Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV Quasispecies Dynamics during Pro-Active Treatment Switching: Impact on Multi-Drug Resistance and Resistance Archiving in Latent Reservoirs

The human immunodeficiency virus (HIV) can be suppressed by highly active anti-retroviral therapy (HAART) in the majority of infected patients. Nevertheless, treatment interruptions inevitably result in viral rebounds from persistent, latently infected cells, necessitating lifelong treatment. Virological failure due to resistance development is a frequent event and the major threat to treatment success. Currently, it is recommended to change treatment after the confirmation of virological failure. However, at the moment virological failure is detected, drug resistant mutants already replicate in great numbers. They infect numerous cells, many of which will turn into latently infected cells. This pool of cells represents an archive of resistance, which has the potential of limiting future treatment options. The objective of this study was to design a treatment strategy for treatment-naive patients that decreases the likelihood of early treatment failure and preserves future treatment options. We propose to apply a single, pro-active treatment switch, following a period of treatment with an induction regimen. The main goal of the induction regimen is to decrease the abundance of randomly generated mutants that confer resistance to the maintenance regimen, thereby increasing subsequent treatment success. Treatment is switched before the overgrowth and archiving of mutant strains that carry resistance against the induction regimen and would limit its future re-use. In silico modelling shows that an optimal trade-off is achieved by switching treatment at days after the initiation of antiviral therapy. Evaluation of the proposed treatment strategy demonstrated significant improvements in terms of resistance archiving and virological response, as compared to conventional HAART. While continuous pro-active treatment alternation improved the clinical outcome in a randomized trial, our results indicate that a similar improvement might also be reached after a single pro-active treatment switch. The clinical validity of this finding, however, remains to be shown by a corresponding trial.
Anti-Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival.

PURPOSE Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and small-cell lung cancer (SCLC). High titers of HuAb were initially reported in serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of these patients may grow more indolently. Based on these observations, we conducted a multicenter prospective study of SCLC patients without PEM/SN to determine the incidence and prognostic implications of HuAb. METHODS Serum samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb were determined by immunoblot of purified recombinant HuD antigen. RESULTS HuAb were detected in 32 (16%) of the 196 patients. Of the 170 patients who received treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy (55.6% v 19.6%; P < .001), and longer survival (14.9 v 10.2 months; P = .018). In a logistic regression analysis, HuAb status was an independent predictor of complete response induction. The probability of achieving a complete response was more than five times higher in HuAb-positive than in HuAb-negative patients (odds ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate analysis indicated that HuAb status was not independently associated with survival. CONCLUSION The presence of HuAb at diagnosis of SCLC is a strong and independent predictor of complete response to treatment. This feature accounts for the association between HuAb and longer survival.
Silicon Phthalocyanine Pc 4 and Red Light Causes Apoptosis in HIV‐infected Cells

The silicon phthalocyanine HOSiPcOSi(CH3)2(CH2)3 N(CH3)2 (Pc 4), is being studied as a photosensitizer for virus inactivation in red blood cell concentrates (RBCC). The RBCC spiked with cell-free human immunodeficiency virus (HIV) or with HIV actively replicating in the T-lymphocytic cell line CEM can be successfully inactivated (> or = 6 log10) when exposed to 2 microM Pc 4 and 90 J/cm2 red light (600-800 nm). Inactivation of > or = 6 log10 inducible HIV in the latently infected promonocytic cell line U1 occurred at 22.5 J/cm2 (H. Margolis-Nunno et al., Transfusion 36, 743-750, 1996). In order to understand the reason for the increased susceptibility of U1 to photosensitized inactivation we looked for induction of apoptosis by photodynamic treatment (PDT). Agarose gel electrophoresis was used to observe the appearance of a characteristic 180-200 base pair DNA ladder, which can indicate apoptosis. Using this assay it is shown that Pc 4 treatment induced apoptosis in U1 cells in a light dose-dependent manner, starting 30 min after light exposure. Using the ApopTag Plus kit (which attaches a fluorescent label to the 3'-OH ends of the degraded DNA) and flow cytometry, the percentage of cells undergoing apoptosis was quantitated. At 10.5 J/cm2, 3 h after light exposure, about 92.5% of the cells were apoptotic. Under these conditions 99% of the cells eventually die. The CEM cells similarly treated underwent apoptosis at slower kinetics and required higher light doses. Other cell lines latently infected with HIV (ACH-2 and OM 10.1) were as sensitive as U1 to HIV inactivation by Pc 4-PDT (H. Margolis-Nunno et al., Transfusion 36, 743-750, 1996) and underwent apoptosis at a similar kinetic. These results suggest that the enhanced inactivation of HIV in latently infected cells compared to CEM cells by Pc 4-PDT may be due, at least in part, to apoptosis in the former.
Influence of rifampicin on the expression and function of human intestinal cytochrome P450 enzymes.

AIMS To investigate the potential induction by rifampicin of intestinal CYP2C8, CYP2C9, CYP2D6 and CYP3A4 using preparations of human enterocytes. METHODS Using a multilumen perfusion catheter shed human enterocytes were collected from 6 healthy subjects before and after 10 days of 600 mg day(-1) oral rifampicin administration. The protein expression of CYP2C8, CYP2C9, CYP2D6 and CYP3A4 as well as that of CYP3A4 mRNA was determined using Western blotting and RT-PCR, respectively. RESULTS CYP3A4 mRNA expression in shed enterocytes increased from 74.6 +/- 44.2 to 143.2 +/- 68.4 a.u. (P < 0.05, 95% CI: 21.8-115.3). Expression of CYP2C8 and CYP2C9 increased from 5.1 +/- 0.9 to 10.4 +/- 2.3 pmol mg(-1) protein (P < 0.01, 95% CI: 2.8-7.7) and from 4.2 +/- 1.4 to 5.7 +/- 1.1 pmol mg(-1) protein (P < 0.01, 95% CI: 0.6-2.4), respectively. No significant difference in CYP2D6 expression before and during rifampicin intake was observed. Rifampicin administration also resulted in a significant induction of CYP3A4 protein (34.1 +/- 10.7 vs. 113.9 +/- 31.1 pmol mg(-1) protein (P < 0.001, 95% CI: 51.8-107.6)). Ex vivo incubation of enterocyte homogenates with verapamil resulted in a significantly increased production of the metabolites formed via CYP3A4 (D-617: 125.9 +/- 118.8 vs. 277.2 +/- 145.5 pmol min(-1) mg(-1) protein (P < 0.05, 95% CI: 30.1-272.5); norverapamil: 113.0 +/- 57.9 vs. 398.4 +/- 148.2 pmol min(-1) mg(-1) protein (P < 0.05, 95% CI: 47.2-523.6)). CONCLUSION Our findings indicate that shed enterocytes are a useful tool to study the expression, regulation and function of drug metabolizing enzymes. Induction of intestinal CYP2C8 and CYP2C9 might contribute in part to rifampicin - mediated drug interactions, in addition to their hepatic counterparts and intestinal and hepatic CYP3A4.
A System for the Automatic Classification of Ice Sheet Subsurface Targets in Radar Sounder Data

Exhaustive investigations of the ice sheet subsurface can be carried out by analyzing the information contained in the huge archives of radargrams acquired by dedicated radar sounder (RS) instruments. The analysis can be done by using properly designed automatic techniques for a quantitative, objective, and reliable extraction of information from radargrams. Unfortunately, the definition and development of such automatic techniques have only been marginally addressed in the literature. In this paper, we propose a novel and efficient system for the automatic classification of ice subsurface targets present in radargrams. The core of the system is represented by the extraction of a set of features for target discrimination. The features are based on both the specific statistical properties of the RS signal and the spatial distribution of the ice subsurface targets. Such features are then provided as input to an automatic classifier based on support vector machine. Experimental results obtained on two real-world data sets acquired by airborne-mounted RSs in large regions of Antarctica confirm the robustness and effectiveness of the proposed classification system.
Novopen Echo® for the Delivery of Insulin: A Comparison of Usability, Functionality and Preference among Pediatric Subjects, Their Parents, and Health Care Professionals

Background: Despite advances in insulin pen design and functionality, the selection of pens available for children with diabetes is limited. This study assessed the usability, functionality and attitudes towards NovoPen Echo®, a new durable insulin pen designed for pediatric patients that combines a simple memory function with half-increment dosing, versus NovoPen® Junior and HumaPen® Luxura® HD in pediatric subjects, their parents, and health care professionals (HCPs). Methods: Pens were evaluated in random order during 1:1 interviews in the three target groups (pediatric subjects, parents, and HCPs) in Germany, France, and Canada. Study participants were asked to prepare each pen, perform injections into foam cushions, and provide feedback via a standardized questionnaire. Results: In total, 205 participants were included in the study. On a scale of 1–6 (1 = most favorable; 6 = least favorable regarding overall appearance, shape, colors, thickness and length), NovoPen Echo received the most favorable rating for design and overall appearance (mean ± standard deviation = 1.71 ± 0.79) compared with NovoPen Junior (2.02 ± 0.93) and HumaPen Luxura HD (2.36 ± 1.01). Furthermore, 89% of pediatric subjects and 94% of parents rated the memory function of NovoPen Echo as very easy/easy to use. When asked to rate the pens overall, 80% of participants preferred NovoPen Echo to the other pens (p < 0.0001). Conclusions: The results demonstrate a high overall level of satisfaction with NovoPen Echo among pediatric subjects, parents, and HCPs. The novel design aspects of NovoPen Echo, namely t1468-he simple memory function, half-increment units and, ease of use and design, may contribute towards promoting treatment adherence, which is essential in the pediatric setting.
Independent Recognition of Staphylococcus aureus by Two Receptors for Phagocytosis in Drosophila*

Background: How multiple receptors for phagocytosis contribute to host immunity against bacterial infection has been elusive. Results: Drosophila phagocytes use two receptors, integrin and Draper, to effectively recognize and engulf Staphylococcus aureus. Conclusion: Dual recognition system exists in Drosophila for phagocytic removal of pathogenic bacteria. Significance: Study of cellular immune response is important for understanding host defense against infectious diseases. Integrin βν, one of two β subunits of Drosophila integrin, acts as a receptor in the phagocytosis of apoptotic cells. We here examined the involvement of this receptor in defense against infection by Staphylococcus aureus. Flies lacking integrin βν died earlier than control flies upon a septic but not oral infection with this bacterium. A loss of integrin βν reduced the phagocytosis of S. aureus and increased bacterial growth in flies. In contrast, the level of mRNA of an antimicrobial peptide produced upon infection was unchanged in integrin βν-lacking flies. The simultaneous loss of integrin βν and Draper, another receptor involved in the phagocytosis of S. aureus, brought about a further decrease in the level of phagocytosis and accelerated death of flies compared with the loss of either receptor alone. A strain of S. aureus lacking lipoteichoic acid, a cell wall component serving as a ligand for Draper, was susceptible to integrin βν-mediated phagocytosis. In contrast, a S. aureus mutant strain that produces small amounts of peptidoglycan was less efficiently phagocytosed by larval hemocytes, and a loss of integrin βν in hemocytes reduced a difference in the susceptibility to phagocytosis between parental and mutant strains. Furthermore, a series of experiments revealed the binding of integrin βν to peptidoglycan of S. aureus. Taken together, these results suggested that Draper and integrin βν cooperate in the phagocytic elimination of S. aureus by recognizing distinct cell wall components, and that this dual recognition system is necessary for the host organism to survive infection.
Precise analysis of head deformation at falling shock

