9 research outputs found

    The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel

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    Background: Versutoxin (delta-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. delta-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; delta-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of delta ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of delta-ACTX-Hv1, determined using NMR spectroscopy, comprises a core beta region containing a triple-stranded antiparallel beta sheet, a thumb-like extension protruding from the beta region and a C-terminal 3(10) helix that is appended to the beta domain by virtue of a disulphide bond. The beta region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with mu-agatoxin-l, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, delta-ACTX-Hv1 shows both sequence and structural homology with gurmarin, a plant polypeptide. This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. Conclusions: delta-ACTX-Hv1 shows no structural homology with either sea anemone or alpha-scorpion toxins, both of which also modify the inactivation kinetics of voltage-gated sodium channels by interacting with channel recognition site 3. However, we have shown that delta-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and alpha-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels

    The molecular genetics of bipolar affective disorder : South African populations, endophenotypes, and environmental influence

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    Includes bibliographical references.The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance that may include by genetic heterogeneity, genetic epistasis, gene-environment interactions, incomplete penetrance and variable expressivity. In this thesis three strategies were employed to ameliorate these confounding factors. The first strategy was to focus on a theoretically genetically-homogeneous population with BPD. A unique South African sample including 190 individuals of the relativity reproductively-isolated Afrikaner population yielded promising evidence of linkage to chromosome 1 q31-32 and weaker peaks at lOq23 and 13q32, regions previously implicated in the disorder. A family-based analysis suggested that the 3' variable number tandem repeat (VNTR) variant of the dopamine transporter gene (DAT) is associated with bipolar-spectrum illness in the 132-strong sample of British ancestry. The second strategy was to carry out genetic linkage and association analyses using quantitative traits (elldophenotypes) that were closely associated with BPD. As part of this process a variety of personality traits were evaluated in the cohort, and anxiety related, novelty-seeking, hyperthymic, and cyclothymic personality traits were found to aggregate in participants with BPD and to a lesser extent repeated unipolar illness (MDE-R). These traits were therefore used as quantitative markers or endophenotypes of BPD. The quantitative linkage analysis indicated that a variant in the region of 13q32 may influence the development of novelty-seeking-related traits in the largest Afrikaner pedigree, while the personality trait, ""Stability"", was weakly linked to 4p16 in the total sample. The catechol-o-methytransferase (COM1) Va1l58Mct and the Brain Derived Neurotrophic Factor (BDNF) Va1l66Met polymorphisms were associated with mood-labile-cyclothymic and hyperthymic·-novelty-seeking traits, respectively. the DA T VNTR and the Notch4 exonic repeat variants were associated with a broad range of ""pathological"" personality traits in the sa11lples of British and Afrikaner origin, respectively. The sample was also evaluated with a battery of neuropsychological tasks and the BPD 1 and MDE-R groups displayed both verbal and visual memory recall deficits while the BPD 1 sample also suffered from recognition memory deficits. The neurocognitive trait, ""Memory"" was therefore used as a second endophenotype generating potential linkage signals on IOq23 and 22q 11. The exonic 48bp VNTR polymorphism in the dopamine 4 receptor (DRD4) gene was associated with '""Memory"" performance. As a third strategy, a potentially important aetiological factor, childhood trauma, was measured, and used to test for gene-environment interactions between the various candidate genes and bipolar-illness or BPD-related endophenotypes in the cohort. BPD and M DE-R individuals displayed significantly higher levels of emotional and physical abuse, and the former variable was also associated with the development of anxiety-related and unstable personality traits. A functional variant of the COM1 gene was found to interact with abuse to predispose to anxiety-related, unstable cyclothymic and novelty-seeking related personality traits. The combination of childhood abuse and possession of low-activity MAO-A gene variants was also associated the development of more anxious and unstable personality traits. All interaction between sexual abuse and the B])NF gene modulated performance on verbal and visual memory tasks. A similar interaction between the ApoE gene and sexual abuse was observed. Although a number of theoretical obstacles remain to be resolved, the analyses of isolated populations coupled with the use of endophenotypes and the testing or gene environment interactions, holds out great promise for the eventual elucidation of the genetic basis of hi polar affective disorder

    0002

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    THE DAILY PALO ALTO TIMES^ SCHOOL BOOKS Our patrons are reminded that all the wholesale dealers In school books and school supplies were burned out in San Francisco. As yet only one firm has been re-established on a partial scale. Despite these drawbacks, we will be able to take care of our regular business. Stocks have been purchased in New York and Chicago. Every effort will be made to anticipate your needs, and to supply the goods when needed. NEW STORE Painters and carpenters may be in the way a little for a while, but after you get in once you will see that the store has been restored in better shape than it was before its destruction in April. We have been here fourteen vears, and if you are a stranger we want to give you the benefit of our experience In furnishing the goods you need and at the correct price. We want to know you. H. W. SIMKINS Bookseller and Stationer M4MM »« CHOCOLATE AND CARAMEL THESE ARE DAINTIES LOVERS PRIZE; WHO WOULD SPEED HIS WOOING WELL- BE SHE PEASANT MAID OR BELLE- NEEDS BU7' TO BE CANDY-WISE. CARAMEL AND CHOCOLATE THESE TO COURTING ADD A ZEST; HE HAT SAFELY BRAVE HIS FATE WHO HAS LAND-MARKED EVERT "DATE" with box of Wilson's Best MM>»«I»»* WILL WED MD SAVE LEGAC; C frill Kl\L KM M Kit LI NO T STAItT WK8T TO CARRY OUT POVIHION OK WILL. ♦Beorge Gregory Denies All Know I *■!.;■ of lite H. |-almi.- Of Young Woman to Become llrldc. Johnstown. Pa., Sept. 26.—Goorg Gregory ol Cenervllle, Cal., wilt no. lose bts legacy, although his latin ; • will stipulate* that he marry Oath* erln" Emmerllug of Johnstown, Pa. before he could Inherit the fortu:: Although Gregory Sr. died but* 0 month ago. Miss Emmerllnit has already made up her mind lo act In. mediately nnd will leave for Col.' fornlit tonight. Mlku> Emnierllng Is an ncrov pllrilivd Boeleiy woman of this el' and Ii acting" under the full cons... of her father, John Em merlin*,, . wenliliy brewer. At the Emmcrltng mansion no d- nit. statement will be given Ngv ! tin: Minx Kmmerllng's plans, and i was from one of her college frleti that It was learned that she woul go to California. Other members oi the titinlly nro preparing for a IT and It Is possible that her youm: sister Stella will accompany he From another sourco It Is stat< that Miss Emmerllug Is having I elaltorato wedding trousseau pr* pared. Oakland. Cal-. Sspt. 26.—Wh* stilted today If he was aware thi thv bride picked for him by h father was nn'.hor way to the con: George Gregory donlsd evsrythl; connected with the strange pro*. I atom of his father's wilt, and arc went so far as lo suggest that 1> would attempt to have the docunte; set aside. RUSSIANS DYING PIU>M PBKsH. Revolutionary Crimes Work Ifu1. Among Ulgh Officials. Paris, Sept. it.—Professor All - ander Ular, who Is regarded In P«r.. aa tbe mouthpiece of Count Wit . says that many of the blaher Ruk^'- : , functionaries are dying from fright or are oa the point of leaving l*"> country. In these eases bombs an knives are no longer necessary. Professor War says thal_ Genera! Skellon. Governor General of Polar '. with the drums of both his ears d stroyed by the explosion of a bor. Is ln a state of tmb**clle collapse, an.' probably will be succeeded by Rent', al Kennenkainpf. Admiral Oubassoff, author of ti horrors st Moscow, whose log ■ blown off, nan received a present ' 1,000.000 roubles Iroi the Crar In comitensatlon, but I repressive zeal Is at on end am! i bas decided to spend the rest of !:'• life in foreign watering plares. Ex-Minister of the Interior Dmto- vo took refuge In Paris, but. 'at u practically expelled by M. Clemen- cCnti for trying to'oYganlxe a Rusk!) i police system there. His whereabouts are absolutely unknown. AWOMAR IS TORTURED ROBBERS _APPLY HATCHES TO lii:it FKKT TO FORCE HER TO TKLL WHERE MONEY IS. BADLY BEATEN FOR SIX CENT Man Hrulally Beats Ills Wife f Spending six cent*. New York, Sept. 26.—Because h wife spent six cents without his p mission Wllllnm l^onnrd. of 91 J- any street, Psterson, N. J., attnc;: the woman. It Is alleged, and litter savagely with an ax handle. I Is ln 8t. .in -'ill's Hospital, and said to.be In a precarious conditio Leonard Is under arrest. Only a few minutes before the : aautl l-conard and two ot hla coil ren wore playing ball In the yard > their home. I^eomtnl went Into * house and missed six cents be '■• left on a table. His wife expln:- thal she had sent one of the ahlldi to buy tome household article. Le ard became furious, and nc-lgbi claim to have,beard him say: "■• produce that money or I'll kill ) before tbe day Is orer." Liberty. Ind., Sept. 26.—a pm* composed of SherllT Charles Waldos Marshal William Line, Deputy Ma shal Snyder und others Is scouri . the country about Liberty for ti robbers who took 1*00 from tl home of Mrs. Ora Miller last event* after torturing her by burning It. feet and setting Are to ber clothi* ln an effort to make her disclose :. hiding place of the money. Mrs. Miller Is In such a seri< condition as a result of her a.v experience thai she could not t but little about bar aaaallants ti day. Mr. Miller had loft the house t a few minutes when the two m< walked Into the house. Mrs. Ml! Bays she wits dragged to the floor : her head, a revolver was thrust hi r face, ihe robbers demanding thai she tell where her husband had bid* den bis money, and warning h«r not to scream, She protested that her husliand had left no money In ili- house. When they saw that she wotiln not tell, ihe two msn bound anu fi&gKnd her. While one held htr the other then applied matches lo her toot. Though the puln wits intense she refused lo divulge anything. One of the m n continued to torture her. ■ !.- . her, twisting her wrists, burning h ■. feel nnd limbs and setting fire to l u gown. The other ransacked I it house for the money. At last M *.. Miller lost consciousness. When she came to the robbers hav. gone. Weber Is to Be Hanged. Sacramento, Sept. 26.—1'nb Governor Pardee Intervenes, Adol Weber will be hanged al Poll prison tomorrow for the murder i his father, mother, brother and - ter. He was tried on only one QtuUT Governor Pardee was asked to: If he would Indicate what action will take on Ihe petition for a co- mutation of sentence and he rooll* tbat be would not dlscusa the es It Is not believed the Governor w! take any action whatever, thus •• milling tho law to take lu course. Want Free Pilot line for River.. Portland. Ore., Sept. 26.—Prot pilotage across tbe Columbia rivii bar, the ellmlnullon of pilotage for coastwise vessels carrying a cuatoi u license, and free docks at Porllan.t, where nil craft may moor v*. .; ■• charge and load cargoes, are feature* of the program for ths next session of the Legislature. Tbe granting of thuse conceSHlo.i: lo msrlnc* commerce of the fori I guaranteed by the flourd of Trade. Postal Savings Banks. Chicago. Sopt. 26—The City Conn* ell last night passed a r«**olutlon coir- mending and Indorsing the mo v- ment to establish United States postal savlngB banks. The resoluil.ii cites the wrecking of the MUwmImu Avenue State Bank as one ot the n. sons why such n law should be eon ed, and urges the representatives >.:'. Chicago In Congress to assist In tb* work of establishing these banks by their Influence and votes. Three Hundred Ai-rasted. Atlanta, Oa., Sept. 26.—In ordc to resume law and order ths t. I . tary have begun to disarm the ne gross. This policy will be pursued until every aegro In Atlanta Is ■'.., armed. There are 1,000 Infantry m- on duty hers. Thrss hundred bis-. has* already been arrasud. TELEGRAPHIC BREVITIES. The magnificent new buildings ot the Harvard Medical School wer*- dedicated yesterday. Washams A Curtis' salmon canneries at Blnln. Wash., were con pletely destroyed by firs yesterdo. morning. 1-oas. $40,000. Dr. Joseph Snlvnnc last night. :■ Ottawa. Kit-., shot his wife am mother-in-law. Mrs. David Mitch.:: Both women are In a serious eotuU* Uon. Charlemagne Tower. AmerlciM. Ambassador to German. Vks a pi ■ senger on the steamer Kron Prim Wllhelm. which arrived ysstertiu-- from Bremen. A boat containing 200 persons ego* slied In midstream while CRwd t tho Rlrsr Indus. Th** pasaeng"' wore swept down the stream tod only thirty were saved. Several hundred men and womei passengers In the Pennsylvania its tlon In New Vork. saw a loeomotlv. run over and mangle Charles Tea bout, a colored porter, who tried i cross the track, yesterday, ln front of the moving engine. Tbe Mexican Chamber of Dopurli" has appropriated 1760,000 for the purpose of Improving the tin** of ta* Vera Crus Railway, a OOVWBUCOI property. The Government has nl-' appropriated 1260.000 to compVie the breakwater at the port of Mao- tanlllo. on the.Pacific coast. Miss Fairy Plumb, a Goshen aattaag. formerly of South Bend. Ind., Is |>m- parlrig lo enter suit against the West' era Union Telegraph Company tn damages. The company failed tf deliver a message sent by her to * theatrical manager, thereby causit* h**r to lose an engagsmsnt with theatrical company. Marcus Powelson, of Nutley, N J. bas beea arrested for keeping hi* horse and three dogs tied up without giving them food or drink. When -e- tsased ths borss dropped dead fron> the effsets of starvation. The deg* were In such a pltable condition ths: ihoy b«d to be shot- MANY TO LOSE FREE PASSES THE EXECt TIVE COMNITTBI. AP* PtHNTBO BV RAILBOAIH*) MHh HIT THEIR REPORT. New Rate law Will Prevent Rail* viajs Proa Kit end Ing Privileges lo cl.i-.-i-- Now I ii.nr.il. Chicago, Sept. 26.—J. C, Stubbs. chairman of the executive' officer: Sommltteo, appointed about twd inouttis ago by all tho railroads west oi Chicago io study tho doubtful points In the new rate law and H aecure the advice of counsel regard- lag 'In- matter, has completed th' preparation- of the committee report on pitstst-nger matters and It will bt> formally submitted at a meeting oi the Transcontinental Passenger Association today. Tin' report says: Free transportation cannot be given to land or Immigration agent* unless ihey are employes In suet* sense that the carriers legally coui>* give them tran*i|*Mrlatloni There Is no uuthorlty In law toi making lower rate* to land mamatt And settlers than for other travel*-™. This Interpretation smims to abolish the honn>-Hi**'fcers' excursion which all lines have been running for years Tho law roiiimlttee advises tha' transportation cannot be Issued Ir payment for advertising. It la gener ally accepted, however, tbat carrier: muy carry mi oi.-n account with pub* Ushers and that publishers may cam an open aocouni with carriers tor advertising, nud these accounts can bt balanced pozceptlblj. Tbe balance whatever It Is, must be paid In ca.«b The transaction must be devoid 0. previous agreement that the aervlc*. done by cither party for the othr-i Is to be paid for In any other way than by canli. - Special reduced rates may be mad* for Federal and State troops and officers and employes of the United States Geological Survey and reels niation service In tbe future aa la th*: past. The words of the law excepting "Inmates of hospitals and chartt- able and eh-mosynary Institution, and 11-■ - - ■>",:■ engagsd In charitable and mlsslonsry work" from the fret- pass prohibition are held to apply tc doctors, nurses and other employes Nuns, sisters of charity, missionaries, national or State officers of re llgfotiH organizations, teachers ati'J pupils In Indian schools, officers M the Salvation Army and Volunteer of America. It is held, may be given free transportation. Special rates for theatrical companies, ii;.-- o:ili clubs, etc., are held to bu discriminatory. Tbey should be taken under the party rats rules.' the report says. Special rates for army and navy officers and their families, which al ways have been made lu the pan'., are held unlawful for the same reason. Regsrdlng the Interchange o. transportation by common carrier* tor the use of officers and employes and thslr families, the committee decides such interchange may be madt* with sleeping car, express and steam* ahlp companies, but not with telegraph and telephone companies. H Is bold that free transportation ma> not be Issued to members of railroad unions who are not In the employ ot the company. Want lo Entl Vict* in Vallejo. Washington. Sept. 26.—During hli brief stay at tbe Nary Department yesterday. Secretary Bonaparte had' a conference with F. H. Brown oi Vallejo. regarding the efforts to eradlcstfi from that city, which Is the seat of the Mare Island Navy Yard, the gambling dens, brothels and low saloons. Mr. Brown presented to Secretary Bonaparte affidavits and other evidences tending to show tbat employes of the Navy Yard of the United Stales sailors and marine, were being made victims of tbese dens of vice and he aaked tbat thr Secretary use the Influence of the Government to assist the people oi Vallejo fn remedying the evil. Th*» Secretary expressed Interest In ths presentation made by Mr. Brows and promised to give It his personal st- ten tlon. Typhoid Thrroteas Han On-mia. San Queolln, Sept. 26.—Dr. N. K Poster, secretary of the Stats Board of Health, has made tbe startling report tbat be has ordered tbe author! ties of this place to place the town on a sanitary basts at one* or h* would order San Quentln placed under a quarantine It appears that typholr fever Is quit* prevalent here a* present, and scoordlng to Dr. Post**) unless drastic mvaaursa are taken a. s typhoid may spread to th* Stats Prison, which Is close to th* town

    ViewScan_0007

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    PAGE EIGHT DAILY 1-Al.L AI.TO 'alMES SATURDAY. NOV. y. 191.1. Homes in Palo Alto SACRIFICED At From One-Half to Two- Thirds Theii Value. A Bargain In corner lot lOOx 125 right down town at about 2,500, easy terms. D. J. Williams REAL ESTATE INSURANCE City and Country Property Country Lands Phone Palo Alto 54. *>3 Univeraity Avenue. P. O Box 37. PALO ALTO. .....aaaaa aaa.».........».».»..*a»...»».............aaaaaaa...a Jewel Theatre THE HOUSE OF QI'ALITT Miss pruni 1 ■> Howard, Musical Director. PROGRAM thk ROARDMAN rtisTKiw—[iiMiiita mua uvun of tha rnriiir ctMM—i-»|M-rt I'liarncler rlinti_r nrlM*. THK HOWARD-—Hknturial nrtJMa. HI.WCHK AUIHIKY—Tb«* fanirlle Illu-iraU-d Moogater. PHOTOPLAYS THK UltKCKKHs—I j-mrrfnl *_-« drmmn. THK Kl«HTI\1ct'in. «wt*-*t vocwIUt. »»♦♦♦♦♦»»♦♦♦♦♦♦••*»•♦»♦♦♦♦♦♦♦»•♦» Palo Alto Upholstering Company Richard Brasor, Manager. 043 Emerson Street To the People of Palo Alto: If you an* told that I cannot re work for 92 rach remember thi*: making mallrnui** for _n year', nt i a I to *".. Kin] Jn Unci tun. the sn. t from -jr. u> T.l rent* each per maCta I bare inuilc uliir** I lutvc «t_ri*-il In !■ one ill' -.■!>■.ii.-. 1 customer ami In* of imabUMa 1 Mill _in ni) place money |.siiil. HIGHEST GRADE UPHOLSTERING OBTAINABLE \\ ANYWHERE. ♦♦»»»as>»»tss»»s»»»»eetss»s»>st»»»»»»f>»»tt>t^>>t< ! Two New Stanford Trustees Named (Contli.ued from pntt 1.1 rector of fifteen large concerns In Load00. An civlileiice of the esteem In which Hoover In held abroad was tin- recent Invitation extended to him to Join the Association of the Ctrl! Knalneers of France. Hoover Is now In California rep- reeenilnK Ihe English group which has taken pari In ihe financing of . the General Petroleum Company and supplied a portion of the funds for (he purrhasc of the I'nion OH Company br the Genera! Petroleum Company. Hoover Is ibe author of a well known textbook on the prlnclplea of mining, a nd his most recent production, a biography of George A_rl. cola, together with a translation from the I.j.Mti of iln- grent fifteenth century engineering classic by that author, has attracted considerable attention in literary and, scientific circle*. Hoover married Mis* l.nu Henry of the rtass of 1S9R. They bave two sons, both of whom have been around the world several times. U , M. Newlwll. Mr. Newhall OOmea from a dle- tingulslied and wealthy pioneer family of California. He Is a graduate of Yale Cnlverslty and also of the Columbia l-*w School. He doea not practice his profession, as his large business Interests demand his time. 1l<* Ins" Die management of the great Newhiili rnncheH and It is Hi ought that his training in this line will be of value In the direction of the large land holding" of the university*. For a number of years he has been trustee of the San Francisco Slate .S'ormal School. —And when you come i Warmth With. out Weight— 'Sound sleep in A OftelUefoQulch Bohetne. Iiy United Pmm laOitclon. Nov. no — Apparently in- aplretl by the report that Gaby Deelrs Is receiving *:..(JOO a week during her preeenl Atnerlean 'our. n pretty danseuK.. hi Merlin wrote to ax-K1ng 'Manuel iH'Kuitii; hint to protnlae that if she eame to London he would ■compromise" her by hla attention!*. Al least, flint It- the h(o- ry they nre telling hi Ibe cloba f Pall Mull nnd Pi. ca.lllly. "I am and want to remain a good girl."' she Is said lo h.ire wrlttcu: "hui with an adveflleemenl each as y!ni could give nn* I could gel rich." HeiiiK defleleni lo a aenae of humor, bin ex-iiinji'nty in leporied lo hnin 1 n <*\cc*villngly nunoyeil by the incident. Aeronaut Visits Mayfleld. Clinrl.'* Bitot, cashier of Hie May. field Hank and Trust Company hud Hie honor Thanksgiving day of entertaining at his home to dinner the noted neronaut Janien MnDln. one of Hie greatest aeronauts ln the world. Mr. Eliet is Inlereeted in ihe hittire plana of Captain Mdrtln, M lii'-v linve it bearing on the probable location of an aeronautic school in tliin locality. Captain Martin In a member of the I'nlted States aeronautic r.MMTve and ranking captain Thanksgiving. Nobory ever had a loftier conception of Deity than our Puritan Fathers. Hut they were penterated with gratitude and ansiou* to remember Deity fitly. Tbat was the rub—fitly The Greek* and Romans offered gold nnd silver, but our Puritan Fntliers. with tbelr eonaecrated Insight, raueelved that Deity did not relish having the circulating medium reduced In ihat way at the risk of bringing on a stringency. The Jewlah custom of offering burned ment * ts even more objectionable f tou/se. Deity did not wish the hnnd of Ibe beef iru*t to I..* played Into. Finally, i>-ity being n Prohibitionist, libations of wine were out of the elocution So our Piirlian Fathers hit tiponj the expedient of giving thanks.! Thanks were nol a competitive com-, modlty, ami could be given in any! quantity wllhoul dlxturhlng trade I.lfc* -title. of Wi 11.' Mrs. M. Det«*Is and her son Martin are visiting friends In Napa. Vacuum Carpet Cleaning Pbone Palo Alto 70 rontemplatea flying across il lautir in the near Future. He or- gnnlsi'd Ibe Harvard Aeronautic Society anil nmnuged It for n time* dur- loff Which he made a number of xm-ceasful lllghta. He has made fights In France and England, and for two yearn wa* Instructor at Gra- I lis.in While'* celebrated school In London. CapUta Martin wns pleaeed with his visit In Mayfleld. nnd considers Stanford University as n sultnble location for an aeronautic school. The' proapeeta for the development of this movement will det>end largely! on the interest shown by the people ;of this locality. FORGER IS ARRESTED AND MAKES ESCAPE A young man who Is n stranger In this In. .'i'U v passed a couple >'t forgj-d checks for small Amount in Mat field yesterday. Suspicion wat arouHcil nnd when H war. found 'I"*' Ihe 'lifik- were worthless Hie forger, who gnve the name of Wilson , was ' arrested by Constahle Hind- [ ■haw. but later succeeded In making! hfs escape At the time of thci latest re|Miri he had not yet been ■"*"-' captured Mi sicnl Program Melhodtat < hurch, Stinda rem her 1st: Morning- Voluntary-- •O I'om*. Let Worshtp" Mend Male quart i ' Nearer. My to Thee" I requested! . . . . FIREWOOD FOR SALE CHEAP 8 PER CORD lot CI1HT.E. I'll ONE OO Can give yon oak, gnnt, ecc 4-foot wood, stovewood. heater blocks. chunk*. 1 fOof, 10 Inrhe- or 2 feet long- Will ar)) j..11 wood cheap, a* I weed the money and need It now. Hi- Suffrmrette Throw* Her SIhn*. r.1 I'i, Aberdeen. Scotland. Nov. 20.— Mlstnklng the Rev. Forbe* Jackson for l.loyd Mleorge, the noted statee- a suffragette disfigured the face of tbe reverend gentlvman with a hoitewhlp. Sbe wa* arrested, together with four other suffragette*, and when taken Into court on Grace Lorke took off her *hoe and threw It nt (he magistrate. She wa* Jailed on ;i charge of contempt. God. Offertory "Andante" Hervti Duet—"Rock of Ages" trepeated 1 plbpl Mr. Werry und Mr. Jeffer*. Postlude- "Rereislonal" . . Thorn Evening— Voluntary "1 Heard ihe Voice of Harpers" Gai Male Qtmnet "Drltiing. Drifting" Mel.! .Hi.,!.:■!! J I Offertory "Nixturne" .... Chopl 1'cis-hiilc "l,it iIn* Heavens Rejoice" tleti ^DEPENDENT EXPRESS & TRANSFER CO. A. H. MrOsw. Mssigrr, S30 Oowpae Btreot. TRUNKS nami: CTTT URITS SO CKim. _T01L_GB. Phone SI OK—Smith'* Cydery. RnsMeaee pbo_e B48L I»ct«-ctlvr on eh.