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The human visual ability to recognize objects and scenes is widely thought to rely on representations in category-selective regions of the visual cortex. These representations could support object vision by specifically representing objects, or, more simply, by representing complex visual features regardless of the particular spatial arrangement needed to constitute real-world objects, that is, by representing visual textures. To discriminate between these hypotheses, we leveraged an image synthesis approach that, unlike previous methods, provides independent control over the complexity and spatial arrangement of visual features. We found that human observers could easily detect a natural object among synthetic images with similar complex features that were spatially scrambled. However, observer models built from BOLD responses from category-selective regions, as well as a model of macaque inferotemporal cortex and Imagenet-trained deep convolutional neural networks, were all unable to identify the real object. This inability was not due to a lack of signal to noise, as all observer models could predict human performance in image categorization tasks. How then might these texture-like representations in category-selective regions support object perception? An image-specific readout from category-selective cortex yielded a representation that was more selective for natural feature arrangement, showing that the information necessary for natural object discrimination is available. Thus, our results suggest that the role of the human category-selective visual cortex is not to explicitly encode objects but rather to provide a basis set of texture-like features that can be infinitely reconfigured to flexibly learn and identify new object categories.
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Córtex Visual , Vias Visuais , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Reconhecimento Visual de Modelos , Estimulação Luminosa , Percepção VisualRESUMO
In the present investigation, we present the comparison of the structural, magnetic, magnetocaloric and magnetoresistance behavior of solid state and sol-gel derived La0.7Sr0.3MnO3. X-ray diffraction together with Rietveld refinement confirms the rhombohedral structure of the synthesised samples with the R3Ìc space group. The ferromagnetic-to-paramagnetic transition temperature decreases from 360 K to 346 K for the nanocrystalline sample. The XPS measurements confirm the presence of Mn3+ in the synthesised samples. Furthermore, the polycrystalline sample exhibits a considerable -ΔSM of 4.68 J kg-1 K-1 at 360 K for a field change of 50 kOe and a relative cooling power (RCP) of 205 J kg-1. A -ΔSM of 1.14 J kg-1 K-1 was obtained for the nanocrystalline sample at 346 K with an RCP of 83 J kg-1. Critical exponent analysis has also been performed on both samples to establish the universality class. Both samples exhibit a distinct metal-to-insulator transition, which increases with grain size from 187 K to 334 K as a result of grain growth and decreased grain boundary. As the grain size increases, the resistivity decreases and shifts towards high temperatures with increasing magnetic fields. The itinerant electron model (IEO) which is based on the hopping of O 2p itinerant electrons has been used to explain the resistivity behaviour of the samples. It is found that the negative magnetoresistance also increases with a decrease in grain size where the highest %MR of 26% can be observed for the nanocrystalline sample. These results make La0.7Sr0.3MnO3 a suitable candidate for multifunctional applications.
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PURPOSE: To identify the influence of residency program characteristics, including the presence of under-represented minorities in medicine (URiM) and/or female program directors (PDs), on the race and sex distribution of orthopaedic surgery residency trainees. METHODS: All active and Accreditation Council for Graduate Medical Education-accredited orthopaedic surgery residency programs from 2017-2021 that reported usable information in the Residency Explorer Tool were included. Data collected included program characteristics, as well as faculty and resident sex distribution, ethnicity, race, and demographic characteristics. The PDs' specific sex, ethnicity, race, and demographic characteristics were collected using residency program websites. The prevalence of factors in programs with the top quartile of female and URiM residents was compared with that in programs with the bottom 3 quartiles. RESULTS: Data were obtained from 148 of 200 Accreditation Council for Graduate Medical Education-accredited programs (3,694 residents). The 52 excluded programs had no usable information in the Residency Explorer Tool or on an identifiable program website. Overall, 15.9% of residents in orthopaedic surgery residency programs were women and 14% were under-represented minorities. The rates of female PDs and chairs were 12.4% and 6.9%, respectively, whereas those of URiM PDs and chairs were 8.3% and 4.6%, respectively. Programs with more female residents were not associated with female PDs (P = .79) or URiM PDs (P = .48). Programs with a greater percentage of URiM residents were not associated with URiM PDs (P = .16). Larger programs (P = .021) and university-based programs (P = .048) had a greater percentage of female residents. Orthopaedic residency programs with visa sponsorship had a greater percentage of URiM residents (P = .017). CONCLUSIONS: Programs with a higher percentage of female or URiM residents did not show a significant association with having female or URiM PDs. Larger programs and university-affiliated programs were more likely to have a larger percentage of female residents, whereas programs that offered visa sponsorship had a higher percentage of URiM residents. CLINICAL RELEVANCE: This study highlights factors influencing diversity among orthopaedic surgery residents. Although the presence of female or URiM PDs does not influence the percentage of female or URiM residents, other program characteristics such as size, affiliation, and visa sponsorship offer potentially actionable insights for promoting greater diversity in orthopaedic training. Doing so may increase under-represented groups within the field and could ultimately impact patient care and improve health care equity.
