Advancements in mammalian display technology for therapeutic antibody development and beyond: current landscape, challenges, and future prospects.

The evolving development landscape of biotherapeutics and their growing complexity from simple antibodies into bi- and multi-specific molecules necessitates sophisticated discovery and engineering platforms. This review focuses on mammalian display technology as a potential solution to the pressing challenges in biotherapeutic development. We provide a comparative analysis with established methodologies, highlighting key aspects of mammalian display technology, including genetic engineering, construction of display libraries, and its pivotal role in hit selection and/or developability engineering.

A novel multi-stage distributed authentication scheme for smart meter communication.

Smart meters have ensured effective end-user energy consumption data management and helping the power companies towards network operation efficiency. However, recent studies highlighted that cyber adversaries may launch attacks on smart meters that can cause data availability, integrity, and confidentiality issues both at the consumer side or at a network operator's end. Therefore, research on smart meter data security has been attributed as one of the top priorities to ensure the safety and reliability of the critical energy system infrastructure.

Association of Wnt9B rs1530364 and Wnt5A rs566926 Gene Polymorphisms with Nonsyndromic Cleft lip and Palate in South Indian Population using Deoxyribonucleic Acid Sequencing.

Context: Nonsyndromic cleft lip with or without cleft palate (CL/CP) is a common congenital facial malformation without any other structural or developmental abnormalities.

Aims And Objectives: To test the association of Wnt9B rs1530364 and Wnt5A rs566926 gene variants with the nonsyndromic CL/CP patients in South Indian population.

Methods: Deoxyribonucleic acid (DNA) samples of 25 subjects with nonsyndromic cleft lip and palate (NSCLP) and 25 unrelated controls collected from the department were used for the study.

Asymmetric confinement for defining outgrowth directionality.

Directional connectivity is required to develop accurate in vitro models of the nervous system. This research investigated the interaction of murine neuronal outgrowths with asymmetric microstructured geometries to provide insights into the mechanisms governing unidirectional outgrowth bias. The structures were designed using edge-guidance and critical turning angle principles to study different prohibitive to permissive edge-guidance ratios.

Serial integration of Dean-structured sample cores with linear inertial focussing for enhanced particle and cell sorting.

In this contribution, a channel aspect ratio of >2 was used to access high velocity regimes to provide confined sample cores by Dean focussing in advance of linear inertial focussing. This produces a singular separation origin with a mirrored transport path for efficient particle and blood cell sorting, while also increasing the spatial resolution for multiscale sorting.

Long-term maintenance of a microfluidic 3D human liver sinusoid.

The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip, using human cells only for a period of 28 days.

Integration of the Herbst and Begg appliance in the management of severe Class II malocclusion.

The efficacy of the Herbst appliance in a normalizing sagittal relationship in patients with a Class II malocclusion is well-documented. This case report describes the treatment of a 14-year-old male patient with severe Class II Division 1 malocclusion due to retrognathic mandible and mildly prognathic maxilla, convex profile, and lip trap. He had severely proclined maxillary incisors and retroclined mandibular incisors, overjet of 13 mm and overbite of 7 mm.

Long-term coculture strategies for primary hepatocytes and liver sinusoidal endothelial cells.

Hepatocytes and their in vitro models are essential tools for preclinical screening studies for drugs that affect the liver. Most of the current models primarily focus on hepatocytes alone and lack the contribution of non-parenchymal cells (NPCs), which are significant through both molecular and the response of the NPCs themselves. Models that incorporate NPCs alongside hepatocytes hold the power to enable more realistic recapitulation and elucidation of cell interactions and cumulative drug response.

Mandibular incisor extractions in orthodontics: pitfalls and triumphs: a report of three cases.

