Natural product libraries: Assembly, maintenance, and screening

This review discusses successful strategies and potential pitfalls to assembling a natural product-based library suitable for high-throughput screening. Specific extraction methods for plants, microorganisms, and marine invertebrates are detailed, along with methods for generating a fractionated sub-library. The best methods to store, maintain and prepare the library for screening are addressed, as well as recommendations on how to develop a robust high-throughput assay. Finally, the logistics of moving from an assay hit to pure bioactive compound are discussed

Fragmented endocardial signals and early afterdepolarizations during torsades de pointes tachycardia

Background: Bradycardia-induced torsade de pointes (TdP) tachycardia in patients with spontaneous high-degree atrioventricular block (AVB) is common. The aim of this study was to analyze endocardial recordings during TdP in spontaneous high-degree AVB in humans to better understand the electrophysiological mechanisms underlying this phenomenon. Methods: The study group consisted of 5 patients with typical episodes of TdP during spontaneous high-degree AVB. A standard (USCI) temporary bipolar endocardial catheter positioned at the apex of the right ventricle (RV) and bipolar chest leads from two precordial leads V1 and V4 were used to record the tracings during TdP. Results: The presence of a wide spectrum of fragmentations was noted on endocardial electrograms (EGMs), which were invisible on the surface electrocardiogram (ECG) tracing. Endocardial signals indicated that TdP started in the proximity of the RV apex, since the local EGM began prior to the QRS complex on the surface ECG. Early afterdepolarizations (EADs) were observed in 2 out of 5 cases confirming a common opinion about the mechanism of TdP. However, this phenomenon was not observed in 3 other patients suggesting that the arrhythmia was the result of a different mechanism originating in proximity to the RV apex. Conclusions: This work demonstrated early endocardial signals in the RV apex during TdP associated with high-degree AVB in humans, and exhibits a spectrum of fragmented signals in this area occurring on a single or multiple beats. These fragmentations indicate areas of poor conduction and various degrees of intramyocardial block, and therefore a new mechanism of TdP tachycardia in some patients with spontaneous high-degree AVB

NMscatt: a program for calculating inelastic scattering from large biomolecular systems using classical force-field simulations

Computational tools for normal mode analysis, which are widely used in physics and materials science problems, are designed here in a single package called NMscatt (Normal Modes & scattering) that allows arbitrarily large systems to be handled. The package allows inelastic neutron and X-ray scattering observables to be calculated, allowing comparison with experimental data produced at large scale facilities. Various simplification schemes are presented for analysing displacement vectors, which are otherwise too complicated to understand in very large systems.Comment: 13 pages, 5 figures, preprint submitted to Computer Physics Communication

Even Galois Representations and the Fontaine--Mazur conjecture II

We prove, under mild hypotheses, that there are no irreducible two-dimensional_even_ Galois representations of \Gal(\Qbar/\Q) which are de Rham with distinct Hodge--Tate weights. This removes the "ordinary" hypothesis required in previous work of the author. We construct examples of irreducible two-dimensional residual representations that have no characteristic zero geometric (= de Rham) deformations.Comment: Updated to take into account suggestions of the referee; the main theorems remain unchange

The Ursinus Weekly, March 10, 1958

Spray of Springtime theme of the junior prom, Mar. 21 • Group production of French farce now in rehearsal • Fireside chats and art forum on Y agenda for March • IFC weekend, Apr. 25-26; Dances, picnic planned • Roland\u27s rendezvous theme of soph hop, Sat. • Band members at festival • Council reviews rules; Revises judiciary powers • Fraternities bid men today at noon • Selective Service department test applications due • Ursinus alumni to hold a dinner dance, March 22 • Curtain Club to present famous art historian tomorrow, Mar. 11 • Final week of Campus Chest drive; Goal $1500 • 105 on Dean\u27s list for Fall semester • Gold in the hills adds to 1958 Ruby coffers • Editorial: Give once for all • Letters to the editor • Review: Gold in the hills • Time has come • Off the cuff fashions for men • \u2758 basketball season roundup shows 1 win • Badminton belles win two games • Belles down Beaver 56-50 for third win in a row • U.C. dunks Drexel; Loses to Chestnut Hill, Bryn Mawr • Many fields included in Feb. Library accessions • Special feature: Hands • R. Usher in officer traininghttps://digitalcommons.ursinus.edu/weekly/1402/thumbnail.jp

The response of ground-dwelling spiders (Araneae) and hoverflies (Diptera: Syrphidae) to afforestation assessed using within site tracking

