First Retreat Parade being presented to Col. F.C. Rogers by Student-Major Alexander

To left of Col.-Major Vollrath, executive, Lt. C.D. Vaughan, adjutant, Major Carl K. Hart, Lt. Ralph L. Bergh, and Harry H. Wilson.

A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a potent new antiinflammatory drug

Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of compounds is synthesized for research purposes on milligram scales by solid-phase methods, but if the potential of macrocyclic peptidomimetics is to be realized, low-cost larger scale solution-phase syntheses need to be devised and optimized to provide sufficient quantities for preclinical, clinical, and commercial uses. Here, we describe a cheap, medium-scale, solution-phase synthesis of the first reported highly potent, selective, and orally active antagonist of the human C5a receptor. This compound, Ac-Phe[Orn-Pro-D-Cha-Trp-Arg], known as 3D53, is a macrocyclic peptidomimetic of the human plasma protein C5a and displays excellent antiinflammatory activity in numerous animal models of human disease. In a convergent approach, two tripeptide fragments Ac-Phe-Orn-(Boc)-Pro-OH and H-D-Cha-Trp(For)-Arg-OEt were first prepared by high-yielding solution-phase couplings using a mixed anhydride method before coupling them to give a linear hexapeptide which, after deprotection, was obtained in 38% overall yield from the commercially available amino acids. Cyclization in solution using BOP reagent gave the antagonist in 33% yield (13% overall) after HPLC purification. Significant features of the synthesis were that the Arg side chain was left unprotected throughout, the component Boe-D-Cha-OH was obtained very efficiently via hydrogenation Of D-Phe with PtO2 in TFA/water, the tripeptides were coupled at the Pro-Cha junction to minimize racemization via the oxazolone pathway, and the entire synthesis was carried out without purification of any intermediates. The target cyclic product was purified (>97%) by reversed-phase HPLC. This convergent synthesis with minimal use of protecting groups allowed batches of 50100 g to be prepared efficiently in high yield using standard laboratory equipment. This type of procedure should be useful for making even larger quantities of this and other macrocyclic peptidomimetic drugs.

Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)1, 2. These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case–control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer’s disease in seven independent case–control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer’s disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer’s disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer’s disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

Les plateaux de carrière : élaboration d'une grille afin d'identifier le plateau de carrière et établissement des liens avec la congruence des intérêts

Cette étude vise à établir des liens entre la situation de plafonnement de carrière et l'incongruence vocationnelle. De façon plus spécifique, il s'agit de vérifier, au moyen d'une étude, la relation entre la situation de plafonnement de carrière, largement étudiée jusqu'à présent par plusieurs auteurs et la congruence des intérêts. Ces auteurs s'interrogent sur la question des ressources humaines (tels par exemple Tremblay, Cardinal, Lamoureux, Hoyt, Charest) de laquelle, nous tenterons d'établir la congruence des intérêts professionnels en lien avec la typologie de Holland. Holland prévoit (6) six types: Réaliste (R), Investigateur (I), Artistique (A), Social (S), Entreprenant (E), et Conventionnel (C). Ces types peuvent être octroyés sur deux plans distinctifs. Il est en effet possible de d��finir le patron typologique sur les plans environnemental et individuel. C'est à partir de ces deux patrons typologiques, constitués de trois lettres, qu'on établira la correspondance entre les données provenant de l'individu et de l'environnement. C'est donc à partir de celles-ci que l'on peut calculer le niveau de congruence, en appliquant l'indice de lachan qui constitue une mesure de congruence. Deux instruments de mesure inclus dans une batterie d'inventaires seront donc proposés à soixante travailleurs de la Ville de Montréal. Il s'agit premièrement d'une grille d'évaluation élaborée à partir de critères spécifiques issus d'enquêtes différentes liées au plafonnement de carrière. L'instrument de mesure comporte sept échelles : le temps et l'âge, des informations relatives au travail, le positionnement par rapport aux collègues de travail, l'impact du changement sur l'individu, les rémunérations et • conditions salariales, la formation, les intérêts et loisirs reliées à la profession. Le plafonnement de carrière tel que nous le percevons, constitue un concept complexe nécessitant une vision systémique ; c'est-à-dire que le problème doit être consid��ré dans son ensemble, à savoir l'individu et son environnement. La deuxième étape consiste en la passation de l'inventaire des préférences professionnelles, abrégé (I.P.P.A.). Pour chacune des personnes évaluées, un patron typologique de l'environnement professionnel sera établi à partir du Codes Holland pour C. C. D. P. Les résultats obtenus par l'intermédiaire de l'I.P.P A. et transférés en types par l'intermédiaire du Guide : Codes Holland pour C.C.D.P., seront soumis à l'indice de lachan qui évalue la congruence entre deux séries de données. Le score du niveau de congruence sera par la suite confronté au score obtenu par l'intermédiaire de la grille/questionnaire par une simple corrélation. De cette façon, nous pourrons établir les liens et ainsi vérifier l'hypothèse de recherche. Cette recherche se propose donc d'identifier des plateaux de carrière à l'aide de la grille/questionnaire, pour ensuite vérifier s'il existe véritablement des liens entre la situation de plafonnement de carrière et la congruence d'intérêts. Cette d��marche tend à confirmer l'hypothèse suivante : l'incongruence entre les intérêts individuels et ceux du milieu est responsable du plafonnement de carrière. En ce sens, elle entraîne entre autres une d��motivation de l'individu à s'impliquer dans son travail, à mettre ses connaissances à jour. La présence du plafonnement de carrière peut d��courager l'organisation et l'entourage immédiat de travail à justifier un accroissement des responsabilités ou toutes autres mobilités. Cette situation peut entraîner un malaise important tant chez l'employé que dans l'environnement de travail. La méthodologie proposée permet d'envisager la problématique sous différents angles, • étant donné que le plafonnement de carrière est à la fois la cause et l'effet d'un ensemble de facteurs difficilement mesurables.

Frecuencia, manifestaciones clínicas y de laboratorio de infecciones respiratorias en pacientes con V.I.H./S.I.D.A. del Hospital Vicente Corral Moscoso de la ciudad de Cuenca período 2001-2007

Estudio descriptivo, se revisó y recolectó la información necesaria obtenidas de las historias clínicas de todos los pacientes diagnosticados de V.I.H.(+) en el departamento de clínica. Para el análisis estad��stico: se utilizó los programas S.P.S.S. versión 10.0 para Windows y Microsoft Excel 2007, en la presentación de los datos se utilizó cuadros y gráficos en correspondencia con el tipo de variable y asociación que se deseó. Resultados: de un total de 7709 hospitalizados, 200 pacientes se encontraron infectados con V.I.H.(+), de los cuales 81 pacientes presentaron afección respiratoria, el 78de estos correspondió a los hombres, la mayoría se encontró entre los 26-35 años, la mortalidad se presentó en el 27,16; en los datos demográficos se encontró que los residentes de la sierra, católicos, solteros, un tipo de educación secundaria, la actividad manual sobresalían en los grupos de los pacientes; las principales patologías encontradas fueron Candidiasis Orofaríngea, Neumonía por P. Jirovecii, Tuberculosis Pulmonar y Neumonía Adquirida en la Comunidad. Se encontraron patrones en Radiología y Linfocitos CD4+ según principales patologías respiratorias. Conclusiones: el sexo masculino es el más frecuente dentro de los 81 pacientes V.I.H. que presentaron patologías respiratorias en el área de clínica, donde el sexo masculino fue el más frecuente, se presentó mortalidad alta en las primeras dos semanas de hospitalización, los datos demográficos son semejantes a nuestra región, la Candidiasis Oral y neumonía por P. Jirovecii fueron las principales afecciones en vías aéreas superior e inferior respectivamente, se encontró relación entre características radiológicas y linfocitos C.D.4+ asociadas con infecciones respiratorias en pacientes con VIH/SIDA

Un aporte a la comprensión de las estrategias emergentes en las organizaciones a través del concepto de improvisación y la metáfora musical

Este trabajo se inscribe en uno de los grandes campos de los estudios organizacionales: la estrategia. La perspectiva clásica en este campo promovió la idea de que proyectarse hacia el futuro implica diseñar un plan (una serie de acciones deliberadas). Avances posteriores mostraron que la estrategia pod��a ser comprendida de otras formas. Sin embargo, la evolución del campo privilegió en alguna medida la mirada clásica estableciendo, por ejemplo, múltiples modelos para ‘formular’ una estrategia, pero dejando en segundo lugar la manera en la que esta puede ‘emerger’. El propósito de esta investigación es, entonces, aportar al actual nivel de comprensión respecto a las estrategias emergentes en las organizaciones. Para hacerlo, se consideró un concepto opuesto —aunque complementario— al de ‘planeación’ y, de hecho, muy cercano en su naturaleza a ese tipo de estrategias: la improvisación. Dado que este se ha nutrido de valiosos aportes del mundo de la música, se acudió al saber propio de este dominio, recurriendo al uso de ‘la metáfora’ como recurso teórico para entenderlo y alcanzar el objetivo propuesto. Los resultados muestran que 1) las estrategias deliberadas y las emergentes coexisten y se complementan, 2) la improvisación está siempre presente en el contexto organizacional, 3) existe una mayor intensidad de la improvisación en el ‘como’ de la estrategia que en el ‘qué’ y, en oposición a la idea convencional al respecto, 4) se requiere cierta preparación para poder improvisar de manera adecuada.

Beam-energy Dependence Of The Directed Flow Of Protons, Antiprotons, And Pions In Au+au Collisions.

Rapidity-odd directed flow (v1) measurements for charged pions, protons, and antiprotons near midrapidity (y=0) are reported in sNN=7.7, 11.5, 19.6, 27, 39, 62.4, and 200 GeV Au+Au collisions as recorded by the STAR detector at the Relativistic Heavy Ion Collider. At intermediate impact parameters, the proton and net-proton slope parameter dv1/dy|y=0 shows a minimum between 11.5 and 19.6 GeV. In addition, the net-proton dv1/dy|y=0 changes sign twice between 7.7 and 39 GeV. The proton and net-proton results qualitatively resemble predictions of a hydrodynamic model with a first-order phase transition from hadronic matter to deconfined matter, and differ from hadronic transport calculations.

Impaired Compensatory Beta-cell Function And Growth In Response To High-fat Diet In Ldl Receptor Knockout Mice.

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr-/- mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr-/- mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr-/- mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr-/- mice showed no significant changes in beta-cell mass, but lower islet-duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr-/- mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion.

The Effect Of Pelvic Floor Muscle Training Alone Or In Combination With Electrostimulation In The Treatment Of Sexual Dysfunction In Women With Multiple Sclerosis.

Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS) patients and pelvic floor muscles (PFMs) play an important role in the sexual function of these patients. The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS. Thirty MS women were randomly allocated to one of three groups: pelvic floor muscle training (PFMT) with electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS) (Group III). Assessments, before and after the treatment, included: PFM function, PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and the Female Sexual Function Index (FSFI) questionnaire. After treatment, all groups showed improvements in all domains of the PERFECT scheme. PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II. All groups improved in arousal, lubrication, satisfaction and total score domains of the FSFI questionnaire. This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD.

Combined Analysis Of νμ Disappearance And νμ→νe Appearance In Minos Using Accelerator And Atmospheric Neutrinos.

We report on a new analysis of neutrino oscillations in MINOS using the complete set of accelerator and atmospheric data. The analysis combines the ν(μ) disappearance and ν(e) appearance data using the three-flavor formalism. We measure |Δm(32)(2)| = [2.28-2.46] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.35-0.65 (90% C.L.) in the normal hierarchy, and |Δm(32)(2)| = [2.32-2.53] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.34-0.67 (90% C.L.) in the inverted hierarchy. The data also constrain δ(CP), the θ(23} octant degeneracy and the mass hierarchy; we disfavor 36% (11%) of this three-parameter space at 68% (90%) C.L.

Compartment Syndrome After South American Rattlesnake (crotalus Durissus Terrificus) Envenomation.

In order to report the outcome of a patient who developed compartment syndrome after South American rattlesnake (Crotalus durissus terrificus) envenomation, confirmed by subfascial pressure measurement and magnetic resonance imaging (MRI). A 63-year-old male was admitted 1 h after being bitten on the right elbow by a large snake, which was not brought for identification. Physical and laboratory features upon admission revealed two fang marks, local tense swelling, paresthesia, intense local pain, hypertension, coagulopathy, and CK = 1530 U/L (RV < 170 U/L). The case was initially treated with bothropic antivenom (80 mL, intravenously), with no improvement. Evolution within 13-14 h post-bite revealed generalized myalgia, muscle weakness, palpebral ptosis, and severe rhabdomyolysis (CK = 126,160 U/L) compatible with envenoming by C. d. terrificus. The patient was then treated with crotalic antivenom (200 mL, intravenously), fluid replacement, and urine alkalinization. Twenty-four-hour post-bite MRI showed marked muscular edema in the anterior compartment of the right forearm, with a high subfascial pressure (40 mmHg) being detected 1 h later. ELISA of a blood sample obtained upon admission, before antivenom infusion, revealed a high serum concentration of C. d. terrificus venom. No fasciotomy was performed and the patient was discharged seven days later without sequelae. Snakebite by C. d. terrificus with subfascial venom injection may lead to increased intracompartmental pressure.

