Miracle-dz/UniFAR-FTUs huggingface dataset:
Design of flexible GF(2/sup m/) elliptic curve cryptography processors

The design of flexible elliptic curve cryptography processors (ECP) is considered in this paper. Novel word-level algorithms and implementations for the underlying GF(2m) multiplication and squaring arithmetic which enable improved flexibility versus performance tradeoffs, are presented and employed in the design of an efficient flexible ECP architecture; corresponding field-programmable gate-array (FPGA) prototyping results for two different processor word lengths are also included for evaluation
Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication

ABSTRACT Viral inclusion bodies (IBs), or replication factories, are unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication, but little is known about the mechanism underlying IB formation and fusion. Our previous study demonstrated that the interaction between the nucleoprotein (N) and phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3), an enveloped virus with great medical impact, can form IBs. In this study, we found that small IBs can fuse with each other to form large IBs that enhance viral replication. Furthermore, we found that acetylated α-tubulin interacts with the N-P complex and colocalizes with IBs of HPIV3 but does not interact with the N-P complex of human respiratory syncytial virus or vesicular stomatitis virus and does not colocalize with IBs of human respiratory syncytial virus. Most importantly, enhancement of α-tubulin acetylation using the pharmacological inhibitor trichostatin A (TSA), RNA interference (RNAi) knockdown of the deacetylase enzymes histone deacetylase 6 (HDAC6) and sirtuin 2 (SIRT2), or expression of α-tubulin acetyltransferase 1 (α-TAT1) resulted in the fusion of small IBs into large IBs and effective viral replication. In contrast, suppression of acetylation of α-tubulin by overexpressing HDAC6 and SIRT2 profoundly inhibited the fusion of small IBs and viral replication. Our findings offer previously unidentified mechanistic insights into the regulation of viral IB fusion by acetylated α-tubulin, which is critical for viral replication. IMPORTANCE Inclusion bodies (IBs) are unique structures generated by viral proteins and some cellular proteins as a platform for efficient viral replication. Human parainfluenza virus type 3 (HPIV3) is a nonsegmented single-stranded RNA virus that mainly causes lower respiratory tract disease in infants and young children. However, no vaccines or antiviral drugs for HPIV3 are available. Therefore, understanding virus-host interactions and developing new antiviral strategies are increasingly important. Acetylation on lysine (K) 40 of α-tubulin is an evolutionarily conserved modification and plays an important role in many cellular processes, but its role in viral IB dynamics has not been fully explored. To our knowledge, our findings are the first to show that acetylated α-tubulin enhances viral replication by regulating HPIV3 IB fusion.
Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection

ABSTRACT HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1 infection with a longitudinal retrospective study design. Gag-specific T-cell responses were assessed by in vitro intracellular polycytokine production quantified by flow cytometry. Viral diversity determinations and sequence dating were performed in proviral DNA by PCR amplification at limiting dilution of env and gag genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity, and high proinflammatory cytokine levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r = −0.8; P = 0.02). RANTES was a potential biomarker of transient control. This study identified virological and immunological factors, including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in better clinical management of these individuals and in the development of future curative approaches. IMPORTANCE There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so-called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work, we found differences in virological and immune factors, including soluble inflammatory biomarkers, between subjects with persistent control of viral replication and EC that will lose virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose natural control of viral replication and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV infection.
The N-Terminal Region of IFITM3 Modulates Its Antiviral Activity by Regulating IFITM3 Cellular Localization

ABSTRACT Interferon-inducible transmembrane (IFITM) protein family members IFITM1, -2, and -3 restrict the infection of multiple enveloped viruses. Significant enrichment of a minor IFITM3 allele was recently reported for patients who were hospitalized for seasonal and 2009 H1N1 pandemic flu. This IFITM3 allele lacks the region corresponding to the first amino-terminal 21 amino acids and is unable to inhibit influenza A virus. In this study, we found that deleting this 21-amino-acid region relocates IFITM3 from the endosomal compartments to the cell periphery. This finding likely underlies the lost inhibition of influenza A virus that completes its entry exclusively within endosomes at low pH. Yet, wild-type IFITM3 and the mutant with the 21-amino-acid deletion inhibit HIV-1 replication equally well. Given the pH-independent nature of HIV-1 entry, our results suggest that IFITM3 can inhibit viruses that enter cells via different routes and that its N-terminal region is specifically required for controlling pH-dependent viruses.
Decreased eccentric muscle endurance in the conservatively treated anterior cruciate‐deficient knee

Concentric (CON) and eccentric (ECC) isokinetic knee extensor endurance, during 100 repetitive isokinetic contractions, were analysed in 32 consecutive patients with conservatively treated unilateral anterior cruciate ligament ruptured knees. There were 20 men and 12 women (mean age 34 years). The test was performed 6.8 years after the injury (range 4–14). The uninjured leg in each patient served as control. Lysholm subjective score, Tegner activity score and IKDC grading were used to relate the subjective knee function to muscle performance. Knee extensor endurance for concentric as well as for eccentric contractions were significantly lower in the injured side than the uninjured side. The magnitude of decrease in muscle performance was 7.6% for concentric (range‐12 to 27%) and 15.3% for eccentric (range ‐9 to 50%) endurance. The eccentric injured/uninjured endurance ratio correlated significantly to the Lysholm subjective score. We conclude that the knee extensor endurance is decreased in patients with conservatively treated anterior cruciate ligament‐ruptured knees. The eccentric endurance test seems to reflect the patients' subjective knee functioning.
Protective Effect of the Aqueous Leaf and Seed Extract of Phyllanthus amarus on Alcohol-Induced Hepatotoxicity in Rats

Various parts of Phyllanthus amarus (PA) Schum. and Thonn. (family: Euphorbiaceae) are associated with diverse phytotherapeutic properties including hepatoprotective functions. In the present study, of the aqueous leaf and seed extract of PA (50-300 mg/kg) was investigated for its hepatoprotective activities on ethanol-induced liver injured, non-hepatectomised adult male Wistar rats, for 7 days. Of the five (5) groups of rats each, four (4) groups had alcohol hepatotoxicity induced by repeated daily oral dosing with 5g/kg of 50% ethanol for 14 days. Three groups of treated rats were then orally administered 50-300 mg/kg/day of PA for additional 7days. Hepatotoxic enzyme markers consisting of serum transaminases (AST, ALT, ALP) and serum triglyceride (STG), were assayed for after blood samples were obtained by cardiac puncture under ether anesthesia. Oral treatment of rats with 5 g/kg b.w. /day of 50% ethanol for 14 days reliably established ethanol-induced hepatotoxicity as evidenced by significant (p Keywords : Phyllanthus amarus , protective activity, ethanol-induced hepatotoxicity West African Journal of Pharmacology and Drug Research Vol. 22/23 2007: pp. 42-50
Different Tempo and Anatomic Location of Dual-Tropic and X4 Virus Emergence in a Model of R5 Simian-Human Immunodeficiency Virus Infection

ABSTRACT We previously reported coreceptor switch in rhesus macaques inoculated intravenously with R5 simian-human immunodeficiency virus SF162P3N (SHIVSF162P3N). Whether R5-to-X4 virus evolution occurs in mucosally infected animals and in which anatomic site the switch occurs, however, were not addressed. We herein report a change in coreceptor preference in macaques infected intrarectally with SHIVSF162P3N. The switch occurred in infected animals with high levels of virus replication and undetectable antiviral antibody response and required sequence changes in the V3 loop of the gp120 envelope protein. X4 virus emergence was associated with an accelerated drop in peripheral CD4+ T-cell count but followed rather than preceded the onset of CD4+ T-cell loss. The conditions, genotypic requirements, and patterns of coreceptor switch in intrarectally infected animals were thus remarkably consistent with those found in macaques infected intravenously. They also overlapped with those reported for humans, suggestive of a common mechanism for coreceptor switch in the two hosts. Furthermore, two independent R5-to-X4 evolutionary pathways were identified in one infected animal, giving rise to dual-tropic and X4 viruses which differed in switch kinetics and tissue localization. The dual-tropic switch event predominated early, and the virus established infection in multiple tissues sites. In contrast, the switch to X4 virus occurred later, initiating and expanding mainly in peripheral lymph nodes. These findings help define R5 SHIVSF162P3N infection of rhesus macaques as a model to study the mechanistic basis, dynamics, and sites of HIV-1 coreceptor switch.
Isolated Pulmonary Recurrence After Resection of Colorectal Hepatic Metastases—Is Resection Indicated?

BACKGROUNDResection of colorectal hepatic metastases is an accepted treatment modality for stage IV colorectal cancer. Concurrent or sequential pulmonary metastasectomy continues to be a controversial strategy. We analyzed factors that predicted pulmonary recurrence in patients with resected hepatic metastases and examined the efficacy of these combined interventions in the treatment of metastatic colorectal cancer. METHODSA retrospective review of a database of patients who underwent resection of colorectal hepatic metastases was performed to identify patients who either had synchronous pulmonary metastases (defined as pulmonary recurrence at the time of or within 3 months of hepatic metastasectomy) or subsequently experienced pulmonary metastases. Patient demographics, operative interventions, and overall survival were analyzed. Statistical methods included unpaired Student's t-test, actuarial survival and log-rank analysis. RESULTSTwenty-one patients (19%) had pulmonary metastases after hepatic resection, of which 12/21(57%) underwent pulmonary resection. No differences were observed between the resection group, the nine patients with pulmonary metastases who did not undergo resection, and the 87 patients without pulmonary metastases with regard to age, sex, race, or extent of hepatic metastases. When comparing the resected versus the unresected pulmonary recurrences, the disease-free interval from hepatic resection to detection of pulmonary metastases was 21 ± 20 months (range, 3–72 months) versus 16 ± 8 months (range, 4–25 months), respectively. All patients with pulmonary recurrence who underwent pulmonary metastasectomy had unilateral disease. Seven of 12 (58%) underwent wedge/segmental resections, and the remaining five (42%) required lobectomy in order to obtain a complete resection. Four patients who underwent pulmonary resection had multiple lung metastases (two to four lesions), and eight had isolated metastasis. There were no perioperative deaths in the pulmonary metastasectomy group. Contraindications to pulmonary resection included extensive pulmonary disease and concurrent extrapulmonary disease. A survival benefit was noted at 3 years for the resected versus the unresected group (60% vs 31%). Survival was no different between the resected pulmonary recurrence patients and the resected hepatic metastases only patients (60% vs 54%). CONCLUSIONSPulmonary metastasectomy can be performed safely and effectively in patients with recurrent disease after hepatic resection for colorectal metastases. Prolonged survival can be achieved with resection of isolated pulmonary recurrence after hepatic resection for colorectal cancer. Further studies that delineate selection criteria for pulmonary resection of colorectal metastases are warranted.
A 3–10 GHz, 14 Bands CMOS Frequency Synthesizer With Spurs Reduction for MB-OFDM UWB System

This paper presents the design of a 14 bands CMOS frequency synthesizer with spurs reduction for MB-OFDM UWB system. Based on a single phase-locked loop and two-stage frequency mixing architecture, it alleviates harmonics mixing and frequency pulling to diminish spurs generation. Also, only divide-by-2 dividers are needed in the feedback path of the PLL. Thus more precise I/Q sub-harmonics can be derived for the SSB mixer in the 14 bands carrier generation. The image spurs are suppressed below -45 dBc and improved by more than 22 dB incorporating with I/Q calibration. Implemented in a 0.18-μm CMOS technology, this chip drains 65 mA from a single 1.8 V supply. The chip size is 2.5 by 2.2 mm2 providing 14 bands I/Q phases.
Identifying Challenging Job and Environmental Demands of Older Nurses Within the National Health Service

Objectives: To explore the existing theoretical contexts of the job and environmental demands of the nursing profession in the National Health Service (NHS) and to investigate how these job and environmental demands impact on the personal constructs of older nurses within the NHS. Background: Nursing is the single most widely practiced profession in the healthcare sector in the United Kingdom. However, nurses contend with challenging job and environmental demands on a daily basis, which deplete them of personal constructs (or resources) required to stay in the profession. Methods: A multilevel exploratory qualitative research design was employed. Ten managers were interviewed for the preliminary study, based on which the three characteristics of an age-friendly NHS workplace were established: health, retirement, and flexibility. Then an in-depth literature review revealed that the most adversely affected job within the NHS was the nursing profession. Finally, a focus group study was undertaken with six older nurses working in the NHS. Results: The most compelling finding of this study is that older nurses would generally not want to stay on the job if they had to work in the ward area. The physical, cognitive, and sensory constructs of older nurses are negatively affected by the job and environmental demands of the ward areas. Conclusions: Understanding how these job and environmental demands of the workplace affect an older nurse’s personal constructs may help support a better design of nurse work and the wards and help extend the working lives of older nurses in the NHS.
Low-Cost Self-Test Techniques for Small RAMs in SOCs Using Enhanced IEEE 1500 Test Wrappers

This paper proposes an enhanced IEEE 1500 test wrapper to support the testing and diagnosis of the single-port or multi-port RAM core attached to the enhanced IEEE 1500 test wrapper without incurring large area overhead to small memories. Effective test time reduction techniques for the proposed test scheme are also proposed. Simulation results show that the additional area cost for implementing the enhanced IEEE 1500 test wrapper is only about 0.58% for a 64 K-bit single-port RAM and only 0.57% for a 64 K-bit two-port RAM in 90-nm technology.
Does Space Matter? An Exploratory Study for a Child–Adolescent Mental Health Inpatient Unit

