161 research outputs found
MODUL BIOLOGI PADA MATERI KONSEP DASAR SEL MELALUI PEMBELAJARAN BIBLE BASED INTEGRATION UNTUK MENINGKATKAN HASIL BELAJAR BIOLOGI
The aim of the biology module is on cell basic concepts by using Bible-based integration to improve learning outcomes of students of Class XI IPA Kalam Kudus Christian Jayapura. The results of this study are: There is an increase in learning achievement of class XI students using the Bible Based Integration learning module with n-Gain RPP-1 0.61, n-Gain RPP-2 0.67, n-Gain RPP-3 0.74. The average n-Gain RPP is 0.67 with the medium category
Percepta Genomic Sequencing Classifier and decision-making in patients with high-risk lung nodules: A decision impact study
BACKGROUND: Incidental and screening-identified lung nodules are common, and a bronchoscopic evaluation is frequently nondiagnostic. The Percepta Genomic Sequencing Classifier (GSC) is a genomic classifier developed in current and former smokers which can be used for further risk stratification in these patients. Percepta GSC has the capability of up-classifying patients with a pre-bronchoscopy risk that is high (\u3e 60%) to very high risk with a positive predictive value of 91.5%. This prospective, randomized decision impact survey was designed to test the hypothesis that an up-classification of risk of malignancy from high to very high will increase the rate of referral for surgical or ablative therapy without additional intervening procedures while increasing physician confidence.
METHODS: Data were collected from 37 cases from the Percepta GSC validation cohort in which the pre-bronchoscopy risk of malignancy was high (\u3e 60%), the bronchoscopy was nondiagnostic, and the patient was up-classified to very high risk by Percepta GSC. The cases were randomly presented to U.S pulmonologists in three formats: a pre-post cohort where each case is presented initially without and then with a GSG result, and two independent cohorts where each case is presented either with or without with a GSC result. Physicians were surveyed with respect to subsequent management steps and confidence in that decision.
RESULTS: One hundred and one survey takers provided a total of 1341 evaluations of the 37 patient cases across the three different cohorts. The rate of recommendation for surgical resection was significantly higher in the independent cohort with a GSC result compared to the independent cohort without a GSC result (45% vs. 17%, p \u3c 0.001) In the pre-post cross-over cohort, the rate increased from 17 to 56% (p \u3c 0.001) following the review of the GSC result. A GSC up-classification from high to very high risk of malignancy increased Pulmonologists\u27 confidence in decision-making following a nondiagnostic bronchoscopy.
CONCLUSIONS: Use of the Percepta GSC classifier will allow more patients with early lung cancer to proceed more rapidly to potentially curative therapy while decreasing unnecessary intervening diagnostic procedures following a nondiagnostic bronchoscopy
Multi-Element Abundance Measurements from Medium-Resolution Spectra. I. The Sculptor Dwarf Spheroidal Galaxy
We present measurements of Fe, Mg, Si, Ca, and Ti abundances for 388 radial
velocity member stars in the Sculptor dwarf spheroidal galaxy (dSph), a
satellite of the Milky Way. This is the largest sample of individual alpha
element (Mg, Si, Ca, Ti) abundance measurements in any single dSph. The
measurements are made from Keck/DEIMOS medium-resolution spectra (6400-9000 A,
R ~ 6500). Based on comparisons to published high-resolution (R >~ 20000)
spectroscopic measurements, our measurements have uncertainties of
sigma([Fe/H]) = 0.14 and sigma([alpha/Fe]) = 0.13. The Sculptor [Fe/H]
distribution has a mean = -1.58 and is asymmetric with a long,
metal-poor tail, indicative of a history of extended star formation. Sculptor
has a larger fraction of stars with [Fe/H] < -2 than the Milky Way halo. We
have discovered one star with [Fe/H] = -3.80 +/- 0.28, which is the most
metal-poor star known anywhere except the Milky Way halo, but high-resolution
spectroscopy is needed to measure this star's detailed abundances. As has been
previously reported based on high-resolution spectroscopy, [alpha/Fe] in
Sculptor falls as [Fe/H] increases. The metal-rich stars ([Fe/H] ~ -1.5) have
lower [alpha/Fe] than Galactic halo field stars of comparable metallicity. This
indicates that star formation proceeded more gradually in Sculptor than in the
Galactic halo. We also observe radial abundance gradients of -0.030 +/- 0.003
dex per arcmin in [Fe/H] and +0.013 +/- 0.003 dex per arcmin in [alpha/Fe] out
to 11 arcmin (275 pc). Together, these measurements cast Sculptor and possibly
other surviving dSphs as representative of the dwarf galaxies from which the
metal-poor tail of the Galactic halo formed.Comment: Accepted to ApJ on 2009 Sep 15, 22 pages, 23 figure
Efficacy and Safety of Fezolinetant in Moderate-to-Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT.
