gebhart/patrepeval huggingface dataset:
Formulation and Evaluation of Sustained Release Matrix Tablets of Glipizide (2009)

The purpose of this study was to develop a new monolithic matrix tablet to completely deliver glipizide in a zero order manner over a sustained period. Two approaches were examined using drug in a formulation that contain polymer like hydroxylpropyl methylcellulose K 100 (HPMCK) and Eudragit L 100. The granules were prepared by wet granulation method and thereby formulated as F-1, F-2. F-3 and F-4 by using the above bring up polymers with other ingredients. The granules of different formulations were evaluated for angle of repose, loose bulk density and tapped density, compressibility index, total porosity, and drug content. The angle of repose and compressibility index (%) ranged from 25.0±0.8 to 28.0±1.1 and 12.92±0.02 to 13.08±0.03, respectively. The results of angle of repose (<30) indicate good flow properties of the granules. This was further supported by lower compressibility index values. The granules showed satisfactory flow properties, compressibility and drug content. All of the formulations showed uniform thickness (C.V< 0.5%), uniform weight with little significance difference were observed with varying formulation composition. In the weight variation test, the pharmacopoeial limit for the percentage of deviation for tablets of more than 130 mg to 324 mg is 7.5 % difference. Technological characterizations (thickness, diameter, weight variation test, drug content, hardness, and friability) were conceded with the formulated matrix tablet and in vitro drug release was measured by means of dissolution apparatus. Of the various formulation distinguished, out of which, the formulation (F3) were preferred to be full of 30 mg of HPMCK and 35 mg of Eudragit L100 was subjected to stability were accomplished studies for three months at 4 °C. The room temperature (25 °C) and (45 °C) with relative humidity 75±5% were maintained and its stability with respect to release pattern. The kinetic release treatment showed that the release of drug follows zero order kinetic (r 2 = 0. 9959), Koresmeyer equation gave value of r 2 = 0.9853 which was close to one indicating that the drug was released by zero order kinetic. According to Koresmeyer equation, the formulation F-1, F-2, and F-4 showed the regression values of 0.9823, 0.9785, and 0.9742, respectively. The identical plot for (log cumulative percentage drug release vs time) for Koresmeyer-Peppas equation indicated a good linearity for the commercially available sustained release tablet and formulation F3 with regression values of 0.9619 and 0.9959, respectively. Scanning electron microscope confirmed both diffusion and erosion mechanism for the optimized batch of matrix tablet F-3. Results suggest that the formulated tablet F-3 of glipizide could perform therapeutically better than the reachable marketed drug leading to improve better efficacy.
High-fidelity genome editing using NextGEN CRISPR (Clo51-dCas9) system for the production of allogeneic CAR-T cells. (2017)

3048 Background: Autologous chimeric antigen receptor (CAR) T therapies are highly efficient at targeting hematological malignancies, but the clinical applications have been limited by individualized manufacturing. Furthermore, there has been little success in treating solid tumors due to immunosuppressive microenvironments. Currently, genome editing technologies are being used to address both issues. However, the CRISPR/Cas9 system has significant safety concerns due to high incidence of off-target mutations and TALEN only works sufficiently in activated cells. A hybrid gene editing system, NextGEN (NG) Clo51-dCas9, can be targeted using gRNA, like CRISPR/Cas9, but exhibits little-to-no off-target cutting like TALEN, thereby overcoming limitations in the genome editing of resting T cells. Methods: We successfully developed a platform for production of allogeneic CAR-T cells with reduced receptivity to inhibitory signaling. Here, T cells were modified by piggyBac-mediated BCMA CAR gene delivery, along with NG reagents to knock out critical genes mediating rejection responses. Gene edited CAR-T cells were assessed by mixed lymphocyte reaction (MLR) and tumor killing. In addition, NG was used to knockout multiple checkpoint inhibitory receptors known to mediate key suppressive signals in T cells. Results: NG demonstrated high gene disruption efficiencies for all targets (84% for TCRα, 91% for TCRβ, 64% for β-2 microglobulin, and 40-60% for the surface inhibitory receptors PD-1, CTLA-4, Tim3, Lag-3, and TGFBRII). In contrast to CRISPR/Cas9, no off-target mutations were detected for multiple targets by deep-sequencing. In MLRs, disruption of TCR eliminated the GvHD response, while disruption of MHCI completely abrogated graft-rejection. Lastly, TCR/MHCI double knockout did not affect the ability to kill BCMA+ multiple myeloma cells in vitro. Conclusions: NG overcomes significant limitations of the CRISPR/Cas9 and TALEN systems with highly efficient genome editing in resting T cells. NG has great potential and flexibility for the manufacture of allogeneic CAR-T cells and for enhancing efficacy against solid tumors.
[Chronic renal dysfunction in workers exposed to cadmium oxide fume. Medical examinations of welders using cadmium containing silver solder]. (1984)

