Alkaloids Used as Medicines: Structural Phytochemistry Meets Biodiversity—An Update and Forward Look

Selecting candidates for drug developments using computational design and empirical rules has resulted in a broad discussion about their success. In a previous study, we had shown that a species’ abundance [as expressed by the GBIF (Global Biodiversity Information Facility)] dataset is a core determinant for the development of a natural product into a medicine. Our overarching aim is to understand the unique requirements for natural product-based drug development. Web of Science was queried for research on alkaloids in combination with plant systematics/taxonomy. All alkaloids containing species demonstrated an average increase of 8.66 in GBIF occurrences between 2014 and 2020. Medicinal Species with alkaloids show higher abundance compared to non-medicinal alkaloids, often linked also to cultivation. Alkaloids with high biodiversity are often simple alkaloids found in multiple species with the presence of ’driver species‘ and are more likely to be included in early-stage drug development compared to ‘rare’ alkaloids. Similarly, the success of an alkaloid containing species as a food supplement (‘botanical’) is linked to its abundance. GBIF is a useful tool for assessing the druggability of a compound from a certain source species. The success of any development programme from natural sources must take sustainable sourcing into account right from the start

Penilaian Potensi Daya Tarik Danau Bekat untuk Objek Wisata di Kecamatan Tayan Hilir Kabupaten Sanggau

Tayan Downstream is one of the District that is located in Regency Sanggau, West Borneo. In the Tayan Downstream there are several Lakes that each has its own potential, one of which is Lake Bekat. In the Tayan Downstream there are several Lake sthate ach has its own potential,one of which is Lake Bekat. In Lake Bekat there are many types of fishe specially the most prominent is Toman (Orheichepalus micropeltes), Kerandang (Ophiocephalus pleurophthamus) and Biawan (Hellostomata temincki). With the vastexpanse of nature through out the area + 2136.52 Ha and the beautiful scenery around the Lake,Because in the absence of Tayan Downstream nature associated with water attractions (Lake) there should be an assessment of the potential for tourist attraction on Lake Bekat. This study aims to identify andassess the potential attractiveness Lake Bekat to be developed as a tourist attractionand from this study are expected to provide information about the potential value for development Lake Bekat attractions. Thi sresearch uses descriptive methods and techniques of data collection in the field using the method of observation.From theresults of the study obtaineda value of135.98.This value is multiplied by the weighting criteria appeal to the area that is 6so135.98 x 6=815.9 or C. From the research, the need for cooperation with relevant institutions in order to in crease the potential values​​in Lake Bekat and the need for status determination so as not to conflicttareas in the future. Key words : Lake, Lake Bekat, Attraction, Tayan Downstrea

Single donor ionization energies in a nanoscale CMOS channel

One consequence of the continued downwards scaling of transistors is the reliance on only a few discrete atoms to dope the channel, and random fluctuations of the number of these dopants is already a major issue in the microelectonics industry. While single-dopant signatures have been observed at low temperature, studying the impact of only one dopant up to room temperature requires extremely small lengths. Here, we show that a single arsenic dopant dramatically affects the off-state behavior of an advanced microelectronics field effect transistor (FET) at room temperature. Furthermore, the ionization energy of this dopant should be profoundly modified by the close proximity of materials with a different dielectric constant than the host semiconductor. We measure a strong enhancement, from 54meV to 108meV, of the ionization energy of an arsenic atom located near the buried oxide. This enhancement is responsible for the large current below threshold at room temperature and therefore explains the large variability in these ultra-scaled transistors. The results also suggest a path to incorporating quantum functionalities into silicon CMOS devices through manipulation of single donor orbitals

CAFE: an R package for the detection of gross chromosomal abnormalities from gene expression microarray data

SUMMARY: The current methods available to detect chromosomal abnormalities from DNA microarray expression data are cumbersome and inflexible. CAFE has been developed to alleviate these issues. It is implemented as an R package that analyzes Affymetrix *.CEL files, and comes with flexible plotting functions, easing visualization of chromosomal abnormalities. AVAILABILITY: CAFE is available from https://bitbucket.org/cob87icW6z/cafe/ as both source and compiled packages for Linux and Windows. It is released under the GPL version 3 license. CAFE will also be freely available from Bioconductor. CONTACT: [email protected], [email protected]

The origin of late archaean granitoids in the Sukumaland greenstone belt of Northern Tanzania: geochemical and isotopic constraints

