225 research outputs found

    The Right to Vote

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    Originally published in 1965. The Right to Vote covers the immediate background, passage, and ratification of the Fifteenth Amendment. Gillette contends that the Fifteenth Amendment was intended to give voting rights to African Americans in the north, sidelining those in the south. African American suffrage, in other words, had the pragmatic effect of bringing power to the Republicans of the north. In short, the Fifteenth Amendment was not a radical document but rather was pushed by Republican moderates in an effort to consolidate their power

    Physics of windblown particles

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    A laboratory facility proposed for the Space Station to investigate fundamental aspects of windblown particles is described. The experiments would take advantage of the environment afforded in earth orbit and would be an extension of research currently being conducted on the geology and physics of windblown sediments on earth, Mars, and Venus. Aeolian (wind) processes are reviewed in the planetary context, the scientific rational is given for specific experiments to be conducted, the experiment apparatus (the Carousel Wind Tunnel, or CWT) is described, and a plan presented for implementing the proposed research program

    997-90 Right (RV) and Left Ventricular (LV) Geometry and Myocyte Contractile Processes with Dilated Cardiomyopathy (DCM): Disparity Between Myocyte Growth and β-Adrenergic Responsiveness

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    The progression of DCM has been assumed to be a homogenous process for both the RV and LV. However, this assumption has never been tested. Accordingly, we measured myocyte contractile performance (velocity of shortening, VELSHORT; percent shortening, PERSHORT) at baseline (BASE) and after β-adrenergic receptor stimulation (βAR, 25 nM isoproterenol) of isolated myocytes taken from the RV and LV of 5 pigs with pacing induced DCM (240 bpm, 3 weeks) and 5 control pigs (CON). RV and LV mass/body weight (MASS) and myocyte length and cross-sectional area (CSA) were also determined.CON-RVCON-LVDCM-RVDCM-LVVELSHORT-BASE (μm/s)90±5+50±148±2*,+32±1*VELSHORT-βAR (μm/s)206±8+150±5123±8*111±9*PERSHORT-BASE (%)5.8±0.2+4.6±0.13.1±0.1*,+2.2±0.1*PERSHORT-βAR (%)11.5±0.3+10.2±0.359±0.3*5.2±0.4*Length (μm)150±2+137±1179±2*,+173±2*CSA (μm2)176±4+362±8232±4*,+292±5*Mass (gm/kg)0.8±0.1+2.8±0.11.6±0.1*,+2.9±0.2+p<0.05 vs LV*p<005 vS CONIn controls, RV myocytes were longer and had a smaller CSA, but enhanced contractile performance at baseline and with β-adrenergic stimulation. With DCM, no LV hypertrophy occurred. In contrast, RV chamber and cellular hypertrophy occurred and was associated with a persistent increase of RV myocyte baseline contractile function.SummaryThis study demonstrated, for the first time, that differences in RV and LV myocyte function and β-adrenergic responsiveness exist in normal and DCM states. More importantly, a disparity in RV and LV myocyte growth with DCM occurred. Thus, in this model of DCM, RV and LV growth and changes in contractile performance are not a homogenous process, and suggest that inherent differences exist in the response of RV and LV myocytes to stress

    Identification of Highly Expressed, Soluble Proteins Using an Improved, High-Throughput Pooled ORF Expression Technology

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    This article describes an improved pooled open reading frame (ORF) expression technology (POET) that uses recombinational cloning and solution-based tandem mass spectrometry (MS/MS) to identify ORFs that yield high levels of soluble, purified protein when expressed in Escherichia coli. Using this method, three identical pools of 512 human ORFs were subcloned, purified, and transfected into three separate E. coli cultures. After bulk expression and purification, the proteins from the three separate pools were digested into tryptic peptides. Each of these samples was subsequently analyzed in triplicate using reversed-phase high-performance liquid chromatography (LC) coupled directly online with MS/MS. The abundance of each protein was determined by calculating the average exponentially modified protein abundance index (emPAI) of each protein across the three protein pools. Human proteins that consistently gave high emPAI values were subjected to small-scale expression and purification. These clones showed high levels of expression of soluble protein. Conversely, proteins that were not observed by LC-MS/MS did not show any detectable soluble expression in small-scale validation studies. Using this improved POET method allows the expression characteristics of hundreds of proteins to be quickly determined in a single experiment

    799-2 Left Ventricular (LV) and Myocyte Electrophysiology with the Development of Dilated Cardiomyopathy (DCM); Effects of Angiotensin II Receptor (AT1 AT-II) Blockade

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    Ventricular arrhythmias are a significant cause of morbidity and mortality with DCM, and AT1 AT-II receptor activation has been implicated to play a role in arrhythmogenesis. However, the effects of AT1, AT-II receptor activation on changes in LV function and myocyte electrophysiology during the progression of DCM remain unexplored. Accordingly, this study measured weekly changes in LV function (ejection fraction, LVEF; peak systolic wall stress, LVWS) and surface electrocardiography (R-R interval, QRS duration, QTc interval), and myocyte action potentials (resting membrane, RM; upstroke velocity, Vmax; duration at 90% repolarization, APD90) at terminal study in 3 groups of dogs (n=6/group): DCM, chronic pace (216 bpm, 4 weeks); DCM/AT-BLOCK, chronic pace and treatment with a specific non-peptide AT1 AT-II antagonist (SR 47436 (BMS 186295); 30mg/kg BID); and control (CON). All measurements were made with the pacemaker deactivated.LVEF (%)LVWS (g/cm2)R-R (ms).QRS (ms).QTc (ms)Week 2:CON68.7±3.2133±14646±9958.4±1.3291±13DCM40.9±4.1*184±16*519±4060.7±1.9316±9DCM/AT-Block44.1±3.7*138±10+540±566.32±1.2*325±9Week4:CON73.1±2.4127±10629±4557.6±1.4314±9DCM35.2±3.5*223±16*505±41*62.0±1.9313±9DCM/AT-Block35.2±2.7*160±13*+578±4865.7±1.5*296±6*p<0.05 vs CON+p<0.05 vs DCMWith DCM, RM (-71±l* vs -78±1mV) and APD90 (257±9* vs 226±7ms) increased, and Vmax decreased (121±5* vs 158±9V/s) compared to CON. In contrast, with AT-BLOCK, RM became more negative (-76±1+mV), APD90 was reduced (183±14*+) and Vmax increased (165±13+).SummaryAT1 AT-II receptor blockade during the progression of DCM caused significant changes in LV myocardial conduction and myocyte action potentials. These results suggest that AT1 AT-II receptor activation plays a contributory role toward the changes in LV electrophysiology with DCM

    Developmental differences in myocyte contractile response after cardioplegic arrest

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    AbstractAlthough developmental differences in left ventricular function after cardioplegic arrest and rewarming have been postulated, whether differences exist at the level of the myocyte remains unexplored. This project tested the hypothesis that there is a differential effect of hypothermic hyperkalemic cardioplegic arrest with subsequent rewarming on contractile function of immature compared with adult ventricular myocytes. Myocytes were isolated from the left ventricular free wall of five immature and five adult rabbits and incubated for 2 hours in hyperkalemic modified Ringer's solution at 4° C (cardioplegia) or for 2 hours in cell culture medium at 37° C (normothermia). Myocytes were resuspended (“rewarmed”) in 37° C cell culture medium after the incubation protocol. Normothermic baseline contractile performance was lower in immature, compared with adult, myocytes. Specifically, myocyte shortening velocity was 62 ± 4 μm/sec in immature and 112 ± 6 μm/sec in adult myocytes (p < 0.01). After cardioplegia and rewarming, immature myocyte contractile function was unchanged, whereas adult myocyte contractile function was significantly diminished. For example, myocyte shortening velocity was 65 ± 4 μm/sec in immature and 58 ± 3 μm/sec in adult myocytes (p < 0.01 versus normothermic). Myocyte surface area, which reflects myocyte volume, was increased after cardioplegia and rewarming in adults (3582 ± 55 versus 3316 ± 46 μm2, p < 0.01), but remained unchanged in immature myocytes (2212 ± 27 versus 2285 ± 28 μm2, p = not significant). These unique findings demonstrate a preservation of myocyte contractile function and volume regulation in immature myocytes after cardioplegic arrest and rewarming. Thus this study directly demonstrates that developmental differences exist in myocyte responses to hypothermic hyperkalemic cardioplegic arrest with subsequent rewarming. (J THORAC CARDIOVASC SURG 1996;111:1257-66

    Report of Meeting for the Purpose of Obtaining the Views of the Three Affiliated Tribes of the Fort Berthold Reservation on the Lieu Lands Offered by the Secretary of War, 1946

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    Notice of meeting in the Secretary\u27s conference room to obtain the views of the Three Affiliated Tribes of the Fort Berthold Reservation of the lieu lands offered by the Secretary of War. Provides a copy of the transcript for the meeting and the exhibits explained during the meeting. Includes: Section 6 Public Law 374, 79th Congress 2d session, memorandum to Secretary of the interior from the acting commissioner of Indian Affairs on subject of Transmitting correspondence to Secretary, Letter from Chairman George Gillette accepting invitation to have representatives of the Three Affiliated Tribes at a special hearing. Also includes: notice to all members of the Three Affiliated Tribes of the Fort Berthold Reservation listing a schedule of meetings to be held to discuss offer and inform tribe of schedule; list of attendees and comments for meeting in Lucky Mound District on December 5, 1946; list of attendees and comments in Red Butte District on December 5, 1946; List of attendees and comments in Charging Eagle District on December 6, 1946; List of attendees and comments in Independence District on December 7, 1946; List of attendees and comments in Nishu District on December 8, 1946; List of attendees and comments in Shell Creek District on December 9, 1946; Resolution announcing rejection to offer for the lieu lands offered to the Three Affiliated Tribes; and Exhibit 4 - formal rejection of offer, and Exhibit 5 - letter from J.A. Krug, Secretary of the Intererior) warranted a restudy of the lands. See also: Report of Second Meeting for the Purpose of Obtaining the Views of the Three Affiliated Tribes of the Fort Berthold Reservation on the Lieu Lands Offered by the Secretary of War, 1946https://commons.und.edu/langer-papers/1144/thumbnail.jp