Mandibular incisor extraction therapy has been used as a treatment option since the early 1900s to relieve tooth size-arch length discrepancies in the anterior segment of the mandible. The advantages of this therapy include potential reduction in treatment time, possibility of achieving better long-term stability in the mandibular anterior segment since inter canine width is not increased and maintenance of the soft-tissue profile because retraction of the mandibular incisors is less compared with mandibular premolar extractions These advantages are counterbalanced, however, by some potential disadvantages. The most significant of these is the possibility of the space reopening in the long term, an occlusal result less than ideal because of a significant tooth-mass reduction in the anterior mandibular region, development of an open gingival embrasure and the need for permanent or long term retention.

A novel ultrathin collagen nanolayer assembly for 3-D microtissue engineering: Layer-by-layer collagen deposition for long-term stable microfluidic hepatocyte culture.

The creation of stable hepatocyte cultures using cell-matrix interactions has proven difficult in microdevices due to dimensional constraints limiting the utility of classic tissue culture techniques that involve the use of hydrogels such as the collagen "double gel" or "overlay". To translate the collagen overlay technique into microdevices, we modified collagen using succinylation and methylation reactions to create polyanionic and polycationic collagen solutions, and deposited them layer-by-layer to create ultrathin collagen nanolayers on hepatocytes. These ultrathin collagen layers covered hepatocytes in microdevices and 1) maintained cell morphology, viability, and polarity, 2) induced bile canalicular formation and actin reorganization, and 3) maintained albumin and urea secretions and CYP activity similar to those observed in hepatocytes in collagen double gel hepatocytes in plate cultures.

Dynamic interplay of flow and collagen stabilizes primary hepatocytes culture in a microfluidic platform.

The creation of stable flow cultures of hepatocytes is highly desirable for the development of platforms for drug toxicity screening, bio-artificial liver support devices, and models for investigating liver physiology and pathophysiology. Given that hepatocytes cultured using the collagen overlay or in 'sandwich' configuration maintain a wide range of differentiated functions, we describe a simple method for adapting this culture configuration within a microfluidic device. The device design consists of a porous membrane sandwiched between two layers of PDMS resulting in a two-chambered device.

In vitro platforms for evaluating liver toxicity.

The liver is a heterogeneous organ with many vital functions, including metabolism of pharmaceutical drugs and is highly susceptible to injury from these substances. The etiology of drug-induced liver disease is still debated although generally regarded as a continuum between an activated immune response and hepatocyte metabolic dysfunction, most often resulting from an intermediate reactive metabolite. This debate stems from the fact that current animal and in vitro models provide limited physiologically relevant information, and their shortcomings have resulted in "silent" hepatotoxic drugs being introduced into clinical trials, garnering huge financial losses for drug companies through withdrawals and late stage clinical failures.

Establishment of soft tissue norms for the north Indian population based on laymen perception.

In this study we aimed to determine the soft tissue norms for the North Indian population based on the laymen perception of facial esthetics and to test the hypothesis that there are racial differences in cephalometric measurement between North Indians and White Americans norms. Two sets (Facial frontal and profile photographs) of 170 standardized facial photographs (76 males and 94 females in the age group of 18-28 years) were taken. A panel of judges which consisted of 20 laymen evaluated the photographs on the visual analogue scale to select a sample of 120 subjects (60 males and 60 females), which included individuals with esthetically pleasing appearance.

Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans.

Although the process of drug development requires efficacy and toxicity testing in animals prior to human testing, animal models have limited ability to accurately predict human responses to xenobiotics and other insults. Societal pressures are also focusing on reduction of and, ultimately, replacement of animal testing. However, a variety of in vitro models, explored over the last decade, have not been powerful enough to replace animal models.

Multiple supernumerary teeth associated with an impacted maxillary central incisor: Surgical and orthodontic management.

Various anomalies in the size, shape, number, structure and eruption of the teeth are often observed clinical conditions. Supernumerary teeth can be found in almost any region of the dental arch, and most of the times they are asymptomatic, and are routinely found during radiographic evaluation. The most common cause of impacted maxillary incisors is the presence of the supernumerary teeth.

Gingival enlargement and mesiodens associated with generalized aggressive periodontitis: a case report.

