We use the recently developed Heat-bath Configuration Interaction (HCI) algorithm as an efficient active space solver to perform multiconfiguration self-consistent field calculations (HCISCF) with ...large active spaces. We give a detailed derivation of the theory and show that difficulties associated with non-variationality of the HCI procedure can be overcome by making use of the Lagrangian formulation to calculate the HCI relaxed two-body reduced density matrix. HCISCF is then used to study the electronic structure of butadiene, pentacene, and Fe–porphyrin. One of the most striking results of our work is that the converged active space orbitals obtained from HCISCF are relatively insensitive to the accuracy of the HCI calculation. This allows us to obtain nearly converged CASSCF energies with an estimated error of less than 1 mHa using the orbitals obtained from the HCISCF procedure in which the integral transformation is the dominant cost. For example, an HCISCF calculation on the Fe–porphyrin model complex with an active space of (44e, 44o) took only 412 s per iteration on a single node containing 28 cores, out of which 185 s was spent in the HCI calculation and the remaining 227 s was used mainly for integral transformation. Finally, we also show that active space orbitals can be optimized using HCISCF to substantially speed up the convergence of the HCI energy to the Full CI limit because HCI is not invariant to unitary transformations within the active space.
Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit unexplained differences in age distribution of human cases. Using data from all known human cases of these viruses, we ...show that an individual's first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes in the same phylogenetic group. Statistical modeling shows that protective HA imprinting is the crucial explanatory factor, and it provides 75% protection against severe infection and 80% protection against death for both H5N1 and H7N9. Our results enable us to predict age distributions of severe disease for future pandemics and demonstrate that a novel strain's pandemic potential increases yearly when a group-mismatched HA subtype dominates seasonal influenza circulation. These findings open new frontiers for rational pandemic risk assessment.
Category 4 landfalling hurricane Harvey poured more than a metre of rainfall across the heavily populated Houston area, leading to unprecedented flooding and damage. Although studies have focused on ...the contribution of anthropogenic climate change to this extreme rainfall event
, limited attention has been paid to the potential effects of urbanization on the hydrometeorology associated with hurricane Harvey. Here we find that urbanization exacerbated not only the flood response but also the storm total rainfall. Using the Weather Research and Forecast model-a numerical model for simulating weather and climate at regional scales-and statistical models, we quantify the contribution of urbanization to rainfall and flooding. Overall, we find that the probability of such extreme flood events across the studied basins increased on average by about 21 times in the period 25-30 August 2017 because of urbanization. The effect of urbanization on storm-induced extreme precipitation and flooding should be more explicitly included in global climate models, and this study highlights its importance when assessing the future risk of such extreme events in highly urbanized coastal areas.
Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, ...radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredients (APIs) used in chemotherapy are highly cytotoxic to both cancer and normal cells. Accordingly, targeting the tumour vasculatures is essential for tumour treatment. In this context, encapsulation of anti-cancer drugs within the liposomal system offers secure platforms for the targeted delivery of anti-cancer drugs for the treatment of cancer. This, in turn, can be helpful for reducing the cytotoxic side effects of anti-cancer drugs on normal cells. This short-review focuses on the use of liposomes in anti-cancer drug delivery.
CONTEXT: The Amur tiger and leopard, once roaming over the Eurasian continent, are now endangered and confined to the Sikhote-Alin Mountains, Russia—a landscape that has been increasingly fragmented ...due to human activities. The ultimate fate of these big cats depends on whether they can resettle in their previous main historical range in NE China. Recent sightings of these animals along the China–Russia border have aroused new hope, but direct evidence is lacking. OBJECTIVES: The main objectives of our study were (1) to determine the abundance and spatiotemporal patterns of tigers, leopards, and primary prey; (2) to investigate factors influencing the resettlement of the two big cats; and (3) to propose a landscape-scale conservation plan to secure the long-term sustainability of the Amur tiger and leopard. METHODS: We monitored the two felids, their prey, and human activities, with 380 camera-trap stations, for a total of 175,127 trap days and over an area of 6000 km² in NE China. We used the constraint line method to characterize cattle grazing and human influences on tigers, leopards, and their prey species. RESULTS: Our results show that, unexpectedly, at least 26 tigers and 42 leopards are present within China, which are confined primarily to a narrow area along the border with Russia. We have further identified that cattle grazing and human disturbances are the key hurdles to the dispersal of the tigers and leopards farther into China where suitable habitat is potentially available. CONCLUSIONS: Amur tigers and leopards are returning to China, indeed, but their long-term resettlement is not likely without active and timely conservation efforts on landscape and regional scales. To overcome the hurdles to the resettlement of tigers and leopards in China, we propose a “Tiger and Leopard Resettlement Program” that will engage the government, local communities, and researchers, so that the long-term sustainability of the Amur tigers and leopards can be ensured.