* Sl«ml Py United -.. Indianapolis. Nov. 3i -> Haymond ilurns. son of Detective Hums, continued bin story of Hoefalna' doubte- cronalng today. He teaflfled that In February, Ifll, he ankod I lock in what hod btcono of Caplan ami Schmidt, and Hockln replied that Tveltmoe wa* taking care of them, that Tveltmoe waa furnishing t'ie money and a Chicago labor leader wga paying them Hockln also aald that Tveltmoe and John MrNnmar* had a conference In St. Loul* In 1910 and arranged for three eiplo- slons in Los Angela*. —-don't faiJ to sec our display of thc new Maish comfort designs. Every pattern is distinctly new—created exclusively for Maish comforts. There are all the new shades plain and bordered. You will find in this display just what you have been looking for to harmonize with the color scheme of your bedroom. This winter free yourself from heavy covers—sleep under the Maish. It keeps you warm on the coldest cold fresh air nights—yet IS BO wonderfully light ««. more lives flnd fluffy than science-- ^ it DCVef fatigues Sir Joseph Us you— ^ ^*___ _,.-_ A —, ter, tainoiis I.on- meigin yon dot (ion surgeon- Maish Comfort % make such »lcC[. posMJble. The Ugh ter Yonr Bed Covering the Better In the Maish Comforts you get warmth without weight. Nothing cm* iuustft >".i a* do heavy bed clothes. To get rest that creates energy, tbat gives strength. »leep under the Maish Comfort. Maish Comforts are handled by us only. We are the sole agents for Palo Alto. Wc arc well slocked with a large variety ol* styles and new colors to select from. Extra sizes for double beds. Maish Comforts arc all labeled with the Maish trademark. I.ook for it and if you don't see tbe yellow and black label with thc name Maish, don't take it. Maish Comforts al .1.50..1.50. .1.75. 4.00,4.00, 4.50. 5.00.ST..00.5.00. ST..00. 7.00. 750toS.OOeach.OthergradesofComfortsatSA25.7 50 to S'.OO each. Other grades of Comforts at S-A25. 3.00. 2.75.2.75. 2.50 to 1.00each.EiderdownComfurtiAgoodassortmentoflineDownComfortsinfineSateensandSilksingoodlargesizes,largeenoughtocoveradoublebed.at1.00 each. Eiderdown Comfurti A good assortment of l-'ine Down Comforts in fine Sateens and Silks in good large sizes, large enough to cover a double bed. at .00, 7.00,7.00, 8.00. .00.'.00. 10.00. 11.00to11.00 to 15.00 each. What Every Family Needs these cold frosty nights is one or more pairs of Good Wool Blankets and a Maish Comfort. We arc handling an elegant line of fine all-wool Illankcts at popular prices in pure white, fancy checks. Plaids and Stripes in delicate shades of Tan. lilucs. Pinks and Reds. These colors are in soft tones and will take the place of a white blanket. Also dark nnd light Grey Blankets for real service— sleeping outside and camping. Prices 4.00.4.00. 4.50. 4.75.4.75. 5.00. 5.25.S5.50.SC..00.S..50.5.25. S5.50. SC..00. S..50. 7.00. S7.50. 8.00.8.00. 8.50. <).00to<).00 to 18.00 pair. Other grades Sheeting Blankets ,u 75c. 85c. 1.00.1.00. 1.25. SI.50. S1.75 to .?50pair.BathRobeBlanketsJuslreceivedalateshipmentofRobeIllankctsinveryprettyshades,softcoloringsandanextrafinequality;25differentpatternstochoosefromat.?50 pair. Bath Robe Blankets Jusl received a late shipment of Robe Illankcts in very pretty shades, soft colorings and an extra fine quality; 25 different patterns to choose from at 2.50 each. Children's Coveralls for Boys and Girls. The only garment for children to romp and play and have their freedom in. Colors and wear are guaranteed. Vou will get your money's worth onl ol them and then some. Sec the Coverall Kids at play on their Teetering Hoard in our University avenue window for a few days longer. Sole Agents FOR Ideal Ladies' Tailored Suits and Goats v Come in nnd talk to us about \ Suit or Coat cm ami ma<l« i.i your own individual measure at very little more than shop suit--. Come in and look at portfolio ot fashions and our large book of sample-— more than 76 styles, and 300 new fabrics to select from. Von can't make a mistake. Fit and entire satisfaction is our guarantee. Jffiendenhall Gl PALO ALT

    Physical controls on salmon spawning habitat quality and embryo fitness: an integrated analysis

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    The research focusses on the river Lugg – a cross-border catchment and major tributary of the river Wye, the most important Atlantic salmon river in England and Wales. The problem of declining Atlantic salmon populations in the catchment is addressed through investigating recruitment from egg fertilization to the emergent life stage and beyond using multiple field-based and laboratory techniques. The approach adopted is multidisciplinary and addresses the need for holistic approaches to habitat degradation which is increasingly recognised as systemic in nature; often with multiple stressors acting interactively. The initial premise of deleterious fine sediment infiltration into spawning gravels was addressed by a sediment fingerprinting study to ascertain the provenance of infiltrated redd sediment from a range of land-use types. In addition, nine artificial redd sites were constructed and assessed for fine sediment infiltration, intragravel dissolved oxygen levels, intragravel flow velocity and other hyporheic pore water characteristics, in relation to survival to emergence over two field seasons.A study examining the quality of emergent fry was also carried out using fitness tests and individual stress levels. Additionally, a study on long-residence groundwater infiltration into the incubation environment was carried out. The main fine sediment contributor was derived from agricultural sources, particularly during wetter periods. The average contribution of fine sediment from agricultural sources was 60%. Survival ranged from 12% to 70% during the 2008 flood season and from 76% - 93% during the 2009 dry season. Fine sediment mass as a stand-alone index was only weakly correlated with survival but is thought to influence other factors; medium strength correlations of survival with dissolved oxygen, intragravel flow velocity and oxygen supply in particular were observed. Evidence of groundwater-surface water interactions were detected at two of three sites investigated and is proposed as an additional controlling mechanism for embryonic survival in the catchment. Sublethal fitness tests demonstrated variations between cohorts in the 2009 period despite a relatively small range of oxygen concentrations. The results highlight both temporal and spatial variations in spawning habitat quality, which influence not only survival to hatch but also posthatch fitness

    Adult and community education in the wear valley district of county Durham

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    Throughout the 1980's traditional liberal adult education * in Britain has been in crisis. Changes in the ways it is funded and organised, coupled with the breakdown of the liberal progressive ideologies which have informed its theory and practice since the turn of the century, cast doubt upon the extent to which adult education still exists as an identifiable part of the British educational system and idea. The public image of adult education is ambiguous and informed by very little public debate about the role or purpose of adult education in modern societies. its practitioner image is still, predominantly, one of public service. in this thesis i describe what happened when I set out to examine the extent to which there was still a viable adult education service (particularly for unemployed people) in a small area of the north east of England characterised by long term social and economic decline. There is very little sociology of adult education. There is no theoretical knowledge base upon which to ground this study and no methodological framework within which to situate it. The research has been, primarily, a search for methods of research which would allow that adult education is both a social construction and a cultural phenomenon. I have drawn heavily upon the methods of both cultural studies and cultural anthropology while eschewing their more descriptive moments, believing, in the end, that sociology has a definite de-mystifying purpose: that it is, or should be, 'the critic of the absurd and not its high priest'

    4

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    All the Railroads Lead to Camp Curry, Yosemite Vou can buy rail, stage and camp accommodations wherever Santa Fe or Southern Pacific tickets are sold Garden Hose - ~ ~ Yours is Leaky MINE FOR SALE IS RIGHT IN MAKE ----- MINE FOR SALE IS RIGHT IN PRICE UTTLIJ SHORT ONES. , but ; Frslay to Mr I dau*.hter * i-d Mr*. 11. W. mmatk. • outrart.-raiid Mr*. J. W. Well, will - ..s.-atto,, ftrt-ati.il it. Ihv lU-t. '. >-t.m>w i- May Uayi and M lay ls> l for tbo c .Hector of the lute Pinlay in Bl aeaattW Mr- BttB l-uea* *p*Bl a port*.* of ltd* werk at IVUlua-a, Um- piest of Tab. Alb> will ba well rn on-tented at BVooraoHtoM -Baying al ltnlw."*H'ity Mom lay. BOagBMOl 1-- name: UK < lAM K! I BOB the WatU*a lair *t Ihe itiprntc of FUatem* have l-eii-ao »v*k >*i tlie r-^iijicti naialeim- al t'tilten*il) av.-uui .nat Milllelleld road. Tl** sia-nHim Itotise n I'hannliij: etni-t, l.-lnt Imill I*, h ready Ln- pla.tcrer* THe **a*n J.ae I'itaiiit-r id t'ouitnsn-e \ao v.1,.1 lo atlrtid the Kuartb <d July p-b-ltration *l lain All*.'. Oploiu Tlw-rnaa llsuk-msn sill n■■ lion soon Inuii Hm I'liilliplu,-* with whom be will lour Hie BtObM, Jeba, Mi-Naiinbl. mauauvr of ll«* Boo Ftaaabao Call will -i--.k at Um Mirth h Kir at A—-ml l> ball. W.-ln —1*>. Matil-mt fliariaacj.bstltnB pieacnp- Ji.«i dn.iiBri.ts, I'liiteri-ily avenue, BB Mo* I'lr*-Ir. I»ivib» ihlititi*! slit a la-re. At MoiiuUiii!Vii*w mi Sunday, Omit VIa.tr.me Socle) elul. of lbs Forest*]* of * merit*, of lte.lwi.tl. -trill l.-.i.t,. piaiie .Mr-. M. J,,l.ti-..i.'*lilll-...i. Karl (ell Thurehty »i*l bn-ke hi* arm. Tl»- astn* lame* a, i,- l-t*kin only lw*» **-nth* ■0*0.- l'reh****.r Slnnakcr's hand-mie new residence i- m-ariuir completion, ll h the pride f Hie n -i*lih-irh..>l in whii-li *tlu*l.*I. Mr- farh-l-iii atfl *>>n. 1'. I. laitet-.u. left Tl.ur-.lay fnr Helena. Montana, sltere ll.-) aill *|*a*l a puititsi ,d thr sunt liter. Allorney* N. B. Malcolm ami John A. .1.'lint".it were at l*.in I'laiim--.. oil Thursday lookinit alter insttci* ol a Jf-oefMflial lialiir.-. Afi*.t O'K-refe ol tlie ltrdsrr.*| t'ity r.it..- t.j-- M-- a*s in I'.:.' l.i' lew lean* **ti M"ii.Iar tuukinjt after The t'ilMen [tayiuic every ci-nl of Iruro tlie time id starting until th* time >f returning to I'alo Alto. JY.-i (-.hi ,-lip ■ -iitj..;,* t..|j-riur heart's ■ntent. l*ook lor lite frec-lrip-tn-lhe- H*,.rlrf'*-K*lr 1-nup.m «-l*,-*liere In tl.i- i-*.ie«t TlieCiti-trii. taelter* rerelv.nl hy friemt* here lull irate tliat Mr*. A. T. Wallace ttachnl Taoirieni alter a t.,-:.-h *•* irip fnan A. At -sttil*-. on Ka.ter. Mn>. Wallace **« tier tint and i*-i l-ult fight. I»r. A. II. Mai be* ha* jml BatO|di '<*! leauikoli.tiitilii! in a tat,..- 1. :- tm-ky blue ui*t. nt hi* h- P*. rertisi ne I m* i mss. A par*.) *a* eiilertainetl Uti eveni at the home of Wm Stevens, at I Oaks. A niula-r of Palo Aim ytmng |r«|de were prsarnl. The t'slif'trnia t* -lhv -d l'la-t"«r*ph Bith la-a-bpuirtLfsn. in I'alo All" ami with a capital .1.. k ,4 |.''..«n. fT-Vl mt WmUk b pultH-fila.l, Its. I. rn ities.rp 'isli'l. Itt. Tliiuiia. latliolle chunh |r*vi' s Ann parly IVnlnesday evening Hist wai emry kiik-.lt |«tn*ni<n*t. Tlie pn**i*t*h iii-ti, le given to thechurch iHillditig Klletl lllfl. •.**!.41 Wll I l-ii.-ti^liiii.i.* will receive attention ie t'jii.p.i.. a truck bomm i* !■»■ a-i-ni nn Selvatierra street ami i aratus sill U- iurtallnl in lite It rill I ud sonic ill. Ats «|..ia! merlin; of the I Tr*.]*- neat Tuc-.l*y event tif •H-ale ami I' M Wi-tsli-r uill.-v In ii.i.iit.i for tract. A eoftltrmatlon via** id inn. tfiven the rite* at All Saints i Friday aIlrrtM*>*i. with tlie lit. William K. Nhleda, ltiali*. t aliiorni* In clai-ye of the • Work uu Die lanictile library la pro- *'.. twin* in * ttstUfactiisy mauni-r II. II. Ilatlwasy, having l*-*-n v'r*ii'-*l a i .i-im—em by tlie UuiltKn*-Trade* t o«n- eil (4 t-ati Jot-, aill pi...-I allh the paintinB in a .liort lime. I'oiilraet.tr H. X. Hi-ltliiBcr i-s|*tI. (-.leave for the i-ust atsoit June 1, for a vlall of two or three iminlbs st -. laails, t'liit-Nipt, Waahii.^ton and nther .tt... id Impsrtanre. It aill be bl* llrst teal u.iitini In flflern year*. Th* retam ,4 Mr*. Jane I. Stanf-ml ir-.iu the trip to India ;- I--.I*.-I l>.i nut week. tt Is ,. |-.-;*l tliat sit* will remain here only » short time hef..rr ■turtliiKun a Joiini.-v to Kumi*- uhen die ttlli st-ml Hn- reuislmler ol Hit I*ul>lislier fttaninir. ltsrsJ.airt.il. mad* hi* visit* to I'al.* All. ,.[ il,. Tips 1'n.fet. r. itie v.,11 I alii-rtheelistte i.l the I'liivereity f. nimtnei v**-»tipu. for I'nritt, t.^-tk*-* slmly the HibllittCsiiH- IVler . sourte .. N'stlonah- J. B. Ualey bis just" ndd I, Milieu tlie llti.tr ,t,it»;- uo lA-enoe. Il it a fine pn*]serty ami it enden.1.«.| ll.at Mr. Mnllen art il at B irarysilt Miw Stella Ikilan, of Wasliimilon t>WB, .itti',1-,1 I' i.-..t.t-.' for i vi.ii at tb, ieiu* nf Mr. and Mr*. C. I- Webb ft he may decide b> remain permMisuiIt ttt-rafifernia. AHotney M.wrnr Thomas was at Sap* fcis week. Itavin); l.-eu call,.I there ,-. Mtifsy hy a teh-pram aummiiciiiB Ihe fcUl illur** nl his father, *.»»* death ecv-ui-red later on lh*l day. C. C. i'erry of tiwiilleLl, Itidlana, •at hare fue a- eisit Tuesday uf litis Bttab. He., a pnt-uiumi Unndry-aan fei'bis town and ealipi on tbmm In thai Un** of work while visitinp here. I'.-i-"ii i„liii,,- t., *,,-, :t,. TheCIllrrn eseli week are re.ioMie.1 lo report thr Im-i :it ihia .Him. :„ onlcr thai ibe.rn-rl ef the eity cirvulauir or the csrri*-!*— it b bo their crmr—uiay he recti&e,!. Mrs. -' C. Hashes enterUlnnf st ■ fire-buntred" card party Satunlay. Wotri' slia-mr..::. A number of ttl< l'li-j-..| al tlu- mat t*as la "looilitjt up that Hue Im-ally. M.ti;-..| i ...l(e of thr if-:.".- (inter id l'niie.| Wuekmen will bIvt a .i.i',l tall i-atunlay .-t, nm.-. May 11. si A. ". IV W. hall lu Hist mimm, Tliere aill lie ir.-d uiosir ami a p*t-I time it attired all who may attend. Tirket* .'-i eeiils h.r KeiiHetueii. The destli of Mis* l-flcia A. Mini't. Hie l**-yrat-**l dansbtsr ol Mr. sod Mr*. I"-..i- Mim-I, *..-. I'nivrndty ave- ane, owurrnl at 1 o'ebafe Kralay a iter - mum. Thr funeral aill he hebl at III aVbok Mnmlay ami interment v tti U in Cypress lam n. Tlie sail news of the death of Mm. Hruest llarlmlts at Fertile, Minm-voia, h*s been recrUnt here. It I* .- u.-,. m frnoi Kertlle, that she nmlt... 1.11 ■liitt-k it-tniuiiip|it>ti while attemlinB I-r Int-lonH Umsi^li his lost illm-. Tlie} tortuerly livnl Itere. A lartfe numU-r of men are at work it the lU-iirpe Imrtt hulhlini* InuitiliK n Kmrmin street and Ilumllloti venue. The activity IbaiaabuOH might t.-a.l stranitrr* to think ItimiUn-t's llir*-e-rni_-ein-ut h»l .f-Tii.- tn town ami as* pretarinc f-r «u evhil.tit.-ti. Tliree aasiin-ii fn*m Xt-w V.*rk have tteeti llere the [Mat ne,k or Iwo I...kiiih' forasiia for a mlli-pe for yimnit hidli-s, ttmt-irllt-hn llu' i*|iiiil In t'tviy'Wtny id' SIGet in on I,. IIIIK-I the Ground Floor-See? It is up to the wide awake people of Palo Alto to attend the big AUCTi;0N SALEof lots and villa sites at the SEALE TRACT on next Saturday and to avail themselves of the opportunity afforded to buy some of those splendid pieces of land to be knocked down to the highest bidder. Saturday, May .Seventh There will be a swarm of city buyers on the grounds but the advantage will lie with the people who" know the property and who get in ON THE GROUND FLOOR. Big excursion from San Francisco and San Jose-Bus rides and a lunch for the visitors. Sale begins at I o'clock on the grounds. Big live oak trees on almost every (ot. 4 the *-*nt atrial lastlne* II Ibe 1'ah- All the famous V ou the |t.'iiiii**d* have bno M Tlie MIM are Mr*. J. II. Hi I■■■ t*. E. !*qoirea and Mis* K. ataam I*.**ii*e i.f Hie t'luitiTi's tin . (tvtt.i at the oilier ..f tbe b I j-aiiy, there Is more or 1,-k. ■ ., . thc hii; swllehlttanl with the ■■■ sull Hull iiiccoald yeslentny hear no I,- than flfly voice* by Ukinjr.ti.ttn th-- - - and IbiebinB for arecnrxl. t ■ 11 U reii,..li,*l wttUtna .■ - - - linn*. - Jtshn I,.union Mi-an-. i a ill . field mad, eiilt-rtainnl inl..rn.ally Thursday Bflonwaa, Hi-r picsl* were MrMlame* .-*lef-*n-H.u .4 Menlo. Tb-mi|t- uailal)tar*.t-mtclirrali.|Tiirpev; Hovfe, Henry. H*nW. ami Tboiupaoa. Ldacb au eerrrd at two. Rom* were tbe princiial decntati'*** In hrparloes. Otter PamV Alt., pajtew start tliinp. hat Suit- .mt'. It i-rutaiui ft* the little 'iii/sti t.< rinri uml iiiaiiitaiu ■ tailing i " willlH'pnoIoctivcufresult*.! STANFORD PROGRAM. Official Announcement of Hvcnlt For Commencement Week at University. .itut.-ii.eiit week al Stanford ftiiver- Thnrwlay, May 1-th. SeabM oj**ra iM-tulde liall. Ittlt, Friday. Mar l*tlh, llrevptio* t..**,i.i.-i la-, hv Pr. and Mn>. Joidaii, 2uobaa Ma' H. Fat . "■:!.. r*t.-s-.tij:t:. jtt- st I l,d Manhml Jr.Mei Wnlft**.lat, Mst 1-..1.. t'oiut... ...-.- ii.eiit. .\—i,.l.1v Huh. UA; a.l'li. -• I-.* Dr.O. L. Elliott. ACTIVE AT THE GYA. Pulo Alio Institution a Sort ol "Preparatory" for Stanford Uymf. (In Moiitlny. Mat- ire ».t 1 1*1 pel I"- Hi* I.. muke Hie Put.. All" t.j n titi-im parnl'.it illtlitUlioll fir llir V fViunssiuin*, BO that .ttvlent. tlie loiter iusv \w prej-sn-1 f**r i till .-n.Itipai.-l .11 I-- l-.l. t-l A100RE BADLY HURT Southern Pacific I*;l-.;;;;t-.-.vm:ti. Crushed Uclwccn Pilot and Turn Tabic. Notice! While r*l hut pulls light, Itair on the pilot of theeiittiue Iheatn- tniiu Mouihiy -iiiiin ~i:.l .ll.sslv was nl aunim-t Hi- tin.Kn. ■■ in the I . ill yanls. ■ at*i*lv,l him to a [ 'at*- i-ukl n-tl . .tly It li** come to our attention that car- l*-tii.-r-. rtc, are refatinjc in certain ii.-Uiti-i*. to I uti. 11,- mst. ri*U i*ireltase(l fn.iu our -lot.-. Rinl delivered to Immea jn I'alo Alto.- Jn east* ol this kind II pi i re lister* will I eh-plume us or. Coin e tu our ston- and report Hit* facts, we will fiirtii-.li Hie ii, ,. -■ ,> i i.i-|,i;:,'t or ulber ti.ss lisi.is- lo i<t-rf.