The Generality of the GUGA MRCI Approach in COLUMBUS for Treating Complex Quantum Chemistry

The core part of the program system COLUMBUS allows highly efficient calculations using variational multireference (MR) methods in the framework of configuration interaction with single and double excitations (MR-CISD) and averaged quadratic coupled-cluster calcu- lations (MR-AQCC), based on uncontracted sets of configurations and the graphical unitary group approach (GUGA). The availability of analytic MR-CISD and MR-AQCC energy gradients and analytic nonadiabatic couplings for MR-CISD enables exciting applications including, e.g., investigations of π-conjugated biradicaloid compounds, calculations of multitudes of excited states, development of dia- batization procedures, and furnishing the electronic structure information for on-the-fly surface nonadiabatic dynamics. With fully vari- ational uncontracted spin-orbit MRCI, COLUMBUS provides a unique possibility of performing high-level calculations on compounds containing heavy atoms up to lanthanides and actinides. Crucial for carrying out all of these calculations effectively is the availability of an efficient parallel code for the CI step. Configuration spaces of several billion in size now can be treated quite routinely on stan- dard parallel computer clusters. Emerging developments in COLUMBUS, including the all configuration mean energy multiconfiguration self-consistent field method and the graphically contracted function method, promise to allow practically unlimited configuration space dimensions. Spin density based on the GUGA approach, analytic spin-orbit energy gradients, possibilities for local electron correlation MR calculations, development of general interfaces for nonadiabatic dynamics, and MRCI linear vibronic coupling models conclude this overview

Detection of hypoglycemia with the GlucoWatch biographer

WSTĘP. Hipoglikiemia jest częstym, ostrym powikłaniem leczenia cukrzycy. Urządzenie monitorujące GlucoWatch zapewnia częste automatyczne pomiary glukozy z możliwością ustawienia progu alarmu niskiej glikemii. W badaniu przeanalizowano działanie biomonitora jako urządzenia służącego wykrywaniu hipoglikemii zdefiniowanej jako stężenie glukozy we krwi Ł 3,9 mmol/l. MATERIAŁ I METODY. Analizy dokonano w czterech badaniach klinicznych, w których biomonitor zastosowano 1091 razy, co pozwoliło uzyskać 14 487 par pomiarów (odczyt z biomonitora i stężenie glukozy we krwi). WYNIKI. Wyniki wskazują, że wraz z podwyższaniem granicy alarmu niskiej glikemii liczba rzeczywiście dodatnich alarmów (sygnał dźwiękowy i glikemia Ł 3,9 mmol/l) i fałszywie dodatnich alarmów (sygnał dźwiękowy, ale glikemia > 3,9 mmol/l) wzrasta. Po analizie wyników w zależności od poziomów sygnałów niskiej glikemii określono krzywe charakterystyki operatora odbiornika, które odpowiadają urządzeniu diagnostycznemu o wysokiej użyteczności. Ustawienie alarmu na poziomie 1,1–1,7 mmol/l powyżej hipoglikemii wydaje się optymalnym rozwiązaniem dla każdego użytkownika, dającym najlepszą proporcję wyników prawdziwie dodatnich i fałszywie dodatnich. Analiza tych samych danych dotyczących stężenia glukozy we krwi, względem metody typowej samokontroli (2–4 pomiary dziennie), wskazuje, że wykrywanych jest mniej incydentów hipoglikemii niż za pomocą urządzenia monitorującego. WNIOSKI. Częste i automatyczne odczyty stężenia glukozy we krwi pozwalają na efektywniejsze wykrywanie hipoglikemii.INTRODUCTION. Hypoglycemia is a common acute complication of diabetes therapy. The GlucoWatch biographer provides frequent and automatic glucose measurements with an adjustable low-glucose alarm. We have analyzed the performance of the biographer low-glucose alarm relative to hypoglycemia as defined by blood glucose £ 3.9 mmol/l. MATERIAL AND METHODS. The analysis was based on 1,091 biographer uses from four clinical trials, which generated 14,487 paired (biographer and blood glucose) readings. RESULTS. The results show that as the low-glucose alert level of the biographer is increased, the number of true positive alerts (alarm sounds and blood glucose £ 3.9 mmol/l) and false positive alerts (alarm sounds but blood glucose > 3.9 mmol/l) increased. When analyzed as a function of varying low-glucose alert levels, the results show receiver operator characteristic curves consistent with a highly useful diagnostic tool. Setting the alert level from 1.1 to 1.7 mmol/l above the level of concern is likely to optimize the trade-off between true positives and false positives for each user. When the same blood glucose data are analyzed for typical monitoring practices (two or four measurements per day), the results show that fewer hypoglycemic events are detected than those detected with the biographer. CONCLUSIONS. The frequent and automatic nature of the biographer readings allows more effective detection of hypoglycemia than that achieved with current medical practice

The generality of the GUGA MRCI approach in COLUMBUS for treating complex quantum chemistry

The core part of the program system COLUMBUS allows highly efficient calculations using variational multireference (MR) methods in the framework of configuration interaction with single and double excitations (MR-CISD) and averaged quadratic coupled-cluster calculations (MR-AQCC), based on uncontracted sets of configurations and the graphical unitary group approach (GUGA). The availability of analytic MR-CISD and MR-AQCC energy gradients and analytic nonadiabatic couplings for MR-CISD enables exciting applications including, e.g., investigations of π-conjugated biradicaloid compounds, calculations of multitudes of excited states, development of diabatization procedures, and furnishing the electronic structure information for on-the-fly surface nonadiabatic dynamics. With fully variational uncontracted spin-orbit MRCI, COLUMBUS provides a unique possibility of performing high-level calculations on compounds containing heavy atoms up to lanthanides and actinides. Crucial for carrying out all of these calculations effectively is the availability of an efficient parallel code for the CI step. Configuration spaces of several billion in size now can be treated quite routinely on standard parallel computer clusters. Emerging developments in COLUMBUS, including the all configuration mean energy multiconfiguration self-consistent field method and the graphically contracted function method, promise to allow practically unlimited configuration space dimensions. Spin density based on the GUGA approach, analytic spin-orbit energy gradients, possibilities for local electron correlation MR calculations, development of general interfaces for nonadiabatic dynamics, and MRCI linear vibronic coupling models conclude this overview

Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 variants Alpha and Iota.

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (Rt) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the Rt of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19

The cyclic-di-GMP signaling pathway in the Lyme disease spirochete,

In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease