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Taniguruma, Ryuji, Katsumi Fukuda e Masao Iinuma. "101. Remote-controlled universal radiographic diagnostic table RSZ-200". Japanese Journal of Radiological Technology 47, n.º 8 (1991): 1136. http://dx.doi.org/10.6009/jjrt.kj00003323845.
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Lupu, D., I. Coldea, I. Misan, M. Lazar e G. Blanita. "Hydrogen storage potential in MIL-101 at 200 K". International Journal of Hydrogen Energy 44, n.º 25 (maio de 2019): 12715–23. http://dx.doi.org/10.1016/j.ijhydene.2018.10.099.
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Campbell, Richard A., Eric Sanchez, Haiming Chen, Lauren Turker, Mingjie Li, Olivia Trac, Dror Shalitin et al. "ZIO-101, a Novel Organic Arsenic, Inhibits Human Myeloma Cell Growth in a SCID-hu Model." Blood 108, n.º 11 (16 de novembro de 2006): 3462. http://dx.doi.org/10.1182/blood.v108.11.3462.3462.
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Abstract Inorganic arsenics like arsenic trioxide (ATO) are novel anti-cancer drugs active in acute promyelocytic leukemia (APL) and multiple myeloma (MM). ATO induces apoptosis of plasma cells by several mechanisms including down-regulation of BCL-2 expression and inhibition of DNA-binding by NF-κB. The amount of ATO that can be safely given is low because of QTc-prolongation. ZIO-101, a new organic arsenic, is in phase-1/-2 trials. ZIO-101 can be safely given at much higher doses than ATO. We evaluated the in vivo anti-myeloma activity of ZIO-101 in a SCID-hu mouse model of human myeloma. LAGλ-1 was developed from a person with melphalan-resistant and LAGλ-1B from a person with bortezomib-resistant myeloma. Each severe combined immunodeficient (SCID) mouse was implanted with a 2–4 mm3 fragment of LAGλ-1B or LAGλ-1 into the left superficial gluteal muscle. Fragments were allowed to grow for 14 d when human IgG was first detectable. ZIO-101 was given IV 1 or 2 times/d using three different schedules: one day/w, 3 days/w or 5 days/w at doses of 50– 200 mg/kg/d. Tumor volume and human IgG were assessed weekly. Doses up to 200 mg/kg were well-tolerated. Anti-myeloma effects were observed in both models at doses of 100 – 200 mg/kg on all 3 schedules. Mice receiving 100 mg/kg twice daily thrice weekly and those receiving 200 mg/kg once weekly showed marked anti-myeloma activity (100 mg/kg, P = 0.03; 200 mg/kg, P = 0.001) and reduced human IgG levels (100 mg/kg, P < 0.001; 200 mg/kg, P = 0.01) compared to controls. We are evaluating ZIO-101 in other SCID-hu models of human myeloma and exploring different doses and schedules of ZIO-101 alone or combined with other anti-myeloma agents. In summary, these data show activity of ZIO-101 in human myeloma in vivo. These studies provide the bases for future clinical trials.
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Nag, Nitin Kumar. "An Economics Analysis of Honey Production in Baghpat District of Western Uttar Pradesh". Indian Journal of Pure & Applied Biosciences 10, n.º 1 (28 de fevereiro de 2022): 47–53. http://dx.doi.org/10.18782/2582-2845.8876.
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This study of Beekeeping, considered to be a 'no investment-profit-giving' venture, is an age-old tradition in India. The diversity of Bee- flora and varied agro-climate conditions in Uttar Pradesh offers enormous potential for the development and growth of apiculture. The district has six development blocks out of which two bocks, namely Baraut and Baghpat blocks were selected randomly for the study. Keeping low number of Honey bee producers in the study area, all 10 Honey bee producers. On the basis of Honey box unit, these bee producers were categories in two categories, i.e. 1-100 box and 101-200 box. The primary data were collected by survey method with respondents through scheduled personal interviews. The income from honey / box / annum came to Rs. 8077.36 in 1-100 box category while Rs. 8514.36 in 101-200 box category and the average income / box / annum came to Rs. 8295.83. The table also shows the category wise input-output ratio. The average of Input-Output Ratio came out to 1:3.65, while category wise, it came to 1:3.45 for 1-100 box category and 1:3.85 for 101-200 box category. The Operational cost of honey production/kg came to Rs. 57.87 for 1-100 box category while Rs. 50.91 for 101- 200 box category. The average operational cost came to Rs. 54.39. The operational cost of 1-100 box category and 101-200 box category came to Rs. 162.13 and Rs. 169.09 respectively. The average return over operational cost came to Rs. 165.61. This study is that Honey Production is a good combination for mixed farming because it requires less area of land, small capital, and high return. So those farmers who have less area of land should adopt honey production as a subsidiary occupation.
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Brokmeier, H. G. "Texture Analysis of a Zinc Layer on a Steel Substrate Using Neutron Diffraction". Textures and Microstructures 21, n.º 2-3 (1 de janeiro de 1993): 71–78. http://dx.doi.org/10.1155/tsm.21.71.
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This paper describes the application of neutron diffraction to investigate the texture of a zinc layer 8 μm in thickness. In a nondestructive way both the texture of the zinc layer as well as the texture of the steel substrate were studied. Therefore, pole figures of iron ((110), (200) and (211)) and of zinc ((0002), (101¯0), (101¯1); and (101¯3)/(112¯0)) were measured; additionally the orientation distribution function of iron and zinc were calculated.
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Tenforde, Mark W., Charles Muthoga, Ponego Ponatshego, Julia Ngidi, Madisa Mine, Greg Greene, Alexander Jordan, Tom Chiller, Bruce A. Larson e Joseph N. Jarvis. "Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101–200 cells/µL in Botswana". Wellcome Open Research 6 (10 de março de 2021): 55. http://dx.doi.org/10.12688/wellcomeopenres.16624.1.
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Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101–200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101–200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101–200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved). While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101–200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.
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Tenforde, Mark W., Charles Muthoga, Ponego Ponatshego, Julia Ngidi, Madisa Mine, Greg Greene, Alexander Jordan, Tom Chiller, Bruce A. Larson e Joseph N. Jarvis. "Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101–200 cells/µL in Botswana". Wellcome Open Research 6 (9 de dezembro de 2021): 55. http://dx.doi.org/10.12688/wellcomeopenres.16624.2.
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Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101–200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101–200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101–200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved). While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101–200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.
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Boudreault, Catherine, Yves Bergeron e Darwyn Coxson. "Factors controlling epiphytic lichen biomass during postfire succession in black spruce boreal forests". Canadian Journal of Forest Research 39, n.º 11 (novembro de 2009): 2168–79. http://dx.doi.org/10.1139/x09-127.
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Alectorioid lichens are the dominant group of epiphytic lichens in boreal forests. Epiphytic lichen richness and abundance generally increase with stand age and within-stand heterogeneity. The objective of this study was to evaluate the importance of time elapsed since the last fire, stand structure, tree size, tree age, and branch height for epiphytic lichen biomass of the boreal forest of western Quebec. We sampled 12 sites belonging to four forest age classes (from 50 to >200 years). We assessed epiphytic lichen biomass of three species groups ( Bryoria , Evernia , and Usnea ) on 12 trees in each site. Our results showed that biomass of Bryoria and Usnea was higher in intermediate stages (between 101 and 200 years) compared with younger (50–100 years) and older (>200 years) stages. Biomass of the three species groups was greater on larger diameter trees (>16 cm) compared with smaller ones (<16 cm). These results indicate that the protection of postfire stands aged between 101 and 200 year should be prioritized to maintain the functional role of epiphytic lichens in managed landscapes.
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Zou, Minmin, Hexin Zhu, Ming Dong e Tian Zhao. "Template Method for Synthesizing Hierarchically Porous MIL-101(Cr) for Efficient Removal of Large Molecular Dye". Materials 15, n.º 16 (20 de agosto de 2022): 5763. http://dx.doi.org/10.3390/ma15165763.
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As one of the most important prototypical chromium-based MOFs, MIL-101(Cr) is well-studied and widely employed in various scientific fields. However, due to its small capture window sizes and curved internal apertures, its application in large molecular removal is quite limited, and given its high stability and high synthetic temperature (>200 °C), it is difficult to achieve hierarchically porous MIL-101(Cr). In our study, hierarchically porous MIL-101(Cr) involving a high macro-/meso-/micropores ratio was designed and synthesized using acetic acid as an additive and silicon dioxide (SiO2) nanoparticles as a template. The optimal hierarchically porous MIL-101(Cr) (A-4) possessed a high specific surface area (2693 m2 g−1) and an abundant macro-/mesoporous structure with the addition of SiO2 of 200 mg. Compared with the control sample (A-0) with a less macro-/mesoporous structure, A-4 showed good adsorption properties for both coomassie brilliant blue R-250 (CBB, 82.1 mg g−1) and methylene blue (MB, 34.3 mg g−1) dyes, which were 1.36 times and 9.37 times higher than those of A-0. Moreover, A-4 also had good recyclability, and the removal rate of CBB was still higher than 85% after five cycles of adsorption.
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Glicksman, Allen, e Lauren Ring. "Defining Poverty as an Eligibility Requirement for Supportive Services". Innovation in Aging 5, Supplement_1 (1 de dezembro de 2021): 426–27. http://dx.doi.org/10.1093/geroni/igab046.1656.
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Abstract Deciding which individuals qualify as “poor” often depends on how each country or municipality defines the term ‘poverty’. In the United States, program eligibility is often tied to the Federal Poverty Level (FPL), using 100% of the FPL as a cut-off for receipt of services. However, research has shown that incomes of 200% of the FPL and higher are often needed to establish even minimum levels of economic security. Using data from an omnibus health study conducted in 2018 that included 1,581 persons ages 60+ who were asked about their health and service needs, we compared persons making 100% of the FPL or less to persons making 101%-199% and 200%+, respectively. Results show that poor health status and need for services among persons in the 101%-199% are similar to those with incomes less than 100% FPL, and significantly higher than persons with incomes at 200%+ of the FPL.
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Khanijow, V., A. O. Kaseb, M. Hassan, V. I. Machicao, H. M. Hassabo e J. L. Abbruzzese. "Hepatitis C as a predictor of treatment outcome in patients with hepatocellular carcinoma treated with the retinoid derivative, TAC-101." Journal of Clinical Oncology 29, n.º 4_suppl (1 de fevereiro de 2011): 200. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.200.
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200 Background: Most cases of HCC occur in the setting of cirrhosis secondary to alcohol abuse and hepatitis C, in the United States and Europe. Furthermore, recent data from phase III trials of sorafenib showed better survival in patients with HCV-related HCC. Animal studies suggested that TAC 101 regulates the transcription factor activated protein-1, which is constitutively activated by HCV core protein and contributes to hepatocarcinogenesis in persistent HCV infection. We hypothesized that prognostic impact of HCV-related HCC would be more pronounced in patients treated with TAC 101. Methods: This retrospective analysis included 105 patients treated in 3 clinical trials: TAC-101 (n=27), bevacizumab and erlotinib (n=48), and erlotinib alone (n=30) conducted at The University of Texas M. D. Anderson Cancer Center. Univariate and multivariate Cox regression was performed to estimate the adjusted hazard ratio (HR). Results: HCV was present in 35 (33%) patients. Multivariate survival analyses incorporating age, sex, HBV status, α-fetoprotein level, Child-Pugh classification, CLIP score, and BCLC staging did not identify a significant impact of HCV on OS or PFS. However, in patients who received TAC- 101, the presence of HCV was associated with a significantly reduced risk of disease progression (HR: 0.47, 95% CI:0.24-0.90, p= 0.024). Conclusions: These results indicate a possible beneficial interaction between HCV-related HCC and treatment with the retinoid derivative, TAC-101. HCV infection could be useful as a surrogate biomarker of the therapeutic efficacy of TAC-101. Further research is warranted to study the potential role of TAC 101 in HCV-related HCC patients. No significant financial relationships to disclose.
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Trenkwalder, Claudia, Mikko Kuoppamäki, Mikko Vahteristo, Thomas Müller e Juha Ellmén. "Increased dose of carbidopa with levodopa and entacapone improves “off” time in a randomized trial". Neurology 92, n.º 13 (1 de março de 2019): e1487-e1496. http://dx.doi.org/10.1212/wnl.0000000000007173.
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ObjectiveTo investigate whether increased fixed carbidopa doses of 65 or 105 mg (ODM-101/65 and ODM-101/105) in combination with 75, 100, 125, or 150 mg of levodopa and 200 mg of entacapone might improve “off” time in fluctuating Parkinson disease (PD) compared to the standard combination of 4:1 levodopa/carbidopa with the usual 200 mg of entacapone (LCE) during a 4-week treatment period.MethodsThis was a randomized, double-blind, double-dummy, active-controlled, crossover, multicenter, phase II, proof-of-concept study in patients with fluctuating PD.ResultsOne hundred seventeen patients were randomized into the study (mean age 67.0 years; daily “off” time 5.3 hours; mean daily levodopa dose 610 mg). Carryover-adjusted mean changes from baseline “off” times were during ODM-101/65, −1.53 hours (p = 0.02 vs LCE), during ODM-101/105, −1.57 hours (p = 0.01 vs LCE), and during LCE −0.91 hours. Changes in daily “on” time without dyskinesia were 1.54 hours (p = 0.005 vs LCE), 1.38 hours (p = 0.0214 vs LCE), and 0.69 hours, respectively. Changes in “on” time with troublesome dyskinesia were <0.1 hours and not significantly different between treatments. In patients with high-activity COMT genotypes Val/Met or Val/Val, “off” time was reduced more with ODM-101/65 and ODM-101/105 than with LCE (p = 0.015 and p = 0.006). No difference between the treatments was seen in safety and tolerability. The most common treatment-related adverse effects were nausea, dizziness, drug-effect decrease, and dyskinesia, which were in most cases mild or moderate in severity. Treatment-related serious adverse events were diarrhea (ODM-101/105 and LCE), and myocardial ischemia and blood creatine kinase increase (LCE).ConclusionIncreasing the dose of carbidopa in combination with levodopa and entacapone should be considered in the treatment of fluctuating PD to improve daily “off” times. Genotyping patients with PD according to COMT activity may improve individual treatment strategies.ClinicalTrials.gov identifierNCT01766258.Classification of evidenceThis study provides Class II evidence that an increased dose of carbidopa improves motor fluctuations when administered with levodopa and entacapone.
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Bermudez, Luiz E., Kevin Nash, Mary Petrofsky, Lowell S. Young e Clark B. Inderlied. "Clarithromycin-Resistant Mycobacterium avium Is Still Susceptible to Treatment with Clarithromycin and Is Virulent in Mice". Antimicrobial Agents and Chemotherapy 44, n.º 10 (1 de outubro de 2000): 2619–22. http://dx.doi.org/10.1128/aac.44.10.2619-2622.2000.
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ABSTRACT Resistance to clarithromycin in breakthrough Mycobacterium avium complex (MAC) isolates typically occurs 3 to 4 months after the initiation of monotherapy in bacteremic AIDS patients. It has been suggested that continuation of clarithromycin therapy still results in clinical and microbiological improvement. To study this paradox, C57BL/6 beige mice were infected with a clarithromycin-resistant (MIC, ≥128 μg/ml) strain of MAC 101 (CLA-R MAC 101) and treated with 200 mg of clarithromycin per kg of body weight/day alone or in combination with ethambutol (100 mg/kg/day) for 2 weeks. Mice infected with a clarithromycin-susceptible strain of MAC 101 had bacterial loads reduced by 90% in the liver and 91% in the spleen (P< 0.05, compared with the control). Clarithromycin treatment of CLA-R MAC 101 resulted in a 65% reduction of bacterial loads in the liver (P = 0.009) and a 71% reduction in the spleen (P = 0.009), compared with the results for the untreated control. CLA-R MAC 101 and MAC 101 (isogenic strains) had comparable growth rates in murine tissue, ruling out a loss of virulence of CLA-R MAC 101. Strains of MAC currently defined as macrolide resistant may still respond to treatment with an agent such as clarithromycin within infected tissues.
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BOSSHARD, C., R. STEPHAN e T. TASARA. "Application of an F57 Sequence-Based Real-Time PCR Assay for Mycobacterium paratuberculosis Detection in Bulk Tank Raw Milk and Slaughtered Healthy Dairy Cows". Journal of Food Protection 69, n.º 7 (1 de julho de 2006): 1662–67. http://dx.doi.org/10.4315/0362-028x-69.7.1662.
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A light cycler–based real-time PCR assay that targets the F57 sequence was used to collect data on the prevalence of Mycobacterium avium subsp. paratuberculosis (MAP) in 100 bulk tank raw milk samples and in a population of 101 slaughtered dairy cattle. The assay's reproducible detection limit in total genomic DNA templates isolated from 10-ml samples of MAP-spiked raw milk was 100 cells per ml. Similarly, the evaluation of MAP-spiked bovine feces also demonstrated that the assay had a reproducible detection limit of 100 cells if they were contained within 200 mg of fecal sample material. Among the 100 bulk tank milk samples that were tested, we found 3 samples (3%) to be positive for MAP. In the slaughterhouse part of the study, 8.9% (9 of 101) of the cows were positive for MAP DNA in fecal samples, 4.9% (5 of 101) in mesenteric lymph nodes, 0.9% (1 of 101) in ileum tissue, and 3.6% (3 of 84) in milk. Meanwhile, for 2.9% (3 of 101) of the culled cows, MAP DNA was detected in samples of diaphragmatic muscles.
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Webb, Heather K., Hao Chen, Albert S. Yu, Sissy Peterman, Leanne Holes, Brian Lannutti, Langdon L. Miller e Roger G. Ulrich. "Clinical Pharmacokinetics of CAL-101, a p110δ Isoform-Selective PI3K Inhibitor, Following Single- and Multiple-Dose Administration In Healthy Volunteers and Patients with Hematological Malignancies". Blood 116, n.º 21 (19 de novembro de 2010): 1774. http://dx.doi.org/10.1182/blood.v116.21.1774.1774.
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Abstract Abstract 1774 Phosphatidylinositol 3-kinases (PI3Ks) regulate several cellular functions including motility, proliferation, and survival. PI3K pathway signaling is mediated by the Class I PI3K isoforms, α, β, δ and γ. The PI3K p110δ isoform is preferentially expressed in cells of hematological origin and in a variety of malignant cells. CAL-101 is a potent p110δ inhibitor with an EC50 of 62 nM in a whole-blood p110δ assay and >200-fold selectivity for p110δ relative to other PI3K isoforms. Consistent with this target selectivity, nonclinical toxicology and safety pharmacology data supported initial clinical assessment of oral CAL-101 in single-dose, multiple-dose, and food-effect studies in healthy volunteers. Because CAL-101 is a CYP450 3A4 substrate, the effect of ketoconazole (a potent CYP450 3A4 inhibitor) on CAL-101 pharmacokinetics was also evaluated in healthy volunteers. Preliminary evaluation of disposition, metabolism and elimination in healthy volunteers was achieved by coadministering a trace amount of [14C]CAL-101 and unlabeled CAL-101 either orally or intravenously (IV) with samples evaluated by accelerator mass spectrometry. CAL-101 pharmacokinetics (PK) were subsequently evaluated in patients with lymphoid malignancies. In healthy volunteers, CAL-101 was well tolerated at 400 mg (the highest single dose tested) and at 200 mg BID through 7 days (the highest multiple dose tested). The drug has also been symptomatically well tolerated in patients with lymphoid malignancies receiving CAL-101 at dose levels through 350 mg/kg (the highest dose tested) over many months. Monitorable, reversible transaminase elevations have been observed in some patients, most commonly in patients with lymphoma. No maximum tolerated dose (MTD) has been apparent. Increases in Cmax and AUC are less than dose proportional, revealing minimal gains in plasma exposure at dose levels >150 mg BID. The mean volume of distribution was moderate at 57.7 L. The t1/2 was ∼8 hours across all dose levels and there was no plasma accumulation over 7 or 28 days. The collective data support BID dosing at ≥150 mg; dose levels in this range maintain steady-state trough plasma concentrations that are >10-fold above the EC50 for the in vitro whole-blood assay. [14C]CAL-101 was metabolized to only 1 metabolite in plasma and CAL-101-derived materials were primarily excreted in feces (>65% of total dose) with minimal elimination via urine (<15% of total dose). A high-fat, high-calorie meal had no effect on Cmax but slowed absorption, leading to a shift in observed median Tmax from 1.5 h to 4.5 h, and a moderate 1.4-fold increase in AUC; these data suggest that CAL-101 can be given with or without food. When administered following 4 days of ketoconazole, increases in mean CAL-101 Cmax and AUC values were 1.3- and 1.8-fold, respectively; thus, CAL-101 is not a sensitive substrate for CYP450 3A4 and coadministration of CAL-101 with CYP450 3A4 inhibitors does not appear to be contraindicated. Taken together with clinical data documenting PI3K pathway inhibition, modulation of chemokine signaling, and substantial dose-dependent antitumor activity, these findings provide a characterization of CAL-101 clinical pharmacology that supports CAL-101 development as an investigational therapy for cancer and other indications. Disclosures: Webb: Calistoga Pharmaceuticals: Employment. Chen:Calistoga Pharmaceuticals: Employment. Yu:Calistoga Pharmaceuticals: Employment. Peterman:Calistoga Pharmaceuticals: Employment. Holes:Calistoga Pharmaceuticals: Employment. Lannutti:Calistoga Pharmaceutical Inc.: Employment. Miller:Calistoga Pharmaceuticals: Employment. Ulrich:Calistoga Pharmaceuticals: Employment, Equity Ownership.
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Trieu, Vuong. "DDEL-16. DELIVERY OF OT-101 - TGF-Β ANTISENSE- FOR THE TREATMENT OF GLIOBLASTOMA". Neuro-Oncology 24, Supplement_7 (1 de novembro de 2022): vii97. http://dx.doi.org/10.1093/neuonc/noac209.362.
