52 research outputs found
Static Variable: An Electromagnetic Nexus
This project would not have been possible without the help of my supervisors Frederick P. Warnecke and Marta Verde Baqueiro. Their support and encouragement was paramount to the completion of this project. I would also like to thank Pablo Munguia and Elysha Zaide whose critique and advice have been extremely useful throughout the project duration. I am also extremely grateful to KrisĹştian Hofstadter who has always encouraged me to pursue my ambitions regardless of their complexity. I would like to express my loving gratefulness to my parents and my wife for understanding my need to self-isolate for hours long before COVID-19 enforced that upon us. I would also like to thank my neighbours for not calling the cops on me while I carried on with my experiments in sound.https://remix.berklee.edu/graduate-studies-production-technology/1187/thumbnail.jp
Advances in Solid Dispersion Techniques for Enhancing Drug Solubility, Bioavailability and Controlled Release
Solid dispersion (SD) refers to the dispersion of
active ingredients, whether one or more, within inert
carriers in a solid state. This is achieved through methods
like fusion, solvent, or solvent fusion. The solid dispersion
technique is particularly valuable for enhancing the
solubility of inadequately soluble drugs, particularly
those falling under BCS Class II. This technique involves
the utilization of carriers such as polyethylene glycol 4000,
urea, and polyvinylpyrrolidone K 30 to improve the
drug's solubility and dissolution properties. The method
of solid dispersion has been utilized to improve the
solubility, dissolution, and bioavailability of various
natural drug components. Furthermore, solid dispersion
has been investigated as a strategy for developing natural
drug products with controlled or sustained release
characteristics. The mechanism of action of this delivery
system relies on the specific type of solid dispersion, as
well as the interactions among the drugs, carriers, and
other components incorporated into the formulation.
Currently, there are various methods accessible for
characterizing SDs, including X-ray diffraction,
differential scanning calorimetry, FTIR spectroscopy,
and dissolution testing, among others.
The pharmaceutical uses of the Solid Dispersion
technique encompass: augmenting drug absorption,
achieving a uniform distribution of a small drug quantity
in a solid state, and safeguarding unstable drugs by
mitigating processes like hydrolysis, oxidation, and
photooxidation
SOX17 Regulates Conversion of Human Fibroblasts Into Endothelial Cells and Erythroblasts by Dedifferentiation Into CD34+ Progenitor Cells
BACKGROUND:
The mechanisms underlying the dedifferentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast dedifferentiation recapitulates the generation of multipotent progenitors during embryonic development, which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bilineage conversion of fibroblasts by the generation of intermediate progenitors.
METHODS:
CD34+ progenitors were generated after the dedifferentiation of human adult dermal fibroblasts by overexpression of pluripotency transcription factors. Sorted CD34+ cells were transdifferentiated into induced endothelial cells and induced erythroblasts using lineage-specific growth factors. The therapeutic potential of the generated cells was assessed in an experimental model of myocardial infarction.
RESULTS:
Induced endothelial cells expressed specific endothelial cell surface markers and also exhibited the capacity for cell proliferation and neovascularization. Induced erythroblasts expressed erythroid surface markers and formed erythroid colonies. Endothelial lineage conversion was dependent on the upregulation of the developmental transcription factor SOX17, whereas suppression of SOX17 instead directed the cells toward an erythroid fate. Implantation of these human bipotential CD34+ progenitors into nonobese diabetic/severe combined immunodeficiency (NOD-SCID) mice resulted in the formation of microvessels derived from human fibroblasts perfused with mouse and human erythrocytes. Endothelial cells generated from human fibroblasts also showed upregulation of telomerase. Cell implantation markedly improved vascularity and cardiac function after myocardial infarction without any evidence of teratoma formation.
CONCLUSIONS:
Dedifferentiation of fibroblasts to intermediate CD34+ progenitors gives rise to endothelial cells and erythroblasts in a SOX17-dependent manner. These findings identify the intermediate CD34+ progenitor state as a critical bifurcation point, which can be tuned to generate functional blood vessels or erythrocytes and salvage ischemic tissue
Phenotypic and genetic evaluation of production efficiency and life time milk production attributes in Murrah buffaloes
The data of 344 Murrah buffaloes maintained at the university over a period of 20 years from 1993 to 2012 were analysed. From these results, in view of higher heritability estimated for milk yield/day of first calving interval selection on basis of these traits would result in higher genetic improvement in first lactation milk. High genetic and phenotypic correlations of MYFCI with other production efficiency traits also substantiate that, this can be used as a selection criterion. Therefore, selection based on MYFCI would result in improvement in desirable direction through positive correlated response in all the traits under study
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Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.
Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression
Comparative evaluation of valethamate bromide and hyoscine butyl bromide on cervical dilatation in water buffaloes after detorsion
After detorsion, incomplete cervical dilatation is major cause of dystocia. The present study aimed to investigate the comparative efficacy of valethamate bromide and hyoscine butyl bromide on cervical dilation after detorsion and their effect on haematological and biochemical parameters of torsion detorted water buffaloes. A total of 18 buffaloes were selected for study which were divided into three groups of six animals each. After detorsion by Sharma’s Modified Schaffer’s method, animals with grade I and grade II cervix were selected for the study. Group I (control group) buffaloes were administered with dexamethasone (40 mg, I/M), cloprostenol (500 μg, I/M) and mifex (450 mL, slow I/V) after successful detorsion. Along with these drugs, in group II and group III, valethamate bromide (100 mg, I/M) and hyoscine butyl bromide (160 mg, I/M) were administered, respectively. The cervical dilation rate (CDR) of each group was calculated and compared. Blood samples were collected three times: before detorsion, after treatment and at parturition. Group III (2.17±0.07 cm/h) had significantly higher CDR followed by group II (1.39±0.21 cm/h), and control group (0.47±0.19 cm/h). Serum calcium levels were also elevated after treatment. Both drug combinations were found safe haematologically and biochemically
Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)
The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the
India-based Neutrino Observatory (INO) is designed to study the atmospheric
neutrinos and antineutrinos separately over a wide range of energies and path
lengths. The primary focus of this experiment is to explore the Earth matter
effects by observing the energy and zenith angle dependence of the atmospheric
neutrinos in the multi-GeV range. This study will be crucial to address some of
the outstanding issues in neutrino oscillation physics, including the
fundamental issue of neutrino mass hierarchy. In this document, we present the
physics potential of the detector as obtained from realistic detector
simulations. We describe the simulation framework, the neutrino interactions in
the detector, and the expected response of the detector to particles traversing
it. The ICAL detector can determine the energy and direction of the muons to a
high precision, and in addition, its sensitivity to multi-GeV hadrons increases
its physics reach substantially. Its charge identification capability, and
hence its ability to distinguish neutrinos from antineutrinos, makes it an
efficient detector for determining the neutrino mass hierarchy. In this report,
we outline the analyses carried out for the determination of neutrino mass
hierarchy and precision measurements of atmospheric neutrino mixing parameters
at ICAL, and give the expected physics reach of the detector with 10 years of
runtime. We also explore the potential of ICAL for probing new physics
scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration,
Contents identical with the version published in Pramana - J. Physic
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Fecal microbiota transplant rescues mice from sepsis due to multi-drug resistant healthcare pathogens by restoring systemic immunity
Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
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