71] Z  
It could therefore be concluded that tP4z#0r2  
our data illustrate that ;L[N.ZY!  
All these different aspects, as listed above, lead to ti!kJ"q  
In fact, it has already been speculated that mv>-X J+  
It should be furthermore mentioned in this context that u4|) A4n  
To identify and verify the essential factors triggering developmental renin expression, it \1<8'at  
is of interest now to study the development of intrarenal renin expression in mice with ca<OG;R^  
defined gene mutations, using the results of this study as a reference system. V I]~uTV  
In conclusion, using several approaches, we demonstrated that HT7I ~]W  
But we have not provided formal proof yet that r-o+NV  
In summary, our results suggest that ai"N;1/1O|  
In conclusion, we identify )=AWgA  
A better understanding of such regulatory systems may yield novel therapeutic ,*8)aZ1 k  
approaches to glomerular diseases. j{YIVX  
Preliminary results of short-term studies (2 weeks) indicate that 49= K]X  
However, we believe that N ;Cs? C  
However, despite our extensive measurements of these parameters, we found no iy|;xBI,  
relationship between response and initial proteinuria, time to B-cell recovery, the 08/Tk+  
development of antibodies to rituximab, B-cell count in the kidney tissue, nor the degree U/ax` _  
of tubular interstitial damage present. A clear conclusion for efficacy, however, cannot be .Hg{$SAC(w  
obtained from an uncontrolled study, and definitive claims of efficacy should be reserved 4lI&y<F  
for rigorous, prospective, controlled, and randomized trials with the use of rituximab and MAQ-'s@  
that will also look for factors that may determine its efficacy in IMN. 'p)DJUwt  
It has become increasingly clear that W9]0 X  
Form the above discussion, the conclusion can be reached that P MI?PC[;  
The conclusions drawn are also valid Y.kc,~vYL  
In conclusion to this, it becomes obvious that the problem of xx lies not only in... SeuDJxqopD  
We have attempted to introduce some concepts associated with a theory of # )s +I2  
Considerable more work, hopefully, will be done in this area ( yoF  
Employing the compositional rule of inference, the assessment of the xx compatibility in ng9 _c  
achieving prescribed xx projectiles in any level of the hierarchy is made possible. qDgy7kkQ  
This paper has presented a theoretical and experimental study of the xx process and xx &'Xgf!x  
concept. IFW7MF9V  
The experimental research results will hopefully serve as useful feedback information for V9 cj  
improvements for xx work. g ;X K3R  
The scope of this contribution was to introduce a xx method. TP/bX&bjCy  
This has a tremendous impact on our understanding of ]YOWCFAQot  
Significant progress has been made in advancing RNAi therapeutics in a remarkably bdEI vf7  
short period of time mQ9shdvt-  
To date, little is known about… bfYVA2=Z  
Irrespective of the mechanisms and the molecules –which are still largely unknown – 8idIJm%y  
involved in MSC functions, current data suggest that i 1Kq (7  
To better understand N#@v`S  
26 ?y__ Vr w  
Future Research (常用于conclustion 的结尾) ZE1${QFkG  
Thus, first extension of the approach could be, KTwP.!<v  
Further studies are needed to determine the importance of Fc=6 *.hy  
Some improvements to the scheduling aspect of the model may be brought through N8=-=]0G  
additional levels in the hierarchy for more detailed representation of the scheduling f1?%p)C  
activity. T_#8i^;D  
It also unveiled new aspects of the role played by thyroid hormone in response to injury ` k(Q:  
and tissue repair. jVHS1Vsei  
In the near future, the ongoing clinical trials with siRNAs for macular degeneration and 8 qZbsZi4  
RSV may reveal the exciting potential of RNAi therapeutics as the next major class of u9u'5xAO  
drug molecules. i6y=3k  
In the next few years it should become clear whether k ~F ,n  