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PURPOSE: To systematically review the patient-reported outcomes and postoperative complications following tuberoplasty for the treatment of massive irreparable rotator cuff tears. METHODS: A literature search was conducted using PubMed and EMBASE computerized databases from database inception to June 2023 in accordance with the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Included studies evaluated clinical outcomes, postoperative complications, and reoperation rates following tuberoplasty for the treatment of massive irreparable rotator cuff tears. Exclusion criteria consisted of non-English language, cadaveric studies, case reports, animal studies, studies with overlapping cohorts, letters to editors, and review articles. Study quality was assessed using the Methodological Index for Non-Randomized Studies criteria. Clinical outcome scores included the visual analog scale for pain, University of California Los Angeles score, and Constant score. RESULTS: Seven studies from 2002 to 2023 consisting of 123 patients with a mean age of 66.5 years (mean range, 63-70.4 years) were included. The mean follow-up time ranged from 18 to 98 months. The mean Methodological Index for Non-Randomized Studies score was 13.5 (range, 13-15). At final follow-up, the mean postoperative visual analog scale pain scores ranged from 2.3 to 2.5, University of California-Los Angeles shoulder score from 27.2 to 27.7, and Constant scores from 59.2 to 90.6. Postoperative active forward flexion and abduction ranged from 131° to 165°, and 123° to 160°, respectively. The change in acromiohumeral distance postoperatively ranged from -1 mm to -0.6 mm. The rate of postoperative complications ranged from 0% to 19% of patients, while 0% to 19% of patients underwent revision surgery to reverse shoulder arthroplasty. CONCLUSIONS: Tuberoplasty for the treatment of massive irreparable rotator cuff tears results in good clinical outcomes with significant pain relief in select populations. However, the variable reoperation rates should be considered when counseling patients. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.
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Complicações Pós-Operatórias , Lesões do Manguito Rotador , Humanos , Lesões do Manguito Rotador/cirurgia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Reoperação/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Idoso , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Controlling length of stay (LOS) reduces rates of nosocomial infections and falls, facilitates earlier return to daily activities, and decreases strain on the healthcare system. Complications following supratentorial tumor resection present early in the postoperative period, thereby enhancing the prospect of safe, early discharge. Here, the authors describe their initial experience with the development and implementation of an Enhanced Recovery After Cranial Surgery (ERACS) pathway following resection of supratentorial tumors in select patients. METHODS: This was a nonrandomized, ambispective quality improvement study of patients undergoing elective craniotomy for supratentorial tumor resection at New York University Langone Health between November 17, 2020, and May 19, 2022. Eligible patients were prospectively enrolled in either the ERACS pathway or the standard pathway. These prospective cohorts were compared to a retrospective cohort of patients who met eligibility criteria for the pathway. Patients in the ERACS pathway cohort were targeted for discharge on postoperative day 2. The primary outcome metric was hospital LOS. Secondary outcome metrics included duration of intensive care unit (ICU) care and rates of 30-day emergency department visits, readmissions, and complications. RESULTS: Over the study period, 188 of 317 patients (59.3%) who underwent supratentorial tumor resection met inclusion criteria for ERACS pathway enrollment. Sixty-three patients were enrolled in the ERACS pathway, and 125 patients completed the standard pathway. The historical cohort consisted of 332 patients who would have been eligible for ERACS enrollment. Patients in the ERACS pathway cohort had a median LOS of 1.93 days compared with 2.92 and 2.88 days for patients in the standard pathway and historical cohort, respectively (p < 0.001). There was a significant reduction in ICU utilization in ERACS pathway patients (16.0 ± 6.53 vs 29.5 ± 53.0 vs 21.8 ± 18.2 hours, p = 0.005). There were no differences in the rates of 30-day emergency department visits (12.7% vs 9.6% vs 10.9%, p = 0.809) and readmissions (4.8% vs 4.0% vs 7.8%, p = 0.279) between groups. CONCLUSIONS: Patients in the ERACS pathway cohort experienced reduced LOS and ICU utilization, with similar rates of adverse outcomes compared to standard pathway patients. The authors' initial experience suggests that an accelerated recovery pathway can be safely implemented following supratentorial tumor resection in select patients.
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Recuperação Pós-Cirúrgica Melhorada , Neoplasias Supratentoriais , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Centros de Atenção Terciária , Tempo de Internação , Neoplasias Supratentoriais/cirurgia , Complicações Pós-OperatóriasRESUMO
Colloid cysts (CCs) are usually small, benign lesions located at the foramen of Monro. They usually grow to a size of 1-3 cms. We have described here a giant colloid cyst of size 6 x 5.2 x 4.4 cm with a unique radiological appearance of multiple concentric layers with different intensities which has not been described before. This unusual appearance is most probably due to the variation of hydration between the different layers with gradually decreasing concentration of protein from centre to periphery, which correlated well with intraoperative and histopathological findings.
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BACKGROUND: Experiencing racial microaggressions has clear effects on physical and psychological health, including obsessive-compulsive disorder symptoms (OCS). More research is needed to examine this link. Psychological flexibility is an important process to examine in this work. AIMS: This study aimed to examine if, while controlling for depression and anxiety, experiences of microaggressions and psychological flexibility helped explain OCD symptoms within a university-affiliated sample (undergraduate, graduate and law students). This was a pilot exploration of the relationships across themes. METHOD: Initial baseline data from a longitudinal study of psychological flexibility, OCD symptoms, depression, anxiety and experience of microaggressions was utilized. Correlations and regressions were utilized to examine which OCD symptom dimensions were associated with experiencing racial microaggressions in addition to anxiety and depression, and the added role of psychological flexibility was examined. RESULTS: OCD symptoms, experiences of microaggressions and psychological flexibility were correlated. Experiences of racial microaggressions explained responsibility for harm and contamination OCD symptoms above and beyond psychological distress. Exploratory results support the relevance of psychological flexibility. CONCLUSION: Results support other work that experiences of racial microaggressions help explain OCS and they add some support for psychological flexibility as a relevant risk or protective factor for mental health in marginalized populations. These topics should be studied longitudinally with continued consideration of all OCD themes, larger sample sizes, intersecting identities, clinical samples, and continued exploration of psychological flexibility and mindfulness and values-based treatments.
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Microagressão , Transtorno Obsessivo-Compulsivo , Humanos , Projetos Piloto , Estudos Longitudinais , Transtorno Obsessivo-Compulsivo/psicologia , Transtornos de AnsiedadeRESUMO
BACKGROUND: Topotecan is cytotoxic to glioma cells but is clinically ineffective because of drug delivery limitations. Systemic delivery is limited by toxicity and insufficient brain penetrance, and, to date, convection-enhanced delivery (CED) has been restricted to a single treatment of restricted duration. To address this problem, we engineered a subcutaneously implanted catheter-pump system capable of repeated, chronic (prolonged, pulsatile) CED of topotecan into the brain and tested its safety and biological effects in patients with recurrent glioblastoma. METHODS: We did a single-centre, open-label, single-arm, phase 1b clinical trial at Columbia University Irving Medical Center (New York, NY, USA). Eligible patients were at least 18 years of age with solitary, histologically confirmed recurrent glioblastoma showing radiographic progression after surgery, radiotherapy, and chemotherapy, and a Karnofsky Performance Status of at least 70. Five patients had catheters stereotactically implanted into the glioma-infiltrated peritumoural brain and connected to subcutaneously implanted pumps that infused 146 µM topotecan 200 µL/h for 48 h, followed by a 5-7-day washout period before the next infusion, with four total infusions. After the fourth infusion, the pump was removed and the tumour was resected. The primary endpoint of the study was safety of the treatment regimen as defined by presence of serious adverse events. Analyses were done in all treated patients. The trial is closed, and is registered with ClinicalTrials.gov, NCT03154996. FINDINGS: Between Jan 22, 2018, and July 8, 2019, chronic CED of topotecan was successfully completed safely in all five patients, and was well tolerated without substantial complications. The only grade 3 adverse event related to treatment was intraoperative supplemental motor area syndrome (one [20%] of five patients in the treatment group), and there were no grade 4 adverse events. Other serious adverse events were related to surgical resection and not the study treatment. Median follow-up was 12 months (IQR 10-17) from pump explant. Post-treatment tissue analysis showed that topotecan significantly reduced proliferating tumour cells in all five patients. INTERPRETATION: In this small patient cohort, we showed that chronic CED of topotecan is a potentially safe and active therapy for recurrent glioblastoma. Our analysis provided a unique tissue-based assessment of treatment response without the need for large patient numbers. This novel delivery of topotecan overcomes limitations in delivery and treatment response assessment for patients with glioblastoma and could be applicable for other anti-glioma drugs or other CNS diseases. Further studies are warranted to determine the effect of this drug delivery approach on clinical outcomes. FUNDING: US National Institutes of Health, The William Rhodes and Louise Tilzer Rhodes Center for Glioblastoma, the Michael Weiner Glioblastoma Research Into Treatment Fund, the Gary and Yael Fegel Foundation, and The Khatib Foundation.
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Glioblastoma , Glioma , Humanos , Topotecan/efeitos adversos , Glioblastoma/tratamento farmacológico , Convecção , Recidiva Local de Neoplasia/tratamento farmacológico , Glioma/patologiaRESUMO
How does attention enhance neural representations of goal-relevant stimuli while suppressing representations of ignored stimuli across regions of the brain? While prior studies have shown that attention enhances visual responses, we lack a cohesive understanding of how selective attention modulates visual representations across the brain. Here, we used functional magnetic resonance imaging (fMRI) while participants performed a selective attention task on superimposed stimuli from multiple categories and used a data-driven approach to test how attention affects both decodability of category information and residual correlations (after regressing out stimulus-driven variance) with category-selective regions of ventral temporal cortex (VTC). Our data reveal three main findings. First, when two objects are simultaneously viewed, the category of the attended object can be decoded more readily than the category of the ignored object, with the greatest attentional enhancements observed in occipital and temporal lobes. Second, after accounting for the response to the stimulus, the correlation in the residual brain activity between a cortical region and a category-selective region of VTC was elevated when that region's preferred category was attended vs. ignored, and more so in the right occipital, parietal, and frontal cortices. Third, we found that the stronger the residual correlations between a given region of cortex and VTC, the better visual category information could be decoded from that region. These findings suggest that heightened residual correlations by selective attention may reflect the sharing of information between sensory regions and higher-order cortical regions to provide attentional enhancement of goal-relevant information.
