Miracle-dz/UniFAR-FTUs huggingface dataset:
Ipilimumab in the treatment of advanced melanoma – a clinical update

Introduction: Ipilimumab has become an important treatment option for patients with advanced melanoma; however, active research perseveres to resolve many clinical practice issues and to further improve the therapeutic index of this agent. Areas covered: This article aims to provide an update on long-term data, current challenge and recent progress relating to the clinical application of ipilimumab in the treatment of advanced melanoma. A literature search using PubMed database was conducted using search words ipilimumab, melanoma, treatment sequencing, adjuvant therapy, combination therapy, and biomarkers. Data were also obtained from meeting abstracts and clinical trial registries. Expert opinion: Signal of clinical activity as adjuvant therapy in patients with resected high-risk melanoma begins to emerge, but longer follow-up is required for confirmation. Many issues, such as optimal dosing schedules and therapeutic sequences, remain unraveled. At present, treatment should be individualized based on patient- and disease-specific factors. Immunotherapy like ipilimumab still represents the best treatment option for durable remission; however, targeted therapies are more appropriate for patients with BRAF V600-mutated tumor who are symptomatic or have rapidly growing disease. With novel therapeutic options in the pipeline, the role of ipilimumab continues to evolve in the rapidly changing treatment landscape of advanced melanoma. Most likely, this agent will be utilized in combinatorial or sequential approach.
[Retrospective analysis of 2461 patients with maxillofacial fractures].

OBJECTIVE To review the 2461 cases of maxillofacial fractures. METHODS From 2003 to 2009, 2461 maxillofacial fracture cases were treated in Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine. Data regarding sex, age, cause of injury, occupation, geographic distribution, blood type, fracture site, multiple associated injuries, injury severity, the patient's first admitted department, treatment results were reviewed. RESULTS The male and female ratio was 4.28:1, 1424(57.86 %) patients were between 20 and 40 years of age. The most common cause of injury was road traffic accident (938 cases, 40.98%). People in tertiary industry (900 cases, 78.53%) were most vulnerable to injuries. The zygomatic complex (22.08%), nasal bone (20.67%) and mandible (16.35%) were the most frequent fracture sites, which were often associated with skull (21.74%), brain (38.36%) and soft tissue contusion injury (48.84%). 85.98% (2116/2461 cases), of patients' AIS score was less than 2. Orthopaedics (939/2461 cases, 38.16%) was the first admitted department. CONCLUSIONS The traffic accidents are the main cause of the maxillofacial fractures. Most injuries are found in the young and middle-aged people.
Residential housing bubbles in Hong Kong: identification and explanation based on GSADF test and dynamic probit model

Abstract We aim to investigate whether the current high housing price in Hong Kong contains a bubble and to identify the causes of such housing bubble if it exists by combining the generalised sup augmented Dickey–Fuller (GSADF) test and dynamic probit models. Empirical results indicate that the current Hong Kong housing market contains a bubble, and it’s the investors’ speculative demand and the increase of monetary supply that lead to the housing bubbles in Hong Kong. Moreover, speculative investors would prefer the mass markets to the luxury ones considering the outstanding performance of the former. Such preference would contribute to more bubbles in the mass markets than in the luxury ones. In view of these, Hong Kong Government should retrospect the linked exchange rate system and be alert to the impacts of the US monetary policies on Hong Kong residential market. To offset the housing bubble, a targeted and effective approach to the Hong Kong Government is to constrict the speculative demand from investors particularly in the mass markets.
Improved microRNA suppression by WPRE-linked tough decoy microRNA sponges

Our genes are post-transcriptionally regulated by microRNAs (miRNAs) inducing translational suppression and degradation of targeted mRNAs. Strategies to inhibit miRNAs in a spatiotemporal manner in a desired cell type or tissue, or at a desired developmental stage, can be crucial for understanding miRNA function and for pushing forward miRNA suppression as a feasible rationale for genetic treatment of disease. For such purposes, RNA polymerase II (RNA Pol II)-transcribed tough decoy (TuD) miRNA inhibitors are particularly attractive. Here, we demonstrate augmented miRNA suppression capacity of TuD RNA hairpins linked to the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE). This effect is position-dependent and evident only when the WPRE is positioned upstream of the TuD. In accordance, inclusion of the WPRE does not change nuclear export, translation, total levels of TuD-containing RNA transcripts, or cytoplasmic P-body localization, suggesting that previously reported WPRE functions are negligible for improved TuD function. Notably, deletion analysis of TuD-fused WPRE unveils truncated WPRE variants resulting in optimized miRNA suppression. Together, our findings add to the guidelines for production of WPRE-supported anti-miRNA TuDs.
The Attitudes of Extension Faculty Toward Globalizing Extension Programs: A Case Study of Virginia Cooperative Extension