It should be an exciting time for researchers seeking to harness this powerful endogenous 9[lk=1.qN  
pathway to treat human disease. B~J63Os/  
Acknowledgement 5PP^w~n  
The authors are grateful to the insightful work provided by Mr. John W. Harney and all 8i<]$  
of the fellows and students that contributed with some of the studies discussed in this &PFq(4  
article = C/F26=|  
I would like to express my gratitude to all those who gave me the possibility to complete Og?GYe^_  
this thesis. @gmo;8?k  
I want to thank the Department of Transport of the former Interim Government of fu-,<m{  
Namibia for giving me permission to commence this thesis in the first instance, to do the I1s$\NZ~]  
necessary research work and to use departmental data sE!g!ht  
This work was supported by NIH grants AI058695 and AI056900. We thank members of jM-5aj[K  
the laboratory and our collaborators for many useful suggestions. -.L )\  
We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. G]mD_J1$  
Duckman for graphics assistance and A. Capobianco for word processing assistance. \((5Sd  
Author contributions rEbH< |  
All authors were involved in experimental planning and data analysis and contributed to ml!c0<  
manuscript preparation. NJ;m&Tm,DF  
Tables and Figures 0O-"tP8o  
Figure 7-1 sketches these relationships. z\?<j%e!t  
The graphical representation of these functions is shown in Figure 1. u g;~dhe~  
The xx may be depicted as in Figure 1. EB6X Yr  
Figure x shows the schematic diagram of the z2! 4w +2  
Figure 1 though 2 provide a ... that 7W5Cm\  
the architecture of this expert system for .... is illustrated in Figure 2. %az6\"n  
Figure 2 gives the outline of an ... system <(V~eo e  
Table shows the hb %F"Q  
27 )r)ZmS5O  
Time-dependent changes of ; qr?[{G  
as shown in Table 1 and 2 6UL9+9[C  
This concept is illustrated in Figure 2 )|AxQPd  
At the top of Table xx are shown two blocks of data. Pf?15POg&B  
Each table or matrix has constructs xx through xx as row;headings, 8pp;" "b  
xx through xx as column;headings. r6:e 423  
Time course of calculated renin immunoreactive tissue volumes during development of ta PqRsvu  
the mouse kidney. Data are single values per time point. They were derived from the GhjqStjS&l  
kidneys shown in Figure 1. QXl~a%lB  
Yellow color indicates _#{qDG=  
PCT3 cells were pretreated with 50 M PD98059 or 10 M U0126 for 30 min and then DZEq(>mn  
cells were stimulated with 25 g ml-1 CsA for 6 h. ERK and PKB activation were |L:X$oM  
analyzed by western blot using phospho-specific antibodies. $+Z2q<UT  
ERK and PKB activation were measured by western blot using phospho-specific ,068IEs  
antibodies =En1?3?  
The data are the means of three different experiments taking the number of untreated cells _5$L`&  
(vehicle alone) as 100%. NS*Lv  
ERK and PKB activation were then analyzed by western blot with the corresponding JRj{Q 1J  
phospho-specific antibodies. To ensure equal amount of protein in each lane, western {G<1.  
blots against total protein were performed for ERK and PKB. }nO%q6|\V  
The means of optical density (OD) values of the bands detected in western blots of three ap"pQ[t;  
different experiments are plotted, taking the maximal value of phosphorylation of ERK 1\)lD(J\C  
and PKB as 100%. KDA2 H>  
CT3 cells were treated with 25 g ml-1 CsA or vehicle alone for 24 h and then fixed with >*n4j:  
paraformaldehyde and stained with Hoescht as indicated in Materials and Methods. Then 'R42N3|F  
cells were visualized by phase-contrast microscopy (upper panel) and fluorescence t3K9 |8<  
microscopy (lower panel). \ (` C*d  
The data are the means of three experiments performed on different days taking the C#3&,G W  
number of cells at the onset of the experiment as 100%. ej=}OH4  
Rats were killed at 4 h and at days 1, 2, 4, 7, 9, 14, 21, and 28 after disease induction roe_H>  
(n=9 each). fGe"1MfU  
*P<0.05 versus non-nephritic rats. 1' dZ?`O  
