Friends at Mid-Century

The Isaac T. and Lida K. Johnson Lectureship, made possible by their gift, was created by the Executive Committee of the Five Years Meeting in its sessions of April, 1940. The creative minute of the Executive Committee is in part as follows: It is the duty of the Executive Committee to determine the use of this money and the Central Committee submits this recommendation: (1) that the gift be made a continuing memorial to these dear friends and (2) that the memorial be in the form of a lectureship for the Five Years Meeting, and, as it may direct, to be known as the Isaac T. and Lida K. Johnson Lectureship. It is further recommended that these lectures shall within the jurisdiction of the Executive Committee, be restricted to the field of Christian scholarship and the Christian message and its application to life. It is the confident expectation of the Executive Committee that not only the constituency of the Five Years Meeting, but all of Quakerism will be enriched by the successive messages made possible by this gift.https://digitalcommons.georgefox.edu/quakerbooks/1072/thumbnail.jp

Configuration of Stable Evolutionary Strategy of Homo Sapiens and Evolutionary Risks of Technological Civilization (the Conceptual Model Essay)

Stable evolutionary strategy of Homo sapiens (SESH) is built in accordance with the modular and hierarchical principle and consists of the same type of self-replicating elements, i.e. is a system of systems. On the top level of the organization of SESH is the superposition of genetic, social, cultural and techno-rationalistic complexes. The components of this triad differ in the mechanism of cycles of generation - replication - transmission - fixing/elimination of adoptively relevant information. This mechanism is implemented either in accordance with the Darwin-Weismann modus, or according to the Lamarck modus, the difference between them is clear from the title. The integral attribute of the system of systems including ESSH is the production of evolutionary risks. The sources of evolutionary risk for stable adaptive strategy of Homo sapiens are the imbalance of (1) the intra-genomic co-evolution (intragenomic conflicts); (2) the gene-cultural co- evolution; (3) the inter-cultural co-evolution; (4) techno-humanitarian balance; (5) inter- technological conflicts (technological traps). At least phenomenologically the components of the evolutionary risk are reversible, but in the aggregate they are in potentio irreversible destructive ones for bio-social, and cultural self-identity of Homo sapiens. When the actual evolution is the subject of a rationalist control and/or manipulation, the magnitude of the 4th and 5th components of the evolutionary risk reaches the level of existential significance

Characterization of seed nuclei in glucagon aggregation using light scattering methods and field-flow fractionation

<p>Abstract</p> <p>Background</p> <p>Glucagon is a peptide hormone with many uses as a therapeutic agent, including the emergency treatment of hypoglycemia. Physical instability of glucagon in solution leads to problems with the manufacture, formulation, and delivery of this pharmaceutical product. Glucagon has been shown to aggregate and form fibrils and gels <it>in vitro</it>. Small oligomeric precursors serve to initiate and nucleate the aggregation process. In this study, these initial aggregates, or seed nuclei, are characterized in bulk solution using light scattering methods and field-flow fractionation.</p> <p>Results</p> <p>High molecular weight aggregates of glucagon were detected in otherwise monomeric solutions using light scattering techniques. These aggregates were detected upon initial mixing of glucagon powder in dilute HCl and NaOH. In the pharmaceutically relevant case of acidic glucagon, the removal of aggregates by filtration significantly slowed the aggregation process. Field-flow fractionation was used to separate aggregates from monomeric glucagon and determine relative mass. The molar mass of the large aggregates was shown to grow appreciably over time as the glucagon solutions gelled.</p> <p>Conclusion</p> <p>The results of this study indicate that initial glucagon solutions are predominantly monomeric, but contain small quantities of large aggregates. These results suggest that the initial aggregates are seed nuclei, or intermediates which catalyze the aggregation process, even at low concentrations.</p

Identification of antisense nucleic acid hybridization sites in mRNA molecules with self-quenching fluorescent reporter molecules

We describe a physical mRNA mapping strategy employing fluorescent self-quenching reporter molecules (SQRMs) that facilitates the identification of mRNA sequence accessible for hybridization with antisense nucleic acids in vitro and in vivo, real time. SQRMs are 20–30 base oligodeoxynucleotides with 5–6 bp complementary ends to which a 5′ fluorophore and 3′ quenching group are attached. Alone, the SQRM complementary ends form a stem that holds the fluorophore and quencher in contact. When the SQRM forms base pairs with its target, the structure separates the fluorophore from the quencher. This event can be reported by fluorescence emission when the fluorophore is excited. The stem–loop of the SQRM suggests that SQRM be made to target natural stem–loop structures formed during mRNA synthesis. The general utility of this method is demonstrated by SQRM identification of targetable sequence within c-myb and bcl-6 mRNA. Corresponding antisense oligonucleotides reduce these gene products in cells

Acceptance and commitment therapy for symptom interference in metastatic breast cancer patients: a pilot randomized trial

