Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid emergence of telaprevir resistant hepatitis C virus strain from wildtype clone in vivo

Telaprevir is a potent inhibitor of hepatitis C virus (HCV) NS3‐4A protease. However, the emergence of drug‐resistant strains during therapy is a serious problem, and the susceptibility of resistant strains to interferon (IFN), as well as the details of the emergence of mutant strains in vivo, is not known. We previously established an infectious model of HCV using human hepatocyte chimeric mice. Using this system we investigated the biological properties and mode of emergence of mutants by ultra‐deep sequencing technology. Chimeric mice were injected with serum samples obtained from a patient who had developed viral breakthrough during telaprevir monotherapy with strong selection for resistance mutations (A156F [92.6%]). Mice infected with the resistant strain (A156F [99.9%]) developed only low‐level viremia and the virus was successfully eliminated with interferon therapy. As observed in patients, telaprevir monotherapy in viremic mice resulted in breakthrough, with selection for mutations that confer resistance to telaprevir (e.g., a high frequency of V36A [52.2%]). Mice were injected intrahepatically with HCV genotype 1b clone KT‐9 with or without an introduced resistance mutation, A156S, in the NS3 region, and treated with telaprevir. Mice infected with the A156S strain developed lower‐level viremia compared to the wildtype strain but showed strong resistance to telaprevir treatment. Although mice injected with wildtype HCV showed a rapid decline in viremia at the beginning of therapy, a high frequency (11%) of telaprevir‐resistant NS3 V36A variants emerged 2 weeks after the start of treatment. Conclusion: Using deep sequencing technology and a genetically engineered HCV infection system, we showed that the rapid emergence of telaprevir‐resistant HCV was induced by mutation from the wildtype strain of HCV in vivo. (HEPATOLOGY 2011;).
Adjuvant therapy for pancreatic cancer

Pancreatic cancer is uniformly fatal unless it can be surgically resected. Survival rates for the 15% to 20% of patients who have resectable disease, however, are a disappointing 10% to 30%, depending on the status of margins and surrounding lymph nodes. In the mid‐1980s, a landmark study by the Gastrointestinal Tumor Study Group was the first to demonstrate a survival benefit from adjuvant therapy in the form of chemoradiation. Since then, several studies in both North America and Europe have tested the role of adjuvant chemotherapy or chemoradiation in pancreatic cancer, and the results have stirred great controversy. For this review, the evidence for adjuvant therapy in pancreatic cancer was examined, and the significant practice differences that exist between North American and European oncologists were highlighted. The authors investigated the results from the European Study Group for Pancreatic Cancer‐1 trial and the reasons why that study has served to reinforce rather than resolve these trans‐Atlantic differences. They also reviewed preliminary data from more recent adjuvant trials and explored the possible benefits of a neoadjuvant approach. Cancer 2008. © 2007 American Cancer Society.
Comparing neurocognition in severe chronic schizophrenia and frontotemporal dementia

Objective: Previous research has suggested cognitive similarities between schizophrenia and frontotemporal dementia. In the current study, we compared neurocognition in a group of hospitalised patients with chronic schizophrenia, who may have a more severe form of schizophrenia resembling Emil Kraepelin’s dementia praecox, with patients with frontotemporal dementia. We hypothesised minimal group differences in cognitive performance, and a large overlap in between-group score distributions in each cognitive domain. Methods: Retrospective neuropsychological data for 26 patients with severe chronic schizophrenia and 34 patients with frontotemporal dementia (behavioural variant) was collated. Neuropsychological measures were categorised into 16 cognitive domains. Raw scores were converted into standardised z-scores for each measure, which were then averaged across measures within each domain. In addition to difference analysis, equivalence testing was utilised, whereby overlap percentages were computed to reflect the amount of score distribution overlap in each domain between groups. Results: A statistically significant difference was observed only in the executive function sub-domain of Switching. Small-to-moderate and moderate effect sizes were noted in four other domains. Equivalence testing showed more than 85% of overlap in score distribution in most domains. Conclusions: Our findings suggest that some patients with severe chronic schizophrenia have cognitive deficits similar in degree and pattern to patients with frontotemporal dementia. The few differences observed between both groups of patients are important for differential diagnostic purposes. One limitation is the retrospective nature of the study. Suggestions for future research include longitudinal follow-up studies of these two patient populations and studies of aspects beyond neurocognition. An implication of our findings is that the ‘dementia of schizophrenia’ concept may be applicable to patients with severe chronic schizophrenia.
Guest Editorial: Two Proposals Regarding the Terminology of Thyroid Tumors

