Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells
Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand T fh cells
and promote germinal center induction
James J.Moon a,b,Heikyung Suh a,b,c,Adrienne V.Li b,Christian F.Ockenhouse d,Anjali Yadava d,and Darrell J.Irvine a,b,c,e,f,1
a Department of Materials Science and Engineering,Massachusetts Institute of Technology,Cambridge,MA02139;
b Department of Biological Engineering, Massachusetts Institute of Technology,Cambridge,MA02139;d Division of Malaria Vaccine Development,Walter Reed Army Institute of Research,Silver Spring,MD20910;e Koch Institute for Integrative Cancer Research,Massachusetts Institute of Technology,Cambridge,MA02139;f Ragon Institute of Massachusetts General Hospital,Massachusetts Institute of Technology,and Harvard University,Boston,MA02129;and
c Howar
d Hughes Medical Institute,Chevy Chase,MD20815
Edited by Melody A.Swartz,Swiss Federal Institute of Technology(EPFL),Lausanne,Switzerland,and accepted by the Editorial Board November15,2011 (received for review August10,2011)
For subunit vaccines,adjuvants play a key role in shaping immuno-logical memory.Nanoparticle(NP)delivery systems for antigens and/or molecular danger signals are promising adjuvants capable of promoting both cellular and humoral immune responses,but in most cases the mechanisms of action of these materials are poorly understood.Here,we studied the immune response elicited by NPs composed of multilamellar“stapled”lipid vesicles carrying a recombinant Plasmodium vivax circumsporozoite antigen, VMP001,both entrapped in the aqueous core and anchored to the lipid bilayer surfaces.Immunization with these particles and monophosphoryl lipid A(MPLA),a US Food and Drug Administra-tion–approved immunostimulatory agonist for Toll-like receptor-4, promoted high-titer,high-avidity antibody responses against VMP001,lasting more than1y in mice at10-fold lower doses than conventional https://www.wendangku.net/doc/6716002719.html,pared to soluble VMP001mixed with MPLA,VMP001-NPs promoted broader humoral responses,target-ing multiple epitopes of the protein and a more balanced Th1/Th2 cytokine profile from antigen-specific T cells.To begin to under-stand the underlying mechanisms,we examined components of the B-cell response and found that NPs promoted robust germinal center(GC)formation at low doses of antigen where no GC induc-tion occurred with soluble protein immunization,and that GCs nucleated near depots of NPs accumulating in the draining lymph nodes over time.In parallel,NP vaccination enhanced the expan-sion of antigen-specific follicular helper T cells(T fh),compared to vaccinations with soluble VMP001or alum.Thus,NP vaccines may be a promising strategy to enhance the durability,breadth, and potency of humoral immunity by enhancing key elements of the B-cell response.
O utside of sub-Saharan Africa,Plasmodium vivax is the most frequent cause of recurring malaria and infects130–390 million people each year,representing approximately50%of all malaria cases globally(1).Although not as virulent as Plasmo-dium falciparum,P.vivax has a long dormant liver stage,lasting months in some cases,and poses a significant threat to the global health(2).The circumsporozoite protein(CSP)is the most pre-valent protein in Plasmodium sporozoites(3)and has been the target of clinical vaccine trials for P.falciparum(4).T o date,how-ever,there have been limited attempts to advance vaccines for P.vivax.We recently developed VMP001,a recombinant protein antigen composed of CSP core sequences derived from two widespread isolates of P.vivax(5,6).Although VMP001mixed with either alum or Montanide elicits antigen-specific antibody responses(5,6),adjuvants capable of eliciting high-affinity anti-bodies against protective regions within CSP,which may lead to opsonization of sporozoites(7)or inhibition of their entry into hepatocytes(8),are of great interest.
Recently,antigens and adjuvants delivered by synthetic nano-particles(NPs)have emerged as promising vaccine formulations.NPs may allow co-delivery of antigen and immunostimulatory molecules to the same intracellular compartment in antigen-presenting cells(APCs)(9)and promote cross-presentation of antigens,enhancing CD8tT-cell expansion and functionality (10–12).NP delivery of antigens and adjuvant molecules such as T oll-like receptor(TLR)agonists also has been shown to promote humoral immune responses(13,14).However,a greater under-standing of the mechanisms by which synthetic particles enhance immunity will be critical to maximize the potential of NP vaccine strategies.
We recently reported the design of a unique class of lipid-based NPs,interbilayer-crosslinked multilamellar vesicles(ICMVs), possessing many favorable characteristics for vaccine delivery (10).ICMVs,synthesized by forming covalent cross-links across lipid layers within multilayered lipid vesicles,are stable in the ex-tracellular milieu following injection and retain entrapped pro-teins until the particles are internalized into intracellular compartments,thereby increasing the delivery of antigen to APCs in draining lymph nodes(dLNs).Immunization with ICMVs gen-erated strong humoral and cellular immune responses to the model antigen ovalbumin(OVA)(10).In these studies,OVA was entrapped in the aqueous core of ICMVs.However,because cross-linking of B-cell receptors(BCRs)and B-cell stimulation are facilitated by structurally repetitive antigens,such as in viral and bacterial membranes(15,16),we hypothesized that multiva-lent display of antigen on the surfaces of ICMVs would enhance the humoral response.
Here,we tested the efficacy of ICMVs for delivery of the VMP001malaria antigen,and exploited available terminal cy-steine groups in the protein to both encapsulate VMP001in the core of the NPs and anchor a fraction of the protein to the lipid membranes of the vesicle walls,creating VMP001-ICMVs.V ac-cination with VMP001-ICMVs dramatically enhanced both the quantitative strength of the antibody response and qualitative breadth and isotype bias relative to the conventional adjuvants, such as MPLA,alum,or Montanide.ICMV vaccination also pro-moted robust GC formation with the majority of GCs nucleated adjacent to depots of ICMVs accumulating in dLNs.Further-more,ICMVs induced antigen-specific T fh cells,surpassing the Author contributions:J.J.M.and D.J.I.designed research;J.J.M.,H.S.,and A.V.L.performed research;C.F.O.and A.Y.contributed new reagents/analytic tools;J.J.M.,H.S.,A.V.L.,and D.J.I.analyzed data;and J.J.M.and D.J.I.wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.M.A.S.is a guest editor invited by the Editorial Board.
Freely available online through the PNAS open access option.
1To whom correspondence should be addressed.E-mail:djirvine@https://www.wendangku.net/doc/6716002719.html,.
This article contains supporting information online at https://www.wendangku.net/doc/6716002719.html,/lookup/suppl/ doi:10.1073/pnas.1112648109/-/DCSupplemental.
levels induced by10-fold greater doses of antigen adsorbed to alum.Thus,NP vaccines have the capacity to enhance the breadth,avidity,and durability of humoral responses by promot-ing multiple key stages of antibody development.
Results
Design of ICMV NPs Combining Membrane Display and Encapsulation of Soluble Antigen.The synthesis of antigen-loaded ICMVs proceeds in three steps:formation of anionic maleimide(MAL)-functionalized vesicles by hydration of lipid films in the presence of antigen,fusion of vesicles via divalent cations,and finally “stapling”of the vesicles by addition of membrane-perme-able dithiols that cross-link lipid headgroups bilayer-to-bilayer (Fig.S1)(10).We previously showed that immunization with the TLR4agonist MPLA and ICMVs entrapping OVA in their aqueous core provided substantially enhanced antibody re-sponses against the protein,compared to soluble protein/MPLA vaccinations.T o determine whether the effectiveness of ICMVs could be further enhanced by combining aqueous encapsulation with anchoring of a fraction of the antigen to the membranes of the particles,we exploited the MAL groups in ICMV precursor vesicles as sites for both cross-linking of the bilayers and for conjugation to free cysteines of the malaria antigen VMP001 (Fig.S1and Fig.1A).We thus formed ICMVs in the presence of VMP001containing cysteines at the N and C termini.In a typical synthesis,a total of45?8.2μg protein was incorporated in ICMVs per mg of lipids with50?9.1%loading efficiency.PEGy-lated VMP001-loaded ICMVs(VMP001-ICMVs)had hydrody-namic diameters of180?14nm and a relatively narrow size distribution with polydispersity index of0.29?0.021.
T o assess whether VMP001was linked to the membranes of ICMV particles,we probed for surface-accessible VMP001 bound to the NPs using antibodies(Abs)against the C-terminal his-tag of the VMP001protein.Particles incubated with fluoro-phore-conjugated anti-his-tag Abs showed Ab binding to VMP001-ICMVs,but not to OVA-ICMVs or VMP001-ICMVs treated with trypsin to digest surface-bound protein(Fig.1B). Blockade of MAL-mediated coupling by capping the free thiols of VMP001with ethyl maleimide before particle synthesis (ctVMP001-ICMVs)did not affect protein loading efficiency significantly(44?8.5%,p?0.45),but eliminated anti-his-tag Ab binding,suggesting that VMP001display on the particle
surfaces was due to conjugation with MAL lipid headgroups
rather than by surface adsorption.In agreement with these bulk
measurements,confocal micrographs of fluorescently tagged VMP001-ICMVs showed lipid colocalization with anti-his-tag
Ab staining,which was absent for OVA-ICMVs,trypsin-treated
VMP001-ICMVs,or ctVMP001-ICMVs(Fig.1C).