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Abstract OT-101 - a TGF-beta antisense- is active against recurrent glioblastoma in G004- a phase 2 clinical trial [Uckun FM, Qazi S, Hwang L, Trieu VN. Recurrent or refractory high grade gliomas treated by convection enhanced delivery of a TGF-beta2 targeting RNA therapeutic: a post-hoc analysis with long-term follow up. Cancers. 2019, 11:1892]. OT-101 was delivered intratumorally by Convection Enhanced Delivery (CED). To further expand the application of OT-101, we explored the intrathecal delivery of tritiated OT-101 into Sprague-Dawley CD (albino) rats. Throughout the studies, there were no sex differences. After 1 hr intracerebral infusion in rats, OT-101 was limited to the infusion site. Whereas for the 1 hr itravesicular infusion, OT-101 was more widespread with 35X, 19X, 12X higher concentration found in cerebellum, remaining cerebrum, cerebrospinal fluid (CSF), respectively. OT-101 concentration was stable for the first 4 hours post infusion and decayed biexponentially with a slow terminal half life for tissue but not for CSF, suggestive of rapid penetration of the underlying tissue away from the CSF compartment. Minimum amount of OT-101 was detected in the plasma compartment. Intrathecal bolus administration of 0.1mL of OT-101 at 14, 30, 200, 300, and 500 uM into cynomolgus monkies did not result in any single dose toxicity. Histopathology examination revealed no substance-related histomorphological lesions in the cavum subarachnoideale of the lumbar region. No changes were noted in the grey and white matter of the spinal cord, the nerve trunk, and nerve cells did not show any abnormalities. These data suggest that intrathecal administration of OT-101 is a potentially effective delivery route for antisense therapeutics such as OT-101 to the midline ie. for Diffuse Midline Glioma (DMG). A phase 1b/2 clinical trial evaluating OT-101 against DMG is proposed and the trial design will be presented
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Wang, Zhuo, Hao Liu, Yuwen Bao e Yun Gao. "Density Functional Theory Study on the Interfacial Interaction of LiF (200) and Anatase TiO2 (101)". Journal of Nanoscience and Nanotechnology 16, n.º 1 (1 de janeiro de 2016): 739–43. http://dx.doi.org/10.1166/jnn.2016.10824.
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Phan, Quoc-Hung, Van-Tung Nguyen, Chi-Hsiang Lien, The-Phong Duong, Max Ti-Kuang Hou e Ngoc-Bich Le. "Classification of Tomato Fruit Using Yolov5 and Convolutional Neural Network Models". Plants 12, n.º 4 (9 de fevereiro de 2023): 790. http://dx.doi.org/10.3390/plants12040790.
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Four deep learning frameworks consisting of Yolov5m and Yolov5m combined with ResNet50, ResNet-101, and EfficientNet-B0, respectively, are proposed for classifying tomato fruit on the vine into three categories: ripe, immature, and damaged. For a training dataset consisting of 4500 images and a training process with 200 epochs, a batch size of 128, and an image size of 224 × 224 pixels, the prediction accuracy for ripe and immature tomatoes is found to be 100% when combining Yolo5m with ResNet-101. Meanwhile, the prediction accuracy for damaged tomatoes is 94% when using Yolo5m with the Efficient-B0 model. The ResNet-50, EfficientNet-B0, Yolov5m, and ResNet-101 networks have testing accuracies of 98%, 98%, 97%, and 97%, respectively. Thus, all four frameworks have the potential for tomato fruit classification in automated tomato fruit harvesting applications in agriculture.
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Franc, Aleš, Slavomir Kurhajec, Sylvie Pavloková, Dana Sabadková e Jan Muselík. "Influence of concentration and type of microcrystalline cellulose on the physical properties of tablets containing Cornelian cherry fruits". Acta Pharmaceutica 67, n.º 2 (27 de junho de 2017): 187–202. http://dx.doi.org/10.1515/acph-2017-0019.
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AbstractThe aim of this study was to find the optimal tablet composition with maximum content of dried fruits (Cornus mas L.). The effect of three different concentrations (12.5, 25 and 50 %) of two types of microcrystalline cellulose (Avicel®PH 101 and Avicel®PH 200) and three different compression pressures (20, 60 and 100 MPa) on the physical properties of tablet blends and tablets was studied. Tablets containing 50 % Avicel®PH 101 compressed under 100 MPa were found to have the best physical properties. This combination of composition and compression pressure resulted in stable tablets even after storage under accelerated stability conditions (6 months, 40 °C and 75 % RH).
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Badawi, Aliaa A., Mahmoud M. Hegazy, Dina Louis e Mohammed A. Eldegwy. "Solving manufacturing problems for L-carnitine-L-tartrate to improve the likelihood of successful product scale-up". Acta Pharmaceutica 67, n.º 4 (20 de dezembro de 2017): 511–25. http://dx.doi.org/10.1515/acph-2017-0033.
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AbstractL-carnitine-L-tartrate, a non-essential amino acid, is hygroscopic. This causes a problem in tablet production due to pronounced adhesion of tablets to punches. A 33 full factorial design was adopted to suggest a tablet formulation. Three adsorbents were suggested (Aerosil 200, Aerosil R972, talc) to reduce stickiness at three concentrations (1, 3 and 5 %), and three fillers (mannitol, Avicel PH 101, Dibasic calcium phosphate) were chosen to prepare 27 formulations. Micromeritic properties of formulations were studied, and tablets were prepared by wet granulation. Absence of picking, sticking or capping, recording of sufficient hardness, acceptable friability and tablet ejection force indicated formulation success. The resulting formulation prepared using Avicel PH 101 and 1 % Aerosil 200 was submitted to further investigation in order to choose the most suitable compression conditions using a 33full factorial design. Variables included compression force, tableting rate and magnesium stearate (lubricant) concentration. The formulation prepared at compression force of 25 kN, using 2 % magnesium stearate, at a production rate of 30 tablets/ minute, was found to be the most appropriate scale up candidate.
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Lamers, Ryan P., Colleen R. Eade, Alan J. Waring, Amy L. Cole e Alexander M. Cole. "Characterization of the Retrocyclin Analogue RC-101 as a Preventative of Staphylococcus aureus Nasal Colonization". Antimicrobial Agents and Chemotherapy 55, n.º 11 (8 de agosto de 2011): 5338–46. http://dx.doi.org/10.1128/aac.00619-11.
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ABSTRACTNasal colonization ofStaphylococcus aureusis a risk factor for pathogenic autoinfection, particularly in postoperative patients and the immunocompromised. As such, standardized preoperative nasal decolonization ofS. aureushas become a major consideration for the prevention of nosocomial infection. However, only a few treatment options for nasal decolonization are currently available, with resistance to these approaches already a concern. Here we have identified the macrocyclic θ-defensin analogue RC-101 as a promising anti-S. aureusagent for nasal decolonization. RC-101 exhibits bactericidal effects againstS. aureuswith the use ofin vitroepithelium-free systems, while also preventing the pathogen's proliferation and attachment in anex vivohuman nasal epithelial cell adhesion model and an organotypic model of human airway epithelia. Peptide concentrations as low as 2.5 μM elicited significant reductions inS. aureusgrowth in epithelium-free systems, with 10 μM concentrations being completely bactericidal for all strains tested, including USA300. Inex vivonasal colonization models, RC-101 significantly reduced adherence, survival, and proliferation ofS. aureuson human nasal epithelia. Reductions inS. aureusviability were evident in these assays, with as little as 1 μg of peptide per tissue, while 10 μg of RC-101 completely prevented adhesion of all strains tested. Furthermore, RC-101 did not exhibit cellular toxicity to human nasal epithelia at concentrations up to 200 μM, nor did it induce a proinflammatory response in these cells. Collectively, the findings of this study identify RC-101 as a potential preventative ofS. aureusnasal colonization.
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Chevillard, J. P., J. Y. Mandin, C. Camy-Peyret e J. M. Flaud. "The first hexad {(040), (120), (021), (200), (101), (002)} of H218O: experimental energy levels and line intensities". Canadian Journal of Physics 64, n.º 6 (1 de junho de 1986): 746–61. http://dx.doi.org/10.1139/p86-136.
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The spectrum of 18O-enriched water vapor has been recorded between 5900 and 8000 cm−1, with the aid of a Fourier-transform spectrometer. Its analysis allowed the determination of 437 accurate rotational levels belonging to the hexad of interacting states {(040), (120), (021), (200), (101), (002)}of H218O. Among these vibrational states, the (040), (120), and (002) ones had never been observed before. Moreover, 726 line intensities belonging to the 4ν2, ν1 + 2ν2, 2ν2 + ν3, 2ν1, ν1 + ν3, and 2ν3 bands have been measured with an uncertainty of 6%.
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Lovelyn Chinyeaka Ugenyi, Joy Nkeiruka Dike-Ndudim, Henry Chidozie Amah e Chizaram Winners Ndubueze. "Assessment of antibacterial potentials of violacein extract from Chromobacterium violaceum isolated from domestic and recreational water sources in Owerri, Nigeria". World Journal of Advanced Pharmaceutical and Medical Research 1, n.º 2 (30 de setembro de 2021): 007–12. http://dx.doi.org/10.53346/wjapmr.2021.1.2.0024.
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This study was carried out with the aim of assessing the antibacterial potentials of violacein extracted from Chromobacterium violaceum isolated from domestic and recreational water sources in Owerri, Nigeria. Water samples were collected from different locations of the domestic water sources, five different swimming pools, and three borehole stations using sterile amber bottles. The isolation of C. violaceum was done using pour plate method on nutrient agar. The violet colonies of C. violaceum were counted, characterized and identified using standard microbiological and biochemical techniques. The mean viable bacterial counts were high. Water sample from Otamiri station-1 have the highest bacterial count (200 × 101 CFU/ml and 19.50 × 101 CFU/ml) respectively. Swimming pool 1 and 3 bacterial counts were (4.50 × 101 CFU/ml, 11 × 101 CFU/ml and 11.50 × 101 CFU/ml) respectively. For borehole 1, 2 and 3, swimming pool 2, 4 and 5, counts were (0.00 × 101 CFU/ml). Ethanolic extraction of violacein from C. violaceum was performed from a 48-hour culture broth. The sensitivity of the bacteria isolates to violacein was assayed on nutrient agar and nutrient broth by agar diffusion and broth dilution methods respectively. All the bacterial isolates were susceptible to the violacein extract at various concentrations, except MRSA that showed resistance to the violacein at 2.19mg/ml for extract from recreational water isolate and at 17.5mg/ml to 2.19mg/ml for extract from domestic water isolates. Conclusively, violacein has the potential to be used as an antibacterial compound for treatment of multidrug resistant bacterial infections.
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Abbas, Ishraq Kadhim, e Shaimaa Nazar Abddulhameed. "Preparation and Characterization of Bilastine Solid Self-Nanoemulsion using Liquisolid Technique". Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ) 5 (26 de julho de 2023): 78–85. http://dx.doi.org/10.54133/ajms.v5i.160.
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Background: Supersaturable self-nanoemulsion (S-SNE) is an approach for dealing with low oral bioavailability problems. Bilastine (BL) is a selective H1-antihistamine with a bioavailability of 59%. Objective: To use a liquisolid technique to transform liquid BL S-SNE into powder so that both the S-SNE and liquisolid procedures could be used. Methods: Oleic acid, tween 60, transcutol, and soluplus were used to make the liquid BL-loaded S-SNE that was adsorbed onto the Avicel PH101 and Aerosil 200 admixtures. In vitro dissolution and powder flow characteristics were tested. SEM, DSC, X-ray diffraction, FT-IR analysis, and the average droplet size after dispersion in 0.1N HCl were also utilized to define the best formula's solid state. Results: The best liquid-solid composition, SS-F2, is composed of oleic acid, tween 60, transcutol, soluplus, Avicel 101, and Aerosil 200, with a liquid SNE to Avicel 101 ratio of 1.5:1 and an Avicel 200 to Aerosil 200 ratio of 10:1. SS-F2 displayed good flowability and a significant improvement in drug dissolution, with 100% of the medication released after 60 min compared to 62.27% of the marketed BL tablets. According to the solid-state investigation of formula (SS-F2), BL was shown to be in a solvated state in the solidified nanosystem, with no interactions with the excipient used. It also formed a nanoemulsion with mean droplet sizes of 77.57 nm and a PDI of 0.4178, which was similar to liquid S-SNE. Conclusion: The liquisolid technique is a potential method for solidifying a liquid self-emulsifying system while preserving self-nanoemulsion characteristics and increasing dissolving rate.
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Gao, Y., K. L. Merkle, H. L. M. Chang, T. J. Zhang e D. J. Lam. "Microstructure of TiO2 rutile thin films deposited on (110) α−Al2O3". Journal of Materials Research 6, n.º 11 (novembro de 1991): 2417–26. http://dx.doi.org/10.1557/jmr.1991.2417.
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TiO2 rutile thin films grown on (110) sapphire (α−Al2O3) by the MOCVD technique have been characterized by transmission electron microscopy (TEM) and high resolution electron microscopy (HREM). The TiO2 rutile thin films grew on the sapphire with two epitaxial orientations. The epitaxial orientation relationships between the rutile films (R) and the sapphire substrate (S) were found to be (1) (101)[010]R ‖ (110)[0001]s. Detailed atomic structures of near-interface regions have been investigated by HREM, providing a clear picture of the initial stage of film growth. HREM images show that about 70% of the nuclei at the interface are the (101) rutile, but most of them are very small, about 5 nm (or 2% of the film thickness) in the growth direction. The film growth was dominated by the (200) orientation. Nucleation and growth of the films will be discussed in terms of the lattice mismatch at the interface and growth rates along the two orientations. Planar defects such as twin boundaries and special grain boundaries are commonly observed in the films, especially in regions close to the substrate. The twin plane and twinning direction are {101} and 〈101〉, respectively. Special grain boundaries are found to be correlated with nucleation and twinning.
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Salman, Mazen, Mohammad Jawabreh e Basima Abu Rumaileh. "The effect of local fungicides on conidial germination of Spilocaea oleagina in Palestine". مجلة جامعة فلسطين التقنية للأبحاث 2, n.º 1 (9 de fevereiro de 2014): 26–28. http://dx.doi.org/10.53671/pturj.v2i1.25.
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Olive leaf spot (OLS) disease or peacock disease is caused by the fungus Spilocaea oleagina, it is the most destructive disease on olive trees in most regions of Palestine. The disease is controlled by application of copper containing fungicides. Currently, there are more than 20 different fungicides sold in the Palestinian market. The efficacy of these fungicides was not tested on OLS in Palestine. The aim of this work was to test the efficacy of three major fungicides used against the disease. Fungicide solutions containing Fungran, Copper Antracol, and Kocide®101 were prepared by dissolving 0.5 g of each in 200 ml distilled water (DW) according to manufacturer instruction. Five leaves infected with OLS were soaked in each solution for 30 min. Control leaves were placed in 200 ml DW. Leaves were then placed in 9 cm petri dishes containing 3 ml DW to provide high humidity (> 85%). Each day, one leaf was removed, washed in DW and cut into one-cm2 pieces. Leaf pieces holding OLS conidia were printed on olive leaf extract agar media. Results showed that after 24h of fungicide treatment, Kocide®101 was the most effective fungicide followed by Copper Antracol and Fungran with percent conidial germination 2.08, 2.9 and 25.5%, respectively. Interestingly, Fungran efficacy after 48h (2.8% germination) was higher but not significantly different than Kocide®101 and Copper Antracol. This study showed that the efficacy of the three commonly used fungicides against OLS disease in Palestine diminished after four days of treatment. Further studies are needed to test the efficacy of these fungicides under field conditions for a better control planning of peacock disease in Palestine.
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Salman, Mazen, Mohammad Jawabreh e Basima Abu Rumaileh. "The effect of local fungicides on conidial germination of Spilocaea oleagina in Palestine". مجلة جامعة فلسطين التقنية خضوري للأبحاث 2, n.º 1 (9 de fevereiro de 2014): 26–28. http://dx.doi.org/10.53671/ptukrj.v2i1.25.
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Olive leaf spot (OLS) disease or peacock disease is caused by the fungus Spilocaea oleagina, it is the most destructive disease on olive trees in most regions of Palestine. The disease is controlled by application of copper containing fungicides. Currently, there are more than 20 different fungicides sold in the Palestinian market. The efficacy of these fungicides was not tested on OLS in Palestine. The aim of this work was to test the efficacy of three major fungicides used against the disease. Fungicide solutions containing Fungran, Copper Antracol, and Kocide®101 were prepared by dissolving 0.5 g of each in 200 ml distilled water (DW) according to manufacturer instruction. Five leaves infected with OLS were soaked in each solution for 30 min. Control leaves were placed in 200 ml DW. Leaves were then placed in 9 cm petri dishes containing 3 ml DW to provide high humidity (> 85%). Each day, one leaf was removed, washed in DW and cut into one-cm2 pieces. Leaf pieces holding OLS conidia were printed on olive leaf extract agar media. Results showed that after 24h of fungicide treatment, Kocide®101 was the most effective fungicide followed by Copper Antracol and Fungran with percent conidial germination 2.08, 2.9 and 25.5%, respectively. Interestingly, Fungran efficacy after 48h (2.8% germination) was higher but not significantly different than Kocide®101 and Copper Antracol. This study showed that the efficacy of the three commonly used fungicides against OLS disease in Palestine diminished after four days of treatment. Further studies are needed to test the efficacy of these fungicides under field conditions for a better control planning of peacock disease in Palestine.
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Peters, Rinne M., Bas L. E. F. Ten Have, Kyrill Rykov, Liza Van Steenbergen, Hein Putter, Marijn Rutgers, Stan Vos et al. "The learning curve of the direct anterior approach is 100 cases: an analysis based on 15,875 total hip arthroplasties in the Dutch Arthroplasty Register". Acta Orthopaedica 93 (27 de setembro de 2022): 775–82. http://dx.doi.org/10.2340/17453674.2022.4802.
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Background and purpose: In the last decade, the direct anterior approach (DAA) for total hip arthroplasty (THA) has become more popular in the Netherlands. Therefore, we investigated the learning curve and survival rate of the DAA in primary THA, using data from the Dutch Arthroplasty Register (LROI).Patients and methods: We identified all patients who received a primary THA using the DAA in several high-volume centers in the Netherlands between 2007 and 2019 (n = 15,903). Procedures were ordered per surgeon, using date of operation. Using the procedure number, operations were divided into 6 groups based on the number of previous procedures per surgeon (first 25, 26–50, 51–100, 101–150, 151–200, > 200). Data from different surgeons in different hospitals was pooled together. Revision rates were calculated using a multilevel time-to-event analysis.Results: Patients operated on in group 1–25 (hazard ratio [HR] 1.6; 95% CI 1.1–2.4) and 26–50 (HR 1.6; CI 1.1–2.5) had a higher risk for revision compared with patients operated on in group > 200 THAs. Between 50 and 100 procedures the revision risk was increased (HR 1.3; CI 0.9–1.9), albeit not statistically significant. From 100 procedures onwards the HR for revision was respectively 1.0 (CI 0.6–1.6) and 0.8 (CI 0.5–1.4) for patients in operation groups 101–150 and 151–200. Main reasons for revision were loosening of the stem (29%), periprosthetic infection (19%), and dislocation (16%).Interpretation: We found a 64% increased risk of revision for patients undergoing THA using the DAA for the first 50 cases per surgeon. Between 50 and 100 cases, this risk was 30% increased, but not statistically significant. From 100 cases onwards, a steady state had been reached in revision rate. The learning curve for DAA therefore is around 100 cases.
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Apalata, Teke, William H. Carr, Willem A. Sturm, Benjamin Longo-Mbenza e Prashini Moodley. "Determinants of Symptomatic Vulvovaginal Candidiasis among Human Immunodeficiency Virus Type 1 Infected Women in Rural KwaZulu-Natal, South Africa". Infectious Diseases in Obstetrics and Gynecology 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/387070.
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Introduction. We sought to determine the association between HIV-induced immunosuppression, virologic correlates, and vulvovaginal candidiasis (VVC).Methods. This is a retrospective cohort study, where HIV infected and uninfected women were studied with VVC being the primary outcome. Ninety-seven HIV-infected and 101 HIV-uninfected women were enrolled between June and December 2011. Cases of VVC were confirmed. HIV RNA load was determined by RT-PCR and CD4 counts were obtained from medical records.Results. Fifty-two of 97 (53.6%) HIV-infected and 38/101 (37.6%) HIV-uninfected women were diagnosed with VVC (P=0.032). The relative risk for VVC amongst HIV-infected patients was 1.53 (95% CI: 1.04–2P=0.024). Cases of VVC increased at CD4+ T cell count below 200 cells/mm3(P<0.0001) and plasma HIV RNA load above 10 000 copies/mL (P<0.0001). VVC was associated with increased genital shedding of HIV (P=0.002), and there was a linear correlation between plasma HIV load and genital HIV shedding (r=0.540;R2=0.292;P<0.0001). Women on HAART were 4-fold less likely (P=0.029) to develop VVC.Conclusion. CD4 counts below 200 cells/mm3and plasma HIV loads ≥10 000 copies/mL were significantly associated with VVC.
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Mayangsari, Dewi. "Leksikostatistik Bahasa Bugis dan Bahasa Toraja (Lexicostatistic of Bugis Language and Toraja Language)". JALABAHASA 16, n.º 1 (10 de junho de 2020): 83. http://dx.doi.org/10.36567/jalabahasa.v16i1.471.
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Penelitian ini bertujuan menunjukkan waktu pisah dari bahasa proto antara bahasa Bugis dan bahasa Toraja. Pengumpulan data dilakukan dengan metode padan referensial. Analisis data dilakukan dengan metode leksikostatistik. Adapun metode penyajian hasil menggunakan metode informal dan formal. Hasil penelitian ini menunjukkan bahwa bahasa Bugis dan bahasa Toraja memiliki persentase 53% kekerabatan. Berdasarkan perhitungan leksikostatistik, dari 200 kosakata dasar Swadesh pada bahasa Bugis dan bahasa Toraja, ditemukan 101 kosakata kerabat dan 90 nonkerabat. Simpulan penelitian ini adalah bahwa bahasa Bugis dan bahasa Toraja berkerabat serta termasuk dalam tingkatan keluarga bahasa. This study aims to investigates the presumed time of language separation of proto languages, namely Bugis and Toraja languages. The methods applied in this study covers both data collecting method, namely a referential equivalent method, and data analysing method, namely a lexicostatistic method. Moreover, the results of the analysis are presented in both formal and informal methods. The study reveals that Bugis and Toraja languages have a 53% of kinship percentage. Based on lexicostatistic calculations, from 200 Swadesh basic vocabularies in Bugis and Toraja languages there were found 101 relatives and 90 non-relatives. The conclusions of this study are that Bugis and Toraja languages are related and belong to the language family level.
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Flament, Anne, Frédéric Lehmann, Erik Alcantar-Orozco, Emilie Cerf, Caroline Lonez, David Gilham e Charles Morris. "407 A phase 1b KEYNOTE-B79 trial evaluating non-gene edited allogeneic CAR T-cells, CYAD-101, post FOLFOX preconditioning, followed by pembrolizumab, in refractory metastatic colorectal cancer patients". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (novembro de 2021): A438. http://dx.doi.org/10.1136/jitc-2021-sitc2021.407.
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BackgroundThe peptide-based allogeneic chimeric antigen receptor (CAR) T-cell treatment CYAD-101 utilizes an NKG2D receptor that targets eight ligands expressed on tumor cells and non-malignant stromal cells of many cancer types. CYAD-101 also co-expresses a peptide intended to eliminates the potential of graft versus host disease (GvHD). In the phase 1 alloSHRINK study (NCT03692429), CYAD-101 was administered with FOLFOX preconditioning chemotherapy to 15 patients with metastatic colorectal cancer (mCRC). The treatment was well tolerated with no evidence of GvHD, no treatment-related adverse events ≥ Grade 3 and only two patients who presented a cytokine release syndrome grade 1. By contrast, encouraging clinical activity was observed including two partial responses. Evidence of changes in the TCR repertoire and modulation of the cytokine profile four months post-treatment with CYAD-101 were also observed implying that the NKG2D CAR T may also be modulating the immune suppressive environment in patients reflecting that seen in pre-clinical models (ASCO GI 2021 abstract #74).Given the expansion of the T cell repertoire after CYAD-101 therapy, we considered that employing a checkpoint inhibitor to release this expanded T cell population may drive more durable clinical responses beyond that currently seen with the CAR T alone.MethodsThe KEYNOTE-B79 trial evaluates the safety and clinical activity of multiple infusions of CYAD-101, administered post FOLFOX preconditioning chemotherapy, then followed three weeks after CYAD-101 by a pembrolizumab consolidation treatment (200 mg every three weeks for a maximum two years total treatment duration) in microsatellite stable/mismatch-repair proficient mCRC patients with recurrent/progressing disease after at least one metastatic line of therapy which must include FOLFOX chemotherapy.The schedule of administration of three CYAD-101 infusions at the dose 1x109 cells/infusion Q2W post-FOLFOX preconditioning chemotherapy are based on the alloSHRINK study.This sequencing of checkpoint inhibitor at a timepoint after CYAD-101 therapy ensures that the modulated endogenous immune response is enabled by pembrolizumab. This study is not focused on impacting the CAR T cell itself largely since CYAD-101 cells at the time of manufacture show negligible expression of PD-1 and that this sequencing ensures no overlap of potential toxicities that could arise from the CAR T or checkpoint inhibitor therapies.The KEYNOTE-B79 study is planned to be initiated in Q4-2021.Ethics ApprovalThe study was approved by all relevant authorities and submitted to Institution’s Ethics Boards for their approval before study initiation.
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Naranbhai, Vivek, Christina C. Chang, Wilfredo F. Garcia Beltran, Tyler E. Miller, Michael G. Astudillo, Julian A. Villalba, Diane Yang et al. "High Seroprevalence of Anti-SARS-CoV-2 Antibodies in Chelsea, Massachusetts". Journal of Infectious Diseases 222, n.º 12 (9 de setembro de 2020): 1955–59. http://dx.doi.org/10.1093/infdis/jiaa579.
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Abstract SARS-CoV-2 antibody testing allows quantitative determination of disease prevalence, which is especially important in high-risk communities. We performed anonymized convenience sampling of 200 currently asymptomatic residents of Chelsea, the epicenter of COVID-19 illness in Massachusetts, by BioMedomics SARS-CoV-2 combined IgM-IgG point-of-care lateral flow immunoassay. The seroprevalence was 31.5% (17.5% IgM+IgG+, 9.0% IgM+IgG−, and 5.0% IgM−IgG+). Of the 200 participants, 50.5% reported no symptoms in the preceding 4 weeks, of which 24.8% (25/101) were seropositive, and 60% of these were IgM+IgG−. These data are the highest seroprevalence rates observed to date and highlight the significant burden of asymptomatic infection.
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Uckun, Fatih, Sanjive Qazi, David Nam, Larn Hwang e Vuong Trieu. "ATIM-06. TREATMENT OF RECURRENT/REFRACTORY (R/R) ANAPLASTIC ASTROCYTOMA (AA, WHO GRADE 3) PATIENTS WITH ANTI-TGFß2 RNA THERAPEUTIC OT-101 VERSUS TEMOZOLOMIDE IS ASSOCIATED WITH IMPROVED OVERALL SURVIVAL". Neuro-Oncology 21, Supplement_6 (novembro de 2019): vi2. http://dx.doi.org/10.1093/neuonc/noz175.006.
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Abstract BACKGROUND OT-101 is a first-in-class RNA therapeutic designed to disrupt the immunosuppressive action of TGFß2. During Phase 1 clinical trials, OT-101 induced partial responses in R/R AA patients. We now report our clinical results from a randomized Phase IIB study (NCT00431561) that further evaluated its single agent activity in R/R AA patients in side-by-side comparison with the standard chemotherapy drug temozolomide (TMZ). METHODS OT-101 was administered via high-flow microperfusion with an intratumoral catheter using a convection enhanced delivery (CED) system. 26 AA patients (12: 2.5 mg/cycle; 14: 19.8 mg/cycle) received 7-day cycles of OT-101 every other week via continuous infusion for 4–11 cycles. Response determinations were based on central review of MRI scans by an independent review committee according to standard as well as modified McDonald criteria. 11 patients in the active control arm were treated with TMZ (150–200 mg/m2, 5 days/28-day cycles x up to 6 treatment cycles). Standard statistical methods were applied for the analysis of data. RESULTS 14 of 26 patients (53.8%) treated with 4–11 cycles of OT-101 had either a CR (N=2) or PR (N=12) as their best overall response. The average time until 99% reduction of their tumor volumes ranged from 9.9 to 115.4 (median: 23.7) months. In contrast, only 1 of 10 evaluable patients (10%) treated with TMZ achieved an objective response which was a PR (Fisher’s exact test, 2-tailed, P-value = 0.0002). The median overall survival (OS) was 1154 days (95% CI: 811 - >1743) for the OT-101 group and 590 days (95% CI: 287 - >1137) days for the TMZ group (Log Rank Chi Square = 7.55, P-value = 0.006). CONCLUSION Our results confirm and extend previous studies and provide early evidence that the anti-TGFß2 RNA therapeutic OT-101 is at least as active as TMZ in salvage therapy of R/R AA patients.
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Cho, Byoung Chul, Sang Joon Shin, Jae-Lyun Lee, Byoung Yong Shim, Hyung Soon Park, Nari Yun, Mina Ham, Young Jun Koh e Myoung Ho Jang. "470 A phase 1/2, open-label, dose escalation and expansion study of GI-101 as a single agent and in combination with a pembrolizumab, lenvatinib or local RT in advanced solid tumors (KEYNOTE-B59)". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (novembro de 2021): A499. http://dx.doi.org/10.1136/jitc-2021-sitc2021.470.
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BackgroundGI-101 is a novel bispecific fusion protein containing CD80 and interleukin-2 (IL-2) variant, designed to exhibit high affinity to cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and preferential binding to IL-2Rβ subunit. In various animal models, GI-101 exerted strong anti-tumor efficacy, accompanied by robust stimulation of CD8+ T and NK cell proliferation without a significant increase in regulatory T cells. GI-101 also elicited synergistic anti-tumor efficacy when used in combination with pembrolizumab (anti-PD1 agents), lenvatinib (tyrosine kinase inhibitor) and radiation in in vivo.1 Given the complementary mechanisms of action of GI-101 via blocking CTLA4 with IL-2 activity to enhance the proliferation and activation of effector T and NK cells, it was hypothesized that GI-101 as a single agent or in combination with other immunotherapies, VEGF inhibitors or RT may exert anti-tumor activity in cancers with high unmet needs.MethodsKEYNOTE-B59 (NCT04977453) is an ongoing phase 1/2 study composed of 4 parts. This study is planned to enroll approximately 374 patients across the indications. Patients assigned to Part A and B receive either GI-101 monotherapy (Part A) or GI-101 + 200 mg of pembrolizumab (Part B) via IV infusion on every 3 weeks (q3w). In Part C, patients will receive GI-101 q3w in combination with lenvatinib (oral, once daily). In Part D, patients will be given GI-101 q3w in combination with local tumor irradiation. Each part is initiated with dose-escalation/optimization phases which will enroll patients with advanced solid tumors, except Part D that enrolls advanced melanoma and sarcoma only. This phase utilizes conventional 3+3 design to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of GI-101 as a monotherapy and in combination. Once RP2D is determined, patients will be enrolled in dose-expansion phases of each part that includes specific tumor types, such as solid cancers failed on standard of care, treatment-naïve unselected or CPI-treated solid tumors. Patients with advanced solid tumors and recovered from prior therapy will be enrolled. This study will assess safety, tolerability, dose-limiting toxicities, MTD, RP2D, preliminary anti-tumor activity, and pharmacokinetics/pharmacodynamics of GI-101 as a single agent and in combination.ResultsThis study is currently enrolling patients with advanced or metastatic solid tumors.AcknowledgementsThe authors would like to thank all the patients who are participating in this study. The study is sponsored by GI Innovation, Inc.Trial RegistrationNCT04977453ReferencePyo KH, Synn CB, Koh YJ, et al. Comprehensive preclinical study on GI-101, a novel CD80-IgG4-IL2 variant protein, as a therapeuticantibody candidate with bispecific immuno-oncology target. Cancer Res 2021;81(13_Suppl).Ethics ApprovalThis study was approved by Severance hospital institutions’ Ethics Review Board (IRB); approval number 4-2021-0185, Asan Medical center‘s IRB; approval number 2021-0669.
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Gutierrez, Martin, Darren Sigal, Kevin Berth, Adam Kuehn, John Colerangle, Sharmila Koppisetti, Shawn He, William van der Touw, Robert Hariri e Mark S. Awadalla. "A phase I/IIa open label, nonrandomized, multicenter study of CYNK-101 in combination with trastuzumab and pembrolizumab in patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma." Journal of Clinical Oncology 41, n.º 4_suppl (1 de fevereiro de 2023): TPS478. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.tps478.
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TPS478 Background: CYNK-101 is a human placental hematopoietic stem/progenitor cell derived NK cell product, that is genetically modified to express a variant of CD16, FcγRIII, via lentiviral vector transduction. The CD16 variant has amino acid modifications to enable high affinity and proteolytic cleavage-resistance for ADCC enhancement. Results from preclinical studies demonstrated enhanced ADCC activity of CYNK-101 in combination with trastuzumab against HER2+ gastric cancer cell lines in vitro, ex vivo and in vivo. Methods: A Phase I/IIa study is a first-line treatment of patients with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Patients are required to have confirmation of HER2 positivity defined as either IHC 3+ or IHC 2+ with a positive FISH or FISH + alone. Following the completion of screening assessments, patients are enrolled to the initial induction period of the trial and receive pembrolizumab, trastuzumab and a fluoropyrimidine/platinum based-chemotherapy for up to six 21-day cycles. In Phase I, patients may skip the initial induction period if they had previously been treated with pembrolizumab or, trastuzumab and a fluoropyrimidine/platinum based-chemotherapy and have not achieved an adequate response. Patients complete a disease assessment and then proceed to a lymphodepletion regimen of cyclophosphamide 900 mg/m2 and fludarabine 30 mg/m2 with MESNA for 3 days. Following 2 days of rest, the NK-cell re-induction period of the study begins with pembrolizumab 200 mg and trastuzumab 6 mg/kg on Day 1 of that cycle and 6M IU of rhIL-2 with CYNK-101 on days 1, 8, 15. CYNK-101 will be administered based on the calculated number of transduced cells per body weight as measured in kilograms (kg). Two dose levels of CYNK-101 (36 x 106 transduced cells/kg, and 72 x 106 transduced cells/kg) will be evaluated for the NK-Cell reinduction period during the Phase 1 portion of the study in a standard “3+3” dose escalation fashion. Once the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is determined in Phase I, the designated dosing Cohort level of the NK-Cell re-induction period will be used for the Phase IIa Expansion portion of the study. Both study periods will contain maintenance dosing of pembrolizumab 200 mg, trastuzumab 6 mg/kg and 6M IU rhIL-2 with 3.6 x 106 transduced cells/kg of CYNK-101 on Day 1 of a 21-day cycle. Endpoints: Primary endpoints for Phase I, include the incidence of adverse events defined as dose-limiting toxicities (DLTs). Phase IIa will evaluate efficacy as measured by overall response rate and a complete response rate as determined by RECIST 1.1. Approximately 52 patients are planned for this Phase I/IIa study. Clinical trial information: NCT05207722 .
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Wahyudi Efendi, Aco. "Analysis and Management of Senayan PLTD Noise Pollution". Jurnal Ekologi, Masyarakat dan Sains 4, n.º 2 (4 de julho de 2023): 54–63. http://dx.doi.org/10.55448/kt0bf693.
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PLTD activities must pay attention to environmental conditions on the important impacts that occur, specifically regarding the impact of noise that occurs from the operation of the machine. This study's intention is to quantify the degree to which the Senayan 101 MW PLTD's operation has an adverse effect on the neighborhood's noise levels. Constant Noise Type having a broad frequency range. It is advised to install a barrier made of concrete blocks 200 x 200 x 400 with a thickness of 300 mm as high as 6000 mm and a distance of 3000 mm in areas where the noise level is above 70 dB.A. This will help to reduce noise pollution by 20.05 dB.A, bringing the initial noise level down to 68.65 dB. A.
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Lindner, Donna L., Sandra Manfra Marretta, Gerald J. Pijanowski, Ann L. Johnson e Charles W. Smith. "Measurement of Bite Force in Dogs: A Pilot Study". Journal of Veterinary Dentistry 12, n.º 2 (junho de 1995): 49–52. http://dx.doi.org/10.1177/089875649501200202.
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A force transducer was developed to measure bite force in dogs. A total of 101 readings was obtained from 22 pet dogs ranging in size from 7 to 55 kg. Bite forces ranged from 13 to 1394 Newtons with a mean for all dogs of 256 Newtons and a median of 163 Newtons. Most measurements fell within the low end of the range, with 55% of the biting episodes less than 200 Newtons and 77% less than 400 Newtons.
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Abeni, Fabio, Francesca Petrera e Andrea Galli. "A Survey of Italian Dairy Farmers’ Propensity for Precision Livestock Farming Tools". Animals 9, n.º 5 (28 de abril de 2019): 202. http://dx.doi.org/10.3390/ani9050202.
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A targeted survey was designed with the aim of describing the diffusion of precision livestock farming (PLF) tools in one of the most intensive dairy farming provinces in Italy. Technicians at the Provincial Breeder Association of Cremona interviewed 490 dairy farmers and obtained data regarding the role and age of the respondents; the land owned by the farmers; their herd sizes (HS, lactating plus dry cows; small HS < 101, medium HS 101–200, large HS > 200 cows/herd); their average 305 day milk yield (low MY < 9501, medium MY 9501–10,500, high MY > 10,500 kg/head); the cow to employed worker ratio (low CW < 33, medium CW 33–47, high CW > 47 cows/worker); the use of PLF tools to monitor production, reproduction, and health; and the criteria and motivations for investing in PLF tools. The use of automated MY recording and estrus detection systems was primarily associated with HS (more present in larger farms), followed by MY (more present in more productive farms), and then CW (more present with a high cow: worker ratio). Concern about the time required to manage data was the most common subjective issue identified as negatively affecting the purchase of these tools. The future of PLF use in this region will depend upon the availability of an effective selection of tools on the market.
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Pitawati, Ni Luh Putu, e Ni Made Trismarani Sultradewi Kesuma. "Characteristics of condyloma acuminata patients with HIV/AIDS at Prof. Dr. Sulianti Saroso infectious diseases hospital during 2019-2023". Indonesia Journal of Biomedical Science 17, n.º 2 (4 de outubro de 2023): 211–14. http://dx.doi.org/10.15562/ijbs.v17i2.493.
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Introduction: Condyloma acuminata (CA) or genital warts is a sexually transmitted infection caused by the Human Papillomavirus (HPV). Individuals with CA are more susceptible to HIV compared to those without the condition. CA increases the risk of HIV occurrence and vice versa. This study examines characteristics of CA patients with HIV/AIDS visiting the Dermatology and Venereology Clinic of Prof. Dr. Sulianti Saroso Infectious Diseases Hospital during 2019-2023. Method: The research methodology employed in this study is a retrospective descriptive approach with a cross-sectional design. The sampling technique utilized was the total sampling method. Result: Among 22 recorded cases, 11 fulfilled the study criteria. Most patients were aged 19-44 years (86.7%), male (81.8%), with a history of homosexual relations (54.5%), and exhibited lesions primarily in the perianal region (54.5%). All patients received antiretroviral therapy (ART) (100%), and CD4 count results predominantly ranged from 101-200/mm3 (63.6%). Trichloroacetic acid (TCA) therapy was the most prevalent treatment modality (81.8%). Conclusion: The highest prevalence was noted within the age range of 19-44 years, with a majority of male patients. Unmarried status was most common among the patients. Homosexual history emerged as the predominant pattern of sexual intercourse. The perianal region was the most frequent location. The average CD4 count ranges from 101 to 200/mm3. The predominant treatment method utilized was the application of trichloroacetic acid (TCA).
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Colevas, Alexander Dimitrios, Christine H. Chung, Douglas Adkins, Cristina P. Rodriguez, Jong Chul Park, Michael K. Gibson, Ammar Sukari et al. "A phase 1 dose-escalation and expansion study of CUE-101, given as monotherapy and in combination with pembrolizumab, in patients with recurrent/metastatic HPV16+ head and neck squamous cell cancer (R/M HNSCC)." Journal of Clinical Oncology 42, n.º 16_suppl (1 de junho de 2024): 6004. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.6004.
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6004 Background: Immuno-STATs are modular T cell engagers engineered to selectively activate tumor-antigen specific CD8+ T cells via targeted delivery of cytokines. CUE-101, the first Immuno-STAT in clinical trials, is composed of a human leukocyte antigen (HLA) complex, HLA-A*0201, a peptide epitope derived from the HPV16 E7 protein and 4 molecules of attenuated human interleukin-2 (IL-2), to bind, expand, and activate HPV16-specific CD8+ T cells for the treatment of HPV16+ HNSCC. Methods: CUE-101-01 is an ongoing first-in-human study in HLA-A*0201 patients with HPV16+ R/M HNSCC. Escalating doses of CUE-101 monotherapy (0.06 mg/kg to 8 mg/kg) were evaluated in R/M HNSCC refractory to ≥ 1 platinum or checkpoint inhibitor (CPI) based therapy, alone or combined with pembrolizumab (1 mg/kg to 4 mg/kg + 200 mg pembrolizumab) in the first line treatment of PD-L1+ R/M HNSCCs. Enrollment at the recommended phase 2 dose (RP2D) was expanded. Therapy was administered every 3 weeks (Q3W) until disease progression or intolerable toxicity. Safety, PK/PD, and antitumor activity were assessed. Results: Enrollment in both monotherapy and combination cohorts is now completed (N=80 patients, 49 in monotherapy and 31 CUE-101 plus pembrolizumab). Following dose escalation, 4 mg/kg Q3W of CUE-101 was selected for RP2D for both monotherapy and pembrolizumab combination cohorts. At data cut-off, adverse events (AEs) have been manageable and 92% grade ≤2. The most frequent grade 3 AEs reported include lymphocyte count decreased (7.6%), anemia (6.3%), decreased appetite (5.1%) and infusion-related reactions (5.1%). In combination with pembrolizumab no unanticipated significant safety concerns have emerged. Exposure-dependent PD effects of CUE-101 are consistent with IL-2 pharmacology and indicate preferential expansion of CUE-101 on E7-specific T cells. Among the 19 evaluable patients treated with the RP2D of CUE-101 plus pembrolizumab, an ORR of 47% (1 CR, 8 PRs), a Disease Control Rate (ORR + durable SDs) of 74%, and mPFS of 5.8 months [95% CI 2.56; NA] were observed. A median OS has not been reached. Of the 9 patients with confirmed objective responses, all achieved >99% reduction in HPV16 cfDNA in plasma during their treatment course. Among the 19 evaluable monotherapy RP2D patients, 1 PR and 6 durable SD (SD ≥ 12 weeks) and mOS of 20.8 months [95% CI 11.0; NA] were observed. Conclusions: An ORR of 47% and a mPFS of 5.8 months were observed in R/M HNSCC patients treated with CUE-101 4 mg/kg + pembrolizumab as 1L therapy. A median OS of 20.8 was observed in patients treated with CUE-101 monotherapy as post-platinum/CPI therapy. CUE-101 continues to demonstrate safety, tolerability and meaningful clinical benefit in patients with HPV16+ R/M HNSCC. Clinical trial information: NCT03978689 .
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Baltazar Vilchis, Carlos Alberto, Yenit Martínez Garduño e Antonio Sámano Ángeles. "La importancia de la analítica de datos en el seguimiento a estudiantes para el logro de certificaciones profesionales de TI: Estudio de caso". Tecnología Educativa Revista CONAIC 8, n.º 1 (30 de novembro de 2021): 70–75. http://dx.doi.org/10.32671/terc.v8i1.195.
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La analítica de datos es una rama de la Informática que apoya a la toma de decisiones en diversas áreas del conocimiento, la educación no es la excepción, año tras año los docentes imparten sus unidades de aprendizaje en donde la aplicación de exámenes arroja un sin fin de información que, en el mejor de los casos queda almacenada en el equipo de cómputo que funja como servidor y ofrezca un Sistema para Gestión de Aprendizaje (Learning Management System – LMS por sus siglas en inglés) como puede ser Moodle, y queda sin utilizarse. El aplicar técnicas de análisis de datos a esta información se puede ponderar el grado de avance en cuanto al dominio de una habilidad en Tecnologías de la Información y la Computación (TIC), como pueden ser las certificaciones que otorga la empresa CISCO®, hoy sabemos que las certificaciones se han vuelto indispensables para lograr una ventaja competitiva entre los profesionistas de las TIC y dar una oportunidad para posicionarse en un buen empleo en un mundo globalizado. El presente trabajo de investigación analiza, mediante un estudio de alcance descriptivo, comparativo y correlacional, la unidad de aprendizaje “Comunicación entre Computadoras” de las generaciones 2016 a la 2020 de los grupos de la Licenciatura en Informática Administrativa LIA D1, LIA D2, LIA D3 y LIA D4 del Centro Universitario UAEM Atlacomulco, a través de una minería de datos al sistema de reactivos de exámenes aplicados por el docente ubicados en una plataforma LMS Moodle, para posteriormente codificarlos y compararlos con las certificaciones CISCO® CCNA 100-101 (ICND1), 200-101 (ICND2) y 200- 120 (CCNA R & S) para determinar si los discentes tienen las habilidades requeridas para presentarlas y aprobarlas.
Data analytics is a branch of Computer Science that supports decision-making in various areas of knowledge, education is no exception, year after year teachers teach their learning units where the application of exams yields endless of information that, in the best of cases, is stored in the computer equipment that acts as a server and offers a Learning Management System (LMS) such as Moodle, and remains unused . By applying data analysis techniques to this information, the degree of progress in mastering a skill in Information and Computing Technologies (ICT) can be weighted, such as the certifications granted by the CISCO® company, today we know that certifications have become essential to achieve a competitive advantage among ICT professionals and provide an opportunity to position themselves in a good job in a globalized world. The present research work analyzes, through a descriptive, comparative and correlational study, the learning unit "Communication between Computers" from the generations 2016 to 2020 of the groups of the Bachelor's Degree in Administrative Informatics LIA D1, LIA D2, LIA D3 and LIA D4 of the UAEM Atlacomulco University Center, through data mining to the system of test items applied by the teacher located on an LMS Moodle platform, to later code and compare them with the CISCO® CCNA 100-101 certifications (ICND1 ), 200-101 (ICND2) and 200-120 (CCNA R & S) to determine if learners have the required skills to present and pass them.
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Amin, Asim, Mohammed M. Milhem, Georgina V. Long, Christopher J. Hoimes, Theresa Michelle Medina, Robert Martin Conry, Christopher D. Lao et al. "Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced/metastatic melanoma resistant to anti-PD-1/PD-L1 therapy." Journal of Clinical Oncology 37, n.º 15_suppl (20 de maio de 2019): 9555. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.9555.
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9555 Background: SD-101 is a synthetic CpG-ODN agonist of TLR9 that stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells - activating T cell anti-tumor responses. Pembrolizumab has demonstrated activity in melanoma. SYNERGY-001/KEYNOTE-184 study assesses the safety and preliminary efficacy of the combination of intratumoral SD-101 and intravenous pembrolizumab in PD1/PDL 1 resistant unresectable stage IIIC- IV melanoma. A prior phase 2 study with SD-101 at 8 mg per injection resulted in a 21.4% ORR in this population (Abstract 3781, ESMO 2018). We report preliminary data in this ongoing phase 2 trial evaluating efficacy at a lower SD-101 dose of 2 mg per injection. Methods: PD1/PDL 1 resistant melanoma patients received 2 mg of SD-101 intratumorally per lesion in 1-4 lesions (weekly x 4 doses followed by Q3W x 7). Pembrolizumab was administered at a dose of 200 mg intravenously Q3W. Scans were performed Q9W. Responses were assessed per RECIST v1.1. Results: 23 patients have been enrolled with baseline characteristics: median age 65 years; male: 77%; stage at screening: IIIC = 26%; IV = 57%, unknown = 17%; LDH > ULN: 36%. Lines of prior therapy: 1: 52%; 2: 22%; > 2: 26%. Prior anti CTL-A4 therapy: 39%. Best overall response on prior antiPD-1/PD-L1: PD: 88%, PR/CR: 8%, SD: 4%. Safety: Grade ≥3 treatment-related AEs: pneumonia and constipation (8%). No immune-related AEs reported. 2 non-treatment related SAEs reported from 2 patients: pneumonia and intussusception. 4 patients discontinued treatment early: 1 post SAE, per patient’s request, 3 due to PD. 1 patient died due to malignant pleural effusion after 1 dose of SD 101 and Pembrolizumab. No treatment related deaths. Efficacy: Mean duration on treatment: 39 days (1 - 169). mITT population: six patients at time of first CT scan at day 64: PR: 1, SD: 1, PD:3; non-evaluable: 1. 17 patients on study have not yet had first CT scan. Conclusions: The TLR9 innate immune stimulant, SD-101, in combination with pembrolizumab is well tolerated. Mature efficacy data, with additional first and second follow-up CT scans, will be presented at the meeting. Clinical trial information: NCT02521870.
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Salih, Amer M., Zuheer N. Majeed e Sabri J. Mohammed. "Graphene and its Effect on the Structural and Optical Properties of TiO2 Nano Thin Films Prepared by PLD Technique". NeuroQuantology 20, n.º 5 (2 de maio de 2022): 179–84. http://dx.doi.org/10.14704/nq.2022.20.5.nq22161.
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In this study, thin films were prepared from pure titanium dioxide doped with graphene (1, 3, 5, 7%) wt using pulsed laser deposition (PLD) technique. The X-ray diffraction results showed that the prepared films were polycrystalline with a quaternary structure. It is noted that there are diffraction peaks corresponding to the levels (101, 004, 200, 211), and in the preferential direction (101), we notice that the intensity of the peak (101) decreases with increasing doping with the appearance of a new peak when doping at rates (5, 7%)and angle (26.5 ) This peak represents graphene oxide, and that the grain size decreased with increasing doping with graphene, where the grain size ranged between (20-40) nm. EDX analysis also shows that the results of the ratios were close to the required ratios, The results showed in the scanning electron microscope that the increase in the percentage of doping leads to the crystallization and agglomeration of graphene oxide and its rise over the Titanium dioxide (TiO2) until the surface reaches the state of collapse. The optical properties revealed an increase in the value of the energy gap by increasing the doping with graphene oxide, as it ranged between (3.15-3.7) eV.
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Clowers, Michael J., Cody Chou, Bo Yuan, Walter V. Velasco, Melody Zarghooni, Stephen Peng, T. Kris Eckols, Humam Kadara, David J. Tweardy e Seyed Javad Moghaddam. "Abstract 2095: Selective inhibition of the STAT3 pathway suppresses K-ras mutant lung tumorigenesis". Cancer Research 82, n.º 12_Supplement (15 de junho de 2022): 2095. http://dx.doi.org/10.1158/1538-7445.am2022-2095.
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Abstract K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-drug cancer subtype characterized by a chronic inflammatory tumor microenvironment (TME). Resistance to therapies, including immune checkpoint blockade (ICB), necessitates therapies that target this inflammatory TME. A major transcription factor that mediates chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3). Inhibiting STAT3 may attenuate pro-tumor inflammation. Moreover, STAT3 modulates PD-L1 transcription, so STAT3 inhibitors in conjunction with ICB may increase ICB response rates. Here, we tested the anti-tumor ability of TTI-101, a selective STAT3 inhibitor, in a STAT3 addicted lung cancer cell line (MDA-F471) and in a transgenic mouse model of KM-LUAD (CCSPCre/LSL-KrasG12D, CC-LR). For in vivo experiments, CC-LR mice were treated daily with 50 mg/kg TTI-101 by oral gavage from 10 to 14 weeks of age to model a preventative regimen or from 14 to 18 weeks of age to survey the treatment effect on established tumors. TTI-101 was compared to anti-PD-1 ICB, with 200 μg injected intraperitoneally 3 times per week. In MDA-F471 cells, TTI-101 treatment decreased cell viability, with an IC50 of ~ 20 μM. In mice treated from 10 to 14 weeks of age, TTI-101 therapy significantly reduced the tumor burden compared to ICB. TTI-101 also reduced the number of proliferating cells within tumors. Mice in the 14-18-week group displayed similar trends, but these experiments are ongoing, as are combination TTI-101 and ICB treatment regimens. Our studies show that TTI-101 can reduce K-ras driven tumor cell proliferation in vitro and in vivo, suggesting STAT3 inhibition as an alternative preventive and therapeutic modality for KM-LUAD. The ongoing combination treatments and the 14-18-week cohorts will elucidate the timing of treatments as well as reveal if by targeting the inflammatory TME we are able to improve response to ICB. Funded by: R01 grant from NIH/NCI (R01CA225977) Citation Format: Michael J. Clowers, Cody Chou, Bo Yuan, Walter V. Velasco, Melody Zarghooni, Stephen Peng, T Kris Eckols, Humam Kadara, David J. Tweardy, Seyed Javad Moghaddam. Selective inhibition of the STAT3 pathway suppresses K-ras mutant lung tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2095.
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Flinn, Ian W., John C. Byrd, Richard R. Furman, Jennifer R. Brown, Don M. Benson, Steven E. Coutre, Brad S. Kahl et al. "Evidence of Clinical Activity in a Phase 1 Study of CAL-101, An Oral P110Δ Isoform-Selective Inhibitor of Phosphatidylinositol 3-Kinase, in Patients with Relapsed or Refractory B-Cell Malignancies." Blood 114, n.º 22 (20 de novembro de 2009): 922. http://dx.doi.org/10.1182/blood.v114.22.922.922.