ii ACKNOWLEDGMENT. iv DEDICATION.v LIST OF TABLES. ix CHAPTER 1.0 INTRODUCTION . 1 1.1 Background for this Study . 1 1.2 Theoretical Framework.2 1.2.1 Attitude Theory.2 1.2.1.1 Attitude Definition . 2 1.2.1.2 Attitude Formation.2 1.2.1.3 Attitude Change . 3 1.2.1.4 Attitude/Behavior Relationship . 3 1.2.2 Cooperative Extension . 3 1.2.3 Current Situation.5 1.3 Statement of the Problem.6 1.4 Purpose of the Study . 7 1.5 Study Limitations.7 1.6 Definition of Terms.8 CHAPTER 2.0 REVIEW OF LITERATURE.10 2.1 Globalization and U.S. Agriculture . 10 2.1.1 International Trade.10 2.1.2 Influence of Developing Countries on U.S. Agriculture . 11 2.2 The Importance of Globalization to Extension.12 2.2.1 4-H Youth Development.14 2.2.2 Family and Consumer Sciences . 14 2.2.3 Agriculture and Natural Resources.15 2.2.4 Staff Development . 16 2.3 Attitude/Behavior Theory . 17 2.4 Attitude Measurement.18 2.4. 1 Basic Assumptions.18 2.4. 2 Attitude Scaling . 18 2.4. 2.1 Likert Scale . 18 2.5 Summary of Chapter . 19 CHAPTER 3.0 RESEARCH METHODOLOGY . 21 3.1 Population . 21 3.2 Research Design.21 3.3 Instrumentation . 22 3.3.1 Construction of the Instrument . 24
Specific interactions of three proliferating cell nuclear antigens with replication‐related proteins in Aeropyrum pernix

Proliferating cell nuclear antigen (PCNA) is a well‐known multifunctional protein involved in eukaryotic and archaeal DNA transactions. The homotrimeric PCNA ring encircles double‐stranded DNA within its central hole and tethers many proteins on DNA. Plural genes encoding PCNA‐like proteins have been found in the genome sequence of crenarchaeal organisms. We describe here the biochemical properties of the three PCNAs, PCNA1, PCNA2 and PCNA3, from the hyperthermophilic archaeon, Aeropyrum pernix. PCNA2 can form a trimeric structure by itself, and it also forms heterotrimeric structures with PCNA1 and PCNA3. However, neither PCNA1 nor PCNA3 can form homotrimers. The DNA synthesis activity of DNA polymerase I and II, the endonuclease activity of FEN1, and the nick‐sealing activity of DNA ligase were stimulated by the complex of PCNA2 and 3 or PCNA1, 2 and 3. These results suggest that the heterotrimeric PCNA at least including PCNA2 and 3 function as the clamp in the replisome. However, PCNA2 is the most abundant in the cells throughout the growth stages among the three PCNAs, and therefore, PCNA2 may perform multitasks by changing complex composition.
Is Kenyan Sign Language a sister language of ASL

This study investigates lexicostatistical, phonological and morpho-syntactic features of Kenyan Sign Language (KSL) and compares them with those of ASL. It concludes that evidence shows KSL is not a sister language of ASL for three major reasons. The first reason is that core vocabulary cognates are only 13-22% between the two languages. The second reason is that there are phonological differences, especially those of H2 hand-shape distribution. The third reason is that there are morpho-syntactic differences, such as three arguments and word-order, between the two languages. The findings of the current research project should next be confirmed by comparative research between different sign languages in the area. We could have a newer view of KSL as a language developed with the nativity of signed languages in the whole of eastern Africa.
Observing the implementation of a school-based curriculum by teachers of different mind styles : a case study in Hong Kong

Teacher autonomy within Hong Kong’s schools is constrained by a highly bureaucratic system in which their individual teaching styles are compromised. This could be reflected in the former studies on the school-based curriculum development (SBCD) schemes initiated by the Hong Kong government, in which what was supposed to be a bottom-up innovation had turned into a highly centralized initiative. Whereas the aim of SBCD should be to allow teachers to make decisions at the school level to cater for pupils’ needs, the government-initiated SBCD schemes targeted to satisfy bureaucratic requirements instead. At issue is bureaucratisation of school-based innovations, which threatens to usurp teachers’ autonomy to make sensible judgments in response to contextual concerns. To provide a different perspective, this qualitative case study takes an insider approach to examine the implementation of a teacher-initiated school-based curriculum in a Hong Kong secondary school. English lessons delivered by four Secondary 5 (equivalent to Year 11) teachers were observed in 2013. Running logs were used to record how the four teachers delivered the school-based materials in one of their English lessons and were compared. The Gregorc Style Delineator instrument was used to identify the teachers' mind styles following the classroom observations. The research found that three teachers held the same mind style of Concrete Sequential, and their lesson activities shared many common features. However, the teacher who held the mind style of Abstract Sequential adopted a different approach in her teaching. Coupled with the classroom observations were semi-structured interviews which were designed to elicit the four participants' attitudes towards the SBCD in this study. Whilst all teachers held positive attitudes towards the curriculum and mentioned some of the benefits of SBCD that were aligned with overseas studies, they also made adaptations to the materials in accordance with their preferred teaching styles. The findings thus contrast sharply with former studies on government-initiated SBCD schemes, in which teachers tended to conform to the official requirements. Finally, this study discusses the extent to which the factor of mind styles should be incorporated into curriculum design, and provides some guidelines for how SBC could be implemented and developed.
Cardiac troponin-T in pre-end stage kidney disease.

BACKGROUND Cardiac troponin T level (cTnT) is commonly increased in end stage chronic kidney disease (CKD) in the absence of acute myocardial infarction. There are few data available on serum cTnT concentration in patients with pre-end stage CKD. OBJECTIVE To evaluate the correlation of cTnT level and severity of kidney disease in patients with CKD stage 3 and 4 and to evaluate whether there is a relationship between left ventricular mass index and cTnT level. MATERIAL AND METHOD Patients (103) with CKD stage 3-4 between 26 and 85 years of age (mean 60.0 +/- 11.9) entered the present study. Serum cTnT determined using a third-generation electrochemiluminescent immunoassay on an Elecsys 2010 analyzer (Roche Diagnostics Ltd.). All patients underwent echocardiography. Left ventricular hypertrophy (LVH) was considered when LV mass index exceeded 125 g/m2. RESULTS Overall, 28 patients (28.2%) had cTnT > 0.01 micro/L and two patients (1.8%) had cTnT > 0.1 microg/L cTnT concentration was commonly increased in more severe CKD (9 patients in stage 3 and 20 patients in stage 4). LVH was not associated with increased cTnT (p=0.105). CONCLUSION The present study demonstrated that the elevated cTnT > 0.01 microg/L is relatively common in patients with CKD stage 3-4 who do not require dialysis treatment, however serum cTnT level above > 0.1 microg/L is uncommon in this population. Increased serum cTnT is associated with decreased renal clearance but not LVH.
Immunological changes in growing mice fed on diets containing casein or peas (Pisum sativum var. Belinda) as the source of protein

The effects of two different sources of protein: peas (Pisum sativum var. Belinda) and casein on immunocompetence, nutritional utilization and growth performance have been investigated in recently weaned mice. Feeding these animals on a pea diet resulted in an impairment in growth and significant decreases in the weights of liver, muscle, kidneys and femur, while intestine weights increased. No differences in food consumption were observed, but food conversion efficiency (food intake: weight gain) was increased in pea-fed animals compared with those offered the casein diet. Packed cell volume and serum Fe and Zn levels fell significantly after legume-protein intake, and, by contrast, Cu values increased slightly. Serum albumin levels showed a statistically significant reduction in mice fed on the diet containing peas. However, y-globulins and immunoglobulin G titres were markedly increased. The characterization of spleen-cell subsets using monoclonal antibodies revealed a significantly higher percentage of T-lymphocytes in the pea group compared with casein-fed animals, while no changes were observed in the proportions of B-lymphocytes and macrophages. In vitro mitogenic responses to phytohaemagglutinin, concanavalin A and Escherichia coli lipopolysaccharide S were slightly, but not significantly, lower in the pea-fed animals. Our results describe, apparently for the first time in mice, some immunological disturbances after peak intake. These results may lead to a better understanding of the possible role of antigenic proteins in gastrointestinal disorders and the poor individual performance after legume intake.
Intrauterine growth restriction influences vascular remodeling and stiffening in the weanling rat more than sex or diet.