T o test the impact of membrane conjugation on the immuno-
genicity of ICMVs,mice were immunized with VMP001-ICMVs,
where antigen was both membrane-conjugated and encapsulated,
or with ctVMP001-ICMVs,where antigen was only encapsulated
in a soluble state in the particle interior.Mice in each group were
primed and then boosted on day21with a total of1μg VMP001
and0.1μg MPLA.Measurement of resulting serum VMP001-
specific IgG titers showed that membrane display of the antigen
clearly increased the potency of ICMV vaccination,as homolo-
gous VMP001-ICMV immunization elicited IgG titers approxi-
mately9-fold greater than homologous ctVMP001-ICMV
immunization(p<0.05,Fig.1D).Heterologous immunizations
with VMP001-ICMVs and ctVMP001-ICMVs revealed that vaccination with antigen bound on particle membranes during the
prime rather than boost was more critical to elicit high IgG
titers(Fig.1D).
VMP001-ICMV Vaccination Induces Durable Antibody Responses at 10-Fold Lower Doses of Antigen than Soluble Protein with Traditional Adjuvants.Immunization of C57Bl/6mice with VMP001-ICMVs mixed with MPLA as a molecular adjuvant elicited durable,high
titers of serum anti-VMP001IgG,sustained for more than1y
following a prime and boost with as little as100ng of the malaria
antigen(Fig.2A).In contrast,vaccines composed of soluble
VMP001mixed with MPLA or adjuvanted with Montanide or
alum required at least10-fold more protein to elicit a response,
and exhibited waning titers over time(Fig.2A).VMP001-ICMV
+MPLA vaccination induced antigen-specific IgG1and IgG2c
isotype responses,while soluble protein+MPLA elicited only
Th2-skewed IgG1antibodies(Fig.2B and C).Priming of a more
balanced Th1/Th2antibody response correlated with the en-hanced production of IFN-γand TNF-αby splenocytes from NP-immunized mice,compared to soluble protein vaccination (Fig.2D).VMP001-ICMVs incubated with sera from
na?ve,
Fig.1.ICMVs with surface-conjugated VMP001induce po-
tent humoral immune responses.(A)Schematic illustration
of VMP001-loaded ICMVs:VMP001is surface-displayed on
ICMVs via coupling of cysteine residues with MAL-functiona-
lized lipids.(B and C)(i)VMP001bound on membranes of
ICMVs was detected by staining with anti-his-tag Ab(recog-
nizing the C terminus of the antigen)followed by a labeled secondary Ab;bound Abs(green)on particles(lipids,red)
was detected by(B)a fluorescence plate reader or(C)con-
focal microscopy(colocalization of Ab with lipids appears yellow).Controls included(ii)ICMVs treated with trypsin
to digest surface-exposed antigens,or loaded with
capped-thiol VMP001[(iii)ctVMP001]or(iv)OVA.(D)
C57Bl/6mice were immunized with either VMP001-ICMVs
or ctVMP001-ICMVs in different combinations(prime day
0,boost day21;1μg VMP and0.1μg MPLA).Anti-
VMP001IgG sera titers were measured on day50by ELISA.
Scale bars,10μm.Data represent mean?SEM of two to
three independent experiments conducted with n?3.
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VMP001-ICMV-,or OVA-ICMV-immunized mice had detect-able binding only to VMP001-ICMV sera,indicating minimal
cross-reactivity of elicited IgG to nonprotein components of
ICMVs;i.e.,maleimide,lipids,or PEG(Fig.S2).Notably, VMP001-ICMVs reconstituted in saline from lyophilized pow-
ders maintained their original particle diameter and size distribu-
tion(diameter of200nm?11,polydispersity index of0.23?0.05),and elicited similar humoral responses,suggesting that freeze-dried materials could be used to enhance the storage life
of ICMV vaccines(Fig.S3).
Enhanced Immunogenicity of NP-Formulated Antigen Enables Dose Sparing of MPLA.Strategies to reduce the dose of potent immu-nostimulatory adjuvants such as MPLA or other TLR agonists are attractive,to lower the risk of reactogenicity or other side effects that could hamper the safety of vaccine candidates.T o determine whether the enhanced immunogenicity of ICMVs would permit dose sparing of MPLA,we titrated down the dose of MPLA with a fixed dose of VMP001antigen(1μg)in soluble or ICMV form.Strikingly,the peak IgG response was comparable for25μg or1μg MPLA given with VMP001-ICMVs,and MPLA doses as low as100ng elicited IgG titers comparable to a250-fold greater dose of MPLA given with soluble protein(Fig.2E).
NP Delivery Increases the Breadth and Avidity of the Humoral Re-sponses.Several studies thus far have suggested that a humoral response against the T ype I repeat in P.vivax CSP,specifically toward the AGDR motif within the VK210sequence,may confer protective immunity against sporozoites(17–19).Thus,to evalu-ate the quality of the antibody response raised against VMP001, we assessed the avidity and epitope specificity of sera from immunized animals.ICMV vaccinations elicited IgG responses with up to4.3-fold higher avidity than soluble protein immuniza-tion(VMP001-ICMV vs.VMP001at1μg,p<0.05)(Fig.3A). Sera from mice immunized with VMP001-ICMVs bound the T ype I repeat sequence with significantly higher titers,and expli-citly recognized the AGDR motif,while sera from soluble protein immunizations did not recognize this fragment(Fig.3B).ICMV vaccination also generated antibodies capable of recognizing the Region I domain,which may inhibit sporozoite invasion into hepatocytes by blocking receptor-ligand interactions during para-site entry(8).In contrast,the C-terminal fragment of VMP001 and the Region II domain,which share sequence homology to
endogenous thrombospondin(20),were not recognized by anti-bodies elicited with either vaccine,suggesting lack of activation
of self-reactive B cells.T aken together,these results suggest that
NP vaccination generates antibody responses that are more dur-able and have higher avidity than those elicited by traditional ad-
juvants even using10-fold less antigen,and elicit broader humoral responses with the capacity to recognize the sporozoite domains
thought to be critical in protective immunity against infection. Enhanced Antigen Delivery and Germinal Center Formation Triggered by ICMVs.Durable and high-affinity humoral responses elicited by ICMVs suggest that NP vaccines may effectively stimulate formation of GCs,where activated B cells proliferate,undergo
immunoglobulin isotype-switching and somatic hypermutation,
and eventually form memory B cells that can rapidly differentiate into plasma cells on re-exposure to antigen(21,22).T o investi-gate GC induction and its anatomic relationship with NP delivery to dLNs,we immunized mice with fluorophore-conjugated OVA (soluble or encapsulated in fluorescent ICMVs)and MPLA,and carried out histological analyses of dLNs at serial time points.So-luble OVA was detected in the dLNs within4h,but was rapidly cleared within24h(Fig.4A).In contrast,OVA-loaded ICMVs were detected at the subcapsular sinus(SCS)of dLNs by24h, with continued accumulation over the next2wk,depositing a large amount of antigen beneath the SCS(Fig.4A).Flow cyto-metry and histological analysis of OVAtcells on1or4d post NP injection showed that the major APC population acquiring par-ticles were LN-resident macrophages,although OVAtCD11btCD11ctDCs were also detected(Fig.S4),suggesting that both free draining and cell-mediated transport of particles to the dLN contributed at both time points.
OVA-ICMV immunizations elicited prominent GC formation,
and notably,in the majority of cases,GCs were nucleated within
100μm of ICMV-draining sites in dLNs(Fig.4A and B).Immu-nization with VMP001-ICMVs also induced GCs;compared with soluble VMP001+MPLA immunizations,NPs induced a signifi-cantly enhanced frequency and8-fold increase in the absolute number of isotype class-switched GC B cells(B220tIgD low GL-7tPNAt)in dLNs by day14(p<0.05,Fig.4C and D).His-
+MPLA+MPLA Fig.2.VMP001-ICMV vaccines elicit robust,durable antibody titers with significantly reduced antigen/ad-juvant doses.C57Bl/6mice were immunized s.c.on day 0and day21with the indicated doses of VMP001in ICMVs mixed with25μg MPLA,or as soluble proteins mixed with either25μg MPLA,Montanide ISA-50,or alum.(A)Anti-VMP001IgG sera titers were assessed over time by ELISA.Anti-VMP001IgG sera were further characterized on day90for(B)IgG1and(C)IgG2c titers (n.d.,not detected).(D)Splenocytes isolated7d after priming and boosting with1μg VMP001and0.1μg MPLA were stimulated with PBS(white bars)or 2μg∕mL VMP001-ICMVs(black bars)ex vivo,and the cell media were analyzed on day2for the concentra-tions of cytokines.(E)Mice were immunized with ti-trated amounts of MPLA mixed with1μg of VMP001in either soluble or ICMV formulations. Shown are anti-VMP001IgG sera titers measured by ELISA on d50.Data represent the mean?SEM of two independent experiments with n?3–4per group.
tological analysis revealed 2–5GCs per dLN in mice immunized with 100ng VMP001-ICMV+MPLA,in contrast to their com-plete absence in the VMP001+MPLA immunization groups (Fig.4E and F ).Notably,as observed with OVA,VMP001-ICMVs promoted GCs in close proximity to the particle-draining sites,with approximately 75%of GCs observed directly adjacent to NP deposits (Fig.4B and G ).
ICMV Vaccination Enhances the Generation of Antigen-Specific T fh Cells.Strong humoral immune responses,characterized by GC
formation and long-lived plasma and memory B cells,are depen-dent on help provided by CD 4tT fh cells (23,24).T o determine whether ICMVs amplify the humoral response in part by en-hanced CD 4tT-cell differentiation,we turned to a model system to trace antigen-specific T helper responses:TCR-transgenic CD 45.2tOT-II CD 4tT cells recognizing OVA peptides were adoptively transferred into CD 45.1trecipient mice that were subsequently immunized with 1μg MPLA mixed with 10μg soluble OVA or OVA-ICMVs.As an additional comparison,mice were also immunized with the traditional adjuvant alum and a
10-fold greater dose of OVA (100μg).Eight days post priming,soluble protein immunization induced 6.3-fold expansion of OT-II CD 4tT cells in spleens compared to mice treated with PBS after adoptive transfer;in contrast,OVA-ICMV vaccination induced a 21-fold expansion of the transferred cells,compared with PBS controls (p <0.05,Fig.5A ).Alum also induced robust expansion of OVA-specific T cells (23-fold increase,compared to PBS,p <0.05).Notably,OVA-ICMV vaccination promoted differentiation of OT -II CD 4tT cells toward T fh phenotypes (CXCR 5tPD-1t),leading to a substantially increased frequency of antigen-specific T fh cells,compared to the other immunization regimens (Fig.5B and C ).T aken together,these results suggest that the enhanced humoral responses elicited by ICMVs compared to soluble vaccines or other traditional adjuvants are a product of enhanced GC formation and increased expansion/differentiation of antigen-specific CD 4tT cells toward T fh phenotypes.Discussion
Strategies to enhance the efficacy of recombinant protein subunit vaccines without sacrificing safety are of great interest,due to the weaker magnitude and durability of immune responses eli-
A v i d i t y i n d e x
A
Fig.3.VMP001-ICMV immunization elicits antibodies with high avidity and broader specificity than soluble protein vaccination.C57Bl/6mice were immunized with VMP001-ICMVs or soluble VMP001(25μg MPLA with 0.1or 1μg protein)as in Fig.2and avidity and specificity of sera were analyzed on day 90.(A )Avidity index of sera from immunized mice binding to whole VMP001protein.(B )Anti-VMP001IgG antibodies elicited with VMP001-ICMVs +MPLA (blue)or VMP001+MPLA (red)were further analyzed for binding to fragments of VMP001,including the Type I insert,AGDRx5,Region I,Region II,C terminus,or a scrambled peptide negative control.Data represent the mean ?SEM of two independent experiments conducted with n ?3.
Fig.4.ICMV immunization sustains antigen deposition in dLNs and induces germinal center (GC)formation.(A and B )C57Bl/6mice were immunized with 100μg fluorophore-conjugated OVA (shown in red)either in soluble or ICMV (shown in blue)formulations with 5μg MPLA,and dLNs excised at indicated time points were examined by immunohistochemical analysis.(A )Representative confocal sections of dLNs;pink signals indicate colocalized OVA/ICMV lipids.Day 14sections were stained with anti-GL-7to identify GCs.(B )Enumeration of GCs located within 100μm of ICMV-draining sites in dLNs.(C –G )C57Bl/6mice were immunized with 1μg VMP001and 0.1μg MPLA in either soluble or ICMV formulations,and dLNs were analyzed for GC formation on day 14.Shown are representative flow cytometry scatter plots of (C )isotype-switched GC B cells (GL-7tPNA t),gated on B 220tIgD low populations,and (D )their absolute numbers in dLNs.(E )Number of GCs observed in sections from whole dLNs (n ?4),cryosectioned and stained with anti-B220and anti-GL-7.(F and G )Representative confocal micrographs of dLNs from immunized animals.Scale bars,200μm.Data represent the mean ?SEM of two to three independent experiments con-ducted with n ?2–3.
A P P L I E D
B I O L O G I
C A L S C I E N C E S
cited by subunit vaccines relative to more potent live attenuated or recombinant vectors.This is particularly relevant in the context of malaria,where short-lived immunity has been observed in the field trials of candidate subunit vaccines(4,25).Analogous to the development of recombinant live viruses or bacteria as vectors to deliver nucleic acid-encoded antigens,synthetic NPs are emer-ging as promising vectors for the delivery of protein subunit antigens.Like live vectors,NPs can serve multiple roles in vacci-nation,carrying antigen into target tissue sites,controlling the antigen uptake by immune cells,and co-delivering“danger”sig-nals that provide critical cues for the development of early effec-tors and late memory(10–14).Here using ICMVs as a lipid-based NP vector,we assessed the impact of NP delivery on immune responses elicited by a candidate P.vivax subunit vaccine,and par-ticularly focused on defining qualitative and quantitative aspects of the humoral response and biological pathways contributing to this response.
We first optimized antigen incorporation into ICMVs with the goal of promoting the antibody response.Our original NP design was based on the entrapment of soluble antigen in the core of these multilamellar“stapled”lipid vesicles(10).Although T-cell responses rely on recognition of antigen fragments following intracellular antigen processing by APCs,antibody responses are ultimately linked to B-cell recognition of intact antigen via cell surface BCRs.Therefore,we hypothesized that particles with antigens anchored to their surfaces,mimicking the multivalent display of epitopes on the surfaces of pathogens,may facilitate cross-linking of BCRs and enhance the activation of B cells for stronger humoral immune responses,compared to soluble bolus injection of antigens(15,16).T o achieve such antigen sur-face-display,we exploited available cysteine residues in VMP001 and utilized maleimide groups in ICMV precursor vesicles for the dual purpose of both“stapling”the vesicle walls together in the presence of cross-linker and anchoring a fraction of the antigen to the vesicle membranes.Notably,we found that ICMVs incorpor-ating VMP001by both entrapment in the core and anchoring to the membranes enhanced the antigen-specific antibody response by9-fold relative to NPs that contained protein only in the particle core(Fig.1D).
VMP001-ICMVs adjuvanted with MPLA elicited strong anti-body titers,surpassing the response induced by soluble VMP001 injected with MPLA or the conventional adjuvants alum or Mon-tanide,and maintaining high titers for more than1y in mice. ICMV vaccines required10-fold and250-fold less antigen and MPLA,respectively,to produce similar antibody titers as soluble formulations.In addition to these quantitative effects on the anti-body response,VMP001-ICMV immunization also changed the qualitative nature of the antibody response,promoting a more balanced Th1/Th2response(both in terms of T-cell cytokine production and antibody isotypes)and broadening the antibody targets within VMP001,including epitopes implicated in pro-tection against Plasmodium(5).We previously reported that immunization with Freund’s adjuvant,a very strong but toxic adjuvant for small-animal experimental immunization,could eli-cit responses against multiple epitopes within VMP001(5).Here we have made the important advance of achieving broad antibody responses using clinically relevant adjuvant materials.Previous studies using recombinant proteins or multipeptide constructs to target multiple vivax CSP regions showed evidence of immu-nodominance with some peptide combinations,with antibody responses focused on only a single epitope(19)or responses that failed to bind the critical protective AGDR sequence(26). Although the precise mechanism underlying NP-mediated broad-ening of the antibody response is the subject of further studies beyond the scope of this first report,we speculate that multivalent display of VMP001on ICMVs may stimulate a more diverse set of na?ve B cells,by allowing some lower-avidity B cells to compete for the antigen.
In order to gain a deeper mechanistic understanding of how NP-mediated delivery of antigen generates high-affinity,long-lasting antibody responses,we examined antigen distribution in dLNs following ICMV immunizations and subsequent B-and T-cell differentiation.Whereas soluble OVA injected s.c.drained to dLNs and was rapidly cleared within24h,OVA-loaded ICMVs drained to the SCS in dLNs after24h and accumulated over the next2wk(Fig.4A).The ability of particles in the200–300nm size range to drain to LNs is consistent with recent work characteriz-ing the transport of similarly sized synthetic or viral particles to LNs(27,28),and other studies have reported that synthetic particles can continue to drain from s.c.injection sites to dLNs for at least8d(29).GC formation tended to occur directly adjacent to NP accumulation sites,suggesting that increased deposition/retention of antigen drives B-cell responses locally in the tissue.Indeed,we have shown previously that ICMV vaccines effectively increased antigen delivery to dLNs,enhancing antigen presentation by DCs,compared with soluble protein immuniza-tions(10).Prolonged antigen presentation mediated by ICMV vaccines may have also contributed to enhanced development of CD4tT fh cells(Fig.5B and C)(24),which provide critical cytokines and signals required to initiate somatic hypermutation and affinity maturation for B cells(23).
In summary,ICMV lipid NP vectors enhanced a range of quantitative and qualitative features of the immune response to the VMP001CSP antigen,suggesting their utility in recombi-nant protein subunit vaccination.Enhanced humoral responses correlated with enhanced GC formation and induction of anti-gen-specific T fh cells.Here we focused on vaccination using a single TLR agonist,MPLA,and future studies will be needed to determine if other clinically relevant molecular adjuvants com-bined with the current NP vaccine may allow further
amplifica-Fig.5.ICMV immunization enhances follicular helper T-cell expansion.(A–C)One day after adoptive transfer of105CD45.2tCD4tOT-II T cells i.v.into na?ve CD45.1tC57Bl/6mice,recipient mice were immunized s.c.with100μg OVA in alum or10μg OVA and1μg MPLA in either soluble or ICMV formulations.(A)On day8after immunization,CD45.2tCD4tOT-II T cells were enumerated from spleens and dLNs.(B and C)CD45.2tCD4tOT-II T cells from spleens were further analyzed for expression of T fh markers(CXCR5tPD-1t).(B)Representative flow cytometry scatter plots,gated on CD45.2tCD4tOT-II T cells in spleens,are shown with the percentages of CXCR5tPD-1tpopulations,and(C)the percentage of OT-II cells with T fh phenotypes were enumerated.Data represent mean?SEM of two independent experiments conducted with n?3.
tion of humoral immune responses in a synergistic manner,thus enhancing the protective efficacy of the NP vaccine.Materials and Methods
Synthesis of ICMVs Loaded with VMP001.VMP001was prepared as previously described (5,6).Synthesis of ICMVs was performed as described previously with slight modifications (10).Briefly,dried films of 1.26μmol of lipids [DOPC ∶DOPG ∶MPB (1,2-dioleoyl-sn -glycero-3-phosphoethanol amine-N-[4-(p-maleimidophenyl)butyramide)at 4∶1∶5mol ratio (Avanti Polar Lipids)]were rehydrated in 20mM bis-tris propane at pH 7.0with 50μg VMP001or ovalbumin (Worthington)for 1h with vortexing every 10min,and soni-cated in alternating power cycles of 6W and 3W in 30s intervals for 5min on ice (Misonix Microson XL probe tip sonicator).DTT and Ca 2twere then sequentially added at final concentrations of 3mM and 40mM,respectively,and incubated for 1h at 37°C to form ICMVs.The particles were recovered by centrifugation,washed twice,and incubated with 10mg ∕mL 2kDa PEG-thiol (Laysan Bio)for 30min at 37°C.For some experiments,capped-thiol VMP001(ctVMP001)was prepared by incubating 0.5mg VMP001with 3.6mM TCEP for 2h at 25°C,followed by incubation with 40mM ethyl-maleimide (Pierce)at 37°C for 2h.The extent of thiol protection was measured to be >98%by Ellman ’s assay.Characterization of ICMVs is described in SI Materials and Methods .
Immunizations.Animals were cared for following National Institutes of Health,state,and local guidelines.Groups of 6-to 10-wk-old female C57Bl/6mice
(Jackson Laboratories)were immunized s.c.at the tail base with VMP001-ICMVs and indicated doses of MPLA (Sigma-Aldrich)in 100μL PBS on day 0and 21.Control immunizations with soluble VMP001were performed using MPLA,Montanide ISA-50V2(Seppic),or alum (Imject alum,Pierce)at an adjuvant ∶protein solution volume ratio of 1∶1following the manufacturer ’s instructions.Characterization of humoral responses,germinal center forma-tion,and follicular helper T-cell analysis is described in SI Materials and Methods .
Statistical Analysis.Datasets were analyzed using one-or two-way analysis of variance (ANOVA),followed by Tukey ’s honestly significant difference (HSD)test for multiple comparisons with Prism 5.0(GraphPad Software).P values less than 0.05were considered statistically significant,and marked with one asterisk.P values less than 0.01were marked with two asterisks.All values are reported as mean ?SEM.
ACKNOWLEDGMENTS.This work was supported in part by the Ragon Institute of Massachusetts General Hospital,Massachusetts Institute of Technology,and Harvard University;the Gates Foundation;the Department of Defense (Contract W911NF-07-D-0004);and National Institutes of Health (AI095109and 1U19AI091693).D.J.I.is an investigator of the Howard Hughes Medical Institute.The opinions or assertions contained herein are the private views of the authors,and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
1.Price RN,et al.(2007)Vivax malaria:Neglected and not benign.Am J Trop Med Hyg 77:79–87.
2.Mueller I,et al.(2009)Key gaps in the knowledge of Plasmodium vivax,a neglected human malaria https://www.wendangku.net/doc/6716002719.html,ncet Infect Dis 9:555–566.
3.Nussenzweig V,Nussenzweig RS (1985)Circumsporozoite proteins of malaria para-sites.Cell 42:401–403.
4.Ballou WR (2009)The development of the RTS,S malaria vaccine candidate:Challenges and lessons.Parasite Immunol 31:492–500.
5.Yadava A,et al.(2007)A novel chimeric Plasmodium vivax circumsporozoite protein induces biologically functional antibodies that recognize both VK210and VK247sporozoites.Infect Immun 75:1177–1185.
6.Bell BA,et al.(2009)Process development for the production of an E.coli produced clinical grade recombinant malaria vaccine for Plasmodium vivax.Vaccine 27:1448–1453.
7.Schwenk R,et al.(2003)Opsonization by antigen-specific antibodies as a mechanism of protective immunity induced by Plasmodium falciparum circumsporozoite protein-based vaccine.Parasite Immunol 25:17–25.
8.Ancsin JB,Kisilevsky R (2004)A binding site for highly sulfated heparan sulfate is identified in the N terminus of the circumsporozoite protein:Significance for malarial sporozoite attachment to hepatocytes.J Biol Chem 279:21824–21832.
9.Blander JM,Medzhitov R (2006)Toll-dependent selection of microbial antigens for presentation by dendritic cells.Nature 440:808–812.
10.Moon JJ,et al.(2011)Interbilayer-crosslinked multilamellar vesicles as synthetic
vaccines for potent humoral and cellular immune responses.Nat Mater 10:243–251.11.Reddy ST,et al.(2007)Exploiting lymphatic transport and complement activation in
nanoparticle vaccines.Nat Biotechnol 25:1159–1164.
12.Heit A,Schmitz F ,Haas T,Busch DH,Wagner H (2007)Antigen co-encapsulated with
adjuvants efficiently drive protective T cell immunity.Eur J Immunol 37:2063–2074.13.Kasturi SP ,et al.(2011)Programming the magnitude and persistence of antibody
responses with innate immunity.Nature 470:543–547.
14.Demento SL,et al.(2010)TLR9-targeted biodegradable nanoparticles as immunization
vectors protect against West Nile encephalitis.J Immunol 185:2989–2997.
15.Jegerlehner A,et al.(2002)Regulation of IgG antibody responses by epitope density
and CD21-mediated costimulation.Eur J Immunol 32:3305–3314.
16.Liu W,Chen YH (2005)High epitope density in a single protein molecule significantly
enhances antigenicity as well as immunogenicity:A novel strategy for modern vaccine development and a preliminary investigation about B cell discrimination of mono-meric proteins.Eur J Immunol 35:505–514.
17.Jones TR,et al.(1992)Low immunogenicity of a Plasmodium vivax circumsporozoite
protein epitope bound by a protective monoclonal antibody.Am J Trop Med Hyg 47:837–843.
18.Wirtz RA,et al.(1991)Evaluation of monoclonal antibodies against Plasmodium vivax
sporozoites for ELISA development.Med Vet Entomol 5:17–22.
19.Udhayakumar V,et al.(1998)Immunogenicity of Plasmodium falciparum and Plasmo-dium vivax circumsporozoite protein repeat multiple antigen constructs (MAC).Vac-cine 16:982–988.
20.Bilsborough J,Baumgart K,Bathurst I,Barr P ,Good MF (1997)Fine epitope specificity
of antibodies to region II of the Plasmodium vivax circumsporozoite protein correlates with ability to bind recombinant protein and sporozoites.Acta Trop 65:59–80.
21.McHeyzer-Williams LJ,McHeyzer-Williams MG (2005)Antigen-specific memory B cell
development.Annu Rev Immunol 23:487–513.
22.Nutt SL,Tarlinton DM (2011)Germinal center B and follicular helper T cells:Siblings,
cousins or just good friends?Nat Immunol 131:472–477.
23.Breitfeld D,et al.(2000)Follicular B helper T cells express CXC chemokine receptor 5,
localize to B cell follicles,and support immunoglobulin production.J Exp Med 192:1545–1552.
24.Deenick EK,et al.(2010)Follicular helper T cell differentiation requires continuous
antigen presentation that is independent of unique B cell signaling.Immunity 33:241–253.
25.Bojang KA,et al.(2001)Efficacy of RTS,S/AS02malaria vaccine against Plasmodium
falciparum infection in semi-immune adult men in The Gambia:A randomised https://www.wendangku.net/doc/6716002719.html,ncet 358:1927–1934.