Unlabelled: This case report describes the management of an 18-year-old female who presented with generalized aggressive periodontitis, gingival enlargement and a mesiodens. Diagnosis for aggressive periodontitis was determined based on history, clinical findings and radiographic examination. Treatment included oral prophylaxis, extraction of the mesiodens and elimination of infectious microorganisms, using a combination of surgical intervention and antimicrobial therapy with long-term maintenance.

Interkingdom adenosine signal reduces Pseudomonas aeruginosa pathogenicity.

Pseudomonas aeruginosa is becoming recognized as an important pathogen in the gastrointestinal (GI) tract. Here we demonstrate that adenosine, derived from hydrolysis of ATP from the eucaryotic host, is a potent interkingdom signal in the GI tract for this pathogen. The addition of adenosine nearly abolished P.

A microfluidic device for high throughput bacterial biofilm studies.

Bacteria are almost always found in ecological niches as matrix-encased, surface-associated, multi-species communities known as biofilms. It is well established that soluble chemical signals produced by the bacteria influence the organization and structure of the biofilm; therefore, there is significant interest in understanding how different chemical signals are coordinately utilized for community development. Conventional methods for investigating biofilm formation such as macro-scale flow cells are low-throughput, require large volumes, and do not allow spatial and temporal control of biofilm community formation.

Synthetic quorum-sensing circuit to control consortial biofilm formation and dispersal in a microfluidic device.

To utilize biofilms for chemical transformations in biorefineries they need to be controlled and replaced. Previously, we engineered the global regulator Hha and cyclic diguanylate-binding BdcA to create proteins that enable biofilm dispersal. Here we report a biofilm circuit that utilizes these two dispersal proteins along with a population-driven quorum-sensing switch.

Chemotaxis to the quorum-sensing signal AI-2 requires the Tsr chemoreceptor and the periplasmic LsrB AI-2-binding protein.

AI-2 is an autoinducer made by many bacteria. LsrB binds AI-2 in the periplasm, and Tsr is the l-serine chemoreceptor. We show that AI-2 strongly attracts Escherichia coli.

Microfluidic co-culture of epithelial cells and bacteria for investigating soluble signal-mediated interactions.

The human gastrointestinal (GI) tract is a unique environment in which intestinal epithelial cells and non-pathogenic (commensal) bacteria coexist. It has been proposed that the microenvironment that the pathogen encounters in the commensal layer is important in determining the extent of colonization. Current culture methods for investigating pathogen colonization are not well suited for investigating this hypothesis as they do not enable co-culture of bacteria and epithelial cells in a manner that mimics the GI tract microenvironment.

Co-culture of epithelial cells and bacteria for investigating host-pathogen interactions.

The human gastrointestinal (GI) tract is a unique environment in which intestinal epithelial cells and non-pathogenic (commensal) bacteria co-exist. This equilibrium is perturbed by the entry of pathogens into the GI tract. A key step in the infection process is the navigation of the pathogen through the commensal bacterial layer to attach to epithelial cells.

The neuroendocrine hormone norepinephrine increases Pseudomonas aeruginosa PA14 virulence through the las quorum-sensing pathway.

It has been proposed that the gastrointestinal tract environment containing high levels of neuroendocrine hormones is important for gut-derived Pseudomonas aeruginosa infections. In this study, we report that the hormone norepinephrine increases P. aeruginosa PA14 growth, virulence factor production, invasion of HCT-8 epithelial cells, and swimming motility in a concentration-dependent manner.

Indole cell signaling occurs primarily at low temperatures in Escherichia coli.

We have shown that the quorum-sensing signals acylhomoserine lactones, autoinducer-2 (AI-2) and indole influence the biofilm formation of Escherichia coli. Here, we investigate how the environment, that is, temperature, affects indole and AI-2 signaling in E. coli.

Drug utilization pattern in dental outpatients in tertiary care teaching hospital in western Nepal.

A high incidence of dental disease has been reported in Nepal. Previous studies, both in the Manipal Teaching Hospital, Pokhara, Nepal, and other centers revealed problems in the use of medicines in dentistry. A number of initiatives to improve prescribing have been carried out.