In conclusion it is necessary to note that heterocycles (11a, b) are of interest as a starting material for further re- search on the synthesis of carbocyclic steroids. Compounds (15, 16a, b, c) are of interest in terms of biologicaltesting for oestrogenic activity because coumarine analogs of steroids are known to show this activity and keep it for much longer period than natural compounds .
The phrase “drugs that wouldn’t die” is taken from an article by Weintraub and Northington (4). They described case histories of five unprofitable drugs that were taken off the market, but later were reintroduced as a result of pressure from physicians, patients and other health professionals. Each of these drugs is an orphan, either based on the small size of the disease population or because the drug is unprofitable and only benefits a small segment of patients with a common disease. Some of the potential drugs get killed by over publicity. An example of such a drug is thalidomide, which was initially used indiscriminately and injudiciously. The drug had teratogenic effect, which led to serious adverse effects in large population, particularly children and this was followed by large number of court cases for teratogenicity (2). Discovery to orphan drugs is similar to that of non-orphan drugs i.e. preclinical evaluations and clinical trials. Preclinical activities leading to discovery of orphan drugs include chemical synthesis targeted to find a drug for the treatment of rare diseases, biologicaltesting of compound/molecules in an animal model of a rare disease with the aim of finding a new activity, serendipitously found biological activities in animal studies that suggest a potential clinical usefulness of molecule/compound in treating a rare disease and a new theory proposed to suggest that the lead molecule has activity for a rare disease (2,5). Most common mode of discovery of orphan drug is by serendipitously found clinical activity in patients with a specific rare disease. These patients often have a co-existent rare disease along with the disease for which he/she is being treated and during the course of treatment; it is found to have activity for the rare disease with which the patient is suffering in some other cases, the physicians managing their patients with a rare disease have a personal belief or theory that the drug might be helpful for the treatment of a rare disease and they test the drug and thus some of the drugs for rare diseases or novel indications for humans were found (2,4).
The last area of research to be discussed here is also the most recent, being driven by the developments in combinatorial chemistry and high-throughput screening that took place in the early Nineties. These technological improvements meant that it was now possible to synthesise and to test vastly more molecules than had previously been the case. However, real-world experiments were still expensive and there was hence much interest in computational methods to ensure that those molecules that were put forward for testing could provide the maximum amount of information to support lead discovery in a cost-effective manner. This requirement led initially to work on maximising the structural diversity (i.e., the level of dissimilarity) of the molecules that are submitted for biologicaltesting, whilst minimising the numbers of molecules that are tested. The Similar Property Principle discussed in Section 4 implies that structurally similar molecules are likely to exhibit the same bioactivity, and hence the synthesis of large numbers of structurally related molecules is unlikely to result in a commensurate amount of useful structure-activity data. Patterson et al.  postulated the related, but distinct, concept of Neighbourhood Behaviour, which states that structurally dissimilar molecules may give different biological responses. The maximum amount of structure-activity information that can be extracted from testing some fixed number of molecules (as determined by the testing capacity that is available) will thus be obtained by selecting a set of molecules that are as diverse as possible.
The present investigation has proved the chromotoxic behaviour of heeng as Homoeopathic drug. Various types of cytological & cytogenetical aberrations were observed by biologicaltesting of heeng as Homoeopathic drug on Vicia faba plant. The mitotic index inhibit by the effect of heeng with increase in concentration & duration. Kuras et al (2009) found alkaloids from Licaria fomentosa bark were retard or inhibit mitosis & change mitotic phase in Allium cepa. Palani & Pannerselvam (2007) tested cytogenetic effect or mitotic effect of food preservation on root tips of Allium cepa. Amato (1949, 1952) suggested that reduced MI by the chemical mutagens has resulted due to prophase poisoning and restriction of the dividing cells of prophase or interphase. Chandra et. al. (1989) reported that the certain Homoeopathic drugs are also pressive due to inhibition of cell division & germination of spores in various fungi. Sadia & Vahidy (1994), Kumar and Shrivastva (2011) reported that boron as food preservative disturb the normal cell cycle & reduced the mitotic index ( Abdel-Hady and Barakat 2005, Sifa 2007).
