How Do Drugs And Biologics Differ
Drugs versus Biologics
Generics Drugs versus Follow-On Biologics
- To be approved as a generic, a drug must have the same active ingredient, strength, dosage form, and route of administration as the reference drug, and it must also be “bioequivalent.” This means that generic drugs are the same chemically as their innovator counterparts and that they act the same way in the body. The bioequivalence of the generic drug is demonstrated through relatively simple analyses such as blood level testing, without the need for human clinical trials. In approving a generic drug under 505 of the FDCA, FDA determines that the generic is “therapeutically equivalent” to the innovator drug, and is interchangeable with it.
- FDA has stated that it has not determined how interchangeability can be established for complex proteins . Historically, FDA has permitted interchangeability only when two products are “therapeutic equivalents.” However, when the follow-on manufacturer establishes a new manufacturing process, beginning with new starting materials, it will produce a product that is different from and not therapeutically equivalent with that of the innovator. Because of the complexity of biologics, the only way to establish whether there are differences that affect the safety and effectiveness of the follow-on product is to conduct clinical trials.
What Is Oparin Haldane Theory
The Oparin–Haldane hypothesis suggests that life arose gradually from inorganic molecules, with building blocks like amino acids forming first and then combining to make complex polymers. … Some scientists support the RNA world hypothesis, which suggests that the first life was self-replicating RNA.
Water Is The Universal Solvent
As a polar molecule, water interacts best with other polar molecules, such as itself. This is because of the phenomenon wherein opposite charges attract one another: because each individual water molecule has both a negative portion and a positive portion, each side is attracted to molecules of the opposite charge. This attraction allows water to form relatively strong connections, called bonds, with other polar molecules around it, including other water molecules. In this case, the positive hydrogen of one water molecule will bond with the negative oxygen of the adjacent molecule, whose own hydrogens are attracted to the next oxygen, and so on . Importantly, this bonding makes water molecules stick together in a property called cohesion. The cohesion of water molecules helps plants take up water at their roots. Cohesion also contributes to waters high boiling point, which helps animals regulate body temperature.
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The Possible Molecular Basis For The Opposite Activity Of Iaspp And Aspp2
Previous studies performed in our lab suggested that an important parameter in the molecular basis for the different activity of the ASPP proteins is the different electrostatic potential of the surfaces of their Ank-SH3 domains. The binding interface of ASPP2 has a higher negative charge compared to its homologous surface in iASPP. Examining the sequences of the ASPP proteins revealed that indeed the first Ank repeat and n-src loop of ASPP2 are more negatively charged than these areas in iASPP, while the fourth Ank repeat of iASPP is more negatively charged than this area in ASPP2. The RT loops of both ASPP proteins have the same charge, but there is a difference in the location of their negatively charged residues.
Other examples of highly homologous proteins that bind differentially to their ligands were reported. Sequence variability in the RT and n-src loops in SH3 domains can lead to binding specificity, for example the HIV-1 Nef protein interacts only with the SH3 domain of the Hck protein but not with similar src family members due to one different residue in its RT loop. There are other examples of structurally homologous proteins that bind similar ligands in different ways, but the activity of the proteins is not opposite. For example the retinoid transport proteins bind and transport retinoids in different sub-cellular areas and tissues. Although they have very similar architectures they bind the retinoids in different ways.
Protein Expression And Purification
was expressed in Escherichia coli Rosetta2 . Bacteria were grown in 2xYT medium containing 1% glucose at 37°C. Induction was performed at A600 nm=0.6 with 0.4mM Isopropyl -D-1-thiogalactopyranoside . Cells were harvested after 16h of incubation at 17°C. Bacterial cells expressing HLT-iASPP Pro were lysed using a Microfluidizer . HLT-iASPP Pro showed a high tendency to aggregate. To overcome this, we screened different expression conditions, which included different buffers, NaCl concentrations and additives that included Arginine, Glutamate, Tween 20, Tween 80, zwitergent, trehalose and Trimethylamine N-oxide. Aggregation of HLT-iASPP Pro was minimized in phosphate buffer pH=7, 300mM NaCl, 10% glycerol and in the presence of 0.001% Tween 20. HLT-iASPP Pro was lysed in buffer A containing 1% Tween20, lysozyme, DNase, 0.2mM MgSO4 and 1:200 protease inhibitor P-8849 and purified using an Äkta Explorer FPLC system . The soluble fraction was purified using a Nickel Sepharose FF 4ml column. Elution was performed using an imidzole gradient . HLT-iASPP Pro was further purified using size exclusion chromatography on a Sephacryl S200, 500ml column. Elution was performed with buffer A+0.001% Tween 20, which was also used as the storage buffer. The final concentration of HLT-iASPP Pro was 15M.
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Divergent Secretory Behavior Of The Opposite Ends Of Aggrecan*
- Wei LuoAffiliationsDepartment of Biostructure and Function, School of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030-3705
- Timothy S. KuwadaAffiliationsDepartment of Biostructure and Function, School of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030-3705
- FootnotesAffiliationsDepartment of Biostructure and Function, School of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030-3705
- Jing ZhengAffiliationsDepartment of Biostructure and Function, School of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030-3705
- AffiliationsDepartment of Biostructure and Function, School of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030-3705
- Author Footnotes* This research was initiated under National Institutes of Health Grant AR12683 and supported in part by a grant and graduate fellowships from the University of Connecticut Health Center. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Present address: NCI, National Institutes of Health, Bethesda, MD 20892.
J. Biol. Chem.J. Cell Sci.
What Is The Chemical Evolution Theory
A third theory of life’s origin is known as chemical evolution. In this idea, pre-biological changes slowly transform simple atoms and molecules into the more complex chemicals needed to produce life. … This modern theory then suggests that life originated on Earth by means of a rather slow evolution of nonliving matter.
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What Is Biological And Psychological Positivism
psychology, and economics), positivism refers to the application of the scientific method to explain. human behavior. Early criminological positivists were primarily biological theorists who sought to. explain criminality by identifying physical characteristics and genetic differences that distinguish.
What Are The Principles Of Positivism
The basic principle of Positivism is that all factual knowledge is based on the “positive” information gained from observable experience, and that any ideas beyond this realm of demonstrable fact are metaphysical. Only analytic statements are allowed to be known as true through reason alone.
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What Can Cause Food Contamination
Infectious organisms including bacteria, viruses and parasites or their toxins are the most common causes of food poisoning. Infectious organisms or their toxins can contaminate food at any point of processing or production. Contamination can also occur at home if food is incorrectly handled or cooked.
What Is An Example Of Biological Contamination In Food
A general definition of a hazard as related to food safety is conditions or contaminants that can cause illness or injury. Biological hazards include microorganisms such as bacteria, viruses, yeasts, molds and parasites. Examples of biological hazards include Salmonella, E. coli and Clostridium botulinum.
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Biological Specificity Within Homo Sapiens
Morphologically, humans have an enlarged cranial capacity and more gracile features in comparison to other hominins. The reduction of dentition is a feature that allows for the advantage of adaptability in diet and survival. As a species, humans are culture dependent and much of human survival relies on the culture and social relationships. With the evolutionary change of the reduction of the pelvis and enlarged cranial capacity events like childbirth are dependent on a safe, social setting to assist in the childbirth a birthing mother will seek others when going into labor. This is a uniquely human experience, as other animals are able to give birth on their own and often choose to isolate themselves to do so to protect their young.
An example of a genetic adaptation unique to humans is the gene apolipoprotein E on chromosome 19. While chimpanzees may have the APOE gene, the study The apolipoprotein E gene appears functionally monomorphic in chimpanzees shows that the diversity of the APOE gene in humans in unique. The polymorphism in APOE is only in humans as they carry alleles APOE2, APOE3, APOE4 APOE4 which allows human to break down fatty protein and eat more protein than their ancestors is also a genomic risk factor for Alzheimer’s disease.
Biological Roles Of Water: Why Is Water Necessary For Life
figures by Daniel Utter
Water makes up 60-75% of human body weight. A loss of just 4% of total body water leads to dehydration, and a loss of 15% can be fatal. Likewise, a person could survive a month without food but wouldnt survive 3 days without water. This crucial dependence on water broadly governs all life forms. Clearly water is vital for survival, but what makes it so necessary?
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Which God Is Most Powerful In The World
Shiva is also considered as the God of Gods. The existence which represents infinity itself. He is the supreme masculine divinity in this universe and is lord of the three worlds and is second to none in wrath and power. Sarvaripati Shiva is one of the most fearsome manifestation of the supreme God.
What Is Cesare Lombroso’s Biological Positivist Theory
In so doing, Lombroso suggested that involvement in crime was a product of biology and biological characteristics: criminals were born that way. Lombroso’s theory is essentially a theory of biological positivism. … positivism is a research tradition that seeks to establish objective causes of individual behaviour.
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Nickel Affinity Pulldown Assay
30l Nickel-NTA beads were incubated with: 500l buffer C 250l 31M HLT 2ml 1.7M HLT-iASPP Pro for 1hour with gentle mixing at 4°C and in the presence of 40mM imidazole. The samples were centrifuged and washed with buffer C . 80l of 80M iASPP Ank-SH3 in 20mM Phosphate buffer pH=7.0, 150mM NaCl, 5mM Me, 10% glycerol, 0.02% NaN3, 15mM imidazole were added to the three samples. For diluting iASPP Ank-SH3, each sample was added to 1ml 25mM phosphate buffer pH=7.0, 10% glycerol, 25mM Imidazole and 100mM NaCl. The Nickel-NTA beads and iASPP Ank-SH3 were gently mixed for 2hours at 4°C. The samples were centrifuged and the supernatants were collected. The samples were washed three times with 1ml buffer C and the third washes were kept. The beads were eluted by boiling them in SDS sample solution. Samples were analyzed on a 10% SDS-PAGE gel.
Chemical Reactions Of Water
Water is directly involved in many chemical reactions to build and break down important components of the cell. Photosynthesis, the process in plants that creates sugars for all life forms, requires water. Water also participates in building larger molecules in cells. Molecules like DNA and proteins are made of repetitive units of smaller molecules. Putting these small molecules together occurs through a reaction that produces water. Conversely, water is required for the reverse reaction that breaks down these molecules, allowing cells to obtain nutrients or repurpose pieces of big molecules.
Figure 4: Water acts as a buffer by releasing or accepting hydrogen atoms.
In conclusion, water is vital for all life. Its versatility and adaptability help perform important chemical reactions. Its simple molecular structure helps maintain important shapes for cells inner components and outer membrane. No other molecule matches water when it comes to unique properties that support life. Excitingly, researchers continue to establish new properties of water such as additional effects of its asymmetrical structure. Scientists have yet to determine the physiological impacts of these properties. Its amazing how a simple molecule is universally important for organisms with diverse needs.
Molly Sargen is a first-year PhD Student in the Biological and Biomedical Sciences Program at Harvard Medical School.
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How Is Chemical Evolution Different From Biological Evolution
So to sum things up: The main difference between chemical evolution and biological evolution, is that chemical evolution can produce new characteristics and abilities, without depending on reproduction. Because of this, chemical evolution is being investigated as a possible cause for the origin of life.
What Are The Three Basic Premises Of Positivism
The three central tenets of positivism identified by commentators are:
- phenomenalism:. …
- causality: that phenomena are interrelated via causal propositions.
- objectivism: that scientific enquiry should be objective and value-free, its methods should be independent of the researcher, repeatable and reliable.
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The Binding Interface Between The Iaspp Domains
Our results show that iASPP Ank-SH3 and the full iASPP Pro 1-602 interact in vitro. It was shown before that the interaction of iASPP Pro with iASPP Ank-SH3 in cells is inhibited by phosphorylation of iASPP Pro on S84 and S113 by B1/CDK1. However it is not clear from the cellular studies or from our in vitro studies if the interaction between the iASPP domains is intramolecular or intermolecular,. The fact that iASPP Pro is intrinsically disordered might support the intramolecular possibility because many proteins that are regulated by autoinhibitory mechanism have intrinsically disordered regulatory domains. Many of these regulatory domains undergo alternative splicing, such as in the ASPP proteins and have many phosphorylation sites,. In any case, the final regulatory outcome is the same regardless of whether the domain-domain interaction is intramolecular or involves dimerization.
The Binding Interfaces In Iaspp Vs Aspp2
Comparing the Pro – Ank-SH3 interaction interfaces in iASPP and ASPP2 revealed distinct and specific binding sites, which are totally different from each other. iASPP Pro binds the fourth Ank repeat , RT loop and C-terminal residues of iASPP Ank-SH3. ASPP2 Pro binds the first Ank-repeat and n-src loop of ASPP2 Ank-SH3 . The interface in iASPP Pro that mediates the interaction with its Ank-SH3 domain is much larger than the corresponding interface in ASPP2 Pro, probably because iASPP Pro is more than twice longer than ASPP2 Pro.
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What Are The Sources Of Meat Contamination
Rubber, plastic and wood: There are many ways these materials can make their way into meat and poultry products. From rubber gaskets and rubber gloves to heavy plastic tools, packaging and even the handles of tools, machine parts and equipment used by workers all have the potential to contaminate food.
Development Of A New Protocol Protocol For The Expression And Purification Of Iaspp Pro
HLT-iASPP Pro was expressed in E.coli Rosetta2 as described in materials and methods. HLT-iASPP Pro initially showed a high tendency to aggregate. Following the screening of conditions as described in materials and methods, aggregation was minimized in 50mM phosphate buffer pH=7, 300mM NaCl, 10% glycerol and 0.001% Tween 20. HLT-iASPP Pro was purified in two steps, including affinity chromatography using a Nickel Sepharose column followed by size exclusion chromatography . An imidazole gradient was used for eluting HLT-iASPP Pro from the Nickel column. HLT-iASPP Pro eluted in 100% elution buffer containing 300mM Imidazole. Unspecific bound contaminations eluted in 10%20% elution buffer. The 602 residues iASPP-Pro was expressed with it truncated forms. These impurities, which eluted with the full protein from the Nickel column, were separated from the full length protein by using size exclusion chromatography. The full protein eluted first from the size exclusion column and was successfully separated from its truncated forms. We did not cleave the HLT tag to avoid the aggregation of the protein. The final concentration of HLT-iASPP Pro was 15M.
Purification of HLT-iASPP Pro.
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What Is Biological Sex Really
One of the dominant narratives in gender theory and queer activism right now is the idea of a separation between gender and sex, wherein gender is a personal identity and gender categories are socially constructed, while sex is biological. Interestingly, most writers that use this concept dont bother to define what, specifically, defines these natural and biological categories of sex, as though readers should automatically know what they are talking about.
Of course, most readers do automatically know what they are talking about, and therein lies the problem.
I do not contest that there is much value in recent gender discourses. Unraveling and examining the ways in which gender fables establish and circulate the misnomer of natural facts has been an important step forward in discourses around gender. However, such discourses often leave examined the notion of biological sex.
Perhaps this has been done as an attempt to placate more conservative minds. To make modern gender politics easier to swallow, by allowing the strict binary of male/female to continue to exist, so long as it remains in the realm of sex rather than gender. Perhaps not.
Recently, people seem to jump at any chance to challenge the very basis of feminist thought that there are 2 sexes and there are 2 genders . And yet one must wade through the veritable sea of critiques of the gender binary to find even the smallest suggestion that sex is just as socially contrived.