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Atenção/fisiologia , Formação de Conceito/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Lobo Temporal/fisiologia , Adolescente , Adulto , Reconhecimento Facial/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Lobo Temporal/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Revision total hip arthroplasty (THA) for adverse local tissue reactions (ALTRs) secondary to head-neck taper corrosion is associated with a high complication rate. Diagnosis of ALTR is based on risk stratification using the patient's history and examination, implant risk, serum metal ion levels, and imaging. The purpose of this study was to determine if stratification using similar risk factors is predictive of outcomes following revision THA for metal-on-polyethylene (MoP) ALTR. METHODS: We performed a retrospective review on 141 patients revised for ALTR due to head-neck taper corrosion. Pain outcomes following surgery were analyzed using a generalized linear mixed model. Complications were defined as instability/dislocation, infection, fracture, nerve palsy, leg-length discrepancy, or reoperation. RESULTS: The overall complication rate was 17.7%. The odds of having pain decreased by 44% after revision surgery (Odds Ratio = 0.56, 95% Confidence Interval: 0.324 to 0.952). There was no significant difference in instability/dislocation based on either increased or decreased head-neck offset (P = .67) or magnetic resonance imaging findings of abductor loss, effusion size, and degree of ALTR (P = .73). Increased serum cobalt (P = .31) and chromium (P = .08) levels did not predict complications; however, a decreased cobalt-chromium ratio was associated with postoperative complications (2.8 versus 3.5; P = .002). CONCLUSION: These findings are the first to suggest that patients who have ALTR after MoP THA undergoing revision surgery demonstrated major pain relief. Increasing femoral head offset did not change rates of instability/dislocation. In clinical scenarios where preoperative cobalt-chromium femoral head offsets were greater than available ceramic head offsets, a mandatory decrease in femoral head offset did not increase rates of instability/dislocation.
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Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/efeitos adversos , Reoperação/efeitos adversos , Prótese de Quadril/efeitos adversos , Falha de Prótese , Desenho de Prótese , Polietileno , Cobalto , Cromo , Corrosão , Metais , Medição de Risco , Dor/etiologiaRESUMO
Anti-epidermal growth factor receptor (EGFR) antibodies and anti-programmed cell death 1 protein (PD-1) antibodies have been used separately to treat metastatic cutaneous squamous cell carcinoma (cSCC). While two anti-EGFR antibodies have similar clinical activity, cetuximab is administered weekly, whereas panitumumab is administered every two weeks. This report details findings using panitumumab in combination with anti-PD-1 antibody in patients with relapsed refractory cSCC. Three consecutive patients with poor performance status and rapidly progressive recurrent cutaneous squamous cell carcinoma (cSCC) of the face or scalp signed informed consent to receive an anti-PD-1 antibody with the option to add panitumumab were there inadequate response. After 2, 5, and 7 cycles of anti-PD-1 antibody treatment, respectively, panitumumab was added and the combination was continued for 27, 7, and 5 cycles, respectively. Fatigue, rash, and hypomagnesemia were reported, consistent with expectations for either agent alone. All three patients achieved durable complete response. The favorable clinical outcomes support further evaluation of the combination of anti-PD1 and anti-EGFR antibodies to control refractory cSCC of the face or scalp. J Drugs Dermatol. 2021;20(8):901-904. doi:10.36849/JDD.6175.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Panitumumabe/uso terapêutico , Neoplasias Cutâneas , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológicoRESUMO
INTRODUCTION: Frontal extradural hematoma (EDH) extending into orbit is an uncommon entity. Clinical presentation can be subacutely progressive proptosis following head injury. CASE PRESENTATION: We present a case of frontal EDH with orbital extension which had delayed progressive proptosis. The patient improved clinically after surgical evacuation of EDH. CONCLUSION: It is important to look for orbital roof fractures, orbital hematoma in cases of head injury. Such cases should be treated surgically at the earliest.
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Traumatismos Craniocerebrais , Exoftalmia , Hematoma Epidural Craniano , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/cirurgia , Exoftalmia/etiologia , Hematoma , Hematoma Epidural Craniano/diagnóstico por imagem , Hematoma Epidural Craniano/etiologia , Hematoma Epidural Craniano/cirurgia , HumanosRESUMO
BACKGROUND: Diagnosis of adverse local tissue reaction (ALTR) in metal-on-polyethylene (MoP) total hip arthroplasty (THA) secondary to head-neck taper corrosion is challenging. The purpose of this study is to compare differences between asymptomatic and symptomatic ALTR in an observational cohort, including presentation, metal ion differences, and metal artifact reduction sequence (MARS) magnetic resonance imaging (MRI) findings. METHODS: We performed a retrospective review of an observational cohort of 492 MoP THA patients at increased risk of developing ALTR. Ninety-four patients underwent revision arthroplasty for ALTR. Patients were stratified into symptomatic and asymptomatic ALTR groups. Presentation, metal ion levels, and imaging findings were compared. RESULTS: For patients with confirmed ALTR, 41% were asymptomatic. There was a statistically significant difference in the serum chromium levels between symptomatic and asymptomatic ALTR patients (2.2 µg/L vs 3.1 µg/L, P = .05). There was no statistically significant difference between the serum cobalt levels or MRI findings in these 2 groups. We observed that extracapsular disease associated with ALTR could be misinterpreted as trochanteric bursitis. CONCLUSION: Almost half of the MoP THA ALTR cases identified were asymptomatic. Cobalt levels could not differentiate between symptomatic and asymptomatic pseudotumor formation. Symptomatic and asymptomatic MoP ALTRs have similar MARS MRI characteristics. Our findings suggest that it is essential to risk stratify patients who could potentially have ALTR based on implant type, symptoms, ion levels, and MARS MRI.
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Artroplastia de Quadril , Prótese de Quadril , Artroplastia de Quadril/efeitos adversos , Cromo , Cobalto/efeitos adversos , Corrosão , Prótese de Quadril/efeitos adversos , Humanos , Desenho de Prótese , Falha de Prótese , Reoperação , Estudos RetrospectivosRESUMO
The quantum approximate optimization algorithm (QAOA) has rapidly become a cornerstone of contemporary quantum algorithm development. Despite a growing range of applications, only a few results have been developed towards understanding the algorithm's ultimate limitations. Here we report that QAOA exhibits a strong dependence on a problem instances constraint to variable ratio-this problem density places a limiting restriction on the algorithms capacity to minimize a corresponding objective function (and hence solve optimization problem instances). Such reachability deficits persist even in the absence of barren plateaus and are outside of the recently reported level-1 QAOA limitations. These findings are among the first to determine strong limitations on variational quantum approximate optimization.
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Dilute magnetic semiconductors based on TiO2 nanocrystals are the most promising class of materials exhibiting unique optical and magnetic properties. In the present investigation, we have performed a systematic study on the structural, morphological, optical and magnetic behavior of Ni-doped TiO2, synthesized via a simple, cost-effective sol-gel route. X-ray diffraction patterns together with Raman spectra confirmed the tetragonal anatase phase of Ni-doped TiO2. High-resolution transmission electron microscopy images indicated the formation of highly crystalline nanocrystals, and the compositional homogeneity of all the samples was confirmed from energy dispersive X-ray fluorescence spectroscopic studies. The functional groups in the samples were identified by Fourier transform infrared spectroscopy. UV-visible and photoluminescence (PL) spectroscopy were performed to provide an insight into the band-gap narrowing in the Ni-doped TiO2 nanocrystals. X-ray photoelectron spectroscopy results signified the existence of Ti4+ and Ni2+ in all the prepared samples. A decrease in coercivity was observed with Ni substitution, and at lower Ni concentration, the magnetic behavior was attributed to the bound magnetic polarons associated with the oxygen vacancy defects arising during the synthesis procedure. PL analysis revealed the presence of defects in the system and Langevin fitting was employed to estimate the concentration of bound magnetic polarons arising as a result of these defects. The band-gap narrowing and the enhanced magnetic moment observed in Ni-doped TiO2 reveal the potential of this semiconductor for advanced functional applications such as magneto-optics and spintronics.