Granitoids intruding the late Archaean sequences of the Sukumaland Greenstone Belt of northern Tanzania belong to two distinct geochemical suites. Suite 1 is characterised by Na2O/K2O > 1 (1.04 – 4.67), high Sr/Y (56 – 204) and Ba/Rb ratios (6.1 – 27.1) and low Rb/Sr ratios (0.08 - 0.25). The rocks are enriched in Sr (405 – 1264 ppm) and depleted in Yb (0.17 – 0.93 ppm) and Rb (56 – 132 ppm). On chondrite-normalised REE diagrams, the rocks display highly fractionated patterns characterised by relative LREE enrichment ((La/Yb)N = 23 – 128 and (Gd/Yb)N = 3.10 – 8.54) and lower concentrations of the HREE (YbN = 0.80 – 4.45). On primitive mantle-normalised spidergrams, Nb and Ti, together with P and Y are depleted relative to adjacent elements. The major and trace element characteristics of Suite 1 are comparable to those of typical Archaean TTG suites and High Silica Adakites (HSA). Suite 2 granitoids are characterised by Na2O/K2O < 1, low Sr/Y (2.80 – 41.7) and Ba/Rb (0.40 – 8.91) ratios and high Rb/Sr (0.30 – 6.27) ratios. Suite 2 is also characterised by low Sr (53 - 326 ppm) and high Rb (40 - 365 ppm) and Yb (0.44 – 1.36 ppm) contents. Compared to Suite 1, Suite 2 rocks display less fractionated REE patterns ((La/Yb)N = 15 – 86 and (Gd/Yb)N = 1.73 – 6.74) and are characterised by higher concentrations of the HREE (YbN = 2.1 – 6.5). On primitive mantle-normalised spidergrams, Suite 2 samples, like those of Suite 1, show relative depletion in Th, Nb and Ti, together with P and Y relative to adjacent elements. Sm-Nd mean crustal residence ages for both suites are indistinguishable and range between 2470 and 2720 Ma with a mean of 2610 &#61617; 35 Ma (2 SE), similar to the emplacement age of 2620 &#61617; 40 Ma. The granitoids are interpreted to have formed by partial melting at the base of a late Archaean thickened sub-arc basaltic crust. Melting to form the Suite 1 granitoids occurred in the eclogite stability field whereas Suite 2 formed by melting at shallower depth in the garnet amphibolite stability field. Tanzania Journal of Science Vol. 32 (1) 2006: pp. 75-8

Atypical PKC-iota Controls Stem Cell Expansion via Regulation of the Notch Pathway

SummaryThe number of stem/progenitor cells available can profoundly impact tissue homeostasis and the response to injury or disease. Here, we propose that an atypical PKC, Prkci, is a key player in regulating the switch from an expansion to a differentiation/maintenance phase via regulation of Notch, thus linking the polarity pathway with the control of stem cell self-renewal. Prkci is known to influence symmetric cell division in invertebrates; however a definitive role in mammals has not yet emerged. Using a genetic approach, we find that loss of Prkci results in a marked increase in the number of various stem/progenitor cells. The mechanism used likely involves inactivation and symmetric localization of NUMB, leading to the activation of NOTCH1 and its downstream effectors. Inhibition of atypical PKCs may be useful for boosting the production of pluripotent stem cells, multipotent stem cells, or possibly even primordial germ cells by promoting the stem cell/progenitor fate

The Use of Control Interventions in Adult Mental Health Inpatient Services in Ontario Hospitals and Identification of Risk Factors

The use of control interventions (CI) such as mechanical/physical restraints (MP), chairs that prevent rising (Chair), and acute control medications (ACM) with mental health (MH) patients is not without controversy. Clinicians report using CIs with patients to gain immediate control of a situation of harm or imminent risk of harm involving the patient and/or others and not unexpectedly, there are unintended physical, psychological, emotional injuries and in the most serious of unintended consequences, death. Despite these substantial negative consequences, there is a dearth of research on the use of CIs in MH hospital services. The goals of the current study were three-fold: to establish the prevalence of CI use and to profile the sociodemographic, MH service use, and MH clinical characteristics of adult MH inpatients with CI use; to better understand the potential risk factors for the use of MP, Chair, ACM, and an inclusive category of “any control intervention”; and thirdly to examine the use of CIs with adult MH inpatients in the absence of a psychiatric emergency situation (NoPES). Methods: The study sample included adult inpatient mental health patients with an admission Resident Assessment Instrument- Mental Health assessment between 2006 and 2010 in Ontario. A descriptive analysis was conducted and multivariate logistic regression was used to investigate potential risk factors for the use of control interventions and the same investigation was conducted for a subsample comprised of patients presenting in hospital without a psychiatric emergency situation. Control interventions included mechanical/physical restraints, chairs that prevent rising and acute control medications. Findings: In Ontario, 21.0% of MH adult inpatients had at least one kind of CI use in the study sample (N = 115,384). The most frequently used CI type was ACM (18.6%) followed by MP (6.5%), and Chair (0.9%). The risk models for each CI type was more informative than for an all-inclusive category of Any-CI. Aggressive behaviour, mania, positive signs and symptoms, risk of harm to others and severity of self-harm increased the risks for CI use. Non-voluntary admission increased the risk of use for all CI types. Unexpectedly greater deficits in performing of activities of daily living, instrumental activities of daily living, cognitive performance, self-care, and having a history of falls increased the risk of CI use. A focus on these latter risk factors will be important in the development of CI reduction strategies. Sociodemographic and history of health service use variables were also considered in the model including older age which was uniquely a risk for Chair use whereas younger age was a risk for MP and ACM showing a bias or preference for Chair use with older patients. Gender was a significant risk factor for MP, ACM use, and only for Chair use with NoPES. Seventy four percent (or 85,514) of the sample did not present in the three days prior to assessment with a psychiatric emergency situation (NoPES) such as extreme behaviours that may put the patient or others at risk of harm. Of these NoPES patients 12,097 (14%) experienced CI use regardless. The identification of NoPES patients is an immediate opportunity for reducing the use of control interventions in MH. The risk models developed in the current research can inform the development of CI reduction strategies; deficits in functional performance increased the risk of CI use as did a history of falls, and attenuated aggressive behaviour, mania, positive signs and symptoms and risk of harm to others. If CI use could be eliminated for the NoPES patients, Ontario could reduce its CI use to less than 10% achieving a major step to providing higher quality patient care for patients and increasing staff satisfaction with the care. Conclusion: This study made use of the new interRAI Control Intervention clinical assessment protocol (CAP) which is embedded in the RAI-MH tool to identify the NoPES patients. This innovation in the RAI-MH is readily available to all hospitals currently using the hospital-based MH assessment instruments. Ontario is in a unique position to immediately use this capability to advance a quality improvement initiative to reduce the use of CIs in MH. The data is readily available enabling public reporting and benchmarking on CI use rates as a patient safety indicator as well as providing hospital-level reports. Additionally, more study is needed nationally and internationally to increase our knowledge of why CIs are used in MH and consequently create effective staff education/training strategies to reduce their use. In conclusion, the use of CIs in adult MH inpatient services in Ontario requires the attention of policy makers and hospital administrators. If CI use in adult MH inpatient services was identified as a priority patient safety concern by government (as it has done for hand hygiene, hospital mortality, and medication safety), Ontario could use readily available data on CI use to immediately measure prevalence, establish performance targets, and report on the progress of improving the quality and safety of care of adult MH inpatients.1 yea