26.Charoenvit Y ,et al.(1991)Inability of malaria vaccine to induce antibodies to a
protective epitope within its sequence.Science 251:668–671.
27.Carrasco YR,Batista FD (2007)B cells acquire particulate antigen in a macrophage-rich
area at the boundary between the follicle and the subcapsular sinus of the lymph node.Immunity 27:160–171.
28.Junt T,et al.(2007)Subcapsular sinus macrophages in lymph nodes clear lymph-borne
viruses and present them to antiviral B cells.Nature 450:110–114.
29.Manolova V,et al.(2008)Nanoparticles target distinct dendritic cell populations
according to their size.Eur J Immunol 38:1404–1413.
30.Yue Y ,Xu W,Hu L,Jiang Z,Xiong S (2009)Enhanced resistance to coxsackievirus
B3-induced myocarditis by intranasal co-immunization of lymphotactin gene encap-sulated in chitosan particle.Virology 386:438–447.
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中考语文课外阅读题小说题库
中考语文课外阅读题（小说）题库 （一） 我家最富的时刻 第二次世界大战前，我们家是城里唯一没有汽车的人家。我母亲安慰家里人说：“一个人有骨气，就等于有了一大笔财富。” 几个星期后，一辆崭新的别克牌汽车在街上展出了。这辆车已定在今夜以抽奖的方式馈赠给得奖者。当扩音器里大声叫着我父亲的名字，明白无误地表示这辆彩车已属于我们家所有时，我简直不相信这是事实。 父亲开着车缓缓驶过拥挤的人群，我几次想跳上车去，同父亲一起享受这幸福的时刻，却被父亲给赶开了。最后一次，父亲甚至向我咆哮：“滚开，别呆在这儿，让我清净清净！”我无法A 父亲的举动。当我回家后B 地向母亲诉说的时候，母亲似乎非常理解父亲。她C 我说：“不要烦恼，你父亲正在思考一个道德问题，我们等着他找到适当的答案。” “难道我们中彩得到的汽车是不道德的吗” “过来，孩子。”母亲温柔地说。 桌上的台灯下放着两张彩票存根，上面的号码分别是348和349，中彩号是348。“你能看出两张彩票有什么不同吗”母亲问。 我看了好几遍终于看到其中一张彩票的一角上有用铅笔写的淡淡的K字。 “这K字代表凯特立克。”母亲说。 “吉米·凯特立克，爸爸交易所的老板！”我有些不解。 “对。”母亲把事情一五一十地给我讲了。 当初父亲对吉米说，他买彩券时可以代吉米买一张，吉米嘟哝了一声：“为什么不可以呢”老板说完就去干自己的事了，国后可能再也没有想到过这件事。348那张是为凯特立克买的，可以看出那K字用大拇指轻轻擦过，但仍能看出淡淡的铅笔印。 对我来说，这是件简单的事。吉米·凯特立克是个百万富翁，拥有十几辆汽车，他不会计较这辆彩车。 “汽车应该归我爸爸！”我激动地说。 “你爸爸知道该怎么做的。”母亲平静地回答我。 不久，我们听到父亲进门的脚步声，又听到他在拨电话号码，显然电话是打给凯特立克的。第二天下午，凯特立克的两个司机来到我们这儿，把别克牌汽车开走了，他们送给我父亲一盒雪茄。 直到我成年以后，我们家才有了一辆汽车。随着时间的流逝，我母亲那一句“一个人有骨气，就等于有了一大笔财富”的话语具有了新的含义。回顾以往的岁月，我现在才明白，父亲打电话的时候是我家最富有的时刻。 1．给下列加点的字注音。 馈赠 ．．（）（）彩券．（） ．．（）（）咆哮 2．在文中横线上填写适当的词语。 A．B．C． 3．文章题目的关键词语是什么其含义是什么对你有何启示 答： 。4．文章主要记叙了一件什么事（用简要的文字叙述） 答：。5．文中的“贫”指什么“富”又指什么 答：。（参考答案：1．Kuì zèng páo xiào quàn 2．理解委屈安慰3．关键词是“最富”；其含义是指道德品质的富有。启示：富有不仅指物质和金钱上的富有，更重要的是一个人道德品质的富有。4．主
古代晋灵公不君、齐晋鞌之战原文及译文
晋灵公不君（宣公二年） 原文： 晋灵公不君。厚敛以雕墙。从台上弹人，而观其辟丸也。宰夫胹熊蹯不熟，杀之，寘诸畚，使妇人载以过朝。赵盾、士季见其手，问其故而患之。将谏，士季曰：“谏而不入，则莫之继也。会请先，不入，则子继之。”三进及溜，而后视之，曰：“吾知所过矣，将改之。”稽首而对曰：“人谁无过？过而能改，善莫大焉。诗曰：‘靡不有初，鲜克有终。’夫如是，则能补过者鲜矣。君能有终，则社稷之固也，岂惟群臣赖之。又曰：‘衮职有阙，惟仲山甫补之。’能补过也。君能补过，衮不废矣。” 犹不改。宣子骤谏，公患之，使鉏麑贼之。晨往，寝门辟矣，盛服将朝。尚早，坐而假寐。麑退，叹而言曰：“不忘恭敬，民之主也。贼民之主，不忠；弃君之命，不信。有一于此，不如死也！”触槐而死。 秋九月，晋侯饮赵盾酒，伏甲将攻之。其右提弥明知之，趋登曰：“臣侍君宴，过三爵，非礼也。”遂扶以下。公嗾夫獒焉。明搏而杀之。盾曰：“弃人用犬，虽猛何为！”斗且出。提弥明死之。 初，宣子田于首山，舍于翳桑。见灵辄饿，问其病。曰：“不食三日矣！”食之，舍其半。问之，曰：“宦三年矣，未知母之存否。今近焉，请以遗之。”使尽之，而为之箪食与肉，寘诸橐以与之。既而与为公介，倒戟以御公徒，而免之。问何故，对曰：“翳桑之饿人也。”问其名居，不告而退。——遂自亡也。 乙丑，赵穿①攻灵公于桃园。宣子未出山而复。大史书曰：“赵盾弑其君。”以示于朝。宣子曰：“不然。”对曰：“子为正卿，亡不越竟，反不讨贼，非子而谁？”宣子曰：“呜呼!‘我之怀矣，自诒伊戚。’其我之谓矣。” 孔子曰：“董狐，古之良史也，书法不隐。赵宣子，古之良大夫也，为法受恶。惜也，越竞乃免。” 译文： 晋灵公不行君王之道。他向人民收取沉重的税赋以雕饰宫墙。他从高台上用弹弓弹人，然后观赏他们躲避弹丸的样子。他的厨子做熊掌，没有炖熟，晋灵公就把他杀了，把他的尸体装在草筐中，让宫女用车载着经过朝廷。赵盾和士季看到露出来的手臂，询问原由后感到很忧虑。他们准备向晋灵公进谏，士季说：“如果您去进谏而君王不听，那就没有人能够再接着进谏了。还请让我先来吧，不行的话，您再接着来。”士季往前走了三回，行了三回礼，一直到屋檐下，晋灵公才抬头看他。晋灵公说：“我知道我的过错了，我会改过的。”士季叩头回答道：“谁能没有过错呢？有过错而能改掉，这就是最大的善事了。《诗经》说：‘没有人向善没有一个开始的，但却很少有坚持到底的。’如果是这样，那么能弥补过失的人是很少的。您如能坚持向善，那么江山就稳固了，不只是大臣们有所依靠啊。
农田水利学试题及答案
农田水利学课程考试试题及答案 姓名年级专业学号 一、名词解释（每小题2分共10分） 1.灌水率： 2.排涝模数： 3.平均排除法： 4.（排涝计算中的）设计内水位： 5.容泄区： 二．选择题（共10分） 1.灌溉设计标准是反映灌区效益达到某一水平的一个重要技术指标，一般以( )与( )表示？ A、灌溉设计保证率、抗旱天数。 B、水文年型、降水量。 C、设计灌溉用水量全部获得满足的年数、抗旱天数。 D、水源来水量、灌区需水量。 2.什么叫田间渠系的灌排相邻布置？（） A、灌溉渠道与排水沟道的规划布置。 B、田间各级渠道规划布置的形式。 C、田间灌排渠系并行相邻的布置形式。 D、田间灌排渠系交错的布置形式。