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We have carried out a detailed study of the morphological, structural, optical and magnetic properties of Cr doped TiO2 nanocrystals with doping concentrations varying from 3 to 12 atomic weight%. The results obtained from transmission electron microscopy analysis, size-strain plots of all the Cr-doped samples and crystallite size estimation reveal the particle size of the prepared nanocrystals to be well below 10 nm, which is observed to exhibit a decreasing trend with an increase in the Cr dopant concentration. All the samples crystallize in the anatase tetragonal phase of TiO2, which is confirmed from the Rietveld refinement of the X-ray diffraction patterns and the different modes present in the Raman spectra. The Eg(1) mode shows a clear red shift and broadening with increase in the Cr concentration, which indicates the replacement of Ti ions with Cr ions in the TiO2 lattice. The possibility of the presence of different functional groups present is verified by Fourier transform infra-red spectroscopy. The presence of Cr3+ and Ti4+ is confirmed from the X-ray photoelectron spectroscopy (XPS) results suggesting the formation of oxygen vacancies to compensate for the charge neutrality. The XPS results validate the Cr3+ existence in the Cr:TiO2 system and corroborate with a slight peak shift towards lower diffraction angle and further confirm the substitutional doping in the present case. Enhanced visible range optical absorption and a clear red shift associated with the absorption edge also suggest the incorporation of Cr3+ ions into the host system. The estimated band-gap of Cr-doped TiO2 nanocrystals reveals a decreasing trend with increasing Cr concentration. The Urbach energy associated with all the Cr-doped samples signifies the presence of oxygen vacancy related defects in the present system, which is further verified using photoluminescence (PL) spectra, and the deconvolution of the PL spectra provides an insight into the oxygen vacancy defects associated with the system. Paramagnetic (PM) behaviour is observed with an increase in the PM moment, suggesting the increase in isolated Cr ions with increase in the Cr concentration, which is further explained using a bound magnetic polaron (BMP) model. Isolated BMP formation could be the reason for the observed PM behavior of the present system, where the trapping of 3d electrons associated with Cr3+ in the vacancy sites could ultimately lead to fewer overlapped BMPs, yielding a net PM moment. The present Cr:TiO2 system could be modified with tailored optical and magnetic properties for functional applications such as magneto-optics and optoelectronic devices.
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Emerging evidence from epidemiological studies suggests a link between environmental chemical exposure and progression of aggressive breast cancer subtypes. Of all clinically distinct types of breast cancers, the most lethal phenotypic variant is inflammatory breast cancer (IBC). Overexpression of epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER) negativity is common in IBC tumor cells, which instead of a solid mass present as rapidly proliferating diffuse tumor cell clusters. Our previous studies have demonstrated a role of an adaptive response of increased antioxidants in acquired resistance to EGFR-targeting drugs in IBC. Environmental chemicals are known to induce oxidative stress resulting in perturbations in signal transduction pathways. It is therefore of interest to identify chemicals that can potentiate EGFR mitogenic effects in IBC. Herein, we assessed in ER-negative IBC cells a subset of chemicals from the EPA ToxCast set for their effect on EGFR activation and in multiple cancer phenotypic assays. We demonstrated that endocrine-disrupting chemicals such as bisphenol A (BPA) and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane can increase EGFR/ERK signaling. BPA also caused a corresponding increase in expression of SOD1 and anti-apoptotic Bcl-2, key markers of antioxidant and anti-apoptotic processes. BPA potentiated clonogenic growth and tumor spheroid formation in vitro, reflecting IBC-specific pathological characteristics. Furthermore, we identified that BPA was able to attenuate the inhibitory effect of an EGFR targeted drug in a longer-term anchorage-independent growth assay. These findings provide a potential mechanistic basis for environmental chemicals such as BPA in potentiating a hyperproliferative and death-resistant phenotype in cancer cells by activating mitogenic pathways to which the tumor cells are addicted for survival.