To THE EDITOR: We have been reviewing the pathological findings in several hundred cases of thyroid tumors from children and young adults exposed to fallout from the Chernobyl accident. We will be reporting our detailed findings in due course, but we would like to draw attention to some of the problems that have arisen in applying the WHO classification [1] to this material and to the solutions we have adopted. Diagnostic difficulties have mostly arisen in encapsulated tumors with a follicular architecture. There are two separate problems: deciding whether minor nuclear changes of the type seen in typical papillary carcinomas justify a diagnosis of follicular variant of papillary carcinoma (PTC-FV) and deciding whether minor degrees of capsular penetration justify a diagnosis of malignancy. There is no doubt that nuclear changes play a major role in the diagnosis of papillary carcinoma [2]. However, since the recognition of the follicular variant of papillary carcinoma [3] we believe that there has been a gradual extension of the category to include lesions with minor nuclear changes. Many pathologists will have faced this problem, and it has occurred on a number of occasions in the present study. We suggest that it is more appropriate to recognize this difficulty than to arbitrarily place well-differentiated encapsulated tumors with a follicular architecture where minor nuclear changes are the only indicator of a papillary carcinoma in a definite malignant or definite benign category. We refer to these tumors simply as well differentiated, without specifying either follicular or papillary, and use the terms welldifferentiated tumor of uncertain malignant potential (WDT-UMP) when there is no definite evidence of invasion, and well-differentiated carcinoma not otherwise specified (WDC-NOS) when invasion is present. The latter term has already been proposed in the Third Series AFIP Fascicle of Tumors of the Thyroid Gland [4]. The second problem applies to encapsulated tumors that lack any indication that they are papillary,
Reduction of snapshots for MIMO radar detection by block/group orthogonal matching pursuit

Multiple-input multiple-output (MIMO) radar works on the principle of transmission of independent waveforms at each element of its antenna array and is widely used for surveillance purposes. In this work, we investigate MIMO radar target localization problem with compressive sensing. Specifically, we try to solve the problem of estimation of target location in MIMO radar by group and block sparsity algorithms. It will lead us to a reduced number of snapshots required and also we can achieve better radar resolution. We will use group orthogonal matching pursuit (GOMP) and block orthogonal matching pursuit (BOMP) for our problem.
A narrative of UVM testbench environment for interconnection routers: A practical approach

In contrast to past projections using conventional bus-based interconnections, the use of Network on Chip (NoC) as an interconnection platform has become more promising to solve complex on-chip communication problems due to what it offers from scalability, reusability and efficiency. Moreover, providing a suitable test base to inspect and verify functionality of any IP core is a compulsory stage. To elaborate; Universal Verification Methodology (UVM) is introduced as a standardized and reusable methodology for verifying integrated circuit designs. In this paper, we present an architecture of a complete UVM environment to test generic routers through various test cases providing different scenarios to be applied. We also aim to establish a base on which other researchers can build to proceed towards finding better solutions.
Effects of prestorage application of propolis and storage time on eggshell microbial activity, hatchability, and chick performance in Japanese quail (Coturnix coturnix japonica) eggs.

Propolis, a resinous mixture produced by honeybees from substances collected from plants, has strong antibacterial and antifungal properties. The purpose of the current study was to establish the effects of prestorage application of propolis and storage time on eggshell microbial activity, egg weight loss, hatchability, and chick performance in quail hatching eggs. Treatments were compared in a 2 × 5 factorial design with 2 different storage times (7 and 14 d) and 5 prestorage applications (control, ethyl alcohol 70%, 5% propolis, 10% propolis, and 15% propolis solution). After application, the eggs were stored for 7 or 14 d at 13°C and 75 to 80% RH before incubation. Eggs sprayed with propolis had lower levels of total aerobic mesophilic bacteria, coliform, Salmonella spp. , Staphylococcus spp. , and mold yeasts than control eggs over the storage period and incubation period. Microbial activity in eggs stored for 7 d was significantly higher than in eggs stored for 14 d at the end of the storage. The lowest egg weight loss during storage was obtained in P15 treatment eggs stored for 7 d, whereas the highest egg weight loss was found in the treatment A after storage for 14 d. Although propolis treatment at 3 different doses was not effective on relative growth, only P15 decreased the BW at d 10, compared with the control. Hatchability in eggs stored for 14 d was significantly lower than in eggs stored for 7 d. No significant differences were observed for hatchability and embryonic mortality among propolis treatment groups. Propolis did not have a detrimental effect on hatchability, embryonic mortality, or BW gain. Our results indicate that propolis may be used to effectively reduce microbial activity on the surface of quail hatching eggs during storage and incubation without any detrimental effects on hatchability.
Managing Culture in the E-Workplace: The Practitioners' Perspectives. Innovative Session.