    Shaping the microenvironment: Evidence for the influence of a host galaxin on symbiont acquisition and maintenance in the squid-vibrio symbiosis

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    Most bacterial species make transitions between habitats, such as switching from free-living to symbiotic niches. We provide evidence that a galaxin protein, EsGal1, of the squid Euprymna scolopes participates in both: (i) selection of the specific partner Vibrio fischeri from the bacterioplankton during symbiosis onset and, (ii) modulation of V. fischeri growth in symbiotic maintenance. We identified two galaxins in transcriptomic databases and showed by qRT-PCR that one (esgal1) was dominant in the light organ. Further, esgal1 expression was upregulated by symbiosis, a response that was partially achieved with exposure to symbiont cell-envelope molecules. Confocal immunocytochemistry of juvenile animals localized EsGal1 to the apical surfaces of light-organ epithelia and surrounding mucus, the environment in which V. fischeri cells aggregate before migration into the organ. Growth assays revealed that one repeat of EsGal1 arrested growth of Gram-positive bacterial cells, which represent the cell type first ‘winnowed’ during initial selection of the symbiont. The EsGal1-derived peptide also significantly decreased the growth rate of V. fischeri in culture. Further, when animals were exposed to an anti-EsGal1 antibody, symbiont population growth was significantly increased. These data provide a window into how hosts select symbionts from a rich environment and govern their growth in symbiosis

    Thermal Shift Assay for Small GTPase Stability Screening: Evaluation and Suitability

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    Thermal unfolding methods are commonly used as a predictive technique by tracking the protein's physical properties. Inherent protein thermal stability and unfolding profiles of biotherapeutics can help to screen or study potential drugs and to find stabilizing or destabilizing conditions. Differential scanning calorimetry (DSC) is a 'Gold Standard' for thermal stability assays (TSA), but there are also a multitude of other methodologies, such as differential scanning fluorimetry (DSF). The use of an external probe increases the assay throughput, making it more suitable for screening studies, but the current methodologies suffer from relatively low sensitivity. While DSF is an effective tool for screening, interpretation and comparison of the results is often complicated. To overcome these challenges, we compared three thermal stability probes in small GTPase stability studies: SYPRO Orange, 8-anilino-1-naphthalenesulfonic acid (ANS), and the Protein-Probe. We studied mainly KRAS, as a proof of principle to obtain biochemical knowledge through TSA profiles. We showed that the Protein-Probe can work at lower concentration than the other dyes, and its sensitivity enables effective studies with non-covalent and covalent drugs at the nanomolar level. Using examples, we describe the parameters, which must be taken into account when characterizing the effect of drug candidates, of both small molecules and Designed Ankyrin Repeat Proteins

    http://www.medscape.com/viewarticle/714780_print

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    Abstract and Introduction Abstract The fatigue life of bone is inversely related to strain magnitude. Decreasing stride length is a potential mechanism of strain reduction during running. If stride length is decreased, the number of loading cycles will increase for a given mileage. It is unclear if increased loading cycles are detrimental to skeletal health despite reductions in strain. Purpose: To determine the effects of stride length and running mileage on the probability of tibial stress fracture. Methods: Ten male subjects ran overground at their preferred running velocity during two conditions: preferred stride length and 10% reduction in preferred stride length. Force platform and kinematic data were collected concurrently. A combination of experimental and musculoskeletal modeling techniques was used to determine joint contact forces acting on the distal tibia. Peak instantaneous joint contact forces served as inputs to a finite element model to estimate tibial strains during stance. Stress fracture probability for stride length conditions and three running mileages (3, 5, and 7 miles·d −1 ) were determined using a probabilistic model of bone damage, repair, and adaptation. Differences in stress fracture probability were compared between conditions using a 2 × 3 repeated-measures ANOVA. Results: The main effects of stride length (P = 0.017) and running mileage (P = 0.001) were significant. Reducing stride length decreased the probability of stress fracture by 3% to 6%. Increasing running mileage increased the probability of stress fracture by 4% to 10%. Conclusions: Results suggest that strain magnitude plays a more important role in stress fracture development than the total number of loading cycles. Runners wishing to decrease their probability for tibial stress fracture may benefit from a 10% reduction in stride length
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