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1.
Adv Skin Wound Care ; 36(5): 1-5, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37079794

RESUMO

ABSTRACT: The authors report the case of a patient who presented with a nonhealing sternal wound 3 months after cardiac bypass surgery. The patient was treated with vacuum-assisted closure, surgical debridement, and IV antibiotics. Despite repeated flap closure procedures, a top closure device, and wound dressings, the patient developed an infection, and the wound size increased from 8 × 10 cm to 20 × 20 cm, advancing from the sternal to upper abdominal region. This wound was then treated with hyperbaric oxygen therapy and nonmedicated dressings until the patient was eligible to receive a split-thickness skin graft 1.5 years after initial presentation. The main takeaway from this case was that local and systemic factors affected the outcome of each surgical closure. The failure of each preceding treatment choice that led to further increases in size and area of the wound was the main challenge. Eliminating infection, preventing development of new infection, and managing the local and systemic factors before any definite surgery are key to the eventual wound closure.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Tratamento de Ferimentos com Pressão Negativa , Humanos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/terapia , Cicatrização , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias , Tratamento de Ferimentos com Pressão Negativa/métodos , Terapia Combinada , Desbridamento , Resultado do Tratamento
2.
Environ Geochem Health ; 45(10): 6985-7010, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37578559

RESUMO

The article deals with the integrated and comprehensive study of the coal-bearing horizons from the South Karanpura Basin to delineate the biostratigraphy, palaeovegetation, palaeodepositional settings, and palaeoclimate in and around the investigated area during the deposition of Permian sediments. Highly diversified megafloral assemblages consist 13 genera and 72 species of order Glossopteridales, Cordaitales and Equisetales are documented among which 37 taxa are newly reported from Barakar and Raniganj formations of the area. Palynoassemblages-I and -II are recovered, which demonstrate the biostratigraphic age as Kungurian and Wordian-Capitanian, respectively. Overall the vegetation represents a luxuriant forest subjugated by arborescent deciduous trees bearing Glossopteris foliage with some conifers, cordaites, filicales, and peltaspermales. The biomarker study of the basin illustrates the unimodal distribution of n-alkanes in the sample set ranges from C14 to C29 which suggests major input from a single source of organic matter. The involvement of microbial activity and algal input is suggested for the basin. A relatively moderate-to-high water level condition can be inferred from elevated n-C25. The high CIA, PIA values and A-CN-K plot suggest intense weathering conditions in the source area. The source rocks are characterized by mature clayey type with abundant clay mineral, i.e., kaolinite. The current study portrays that the Permian climate was cooler in initial phase, which later on became warm temperate with high humidity. The palaeofloral entities and geochemical parameters suggest absolute diversification of Permian flora, the existence of continental freshwater setting in the vicinity and oxic to anoxic environment with fluctuating ground water conditions during the deposition of sediments.


Assuntos
Carvão Mineral , Água Subterrânea , Plantas , Tempo (Meteorologia) , Água
3.
Nanotechnology ; 31(22): 225208, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32059203

RESUMO

In this article, we have demonstrated a solid carbon source such as camphor as a natural precursor to synthesize a large area mono/bi-layer graphene (MLG) sheet to fabricate a nanowire junction-based near infrared photodetectors (NIRPDs). In order to increase the surface-to-volume ratio, we have developed Si-nanowire arrays (SiNWAs) of varying lengths by etching planar Si. Then, the camphor-based MLG/Si and MLG/SiNWAs Schottky junction photodetectors have been fabricated to achieve an efficient response with self-driven properties in the near infrared (NIR) regime. Due to a balance between light absorption capability and surface recombination centers, devices having SiNWAs obtained by etching for 30 min shows a better photoresponse, sensitivity and detectivity. Fabricated NIRPDs can also be functioned as self-driven devices which are highly responsive and very stable at low optical power signals up to 2 V with a fast rise and decay time of 34/13 ms. A tremendous enhancement has been witnessed from 36 µA W-1 to 22 mA W-1 in the responsivity at 0 V for MLG/30 min SiNWAs than planar MLG/Si PDs indicating an important development of self-driven NIRPDs based on camphor-based MLG for future optoelectronic devices.

4.
Breast Cancer Res ; 19(1): 56, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28506312

RESUMO

BACKGROUND: The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC. METHODS: We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression. RESULTS: Our results show that MEPs suppress tumor formation by DCIS cells in vivo even in the presence of CAFs. In the in vitro MAME model, MEPs reduce the size of 3D DCIS structures and their degradation of extracellular matrix. We further show that the tumor-suppressive effects of MEPs on DCIS are linked to inhibition of urokinase plasminogen activator (uPA)/urokinase plasminogen activator receptor (uPAR)-mediated proteolysis by plasminogen activator inhibitor 1 (PAI-1) and that they can lessen the tumor-promoting effects of CAFs by attenuating interleukin 6 (IL-6) signaling pathways. CONCLUSIONS: Our studies using MAME are, to our knowledge, the first to demonstrate a divergent interplay between MEPs and CAFs within the DCIS tumor microenvironment. We show that the tumor-suppressive actions of MEPs are mediated by PAI-1, uPA and its receptor, uPAR, and are sustained even in the presence of the CAFs, which themselves enhance DCIS tumorigenesis via IL-6 signaling. Identifying tumor microenvironmental regulators of DCIS progression will be critical for defining a robust and predictive molecular signature for clinical use.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Interleucina-6/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Animais , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal de Mama/patologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Proteoma/genética , Análise Serial de Tecidos , Microambiente Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Phys Chem Chem Phys ; 19(13): 8787-8801, 2017 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-28294263

RESUMO

We report formation of aligned nanostructures on epitaxially grown polar and nonpolar GaN films via wet chemical (hot H3PO4 and KOH) etching. The morphological evolution exhibited stress relaxed faceted nanopyramids, flat/trigonal nanorods and porous structures with high hydrophilicity and reduced wettability. The nanostructured films divulged significant suppression of defects and displayed an enhanced intensity ratio of the near band edge emission to the defect band. Extensive photoemission analysis revealed variation in oxidation state along with elimination of OH- and adsorbed H2O molecules from the chemically modified surfaces. Fermi level pinning, and alteration in the surface polarity with substantial changes in the electron affinities were also perceived. The temperature dependent current-voltage analysis of the nanostructured surfaces displayed enhancement in current conduction. The in-depth analysis demonstrates that the chemically etched samples could potentially be utilized as templates in the design/growth of III-nitride based high performance devices.

6.
Phys Biol ; 13(3): 036007, 2016 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-27232957

RESUMO

The origin of a universal and optimal genetic code remains a compelling mystery in molecular biology and marks an essential step in the origin of DNA and protein based life. We examine a collective evolution model of genetic code origin that allows for unconstrained horizontal transfer of genetic elements within a finite population of sequences each of which is associated with a genetic code selected from a pool of primordial codes. We find that when horizontal transfer of genetic elements is incorporated in this more realistic model of code-sequence coevolution in a finite population, it can increase the likelihood of emergence of a more optimal code eventually leading to its universality through fixation in the population. The establishment of such an optimal code depends on the probability of HGT events. Only when the probability of HGT events is above a critical threshold, we find that the ten amino acid code having a structure that is most consistent with the standard genetic code (SGC) often gets fixed in the population with the highest probability. We examine how the threshold is determined by factors like the population size, length of the sequences and selection coefficient. Our simulation results reveal the conditions under which sharing of coding innovations through horizontal transfer of genetic elements may have facilitated the emergence of a universal code having a structure similar to that of the SGC.


Assuntos
Aminoácidos/genética , Transferência Genética Horizontal/genética , Código Genético/genética
7.
Phys Chem Chem Phys ; 18(11): 8005-14, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26916430

RESUMO

The relationship of the growth temperature with stress, defect states, and electronic structure of molecular beam epitaxy grown GaN films on c-plane (0001) sapphire substrates is demonstrated. A minimum compressively stressed GaN film is grown by tuning the growth temperature. The correlation of dislocations/defects with the stress relaxation is scrutinized by high-resolution X-ray diffraction and photoluminescence measurements which show a high crystalline quality with significant reduction in the threading dislocation density and defect related bands. A substantial reduction in yellow band related defect states is correlated with the stress relaxation in the grown film. Temperature dependent Raman analysis shows the thermal stability of the stress relaxed GaN film which further reveals a downshift in the E2 (high) phonon frequency owing to the thermal expansion of the lattice at elevated temperatures. Electronic structure analysis reveals that the Fermi level of the films is pinned at the respective defect states; however, for the stress relaxed film it is located at the charge neutrality level possessing the lowest electron affinity. The analysis demonstrates that the generated stress not only affects the defect states, but also the crystal quality, surface morphology and electronic structure/properties.

8.
Breast Cancer Res Treat ; 154(2): 251-62, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26502410

RESUMO

Photodynamic therapy (PDT) is a minimally invasive, FDA-approved therapy for treatment of endobronchial and esophageal cancers that are accessible to light. Inflammatory breast cancer (IBC) is an aggressive and highly metastatic form of breast cancer that spreads to dermal lymphatics, a site that would be accessible to light. IBC patients have a relatively poor survival rate due to lack of targeted therapies. The use of PDT is underexplored for breast cancers but has been proposed for treatment of subtypes for which a targeted therapy is unavailable. We optimized and used a 3D mammary architecture and microenvironment engineering (MAME) model of IBC to examine the effects of PDT using two treatment protocols. The first protocol used benzoporphyrin derivative monoacid A (BPD) activated at doses ranging from 45 to 540 mJ/cm(2). The second PDT protocol used two photosensitizers: mono-L-aspartyl chlorin e6 (NPe6) and BPD that were sequentially activated. Photokilling by PDT was assessed by live-dead assays. Using a MAME model of IBC, we have shown a significant dose-response in photokilling by BPD-PDT. Sequential activation of NPe6 followed by BPD is more effective in photokilling of tumor cells than BPD alone. Sequential activation at light doses of 45 mJ/cm(2) for each agent resulted in >90 % cell death, a response only achieved by BPD-PDT at a dose of 360 mJ/cm(2). Our data also show that effects of PDT on a volumetric measurement of 3D MAME structures reflect efficacy of PDT treatment. Our study is the first to demonstrate the potential of PDT for treating IBC.


Assuntos
Neoplasias Inflamatórias Mamárias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caspase 3 , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta a Droga , Feminino , Humanos , Técnicas In Vitro , Neoplasias Inflamatórias Mamárias/terapia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Técnicas de Cultura de Tecidos , Microambiente Tumoral
9.
BMC Cancer ; 15: 584, 2015 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-26268945

RESUMO

BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of invasive breast cancer in which approximately half the patients will progress to invasive cancer. Gaining a better understanding of DCIS progression may reduce overtreatment of patients. Expression of the pro-inflammatory cytokine interleukin-6 increases with pathological stage and grade, and is associated with poorer prognosis in breast cancer patients. Carcinoma associated fibroblasts (CAFs), which are present in the stroma of DCIS patients are known to secrete pro-inflammatory cytokines and promote tumor progression. METHODS: We hypothesized that IL-6 paracrine signaling between DCIS cells and CAFs mediates DCIS proliferation and migration. To test this hypothesis, we utilized the mammary architecture and microenvironment engineering or MAME model to study the interactions between human breast CAFs and human DCIS cells in 3D over time. We specifically inhibited autocrine and paracrine IL-6 signaling to determine its contribution to early stage tumor progression. RESULTS: Here, DCIS cells formed multicellular structures that exhibited increased proliferation and migration when cultured with CAFs. Treatment with an IL-6 neutralizing antibody inhibited growth and migration of the multicellular structures. Moreover, selective knockdown of IL-6 in CAFs, but not in DCIS cells, abrogated the migratory phenotype. CONCLUSION: Our results suggest that paracrine IL-6 signaling between preinvasive DCIS cells and stromal CAFs represent an important factor in the initiation of DCIS progression to invasive breast carcinoma.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Invasividade Neoplásica/patologia
10.
Phys Chem Chem Phys ; 17(23): 15201-8, 2015 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-25991084

RESUMO

A comprehensive analysis of oxygen chemisorption on epitaxial gallium nitride (GaN) films grown at different substrate temperatures via RF-molecular beam epitaxy was carried out. Photoemission (XPS and UPS) measurements were performed to investigate the nature of the surface oxide and corresponding changes in the electronic structure. It was observed that the growth of GaN films at lower temperatures leads to a lower amount of surface oxide and vice versa was observed for a higher temperature growth. The XPS core level (CL) and valence band maximum (VBM) positions shifted towards higher binding energies (BE) with oxide coverage and revealed a downward band bending. XPS valence band spectra were de-convoluted to understand the nature of the hybridization states. UPS analysis divulged higher values of electronic affinity and ionization energy for GaN films grown at a higher substrate temperature. The surface morphology and pit structure were probed via microscopic measurements (FESEM and AFM). FESEM and AFM analysis revealed that the film surface was covered with hexagonal pits, which played a significant role in oxygen chemisorption. The favourable energetics of the pits offered an ideal site for oxygen adsorption. Pit density and pit depth were observed to be important parameters that governed the surface oxide coverage. The contribution of surface oxide was increased with an increase in average pit density as well as pit depth.

11.
Pharm Biol ; 53(9): 1250-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25856695

RESUMO

CONTEXT: Results from various studies indicate that the presence of certain heavy metals such as aluminum (Al), arsenic (As), copper (Cu), lead (Pb), and mercury (Hg) may enhance the aggregation of Aß and oxidative stress levels leading to neuronal toxicity and Alzheimer's disease (AD). Studies also reveal that anomalous brain copper-cholesterol (Cu-Ch) homeostasis may lead to memory deficits in Swiss albino mice. OBJECTIVE: The present study investigates the anti-amnesic potential of clioquinol (5-chloro-7-iodoquinolin-8-ol) in cognitive deficits associated with experimental dementia induced by Cu-Ch. MATERIALS AND METHODS: Administration of Cu-Ch {0.21 mg/kg, per os - 2% w/v, per os for 8 weeks} was used to induce dementia in Swiss albino mice. The Morris water maze (MWM) test was performed to assess the effect on learning and memory. A battery of biochemical estimations was performed following the MWM test such as brain-reduced glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS), acetylcholinestrase (AChE) activity, and serum cholesterol levels. RESULTS: Administration of Cu-Ch produced a marked decline in MWM performance measured during the acquisition (78.9 ± 3.3) and retrieval trials (9.5 ± 2.4), reflecting impairment of learning and memory. Cu-Ch-treated mice also exhibited a marked accentuation of AChE activity (5.8 ± 0.55) and TBARS levels (9.74 ± 1.9) along with a decline in the GSH level (15.4 ± 3.3) and the SOD level (26 ± 2.5) when compared with the untreated control group. Administration of clioquinol significantly attenuated Cu-Ch-induced memory deficits and biochemical alterations. DISCUSSION AND CONCLUSION: The findings demonstrate memory restorative ability of clioquinol which may be attributed to its anti-cholinesterase, antioxidative, and cholesterol-lowering potential.


Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Clioquinol/farmacologia , Cobre , Demência/tratamento farmacológico , Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Acetilcolinesterase/metabolismo , Animais , Anticolesterolemiantes/farmacologia , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Colesterol , Inibidores da Colinesterase/farmacologia , Demência/induzido quimicamente , Demência/metabolismo , Demência/fisiopatologia , Demência/psicologia , Modelos Animais de Doenças , Donepezila , Feminino , Proteínas Ligadas por GPI/metabolismo , Glutationa/metabolismo , Indanos/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/farmacologia , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
12.
Bioorg Chem ; 53: 83-91, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24632507

RESUMO

It has been demonstrated that Lipozyme® TL IM (Thermomyces lanuginosus lipase immobilised on silica) can selectively deacylate the ester function involving the C-5' hydroxyl group of α-anomers over the other acyl functions of anomeric mixture of peracylated O-aryl α,ß-D-ribofuranoside. The analysis of results of biocatalytic deacylation reaction revealed that the reaction time decreases with the increase in the acyl chain length from C1 to C4. The unique selectivity of Lipozyme® TL IM has been harnessed for the separation of anomeric mixture of peracylated O-aryl α,ß-D-ribofuranosides, The lipase mediated selective deacylation methodology has been used for the synthesis of O-aryl α-D-ribofuranosides and O-aryl ß-D-ribofuranosides in pure forms, which can be used as chromogenic substrate for the detection of pathogenic microbial parasites containing glycosidases.


Assuntos
Glicosídeos/metabolismo , Lipase/metabolismo , Resinas Acrílicas/química , Acilação , Biocatálise , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Eurotiales/enzimologia , Glicosídeos/química
13.
Orig Life Evol Biosph ; 44(4): 287-91, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25585805

RESUMO

The origin of a genetic code made it possible to create ordered sequences of amino acids. In this article we provide two perspectives on code origin by carrying out simulations of code-sequence coevolution in finite populations with the aim of examining how the standard genetic code may have evolved from more primitive code(s) encoding a small number of amino acids. We determine the efficacy of the physico-chemical hypothesis of code origin in the absence and presence of horizontal gene transfer (HGT) by allowing a diverse collection of code-sequence sets to compete with each other. We find that in the absence of horizontal gene transfer, natural selection between competing codes distinguished by differences in the degree of physico-chemical optimization is unable to explain the structure of the standard genetic code. However, for certain probabilities of the horizontal transfer events, a universal code emerges having a structure that is consistent with the standard genetic code.


Assuntos
Aminoacil-tRNA Sintetases/química , Códon/química , Código Genético , Origem da Vida , RNA Mensageiro/química , RNA de Transferência Aminoácido-Específico/química , Aminoácidos/química , Aminoácidos/metabolismo , Aminoacil-tRNA Sintetases/metabolismo , Códon/metabolismo , Evolução Molecular , Transferência Genética Horizontal , Genes , Modelos Genéticos , Probabilidade , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , RNA de Transferência Aminoácido-Específico/metabolismo , Seleção Genética
15.
Langmuir ; 29(45): 13853-64, 2013 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-24171489

RESUMO

Here, the layer-by-layer method was applied to assemble films from chitosan paired with either heparin or a semisynthetic cellulose sulfate (CS) that possessed a higher sulfation degree than heparin. Ion pairing was exploited during multilayer formation at pH 4, while hydrogen bonding is likely to occur at pH 9. Effects of polyanions and pH value during layer formation on multilayers properties were studied by surface plasmon resonance ("dry layer mass"), quartz crystal microbalance with dissipation monitoring ("wet layer mass"), water contact angle, and zeta potential measurements. Bioactivity of multilayers was studied regarding fibronectin adsorption and adhesion/proliferation of C2C12 myoblast cells. Layer growth and dry mass were higher for both polyanions at pH 4 when ion pairing occurred, while it decreased significantly with heparin at pH 9. By contrast, CS as polyanion resulted also in high layer growth and mass at pH 9, indicating a much stronger effect of hydrogen bonding between chitosan and CS. Water contact angle and zeta potential measurements indicated a more separated structure of multilayers from chitosan and heparin at pH 4, while CS led to a more fuzzy intermingled structure at both pH values. Cell behavior was highly dependent on pH during multilayer formation with heparin as polyanion and was closely related to fibronectin adsorption. By contrast, CS and chitosan did not show such dependency on pH value, where adhesion and growth of cells was high. Results of this study show that CS is an attractive candidate for multilayer formation that does not depend so strongly on pH during multilayer formation. In addition, such multilayer system also represents a good substrate for cell interactions despite the rather soft structure. As previous studies have shown specific interaction of CS with growth factors, multilayers from chitosan and CS may be of great interest for different biomedical applications.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Celulose/análogos & derivados , Heparina/química , Mioblastos/citologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Celulose/química , Quitosana/química , Concentração de Íons de Hidrogênio , Mioblastos/efeitos dos fármacos , Molhabilidade
16.
Orig Life Evol Biosph ; 43(6): 465-89, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24500541

RESUMO

The origin of the genetic code marked a major transition from a plausible RNA world to the world of DNA and proteins and is an important milestone in our understanding of the origin of life. We examine the efficacy of the physico-chemical hypothesis of code origin by carrying out simulations of code-sequence coevolution in finite populations in stages, leading first to the emergence of ten amino acid code(s) and subsequently to 14 amino acid code(s). We explore two different scenarios of primordial code evolution. In one scenario, competition occurs between populations of equilibrated code-sequence sets while in another scenario; new codes compete with existing codes as they are gradually introduced into the population with a finite probability. In either case, we find that natural selection between competing codes distinguished by differences in the degree of physico-chemical optimization is unable to explain the structure of the standard genetic code. The code whose structure is most consistent with the standard genetic code is often not among the codes that have a high fixation probability. However, we find that the composition of the code population affects the code fixation probability. A physico-chemically optimized code gets fixed with a significantly higher probability if it competes against a set of randomly generated codes. Our results suggest that physico-chemical optimization may not be the sole driving force in ensuring the emergence of the standard genetic code.


Assuntos
DNA/genética , Evolução Molecular , Código Genético , RNA/genética
17.
J Am Med Dir Assoc ; 23(7): 1109-1113.e8, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35660385

RESUMO

OBJECTIVES: The novel coronavirus disease 2019 (COVID-19) deeply affected all forms of long-term care for older adults, highlighting infection control issues, provider and staff shortages, and other challenges. As a comparatively new, community-based long-term care option, the Program of All-Inclusive Care for the Elderly (PACE) faced unique challenges. This project investigated the impact of COVID-19 on operations in all PACE programs in one US state. DESIGN: Qualitative study. SETTING AND PARTICIPANTS: Structured interviews with administrators of all 12 PACE programs in North Carolina. METHODS: Interviews were conducted December 2020 to January 2021 by trained interviewers over Zoom; they were transcribed, coded, and qualitatively analyzed using thematic analysis. RESULTS: Reported COVID-19 infection rates among PACE participants for 2020 averaged 12.3 cases, 4.6 hospitalizations, and 1.9 deaths per 100 enrollees. Six themes emerged from analyses: new, unprecedented administrative challenges; insufficient access to and integration with other health care providers; reevaluation of the core PACE model, resulting in a transition to home-based care; reorientation to be more family-focused in care provision; implementation of new, creative strategies to address participant and family psychological and social well-being in the home; and major reconfiguration of staffing, including transitions to new and different roles and a concomitant effort to provide support and relief to staff. CONCLUSIONS AND IMPLICATIONS: While facing many challenges that required major changes in care provision, PACE was successful in mounting a COVID-19 response that upheld safety, promoted the physical and mental well-being of participants, and responded to the needs of family caregivers. Administrators felt that, after the pandemic, the PACE service model is likely to remain more home-based and less reliant on the day center than in the past. As a result, PACE may have changed for the better and be well-positioned to play an expanded role in our evolving long-term care system.


Assuntos
COVID-19 , Serviços de Saúde para Idosos , Idoso , Humanos , Assistência de Longa Duração , North Carolina/epidemiologia , Pandemias
18.
J Antimicrob Chemother ; 66(11): 2543-55, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21917615

RESUMO

OBJECTIVES: The objective of the present study was to evaluate the antitubercular activity of amino and acyl amino derivatives of coumarins when used alone and in combination with isoniazid, rifampicin, streptomycin or ethambutol, and to decipher the mode of action of the most effective agent. METHODS: A series of amino and acyl amino coumarins were synthesized and screened for activity against the Mycobacterium tuberculosis H37Rv strain. These compounds were further evaluated by standard assay procedures to determine their MBCs, fractional inhibitory concentration index values and cytotoxicities. The MICs for a susceptible and a multidrug-resistant clinical isolate of M. tuberculosis were also determined. Electron and fluorescence microscopy of the test compound-treated mycobacterial samples were also carried out in an attempt to find out the target of action. RESULTS: 7-Amino-4-methylcoumarin (7-amino-4-methyl-2H-chromen-2-one; NA5) displayed the lowest MIC of 1 mg/L against not only H37Rv but also the susceptible as well as the multidrug-resistant clinical isolates. Certain acyl amino coumarins were also found to inhibit the aforementioned strains and isolates with MICs in the range of 1.0-3.5 mg/L. They were also found to act in synergy with isoniazid/rifampicin. Electron microscopy revealed the cell-wall-attacking characteristic of these compounds, while fluorescence microscopy indicated that mycolic acid might be the target of action. CONCLUSIONS: The present study clearly demonstrated the in vitro antitubercular potential of the novel drug candidate NA5. Further studies are warranted to establish the in vivo efficacy and therapeutic potential of NA5.


Assuntos
Antituberculosos/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Etambutol/farmacologia , Isoniazida/farmacologia , Testes de Sensibilidade Microbiana , Ácidos Micólicos/metabolismo , Rifampina/farmacologia , Estreptomicina/farmacologia , Relação Estrutura-Atividade
19.
Sci Rep ; 11(1): 10859, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035437

RESUMO

The fabrication of unique taper-ended GaN-Nanotowers structure based highly efficient ultraviolet photodetector is demonstrated. Hexagonally stacked, single crystalline GaN nanocolumnar structure (nanotowers) grown on AlN buffer layer exhibits higher photocurrent generation due to high quality nanotowers morphology and increased surface/volume ratio which significantly enhances its responsivity upon ultraviolet exposure leading to outstanding performance from the developed detection device. The fabricated detector display low dark current (~ 12 nA), high ILight/IDark ratio (> 104), fast time-correlated transient response (~ 433 µs) upon ultraviolet (325 nm) illumination. A high photoresponsivity of 2.47 A/W is achieved in self-powered mode of operation. The reason behind such high performance could be attributed to built-in electric field developed from a difference in Schottky barrier heights will be discussed in detail. While in photoconductive mode, the responsivity is observed to be 35.4 A/W @ - 3 V along with very high external quantum efficiency (~ 104%), lower noise equivalent power (~ 10-13 WHz-1/2) and excellent UV-Vis selectivity. Nanotower structure with lower strain and dislocations as well as reduced trap states cumulatively contributed to augmented performance from the device. The utilization of these GaN-Nanotower structures can potentially be useful towards the fabrication of energy-efficient ultraviolet photodetectors.

20.
Biomacromolecules ; 11(12): 3413-21, 2010 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-21090703

RESUMO

Nanofibers were prepared by electrospinning from pure polyvinyl alcohol (PVA), polyhydroxybutyrate (PHB), and their blends. Miscibility and morphology of both polymers in the nanofiber blends were studied by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC), revealing that PVA and PHB were miscible with good compatibility. DSC also revealed suppression of crystallinity of PHB in the blend nanofibers with increasing proportion of PVA. The hydrolytic degradation of PHB was accelerated with increasing PVA fraction. Cell culture experiments with a human keratinocyte cell line (HaCaT) and dermal fibroblast on the electrospun PHB and PVA/PHB blend nanofibers showed maximum adhesion and proliferation on pure PHB. However, the addition of 5 wt % PVA to PHB inhibited growth of HaCaT cells but not of fibroblasts. On the contrary, adhesion and proliferation of HaCaT cells were promoted on PVA/PHB (50/50) fibers, which inhibited growth of fibroblasts.


Assuntos
Hidroxibutiratos/química , Nanofibras/química , Poliésteres/química , Álcool de Polivinil/química , Pele/efeitos dos fármacos , Engenharia Tecidual/métodos , Alicerces Teciduais , Adesão Celular , Linhagem Celular , Proliferação de Células , Técnicas de Química Analítica , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Proibitinas , Pele/citologia
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