Objective: The aim of this study is to explore design elements and spaces as a contributing influence to behavior and well-being for patients, staff, and families in a child–adolescent mental health unit. Background: The University of Minnesota Masonic Children’s Hospital Child–Adolescent Mental Health Inpatient Unit embarked on a renovation project to relocate the hospital’s child and adolescent mental health units. Evidence-based strategies were employed for the design of the new unit to enhance the experience for patients, staff, and families and to support changes in operational and procedural strategies. Methods: A mixed-methods approach was utilized to explore the influence of several design strategies intended to induce calm feelings for patients, staff, and families. A comprehensive literature review informed the design process and study design. Methods include patient image surveys (PIS; n = 188), online staff surveys (n = 48), and face-to-face staff interviews (n = 25). Results: Several design elements and spaces were identified through the image survey as influential in eliciting feelings of calm among patients. Additionally, staff were also influenced by the new unit design, generating feelings of calm, safety, and pride in the work environment. Conclusion: Results suggest that design features in which patients have choice and control offer greater perceptions of calm during their stay in the unit. Staff were positively influenced by the colors and artwork throughout the unit as well as the upgraded security and safety features. Findings also show the space has a positive influence on families, demonstrated by its welcoming character and features that help to facilitate better interaction with patients.
Prime-Boost Immunization Strategies against Chikungunya Virus

ABSTRACT Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development and testing of novel DNA replicon and protein CHIKV vaccine candidates and evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous and heterologous prime-boost immunization strategies using novel and previously developed CHIKV vaccine candidates. Immunogenicity and efficacy were studied in a mouse model of CHIKV infection and showed that the DNA replicon and protein antigen were potent vaccine candidates, particularly when used for priming and boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral and cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine candidates and immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies and will form the basis for further preclinical and clinical evaluation of these vaccine candidates. IMPORTANCE As of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine candidates, a vaccine that could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully understand the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different candidates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine candidates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine.
Balance Ability in Acute Stage Rehabilitation Patients

: We measured center of gravity sway while standing still, maximum walking speed and the Berg Balance Scale (BBS) of acute stage stroke and early post-op. stage orthopedic patients, and examined their balance ability. The BBS total score was high for patients who did not require supervision while walking in the hospital, and they had a walking ability which was not at risk of falls. However, if the BBS scores for one-leg standing, turning around 360 degrees, tandem standing and looking behind over the shoulder were low, it was easy for the patients to lose their balance. Furthermore, compared to healthy elderly persons, the area covering the center of gravity sway in standing still, a parameter detailing postural control, was significantly higher, and maximum walking speed was significantly lower. From these results it cannot be said that the patients could maintain their balance or walk like healthy elderly people.
The Amino-Terminal Domain of Alphavirus Capsid Protein Is Dispensable for Viral Particle Assembly but Regulates RNA Encapsidation through Cooperative Functions of Its Subdomains

ABSTRACT Venezuelan equine encephalitis virus (VEEV) is a pathogenic alphavirus, which circulates in the Central, South, and North Americas, including the United States, and represents a significant public health threat. In recent years, strong progress has been made in understanding the structure of VEEV virions, but the mechanism of their formation has yet to be investigated. In this study, we analyzed the functions of different capsid-specific domains and its amino-terminal subdomains in viral particle formation. Our data demonstrate that VEEV particles can be efficiently formed directly at the plasma membrane without cytoplasmic nucleocapsid preassembly. The entire amino-terminal domain of VEEV capsid protein was found to be dispensable for particle formation. VEEV variants encoding only the capsid's protease domain efficiently produce genome-free VEEV virus-like particles (VLPs), which are very similar in structure to the wild-type virions. The amino-terminal domain of the VEEV capsid protein contains at least four structurally and functionally distinct subdomains, which mediate RNA packaging and the specificity of packaging in particular. The most positively charged subdomain is a negative regulator of the nucleocapsid assembly. The three other subdomains are not required for genome-free VLP formation but are important regulators of RNA packaging. Our data suggest that the positively charged surface of the VEEV capsid-specific protease domain and the very amino-terminal subdomain are also involved in interaction with viral RNA and play important roles in RNA encapsidation. Finally, we show that VEEV variants with mutated capsid acquire compensatory mutations in either capsid or nsP2 genes.