CONTEXT
Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause.
OBJECTIVE
We aimed to assess efficacy/safety of fezolinetant for treatment of moderate-to-severe VMS associated with menopause.
METHODS
In this double-blind, placebo-controlled, 12-week (W) phase 3 trial with a 40W active treatment extension (NCT04003142; SKYLIGHT 2) women aged 40-65 years with minimum average 7 moderate-to-severe VMS/day were randomized to 12 weeks' once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to W4 and W12 in VMS frequency and severity. Safety was also assessed.
RESULTS
Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, -1.82 (0.46; P < .001); 45 mg, -2.55 (0.46; P < .001); W12: 30 mg, -1.86 (0.55; P < .001); 45 mg, -2.53 (0.55; P < .001). For VMS severity, W4: 30 mg, -0.15 (0.06; P<.05); 45 mg, -0.29 (0.06; P < .001); W12: 30 mg, -0.16 (0.08; P <.05); 45 mg, -0.29 (0.08; P < .001). Improvement in VMS frequency and severity was observed by W1; maintained through W52. Serious TEAEs were infrequent; these were reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively.
CONCLUSIONS
Daily fezolinetant 30 mg and 45 mg were efficacious and well-tolerated for treating moderate-to-severe VMS associated with menopause
best practices in bioassay development to support registration of biopharmaceuticals
Biological activity is a critical quality attribute for biopharmaceuticals, which is accurately measured using an appropriate relative potency bioassay. Developing a bioassay is a complex, rigorous undertaking that needs to address several challenges including modelling all of the mechanisms of action associated with the biotherapeutic. Bioassay development is also an exciting and fast evolving field, not only from a scientific, medical and technological point of view, but also in terms of statistical approaches and regulatory expectations. This has led to an industry-wide discussion on the most appropriate ways to develop, validate and control the bioassays throughout the drug lifecycle
Multi-Element Abundance Measurements from Medium-Resolution Spectra. II. Catalog of Stars in Milky Way Dwarf Satellite Galaxies
We present a catalog of Fe, Mg, Si, Ca, and Ti abundances for 2961 red giant
stars that are likely members of eight dwarf satellite galaxies of the Milky
Way (MW): Sculptor, Fornax, Leo I, Sextans, Leo II, Canes Venatici I, Ursa
Minor, and Draco. For the purposes of validating our measurements, we also
observed 445 red giants in MW globular clusters and 21 field red giants in the
MW halo. The measurements are based on Keck/DEIMOS medium-resolution
spectroscopy combined with spectral synthesis. We estimate uncertainties in
[Fe/H] by quantifying the dispersion of [Fe/H] measurements in a sample of
stars in monometallic globular clusters. We estimate uncertainties in Mg, Si,
Ca, and Ti abundances by comparing our medium-resolution spectroscopic
measurements to high-resolution spectroscopic abundances of the same stars. For
this purpose, our DEIMOS sample included 132 red giants with published
high-resolution spectroscopy in globular clusters, the MW halo field, and dwarf
galaxies. The standard deviations of the differences in [Fe/H] and [alpha/Fe]
(the average of [Mg/Fe], [Si/Fe], [Ca/Fe], and [Ti/Fe]) between the two samples
is 0.15 and 0.16, respectively. This catalog represents the largest sample of
multi-element abundances in dwarf galaxies to date. The next papers in this
series draw conclusions on the chemical evolution, gas dynamics, and star
formation histories from the catalog presented here. The wide range of dwarf
galaxy luminosity reveals the dependence of dwarf galaxy chemical evolution on
galaxy stellar mass.Comment: 26 pages, 22 figures, 4 machine-readable tables (available in the
source file; click "Other formats"); accepted for publication in ApJ
Supplements; updated acknowledgments in v
Selection of Clostridium spp. in biological sand filters neutralizing synthetic acid mine drainage
In this study, three biological sand filter (BSF) were contaminated with a synthetic iron- [1500 mg L-1 Fe(II), 500 mg L-1 Fe(III)] and sulphate-rich (6000 mg L-1 SO2/4-) acid mine drainage (AMD) (pH = 2), for 24 days, to assess the remediation capacity and the evolution of autochthonous bacterial communities (monitored by T-RFLP and 16S rRNA gene clone libraries). To stimulate BSF bioremediation involving sulphate-reducing bacteria, a readily degradable carbon source (glucose, 8000 mg L-1) was incorporated into the influent AMD. Complete neutralization and average removal efficiencies of 81.5 (±5.6)%, 95.8 (±1.2)% and 32.8 (±14.0)% for Fe(II), Fe(III) and sulphate were observed, respectively. Our results suggest that microbial iron reduction and sulphate reduction associated with iron precipitation were the main processes contributing to AMD neutralization. The effect of AMD on BSF sediment bacterial communities was highly reproducible. There was a decrease in diversity, and notably a single dominant operational taxonomic unit (OTU), closely related to Clostridium beijerinckii, which represented up to 65% of the total community at the end of the study period.Web of Scienc
