A MATHEMATICAL APPROACH TO MANAGING WAIT TIMES IN HEALTHCARE FACILITIES USING QUEUING THEORY

Efficient management of patient wait times in healthcare facilities is critical for ensuring patient satisfaction, reducing operational costs, and improving overall healthcare delivery. Queuing theory, a mathematical framework for analyzing waiting lines, provides a robust method to model, analyze, and optimize healthcare service systems. This paper explores the application of queuing theory in healthcare, focusing on strategies to reduce wait times, allocate resources effectively, and predict patient flow. By examining various queuing models, including single-server, multi-server, and network queuing systems, this research highlights their practical applications in different healthcare scenarios such as emergency departments, outpatient clinics, and diagnostic centers. The findings underscore the potential of mathematical modeling in enhancing decision-making, improving resource utilization, and delivering timely care in the healthcare sector

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Rapid production of therapeutic proteins using plant system

Plant molecular farming is simply defined as the production of proteins therapeutics (PT) in plants, which involves transient gene expression in plants and purification of expressed protein to a great scale for diagnosis, treatment and other applications.  This is therapid,economical, safe and reproducible approach for the production of PTas compared to bacterial and mammalian systems. Protein yield and post-translational modifications are the major roadblocks that can be overcome byhigh expression strategies includes over expression constructs, suitable plant host systems and glycoengineering of proteins. The inherent ability of ideally producing safe, functional protein is the most striking phenomenon recognized by the pharmaceutical industries and developed many therapeutic products within few weeks to meet escalating demands during pandemic/epidemic outbreaks recentl

Immunotherapy targeting isoDGR-protein damage extends lifespan in a mouse model of protein deamidation

\ua9 2023 The Authors. Published under the terms of the CC BY 4.0 license. Aging results from the accumulation of molecular damage that impairs normal biochemical processes. We previously reported that age-linked damage to amino acid sequence NGR (Asn-Gly-Arg) results in “gain-of-function” conformational switching to isoDGR (isoAsp-Gly-Arg). This integrin-binding motif activates leukocytes and promotes chronic inflammation, which are characteristic features of age-linked cardiovascular disorders. We now report that anti-isoDGR immunotherapy mitigates lifespan reduction of Pcmt1−/− mouse. We observed extensive accumulation of isoDGR and inflammatory cytokine expression in multiple tissues from Pcmt1−/− and naturally aged WT animals, which could also be induced via injection of isoDGR-modified plasma proteins or synthetic peptides into young WT animals. However, weekly injection of anti-isoDGR mAb (1 mg/kg) was sufficient to significantly reduce isoDGR-protein levels in body tissues, decreased pro-inflammatory cytokine concentrations in blood plasma, improved cognition/coordination metrics, and extended the average lifespan of Pcmt1−/− mice. Mechanistically, isoDGR-mAb mediated immune clearance of damaged isoDGR-proteins via antibody-dependent cellular phagocytosis (ADCP). These results indicate that immunotherapy targeting age-linked protein damage may represent an effective intervention strategy in a range of human degenerative disorders

Immunotherapeutic targeting of aging-associated isoDGR motif in chronic lung inflammation

\ua9 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age-related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing age-linked lung inflammation. We observed age-dependent accumulation of the isoDGR motif in human lung tissues, as well as an 8-fold increase in isoDGR-damaged proteins in lung fibrotic tissues compared with healthy tissue. This increase was accompanied by marked infiltration of CD68+/CD11b + macrophages, consistent with a role for isoDGR in promoting chronic inflammation. We therefore assessed isoDGR function in mice that were either naturally aged or lacked the isoDGR repair enzyme. IsoDGR-protein accumulation in mouse lung tissue was strongly correlated with chronic inflammation, pulmonary edema, and hypoxemia. This accumulation also induced mitochondrial and ribosomal dysfunction, in addition to features of cellular senescence, thereby contributing to progressive lung damage over time. Importantly, treatment with anti-isoDGR antibody was able to reduce these molecular features of disease and significantly reduced lung pathology in vivo

The connected vertex monophonic number of a graph

For a connected graph G of order p ≥ 2 and a vertex x of G, a set S ⊆ V (G) is an x-monophonic set of G if each vertex v ∈ V (G) lies on an x − y monophonic path for some element y in S. The minimum cardinality of an x-monophonic set of G is defined as the x-monophonic number of G, denoted by mx(G). A connected x-monophonic set of G is an x-monophonic set S such that the subgraph G[S] induced by S is connected. The minimum cardinality of a connected x-monophonic set of G is defined as the connected x-monophonic number of G and is denoted by cmx(G). We determine bounds for it and find the same for some special classes of graphs. If p, a and b are positive integers such that 2 ≤ a ≤ b ≤ p − 1, then there exists a connected graph G of order p, mx(G) = a and cmx(G) = b for some vertex x in G. Also, if p, dm and n are positive integers such that 2 ≤ dm ≤ p − 2 and 1 ≤ n ≤ p, then there exists a connected graph G of order p, monophonic diameter dm and cmx(G) = n for some vertex x in G

Isolation and partial characterization of the active metabolite of ascidian, Polyclinum madrasensis from the Palk Bay Region, Southeast coast of India

Ascidians are rich source of bioactive agents which could be used for novel antimicrobial drugs. The present investigation inspects the antibacterial potential of ascidian, Polyclinum madrasensis collected from Mandapam, the Palk Bay region, Southeast coast of India. The crude extracts were tested for inhibition of bacterial growth against human pathogens.  Antibacterial assay was carried out by agar well diffusion method. The maximum inhibition zone (12.0±0.5 mm) was observed against the Staphylococcus aureus in crude methanol extract. The consequent zone of 6.5±0.1 mm was observed against S. aureus in ethanol extract and minimum inhibition zone (3.2±0.5 mm) was noticed with Pseudomonas aeruginosa. Molecular weight of tissue protein was determined through sodium dodecyl sulphate polyacryalamide gel electrophoresis (SDS-PAGE) and active metabolites were characterized by Fourier Transform Infrared spectroscopy (FTIR) analysis. The protein bands were at 36.5, 20.5, and 10.5 kDa, in SDS-PAGE and O-H stretch carboxylic acid compounds identified at the peak 3533.59 cm-1. It could be concluded from the present study that crude extract of the ascidian, P. madrasensis has potential antimicrobial effect against human pathogens.Keywards: Polyclinum madrasensis, bioactive compounds, Fourier Transform Infrared spectroscopy (FT-IR), sodium dodecyl sulphate polyacryalamide gel electrophoresis (SDS-PAGE).African Journal of Biotechnology, Vol 13(48) 4471-447

Response surface method to optimize the low cost medium for protease production using anchovy meal from ascidian associated Bacillus sp. GA CAS10

A protease producing Bacillus sp. GA CAS10 was isolated from ascidian Phallusia arabica, Tuticorin, Southeast coast of India. Response surface methodology was employed for the optimization of different nutritional and physical factors for the production of protease. Plackett-Burman method was applied to identify important factors (anchovy waste, KH2PO4, NaCl and temperature) influencing protease production. Further optimization was done by response surface methodology using central composite design. Under the optimized conditions by central composite design, the protease experimental yield (842.102 U/ml) closely matched the predicted yield by the statistical model (830.307 U/ml) with R2 = 99.94%. The time course of protease production was increased using the RSM optimized medium (856.29 U/ml) (anchovy waste 20.50 g/l, KH2PO4 3.06 g/l, NaCl 42.91 g/l, temperature 43.36°C, 42 h and pH 9) compared with the un-optimized basal medium (267.33 U/ml). The improvement of protease production by microbial conversion of anchovy waste suggested its potential utilization to generate high value added products using cheap carbon and nitrogen substrates.  Keywords: Protease, anchovy waste, statistical optimization, ascidian associated bacteria.African Journal of Biotechnology Vol 13(27) 2741-274