Workers, who had been exposed to cadmium oxide fume, i.e., engaged in welding work with cadmium containing silver solder in an automobile parts manufacturing factory, were examined in 1975. Twenty two male welders were 22 to 55 years old and exposed to cadmium for periods ranging from 7 months to 23 years. Excreted urinary cadmium levels varied from 5.7 micrograms to 184.9 micrograms per day, and these values were useful indices of most recent exposures in workshop environments. The examinees were divided into three groups according to excreted urinary cadmium levels: five of them in high, eleven in middle, and six in low group, respectively. Workers in high-excretion group complained of considerable subjective symptoms and their urinary protein showed a remarkable increase, compared to middle- and low-excretion groups, and the electrophoretic pattern of urinary proteins showed preponderance of globulins. Urinary calcium and beta 2-microglobulin in the high-excretion group showed a remarkable increase. In all examinees, urinary phosphate, calcium, and beta 2-microglobulin were significantly correlated with urinary excreted cadmium. Furthermore, in the high-excretion group showed a considerable increase of serum creatinine values and reduction of creatinine clearance, and percent tubular reabsorption of phosphate, calcium and beta 2-microglobulin decreased. In all examinees, creatinine clearance and percent tubular reabsorption of both phosphate and calcium were significantly negatively correlated with urinary cadmium excretion. Therefore, five high-excretion workers showed evidence of chronic renal tubular dysfunction and one of these was particularly recognized as having remarkable renal damage. The possibility to affirm the effects of exposure to cadmium was suggested on hematological findings related to anemia. Liver function abnormalities were not recognized. A slight reduction of the respiratory function was found in one worker of the high-excretion group, but radiological examination of chest showed no abnormalities in all examinees.
Breast cancer progression in MCF10A series of cell lines is associated with alterations in retinoic acid and retinoid X receptors and with differential response to retinoids. (2004)

In most breast carcinomas and in breast cancer cell lines, retinoic acid receptor beta (RARbeta) is lost or down-regulated, whereas retinoic acid receptor alpha and gamma (RARalpha, gamma) and retinoid X receptors (RXRalpha, beta, gamma) are variably expressed. Little is known about alterations of the above receptors in hyperplastic and premalignant stages of breast cancer development. In this study, we employed the MCF10A series of breast epithelial cell lines (the parental and benign MCF10A, premalignant MCF10AT, and malignant MCF10CA1a) to assess whether in the course of their malignant transformation specific alterations in RARalpha, beta, gamma and RXRalpha, beta, gamma expression occur and whether they may affect the sensitivity of cells to retinoids. Malignant properties of the above cell lines were estimated by the nude mice xenograft transplantation assay. Among the above receptors most significant alterations occurred in RARbeta2, which was detected in the normal breast epithelial cells both, at mRNA and protein levels, but expressed in the MCF10A cell lines at mRNA level only. The transformation of benign MCF10A cells into premalignant MCF10AT and malignant MCF10CA1a was also associated with increase in RARalpha, RARgamma, RXRalpha, and RXRbeta proteins expression. All-trans retinoic acid (atRA), 9-cis retinoic acid (9cRA), and 4-(hydroxyphenyl) retinamide (4-HPR) induced RARbeta2 protein expression exclusively in the benign MCF10A cells and the former two retinoids, mRNA expression in MCF10A and MCF10AT cells, but not in malignant, MCF10CA1a cells, suggesting that the loss of inducible RARbeta expression is associated with the progression and malignant transformation of MCF10A cells. Retinoids also variable decreased the RARalpha, RARgamma and RXRalpha protein expression preferentially in the premalignant and malignant, but not in benign MCF10A cells. Among the above retinoids, 4-HPR was most efficacious in inhibiting the growth of the three cell lines and this apparently was not dependent on the levels of the RARbeta2 transcriptional activation. Thus, our data support the hypothesis that breast epithelial cells in the course of their progression and malignant transformation may differentially respond to retinoids and that not only RARbeta, but RARalpha, gamma and/or RXRalpha, beta may also serve as potential targets for retinoids in breast cancer prevention and therapy trials.
Embedded image coding based on context classification and quadtree ordering in wavelet packet domain (2005)

This paper presents an embedded wavelet packet image coding algorithm which is based on context classification and quadtree ordering (CCAQO). To match up well with the quadtree-based embedded coder, a new cost function for the best basis selection is adopted in discrete wavelet packet transform (DWPT). In addition, combined with the structure of the best wavelet packet basis, a complete quadtree representation of wavelet packet coefficients is established to explore the ordering procedure of embedded image coding. Since subband correlation is mainly captured by significance coding, our focus is on significance coding. The significance probability of wavelet coefficient is estimated by convoluting a 9x9 FIR filter matrix kernel with the significance states of neighboring coefficients, and then a context classifier based on Lloyd- Max algorithm is used to categorize the wavelet coefficients with the same or similar significance probability into several contexts. The significance state of wavelet coefficient with respect to a given threshold is encoded using adaptive arithmetic coder based on the classified context. Due to the optimal context classifier and the flexible quadtree representation ability of wavelet packet coefficients, the proposed CCAQO embedded image coder offers improvement in subjective and objective quality for texture-rich images and experimental results show that it offers coding performance superior to or comparable to the state-of-the-art image coders.
Integrated Circuit Design. (1987)

Abstract : This report describes the results of a study on the chip design of a low-power filter, using state-of-the-art CMOS technology. The filter is for speech applications and is specified to have 1024 type with programmable weights and linear phase. The chip implementation is to have a word length of 8 to 12 bits and consume a maximum of 2.0 mA at 3.6V. Included are current capabilities of CMOS/SOS/bulk, technology, and in particular, the Hughes VHSIC CMOS process. The architecture of the filter is discussed and estimates are made for the power consumption, speed, device count, and projected chip size of the filter implementation. A comparison of a multiple tape and a single tape implementation of the filter is also presented in terms of power consumption and operational speed.
Transfer rate of ozone across the gas-water interface. (1989)

オゾンの水への吸収速度を表わす物質移動容量係数 (液相基準) を酸素の物質移動容量係数とともに気泡塔で測定した。物質移動容量係数を測定するにあたり, 測定上および解析上容易なことからオゾンを水へ吸収させるよりも, 水に溶解させたオゾンを気相に揮散させる方法を採用した。さらに, 水から揮散してくるオゾンの連続的な吸光度測定法を用いたことから,従来の試料採取一分析という方法よりも, より誤差も少なく, より速くオゾン濃度の経時的変化を追跡することができた。また, オゾンの水中での自己分解速度を検討し, オゾン濃度に対しほぼ二次反応となる結果を得た。この知見に基づいて, オゾンの気液界面を通しての物質移動速度に比較してオゾンの自己分解速度が無視できる条件を求め, これらの条件下でオゾンと酸素の物質移動容量係数比を決定した。その値として, 気液混合状態, 温度 (283～313K) およびイオン強度 (μ=0.1～1.0) によらず一定の 0.84 ± 0.03 を得た。したがって, この値に水処理装置における酸素の物質移動容量係数を掛け合わせることにより, その装置でのオゾンの物質移動容量係数が推算でき, 吸収速度が決定できることになる。
The ad hoc chemical design of random PBS-based copolymers influences the activation of cardiac differentiation while altering the HYPPO pathway target genes in hiPSCs (2023)

Cardiac tissue engineering is a cutting-edge technology aiming to replace irreversibly damaged cardiac tissue and restore contractile functionality. However, cardiac tissue engineering porous and perfusable scaffolds to enable oxygen supply in vitro and eventually promote angiogenesis in vivo are still desirable. Two fully-aliphatic random copolymers of poly(butylene succinate) (PBS), poly(butylene succinate/Pripol), P(BSBPripol), and poly(butylene/neopentyl glycol succinate), P(BSNS), containing two different subunits, neopentyl glycol and Pripol 1009, were successfully synthesized and then electrospun in tridimentional fibrous mats. The copolymers show different thermal and mechanical behaviours as result of their chemical structure. In particular, copolymerization led to a reduction in crystallinity and consequently PBS stiffness, reaching values of elastic modulus very close to those of soft tissues. Then, to check the biological suitability, human induced Pluripotent Stem Cells (hiPSCs) were directly seeded on both PBS-based copolymeric scaffolds. The results confirmed the ability of both the scaffolds to sustain cell viability and to maintain their stemness during cell expansion. Furthermore, gene expression and immunofluorescence analysis showed that P(BSBPripol) scaffold promoted an upregulation of the early cardiac progenitor and later-stage markers with a simultaneously upregulation of HYPPO pathway gene expression, crucial for mechanosensing of cardiac progenitor cells. These results suggest that the correct ad-hoc chemical design and, in turn, the mechanical properties of the matrix, such as substrate stiffness, together with surface porosity, play a critical role in regulating the behaviour of cardiac progenitors, which ultimately offers valuable insights into the development of novel bio-inspired scaffolds for cardiac tissue regeneration.
Drug Interactions in Pulmonary Arterial Hypertension and Their Implications (2009)

Medical intervention is necessary in the treatment of pulmonary arterial hypertension (PAH) in order to prevent chronic disease progression and clinical deterioration. Recent years have seen the development of new disease-specific drugs, such as endothelin receptor antagonists (ERAs). However, there remains the potential for drug–drug interactions (DDIs), which can adversely affect drug metabolism and therefore treatment efficacy, an especially significant factor to consider in light of the increasing use of combination therapy in PAH and the ageing patient population who may also suffer age-related diseases requiring concomitant drug therapy. The ERA ambrisentan has demonstrated lower liver toxicity and fewer DDIs than other ERAs. The lack of any significant drug interactions with commonly used adjunct therapies such as warfarin or sildenafil could potentially improve treatment efficacy as well as patient safety.
Developmental Expression of the Fac Gene Correlates with Congenital Defects in Fanconi Anemia Patients (1996)

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by a variety of congenital and skeletal malformations, progressive pancytopaenia and predisposition to malignancies. While the basic defect in this disease is not known, the cloning of the gene defective in FA group C patients (FAC) allows analysis of its expression pattern, which may provide clues about the functional properties of the protein. This paper describes the distribution of Fac transcripts during murine development (8-19.5 days p.c.), using RNA in situ hybridization. Fac is initially expressed (8-10 days p.c.) in the mesenchyme and its derivatives with osteogenic potential. The transcript is also apparent at later stages of bone development (13-19.5 days p.c.), localized to cells of the inner perichondrium, periosteum and zone of endochondral ossification. In the latter, Fac transcripts are seen in cells from both osteogenic and hematopoietic lineages. Fac mRNA is also seen in intramembranous cranial and facial bones. In addition, Fac signal is detected in non-skeletal tissues: brain, whisker follicles, lung, kidney, gut and stomach. Fac expression is high in progenitor cell populations but is downregulated in differentiating cells that give rise to connective tissue. The pattern of Fac expression is consistent with the skeletal and non-skeletal congenital abnormalities in FA patients. As well, expression in rapidly dividing progenitors is consistent with hypotheses regarding the nature of the basic defect in FA: a role of the protein in DNA repair or protection from oxygen toxicity.
CD166/ALCAM Expression Is Characteristic of Tumorigenicity and Invasive and Migratory Activities of Pancreatic Cancer Cells (2014)

CD166+ pancreatic cancer cells are strongly tumorigenic, while CD166- pancreatic cancer cells exhibit comparatively stronger invasive and migratory activities. These findings suggest that CD166 expression is related to different functions in pancreatic cancer cells.
Alveo, a Human Communication Science Virtual Laboratory (2014)

We give a hands-on demonstration of the Alveo Virtual Laboratory, a new platform for collaborative research in human communication science (HCS). Funded by the Australian Government National eResearch Collaboration Tools and Resources (NeCTAR) program, Alveo involves partners from a range of disciplines: linguistics, natural language processing, speech science, psychology, as well as music and acoustic processing. The goal of the platform is to provide easy access to a variety of databases and a range of analysis tools, in order to foster inter-disciplinary research and facilitate the discovery of new methods for solving old problems or the application of known methods to new datasets. Alveo integrates a number of tools and enables non-technical users to process communication resources (including not only text and speech corpora but also music recordings and videos) using these tools in a straightforward manner.
How Important is Selection? Experimental VS. Non-Experimental Measures of the Income Gains from Migration (2010)

How much do migrants stand to gain in income from moving across borders? Answering this question is complicated by non-random selection of migrants from the general population, which makes it hard to obtain an appropriate comparison group of non-migrants. New Zealand allows a quota of Tongans to immigrate each year with a random ballot used to choose among the excess number of applicants. A unique survey conducted by the authors allows experimental estimates of the income gains from migration to be obtained by comparing the incomes of migrants to those who applied to migrate, but whose names were not drawn in the ballot, after allowing for the effect of non-compliance among some of those whose names were drawn. We also conducted a survey of individuals who did not apply for the ballot. Comparing this non-applicant group to the migrants enables assessment of the degree to which non-experimental methods can provide an unbiased estimate of the income gains from migration. We find evidence of migrants being positively selected in terms of both observed and unobserved skills. As a result, non-experimental methods other than instrumental variables are found to overstate the gains from migration by 20–82%, with difference-in-differences and bias-adjusted matching estimators performing best among the alternatives to instrumental variables.
Two novel spliced genes in human cytomegalovirus (2003)

Two novel spliced genes (UL131A and UL128) flanking UL130 were predicted from sequence comparisons between human cytomegalovirus (HCMV) and its closest known relative, chimpanzee cytomegalovirus (CCMV), and the splicing patterns were confirmed by mRNA mapping experiments. Both genes were transcribed with late kinetics and shared a polyadenylation site. Comparisons with wild-type HCMV in infected human tissues showed that three of five isolates passaged in cell culture contained disruptions of UL128, one was frameshifted in UL131A and one exhibited a deletion affecting UL131A and UL130. CCMV and the Colburn strain of simian cytomegalovirus, which have been passaged in cell culture, also exhibit disruptions of UL128. These observations indicate that expression of either one of UL128 and UL131A is deleterious to growth of primate cytomegaloviruses in cell culture. Although the functions of these genes are unknown, sequence comparisons suggest that UL128 encodes a beta-chemokine.
Review Gary ToppingLeonard J. Arrington: A Historian’s Life. (Norman: Arthur H. Clark, 2008. 251 pp. Illustrations, notes, bibliography, index. $39.95.) (2010)

Leonard J. Arrington: A Historian's Life Get access Leonard J. Arrington: A Historian's Life. By Topping Gary. (Norman: Arthur H. Clark, 2008. 251 pp. Illustrations, notes, bibliography, index. $39.95.) Gregory A. Prince Gregory A. Prince Potomac, Maryland Search for other works by this author on: Oxford Academic Google Scholar Western Historical Quarterly, Volume 41, Issue 1, Spring 2010, Pages 102–103, https://doi.org/10.2307/westhistquar.41.1.0102 Published: 01 February 2010
Optimal power allocation based on QoS balance for a multi-rate packet CDMA system with multimedia traffic (2003)

Usually, when combining two or more services (each having their own QoS requirements), it is difficult to achieve a common operation point for all the services. When we satisfy the highest QoS requirement, the other services will be operating at "unnecessary high quality". In this case, a lot of bandwidth is wasted due to a low traffic load. To solve this problem and to achieve higher spectral efficiency, a "QoS balance" method is developed to optimise the allocation of transmission power and evaluated in a wideband DS-CDMA environment integrated with video and voice services. Our simulation results demonstrate that the capacity of the network or spectral efficiency is improved significantly, by this optimal power allocation scheme.