Miracle-dz/UniFAR-FTUs huggingface dataset:
R1626 plus peginterferon Alfa‐2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin

R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time‐dependent and dose‐dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with peginterferon alfa‐2a ± ribavirin in HCV genotype 1‐infected treatment‐naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + peginterferon alfa‐2a; n = 21); DUAL 3000 (3000 mg R1626 bid + peginterferon alfa‐2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + peginterferon alfa‐2a + ribavirin; n = 31); or standard of care (SOC) (peginterferon alfa‐2a + ribavirin; n = 20). At 4 weeks HCV RNA was undetectable (<15 IU/mL) in 29%, 69%, and 74% of patients in the DUAL 1500, DUAL 3000, and TRIPLE 1500 arms, respectively, compared with 5% of patients receiving SOC, with respective mean reductions in HCV RNA from baseline to week 4 of 3.6, 4.5, 5.2, and 2.4 log10 IU/mL. Synergy was observed between R1626 and peginterferon alfa‐2a and between R1626 and ribavirin. There was no evidence of development of viral resistance. Adverse events (AEs) were mainly mild or moderate; seven patients had nine serious AEs (including one patient with one serious AE in SOC). The incidence of Grade 4 neutropenia was 48%, 78%, 39%, and 10% in DUAL 1500, DUAL 3000, TRIPLE 1500, and SOC, respectively, and was the main reason for dose reductions. Conclusion: A synergistic antiviral effect was observed when R1626 was combined with peginterferon alfa‐2a ± ribavirin; up to 74% of patients had undetectable HCV RNA at week 4. Dosing of R1626 was limited by neutropenia; a study of different dosages of R1626 in combination with peginterferon alfa‐2a and ribavirin is underway. (HEPATOLOGY 2008.)
Laser Modulation of Heat and Capsaicin Receptor TRPV1 Leads to Thermal Antinociception

Er,Cr:YSGG lasers are used clinically in dentistry. The advantages of laser therapy include minimal thermal damage and the alleviation of pain. This study examined whether the Er,Cr:YSGG laser has in vivo and in vitro antinociceptive effects in itself. In capsaicin-evoked acute licking/shaking tests and Hargreaves tests, laser irradiation with an aerated water spray suppressed nociceptive behavior in mice. Laser irradiation attenuated TRPV1 activation by capsaicin in Ca2+ imaging experiments with TRPV1-overexpressing cells and cultured trigeminal neurons. Therefore, the laser-induced behavioral changes are probably due to the loss of TRPV1 activity. TRPV4 activity was also attenuated, but limited mechanical antinociception by the laser was observed. The laser failed to alter the other receptor functions, which indicates that the antinociceptive effect of the laser is dependent on TRPV1. These results suggest that the Er,Cr:YSGG laser has analgesic effects via TRPV1 inhibition. Such mechanistic approaches may help define the laser-sensitive pain modality and increase its beneficial uses.
Unprofessional or problematic behaviour of medical students outside the learning environment

This paper focuses on the question what to do with unprofessional or problematic behaviour of medical students outside the learning environment. Examples are given to raise awareness of the problem and initiate possible solutions. It is advised that medical schools keep an open eye for problematic behaviour outside the learning environment, also because documented unprofessional behaviour during medical training is a predictor of professional misconduct as a physician.
Wideband Single-Feed Circularly Polarized Antenna

In this paper, a novel wideband single-feed circularly polarized patch antenna is presented. The antenna consists of an L-shaped probe, four parasitic patches perpendicular to the probe, and a planar reflector. By modifying the structure of the patches, two orthogonal radiation modes are created to realize the circular polarization in the broadside direction. This antenna exhibits a wide impedance bandwidth of 82.4% from 2 GHz to 4.8 GHz for the voltage standing wave ratio (VSWR) ≤ 2a nd a 3-dB axial ratio (AR) bandwidth of 56.2% from 2.11 GHz to 3.77 GHz, over which the antenna gains vary from 5.7 dBic to 9.7 dBic. The measured results agree well with the simulated ones. In this paper, in order to enhance the bandwidth of the single-feed circularly polarized antenna, a novel patch antenna with parasitic elements is presented. This antenna is composed of an L-shaped probe and four parasitic patches located perpendicularly to the probe. By slicing pairs of rectangular and L-shaped slots on the patches, wide impedance bandwidth and 3-dB axial ratio bandwidth can be achieved. Experimentally, the proposed antenna delivers an impedance bandwidth of 82.4% and a 3-dB axial ratio bandwidth of 56.2%. Compared with the single-feed patch antennas in (3-7), this antenna has a much wider axial ratio bandwidth of 56.2%.
Work domain modelling for an operational headquarters