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Compostos Benzidrílicos/toxicidade , Carcinógenos Ambientais/toxicidade , Receptores ErbB/genética , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Fenóis/toxicidade , Compostos Benzidrílicos/farmacologia , Carcinógenos Ambientais/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Receptor alfa de Estrogênio/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/patologia , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacosRESUMO
The photocatalytic degradation mechanism of Amaranth, a recalcitrant carcinogenic azo dye, was investigated using mesoporous anatase TiO2 under sunlight. Mesoporous anatase TiO2 of a high photocatalytic activity has been synthesized using a sol-gel method and its photocatalytic activity for the degradation of Amaranth dye has been evaluated with respect to Degussa P25. The effect of bi-dentate complexing agents like oxalic acid, ethylene glycol and urea on the surface properties of TiO2 catalyst has been investigated using TG-DTA, FTIR, HR-TEM, SAED, PXRD, EDS, UV-DRS, PL, BET N2 adsorption-desorption isotherm studies and BJH analysis. The influence of catalyst properties such as the mesoporous network, pore volume and surface area on the kinetics of degradation of Amaranth as a function of irradiation time under natural sunlight has been monitored using UV-Vis spectroscopy. The highest rate constant value of 0.069 min-1 was obtained for the photocatalytic degradation of Amaranth using TiO2 synthesized via a urea assisted sol-gel synthesis method. The effect of the reaction conditions such as pH, TiO2 concentration and Amaranth concentration on the photodegradation rate has been investigated. The enhanced photocatalytic activity of synthesized TiO2 in comparison with P25 is attributed to the mesoporous nature of the catalyst leading to increased pore diameter, pore volume, surface area and enhanced charge carrier separation efficiency. New intermediates of photocatalytic degradation of Amaranth, namely, sodium-3-hydroxynaphthalene-2,7-disulphonate, 3-hydroxynaphthalene, sodium-4-aminonaphthalenesulphonate and sodium-4-aminobenzenesulphonate have been identified using LC-ESI-MS for the very first time, providing direct evidence for simultaneous bond cleavage pathways (-C-N-) and (-N[double bond, length as m-dash]N-). A new plausible mechanism of TiO2 catalysed photodegradation of Amaranth along with the comparison of its toxicity to that of its degradation intermediates and products is proposed.
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Here, we report a simple, cost-effective, surfactant-assisted, and aqueous-based low-temperature reflux method for the synthesis of Bi2Te3 nanocrystals. Thermoelectric properties of n-type bismuth telluride (BT) nanostructures are reported by varying the morphology and crystal structure. Tuning the reaction time from 1 to 36 h enables the phase transformation from BiTe with a hexagonal crystal structure to Bi2Te3 with a rhombohedral crystal structure, which is evident from the refined X-ray diffraction results and high-resolution transmission electron microscopy analysis. A perfect stoichiometric balance is achieved for all the compositions, and temperature variation of the electrical resistivity of all BT nanostructures shows the typical metal to semiconducting transition near room temperature. Seebeck coefficient and Hall measurements confirm electrons as the majority carriers and show the typical characteristics of n-type BT nanostructures. The nanocrystals inherited from the optimized reaction conditions and high densification of nanoparticle interfaces contribute to the considerable reduction of thermal conductivity in BT nanostructures. Highly crystalline, uniformly distributed nanocrystals of Bi2Te3 formed for 24 h reaction time demonstrate a promising figure of merit of 0.81 at 350 K, which can be attributed to their low thermal conductivity while the high electrical conductivity is maintained. Our research could provide new possibilities in low-temperature synthesis where structural, compositional, and morphological tuning of BT nanostructures could promote practical thermoelectric applications near room temperature.
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We demonstrate the use of surface-enhanced Raman spectroscopy (SERS) as an excellent tool for identifying the binding site of small molecules on a therapeutically important protein. As an example, we show the specific binding of the common antihypertension drug felodipine to the oncogenic Aurora A kinase protein via hydrogen bonding interactions with Tyr-212 residue to specifically inhibit its activity. Based on SERS studies, molecular docking, molecular dynamics simulation, biochemical assays, and point mutation-based validation, we demonstrate the surface-binding mode of this molecule in two similar hydrophobic pockets in the Aurora A kinase. These binding pockets comprise the same unique hydrophobic patches that may aid in distinguishing human Aurora A versus human Aurora B kinase in vivo. The application of SERS to identify the specific interactions between small molecules and therapeutically important proteins by differentiating competitive and noncompetitive inhibition demonstrates its ability as a complementary technique. We also present felodipine as a specific inhibitor for oncogenic Aurora A kinase. Felodipine retards the rate of tumor progression in a xenografted nude mice model. This study reveals a potential surface pocket that may be useful for developing small molecules by selectively targeting the Aurora family kinases.