A group of human resource development (HRD) practitioners participated in an innovative session on managing culture in the e-workplace. The session objectives were as follows: (1) bring cultural patterns of the eworkplace to the forefront; (2) discuss the impact of culture on performance improvement in the e-workplace; and (3) share resources for stimulating change in the way people within e-organizations work. The participants, who worked in small groups of six HRD practitioners each, used Senge's Iceberg Model as a lens for viewing culture in their own organizations. They also engaged in reflection and dialogue about responses to the information technology (IT) challenges in their various organizations, resources for addressing the challenges more effectively, and needed research. The innovative session consisted of four phases as follows: (1) a brief introduction to the topic and the Iceberg Model; (2) application of the Iceberg Model to identify IT events and patterns of IT events and discover the commonalities among events and patterns of events across organizations; (3) replication of phase 2 but with a focus on systemic structures and mental models; and (4) an all-group discussion about insights gained from the first three phases and an overview of available resources and research on managing culture in the e-workplace. (Contains 29 references.) (MN) Reproductions supplied by EDRS are the best that can be made from the original document. U.S. DEPARTMENT OF EDUCATION Office of Educational Research and Improvement EDUCATIONAL RESOURCES INFORMATION CENTER (ERIC) eil. _This document has been reproduced as received from the person or organization originating it. Minor changes have been made to improve reproduction quality. Points of view or opinions stated in this document do not necessarily represent official OERI position or policy. PERMISSION TO REPRODUCE AND DISSEMINATE THIS MATERIAL HAS BEEN GRANTED BY TO THE EDUCATIONAL RESOURCES INFORMATION CENTER (ERIC) 2002 AHRD Conference Innovative Session 9
The complex relations between university, society and state: the Ethiopian predicament in establishing a service university

The Ethiopian predicament in establishing a service university is a function of several mismatches Between university, society and state: (a) Between society's mainly low-tech agricultural production and the university's production of academics; (b) Between the state's need for investment finances in new economic activities and the lack thereof, (c) Between the state and the university in terms of proper governance and how organisational changes in higher education should be made; and (d) different opinions Between state and university about the proper balance Between individual academic freedom, institutional autonomy and accountability to society and state. Turning mismatches into constructive national development suggests that the government should attract foreign capital for new production activities, under the specific condition that the foreigners should simultaneously invest a certain percentage in the country's higher education development. An important structural change would be to establish a dynamic and competent decision-making body at government level for science, technology and competence production. Donor countries and agencies ought to be encouraged to support Ethiopian development projects where research, tertiary-level training and business projects can work in an integrated fashion and where the Ethiopian `surplus' academic workforce power could be applied abroad.
Serum testosterone and corticosterone levels in acute experimental autoimmune encephalomyelitis (EAE) in male Wistar rats.

OBJECTIVES Experimental autoimmune encephalomyelitis (EAE) was induced to investigate the levels of circulating total testosterone (TT) and the possible association of corticosterone with the steroid-producing capacity of the testes. SETTING AND DESIGN We determined gonad weights, serum TT and corticosterone levels during the development of EAE in male rats. METHODS Active EAE was induced in young male Wistar rats by injection of whole myelin in complete Freund's adjuvant. All the rats were weighted and monitored daily for clinical signs and blooded during different phases of the disease. Serum TT was measured by radioimmunoassay and circulating corticosterone was determined using a competitive enzyme immunoassay. Also testes and seminal vesicles were removed to determine their weights. RESULTS Seminal vesicle weights and serum TT levels diminished during the acute stage of the disease in all EAE rats and then they began gradually to increase, reaching the normal values at the post-recovery phase. Concomitantly a significant increase in serum corticosterone levels was observed during the acute EAE and the post-recovery phase was accompanied by a decline in corticosterone levels. MAIN FINDING Our results indicated an inverse correlation between serum TT and corticosterone levels during the acute EAE. Moreover, the diminution of TT was not a consequence of an alteration of the testes induced by anti-myelin antibodies neither contributed by apoptosis of testis cells by exposure to corticosterone. CONCLUSIONS The negative correlation between corticosterone and TT levels associated to EAE may be relevant in understanding the association of the endocrine system and the development of autoimmune demyelinating diseases.
Evolutionary accounts of human behavioural diversity

Human beings persist in an extraordinary range of ecological settings, in the process exhibiting enormous behavioural diversity, both within and between populations. People vary in their social, mating and parental behaviour and have diverse and elaborate beliefs, traditions, norms and institutions. The aim of this theme issue is to ask whether, and how, evolutionary theory can help us to understand this diversity. In this introductory article, we provide a background to the debate surrounding how best to understand behavioural diversity using evolutionary models of human behaviour. In particular, we examine how diversity has been viewed by the main subdisciplines within the human evolutionary behavioural sciences, focusing in particular on the human behavioural ecology, evolutionary psychology and cultural evolution approaches. In addition to differences in focus and methodology, these subdisciplines have traditionally varied in the emphasis placed on human universals, ecological factors and socially learned behaviour, and on how they have addressed the issue of genetic variation. We reaffirm that evolutionary theory provides an essential framework for understanding behavioural diversity within and between human populations, but argue that greater integration between the subfields is critical to developing a satisfactory understanding of diversity.
A Novel Mechanism to Support Session Survivability in Heterogeneous MIPv6 Survivability in Heterogeneous MIPv6

In today's heterogeneous network environment a lot of research is focused on supporting multiple interfaces on a device. Mobility in IPv6 networks is supported by Mobile IPv6 (D. Johnson, et al., June 2004). Although MIPv6 and its extensions (G. Dommetry, et al., July 2001), (H. Soliman, et al., July 2001) tackle the problem of mobility in the Internet, they do not support session survivability across interface switch. Session continuity or survivability can be of paramount importance in many real-time applications. Here we present a novel scheme to ensure session continuity across the interface change in mobile multihomed environment. Our scheme is based on site multihoming with IPv6 intermediation (SHIM6). SHIM6 is a proposal presented in IETF by Multio working group. In SHIM6 locator switch is hidden from upper layer protocols (ULPs). Sessions between the communicating hosts continue unperturbed through the switch
On the Use of Historical Control Data for Trend Test in Carcinogenicity Studies

Summary. Historical control data are often available in carcinogenicity studies and are included for testing dose effects in current studies. A new method is developed for incorporating the historical control information into a dose effect test. The method generalizes the test procedures proposed by Tarone (1982, Biometrics38, 215–220) and Ibrahim and Ryan (1996, Biometrics52, 1478–1485) by taking into account the variation resulting from parameter estimation based on historical data. Two examples are discussed for illustrating the proposed method.
High Step-Up High-Efficiency Interleaved Converter With Voltage Multiplier Module for Renewable Energy System

A novel high step-up converter, which is suitable for renewable energy system, is proposed in this paper. Through a voltage multiplier module composed of switched capacitors and coupled inductors, a conventional interleaved boost converter obtains high step-up gain without operating at extreme duty ratio. The configuration of the proposed converter not only reduces the current stress but also constrains the input current ripple, which decreases the conduction losses and lengthens the lifetime of the input source. In addition, due to the lossless passive clamp performance, leakage energy is recycled to the output terminal. Hence, large voltage spikes across the main switches are alleviated, and the efficiency is improved. Even the low voltage stress makes the low-voltage-rated MOSFETs be adopted for reductions of conduction losses and cost. Finally, the prototype circuit with 40-V input voltage, 380-V output, and 1000-W output power is operated to verify its performance. The highest efficiency is 97.1%.
Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia

Infection with the human immunodefiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.
P2X4 Receptor-Dependent Ca2+ Influx in Model Human Monocytes and Macrophages

Monocytes and macrophages express a repertoire of cell surface P2 receptors for adenosine 5′-triphosphate (ATP) a damage-associated molecular pattern molecule (DAMP), which are capable of raising cytoplasmic calcium when activated. This is achieved either through direct permeation (ionotropic P2X receptors) or by mobilizing intracellular calcium stores (metabotropic P2Y receptors). Here, a side-by-side comparison to investigate the contribution of P2X4 receptor activation in ATP-evoked calcium responses in model human monocytes and macrophages was performed. The expression of P2X1, P2X4, P2X5 and P2X7 was confirmed by qRT-PCR and immunocytochemistry in both model monocyte and macrophage. ATP evoked a concentration-dependent increase in intracellular calcium in both THP-1 monocyte and macrophages. The sarco/endoplasmic reticulum Ca2+-ATPase inhibitor thasigargin (Tg) responses to the maximal ATP concentration (100 μM) in THP-1 monocytes, and responses in macrophage were significantly attenuated. Tg-resistant ATP-evoked calcium responses in the model macrophage were dependent on extracellular calcium, suggesting a requirement for calcium influx. Ivermectin (IVM) potentiated the magnitude of Tg-resistant component and slowed the decay of response in the model macrophage. The Tg-resistant component was attenuated by P2X4 antagonists 5-BDBD and PSB-12062 but not by the P2X1 antagonist Ro0437626 or the P2X7 antagonist A438079. shRNA-mediated P2X4 knockdown resulted in a significant reduction in Tg-resistant ATP-evoked calcium response as well as reduced sensitivities towards P2X4-specific pharmacological tools, IVM and PSB-12062. Inhibition of endocytosis with dynasore significantly reduced the magnitude of Tg-resistant component but substantially slowed decay response. Inhibition of calcium-dependent exocytosis with vacuolin-1 had no effect on the Tg-resistant component. These pharmacological data suggest that P2X4 receptor activation contributed significantly towards the ionotropic calcium response evoked by ATP of the model human macrophage.