Reduction in apathy following epilepsy surgery

Introduction: Surgical treatment for patients with epilepsy who do not respond to antiepileptic medication can lead to changes in behavior, including new onset of neuropsychiatric symptoms such as depression and anxiety. In other cases, neuropsychiatric symptoms present before surgery may be alleviated. Because application of diagnostic criteria for primary psychiatric disorders may not be valid in assessing behavior in epilepsy populations, we sought to determine the feasibility of measuring behaviors associated with frontal-subcortical dysfunction using the Frontal Systems Behavior Scale (FrSBe) in patients who had received surgical intervention for medically refractory epilepsy. Materials and Methods: Twenty-three patients who had previously undergone epilepsy surgery and their family member informants completed the FrSBe. The FrSBe includes separate forms for patients and informants to rate symptoms associated with three frontal lobe syndromes - executive dysfunction, disinhibition, and apathy - prior to and following a neurological condition. Patients and informants were asked to rate frontal lobe behaviors before and after epilepsy surgery using the FrSBe. Results: Informants rated patients as showing a significantly greater reduction in apathy on the FrSBe compared to either disinhibition or executive dysfunction subscales. A trend in reduction of apathy following right hemisphere resection was found. Conclusions: Patients who have undergone epilepsy surgery show a reduction in apathy but it is unclear whether this behavioral change is directly related to the surgical intervention. We suggest that these preliminary findings support the utility of implementing dimensional scales such as the FrSBe to study behavioral changes following epilepsy surgery

Paper Session II-C - Data Access and Procedure Generation for the International Space Station

The Intelligent Virtual Station (IVS) has been developed by the Smart Systems Research Laboratory at the NASA Ames Research Center as a solution to some of the training and operations challenges faced by organizations like the International Space Station training facilities and Mission Control engineering teams. At present, astronaut crews are constrained by limited access to physical mockups, which themselves have a built-in 1-g limitation. Mission operations teams are faced with the daunting task of controlling the operations and maintenance of an ever-changing Station in space. Many operations teams create and follow textual procedures without the ability to visualize the given actions or alternatives. The IVS allows users to easily generate and view procedures to enhance training and operations. Because training and mission operations are of crucial importance to the International Space Station and other similarly sophisticated programs, this paper is focused on the IVS integrated procedure tool

The pseudogenes of Mycobacterium leprae reveal the functional relevance of gene order within operons

Almost 50 years following the discovery of the prokaryotic operon, the functional relevance of gene order within operons remains unclear. In this work, we take advantage of the eroded genome of Mycobacterium leprae to add evidence supporting the notion that functionally less important genes have a tendency to be located at the end of its operons. M. leprae’s genome includes 1133 pseudogenes and 1614 protein-coding genes and can be compared with the close genome of M. tuberculosis. Assuming M. leprae’s pseudogenes to represent dispensable genes, we have studied the position of these pseudogenes in the operons of M. leprae and of their orthologs in M. tuberculosis. We observed that both tend to be located in the 3′ (downstream) half of the operon (P-values of 0.03 and 0.18, respectively). Analysis of pseudogenes in all available prokaryotic genomes confirms this trend (P-value of 7.1 × 10−7). In a complementary analysis, we found a significant tendency for essential genes to be located at the 5′ (upstream) half of the operon (P-value of 0.006). Our work provides an indication that, in prokarya, functionally less important genes have a tendency to be located at the end of operons, while more relevant genes tend to be located toward operon starts