In many countries throughout the world, the area of plantation forests continues to increase and they now dominate many landscapes. In recent decades, forest cover in Ireland has expanded largely due to commercial afforestation with non-native conifers. This study provides the first within-site assessment of the response of two important arthropod groups to afforestation in agricultural grasslands in Ireland. Five sites were studied 1 year before and 7 years after afforestation using pitfall trapping for active ground-dwelling spiders and Malaise trapping for hoverflies. Both species groups were studied in grassland habitat, and spiders were also sampled in field boundary hedgerow habitat. Afforestation within the study sites had a positive effect on ground-dwelling spider diversity over the first 7 years; total species richness increased in afforested grassland and hedgerow habitats, and forest specialist species richness increased in afforested grassland habitat. This was concurrent with, and most likely influenced by, the increase in habitat structure created by the forest vegetation, litter and deadwood layers and the increase in canopy cover. There was no effect of afforestation on hoverfly species richness over the first 7 years, possibly due to confounding effects of hoverfly movements across landscapes. Spider and hoverfly species compositions were also positively affected by afforestation. These results indicated that afforestation in our study sites, set within a predominantly agricultural landscape, benefitted arthropod diversity by increasing habitat diversity. Hedgerow habitats were also an important contributor to biodiversity in these newly planted forests. Ecologically oriented planning and management of afforestation must consider the influence of habitat quality in forest plantations, including the protection of biodiversity rich habitats and the quality of the land being afforested, to improve the contribution to biodiversity enhancement and conservation

Right atrial pathology in arrhythmogenic right ventricular dysplasia

Background: Atrial fibrillation (AF) is the most common atrial arrhythmia in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD). Considering the histologic changes known in the right ventricular (RV) in ARVD, the aim of the present study was to examine right atrial (RA) pathology in patients with ARVD. Methods: Histology of RA and RV was assessed from autopsy material in 3 patients with ARVD without persistent atrial arrhythmia. RA histology in 3 patients with permanent AF without ARVD and 5 patients without cardiovascular disease was also studied. Staining with hematoxylin phloxine saffron was performed for the ARVD patients to identify fibrosis, and hematoxylin-eosin for identification of lymphocytes. Masson’s trichrome staining was performed for control groups taken from a collection of standard glass slides. Results: In all 3 ARVD cases, RA anomalies were observed that revealed a reduction of cardiomyocytes, the presence of adipocytes, some of them inside the mediomural atrial layer and interstitial fibrosis. In 2 ARVD cases, interstitial fibrosis was also associated with a focus of replacement fibrosis, which was also observed in patients with permanent AF without ARVD. The histologic specimen of the RA and RV from the control group without cardiovascular disease did not display any evidence of fat or fibrosis with a preserved cardiomyocyte architecture. Conclusions: A similar histopathological substrate, as can be observed in the RV of patients with ARVD can also be seen in the RA of these patients. This may explain the high prevalence of atrial arrhythmias, particularly AF, in patients with ARVD

C-Reactive Protein in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy and Relationship with Ventricular Tachycardia

Background. The relationship between C-reactive protein (CRP) elevation and ventricular tachycardia (VT) in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is unclear. Methods and Results. In 91 consecutive patients with either ARVD/C with or without VT (cases) or idiopathic right ventricular outflow tract (RVOT) tachycardia (controls), blood sampling were taken to determine CRP levels. In ARVD/C patients with VT, we analyzed the association between VT occurrences and CRP level. Sixty patients had ARVD/C, and 31 had idiopathic RVOT VT. Patients with ARVD/C had a significant higher level of CRP compared to those with RVOT VT (3.5 ± 4.9 versus 1.1 ± 1.2 mg/l, P = .0004). In ARVD/C group, 77%, (n = 46) patients experienced VT. Of these, 37% (n = 17) underwent blood testing for CRP within 24 h after the onset of VT and the remaining 63% (n = 29) after 24 h of VT reduction. CRP level was similar in ARVD/C patients with or without documented VT (3.6 ± 5.1 mg/l versus 3.1 ± 4.1 mg/l, P = .372). However, in patients with ARVD/C and documented VT, CRP was significantly higher when measured within 24 hours following VT in comparison to that level when measured after 24 h (4.9 ± 6.2 mg/l versus 3.0 ± 4.4 mg/l, P = .049). Conclusion. Inflammatory state is an active process in patients with ARVD/C. Moreover, there is a higher level of CRP in patients soon after ventricular tachycardia, and this probably tends to decrease after the event