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Abstract Abstract 922 Introduction: The class I phosphatidylinositol 3-kinases (PI3Ks) regulate a variety of cellular functions relevant to oncogenesis, including metabolism, proliferation and survival. The PI3K p110Δ isoform is primarily expressed in cells of hematopoietic origin and plays a key role in normal B cell maturation and function. CAL-101 is an oral, potent inhibitor of PI3K p110Δ (IC50 of 2.5 nM against purified enzyme and EC50 of 65 nM in a whole blood basophil assay) with 40 to 300-fold selectivity compared to other PI3K isoforms. This selectivity may provide a better therapeutic index relative to pan-PI3K inhibitors. In vitro studies of 0.1 to 10 uM CAL-101 showed inhibition of AKT phosphorylation and/or apoptotic effects against primary chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) cells and against a range of leukemia, lymphoma and multiple myeloma (MM) cell lines. Methods and Patients: A Phase 1 study was undertaken to evaluate the safety and clinical activity of CAL-101 in patients with select hematologic malignancies. During initial dose escalation, sequential cohorts of 3 patients with relapsed/refractory CLL or select B-cell non-Hodgkin's lymphoma (NHL) were enrolled to determine dose limiting toxicity (DLT). During subsequent cohort expansion, approximately 12 patients each with CLL, indolent NHL, aggressive NHL, and AML were to be enrolled. CAL-101 was administered orally twice daily (BID) continuously for 28 days per cycle. Clinical response was evaluated at the end of Cycles 1 and 2 and every 2 cycles thereafter. Results: To date, 43 patients have been enrolled and followed for at least 4 weeks, consisting of 17 patients with CLL, 9 patients with indolent NHL, 10 patients with aggressive NHL and 7 patients with AML. The demographic and disease characteristics were 33% female, mean age 65 (60% over age 65), 49% had refractory disease and the median number of prior regimens was 5. During dose escalation (n=12), 3 patients per cohort were administered dose levels of 50 mg, 100 mg, 200 mg or 350 mg BID. In cohort expansion 31 patients were enrolled to either 200 mg (n=17) or 350 mg (n=14) BID. The median duration of treatment at data cutoff was 3 cycles (range 1 to 10). Two patients discontinued early due to adverse events, one for acute on chronic renal failure and one for abnormal liver function tests (LFTs). DLTs were observed in 5 patients with increases in LFTs, which resolved following discontinuation of CAL-101 dosing. No patient had Grade 4 hematological toxicity. Serious infections were reported in 9 patients, with pneumonia being the most frequent. 41 patients were evaluable for clinical response. At data cutoff, the response rate in NHL was 10/18 (56%); all were partial responses (PR). Of the 9 patients with indolent NHL, 5 patients had PR and 2 patients had stable disease (SD) and remained on study. Of the 9 patients with aggressive NHL, 5 patients had PR (all with mantle cell lymphoma) and 1 patient had SD on study. Of the 17 patients with CLL, 6 patients had PR and 7 other patients had >50% reduction in lymphadenopathy and concurrent increase in peripheral blood lymphocytosis to >50% of baseline, suggesting compartmentalization shift of CLL cells. Lymphocytosis was maximal during the first 2 cycles and decreased thereafter. This effect of dislocating CLL cells from the tissue microenvironment suggests that CAL-101 treatment in combination with cytotoxic agents may be particularly active. Of the 6 patients with AML, no patient had responded and 2 patients remained on study. Clinical responses were observed in patients at all 4 dose levels administered. At data cutoff, the longest duration of response was 9 months in a patient with follicular lymphoma, which was longer than the response to any of the 6 prior regimens this patient received, including autologous hematopoietic stem cell transplant. Plasma exposure increased from 50 mg to 200 mg, without further change at 350 mg. At the 200 mg and 350 mg dose levels, mean peak and trough drug concentrations at the end of Cycle 1 were 5 uM and 1 uM, respectively. Enrollment in cohort expansion is continuing with the addition of patients with MM and updated data will be presented at the meeting. Conclusions: Interim results from the first Phase 1 study to evaluate an oral PI3K p110Δ inhibitor, CAL-101, show promising activity in patients with relapsed or refractory B-cell malignancies with acceptable toxicity. Disclosures: Byrd: Calistoga Pharmaceuticals, Inc: Consultant. Furman:Calistoga Pharmaceuticals, Inc: Consultant. Brown:Calistoga Pharmaceuticals, Inc: Consultant. Giese:Calistoga Pharmaceuticals, Inc: Employment, Ownership Interest. Yu:Calistoga Pharmaceuticals, Inc.: Employment, Ownership interest.
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Turpin, Jennifer. "Yuri Druzhnikov. Informer 101: The Myth of Pavlik Morozov. New Brunswick, NJ: Transaction Publishers, 1997. xiv, 200 pp. $29.95." Canadian-American Slavic Studies 33, n.º 2-4 (1999): 417–18. http://dx.doi.org/10.1163/221023999x00445.
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Starikov, V. I., e S. N. Mikhailenko. "Analysis of experimental data for the first hexad {(040), (120), (200), (002), (021), (101)} of H2O molecule interacting states". Journal of Molecular Structure 442, n.º 1-3 (fevereiro de 1998): 39–53. http://dx.doi.org/10.1016/s0022-2860(97)00188-9.
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Chung, Christine H., A. Dimitrios Dimitrios Colevas, Douglas Adkins, Cristina P. Rodriguez, Jong Chul Park, Michael K. Gibson, Barbara Burtness et al. "A phase 1 dose-escalation and expansion study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, given as monotherapy and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer." Journal of Clinical Oncology 41, n.º 16_suppl (1 de junho de 2023): 6013. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.6013.
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6013 Background: Immuno-STATs are modular T cell engagers engineered to selectively activate tumor-antigen specific CD8+ T cells via targeted delivery of cytokines. CUE-101, the first Immuno-STAT in clinical trials, is composed of a human leukocyte antigen (HLA) complex, HLA-A*0201, a peptide epitope derived from the HPV16 E7 protein, and 4 molecules of attenuated human interleukin-2 (IL-2) designed to bind, expand, and activate HPV16-specific CD8+ T cells for the treatment of HPV16+ cancers. Methods: CUE-101-01 is an ongoing first-in-human study in HLA-A*0201 patients with HPV16+ recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Escalating doses of CUE-101 monotherapy (0.06 mg/kg to 8 mg/kg) and in combination with pembrolizumab (1 mg/kg to 4 mg/kg + 200 mg pembrolizumab) were evaluated, followed by expanded enrollment at the recommended phase 2 dose (RP2D). Patients with R/M HNSCC refractory to ≥ 1 platinum-based or checkpoint inhibitor therapy received CUE-101 monotherapy. Patients with previously untreated PD-L1+ R/M HNSCC received CUE-101 + pembrolizumab as first-line treatment. Therapy was administered every 3 weeks until disease progression or intolerable toxicity. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity were assessed. Results: As of January 12, 2023, 67 patients were enrolled. A MTD was not established in monotherapy or combination-treated patients; 4 mg/kg of CUE-101, alone or in combination with pembrolizumab, was chosen as the RP2D dose in both cohorts. Monotherapy RP2D enrollment is complete and combination RP2D enrollment is ongoing. Frequent adverse events include fatigue (45%), anemia (34%), chills (27%), infusion related reactions (25%), constipation (22%), lymphopenia (22%) and nausea (22%). CUE-101 PK data demonstrate dose-dependent increases in drug exposure sustained with repeat dosing. PD data demonstrate selective expansion of HPV-16 E711-20-specific CD8+ T cells, sustained increase in NK cells and transient increase in Treg cells. Among 19 evaluable monotherapy RP2D patients, 1 PR and 6 durable SD (SD ≥ 12 weeks) were observed, with mOS of 24.4 months (9.1, NA). Among 12 evaluable RP2D combination patients to date, 5 PRs, and 2 durable SDs have been observed, with 71% (5/7) of patients expressing PD-L1 CPS ≤ 20. Conclusions: CUE-101 facilitates the targeted delivery of high concentrations of IL-2 to relevant tumor-specific CD8+ T cells. We demonstrate safety and tolerability with encouraging PD signals and antitumor activity with monotherapy and in combination with pembrolizumab in HPV+ R/M HNSCC patients. Enrollment continues in the CUE-101 and pembrolizumab combination cohort. Clinical trial information: Clinical trial information: NCT03978689 .
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Fiveash, John B., Xiaobu Ye, David M. Peerboom, Tom Mikkelsen, Sajeel Chowdhary, Myrna Rosenfeld, Glenn J. Lesser et al. "Clinical trials of R-(-)-gossypol (AT-101) in newly diagnosed and recurrent glioblastoma: NABTT 0602 and NABTT 0702". PLOS ONE 19, n.º 1 (29 de janeiro de 2024): e0291128. http://dx.doi.org/10.1371/journal.pone.0291128.
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Purpose AT-101 is an oral bcl-2 family protein inhibitor (Bcl-2, Bcl-XL, Mcl-1, Bcl-W) and potent inducer of proapoptotic proteins. A prior study of the parent compound, racemic gossypol, demonstrated objective and durable responses in patients with malignant glioma. AT-101 has demonstrated synergy with radiation in animal models. The objectives of trial NABTT 0602 were to determine the MTD of AT-101 concurrent with temozolomide (TMZ) and radiation therapy (RT) (Arm I) and to determine the MTD of AT-101 when given with adjuvant TMZ after completion of standard chemoradiation (Arm 2). Separately in trial NABTT 0702, the survival and response rates of single agent AT-101 were evaluated in patients with recurrent glioblastoma. Methods In NABTT 0602 Phase I, a 3+3 design was used to define MTDs after maximal safe resection, patients with newly diagnosed glioblastoma received standard concurrent RT (60 Gy) and TMZ 75 mg/m2/day followed by adjuvant TMZ 150–200 mg/m2 days 1–5 in 28-day cycles (Stupp regimen). In Arm I, AT-101 was administered M-F during the six weeks of RT beginning 20 mg qd. In Arm 2, concurrent with each adjuvant cycle of TMZ, AT-101 was administered at a starting dose of 20 mg, days 1–21 followed by 7-day break for a maximum of 6 cycles. The PK blood samples were collected in the first three patients in each cohort of arm 1. In NABTT 0702 patients with recurrent glioblastoma received 20 mg p.o. per day for 21 of 28 days in repeated cycles to assess overall survival (OS). Results A total of sixteen patients were enrolled on the two study arms of NABTT 0602. In Arm 1 AT-101 was escalated from 20 to 30 mg where one of six patients experienced DLT (grade 3 GI ulcer). On Arm 2 one patient treated at 20 mg experienced DLT (grade 3 ileus, nausea and diarrhea). The cohort was expanded to include seven patients without observation of DLT. PK results were consistent with drug levels from non-CNS studies. At study closure six patients are still alive. The median survival times for Arm I and Arm II are 15.2 months and 18.2 months, respectively. In NABTT 0702 fifty-six patients were enrolled and forty-three were eligible for imaging response. Sixteen patients (29%) had stable disease as best response and one partial response was observed. The median OS with single agent AT-101 was 5.7 months (95%CI: 3.8–7.6 months) for patients with rGBM. Conclusions AT-101 can be safely administered with radiation therapy and TMZ in patients with newly diagnosed glioblastoma without toxicity unique to patients with CNS tumors. Because of toxicity observed in non-CNS AT-101 clinical trials, further dose-escalation was not attempted. The recommended dose for future studies that utilize continual AT-101 exposure is 20 mg days M-F concurrent with RT/TMZ and 20 mg days 1–21 for each 28-day cycle of TMZ. AT-101 has limited activity as a single agent in unselected patients with recurrent glioblastoma. Future trials should attempt to better understand resistance mechanisms and consider combination therapy.
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Dudhamal, Munjaji E., Jayesh R. Pawar, Vijendra A. Chaudhari, Kashinath A. Bogle e Rajesh Arun Joshi. "Annealing Assisted Structural Modifications in CdS Thin Films". Advanced Materials Research 1169 (18 de março de 2022): 111–15. http://dx.doi.org/10.4028/p-mj98wn.
Texto completo da fonteResumo:
The present article deals with synthesis of CdS thin films using cost effective chemical bath deposition method and study effect of annealing over the structural properties using X-ray diffraction pattern (XRD). The XRD pattern revealed shift in peak position and variation in intensity upon annealing at different temperatures; this may be attributed to annealing assisted modifications in composition of the thin films. The as deposited CdS thin films represents peaks corresponding to (002), (101), (111) and (110) which in case of annealed samples at 200 and 400oC get modified and slightly shifted with rising some new peaks corresponding to (200) and (001) respectively. The crystallite size of the CdS thin films upon annealing is observed to be increased this may be co-related to the fact energy induced grain growth.