Poor seed quality of soybean is often associated with Phomopsis seed decay (PSD), which is one of the most economically important seed diseases. Diaporthe longicolla (syn. Phomopsis longicolla) is ...the primary cause of PSD. Control of PSD is best accomplished by planting PSD-resistant cultivars. Sixteen exotic soybean accessions from the USDA soybean germplasm collection were screened for reaction to PSD at Stoneville, Mississippi. They consisted of maturity groups (MG) II, III and IV. Seeds from inoculated and non-inoculated plots harvested either promptly at maturity, or after a two-week delay in harvest, were assessed for infection by D. longicolla. Seed infection ranged from 0 to 36.7%. Overall, PI 417050 (MG II), PI 417017 (MG III), and PI 594692 (MG IV) had significantly (P ≤ 0.05) lower percentages of seed infected by D. longicolla and higher seed germinations than other genotypes in the same maturity groups. PI 587982A also performed well. As a result of these findings, these resistant accessions were used over multiple cycles of breeding to develop improved breeding lines with resistance to PSD and low seed damage. Breeding line 11043-225-72, with combined resistance from both PIs 417050 and 587982A, had low scores for PSD (6.7%) and seed damage (3.4%), while DS65-1, deriving resistance from PI 587982A, had the lowest seed damage score (1.1%) and the highest seed germination (85.6%) among all lines tested in 2017. DS65-1 and 11043-225-72, along with five other improved breeding lines, were provided to public soybean breeders for developing improved cultivars and germplasm lines. DS31-243 (PI 700941), derived from PI 587982A, was publicly released by the USDA in 2022. This research will lead to future releases of improved germplasm lines and cultivars with PSD resistance and high seed quality. It will also aid in disease management and be a benefit to soybean producers and the industry at large.
To report the relative frequencies of childhood and early onset glaucoma subtypes and their genetic findings in a large single cohort.
Retrospective clinical and molecular study.
All individuals with ...childhood glaucoma (diagnosed 0 to <18 years) and early onset glaucoma (diagnosed 18 to <40 years) referred to a national disease registry.
We retrospectively reviewed the referrals of all individuals with glaucoma diagnosed at <40 years of age recruited to the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG). Subtypes of glaucoma were determined using the Childhood Glaucoma Research Network (CGRN) classification system. DNA extracted from blood or saliva samples underwent sequencing of genes associated with glaucoma.
The phenotype and genotype distribution of glaucoma diagnosed at <40 years of age.
A total of 290 individuals (533 eyes) with childhood glaucoma and 370 individuals (686 eyes) with early onset glaucoma were referred to the ANZRAG. Primary glaucoma was the most prevalent condition in both cohorts. In the childhood cohort, 57.6% of individuals (167/290, 303 eyes) had primary congenital glaucoma (PCG), and 19.3% (56/290, 109 eyes) had juvenile open-angle glaucoma. Juvenile open-angle glaucoma constituted 73.2% of the early onset glaucoma cohort (271/370, 513 eyes). Genetic testing in probands resulted in a diagnostic yield of 24.7% (125/506) and a reclassification of glaucoma subtype in 10.4% of probands (13/125). The highest molecular diagnostic rate was achieved in probands with glaucoma associated with nonacquired ocular anomalies (56.5%). Biallelic variants in CYP1B1 (n = 29, 23.2%) and heterozygous variants in MYOC (n = 24, 19.2%) and FOXC1 (n = 21, 16.8%) were most commonly reported among probands with a molecular diagnosis. Biallelic CYP1B1 variants were reported in twice as many female individuals as male individuals with PCG (66.7% vs. 33.3%, P = 0.02).
We report on the largest cohort of individuals with childhood and early onset glaucoma from Australasia using the CGRN classification. Primary glaucoma was most prevalent. Genetic diagnoses ascertained in 24.7% of probands supported clinical diagnoses and genetic counseling. International collaborative efforts are required to identify further genes because the majority of individuals still lack a clear molecular diagnosis.
Grasses and grasslands are of increasing interest to conservationists, biologists, and gardeners. There are more than 300 species of native California grasses and they are found in almost every ...climate—from cool, wet forests to hot, dry deserts. Native grasses are also important to land restoration as they improve soil quality, increase water infiltration, and recycle nutrients. Their deep roots can tap soil water, which allows them to stay green year-round and to act as fire buffers around residences. Native grasses also provide vital habitat for many species of insects, birds, reptiles, and mammals. Despite their importance, grasslands remain one of the most underprotected of California's vegetation types, and native grasslands have undergone the greatest percentage loss of any habitat type in the state. Grasses are also among the most difficult plants to identify. Organized alphabetically, Field Guide to Grasses of California covers common native and naturalized grasses and, to help identify them, also features over 180 color illustrations.
Return on investment (ROI) has long been accepted as a primary tool for decision‐making for capital investments and even choices among competing operational budget lines. Applying ROI to investments ...intended to prevent or mitigate future risks and hazards can be very difficult, as benefits are typically arduous to define and calculate while risk probabilities can be very small. This paper uses examples from recent research concerning law enforcement, airport security, and airport resiliency to illustrate the feasibility of computing ROI and resiliency ROI (RROI) for such investments and to suggest methodology to approach these computations.
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