-llii the n-i'itrid wrtirk ami inuiantre satitfsrti'ju at jml lia.ll ilBBta J. P. Va nx CO OH was Udly «B, Uoudjr *o» l Yoiinji iiiaiir-Is It not worth your ttliile m ll«ure un that (rev trip to the | World't luir? How many vote* do yuu ! think you aill 1st able to poll? Read ; llie plan ebenhen- in i l.i- la-ac. r: SHOOT AND EAT Palo Alto RHIc Club Hnlcrtaln* Visitor* I-rum San Jose —Scores. -an lose t ','!> Ul III. "1 Good Soaps For LITTLE MONEY are few and far between. Soaps cheap In price arm generally cheap In quala Itv. See our window tor some that are (JHI'.'AI* but coon. Ea$te Orutj Go. yi;llow front Phone. Malm J i Phone. Md t the little Mctijii-l, a eaptuiiit.l I.v ,.. WoudptekM ■SEA MANS Hie I'alo Alt.. Within i ittrk.in.-u « visit tux 'id, r at a A niter i p. Mi THE SPANISH NOVIO. A Oatta*! M Ki. It.rrl, \l rrt. |S* Mi.l,',,-ii II* Vt.flatlt. A aSp.-iiiish iiiiii.ii-n wbo la In tha least attractive la always attended by a younc nan. II* Is called ber novlo, ' And It Is bla privil.-s,' to accompany " her oo ber walks, though of course al- 11 ways with etlbr-r her mother or a rsakl ii lo play propriety. Ills courtship *rl- ii"t:, ends In-his becomlnit encai;-*! to . the ynnng lady, but while It lasts aba | has to be obeillout and loyal to him. WBr Baria. Coatatltied SalrlB*. j it ltL. fonuili ttnwter ala affections I Burton, tba vivacious author of "Tlie ,0 mother fair tlain.el. the Bllfbtad ons i i Anatomy of Me lane holy.*' who had tho has uo redress, for bo Is quite at Ilher- reputatlon ef belns able to raise Uufh-. tjr to do eo, their friendship never be-', I tee la any company, howerer "mute lBj- r^nlnl la the Hsht of a forms! and mopish.- was tu reality constltu. rticaKemeoL Slarrlsre* ore settle*! by 11 Uottally nepresanl. aad It 1* believed, tb. he«d« of Ibe two famllle* chleflj i I that be was at u.t ao overcome by his roncerunl. and until such an arrange. maUdy that be ended his life In a III of | „wul u mad„ ,i„. roxine ^aolaKI may I rlo to aa liinny (rlt-la a* he likes, j I lktys'i-lat—.: Section I. Wed in-la; :it.U to IdO p. ni ; SatunUy*, BfS 10:3Q |*. in. t-tcti-n t, TlmnaUy*..'. to.'t-.tU p. in ; Salunla'p, ID-W lo I.* *. ui. Itutmctor, Mr, Ihinran. UT ITtlVEBAITV A B. PALO ALTO. CAL. R. H. ir.T//.-cr Antnirm an BcnamaataVf t> l« Part.ln.nn III-.A. l-t, mim plan*. a Aim. Iliniw liluts xi C. W. Mosher (""M-BtlT*.* •no Ilnuira IMlBSIr* |!..iii|..', |,iri,i.|,..l„:, ■(! lli..1. nr btillttliiti. |- (k Btaa M>. (St.. Alio. Cat, Malcolm A Johnson AnvasB-r* at Law Not* BY I'CSUC Baaas 1MB faitlBH Mb( twmt llasral L. S. Bean Com BACYOB m.l. MtuUbttl p.o. *»yH. l-*t.> Alt... ro* E. A. Hettinger l'..\TII,l-t"H ami Unum* He-lthiit Asri.l ..ir Ml BaiBii.ii* aim-i. ttiimriMii Mn- ln*-ur- ) i.l llanitml. rmtm Knl IH. H. G. Wyckoft, ft. o. Pa MCtaB **.!> StauanaV. 0»rr, M-Jn-i l-t—^* Batatstta SI.. I'alo All* 'I'hl.ltl, llr-lsta. mclaocbuly. Remember * the day and the place Notice! Iiavin>; l-eeii npjto.iiti'.l ffllicilor l*nr tbt< "Chriltlan Help Band** of San Kntiici**-.., t nm rt-reivim: any ra*t-nfl rluthiu* li.tl aoukl W of U*e to t.-.t poor men, aomrn or children,- and aill receive •*»*** al my .--anatarinm Fund Store, 321 riiU-*i-*ily Al«wotvlf]i will notify me 1 uiH rail at the and eft thrrli.-T. I'. A'allar. A f-.lil CalB. "I understand that prima donna fall ed to etc* ber farewell concert because eh* had a eotd.** "Tc*." answered the msnscer. "How did she contract Ur "Well. It wnan't an ordinary cold. la what Is U-cliulcally known as a oHlce chllL**--Exchange. I una after another. Thla custom baa; : certainly more advautaceti for the men i than It ba* for Ibe maidens, but yet i few ftpanlsb Blrt* would cur.- to be|i without a aorlo. bowevee fickle micbtbe. It- I.l la -Is . Used--Itu you Ilk* Ur. Dinwiddle? Etbet-Oh. ye*: I Uke hint, relatively rfK-aklne. M*ud-Hc1«tlvelj n;teafcliit? What do you mean by tbat! Etbc-I- Tou see. I pnaiilM-d to lie a staler to hlm.-St. Louis Itdjiubllc. ntaarat-aal. "You can't eat your cake and has* It, too." retaarked tba cheerful nan. ' -You can't, ebr creased tbe dyspeptic as he swallowrd a couple of tablets, a j "Thar* oil you know about IL"—I*hlla- dalpbla !:.■:. World's Fair at St. Louin. tnfant ucst|«per will send mm or j-**nng womaB to -Jve r«i»! r la true stvlr, pat it „•■•*,■ Ap-n the puct-jpe,,,^ tri,m .tar, u, ^Z warn.* fin-ov to- -yrandaoo: All actaU„ H b,r a W.I, -rf„iM|.- fSfaa Jura-carriaBKtt drive aUiut tun n. I u^yd a^o 9Muii: Tbe man who ran be notbins but serious or nothlnB but merry .. but lialf a man — UunL TWitiT to know sil.mr St. Inula •I rat— pi*t a» n..n as Ittwibta vi*ir tiamr witlt It. I**ni,-t«rr. I* tier re not a*ne yxir-z .*i*!ll^rn I'scllk <"•*,, or ante wu-i-on iu laluVh-. r1ntn*l UasoH «,„ Fntncisco, call at Inhmiml-WD'J'H »**»"> >""r Wlnt for thc farm i rvsu, l!i;{ MarhK-stHiK. I Itcad Dm aiiimunontm-ut clA'wbe MULLEN & HARMS Blacksmiths -HNE-MORtfiSHOEINC A SPECIALTY tat 1-nt.nplIj Dunr CARRIACE.REPOSITOIvy Rat* t* I'almsiinla. A scJcntlst exploiinit I'.nnpuil.'t says: "The Iiiipiiwtability of l-atatronla mud ia provorhlal. You cannot walk Ibroufib It, aod It takca a sturdy mule to- carry you ibnticb. More often' than not It ta caused by tbe burrowloe ot a tallica* rat known aa tbe turn tucu. Acre* upon acrrs, nmountlnB to square miles even, of olhcrwlse sound nnd wholo- some Btouud nre undermlniM by tbh iiiih-ratlBnble little pest. Ue bold* the couotfy na notblnK *lse holds It unUlt tbeadrent of shrep or cattle (which be [.fcBW tnmftam t-,-.«- RCCT bates) Induce* bim to shift the scssie' IOr **nC Ve™ «*■«-'■ of his rdfibtlT Ial»fa.--Boa*ao Tran-j HAIRCUT In PALO ALTO script EIGHT SHAVES FOR jOCf te alt I Charge I'mler The fitln i pkiti the mart ■":,--*• ti |bharv. -oiiux man or vtvimau tu I'alo itink.-the trip tn ami fotim Htl l llir iaet lmt.l slid! - I'lli.—ti -ttij-l- n-naly In do Ibi WOOD-BARBER llstltre*nSniU SHAMPOOIA'G Scalp treatmeat, rtc Maat. erring. Mateege. ttymroeaeP typed. Try It torhlaekheaa'a. Parlpra, UI3 Emerson Neeeweni- mrmer^m firPg Stord m- iii "m