To provide contextual information about the families assessed in this re- port, parents’ biologicaltesting for opiates and cocaine (Table 4) and their report of their own tobacco, alcohol, marijuana, cocaine, and opiate (Table 5) use is provided. Parents were 3.2 times more likely to refuse hair sam- pling than their teens (99 vs 55; OR: 3.2 [95% CI: 1.89 –5.46]; P ⬍ .001). How- ever, samples were 9.1 times more likely to be obtained from parents than their children because more children had hair too short for adequate sam- pling (14 vs 87; OR: 9.1 [95% CI: 4.43– 19.39]; P ⬍ .001). This difference oc- curs at least in part because most of the parents were female, whereas half of the teens were male. A total of 69 parents (28.3%) had a hair assay pos- itive for cocaine, including 15 (6.6%) who admitted to current cocaine use. Like their teens, parents signiﬁcantly underreported cocaine (Wald 2 ⫽
Even in the absence of major disturbances (e.g., cyclones, bleaching), corals are subject to high levels of partial or whole- colony mortality, often caused by chronic and small-scale disturbances. Depending on levels of background mortality, these chronic disturbances may undermine individual fitness and have significant consequences on the ability of colonies to withstand subsequent acute disturbances or environmental change. This study quantified intraspecific variations in physiological condition (measured based on total lipid content and zooxanthellae density) through time in adult colonies of two common and widespread coral species (Acropora spathulata and Pocillopora damicornis), subject to different levels of biological and physical disturbances along the most disturbed reef habitat, the crest. Marked intraspecific variation in the physiological condition of A. spathulata was clearly linked to differences in local disturbance regimes and habitat. Specifically, zooxanthellae density decreased (r 2 = 26, df = 5,42, p,0.02, B = 2121255, p = 0.03) and total lipid content increased (r 2 = 14, df = 5,42, p = 0.01, B = 0.9, p = 0.01) with increasing distance from exposed crests. Moreover, zooxanthellae density was strongly and negatively correlated with the individual level of partial mortality (r 2 = 26, df = 5,42, p,0.02, B = 2 7386077, p = 0.01). Conversely, P. damicornis exhibited very limited intraspecific variation in physiological condition, despite marked differences in levels of partial mortality. This is the first study to relate intraspecific variation in the condition of corals to localized differences in chronic disturbance regimes. The next step is to ascertain whether these differences have further ramifications for susceptibility to periodic acute disturbances, such as climate-induced coral bleaching.
The anthropogenic discharge of phosphorus (P) needs to be managed as it will cause undesirable eutrophication and water quality deterioration in receiving waters (Cordell et al., 2009; Rittmann et al., 2011). The enhanced biological phosphorus removal (EBPR) process, which enriches and utilizes a group of polyphosphate-accumulating organisms (PAOs) to take up inorganic phosphorus from wastewater by intracellular accumulation, has been demonstrated as a promising method for removal of phosphorus with economic and environmental benefits compared to chemical phosphorus removal (Oehmen et al., 2007). Challenges remain for the EBPR-employed water resource recovery facilities (WRRFs) in complying with more and more stringent effluent P limits due to inconsistent process performance, which is often a result of inadequate or variable influent readily degradable carbon (rbCOD) (Barnard and Abraham, 2006; Gu et al., 2008; Neethling et al., 2005). As an alternative to conventional EBPR, the side-stream EBPR (S2EBPR) process adds a side-stream anaerobic reactor where a portion or all of the return activated sludge (RAS) or mixed liquor suspended solids (MLSS) undergoes hydrolysis and fermentation, and the overflow from this reactor is directed back to the main-stream biological process. Compared to the conventional mainstream EBPR, S2EBPR process requires fewer chemicals, smaller footprint, produces fewer odors, provides additional carbon for denitrification, and can be implemented in a variety of existing EBPR configurations without reliance on influent carbon (Barnard et al., 2016; Tooker et al., 2017).
Large sample sizes are required to detect weak genetic effects influencing disease risk. Thanks to technical advances and the formation of data-sharing consortia in particular, larger GWAS datasets have become available over recent years. However, genotyping and participant recruitment are still cost and work intensive. Especially in rare diseases, taking as an example the analysis of histological subtypes of a disease, it is very challenging to achieve sample sizes that result in adequate power in analyses . Another challenge we face is to understand the biological meaning of detected associations. It is often difficult to interpret the results of GWAS analysis in the elucidation of the precise biological processes and corresponding functional units influencing disease susceptibility. Single-pathway analysis methods are often successful in the identification of genetic effects influ- encing disease susceptibility. However, they usually can not discriminate causal biological processes from isolated effects included in pathways due to gene overlap [6, 7]. Another limitation of many pathway analysis approaches is the lacking ability to predict the disease state, or other outcomes of interest, based on the identified genetic effects.
Citation Brinkmann A, Andrusch A, Belka A, Wylezich C, Höper D, Pohlmann A, Nordahl Petersen T, Lucas P, Blanchard Y, Papa A, Melidou A, Oude Munnik BB, Matthijnssens J, Deboutte W, Ellis RJ, Hansmann F, Baumgärtner W, van der Vries E, Osterhaus A, Camma C, Mangone I, Lorusso A, Marcacci M, Nunes A, Pinto M, Borges V, Kroneman A, Schmitz D, Corman VM, Drosten C, Jones TC, Hendriksen RS, Aarestrup FM, Koopmans M, Beer M, Nitsche A. 2019. Proﬁciency testing of virus diagnostics based on bioinformatics analysis of simulated in silicohigh-throughput sequencing data sets. J Clin Microbiol 57:e00466-19. https://doi.org/10.1128/JCM.00466-19.