Dielectron Mass Spectra From Au+au Collisions At √[s(nn)]=200 gev.

We report the STAR measurements of dielectron (e(+)e(-)) production at midrapidity (|y(ee)|<1) in Au+Au collisions at √[s(NN)]=200  GeV. The measurements are evaluated in different invariant mass regions with a focus on 0.30-0.76 (ρ-like), 0.76-0.80 (ω-like), and 0.98-1.05 (ϕ-like)   GeV/c(2). The spectrum in the ω-like and ϕ-like regions can be well described by the hadronic cocktail simulation. In the ρ-like region, however, the vacuum ρ spectral function cannot describe the shape of the dielectron excess. In this range, an enhancement of 1.77±0.11(stat)±0.24(syst)±0.33(cocktail) is determined with respect to the hadronic cocktail simulation that excludes the ρ meson. The excess yield in the ρ-like region increases with the number of collision participants faster than the ω and ϕ yields. Theoretical models with broadened ρ contributions through interactions with constituents in the hot QCD medium provide a consistent description of the dilepton mass spectra for the measurement presented here and the earlier data at the Super Proton Synchrotron energies.

Beam-energy Dependence Of Charge Separation Along The Magnetic Field In Au+au Collisions At Rhic.

Local parity-odd domains are theorized to form inside a quark-gluon plasma which has been produced in high-energy heavy-ion collisions. The local parity-odd domains manifest themselves as charge separation along the magnetic field axis via the chiral magnetic effect. The experimental observation of charge separation has previously been reported for heavy-ion collisions at the top RHIC energies. In this Letter, we present the results of the beam-energy dependence of the charge correlations in Au+Au collisions at midrapidity for center-of-mass energies of 7.7, 11.5, 19.6, 27, 39, and 62.4 GeV from the STAR experiment. After background subtraction, the signal gradually reduces with decreased beam energy and tends to vanish by 7.7 GeV. This implies the dominance of hadronic interactions over partonic ones at lower collision energies.

Measurement Of Longitudinal Spin Asymmetries For Weak Boson Production In Polarized Proton-proton Collisions At Rhic.

We report measurements of single- and double-spin asymmetries for W^{±} and Z/γ^{*} boson production in longitudinally polarized p+p collisions at sqrt[s]=510  GeV by the STAR experiment at RHIC. The asymmetries for W^{±} were measured as a function of the decay lepton pseudorapidity, which provides a theoretically clean probe of the proton's polarized quark distributions at the scale of the W mass. The results are compared to theoretical predictions, constrained by polarized deep inelastic scattering measurements, and show a preference for a sizable, positive up antiquark polarization in the range 0.05

Beam Energy Dependence Of Moments Of The Net-charge Multiplicity Distributions In Au+au Collisions At Rhic.

We report the first measurements of the moments--mean (M), variance (σ(2)), skewness (S), and kurtosis (κ)--of the net-charge multiplicity distributions at midrapidity in Au+Au collisions at seven energies, ranging from sqrt[sNN]=7.7 to 200 GeV, as a part of the Beam Energy Scan program at RHIC. The moments are related to the thermodynamic susceptibilities of net charge, and are sensitive to the location of the QCD critical point. We compare the products of the moments, σ(2)/M, Sσ, and κσ(2), with the expectations from Poisson and negative binomial distributions (NBDs). The Sσ values deviate from the Poisson baseline and are close to the NBD baseline, while the κσ(2) values tend to lie between the two. Within the present uncertainties, our data do not show nonmonotonic behavior as a function of collision energy. These measurements provide a valuable tool to extract the freeze-out parameters in heavy-ion collisions by comparing with theoretical models.