Private Creeds and their Troubled Authors

This article defends the disputed label “private creeds” as a useful one for describing a number of fourth century texts. Offering such a confession was the normal method for clearing one’s name on charges of heterodoxy in fourth-century Greek Christianity, though writing such a creed made the author susceptible to charges of innovation. A number of letters on Trinitarian doctrine by Basil of Caesarea and Gregory of Nyssa should be read in light of the tradition of private creeds. Indeed, the writings of Basil and Gregory provide unparalleled evidence for the roles such creeds played in Christian disputes of the fourth century

Review of sitagliptin phosphate: a novel treatment for type 2 diabetes

Sitagliptin (Januvia®, Merck Pharmaceuticals) is a dipeptidyl-peptidase inhibitor (DPP-4 inhibitor) that has recently been approved for the therapy of type 2 diabetes. Like other DPP-4 inhibitors its action is mediated by increasing levels of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). Sitagliptin is effective in lowering HbA1c, and fasting as well as postprandial glucose in monotherapy and in combination with other oral antidiabetic agents. It stimulates insulin secretion when hyperglycemia is present and inhibits glucagon secretion. In clinical studies it is weight neutral. This article gives an overview of the mechanism of action, the pharmacology, and the clinical efficacy and safety of sitagliptin in type 2 diabetes therapy

New treatments in the management of type 2 diabetes: a critical appraisal of saxagliptin

Saxagliptin is a novel dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor) for the treatment of type 2 diabetes, with a duration profile for once daily dosing. It is highly selective for DPP-4 in comparison to other enzymes of the dipeptidyl peptidase family. DPP-4 inhibitors elevate plasma concentrations of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). This effect results in a glucose-dependent stimulation of insulin secretion and an inhibition of glucagon secretion without an intrinsic risk for hypoglycemia. In comparison to sulfonylureas and thiazolidinediones that promote weight gain, DPP-4 inhibitors are weight neutral. Saxagliptin has been approved by the FDA for the US and by the EMEA for Europe in 2009. Clinical trials showed a dose-dependent inhibition of DPP-4 by saxagliptin in doses ranging from 2.5 to 100 mg daily without serious side effects. Type 2 diabetic patients receiving 5 mg to 10 mg saxagliptin once daily had a significant lowering of HbA1c and glycemic parameters along with good tolerability and safety. Saxagliptin has demonstrated a good efficacy for glycemic parameters in various patient populations either in monotherapy or in combination with metformin and other oral antidiabetic drugs as well as a favorable cardiovascular profile. With its high selectivity for DPP-4 and its clinical and cardiovascular profile, saxagliptin is an attractive novel DPP-4 inhibitor

God is Not a Thing: A Response to Dale Tuggy

Dale Tuggy has argued that all Trinitarians are committed to the nonsensical belief that the one God is the Trinity (where "is" expresses identity). In his submission to the current journal, Tuggy argues that this position began not, as some Orthodox theologians have claimed, with Augustine, but rather with the Cappadocians. According to Tuggy, in these late fourth century authors, the Trinity "replaced" the Father as the one true God. In this response, it is argued (1) that Tuggy's thesis of historical replacement is unproven, (2) that Tuggy's concept of substance, and therefore his reading of the Cappadocians is anachronistic or confused, and (3) that Tuggy mistakes the names "God" and "Father" for proper names.&nbsp

Semantic Processing of Out-Of-Vocabulary Words in a Spoken Dialogue System

One of the most important causes of failure in spoken dialogue systems is usually neglected: the problem of words that are not covered by the system's vocabulary (out-of-vocabulary or OOV words). In this paper a methodology is described for the detection, classification and processing of OOV words in an automatic train timetable information system. The various extensions that had to be effected on the different modules of the system are reported, resulting in the design of appropriate dialogue strategies, as are encouraging evaluation results on the new versions of the word recogniser and the linguistic processor.Comment: 4 pages, 2 eps figures, requires LaTeX2e, uses eurospeech.sty and epsfi