Multipoint identity-by-descent (IBD) probabilities were estimated by GENEHUNTER and imported into SOLAR to estimate the genetic variance attributable to a hypotheti- cal quantitative trait loci (QTL) linked to any given loca- tion. A test for linkage was carried out by testing whether the QTL additive variance was significantly different from 0 by comparing the likelihood of this model with that of a restricted model in which the genetic variance at the same location was fixed at 0. LOD scores reported in the text and the tables are calculated by SOLAR as the log 10 of the likelihood ratio of these two models.
biological STRATEGIESAREAS EMPLOYERS What can I do with this degree? Research and Development Laboratory Testing Teaching BIOLOGICAL SCIENCES BIOTECHNOLOGY Colleges and universities Pharmaceutical com[.]
Obtaining samples from individuals with dry mouths can be dif- ficult and requires longer collection times. Illicit drugs that reduce oral fluid secretion include amphetamines and cannabis; com- monly used drugs having the same effect include antihistamines, antipsychotics, anticholinergics, and some antidepressants. Oral fluid production can be stimulated by the use of agents such as citric acid sweets and chewing gum, but this inevitably changes the pH and concentration of drug in the oral fluid. A range of specialized collection devices has been developed in order to support the collection of oral fluid samples for DAT. These devices are designed to either preserve samples for safe transport to conventional laboratory-based screening or are instead incorpo- rated into a small testing device capable of providing rapid yes/ no determinations. These devices are ideally suited for oral fluid testing used as part of “driving under the influence of drugs” detection programs, criminal justice programs, and the monitoring of medication compliance and workplace safety schemes. 16
As an alternative to rigid exoskeletons, we have devel- oped a multi-joint soft exosuit [17–22] that uses textiles to provide a more compliant means to interface with the human body (Fig. 1a-b). Our exosuit is lightweight, with the majority of mass worn close to the wearer’s center of mass (Additional file 1: Table S1, which compares the weight with other autonomous exoskeletons), minimizing its impact on the energetics of gait . The soft exosuit transmits moments around the biological joint axes through flexible cable-based transmissions and textiles that anchor to the body. Moreover, the exosuit minimally influences the wearer’ s natural walking kinematics  and is active only when it detects walking. At all other times, the exosuit can be truly transparent when the cables are commanded to go slack. For this study, the exo- suit assisted walking by generating assistive torques at the ankle and the hip, since they are the major power contrib- utors to level-ground walking , via forces in two load
All data science methods have specific assumptions that are made in order for their inferences to be valid. Some assumptions impact statistical significance test- ing and some influence the models themselves. For example, a fundamental assumption of linear regression is that the relationship between the independent and dependent variables is additive such that a unit increase in one leads to a unit increase in the other with some error that can be modeled using a normal distribution. The presence of a nonlinear relationship between the variables vio- lates this assumption and can lead to inaccurate inferences. We demonstrate this here using a simple example from human genetics and then end with some thoughts about the role of biological data mining in revealing nonlinear relation- ships between variables.
Amongst different five membered heterocyclic systems oxadiazole, thiadiazole, triazole and their derivatives have gained importance as they constitute the structural features of many bioactive compounds. Substituted 1,3,4- oxadiazoles have revealed antibacterial , antifungal , anti-inflammatory , analgesic [4,5] and anticonvulsant properties . Compounds possessing oxadiazole moiety show anticancer  and tyrosinase inhibitory activity . 2,5-Disubstituted 1,3,4-thiadiazoles possess various biological properties such as antitumor , anticonvulsant ,
reports. As a consequence, the biological daughters of mothers with high reproductive output (i.e. higher litter mass at weaning) had a higher reproductive output than the biological daughters of mothers with low reproductive output – independent of the mother that actually raised them through lactation. Non-genetic maternal effects during the lactation period did not play a significant role in this effect as SusEI and MEO were not related between pups and their foster mothers and did not differ between daughters of the same mother that stayed with their biological mother or were fostered. Females with a higher SusEI thus raised larger pups and this may benefit their offspring later in life, as many studies have shown that low birth mass is associated with higher risk of cardiovascular diseases, hypertension, diabetes and metabolic syndrome as adults (Whincup et al., 2008), although a relationship between body size and longevity was not found in MF1 mice (Speakman et al., 2004b). Dairy cows have been selected for high milk yields for many years and heritability of milk yield in dairy cows is estimated to lie between 0.04 and 0.67, but varies between different herds, depends on the generation of selection and is subject to sampling errors (Dechow and Norman, 2007; Lee, 1997; Schneider and Vanvleck, 1986; Vanvleck and Bradford, 1964; Veerkamp, 1998). In agreement with the present study, food intake and milk yield (or MEO) have been shown to be highly correlated (0.46–0.65 in dairy cows, 0.72 for MEO in the present study) and estimates for heritability of food intake during lactation and milk yield are generally similar (Veerkamp, 1998).