Letter from Pelham W. Ames to John Muir, 1892 Feb 12.

Prof. John Muir.My dear Sir.President Eliot of Harvard is expected to be in this city next month, and the Harvard Club will entertain him at dinner probably on Tuesday March 15th. – Certainly about that date. If you can arrange to be in town at about that time, we shall hope to have the 01555pleasure of seeing you on that occasion. and I will send you a more formal and exact invitation when our arrangements are perfected. If you can come, you will, I hope, be writing to address the Club on any subject you may prefer. Hoping for a favorable reply.I am yours very trulyPelham W. Ames516 California St.President H[illegible] ClubFeb 12/9

Letter from Pelham W. Ames to John Muir, 1892 Mar 14.

Prof. John Muir.My dear Sir.The Harvard Club of San Francisco request the pleasure of your company at a dinner to be given to Charles [N.?] Eliot, President of Harvard University, at the Palace Hotel, on Tuesday March 22.d – at half past 6 o’clock.Yours SincerelyPelham [N.?] AmesPresident of the Harvard Club.March 14.0156

Accelerometry For Paddling And Rowing

In paddling and rowing, analysis of the acceleration, velocity and impulse of the system (equipment and athlete) can aid in the appraisal of the stroke (technique) and the usefulness of equipment as it relates to each performer. To this point in time, the primary source of analysis has been through the use of cinema and video. Recently at the Sport Science Laboratory, Dalhousie University a convenient method of obtaining on-water acceleration data has been developed. The triaxial g analyst (Valentine Research Inc.), although created specifically for use in land vehicles, can record the horizontal linear acceleration, horizontal lateral acceleration and provide a friction profile of any moving aquatic craft. Synchronization with video allows the coach and athlete to analyze data of one stroke, or a series of strokes, or a complete race. Acceleration data from the g-analyst can be transferred to virtually any PC, and programs easily written to determine velocity and impulse. The g analyst and power source apparatus is light (l kg), easy to handle, and relatively inexpensive. Little room is required to house the apparatus and it does not interfere with the athletes in the canoe, kayak, rowing shell, or scull. Onwater accelerometry using the g analyst may prove to be an important analytical tool for detection of movement faults and for matching equipment to athlete(s) in paddling and rowing

Pharmaceutical treatments to prevent recurrence of endometriosis following surgery:a model-based economic evaluation

OBJECTIVE: Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and 'no treatment' to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation.METHODS: We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported.RESULTS: On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required.CONCLUSIONS: There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.</p

Requirement of a Membrane Potential for the Posttranslational Transfer of Proteins into Mitochondsria

Posttranslational transfer of most precursor proteins into mitochondria is dependent on energization of the mitochondria. Experiments were carried out to determine whether the membrane potential or the intramitochondrial ATP is the immediate energy source. Transfer in vitro of precursors to the ADP/ATP carrier and to ATPase subunit 9 into isolated Neurospora mitochondria was investigated. Under conditions where the level of intramitochondrial ATP was high and the membrane potential was dissipated, import and processing of these precursor proteins did not take place. On the other hand, precursors were taken up and processed when the intramitochondrial ATP level was low, but the membrane potential was not dissipated. We conclude that a membrane potential is involved in the import of those mitochondrial precursor proteins which require energy for intracellular translocatio

Cell-Free Synthesis of the Mitochondrial ADP/ATP Carrier Protein of Neurospora crassa

ADP/ATP carrier protein was synthesized in heterologous cell-free systems programmed with Neurospora poly(A)-containing RNA and homologous cell-free systems from Neurospora. The apparent molecular weight of the product obtained in vitro was the same as that of the authentic mitochondrial protein. The primary translation product obtained in reticulocyte lysates starts with formylmethionine when formylated initiator methionyl-tRNA (fMet-tRNAfMet) was present. The product synthesized in vitro was released from the ribosomes into the postribosomal supernatant. The evidence presented indicates that the ADP/ATP carrier is synthesized as a polypeptide with the same molecular weight as the mature monomeric protein and does not carry an additional sequence

Different Transport Pathways of Individual Precursor Proteins in Mitochondria

Transport of mitochondrial precursor proteins into mitochondria of Neurospora crassa was studied in a cellfree reconstituted system. Precursors were synthesized in a reticulocyte lysate programmed with Neurospora mRNA and transported into isolated mitochondria in the absence of protein synthesis. Uptake of the following precursors was investigated: apocytochrome c, ADP/ATP carrier and subunit 9 of the oligomycin-sensitive ATPase. Addition of high concentrations of unlabelled chemically prepared apocytochrome c (1–10 μM) inhibited the appearance in the mitochondrial of labelled cytochrome c synthesized in vitro because the unlabelled protein dilutes the labelled one and because the translocation system has a limited capacity [apparent V is 1–3 pmol × min−1× (mg mitochondrial protein)−1]. Concentrations of added apocytochrome c exceeding the concentrations of precursor proteins synthesized in vitro by a factor of about 104 did not inhibit the transfer of ADP/ATP carrier or ATPase subunit 9 into mitochondria. Carbonylcyanide m-chlorophenylhydrazone, an uncoupler of oxidative phosphorylation, inhibited transfer in vitro of ADP/ATP carrier and of ATPase subunit 9, but not of cytochrome c. These findings suggest that cytochrome c and the other two proteins have different import pathways into mitochondria. It can be inferred from the data presented that different 'receptors' on the mitochondrial surface mediate the specific recognition of precursor proteins by mitochondria as a first step in the transport process

Import of cytochrome c into mitochondria

The import of cytochrome c into mitochondria can be resolved into a number of discrete steps. Here we report on the covalent attachment of heme to apocytochrome c by the enzyme cytochrome c heme lyase in mitochondria from Neurospora crassa. A new method was developed to measure directly the linkage of heme to apocytochrome c. This method is independent of conformational changes in the protein accompanying heme attachment. Tryptic peptides of [35S]cysteine-labelled apocytochrome c, and of enzymatically formed holocytochrome c, were resolved by reverse-phase HPLC. The cysteine-containing peptide to which heme was attached eluted later than the corresponding peptide from apocytochrome c and could be quantified by counting 35S radioactivity as a measure of holocytochrome c formation. Using this procedure, the covalent attachment of heme to apocytochrome c, which is dependent on the enzyme cytochrome c heme lyase, could be measured. Activity required heme (as hemin) and could be reversibly inhibited by the analogue deuterohemin. Holocytochrome c formation was stimulated 5–10-fold by NADH > NADPH > glutathione and was independent of a potential across the inner mitochondrial membrane. NADH was not required for the binding of apocytochrome c to mitochondria and was not involved in the reduction of the cysteine thiols prior to heme attachment. Holocytochrome c formation was also dependent on a cytosolic factor that was necessary for the heme attaching step of cytochrome c import. The factor was a heat-stable, protease-insensitive, low-molecular-mass component of unknown function. Cytochrome c heme lyase appeared to be a soluble protein located in the mitochondrial intermembrane space and was distinct from the previously identified apocytochrome c binding protein having a similar location. A model is presented in which the covalent attachment of heme by cytochrome c heme lyase also plays an essential role in the import pathway of cytochrome c