The expression of the CCN3 protein was detected by western blot analysis (n=4 each, PC, ((^v sKT  
positive control, M, molecular weight markers). #yEkd2Vy{  
Original magnifications: 200 in A, E, G, H; 600 in B, C, D, F. ?`6Mfpvj96  
Data are means s.d. of four independent experiments. ~SsfkM"  
*P<0.05 versus 0.5 h. rL?{+S]&^)  
PDGF-BB and -DD, but not PDGF-AA and -CC, induce a downregulation of CCN3 `1y@c"t  
mRNA as determined by real-time RT-PCR and normalized to V!e*J ,g  
glyceraldehyde-3-phosphate dehydrogenase mRNA. {Hv kn{{'  
Cell number was counted in duplicate using a Malassez hemocytometer Y$+v "  
Data are means s.d. of four independent experiments. *P<0.05 versus cells treated with dwiLu&]u  
MCDB media for 24 h, #P<0.05. k RSY;V  
28 2|`Mb~E;  
The curves are adjusted for history of coronary artery disease, CRP, and progression to %O7?:#_  
ESRD. $:onKxVM  
Both models are independent of age, gender, baseline GFR and proteinuria, and other  x_/H  
clinical characteristics and traditional and nontraditional cardiovascular risk factors WW7E*kc  
Correlation between serum bone-specific alkaline phosphatase (bAP) and serum PTH c]ga) A(  
(n=99, P<0.0001, r2=0.190) d/YQ6oKU  
Concentration of serum FGF23 concentration before starting and at the end of the 4-h >T n[CgH]7  
hemodialysis procedure in 23 patients, expressed as log10 values (n=23, P<0.0001, 1WY$Vs  
Student's paired t-test). ?4Rq +  
Immunohistochemistry for the hypoxia marker pimonidazole (PIM) and HIF-2 ; X 3ZKN;  
arrow=endothelial cell and CD=collecting duct 4(,X. GVY/  
Magnification: 1000. gDX\ p>7  
A table of .. is developed and significant recommendations are made. Jr>Nc}!U  
CONJUGATION nGTqW/k[+s  
To Indicate Addition C"k]U[%{  
additionally, again, also, and then, as can be easily understood, besides, equally important, e)F_zX  
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broadly speaking H;FzWcm  
To Indicate Cause and Effect hm1.UE  
accordingly, as a result, consequently, for this reason, hence, in short, otherwise, then, T 7M ];@q  
therefore, thus, truly m x2Ov u  
To indicate Comparison QCfR2Nn}  
in a like manner, likewise, similarly , alternatively ]\3<UL  
To Indicate Concession g{m~TVm'  
after all, although this may be true, at the same time, even though, even so , I admit, JS&;7Z$KX  
naturally, of course 8: VRq  
To Indicate Contrast ZP.~Y;Ch;-  
and yet, at the same time, but, for all that, however, yet, in fact, in contrast, in the real life, . B6mvb\  
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still, traditionally, rather, unfortunately, : p7PiqQ  
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after a short time, afterwards, as indicated earlier, as long as, as soon as, at last, at length, P0-K/_g  
at the moment, at that time, at the same time, before, earlier, currently, immediately, in DM{Z#b]  
the meantime, in recent years, lately, later, meanwhile, often, of late, presently, recently, G-DOI  
soon, shortly, since, thereupon, temporarily, therefore, until, when, while x0q `Uc  
29 ,{#Li  
To Indicate Special Features or Examples +3-f$/po  
for example, for instance, incidentally, indeed, in fact, in other words, in particular, in %nj{eT  
practice, specifically, that is, to illustrate, in this respect, theoretically, as mentioned t\-;n:p -  
before / above x< ) T,c5Y  
To Indicate Summary 5g phza  
in brief, in conclusion, in short, in summary, on the whole, to conclude {Ytqs(`   
, in general, to summarize, to sum up, as a result, ultimately, ;QQ/bM&I  
VERB PHASE <{k8 K6  
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build up the key link K%NgZ(x(  
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can be regarded as / achieved / used to/for / found / obtained through 6Vy4]jdT5  
can result in Wi zVw&Iv  
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production information in order to simultaneously Y q-7!  
