CHARMM36m: An improved force field for folded and intrinsically disordered proteins.

The all-atom additive CHARMM36 protein force field is widely used in molecular modeling and simulations. We present its refinement, CHARMM36m (http://mackerell.umaryland.edu/charmm_ff.shtml), with improved accuracy in generating polypeptide backbone conformational ensembles for intrinsically disordered peptides and proteins

Stability and dynamics of free magnetic polarons

The stability and dynamics of a free magnetic polaron are studied by Monte Carlo simulation of a classical two-dimensional Heisenberg model coupled to a single electron. We compare our results to the earlier mean-field analysis of the stability of the polaron, finding qualitative similarity but quantitative differences. The dynamical simulations give estimates of the temperature dependence of the polaron diffusion, as well as a crossover to a tunnelling regime.Comment: 4 pages including 4 .eps figure

Monitoring commercial conventional facilities control with the APS control system: The Metasys-to-EPICS interface

As controls needs at the Advanced Photon Source matured from an installation phase to an operational phase, the need to monitor the existing conventional facilities control system with the EPICS-based accelerator control system was realized. This existing conventional facilities control network is based on a proprietary system from Johnson Controls called Metasys. Initially read-only monitoring of the Metasys parameters will be provided; however, the ability for possible future expansion to full control is available. This paper describes a method of using commercially available hardware and existing EPICS software as a bridge between the Metasys and EPICS control systems

Some Findings Concerning Requirements in Agile Methodologies

gile methods have appeared as an attractive alternative to conventional methodologies. These methods try to reduce the time to market and, indirectly, the cost of the product through flexible development and deep customer involvement. The processes related to requirements have been extensively studied in literature, in most cases in the frame of conventional methods. However, conclusions of conventional methodologies could not be necessarily valid for Agile; in some issues, conventional and Agile processes are radically different. As recent surveys report, inadequate project requirements is one of the most conflictive issues in agile approaches and better understanding about this is needed. This paper describes some findings concerning requirements activities in a project developed under an agile methodology. The project intended to evolve an existing product and, therefore, some background information was available. The major difficulties encountered were related to non-functional needs and management of requirements dependencies

Ocena bezpieczeństwa i efektywność jabłczanu sunitynibu w przerzutowych guzach neuroendokrynnych trzustki (NEN G1/G2) w zależności od liczby i rodzaju wcześniejszych linii terapeutycznych — doniesienie wstępne

Introduction: The objective of this paper was to assess the safety and efficacy of sunitinib malate in patients with well-differentiated metastatic pancreatic neuroendocrine neoplasms (PNENs) who relapsed on standard therapy.Material and methods: Overall, eight patients with well-differentiated pancreatic neuroendocrine tumours/neoplasm (NET/NEN G1/G2, Ki-67 < 20%), who had relapsed on a standard therapy approach, were treated. All had non-resectable, progressive disease. All received therapy using a standard dose of sunitinib malate. Adverse events were evaluated using NCI-CTC AE v. 3.0.Results: Of the eight patients, seven had non-secretor and single secretor tumour (gastrinoma). Partial remission (PR) was noted in three patients (one after a single therapeutic line, two after two lines), five patients had stabilisation (SD) — including three individuals after three lines, one patient after two lines and another after a single line. Haematological adverse events: leukopenia (25%) — occurred in one patient after three lines and in one patient after two lines; anaemia (25%) — in one patient after three lines and in one patient after one therapeutic line. Mucocutaneous lesions were noted in 37.5% of patients after 2–3 lines of treatment. All of them experienced fatigue syndrome irrespective of the number of therapies. The majority of the patients simultaneously received somatostatin analogues, which did not exacerbate the toxicity profile. The median progression-free survival time (PFS) was 11 months.Conclusions: Sunitinib may be considered as a fairly well-tolerated and effective therapeutic option in progressive non-resectable PNEN patients in the second and subsequent lines of treatment, irrespective of the types of treatment previously applied. (Endokrynol Pol 2014; 65 (6): 472–478)Wstęp: Celem pracy była ocena bezpieczeństwa oraz analiza skuteczności jabłczanu sunitynibu u chorych z przerzutowymi wysokozróżnicowanymi guzami neuroendokrynnymi trzustki (PNET) w drugiej i kolejnych liniach leczenia.Materiał i metody: Analizie poddano 8 pacjentów z wysoko zróżnicowanymi guzami neuroendokrynnymi trzustki (NEN G1/G2, Ki-67 < 20%), u których wystąpiła progresja choroby i otrzymali sunitynib. Wszyscy chorzy byli w stadium nieoperacyjnym. Sunitynib był podawany w standardowej dawce. Działania niepożądane oceniono na podstawie kryteriów NCI-CTC AE v. 3.0.Wyniki: Leczono 8 pacjentów; 7 guzów nieaktywnych hormonalnie i 1 o typie gastrinoma. Częściową remisję (PR) uzyskano u 3 chorych (1 po 1 linii terapeutycznej, 2 — po 2 liniach), 5 chorych miało stabilizację (SD) — w tym 3 było po 3 liniach, 1 po 2 liniach i 1 po 1 linii terapeutycznej. Powikłania hematologiczne: leukopenia (25%) — wystąpiły u 1 pacjenta po 3 liniach i u 1 pacjenta po 2 liniach; niedokrwistość (25%) — u 1 pacjenta po 3 liniach i u 1 pacjenta po 1 linii terapeutycznej. U 37,5% chorych wystąpiły zmiany skórno-śluzówkowe po 2–3 liniach leczenia. U 100% chorych obserwowano zespół zmęczenia niezależnie od liczby terapii. Większość chorych jednocześnie otrzymywała SSA, co nie pogorszyło profilu toksyczności. Mediana czasu wolnego od progresji PFS (progression free survival) – wyniosła 11 miesięcy.Wnioski: Sunitynib może być rozważany, jako dość dobrze tolerowana, skuteczna opcja terapeutyczna u chorych z nieresekcyjnymi PNET w drugiej oraz kolejnych liniach leczenia, niezależnie od rodzaju uprzednio zastosowanych metod. (Endokrynol Pol 2014; 65 (6): 472–478

Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

BACKGROUND: Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases. METHODS: Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11). RESULTS: The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p < 0.001) and 124% higher in IPF patients (p < 0.0001) compared with controls. ELN-441 had better diagnostic value in COPD patients (AUC 97%, p = 0.001) than in IPF patients (AUC 90%, p = 0.0001). The odds ratios for differentiating controls from COPD or IPF were 24 [2.06–280] for COPD and 50 [2.64–934] for IPF. CONCLUSIONS: MMP-9 and -12 time-dependently released the ELN-441 epitope from elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings