Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative evaluation of the powder and compression properties of various grades and brands of microcrystalline cellulose by multivariate methods

The present work challenges a newly developed approach to tablet formulation development by using chemically identical materials (grades and brands of microcrystalline cellulose). Tablet properties with respect to process and formulation parameters (e.g. compression speed, added lubricant and Emcompress® fractions) were evaluated by 23-factorial designs. Tablets of constant true volume were prepared on a compaction simulator at constant pressure (approx. 100 MPa). The highly repeatable and accurate force-displacement data obtained was evaluated by simple ‘in-die’ Heckel method and work descriptors. Relationships and interactions between formulation, process and tablet parameters were identified and quantified by multivariate analysis techniques; principal component analysis (PCA) and partial least square regressions (PLS). The method proved to be able to distinguish between different grades of MCC and even between two different brands of the same grade (Avicel®PH 101 and Vivapur®101). One example of interaction was studied in more detail by mixed level design: The interaction effect of lubricant and Emcompress® on elastic recovery of Avicel®PH 102 was demonstrated to be complex and non-linear using the development tool under investigation.
A novel exercise device for venous thromboembolism prophylaxis improves venous flow in bed versus ankle movement exercises in healthy volunteers

Purpose: Venous thromboembolism prophylaxis is crucial. To facilitate active ankle movement in postoperative and bedridden patients, we developed a novel leg exercise apparatus (LEX). We investigated the effect of the LEX by comparing increases in lower extremity venous flow during different modes of exercise using the LEX. Methods: In eight healthy participants, we measured venous flow volume and velocity in the femoral vein using duplex ultrasonography at 1, 10, 20, and 30 min after completing three modes of 1-min LEX exercises. The exercises involved (1) rapid single motion (ankle dorsi–plantar flexion; 60 cycles/min); (2) slow single motion (30 cycles/min); and (3) slow combined leg motion. Results: Flow volumes after modes 1, 2, and 3 were 1.63-, 1.39-, and 1.53-fold above baseline at 30 min, respectively. Short periods of rapid single motion, with the LEX, improved postexercise lower extremity venous flow volumes at 30 min and mean venous flow velocity at 20 min, compared to slow single motion exercise. Even at slow speeds, combined-motion improved flow volume compared to single motion. Conclusion: Short periods of rapid single motion exercise, with the LEX, improved postexercise venous flow volumes in the lower extremities at 30 min and mean venous flow velocity at 20 min. These effects were greater than those produced by slow single motion exercises. However, even at slow speeds, combined-motion exercises improved flow volume compared to single motion. Therefore, LEX may prove effective at preventing thromboembolism in postoperative and bedridden patients.
Calcium‐activated potassium channels in rat muscle inactivate from a short‐duration open state.

Single channel recording techniques were applied to the study of activation and inactivation of Ca2+‐activated K+ channels in excised patches of membrane from rat muscle grown in culture. The concentration of intracellular surface Ca2+ was 0.6 microM in all experiments. The time course of the averaged open probability during depolarizing voltage steps of 1 s duration was biphasic for steps more positive than 20 mV; a rapid activation phase was followed by a much slower apparent inactivation with a single exponential time constant in the range of 400‐800 ms. The peak open probability and degree of inactivation increased as the steps were made more positive (+30 to +80 mV) or the holding potential more negative (+30 to ‐40 mV). A conditional probability analysis of the open intervals immediately adjacent to the long‐duration shut intervals resulting from inactivation revealed that transitions to and from the inactivated state occurred almost exclusively via a short‐duration open state (mean lifetime less than 200 microseconds). The rate of transition from the short‐duration open state to the inactivated state was rapid (typical rate constant 1879/s) and was sufficiently probable that as many as one out of every three short‐duration openings were followed by inactivation. Normal (non‐inactivating) closure of the channel from this open state was also rapid (rate constant 4003/s). At constant voltage (+50 mV) and Ca2+ (0.6 microM), the channel opened to the short‐duration open state approximately every 75 ms, suggesting that the slow inactivation of the averaged open probability might have been limited in part by the rate at which the channel entered the short‐duration open state.
Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids.

This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled beta(2)-agonists with either recently diagnosed asthma (RDA: </= 2 yr, n = 16) or long-standing asthma (LSA: >/= 13 yr, n = 16) and at the influence of an intense inhaled corticosteroid (ICS) treatment on these parameters, in relation to changes in airway responsiveness. Patients had a methacholine inhalation test and a bronchoscopy with bronchial biopsies before and after an 8-wk treatment with inhaled fluticasone propionate (FP), 1,000 microgram/day. Baseline FEV(1) (mean +/- SEM) was normal and similar in both groups (RDA: 98.1 +/- 2.7, LSA: 94.5 +/- 4.6%). Geometric mean methacholine PC(20) was lower in LSA than in RDA (0.44 versus 3.37 mg/ml) at baseline and improved similarly by 1.85 and 1.86 double concentrations with FP treatment. PC(20) normalized (>/= 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm(2) connective tissue surface) for CD3(+), CD4(+), CD8(+), CD25(+), EG1(+), CD45ro(+), and AA1(+) cells were similar in both groups. With FP, EG1(+) (p < 0.001), EG2(+) (p = 0.018), and AA1(+) counts (p = 0.009) decreased significantly in both groups while CD45ro(+) (p = 0.02) counts decreased only in LSA. Baseline type 1 and type 3 collagen deposition underneath the basement membrane was similar in RDA and LSA and did not change significantly after FP. This study shows that recent compared to long-standing mild asthma is associated with a similar degree of airway inflammation and subepithelial fibrosis, and a similar improvement in airway hyperresponsiveness after 8 wk on high-dose ICS. It also indicates that once asthma becomes symptomatic, airway responsiveness cannot normalize in most subjects over such a time period, even with a high dose of ICS.
Cognitive Predictors of Dementia in Parkinson’s Disease: A Community-Based, 4-Year Longitudinal Study

Although mild cognitive impairment and dementia are common and have important clinical consequences for patients with Parkinson’s disease (PD) and their caregivers, it is still unclear whether cognitive symptoms may predict the development of dementia in PD patients. The objective of this study was to determine whether cognitive deficits in nondemented PD patients predicted the development of dementia 4 years later. A total of 76 nondemented PD patients from an epidemiological study of PD in the county of Rogaland, Norway, were assessed at baseline and 4 years later with neurological, psychiatric, and neuropsychological evaluations. Twenty-five (42%) new cases of dementia were diagnosed after 4 years. Time to complete the third card of the Stroop test was the only variable that was independently associated with dementia. The authors concluded that poor performance on a test sensitive to executive dysfunction predicted later development of dementia in PD patients. This finding may have important clinical implications as a marker of subsequent development of dementia.
Cathepsin K: a unique collagenolytic cysteine peptidase

Abstract Cathepsin K has emerged as a promising target for the treatment of osteoporosis in recent years. Initially identified as a papain-like cysteine peptidase expressed in high levels in osteoclasts, the important role of this enzyme in bone metabolism was highlighted by the finding that mutations in the CTSK gene cause the rare recessive disorder pycnodysostosis, which is characterized by severe bone anomalies. At the molecular level, the physiological role of cathepsin K is reflected by its unique cleavage pattern of type I collagen molecules, which is fundamentally different from that of other endogenous collagenases. Several cathepsin K inhibitors have been developed to reduce the excessive bone matrix degradation associated with osteoporosis, with the frontrunner odanacatib about to successfully conclude Phase 3 clinical trials. Apart from osteoclasts, cathepsin K is expressed in different cell types throughout the body and is involved in processes of adipogenesis, thyroxine liberation and peptide hormone regulation. Elevated activity of cathepsin K has been associated with arthritis, atherosclerosis, obesity, schizophrenia, and tumor metastasis. Accordingly, its activity is tightly regulated via multiple mechanisms, including competitive inhibition by endogenous macromolecular inhibitors and allosteric regulation by glycosaminoglycans. This review provides a state-of-the-art description of the activity of cathepsin K at the molecular level, its biological functions and the mechanisms involved in its regulation.
Menin localization in cell membrane compartment

ABSTRACT Menin is encoded by the MEN1 gene, which is mutated in an inherited human syndrome, multiple endocrine neoplasia type 1(MEN1). Menin is primarily nuclear protein, acting as a tumor suppressor in endocrine organs, but as an oncogenic factor in the mixed lineage leukemia, in a tissue-specific manner. Recently, the crystal structures of menin with different binding partners reveal menin as a key scaffold protein that functionally interacts with various partners to regulate gene transcription in the nucleus. However, outside the nucleus, menin also regulates multiple signaling pathways that traverse the cell surface membrane. The precise nature regarding to how menin associates with the membrane fraction is poorly understood. Here we show that a small fraction of menin associates with the cell membrane fraction likely via serine palmitoylation. Moreover, the majority of the membrane-associated menin may reside inside membrane vesicles, as menin is protected from trypsin-mediated proteolysis, but disruption of the membrane fraction using detergent abolishes the detection. Consistently, cellular staining for menin also reveals the distribution of menin in the cell membrane and the punctate-like cell organelles. Our findings suggest that part of intracellular menin associates with the cell membrane peripherally as well as resides within the membrane vesicles.
External debt relief initiatives and economicgrowth in least developed countries

In the late 1990s, the World Bank and the International Monetary Fund (IMF) initiated a series of debt relief programs for highly indebted poor countries (HIPCs) based on the idea that high levels of indebtedness impede growth by discouraging domestic and foreign investment. This paper examines the relationship between external debt and growth with a focus on the effects of multilateral debt relief. In particular, we use a sample of 33 least developed countries (LDCs) over the period 1970-2010 to explore the impact of indebtedness on growth before and after participating in the debt relief initiatives. In contrast to previous studies, we employ a combination of parametric and non-parametric methods to investigate the linear and nonlinear aspects of the debt-growth relationship. In the non-parametric analysis, we model growth as a discreet-time Markov process and estimate the transition probabilities for HIPCs. The results show that lower debt levels stimulate economic growth. The average impact of debt on growth in HIPCs becomes negative at about 64 -78% of GDP depending on the initial growth conditions. In the period after joining the debt relief initiatives, HIPCs generally exhibited a higher chance of moving towards or persisting in the positive range of growth. However, this process was related to lower debt levels mostly in countries that had initially exhibited moderate to rapid growth, while debt relief seems to have been less relevant for future growth in countries that started off in a state of moderate economic decline. Furthermore, the results of the regression analysis show that the marginal effect of public and publicly guaranteed (PPG) debt on growth is negative and significant. Debt relief programs were found to mitigate the negative impact of debt, both after their initiation in 1996 and after the HIPCs reached their decision point. Generally, the overarching policy that can be drawn from this paper is that LDCs, and HIPCs in particular, should strive to reduce their PPG debt levels to at least below 64%-78% of GDP in order to experience and maintain positive growth rates, ceteris paribus. Notwithstanding, our findings also suggest that if HIPCs, and LDCs in general, want to reduce or maintain their debt to sustainable levels, they should adopt some of the conditions imposed by the international financial institutions on HIPCs as part of their macroeconomic policy framework, such as developing and implementing a poverty reduction strategy through a broad based participatory process.
Overlapping Ownership, R&D Spillovers, and Antitrust Policy

This paper considers cost-reducing R&D investment with spillovers in a Cournot oligopoly with overlapping ownership. We show that overlapping ownership leads to internalization of rivals’ profits by firms and find that, for demand not too convex, increases in overlapping ownership increase (decrease) R&D and output for high (low) enough spillovers while they increase R&D but decrease output for intermediate levels of spillovers. There is scope for overlapping ownership to improve welfare and consumer surplus, provided that spillovers are sufficiently large. The results obtained are robust when R&D has commitment value and in a Bertrand oligopoly model with product differentiation.
Sexual coercion and health-risk behaviors among urban Chinese high school students