Towards Understanding Spontaneous Speech: Word Accuracy vs. Concept Accuracy

In this paper we describe an approach to automatic evaluation of both the speech recognition and understanding capabilities of a spoken dialogue system for train time table information. We use word accuracy for recognition and concept accuracy for understanding performance judgement. Both measures are calculated by comparing these modules' output with a correct reference answer. We report evaluation results for a spontaneous speech corpus with about 10000 utterances. We observed a nearly linear relationship between word accuracy and concept accuracy.Comment: 4 pages PS, Latex2e source importing 2 eps figures, uses icslp.cls, caption.sty, psfig.sty; to appear in the Proceedings of the Fourth International Conference on Spoken Language Processing (ICSLP 96

Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide

Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice. The long-acting GLP-1RA, semaglutide, is available for once-weekly injection and in a new once-daily oral formulation. Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e.g., patients with hepatic impairment or renal impairment). The oral formulation represents a useful option to help improve acceptance and adherence compared with injectable formulations for patients with a preference for oral therapy, and may lead to earlier and broader use of GLP-1RAs in the T2D treatment trajectory. Oral semaglutide should be taken on an empty stomach, which may influence the choice of formulation. As with most GLP-1RAs, initial dose escalation of semaglutide is required for both formulations to mitigate gastrointestinal adverse events. There are also specific dose instructions to follow with oral semaglutide to ensure sufficient gastric absorption. The evidence base surrounding the clinical use of semaglutide is being further expanded with trials investigating effects on diabetic retinopathy, cardiovascular outcomes, and on the common T2D comorbidities of obesity, chronic kidney disease, and non-alcoholic steatohepatitis. These will provide further information about whether the benefits of semaglutide extend to these other indications

Sly1 protein bound to Golgi syntaxin Sed5p allows assembly and contributes to specificity of SNARE fusion complexes

Fusion of transport vesicles with their target organelles involves specific membrane proteins, SNAREs, which form tight complexes bridging the membranes to be fused. Evidence from yeast and mammals indicates that Sec1 family proteins act as regulators of membrane fusion by binding to the target membrane SNAREs. In experiments with purified proteins, we now made the observation that the ER to Golgi core SNARE fusion complex could be assembled on syntaxin Sed5p tightly bound to the Sec1-related Sly1p. Sly1p also bound to preassembled SNARE complexes in vitro and was found to be part of a vesicular/target membrane SNARE complex immunoprecipitated from yeast cell lysates. This is in marked contrast to the exocytic SNARE assembly in neuronal cells where high affinity binding of N-Sec1/Munc-18 to syntaxin 1A precluded core SNARE fusion complex formation. We also found that the kinetics of SNARE complex formation in vitro with either Sly1p-bound or free Sed5p was not significantly different. Importantly, several presumably nonphysiological SNARE complexes easily generated with Sed5p did not form when the syntaxin was first bound to Sly1p. This indicates for the first time that a Sec1 family member contributes to the specificity of SNARE complex assembly

Biochemical and genetic evidence for the involvement of yeast Ypt6-GTPase in protein retrieval to different Golgi compartments

Yeast Ypt6p, the homologue of the mammalian Rab6 GTPase, is not essential for cell viability. Based on previous studies with ypt6 deletion mutants, a regulatory role of the GTPase either in protein retrieval to the trans-Golgi network or in forward transport between the endoplasmic reticulum (ER) and early Golgi compartments was proposed. To assess better the primary role(s) of Ypt6p, temperature-sensitive ypt6 mutants were generated and analyzed biochemically and genetically. Defects in N-glycosylation of proteins passing the Golgi and of Golgi- resident glycosyltransferases as well as protein sorting defects in the trans-Golgi were recorded shortly after functional loss of Ypt6p. ER-to-Golgi transport and protein secretion were delayed but not interrupted. Mis-sorting of the vesicular SNARE Sec22p to the late Golgi was also observed. Combination of the ypt6-2 mutant allele with a number of mutants in forward and retrograde transport between ER, Golgi, and endosomes led to synthetic negative growth defects. The results obtained indicate that Ypt6p acts in endosome-to-Golgi, in intra-Golgi retrograde transport, and possibly also in Golgi-to-ER trafficking