    Efectividad in vivo de una nanoemulsión de paramomicina y ftalocianina de aluminio clorada para el tratamiento de leishmaniasis cutánea

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    129 pLa leishmaniasis es una enfermedad metaxénica cuyo vector (Lutzomyia), transmite la enfermedad al penetrar la piel del huésped mamífero e introducir los protozoos de leishmania, quienes dependiendo de la especie dan paso a un tipo de manisfestación clínica específica, con diversos grados de severidad. Aunque existen distintos tratamientos para esta infección (Pentostam®, Glucantime®, pentamidine, anfotericina B y miltefosina), aún nos enfrentamos a múltiples retos: vía de administración, efectos tóxicos hepáticos y renales, fracaso al tratamiento, resistencia farmacológica, estado inmunológico del paciente, condiciones socioeconómicas, cronicidad de las lesiones y especie del parásito. De acuerdo con lo anterior, este estudio tuvo como objetivo, caracterizar el efecto antiparasitario in vivo de un nanoconjugado de Ftalocianina de Aluminio Clorada y paramomicina (NE+FtAlCl/PM15%) activado mediante Terapia Fotodinámica (TFD), en el modelo murino de Leishmaniasis cutánea. Para esto, se realizó la estandarización del modelo de leishmaniasis cutánea en ratones BALB/c evaluado dos inoculados en dos sitios anatómicos de infección (almohadilla plantar y base de la cola). Posteriormente, se evaluó la efectividad de NE-FtAlCl/PM en dos modelos experimentales. Terapia fotodinámica fue aplicada en los grupos tratados con el fotosensibilizador usando luz LED. La efectividad clínica y parasitológica, así como toxicidad aguda relacionada con parámetros hematológicos y bioquímicos, fue evaluada. El tratamiento mostró ser inefectivo para curar lesiones cutáneas por L. (V.) braziliensis en ratones BALB/c. Sin embargo, los resultados mostraron ser similares a los obtenidos con el grupo control tratado con Glucantime (20mg/Kg/día). Adicionalmente, en el modelo con lesión cutánea ulcerada, se observó disminución del tamaño de la úlcera en los ratones tratados con NE-FtAlCl/PM+TFD. No se observaron efectos tóxicos sistémicos del tratamiento. Este estudio es el primero en evaluar la combinación de dos fármacos bioactivos contra Leishmania spp en un mismo nanovehículo. Sin embargo, los fármacos no mostraron curar las lesiones cutáneas causadas por el parásito. La optimización del esquema de tratamiento con NE-FtAlCl/PM+TFD es recomendable.Leishmaniasis is a metaxenic disease whose vector (Lutzomyia) transmits the disease by penetrating the skin of the mammalian host and introducing the protozoa of leishmania, who depending on the species give way to a specific type of clinical manifestation, with varying degrees of severity. Although there are differents treatments (Pentostam®, Glucantime®, pentamidine, amphotericin B and miltefosine), multiple challenges are still unresolved: route of administration, liver and kidney toxic effects, treatment failure, drug resistance, immunological conditions of patient, socioeconomic surroundings, chronicity of the lesions and parasite species. For this, the standardization of the cutaneous leishmaniasis model in BALB/c mice was evaluated using two inoculated in two anatomical sites of infection (plantar pad and tail base). Subsequently, the effectiveness of NE-FtAlCl / PM in two experimental models was evaluated. Photodynamic therapy was applied in the groups treated with the photosensitizer using LED light. Clinical and parasitological effectiveness, as well as acute toxicity related to hematological and biochemical parameters, was tested. The treatment was ineffective in curing skin lesions by L. (V.) braziliensis in BALB/c mice. However, the results were similar to those obtained with the control group treated with Glucantime (20mg/Kg/day). Additionally, in the model with ulcerated skin lesion, a decrease in ulcer size was observed in mice treated with NE-FtAlCl/PM + TFD. No systemic toxic effects of the treatment were observed. This study is the first to evaluate the combination of two bioactive drugs against Leishmania spp in the same nanocarrier. However, the drugs were not shown to cure the skin lesions caused by the parasite. The optimization of the treatment scheme with NE-FtAlCl / PM + TFD is recommendedINTRODUCCIÓN .................................................................................................................................. 1 1.1 LEISHMANIASIS: Generalidades y epidemiología .......................................................... 3 1.1.1. Leishmania spp: ciclo de vida .......................................................................................... 5 1.1.2. Transmisión ...................................................................................................................... 9 1.1.3. Reservorios ..................................................................................................................... 11 1.1.4. Patogénesis ..................................................................................................................... 12 1.1.5. Manifestaciones clínicas................................................................................................. 15 1.1.6. Tratamientos Convencionales ........................................................................................ 21 1.1.7. Tratamientos no Convencionales ................................................................................... 32 1.1.8. Nanobiotecnología aplicada en farmacología ............................................................... 40 2. OBJETIVOS ................................................................................................................................ 43 2.1 OBJETIVO GENERAL .................................................................................................... 43 2.2 OBJETIVOS ESPECÍFICOS ........................................................................................... 43 3. MATERIALES Y MÉTODOS .................................................................................................... 44 3.1 MATERIALES ................................................................................................................. 44 3.1.1. Animales ......................................................................................................................... 44 3.1.2. Cepa de Leishmania ....................................................................................................... 44 3.1.3. Fotosensibilizador y medicamentos ................................................................................ 44 3.1.4. Preparación sistema de nanoemulsión ........................................................................... 45 3.1.5. Sistema de irradiación .................................................................................................... 45 3.2 MÉTODOS ....................................................................................................................... 46 3.2.1. Estandarización del modelo de infección ....................................................................... 46 3.2.2. Modelo animal de Leishmaniasis cutánea ...................................................................... 47 3.2.3. Consideraciones éticas ................................................................................................... 52 3.2.4. Análisis de datos ............................................................................................................. 53 4. RESULTADOS ........................................................................................................................... 54 4.1. Estandarización del modelo de infección ......................................................................... 54 4.1.1. Leishmaniasis cutánea experimental en almohadilla de pata trasera derecha .............. 54 4.1.2. Leishmaniasis cutánea experimental en base de la cola ................................................ 62 4.1.3. Evaluación de parámetros de toxicidad ......................................................................... 64 4.2. Modelo experimental de Leishmaniasis cutánea para la evaluación de la efectividad de la TFD y paramomicina ..................................................................................................................... 70 4.2.1. Modelo de LC murina en almohadilla plantar derecha: evaluación de la eficacia clínica70 4.2.2. Modelo de LC murina en almohadilla plantar derecha: evaluación de la eficacia parasitológica ........................................................................................................................... 73 4.2.3. Modelo de LC murina en almohadilla plantar derecha: evaluación de la toxicidad ..... 76 4.2.4. Modelo de LC murina en almohadilla plantar derecha: Biodistribución FtAlCl y PM . 81 4.2.5. Modelo de LC murina en base de la cola: evaluación de la eficacia clínica ................. 81 5. DISCUSIÓN ................................................................................................................................ 89 6. CONCLUSIONES ............................................................................................................................ 99 7. RECOMENDACIONES ................................................................................................................. 100 8. REFERENCIAS .............................................................................................................................. 101Ej. 1MaestríaMagister en Investigación en enfermedades Infecciosa
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