scholarly journals miR-192, miR-194, miR-215, miR-200c and miR-141 are downregulated and their common target ACVR2B is strongly expressed in renal childhood neoplasms

2012 ◽  
Vol 33 (5) ◽  
pp. 1014-1021 ◽  
Author(s):  
U. Senanayake ◽  
S. Das ◽  
P. Vesely ◽  
W. Alzoughbi ◽  
L. F. Frohlich ◽  
...  
2019 ◽  
Author(s):  
john andraos

This paper proposes a standardized format for the preparation of process green synthesis reports that can be applied to chemical syntheses of active pharmaceutical ingredients (APIs) of importance to the pharmaceutical industry. Such a report is comprised of the following eight sections: a synthesis scheme, a synthesis tree, radial pentagons and step E-factor breakdowns for each reaction step, a tabular summary of key material efficiency step and overall metrics for a synthesis plan, a mass process block diagram, an energy consumption audit based on heating and cooling reaction and auxiliary solvents, a summary of environmental and safety-hazard impacts based on organic solvent consumption using the Rowan solvent greenness index, and a cycle time process schedule. Illustrative examples of process green synthesis reports are given for the following pharmaceuticals: 5-HT2B and 5-HT7 receptors antagonist (Astellas Pharma), brivanib (Bristol-Myers Squibb), and orexin receptor agonist (Merck). Methods of ranking synthesis plans to a common target product are also discussed using 6 industrial synthesis plans of apixaban (Bristol-Myers Squibb) as a working example. The Borda count method is suggested as a facile and reliable computational method for ranking multiple synthesis plans to a common target product using the following 4 attributes obtained from a process green synthesis report: process mass intensity, mass of sacrificial reagents used per kg of product, input enthalpic energy for solvents, and Rowan solvent greenness index for organic solvents.<br>


2021 ◽  
pp. 019262332110094
Author(s):  
Janet M. Petruska ◽  
Maria Adamo ◽  
Jeffrey McCartney ◽  
Ahamat Aboulmali ◽  
Thomas J. Rosol

The most common target organ for toxicity in the endocrine system is the adrenal gland, and its function is dependent upon the hypothalamus and pituitary gland. Histopathologic examination of the adrenal glands and pituitary gland is routinely performed in toxicity studies. However, the function of the adrenal gland is not routinely assessed in toxicity studies. Assessment of adrenal cortical function may be necessary to determine whether a histopathologic finding in the adrenal cortex results in a functional effect in the test species. As juvenile toxicity studies are more commonly performed in support of pediatric indications for pharmaceuticals, it is important to establish historical control data for adrenal gland function. In this study, adrenal cortical function was assessed in control neonatal and weanling beagle dogs as part of an ongoing juvenile toxicology program. Measurements of serum adrenocorticotropic hormone (ACTH), cortisol prior to and following administration of exogenous ACTH, and aldosterone were conducted beginning at 2 weeks of age continuing through 26 weeks of age. Serum electrolyte concentrations were determined at 4, 13, and 26 weeks of age. Dogs as young as 2 weeks of age synthesize and secrete adrenal cortical hormones and exhibit a functional hypothalamic pituitary adrenal axis.


Electronics ◽  
2021 ◽  
Vol 10 (15) ◽  
pp. 1819
Author(s):  
Rasa Bruzgiene ◽  
Konstantinas Jurgilas

Information systems of critical infrastructure provide services on which the core functions of a state and its economy depend as well as welfare of society. Such systems are becoming an increasingly common target for crimes and attacks in cyberspace, as their vulnerabilities can be exploited for malicious activities seeking financial or political gain. One of the main reasons that threatens the security of these systems is the weak control of remote access, otherwise defined as management of a system’s user identity. Management of user identity depends on user authentication, authorization and the assignment of certain rights in the digital space. This paper provides the proposed two-factor (2FA) digital authentication method for remote access to an information system of a critical infrastructure. Results of testing the method’s usability and resilience to cyber threats have shown that the system, in which the method was implemented, is protected from dangerous HTTP requests and publicly available system’s endpoints are protected from threatening inputs that could cause malicious activities on the critical infrastructure. Additionally, the implementation of the authentication API application ensures the rapidity of the method for less than 500 ms for 100 users working in parallel with the system at the same time.


2019 ◽  
Vol 8 (1) ◽  
pp. 787-801
Author(s):  
John Andraos

Abstract This paper proposes a standardized format for the preparation of process green synthesis reports that can be applied to chemical syntheses of active pharmaceutical ingredients (APIs) of importance to the pharmaceutical industry. Such a report is comprised of the following eight sections: a synthesis scheme, a synthesis tree, radial pentagons and step E-factor breakdowns for each reaction step, a tabular summary of key material efficiency step and overall metrics for a synthesis plan, a mass process block diagram, an energy consumption audit based on heating and cooling reaction and auxiliary solvents, a summary of environmental and safety-hazard impacts based on organic solvent consumption using the Rowan solvent greenness index, and a cycle time process schedule. Illustrative examples of process green synthesis reports are given for the following pharmaceuticals: 5-HT2B and 5-HT7 receptors antagonist (Astellas Pharma), brivanib (Bristol-Myers Squibb), and orexin receptor agonist (Merck). Methods of ranking synthesis plans to a common target product are also discussed using 6 industrial synthesis plans of apixaban (Bristol-Myers Squibb) as a working example. The Borda count method is suggested as a facile and reliable computational method for ranking multiple synthesis plans to a common target product using the following 4 attributes obtained from a process green synthesis report: process mass intensity, mass of sacrificial reagents used per kg of product, input enthalpic energy for solvents, and Rowan solvent greenness index for organic solvents.


2016 ◽  
Vol 9 (1) ◽  
pp. 30
Author(s):  
Wei Zhang ◽  
Jun Wang ◽  
Zhiyuan Mi ◽  
Jiangtao Su ◽  
Xiangyu You ◽  
...  

Although misuse and abuse of Cannabis is well known, the health benefits have been proved by various biomedical studies. Tetrahydrocannabinol (THC) is the major active substance in leaves of Cannabis, which is the common target for drug testing. In field drug testing, oral fluid (OF) has its unique advantages over other specimens such as blood, urine, and hair. Thus the study of THC in OF is gaining popularity in Cannabis research. In this review, extraction methods are introduced in three categories, which are Liquid-Liquid Extraction (LLE), Solid Phase Extraction (SPE), and Supercritical Fluid Extraction (SFE). Examples of application with each method will be covered. Advantages and disadvantages of these methods will be compared. In addition, methods in analysis following extraction will be briefly discussed.


Blood ◽  
2015 ◽  
Vol 125 (23) ◽  
pp. 3609-3617 ◽  
Author(s):  
Jinjun Dang ◽  
Lei Wei ◽  
Jeroen de Ridder ◽  
Xiaoping Su ◽  
Alistair G. Rust ◽  
...  

Key Points Heterozygous alterations of Pax5, the most common target of genetic alteration in ALL, promote ALL in mouse mutagenesis models. Leukemia development is accompanied by the acquisition of genetic alterations commonly observed in human leukemia.


2013 ◽  
Vol 16 (4) ◽  
pp. 530 ◽  
Author(s):  
Hitesh B Vaidya ◽  
Abeer A Ahmed ◽  
Ramesh K Goyal ◽  
Sukhinder K Cheema

Purpose. Diabetes mellitus is characterized by hyperglycemia resulting from defects in insulin secretion, action or both. The use of medicinal plants for the treatment of diabetes mellitus dates back from the Ebers papyrus of about 1550 B.C. One of the major problems with herbal drugs is that the active ingredients are not well defined. It is important to know the active components and their molecular interactions which will help to analyze their therapeutic efficacy and also to standardize the product. There are a number of medicinal plants known for their anti-diabetic effect that possess similarities in their active chemical components, e.g. iridoid and secoiridoid glycosides. Methods. In this study, we have compared the structure of various iridoid and secoiridoid glycosides to design a novel pharmacophore. We further developed a structure-activity relationship for the inhibition of glycogen phosphorylase-a. Conclusion. By using docking studies, we are proposing, for the first time, that inhibition of glycogen phosphorylase-a activity is a common target for iridoids and secoiridoids to elicit anti-diabetic effects. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


2018 ◽  
Vol 17 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Tatsuya Sasaki ◽  
Ken Kuwahara ◽  
Ittetsu Kin ◽  
Mihoko Okazaki ◽  
Susumu Sasada ◽  
...  

Abstract BACKGROUND Details of the somatotopy within the subthalamic nucleus (STN) are still poorly understood; however, the STN is a common target of deep brain stimulation (DBS) for Parkinson disease. OBJECTIVE To examine somatotopic organization within the STN and identify optimal stimulation sites from 77 surgical cases with microelectrode recording. METHODS STN-DBS was performed for 77 patients with Parkinson disease between 2010 and 2014. We performed passive movements of each joint and captured single neuronal activities to identify movement-related cells (MRCs). The sites of MRCs and active contacts were determined by measuring their distances from the first contact of DBS electrode. Their positional correlations were directly and indirectly analyzed. RESULTS The number of obtained MRCs was 264, of which 151 responded to multiple joints. The average x-, y-, and z-coordinates of the cells of the upper and lower limbs from the midcommisural point were 13.1 ± 1.1 and 12.7 ± 1.2, 0.22 ± 1.3 and −0.45 ± 1.5, and −2.5 ± 1.1 and −3.0 ± 1.4 mm, respectively. Most MRCs were distributed in the upper third of the STN, in its superior, lateral, and posterior regions, along the DBS electrode routes. Active contacts were observed to lie slightly inferior, medial, and posterior to the average MRC position. CONCLUSION Somatotopic organization of the STN was easier to observe in the present study than in previous studies. Optimal stimulation sites were located inferior, medial, and posterior to the average MRC location. The sites may correspond to associative or motor parts through which fibers from the supplementary motor area pass.


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