PURPOSE: Breast cancer is the leading cause of cancer mortality in women worldwide. With medical advances, metastatic breast cancer (MBC) patients often live for years with many symptoms that interfere with activities. However, there is a paucity of efficacious interventions to address symptom-related suffering and functional interference. Thus, this study examined the feasibility and preliminary efficacy of telephone-based acceptance and commitment therapy (ACT) for symptom interference with functioning in MBC patients. METHODS: Symptomatic MBC patients (N = 47) were randomly assigned to six telephone sessions of ACT or six telephone sessions of education/support. Patients completed measures of symptom interference and measures assessing the severity of pain, fatigue, sleep disturbance, depressive symptoms, and anxiety. RESULTS: The eligibility screening rate (64%) and high retention (83% at 8 weeks post-baseline) demonstrated feasibility. When examining within-group change, ACT participants showed decreases in symptom interference (i.e., fatigue interference and sleep-related impairment; Cohen's d range = - 0.23 to - 0.31) at 8 and 12 weeks post-baseline, whereas education/support participants showed minimal change in these outcomes (d range = - 0.03 to 0.07). Additionally, at 12 weeks post-baseline, ACT participants showed moderate decreases in fatigue and sleep disturbance (both ds = - 0.43), whereas education/support participants showed small decreases in these outcomes (ds = - 0.24 and - 0.18 for fatigue and sleep disturbance, respectively). Both the ACT and education/support groups showed reductions in depressive symptoms (ds = - 0.27 and - 0.28) at 12 weeks post-baseline. Group differences in all outcomes were not statistically significant. CONCLUSIONS: ACT shows feasibility and promise in improving fatigue and sleep-related outcomes in MBC patients and warrants further investigation

Exotic cluster structures in the mean-field theory

Investigations of exotic cluster-like phenomena in the framework of the Skyrme-Hartree-Fock approach are reported. The occurrence of highly excited isomeric states is discussed in connection with the question of their stability in static and time-dependent Hartree Fock (TDHF) calculations. We find rotational stabilization of a 4α chain structure in 16O occurring for a limited range of angular momenta. A toroidal configuration of 40Ca was also stabilized by rotation and provides a very interesting example of rotation about a symmetry axis with a strictly quantized total angular momentum. Finally we look at the formation of nuclear pasta phases in a time-dependent approach and their classification

Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites

BACKGROUND: Drug nonadherence is one of the major challenges faced by resistant hypertension patients, and identification of this problem is needed for optimizing pharmacotherapy. Dried blood spot (DBS) sampling is a minimally invasive method designed to detect and determine the degree of nonadherence. In this study, a DBS method for qualifying 8 antihypertensive drugs (AHDs) and 4 active metabolites was developed and validated using ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). METHOD: The DBS assay was validated analytically and clinically, in accordance with FDA requirements. Analytical validation was accomplished using UHPLC-MS/MS. For clinical validation, paired peak and trough levels of DBS and plasma samples were simultaneously collected and comparatively analyzed using Deming regression and Bland-Altman analyses. All concentrations below the set lower limit were excluded. Deming regression analysis was used to predict comparison bias between the collected plasma and DBS samples, with DBS concentrations corrected accordingly. RESULTS: The UHPLC-MS/MS method for simultaneously measuring 8 AHDs and their metabolites in DBS, was successfully validated. With Deming regression no bias was observed in N = 1; constant bias was seen in N = 6 and proportional bias in N = 11 of the AHDs and metabolites. After correction for bias, only one metabolite (canrenone) met the 20% acceptance limit for quantification, after Bland-Altman analyses. In addition, amlodipine, valsartan, and [enalaprilate] met the 25% acceptance limit. CONCLUSIONS: A novel DBS assay for simultaneously qualifying and quantifying 8 AHDs and their metabolites, has been successfully developed and validated. The DBS assay is therefore a suitable method to detect drug nonadherence. However, with the exception of canrenone, the interchangeable use of plasma and DBS sa

Sistem Pengendali Kecepatan Motor Dc Pada Lift Barang Menggunakan Kontroler Pid Berbasis Atmega 2560

Lift barang adalah angkutan transportasi vertikal digunakan untuk memindahkan barang. Lift ini sangat khusus fungsinya untuk barang saja, lift ini hampir sama dengan lift penumpang namun ada sedikit perbedaan dalam sistem keamanannya. Lift barang yang sekarang memang sudah otomatis tetapi hanya pada gedung bertingkat tinggi. Untuk minimarket atau home industry yang memiliki struktur bangunan 2 lantai, banyak dijumpai masih menggunakan pengkatrolan secara manual oleh tenaga manusia untuk memindahkan barang. Hal ini cukup tidak efisien. Pada penelitian ini telah dirancang sistem pengaturan kecepatan motor DC pada lift barang menggunakan kontoler PID dengan kontruksi sistem yang sederhana. Digunakan Kontroler PID untuk mengurangi kesalahan, sehingga putaran motor dapat sesuai dengan kecepatan yang diinginkan. Dengan bantuan kontroler PID maka lift barang mampu bergerak dengan aman dan halus. Pada skripsi ini digunakan metode Ziegler-Nichols tunning 2. Dalam pembuatannya digunakan Arduino Mega 2560, rotary encoder Autonic E40H8 500-6-L-5, limit switch, dan motor DC. Berdasarkan data respons sistem yang diperoleh dari pengujian dengan menggunakan metode kedua Ziegler-Nichols, maka parameter kontroler PID dapat ditentukan dengan gain Kp = 7.71, Ki = 7.035 dan Kd = 2.113.Kata Kunci— Lift barang, Pengendalian Kecepatan, PID, Arduino Mega 2560

Effect of Tobacco Smoking on the Clinical, Histopathological, and Serological Manifestations of Sjögren’s Syndrome

Objectives To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren’s syndrome (SS) and non-Sjögren’s sicca (non-SS sicca). Methods Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers. Results Current smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22–0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15–0.44, FDR q = 1.52x10E-06), focus score ≥1 (OR 0.22, 95%CI 0.13–0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2–0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39–0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption. Conclusions Current tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration. In spite of the protective effects of tobacco on SS manifestations, it is associated with other serious comorbidities such as lung disease, cardiovascular risk and malignancy, and should thus be strongly discouraged in patients with sicca