3.渠道的输水损失包括以下四个部分：（） A、干渠、支渠、斗渠及农渠等四级渠道的水量损失。 B、渠床土质、地下水埋深、渠道的工作制度及输水时间。 C、自由渗流、顶托渗流、渠床土质、与渠道的工作制度等。 D、渠道水面蒸发损失、渠床渗漏损失、闸门漏水与渠道退水等。 4.什么叫渠道水的利用系数？（） A、灌溉渠系的净流量与毛流量的比值。 B、某一级渠道的净流量与毛流量的比值。 C、田间实际灌入的有效水量与末级渠道的供水量之比。 D、实际灌入农田的有效水量和渠首引入的水量之比。 5.在渠道规划设计中，渠道最小流量有何作用？（） A、用以校核对下一级渠道的水位控制条件。 B、用以校核渠道不淤条件。 C、用以确定修建节制闸的位置。 D、用以校核对下一级渠道的水位控制条件和确定修建节制闸的位置，并按最小流量验算渠道不淤条件。 6.什么叫雨水径流集蓄灌溉工程？（） A、导引、收集雨水径流，并把它蓄存起来加以有效灌溉利用的工程技术措施。 B、田面、坡面、路面及屋面庭院等各类集水工程。
如何翻译古文
如何翻译古文 学习古代汉语，需要经常把古文译成现代汉语。因为古文今译的过程是加深理解和全面运用古汉语知识解决实际问题的过程，也是综合考察古代汉语水平的过程。学习古代汉语，应该重视古文翻译的训练。 古文翻译的要求一般归纳为信、达、雅三项。“信”是指译文要准确地反映原作的含义，避免曲解原文内容。“达”是指译文应该通顺、晓畅，符合现代汉语语法规范。“信”和“达”是紧密相关的。脱离了“信”而求“达”，不能称为翻译；只求“信”而不顾“达”，也不是好的译文。因此“信”和“达”是文言文翻译的基本要求。“雅”是指译文不仅准确、通顺，而且生动、优美，能再现原作的风格神韵。这是很高的要求，在目前学习阶段，我们只要能做到“信”和“达”就可以了。 做好古文翻译，重要的问题是准确地理解古文，这是翻译的基础。但翻译方法也很重要。这里主要谈谈翻译方法方面的问题。 一、直译和意译 直译和意译是古文今译的两大类型，也是两种不同的今译方法。 1．关于直译。所谓直译，是指紧扣原文，按原文的字词和句子进行对等翻译的今译方法。它要求忠实于原文，一丝不苟，确切表达原意，保持原文的本来面貌。例如： 原文：樊迟请学稼，子曰：“吾不如老农。”请学为圃。子曰：“吾不如老圃。”（《论语?子路》） 译文：樊迟请求学种庄稼。孔子道：“我不如老农民。”又请求学种菜蔬。孔子道：“我不如老菜农。”（杨伯峻《论语译注》） 原文：齐宣王问曰：“汤放桀，武王伐纣，有诸？”（《孟子?梁惠王下》） 译文：齐宣王问道：“商汤流放夏桀，武王讨伐殷纣，真有这回事吗？（杨伯峻《孟子译注》） 上面两段译文紧扣原文，字词落实，句法结构基本上与原文对等，属于直译。 但对直译又不能作简单化理解。由于古今汉语在文字、词汇、语法等方面的差异，今译时对原文作一些适当的调整，是必要的，并不破坏直译。例如： 原文：逐之，三周华不注。（《齐晋鞌之战》） 译文：〔晋军〕追赶齐军，围着华不注山绕了三圈。
李文忠《摆渡老人》中考现代文阅读练习及答案
(三）课外阅读（13分） 摆渡老人 李文忠 ①读中学时，学校设在邻村，与我们村有一条河隔着，便认识了那摆渡老人。 ②当时，那老人一直是我们取乐的对象。每到放学，肚子饿得直叫的我们便一窝蜂向渡口跑去，挤在那儿。渡船只要一近岸，大家便争先恐后地向船上跃去。虽然老人很有经验，未到岸边便做好回撑的准备，但超载和落水的事仍然时有发生。超载时，船上的，岸上的，都望着老人手忙脚乱的样子大笑。夏天下雨时，大家总是把伞迎着风，看着渡船被吹到离渡口好远的地方，老人一番折腾，将船撑到渡口，我们便哄笑着上了岸。 ③最有意思的要数冬天（当时我是这样认为的）。冬天很冷，河面结了一层厚厚的冰。每天早晨，当我们赶到渡口时，总看见老人在那边晃着船，好长时间，才把船晃过来。望着老人跳舞似的笨拙姿势，我们总是哄笑，一直到船靠岸。我们往往因此耽误了早读，但我们都挺愿意。于是就希望天再冷些，便可迟点起来，反正去早了也过不了河。我们都为找到一个偷懒的理由而感到高兴。当时的我们，是“心忧读书愿天寒”。 ④那一天特别冷，我因有事起了个早，吃过早饭后，便不紧不慢地向学校走去。到渡口时我惊奇地发现，那老人不是我预料的那样正在“跳舞”，却已经到了这边。我和他攀谈起来。我问他：“你今天怎么这么早？”老人咳嗽了一声，缓缓地说：“许是人老了，早上总起不来。昨天听学校说耽误了学生上早读，今天我就起了早。谁知等了好长时间，才来了你一个人。”说完，便送我过河。 ⑤船到河心，老人忽然回头对我说道：“你们小孩子可要好好读书啊。”那双眼中竟满含着期待和爱意，我心中一震，看着老人瘦弱的身体，沾满冰碴的白胡子，一双手冻得发紫，猛地问道：“你干啥要吃这份苦呢？”好久，老人长叹一声说道：“干啥？哎，以前我也有一个可爱的儿子，他曾吵着要上学，但终究没上成。后来他得病去了，我一直感到对不起他，我在这儿摆渡，接送你们上学，心里好受些。”谈话间，船已到岸。待我上岸后，老人把船向河那边撑去。看着老人的背影，我不再感到笨拙可笑，鼻子有些酸酸的。 ⑥那天，我把老人的故事讲给同学们听了。以后，我们上船再也没有起哄。于是老人饱经风霜的脸上出现了笑容。 ⑦再后来，两岸之间架起了一座桥。最后一次过河时，老人对我们说：“以后不再送你们过河了，你们要记住，好好读书。” ⑧“好好读书”，这句话一直留在我记忆中。 ⑨真想再见见摆渡老人。 20、本文具体描述了摆渡老人接送“我们”过河上学的辛劳。先写老人因“我们”的___________而手忙脚乱，一番折腾；再写因_________，老人好不容易“才把船晃过来”；最后写老人不顾自己__________，特地起大早送“我们”过河上学。（3分） 21.第⑤段中摆渡老人说“我在这儿摆渡，接送你们上学，心里好受些”。请你用自己的语言简要说说为什么老人觉得这样做“心里好受些”。（3分） ________________ 22.第⑤段中划横线的语句表现了“我”当时___________和___________的心情。（2分） 23.结合全文内容回答以下问题。 原先，摆渡老人在孩子们的眼里是一个________________的形象；后来，摆渡老人在孩子们的心中却是一个________________的形象。（2分） 24.“摆渡老人”中的“摆渡”可以理解为老人对“我们”生活、思想上的帮助。其实生活中还有许多这样的“摆渡者”，请你展开联想，按照下面的示例仿写两个句子。
齐晋鞌之战原文和译文
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农田水利学试题及答案资料
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B、用以校核渠道不淤条件。 C、用以确定修建节制闸的位置。 D、用以校核对下一级渠道的水位控制条件和确定修建节制闸的位置，并按最小流量验算渠道不淤条件。 6.什么叫雨水径流集蓄灌溉工程？（） A 、导引、收集雨水径流，并把它蓄存起来加以有效灌溉利用的工程技术措施。 B、田面、坡面、路面及屋面庭院等各类集水工程。 C、各类形式的水窖、水窑窖等蓄水工程。 D、各类最为有效节水的灌溉方式。 7.集流面的处理主要包括哪三类方法？（） A 、采用混凝土、水泥土、三七灰土进行表面处理。 B、采用塑料薄膜、或塑膜复沥青、复草泥。 C、植被管理；地表处理；化学处理。 D、采用钠盐、硅有机树脂及粗石蜡等化学处理方法。 8.蓄水工程有哪几种主要的类型？（） A 、引水渠沟或管道、入水口、拦污栅、沉沙槽、蓄水设施以及放水装置等。 B、涝池、旱井、田间蓄水池、水窖、水窑窖等。 C、引水渠、蓄水窑洞与放水暗管与放水暗渠。 D 、沉沙池、进水管、水窖等。 9.什么叫续灌方式？（） A 、类似于自来水管道可随机用水的供水方式。 B、输配水管道进行输水、配水和灌水的方式。 C、是指上一级管道按预先划分好的轮灌组分组向下一级管道配水的方式。 D 、是指上一级管道向所有的下一级管道同时配水的方式。 10.什么叫集水效率？（） A 、降水特征（次降雨量、降雨强度）和集水面质地、坡度、前期含水量与集水面尺寸。 B、集水面的处理材料、集水面积、集流路径和汇流时间。 C、随降水强度的增大而提高。 D、某时段内或某次降雨集水面的集水量占同一时期内的降雨量的比值。 三、简答题（每题6分，共30分） 1.四种地表取水方式的使用条件
摆渡老人的阅读答案
摆渡老人的阅读答案 摆渡老人 ①读中学时，学校设在邻村，与我们村有一条河隔着，便认识了那摆渡老人。 ②当时，那老人一直是我们取乐的对象。每到放学，肚子饿得直叫的我们便一窝蜂向渡口跑去，挤在那儿。渡船只要一近岸，大家便争先恐后地向船上跃去。虽然老人很有经验，未到岸边做好回撑的准备，但超载和落水的事仍然时有发生。超载时，船上的，岸上的，都望着老人手忙脚乱的样子大笑。夏天下雨时，大家总是把伞迎着风，看着渡船被吹淌到离渡口好远的地方，老人一番折腾，将船撑到渡口，我们便哄笑着上了岸。 ③最有意思的要数冬天。冬天很冷，河面结了一层厚厚的冰。每天早晨，当我们赶到渡口时，总看见老人在那边晃着船，好长时间，才把船晃过来。望着老人跳舞似的笨拙姿势，我们总是哄笑，一直到船靠岸。我们往往因此耽误了早读，但我们都挺愿意。于是就希望天再冷些，便可迟点起来，反正去早了也过不了河。我们都为找到一个偷懒的理由而感到高兴。当时的我们，是心忧读书愿天寒。 ④那一天特别冷，我因有事起了个早。吃过早饭后，便不紧不慢地向学校走去。到渡口时我惊奇地发现，那老人不
是我预料的那样正在跳舞，却已经到了这边。我和他攀谈起来。我问他：你今天怎么这么早?老人咳嗽了一声，缓缓地说：许是人老了，早上总起不来。昨天听学校说耽误了学生上早读，今天我就起了早。谁知等了好长时间，才来了你一个人。说完，便送我过河。 ⑤船到河心，老人忽然回头对我说道：你们小孩子可要好好读书啊。那双眼中竟满含着期待和爱意。我心中一辱，看着老人瘦弱的身体，沾满冰碴的白胡子，一双手冻得发紫，猛地问道：你干啥要吃这份苦呢?好久，老人长叹一声说道：干啥？哎，以前我也有一个可爱的儿子，他曾吵着要上学，但终究没上成。后来他得病去了，我一直感到对不起他，我在这儿摆渡，接送你们上学，心里好受些。谈话间，船已到岸。待我上岸后，老人又把船向河那边撑去。看着老人的背影，我不再感到笨拙可爱，鼻子有些酸酸的。 ⑥那天，我把老人的故事讲给同学们听了。以后，我们上船再也没有起哄。于是老人饱经风霜的脸上出现了笑容。 ⑦再后来，两岸之间架起了一座桥。最后一次过河时，老人对我们说：以后不再送你们过河了，你们要记住，好好读书。 ⑧好好读书，这句话一直留在我记忆中。 ⑨真想再见见摆渡老人。 13、本文具体描述了摆渡老人接送我们过河上学的辛劳。
《鞌之战》阅读答案(附翻译)原文及翻译
《鞌之战》阅读答案（附翻译）原文及翻 译 鞌之战[1] 选自《左传成公二年（即公元前589年）》 【原文】 癸酉，师陈于鞌[2]。邴夏御齐侯[3]，逢丑父为右[4]。晋解张御郤克，郑丘缓为右[5]。齐侯曰：余姑翦灭此而朝食[6]。不介马而驰之[7]。郤克伤于矢，流血及屦，未绝鼓音[8]，曰：余病[9]矣！张侯[10]曰：自始合，而矢贯余手及肘[11]，余折以御，左轮朱殷[12]，岂敢言病。吾子[13]忍之！缓曰：自始合，苟有险[14]，余必下推车，子岂识之[15]？然子病矣！张侯曰：师之耳目，在吾旗鼓，进退从之[16]。此车一人殿之[17]，可以集事[18]，若之何其以病败君之大事也[19]？擐甲执兵，固即死也[20]。病未及死，吾子勉之[21]！左并辔[22]，右援枹而鼓[23]，马逸不能止[24]，师从之。齐师败绩[25]。逐之，三周华不注[26]。 【注释】 [1]鞌之战：春秋时期的著名战役之一。战争的实质是齐、晋争霸。由于齐侯骄傲轻敌，而晋军同仇敌忾、士气旺盛，战役以齐败晋胜而告终。鞌：通鞍，齐国地名，在今山东济南西北。 [2]癸酉：成公二年的六月十七日。师，指齐晋两国军队。陈，
列阵，摆开阵势。 [3]邴夏：齐国大夫。御，动词，驾车。御齐侯，给齐侯驾车。齐侯，齐国国君，指齐顷公。 [4]逢丑父：齐国大夫。右：车右。 [5]解张、郑丘缓：都是晋臣，郑丘是复姓。郤（x ）克，晋国大夫，是这次战争中晋军的主帅。又称郤献子、郤子等。 [6]姑：副词，姑且。翦灭：消灭，灭掉。朝食：早饭。这里是吃早饭的意思。这句话是成语灭此朝食的出处。 [7]不介马：不给马披甲。介：甲。这里用作动词，披甲。驰之：驱马追击敌人。之：代词，指晋军。 [8] 未绝鼓音：鼓声不断。古代车战，主帅居中，亲掌旗鼓，指挥军队。兵以鼓进，击鼓是进军的号令。 [9] 病：负伤。 [10]张侯，即解张。张是字，侯是名，人名、字连用，先字后名。 [11]合：交战。贯：穿。肘：胳膊。 [12]朱：大红色。殷：深红色、黑红色。 [13]吾子：您，尊敬。比说子更亲切。 [14]苟：连词，表示假设。险：险阻，指难走的路。 [15]识：知道。之，代词，代苟有险，余必下推车这件事，可不译。 [16]师之耳目：军队的耳、目（指注意力）。在吾旗鼓：在我们
农田水利学试题六
农田水利学课程考试试题 姓名年级专业学号 一、名词解释（每小题2分共10分） 1、渠道设计流量： 2、灌溉水利用系数： 3、最小流量： 4、田间净流量:： 5、不冲流速： 二．单向选择题（共10分） 1.地下水临界深度是指? （） A、地下水埋藏深度。 B、在一定的自然条件和农业技术措施条件下，为了保证土壤不产生渍害，所要求保持的地下水最小埋深。 C、在一定的自然条件和农业技术措施条件下，为了保证土壤不产生盐碱化和作物不受盐害，所要求保持的地下水最小埋深。 D、在一定的自然条件和农业技术措施条件下，为了保证土壤不产生盐碱化和作物不受盐害，所要求保持的地下水最大埋深。 2.对于控制一定地下水位要求的农田排水系统，下列哪种说法是正确的？（） A、在同一排水沟深度的情况下，排水沟的间距愈大，地下水位下降速度愈快，在一定时间内地下水位的下降值愈大，在规定时间内地下水位的下降值也愈大。 B、在允许的时间内要求达到的地下水埋藏深度ΔH一定时，排水沟的间距愈大，需要的深度也愈大。 C、在允许的时间内要求达到的地下水埋藏深度ΔH一定时，排水沟的间距愈小，需要的深度也愈大。 D、在同一排水沟间距的情况下，排水沟的深度愈小，地下水位下降速度愈快，在一定时间内地下水位的下降值愈大，在规定时间内地下水位的下降值也愈大。
3.设计排涝标准时，需选择发生一定重现期的暴雨，一般选择标准是？（） A、1-5年。 B、5-10年。 C、10-15年。 D、15-20年。 4.对渍害最不敏感的作物是？（） A、小麦； B、玉米； C、高粱； D、水稻。 5.特别适宜防治土壤次生盐碱化的农田排水方式是？（） A、明沟排水； B、竖井排水； C、暗管排水； D、暗沟排水。 6.在进行排水沟设计时，用来校核排水沟的最小流速的设计流量是？（） A、排涝设计流量； B、排渍设计流量； C、日常排水设计流量； D、排涝模数。 7.农田长期渍水不会造成下列后果？ A、土壤的透气性很差。 B、土层都处于强烈的氧化状态。 C、利于硫化氢等硫化物的形成，对作物根系产生永久性伤害。 D、有机质矿化程度低，分解释放的有效养分少，不能满足作物生长的需要。 8.防治土壤盐碱化的水利技术不包括？（） A、明沟排水 B、井灌井排 C、灌水冲洗 D、放淤改良 9.什么叫计划用水？（） A、灌溉水量的分配方法。 B、就是按作物的需水要求与灌溉水源的供水情况，结合渠系工程状况，有计划地蓄水、引水、配水与灌水。 C、是指灌溉水在灌区各级渠系调配、管理的方式。 D、是指灌溉水通过各级渠道流入田间的方法。 10.灌区用水计划一般来说有哪四种主要类型？（） A、水源引水计划、渠系配水计划与田间的用水计划等。 B、水权集中、统筹兼顾、分级管理、均衡受益。 C、年度轮廓用水计划、某灌季全渠系用水计划、干支渠段用水计划及用水单位的用水计划。 D、上下结合、分级编制，统一调度、联合运用。
摆渡老人阅读题答案
摆渡老人阅读题答案 读中学时学校与我们村隔着一条河由此认识了那摆渡老人。当时那老人一直是我们取乐的对象。每到放学肚子饿得直叫的我们便一窝蜂向渡口跑去挤在那儿。渡船只要一靠近岸大家便争先恐后地向船上跃去。虽然老人很有经验来到岸边便做好回撑的准备但超载和落水的事仍然时有发生。超载时船上的岸上的都望着老人手忙脚乱的样子大笑。夏天下雨时大家总是把伞迎着风看着渡船被吹到离渡口好远的地方老人一番折腾将船撑到渡口我们便哄笑着上了岸。 最有意思的要数冬天。冬天很冷河面结了一层厚厚的冰。每天早晨当我们赶到渡口时总看见老人在那边摇着船好长时间才把船摇过来。一直到船靠岸。我们往往因此耽误了早读但我们都挺愿意。于是就希望天再冷些便可迟点起来反正去早了也过不了河。我们都为找到一个偷懒的理由而感到高兴。当时的我们是“心忧读书愿天寒”。 那一天特别冷我因有事起了个早。吃过早饭后便不紧不慢地向学校走去。到渡口时我惊奇地发现那老人不是我预料的那样正在“跳舞”却已经到了这边。我和他攀谈起来。我问他“你今天怎么这么早”老人咳嗽了一声缓缓地说“许是人老了早上总起不来。昨天听学校说耽误了学生上早读今天我就起了早。谁知等了好长时间才来了你一个人。”说完便送我过河。 船到河心老人忽然回头对我说“你们小孩子可要好好读书啊。”那双眼睛竟满含着期待和爱意。我心中一震看着老人疲弱的身体沾满水碴?6?7碴á?6?8小碎块。的白胡子一双冻得发紫的手猛地问到“你干啥要受这份苦呢”好久老人长叹一声说道“干啥哎以前我也有一个可爱的儿子他曾吵着要上学但终究没上成。后来他得病去了我一直感到对不起他。我在这儿摆渡接送你们上学心里好受些。”谈话间船已到岸。待我上岸后老人又把船向河那边撑去。看着老人的背影我不再感到笨拙可笑鼻子有些酸酸的。 那天我把老人的故事讲给同学们听了。以后我们乘船再也没有起哄。于是老人饱经风霜的脸上现出了笑容。 再后来两岸之间架起了一座桥。最后一次过河时老人对我们说“以后不再送你们过河了你们要记住好好读书啊。” “好好读书”这句话一直留在我的记忆中。 真想再见见摆渡老人。 1本文具体描述了摆渡老人接送“我们”过河上学的辛劳。先写老人因“我们”的______而手忙脚乱一番折腾再写因 ______老人好不容易“才把船晃过来”最后写老人不顾自己________特地起大早送“我们”过河上学。用概括的语言填空 2第⑤段中摆渡老人说“我在这儿摆渡接送你们上学心里好受些”。请你用自己的语言简要说说为什么老人觉得这样做“心里好受些”。分析摆渡老人的心理答______________________________________________________ 3第⑤段中加粗的词句表现了“我”当时_______和_______的心情。 4原先摆渡老人在孩子们的眼里是一个______的形象后来摆渡老人在孩子们的心中却是一个______的形象。用自己的话填空5“摆渡老人”中的“摆渡”可以理解为老人对“我们”生活、思想上的帮助。其实生活中还有许多这样的“摆渡者”请你展开联想按照下面的示例仿写三个句子。新题型示例1作家把读者摆渡到精神的彼岸。 训练联想和表达能力 2 “希望工程”把贫穷的孩子摆渡到求知的校园。 仿句1______________________________________________________
《鞌之战》阅读答案附翻译
《鞌之战》阅读答案（附翻译） 《鞌之战》阅读答案（附翻译） 鞌之战[1] 选自《左传·成公二年（即公元前589年）》 【原文】 癸酉，师陈于鞌[2]。邴夏御齐侯[3]，逢丑父为右[4]。晋解张御郤克，郑丘缓为右[5]。齐侯曰：“余姑 翦灭此而朝食[6]。”不介马而驰之[7]。郤克伤于矢， 流血及屦，未绝鼓音[8]，曰：“余病[9]矣！”张侯[10]曰：“自始合，而矢贯余手及肘[11]，余折以御，左轮 朱殷[12]，岂敢言病。吾子[13]忍之！”缓曰：“自始合，苟有险[14]，余必下推车，子岂识之[15]？——然 子病矣！”张侯曰：“师之耳目，在吾旗鼓，进退从之[16]。此车一人殿之[17]，可以集事[18]，若之何其以 病败君之大事也[19]？擐甲执兵，固即死也[20]。病未 及死，吾子勉之[21]！”左并辔[22]，右援枹而鼓[23]，马逸不能止[24]，师从之。齐师败绩[25]。逐之，三周 华不注[26]。 【注释】 [1]鞌之战：春秋时期的著名战役之一。战争的实质是齐、晋争霸。由于齐侯骄傲轻敌，而晋军同仇敌忾、 士气旺盛，战役以齐败晋胜而告终。鞌：通“鞍”，齐
国地名，在今山东济南西北。 [2]癸酉：成公二年的六月十七日。师，指齐晋两国军队。陈，列阵，摆开阵势。 [3]邴夏：齐国大夫。御，动词，驾车。御齐侯，给齐侯驾车。齐侯，齐国国君，指齐顷公。 [4]逢丑父：齐国大夫。右：车右。 [5]解张、郑丘缓：都是晋臣，“郑丘”是复姓。郤（xì）克，晋国大夫，是这次战争中晋军的主帅。又称郤献子、郤子等。 [6]姑：副词，姑且。翦灭：消灭，灭掉。朝食：早饭。这里是“吃早饭”的意思。这句话是成语“灭此朝食”的出处。 [7]不介马：不给马披甲。介：甲。这里用作动词，披甲。驰之：驱马追击敌人。之：代词，指晋军。 [8]未绝鼓音：鼓声不断。古代车战，主帅居中，亲掌旗鼓，指挥军队。“兵以鼓进”，击鼓是进军的号令。 [9]病：负伤。 [10]张侯，即解张。“张”是字，“侯”是名，人名、字连用，先字后名。 [11]合：交战。贯：穿。肘：胳膊。 [12]朱：大红色。殷：深红色、黑红色。 [13]吾子：您，尊敬。比说“子”更亲切。
扬州大学农科农田水利学计算题过程及答案
农田水利学计算题 1、某小型灌区作物单一为葡萄，某次灌水有600亩需灌水，灌水定额为25m 3/亩，灌区灌溉水利用系数为0.75，试计算该次灌水的净灌溉用水量和毛灌溉用水量。 解：W 毛=MA/η水=25*600/0.75=20000（m3） W 净=MA=25*600=15000（m3） 2、某灌区A =0.2万亩，A 蔬菜=0.16万亩，A 花卉=0.04万亩，m 蔬菜=20m 3/亩，m 花卉=15m 3/亩。求综合净灌水定额m 综及净灌溉用水量。 解：m 综=α1m 1+α2m 2=0.8*20+0.2*15=16+3=19（m3/亩） W=m 综*A=19*2000=38000（m3） 3、某小型提水灌区，作物均为果树，面积1000亩，用水高峰期最大灌水定额为25m3/亩，灌溉水利用系数为0.75，灌水延续4天，每天灌水20小时。试计算水泵设计流量。 解：Q 设= =25*1000/(3600*20*4*0.75)=0.12（m3/s ） 4、已知苏南某圩区，F=3.8Km2，其中旱地占20%，水田占80%。水田日耗水e=5mm/d ，水田滞蓄30mm ，旱地径流系数为0.6 。排涝标准采用1日暴雨200mm ，2天排除，水泵每天工作时间22小时。试求泵站设计排涝流量Q 和综合设计排涝模数q 。 解：R 水田=P-h 田蓄-eT=200-30-5*2=160（mm ） 水ηTt A m t T W Q k j j ij i i i 360036001∑==??=
R旱田=αP=0.6*200=120（mm） ∴Q=(R水田F水田+R旱田F旱田)/3.6Tt =(160*3.8*0.8+120*3.8*0.2)/3.6*2*22 =3.65(m3/s) ∴q =Q/F=3.65/3.8=0.96(m3/km2) 5、冬小麦播前土壤最大计划湿润层深度为0.6m，土壤平均孔隙率42.5%（占土壤体积百分比），土壤田间持水率为70%（孔隙百分比）。播前土壤含水率为45.0%（孔隙百分比）。计算冬小麦的播前灌水定额。解：M=667Hn(θmax-θ0)=667*0.6*0.425*(0.7-0.45) =42.5(m3/亩) 6、已知某渠系如图1-4-3所示，干、支渠采用续灌，设计灌水率q=0.78m3/（s·万亩），一支灌溉面积为2万亩，二支灌溉面积为2.4万亩，三支灌溉面积2.5万亩，支渠的灌溉水利用系数为0.82，干渠渠道水利用系数0.9。 【要求】 （1）计算各支渠设计流量； （2）计算干渠设计流量和灌区灌溉水利用系数。 解：（1）Q1=qA1/η支水=0.78*2/0.82=1.90(m3/s) Q2=qA2/η支水=0.78*2.4/0.82=2.28(m3/s) Q3=qA3/η支水=0.78*2.5/0.82=2.38(m3/s) （2）η水=η支水*η干=0.82*0.9=0.74 7、1）下图渠系干、支渠续灌
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