Intrauterine growth restriction (IUGR) increases the incidence of adult cardiovascular disease (CVD). The sex-specific developmental mechanisms for IUGR-induced and Western high-fat diet (HFD) modification of CVD remain poorly understood. We hypothesized a maternal HFD in the Sprague-Dawley rat would augment IUGR-induced CVD in the offspring through decreased cardiac function and increased extracellular matrix (ECM) remodeling and stiffness in a sex-specific manner. HFD or regular diet (Reg) was given from 5 wk before mating through postnatal day (PND) 21. IUGR was induced by uterine artery ligation at embryonic day 19.5 (term = 21.5 days). At PND 21, echocardiographic assessments were made and carotid arteries tested for vascular compliance using pressure myography. Arterial samples were quantified for ECM constituents or fixed for histologic evaluation. The insult of IUGR (IUGR + Reg and IUGR + HFD) led to increased mechanical stiffness in both sexes (P < 0.05). The combination of IUGR + HFD increased diastolic blood pressure 47% in males (M) and 35% in females (F) compared with the Con + Reg (P < 0.05). ECM remodeling in IUGR + HFD caused fewer (M = -29%, F = -24%) but thicker elastin bands (M = 18%, F = 18%) and increased total collagen (M = 49%, F = 34%) compared with Con + Reg arteries. Remodeling in IUGR + HFD males increased medial collagen and soluble collagen (P < 0.05). Remodeling in IUGR + HFD females increased adventitial collagen and wall thickness (P < 0.05) and decreased matrix metalloproteinase 2 (MMP-2), advanced glycosylation end products (AGE), and receptor AGE (RAGE; P < 0.05). In summary, both IUGR + Reg and IUGR + HFD remodel ECM in PND 21 rats. While IUGR + HFD increases blood pressure, IUGR but not HFD increases vascular stiffness suggesting a specific mechanism of vascular remodeling that can be targeted to limit future disease. NEW & NOTEWORTHY We report intrauterine growth restriction (IUGR) increases vascular stiffening in both male and female rats through increased collagen content and altered elastin structure more than a high-fat diet (HFD) alone. Our study shows the importance of stiffness supporting the hypothesis that there are physiologic differences and potential windows for early intervention targeting vascular remodeling mechanisms.
Wealth, Wages, and Wedlock: Explaining the College Gender Gap Reversal

In this paper, I study the role of changes in the wage structure and expectations about marriage in explaining the college gender gap reversal. With strongly diminishing marginal utility of wealth and in the presence of a gender wage gap, single women have a greater incentive than single men to invest in education. Marriage‐market distortions tend to depress the overall benefit of education for women relative to men. I develop a tractable two‐period model and parameterize it using US census data for the cohort born in 1950. I then show that it can generate a reversal and that the most important driving force for this is the decline in marriage rates.
Anti-Human Immunodeficiency Virus Activity of YK-FH312 (a Betulinic Acid Derivative), a Novel Compound Blocking Viral Maturation

