Letter from [Alice Spencer Jones] to John Muir, 1910 Sep 2.

[1][letterhead]Sept 2.— 1910—Dear Good Man,Mr John Muir.—I was just delighted to get your letter. Oh so often we talk about you- and wonder where you are, and what you have been about.—Uncle is now on Mt Wilson with other stars, he will return this (Friday Evening)- He went by auto yesterday, and will bring down a load for dinner at 325 - then they take the 8 P.M train North, Prof W.W. Campbell, among them04866 [2][letterhead][to?] make preparations for the visit of the Notables to his observatory at Mt HamiltonI am so glad aunt [Katharine?] returns so soon, and that you too are soon coming Home, as the old song says- what a meeting that will be when all the saints get Home —I am taking care of the Hooker office for a little while, while Mr Burlew, goes to jury Duty—Later. Sept. 3. I was interrupted in my office work- and now finish- Uncle returned full of high04866 [3][letterhead]spirits from the mountain top- for dinner was served and the gentlemen guests - have gone on their way - rejoicing -Uncle has just read your letter and says, isent that a fine letter ? He send his regards to you Genial John of Mountains. and says Come [on?] - that John of stars will meet John of Mountains when ever you sing out. Mrs Stott is here for Luncheon and sends greetings.Dont stay too long - but come Home Soon- so saysThe Lark.OVER. 04866 [4]The scientists were all intensely interested in uncles Cabinet of Slides — Prof. H. H. [illegible] of Oxford Eng- said — Mr Hooker there is not an observatory in the whole world that can give the fine display of the Heavens, that you can in this room

Letter from [Alice Spencer Jones] to John Muir, 1910 Dec 6.

[4]also greet you — if here.And I- why I would pick out the biggest red apple I could find and pare & eat it with you — and you would give me sugar plums to keep me sweet. We are glad your heart is still in the southland — where there are roses, and muffins yes - and Larks[1]Dec 6 - 1910.325 W. ADAMS STREETLOS ANGELESMy dear good friendJohn Muir.—I, Hark the Lark Jones, miss you oh so much — for I have no one to adorn with the symbol of their officeWe speak about you daily - yea - meally04908 [2]For it is when we assemble around Uncles hospitable table that we miss the absent onesOur house is decorated with your pretty greens - we all enjoy them. Uncle was pleased to receive your kindly message, and also the [accompanying?] document - He says, [accept?] please [3]my greetings and sincere thanks - and also adds - The irreverent wretch salutes him - Fanny sits by reading and says tell you she is here and she wishes you were also -Aunt Katherine is with Wanda & Ellie for [illegible] — and Fred - at the Masons - They woul

Letter from Alice [Spencer Jones] to John Muir, 1910 Sep 8.

325 West AdamsLos Angnles.CalSept. 8, 1 91 0My dear Mr Muir,I am writing right away to thank you for that beautiful snow flownr and your own tribute to thorn. It is so pretty and I asaura you that I treasure it.We are having some glorious days and we are enjoying Just that taste of September that comes to us. It always msana picking apples and and husking oorn to me who have lived so long in Now England.Uncle is to entertain the Board of the Academy of Science to [illegible] tonight for dinner and so there is much going on in our house. He has had a most splandid time With all these great men,\u27 and I have too, for I have kept my eyes and ears- openand feel I am getting very well informed on things Celestial.It will Seem so good to see you all hers again and remember you are not to write and tell us now that you cannot come for that will nevar accepted by this family. You see that my little Muggins is not doing her prettiest today, for I had to put on a new ribbon and it is impossible to get her tonad down, but she is a darling and a very constant Companion. Nothfield Hall is to open with enthueieem. the girls are delighted with the Muir Books are waiting now to have your name in than. Cilia\u27s school is also opening up well,they have many applications and things look very favorable tbr a very prospnrous year.Uncle ia sitting on the poorch, and aanda greetings to you. He goes this afternoon with a company of gentlemen to call upon some representatives of the Smithsonian Institute* who are in our City.I hope that you hear from daughter Helen that she is wall, and with kindest regards to her, ted io manyythanks to you,Verysinoerely, 0487

Letter from [Alice Spencer H.] Jones to [John Muir], 1913 May 16.

[4]trees that I should put in - If you would, I should be so glad - for they would certainly be real aristocrats. I want good things but know so little - Will write again, when get in town. Fred sends his best regrads and I my love-Hark the Lark Jones[in margin: Hooker f[illegible]][1]Sierra MadreMay 16. 1913.My dear Good Friend,So very much do I wish to thank you for the beautiful new Book - It is the very best of all! For it is you, just you!05451 [2]Everybody is going to love it. - especially the children.It brings to Fred and me so very many happy memories of those blissful other days when we were all together among the roses.I am in the[3]country today- and this the only pen.-.We have four acres - a little house under a wonderful live oak tree - surrounded by orange trees.We want some fine trees. Sometime please make me a list of som

A structure-guided molecular chaperone approach for restoring the transcriptional activity of the p53 cancer mutant Y220C

Aim: The p53 cancer mutation Y220C creates a conformationally unstable protein with a unique elongated surface crevice that can be targeted by molecular chaperones. We report the structure-guided optimization of the carbazole-based stabilizer PK083. Materials & methods: Biophysical, cellular and x-ray crystallographic techniques have been employed to elucidate the mode of action of the carbazole scaffolds. Results: Targeting an unoccupied subsite of the surface crevice with heterocycle-substituted PK083 analogs resulted in a 70-fold affinity increase to single-digit micromolar levels, increased thermal stability and decreased rate of aggregation of the mutant protein. PK9318, one of the most potent binders, restored p53 signaling in the liver cancer cell line HUH-7 with homozygous Y220C mutation. Conclusion: The p53-Y220C mutant is an excellent paradigm for the development of mutant p53 rescue drugs via protein stabilization. Similar rescue strategies may be applicable to other cavity-creating p53 cancer mutations

Manipulating the ABCs of self-assembly via low-χ block polymer design

Block polymer self-assembly typically translates molecular chain connectivity into mesoscale structure by exploiting incompatible blocks with large interaction parameters (χ_ij). In this article, we demonstrate that the converse approach, encoding low-χ interactions in ABC bottlebrush triblock terpolymers (χ_(AC) ≲ 0), promotes organization into a unique mixed-domain lamellar morphology, which we designate LAM_P. Transmission electron microscopy indicates that LAM_P exhibits ACBC domain connectivity, in contrast to conventional three-domain lamellae (LAM_3) with ABCB periods. Complementary small-angle X-ray scattering experiments reveal a strongly decreasing domain spacing with increasing total molar mass. Self-consistent field theory reinforces these observations and predicts that LAM_P is thermodynamically stable below a critical χ_(AC), above which LAM_3 emerges. Both experiments and theory expose close analogies to ABA′ triblock copolymer phase behavior, collectively suggesting that low-χ interactions between chemically similar or distinct blocks intimately influence self-assembly. These conclusions provide fresh opportunities for block polymer design with potential consequences spanning all self-assembling soft materials

Acu-TENS Reduces Breathlessness during Exercise in People with Chronic Obstructive Pulmonary Disease

Background. Exertional dyspnoea limits level of physical activity in people with Chronic Obstructive Pulmonary Disease (COPD). This randomized, double-blinded, crossover study evaluated the effect of Acu-TENS, application of Transcutaneous Electrical Nerve Stimulation on acupoints, on breathlessness during exercise in people with COPD. Methods. Twenty-one participants, mean% predicted FEV1  50±21%, attended assessment followed by two intervention days, one week apart. On each intervention day, participants performed two endurance shuttle walk tests (ESWT) (Walk 1 and Walk 2). Walk 1 was performed without intervention and Walk 2 was performed with either Acu-TENS or Sham-TENS, in random order, for 45 minutes before and during Walk 2. Duration of each ESWT and dyspnoea score at isotime of Walk 1 and Walk 2 on each intervention day were compared. Between-group differences in ESWT duration and isotime dyspnoea were also compared. Results. At isotime of Walk 1 and Walk 2, Acu-TENS showed significant reduction in dyspnoea of −0.8 point (95% CI −0.2 to −1.4) but not in Sham-TENS [0.1 point (95% CI −0.4 to 0.6)]. Compared to Sham-TENS, Acu-TENS showed significant reduction in dyspnoea of −0.9 point (95% CI −0.2 to −1.6) while no between-group significance was found in ESWT duration. Conclusion. Acu-TENS alleviated dyspnoea during walking in people with COPD but did not increase walking duration

Pojamide: An HDAC3-selective ferrocene analogue with remarkably enhanced redox-triggered ferrocenium activity in cells.

A ferrocene containing ortho-aminoanilide, N1-(2-aminophenyl)-N8-ferrocenyloctanediamide, 2b (Pojamide) displayed nanomolar potency vs. HDAC3. Compared to RGFP966, a potent and selective HDAC3 inhibitor, Pojamide displayed superior activity in HCT116 colorectal cancer cell invasion assays; however, TCH106 and Romidepsin, potent HDAC1 inhibitors, outperformed Pojamide in cellular proliferation and colony formation assays. Together, these data suggest that HDAC 1 & 3 inhibition is desirable to achieve maximum anti-cancer benefits. Additionally, we explored Pojamide-induced redox-pharmacology. Indeed, treating HCT116 cells with Pojamide, SNP (sodium nitroprusside) and glutathione (GSH) led to greatly enhanced cytotoxicity and DNA damage attributed to activation to an Fe(III) species

The 1.6 micron near infrared nuclei of 3C radio galaxies: Jets, thermal emission or scattered light?

Using HST NICMOS 2 observations we have measured 1.6-micron near infrared nuclear luminosities of 100 3CR radio galaxies with z<0.3, by modeling and subtracting the extended emission from the host galaxy. We performed a multi-wavelength statistical analysis (including optical and radio data) of the properties of the nuclei following classification of the objects into FRI and FRII, and LIG (low-ionization galaxies), HIG (high-ionization galaxies) and BLO (broad-lined objects) using the radio morphology and optical spectra, respectively. The correlations among near infrared, optical, and radio nuclear luminosity support the idea that the near infrared nuclear emission of FRIs has a non-thermal origin. Despite the difference in radio morphology, the multi-wavelength properties of FRII LIG nuclei are statistically indistinguishable from those of FRIs, an indication of a common structure of the central engine. All BLOs show an unresolved near infrared nucleus and a large near infrared excess with respect to FRII LIGs and FRIs of equal radio core luminosity. This requires the presence of an additional (and dominant) component other than the non-thermal light. Considering the shape of their spectral energy distribution, we ascribe the origin of their near infrared light to hot circumnuclear dust. A near infrared excess is also found in HIGs, but their nuclei are substantially fainter than those of BLO. This result indicates that substantial obscuration along the line-of-sight to the nuclei is still present at 1.6 micron. Nonetheless, HIGs nuclei cannot simply be explained in terms of dust obscuration: a significant contribution from light reflected in a circumnuclear scattering region is needed to account for their multiwavelength properties.Comment: 20 pages, 16 figures. Accepted for publication on Ap

At the extremes of exclusion: Deportation, detention and dispersal

Deportation, detention and dispersal have formed an occasional part of Britain's migration regime throughout the twentieth century, though they tended to be used in response to particular events or “crises”. By the end of the twentieth century, however, deportation, detention and, most recently, dispersal have become “normalized”, “essential” instruments in the ongoing attempt to control or manage immigration to Britain. This article outlines the use of detention, deportation and dispersal in the twentieth century exploring how they have evolved and then become an integral part of the migration regime into the twenty-first century. Where appropriate, British practices are compared with those of its European neighbours, where to differing degrees, deportation, detention and dispersal have also become everyday practices. In examining these practices in Britain, we consider the rationale and stated aims of their employment, as well as describing some of the consequences, where known, of detention, deportation and dispersal