Objective To determine the association between health-risk behaviors and a history of sexual coercion among urban Chinese high school students. Design A cross-sectional study was performed among 109,754 high school students who participated in the 2005 Chinese Youth Risk Behavior Survey. Data were analyzed for 5,215 students who had experienced sexual intercourse (1,483 girls, 3,732 boys). Multivariate logistic regression was used to determine the relationship between sexual coercion and the related covariates, and data were stratified by gender. Results Of those students who had had sexual intercourse, 40.9% of the females and 29.6% of the males experienced sexual coercion (p<0.01). When analyses controlled for demographic characteristics, in the study sample, that is, students who had sexual intercourse, drug use (odds ratios [OR], 2.44), attempted suicide (OR, 2.30), physical abuse (OR, 1.74), binge drinking (OR, 1.62), verbal abuse (OR, 1.29), experience of being drunk (OR, 0.68), and smoking of cigarettes (OR, 0.52) were related to a history of sexual coercion. Patterns of health-risk behaviors also differed among female and male students who had experienced sexual coercion. Conclusions Sexual coercion is associated with health-risk behaviors. Initiatives to reduce the harm associated with sexual coercion among high school students are needed.
Glucagon‐like peptide‐1 cells in the gastrointestinal tract and pancreas of rat, pig and man

Abstract. A highly specific monoclonal antibody directed against the C‐terminal part of glucagon‐like peptide‐1 (GLP‐1) was raised to immunohistochemi‐cally evaluate the distribution of GLP‐1 containing cells in the entire gastrointestinal tract including pancreas of rat, pig and man. In the pancreas GLP‐1 ‐immunoreactive cells were found variously shaped and predominantly located in the periphery of the islets. Ultrastructurally, GLP‐1 was co‐localized with gluca‐gon in the α‐granula of A‐cells and was mainly restricted to the electrondense core. In the intestine open type cells reaching the lumen via a slender apical process were stained with the GLP‐1 antibody. They occurred in all parts of the crypts but predominantly in the basal portion. The density of GLP‐1 immuno‐reactive cells varied between species in a characteristic order: rat > pig > man. In pig and human gut a large number of cells occurred in the distal jejunum and ileum. A continuous increase of cell densities was found from the proximal to the distal colon resulting in highest numbers in the rectum. In rats the highest cell density occurred in the ileum. Again, a continuous increase of GLP‐1‐positive cell numbers was evident from the proximal to the distal portion of small and large bowel. GLP‐1 was partly co‐localized with PYY. The GLP‐1 positive cells appeared electronmicrosco‐pically as L‐cells with the typical large granula. This morphological data indicates that GLP‐1‐releasing cells in the small intestine are appropriately positioned in the distal part to sense and respond to the presence of nutrients that have escaped the absorptive surface of the upper small intestine.
Squamous cell carcinoma of the conjunctiva: a series of 26 cases

Aim: To retrospectively study 26 patients with squamous cell carcinoma (SCC) of the ocular surface to determine pathological and clinical characteristics of tumour associated with outcome. Methods: Patients with conjunctival SCC from St Vincent's Hospital and the private ophthalmology practices of the authors were reviewed. Results: Patents were usually male (77%), elderly (69% > 60 years of age), with most lesions (81%) occurring at the limbus. Seven patients (27%) suffered recurrent ocular surface squamous neoplasia (OSSN) within 4–15 months and two of these patients (8%) died of metastatic disease. Intraocular invasion was noted in three patients (11%), while corneal and/or scleral invasion was found in eight (30%). Orbital invasion was noted in four patients (15%). Six required orbital exenteration. Preoperative impression cytology of five patients with minimally invasive disease showed OSSN in four (80%). In situ carcinoma could not be differentiated from minimally invasive disease using impression cytology. Preoperative diagnosis of SCC was made in 35% of cases. Clinical accuracy was higher for larger lesions (>10 mm) and those with hyperkeratosis. Conclusions: Conjunctival SCC occurs in sun damaged ocular surface, usually at the limbus in elderly men. Recurrence of OSSN is common with significantly increased risk for older patients, lesions of large diameter, high proliferation index (Ki-67 score), and positive surgical margins. Orbital exenteration may be required for control of local disease and death from metastatic disease occurs in a small percentage of patients.
High-dose gammaglobulin (IVIG) followed by intrauterine transfusions (IUTs): a new alternative for the treatment of severe fetal hemolytic disease