Accurate evaluation of fall accidents is very important. We have done the experiment in JARI using human-type robot which simulates the human accidental injury. The precise data of acceleration has been taken from the robot. Using the acceleration data, the motion of the head center is derived. The speed and the position of the head center are determined under a realistic condition. The deformation of head surface is also calculated and was found that it is 1.0~1.2 mm in a natural falling. The solutions of a long interval of 324 ms are shown.
Determinants of Normal Coronary Artery Dimensions in Humans

BackgroundStudies of normal human coronary dimensions have been performed primarily in postmortem hearts. We evaluated the influence of age, body habitus, and regional myocardial mass on coronary dimensions in living patients with normal coronary vessels. Methods and ResultsArteriographically normal coronary angiograms were analyzed from the following groups of subjects: group 1 (age, 15–34 years) consisted of 30 post-cardiac transplant patients with donor hearts from male subjects aged 15–34 years, group 2 (age, 35–54 years) consisted of 12 post-cardiac transplant patients with donor hearts from male subjects aged 35–54 years and 26 male subjects investigated for atypical chest pain, and group 3 (age, 55–74 years) consisted of 26 male subjects investigated for atypical chest pain. All angiograms were performed after sublingual nitroglycerin. Measurements of the dimensions of the left main, proximal left anterior descending, proximal left circumflex, and proximal right coronary arteries were made using a computer-assisted edge-detection algorithm. The regional myocardial mass supplied by each vessel was derived from echocardiographically derived total left ventricular mass and a semiquantitative angiographic territory scoring system based primarily on the number and length of its terminal nutrient branches. ConclusionsLinear regression analysis showed that coronary vessel cross-sectional area and total coronary cross-sectional area increase with regional myocardial mass and decrease linearly with age. Multivariate regression analysis revealed that regional myocardial mass and age were independent predictors of cross-sectional area for each vessel and for the total coronary cross-sectional area. We speculate that age-related decline in physical activity, in part, may be responsible.
Global Media: Menace or Messiah?

GlobalMedia:Menace or Messiah? David Demers. Cresskill, NJ: Hampton Press, 1999. 209 pp. $45 hbk. $19.95 pbk. Media companies, their products, and their alleged anti-democratic or monopolistic practices have been criticized throughout the twentieth century but never as analytically as in the last twenty-five years--often by critics who spent many of their working years in those media industries. Particularly critical among recent Cassandras are Ben Bagdikian through several editions of his The Media Monopoly, Doug Underwood in When MBAs Rule the Newsroom, John McManus in MarketDriven journalism, James Squires in Read All About It, and more recently Robert McChesney in-among several examples-his Rich Media, Poor Democracy. David Demers, through his own studies of newspaper concentration in the United States and most helpfully through his 1996 book The Menace of Corporate Newspapers: Fact or Fiction? , has acted as a corrective to this criticism. In The Menace of Corporate Newspapers, Demers reviewed quantitative studies in an effort to test the validity of recent condemnations of newspaper industry concentration. He argued that at best the research evidence was mixed as to whether or not chain and corporate newspapers were serving the information needs of citizens poorly as many have charged in attacks based largely on anecdotal or partial evidence. In Global Media: Menace or Messiah? Demers expands on this subject in what reads as a direct response to recent critiques by McChesney and Edward Herman. As he argued in his earlier book on corporate newspapers, in Global Media, Demers claims the current pattern of media mergers and acquisitions by a dozen transnational media corporations (TMCs) and some of their only slightly smaller corporate cousins results less from conspiring monopolists than from the seemingly contradictory tendency of capitalism to methodically eliminate less efficient and usually smaller media entities. At work is the managerial revolution, an explanation which Demers developed more carefully in The Menace of Corporate Newspapers than he does in Global Media-a revolution whose economies of scale and control systems, according to Demers, provide better products and services to ever more media users worldwide. Demers acknowledges that media critics have a legitimate concern in fearing TMCs will spread Western values, weaken cultural diversity throughout the world, and reflect mainstream values. …
Conformational stability , spectroscopic ( FTIR , FT-Raman ) analysis , fukui function , Hirshfeld surface and docking analysis of Naphthalene-2-lyoxy acetic acid by density functional theory