contains all information necessary to describe :.W</o~\s  
do not make use of production information _t\)W(E&  
deals with p|'Rm ]&jb  
end with failure oJVpJA0IA  
fetch the information from the model directly hrTl:\  
has great potential / yet to be resolved / spurred the development of / 5Q@4@b{C  
been recognized as N##- vV  
site component / cable of / currently implemented for / demonstrated by an example / cW\Y1=Gv|  
finally reached / made equal to / equivalent to / more suitable to / oriented to / u#v];6N  
interpreted as / pointed out / potentially of great benefit in the complex task of / shown !_j6\r=  
in / used to effectively guide the search SSa0 x9T  
makes use of {DbWk>[DkG  
was significantly higher as compared to c"^g*i2&0  
To assess disease-specific alterations, we measured ;v> +D {s  
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make up +{"w5o<CO  
To determine if Z6_E/S  
This statistically significant difference still 3B[u2o>  
They positively correlated with i$ S*5+  
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30 Q (ec>+oi  
contribute to u13v@<HGc  
meets the needs of real life production,/ the current demands placed upon it SyCa~M!}>  
must be justified 53)*i\9&  
point out C+X- Cp  
play an important role I<LIw8LI  
relates to &U0Y#11Cx  
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satisfy the needs P~7p~ke  
determine the total requirements for the ... OIdoe0JR:O  
uses ... as a key to search for...  _V_GdQ  
without relying on oiNt'HQ2/  
will be available/ performed/ overlooked Y5$VWUrB  
NOUN PHASE R\,qL-Br  
a basic technical function of V { yk  
a significant reduction of 6`U]%qx_I  
drug variability n>i}O!agg  
a critical need I18<brZJ  
negatively correlated with X6k-a;  
a key / principle feature of 31=v US  
a substantial impact on Y[Kpd[)[v  
an intensive review was conducted LQ3J$N  
The analysis of the correlations by  dPCn6  
an increasing need for expanding the application of .... u:GDM   
an important component / function / aspect / issue HA0Rv#p  
each rule is numbered in sequence VAet!H+]  
each of these involves 't <hhjPqY  
for this calculation, it is necessary to define _8'z"w F  
in the physical environment / integration of wwVg'V;  
in the reality of situations where … 6UnWtLE  
many aspects of Ze-MB0w  
most past efforts have been spent on ... X;%*+xQ^  
common sense to a well studied and documented technical field. h&j9'  
sources of additional information on ... are listed UcxMA%Pw7$  
systematic and rationally structured format iDrQ4>  
the basis on which a range of ...operations can be established is shown <Pg<F[eDM  
THE basic philosophy / principles of / key element / general hypothesis / candidate list Zq\Vq:MX  
of / concept of ... has attracted wide interest / function is concerned with / heart / h(MS>=  
impact / nature / role / task of / kernel functions X Cf!xIv  
the number of parts needed to -VPda @@w  
the above statement means that ^dCSk==  
the output data is passed to 9i*Xd$ G  
31 R'1L%srTM+  
the proposed method / underlying principle #uillSV  
the recommendations made in this report, if implemented, should n,.t~  
this information resides in EaXD Y<  
this process is composed of ... different ... operation KM jnY2  
along with the use of %2t#>}If!  
concerning general aspects of dpI9DzA;  
due to j+7ok 5J#  
for later use in generating..., kFsq23Ne  
in turn, [tY +P7j9)  
it can be claimed/concluded that ajMI7j^G  
it demonstrates the decisions required of $,L,VYN  
it also provides information to .. dgsD~.((A  
it becomes essential to KQ\ d$fX  
let ... be the probability that *2tG07kI  
once... is written, it is compiled into... !ii'hwFm$  
suppose it is observed that ^vH3 -A;*  
this is because 8NS1*\z  
this results in a u]%>=N(^2  
upon completion of the ... analysis, Ap [}[:U  
when the knowledge is of mathematics or quantum physics, it will also be F9&ae*>,  
recorded in books and papers ,J0BG0jB^u  
selection of rules for using the tools, for generating operation plans, u/8urxp y  
is another matter of preference, since practice varies greatly. =z$XqT.'  
for the sake of convenience ;Pi-H,1b  
correct decision to be reach A+Xk=k5<  
keeping the number of rules to a minimum. B "z`X!\  
a good process plan will result exhibiting several characteristics: VY9|8g/  
practical solutions 79svlq=  
because of rather small job lot sizes {LLy4m  
Backward reasoning can be used to answer the question "should milling tool be select" dw v( 8  
different level of knowledge in the realm of process planning
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