Intrauterine fetal transfusion is currently the therapy of choice in cases of severe anti-D isoimmunisation. However, its efficacy is reduced in patients with early severe hydrops fetalis due to the technical difficulties in performing this procedure before 20 weeks' gestation. The purpose of this study was to determine whether early onset of high-dose gammaglobulin therapy followed by intrauterine transfusions (IUTs) is more effective than IUTs alone in the treatment of very severe isoimmunised fetuses. The population studied in this retrospective clinical research was assigned to one of the following two groups: 1) Gamma group: 30 patients receiving gammaglobulin therapy before 21 weeks' gestation and IUTs after 20 weeks; or 2) IUT group: 39 patients receiving IUT treatment starting at a gestational age of 20-25 weeks. Both groups were statistically similar regarding history of perinatal deaths and anti-D antibody titers. The number of hydropic fetuses at the first IUT and of fetal deaths were significantly higher in the IUT than in the Gamma group. No significant differences were observed between the groups in fetal hematocrit at first IUT and at birth. However, the percentage of severely anemic fetuses was higher in the IUT group. Fetal mortality rate was 36% less in the Gamma group. Our results suggest that high-dose gammaglobulin therapy followed by IUTs may improve fetal survival in these severe cases. Further randomised clinical trials are needed to confirm these results.
Three essays on the empirical market microstructure of money market derivatives

This thesis is the first directly to study the entire limit order book of a large market. Herein, I conduct a population study on the microstructure of the Eurodollar future market, to my knowledge this is a) the first study of its type and b) the largest microstructure study ever conducted. I will build a data-drive model that incorporates information from the entire population of quotes updates and transactions on this type of future market. This thesis aims to provide a comprehensive understanding of the market microstructure on money market derivatives and the impact of high-speed algorithmic trading activity on the market characteristics and quality. I apply a broad battery of market volatility and liquidity measurements, and gauge the proportion of high-frequency algorithmic traders in the market. This thesis provides a standard asymmetric information based theoretical model to predict the relation on the term structure of Eurodollar future contracts. The prediction is a non-linear relation between the saturation of algorithmic traders (ATs) versus the impacts on the quality of the market. Therefore, I develop a novel semi-parametric estimator and model the non-linear relation between the impact of the fraction of algorithmic trading and a large set of different market quality indicators including volatility, liquidity and price informativeness. Finally, I consider the efficiency and the speed of high-frequency prices formation by implementing the return autocorrelations and vector autoregression, and also make a contribution to the trade classification algorithm using the order book data. My findings are fourfold. First, the impact of high-frequency trading (HFT) on market quality is a non-linear by implementing the semi-parametric model. This may partially explain why prior studies have found contradictory results regarding the impact of high-frequency traders (HFTs) on market characteristics. Second, prior studies only including the inside quotes or best bid best ask are limited to reflect all the information in the market. My findings suggest that the second level quoting in the limit order book is by far the most rapidly quoted element of the order book. Furthermore, I find that wavelet variance covariance of the bid and the ask side changes substantially over the term structure; providing further supporting evidence of the non-linear impact of HFTs. Finally, the adjustment time of the trade prices formation process is within one second, and the quote prices are even faster within 200 milliseconds (ms). The mid-quoted return autocorrelation is positive and gradually increase from the shortest time interval to the longest time interval. The trade prices are less sensitive to new information as the contract approaches its maturity.