The experimental and theoretical study on the structure and vibrations of Naphthalene-2lyoxy acetic acid (NLA) are presented. The FT-IR and FT-Raman spectra of the title compound have been recorded in the region 4000-0 cm -1 and 3500-100 cm -1 . The molecular structure, vibrational wave numbers infrared intensities and Raman intensities were calculated using DFT (B3LYP) method with LANL2DZ and LANL2MB basis sets. The conformational behavior of the molecule was also investigated. The vibrational wave numbers were calculated using DFT quantum chemical calculations. The data obtained from the wave number calculations are used to assign vibrational bands obtained through an experiment. The stability of the molecule arising from charge delocalization and hyper-conjugative interaction has been analyzed by NBO analysis. The HOMO and LUMO analysis were used to verify the charge transfer at intervals the molecule and quantum chemical parameters connected to the title compound. From the MEP analysis, it is clear that the ring and are possible sited for electrophilic attack and the positive regions are localized at all the hydrogen atoms as possible sites for nucleophilic attack. Fukui function and Mulliken analysis on atomic charges of the title compound have been discussed. The Hirshfeld surface analysis and fingerprint plots are reported the title molecule and reveal that the structures are stabilized intermolecular interactions. It is clear from the docking studies that NLA has inhibition capability toward the plant growth protein target 4Y31, 4PSB and 4QOK.
Altered T lymphocyte phenotype at birth in babies born to atopic parents

Flow cytometry was used to analyse the cord blood T cells of 33 babies at high risk ‘HR’ for developing allergy (born to at least one atopic, asthmatic parent), and 10 low risk ‘LR’ babies (born to non‐atopic parents), following normal term deliveries. Significantly lower numbers of CD25+, (activated) T cells (p<0.005) were seen in the cord blood of the HR babies who had developed both allergic symptoms and positive skin prick tests by one year of age when compared with the LR group. CD45RO+ (memory) T cells were detected in both HR and LR babies with a trend for lower numbers of memory cells to be detected in HR infants who later developed allergic symptoms and/or positive skin prick tests. Significantly lower numbers of CD4+/CD45RO+ were seen in the cord blood of HR babies who developed allergic symptoms compared to HR babies who showed no sign of allergy by one year and to the LR babies (p<0.05 and p<0.005). The presence of activated and memory T cells at birth implies intra‐uterine priming. The significantly lower numbers of memory T cells in the HR babies suggests a suppression of T cell activation or lack of antigenic priming in this group. This prenatal influence on babies born to atopic parents may have important implications with regard to the mechanisms underlying atopic sensitisation.
Millimeter‐wave emissivity as a metric for the non‐contact diagnosis of human skin conditions

A half‐space electromagnetic model of human skin over the band 30–300 GHz was constructed and used to model radiometric emissivity. The model showed that the radiometric emissivity rose from 0.4 to 0.8 over this band, with emission being localized to a layer approximately one millimeter deep in the skin. Simulations of skin with differing water contents associated with psoriasis, eczema, malignancy, and thermal burn wounds indicated radiometry could be used as a non‐contact technique to detect and monitor these conditions. The skin emissivity of a sample of 30 healthy volunteers, measured using a 95 GHz radiometer, was found to range from 0.2 to 0.7, and the experimental measurement uncertainty was ±0.002. Men on average were found to have an emissivity 0.046 higher than those of women, a measurement consistent with men having thicker skin than women. The regions of outer wrist and dorsal forearm, where skin is thicker, had emissivities 0.06–0.08 higher than the inner wrist and volar forearms where skin is generally thinner. Recommendations are made to develop a more sophisticated model of the skin and to collect larger data sets to obtain a deeper understanding of the signatures of human skin in the millimeter wave band. Bioelectromagnetics. 38:559–569, 2017. © 2017 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.