Medical Sequencing of Candidate Genes for Nonsyndromic Cleft Lip and Palate
Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P) occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Étude du Polymorphisme Humain (CEPH) diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate). Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations
Effects of APOE Genotype on Brain Proteomic Network and Cell Type Changes in Alzheimer's Disease
Polymorphic alleles in the apolipoprotein E (APOE) gene are the main genetic determinants of late-onset Alzheimer's disease (AD) risk. Individuals carrying the APOE E4 allele are at increased risk to develop AD compared to those carrying the more common E3 allele, whereas those carrying the E2 allele are at decreased risk for developing AD. How ApoE isoforms influence risk for AD remains unclear. To help fill this gap in knowledge, we performed a comparative unbiased mass spectrometry-based proteomic analysis of post-mortem brain cortical tissues from pathologically-defined AD or control cases of different APOE genotypes. Control cases (n = 10) were homozygous for the common E3 allele, whereas AD cases (n = 24) were equally distributed among E2/3, E3/3, and E4/4 genotypes. We used differential protein expression and co-expression analytical approaches to assess how changes in the brain proteome are related to APOE genotype. We observed similar levels of amyloid-β, but reduced levels of neurofibrillary tau, in E2/3 brains compared to E3/3 and E4/4 AD brains. Weighted co-expression network analysis revealed 33 modules of co-expressed proteins, 12 of which were significantly different by APOE genotype in AD. The modules that were significantly different by APOE genotype were associated with synaptic transmission and inflammation, among other biological processes. Deconvolution and analysis of brain cell type changes revealed that the E2 allele suppressed homeostatic and disease-associated cell type changes in astrocytes, microglia, oligodendroglia, and endothelia. The E2 allele-specific effect on brain cell type changes was validated in a separate cohort of 130 brains. Our systems-level proteomic analyses of AD brain reveal alterations in the brain proteome and brain cell types associated with allelic variants in APOE, and suggest further areas for investigation into the upstream mechanisms that drive ApoE-associated risk for AD
Therapy with un-engineered naïve rat umbilical cord matrix stem cells markedly inhibits growth of murine lung adenocarcinoma
<p>Abstract</p> <p>Background</p> <p>Lung cancer remains the leading cause of cancer-related mortality despite continuous efforts to find effective treatments. Data from the American Cancer Society indicate that while the overall incidence of lung cancer is declining, it continues to rise in women. Stem cell-based therapy has been an emerging strategy to treat various diseases. The purpose of this paper is to determine the efficacy of an intrinsic anti-cancer effect of rat umbilical cord matrix stem cells (UCMSCs) on lung cancer.</p> <p>Methods</p> <p>A mouse syngeneic lung carcinoma model was used to test the basic ability of UCMSCs to control the growth of lung cancer. Lung tumors were experimentally induced by tail vein administration of Lewis lung carcinoma (LLC) cells derived from the lung of C57BL/6 mouse. Rat UCMSCs were then administered intratracheally five days later or intravenously on days 5 and 7. The tumor burdens were determined by measuring lung weight three weeks after the treatment.</p> <p>Results</p> <p>Co-culture of rat UCMSCs with LLC significantly attenuated the proliferation of LLC cells as monitored by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), a tetrazole cell proliferation assay, thymidine uptake, and direct cell counts. <it>In vitro </it>colony assays with rat UCMSCs as feeder layers markedly reduced LLC colony size and number. Co-culture of rat UCMSCs with LLCs causes G0/G1 arrest of cancer cells. This is evident in the decrease of cyclin A and CDK2 expression. The <it>in vivo </it>studies showed that rat UCMSC treatment significantly decreased tumor weight and the total tumor mass. Histological study revealed that intratracheally or systemically administered rat UCMSCs homed to tumor areas and survived for at least 3 weeks without any evidence of differentiation or adverse effects.</p> <p>Conclusions</p> <p>These results indicate that rat UCMSCs alone remarkably attenuate the growth of lung carcinoma cells <it>in vitro </it>and in a mouse syngeneic lung carcinoma graft model and could be used for targeted cytotherapy for lung cancer.</p
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