Mehnaz mann biography of william

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Abstract

Hereditary Angioedema (HAE) is an autosomal dominant disease characterized by episodic swelling, arising from genetic deficiency in C1-esterase inhibitor (C1INH), a regulator of several proteases including activated Plasma kallikrein (Pka). Many existing C1INH treatments exhibit short circulatory half-lives, precluding prophylactic use. Hexahistidine-tagged truncated C1INH (trC1INH lacking residues 1–97) with Mutated N-linked Glycosylation Sites NQ/NQ/NQ (H₆-trC1INH(MGS)), its murine serum albumin (MSA) fusion variant (H₆-trC1INH(MGS)-MSA), and H₆-MSA were expressed in Pichia pastoris and purified via nickel-chelate chromatography. Following intravenous injection in mice, the mean terminal half-life of H₆-trC1INH(MGS)-MSA was significantly increased versus that of H₆-trC1INH(MGS), by 3-fold, while remaining ~35% less than that of H₆-MSA. The extended half-life was achieved with minimal, but significant, reduction in the mean second order rate constant of Pka inhibition of H₆-trC1INH(MGS)-MSA by 33% relative to that of H₆-trC1INH(MGS). Our results validate albumin fusion as a viable strategy for half-life extension of a natural inhibitor and suggest that H₆-trC1INH(MGS)-MSA is worthy of investigation in a murine model of HAE.

Introduction

Heredit

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Child abuse

Maltreatment or neglect of a child

"Child maltreatment" redirects here. For the journal, see Child Maltreatment (journal).

Child abuse (also called child endangerment or child maltreatment) is physical, sexual, emotional and/or psychological maltreatment or neglect of a child, especially by a parent or a caregiver. Child abuse may include any act or failure to act by a parent or a caregiver that results in actual or potential wrongful harm to a child and can occur in a child's home, or in organizations, schools, or communities the child interacts with.

Different jurisdictions have different requirements for mandatory reporting and have developed different definitions of what constitutes child abuse, and therefore have different criteria to remove children from their families or to prosecute a criminal charge.

History

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As late as the 19th century, cruelty to children, perpetrated by employers and teachers, was commonplace and widespread, and corporal punishment was customary in many countries, but in the first half of the 19th century, pathologists studying filicide (the parental killing of children) reported cases of death from paternal rage,^[1] recurrent physical maltreatment,^[2] starvation,^[3] and sexual ab