ABSTRACT Betulinic acid, a triterpenoid isolated from the methyl alcohol extract of the leaves of Syzigium claviflorum, was found to have a potent inhibitory activity against human immunodeficiency virus type 1 (HIV-1). Betulinic acid derivatives were synthesized to enhance the anti-HIV activity. Among the derivatives, 3-O-(3′,3′-dimethylsuccinyl) betulinic acid, designated YK-FH312, showed the highest activity against HIV-induced cytopathic effects in HIV-1-infected MT-4 cells. To determine the step(s) of HIV replication affected by YK-FH312, a syncytium formation inhibition assay in MOLT-4/HIV-1IIIB and MOLT-4 coculture, a multinuclear-activation-of-galactosidase-indicator (MAGI) assay in MAGI-CCR5 cells, electron microscopic observation, and a time-of-addition assay were performed. In the syncytium formation inhibition assay or in the MAGI assay for de novo infection, the compound did not show inhibitory effects against HIV replication. Conversely, no virions were detected in HIV-1-infected cell cultures treated with YK-FH312 either by electron microscopic observation or by viral yield in the supernatant. In accordance with a p24 enzyme-linked immunosorbent assay of culture supernatant in the time-of-addition assay, YK-FH312 inhibited virus expression in the supernatant when it was added 18 h postinfection. However, Western blot analysis of the cells in the time-of-addition assay revealed that the production of viral proteins in the cells was not inhibited completely by YK-FH312. These results suggest that YK-FH312 might affect the step(s) of virion assembly and/or budding of virions, and this is a novel mechanism of action of an anti-HIV compound.
PENGENDALIAN PERSEDIAAN BAHAN BAKU OBAT DENGAN MENGGUNAKAN METODE EOQ PROBABILISTIK BERDASARKAN PERAMALAN EXPONENTIAL SMOOTHING PADA PT. XYZ

PT. XYZ is one of the manufactures of parmacheutical. Problems which often appeared are surplus and shortage material. Inventory material control not optimum because order only esimate. With exponential smoothing method can be devise of demand next period and EOQ Probabilistic for to know economic order quantity, total safety stock and reorder point so can minimization inventory cost. Purpose of research are to know exponential smoothing method what representatif for manufacture and give recomendation of this research. Results of research are exponential smoothing method representatif for manufacture and EOQ probabilistic method for Antalgin, Paracetamol and Piroxicam material are economic order quantity in the amount of 313 kg, 928 kg and 33 kg, safety stock 160 kg, 403 kg and 2kg and reorder point 325 kg, 1080 kg dan 14 kg. So total inventory cost of Antalgin, Paracetamol and Piroxicam material in the amount of Rp.3. 847.146, Rp.5. 025.081 and Rp.1. 932.255. Keyword : Inventory, Exponential Smoothing, EOQ Probabilistic
A redox-sensitive pathway mediates oxidized LDL-induced downregulation of insulin-like growth factor-1 receptors⃞s⃞ The online version of this article (available at http://www.jlr.org) contains an additional figure. Published, JLR Papers in Press, April 1, 2005. DOI 10.1194/jlr.M400478-JLR200

Oxidized low density lipoprotein (OxLDL) has multiple proatherogenic effects, including induction of apoptosis. We have recently shown that OxLDL markedly downregulates insulin-like growth factor-1 receptor (IGF-1R) in human aortic smooth muscle cells, and that IGF-1R overexpression blocks OxLDL-induced apoptosis. We hypothesized that specific OxLDL-triggered signaling events led to IGF-1R downregulation and apoptosis. We examined OxLDL signaling pathways and found that neither IGF-1R downregulation nor the proapoptotic effect was blocked by inhibition of OxLDL-triggered extracellular signal-regulated kinase, p38 mitogen-activated protein kinase (MAPK), or peroxisome proliferator-activated receptor γ (PPARγ) signaling pathways, as assessed using specific inhibitors. However, antioxidants, polyethylene glycol catalase, superoxide dismutase, and Trolox completely blocked OxLDL downregulation of IGF-1R and OxLDL-induced apoptosis. Nordihydroguaiaretic acid, AA-861, and baicalein, which are lipoxygenase inhibitors and also have antioxidant activity, blocked IGF-1R downregulation and apoptosis as well as reactive oxygen species (ROS) production. These results suggest that OxLDL enhances ROS production possibly through lipoxygenase activity, leading to IGF-1R downregulation and apoptosis. Furthermore, anti-CD36 scavenger receptor antibody markedly inhibited OxLDL-induced IGF-1R downregulation and apoptosis as well as ROS production. In conclusion, our data demonstrate that OxLDL downregulates IGF-1R via redox-sensitive pathways that are distinct from OxLDL signaling through MAPK- and PPARγ-involved pathways but may involve a CD36-dependent mechanism.