This paper presents an application of work domain analysis to a new joint operational headquarters of the Australian Defence Force. Work domain analysis provides a baseline for defining the problem space of operational-level command and control. This analytical framework focuses evaluation on how well the purposive context is satisfied so that, in this context, the design outcome is a usable and flexible headquarters, leading to improved efficiency and effectiveness of staff. The paper describes our attempt to analyse fundamental constraints of the work environment.
An 81-year-old man with imbalance and memory impairment

An 81-year-old man presented for evaluation of balance difficulties and nocturia. From January 1994 through February 1995, he developed progressive dizziness, which he described as a feeling of imbalance or unsteadiness when walking. This sensation occurred independently of changes in position and was not associated with true vertigo. His symptoms were identified shortly after he underwent knee surgery that was complicated by a gastrointestinal bleed requiring a blood transfusion. Over the year, his symptoms progressively worsened; he required a cane due to frequent falls and he lost interest in hunting, fishing, and reading. He developed increased rumination and anxiety with obsessive/compulsive behaviors that included the need to draw blinds, lock doors, or take out the trash immediately upon thinking of these actions. On a daily basis, he would sit at the window waiting for the mail to arrive and had to be the first one to retrieve and open it once it arrived. From March 1995 through February 1996, the patient’s wife noted he was becoming more forgetful and impatient. She took over the household finances by this time. Local evaluation included a head CT scan that by report demonstrated diffuse atrophy and he was diagnosed with Alzheimer disease (AD). A 4-week trial of tacrine hydrochloride was not beneficial. He continued to drive a motor vehicle and reported no traffic violations or motor vehicle accidents. His medical history was remarkable for atrial fibrillation, hypertension, and benign prostatic hyperplasia. His medications included fluoxetine, probenecid, and terazosin, the last of which was discontinued in March 1996. His social history was remarkable for moderate alcohol intake. He did not use tobacco. His family history was negative for gait, cognitive, or other neurologic disorders. Review of symptoms was remarkable for recent complaints of lightheadedness, which was non-positional, and nocturia (three times nightly). He denied …
Dyadic Green's functions in multilayered stratified gyroelectric chiral media

To characterize electromagnetic waves in complex media has been an important topic because of the useful applications and the scientific significance of the physical mechanism. Dyadic Green's functions, as a mathematical kernel or a dielectric medium response, relate directly the radiated electromagnetic fields and the source distribution. In terms of the vector wave functions in cylindrical coordinates, dyadic Green's functions in an unbounded and a planar, multilayered gyroelectric chiral media are formulated. After a general representation of the Green's dyadics is obtained, the scattering coefficients of the Green's dyadics are determined from the boundary conditions at each interface and are expressed in a greatly compact form of recurrence matrices. In the formulation of the Green's dyadics and their scattering coefficients, three cases are considered, i.e. the current source is impressed in (1) the first, (2) the intermediate, and (3) the last regions, respectively. Although the dyadic Green's functions for an unbounded gyroelectric chiral medium have been reported in the literature, the results are either incorrect or suspicious. As compared to the existing results, the current work basically contributes (1) a correct form of the dyadic Green's function for a unbounded gyroelectric chiral medium, (2) the general representation of the dyadic Green's functions for a multi-layered gyroelectric chiral medium, and (3) a convincing and direct derivation of the irrotational Green's dyadic.
DNA ligase I is recruited to sites of DNA replication by an interaction with proliferating cell nuclear antigen: identification of a common targeting mechanism for the assembly of replication factories

In mammalian cells, DNA replication occurs at discrete nuclear sites termed replication factories. Here we demonstrate that DNA ligase I and the large subunit of replication factor C (RF‐C p140) have a homologous sequence of ∼20 amino acids at their N‐termini that functions as a replication factory targeting sequence (RFTS). This motif consists of two boxes: box 1 contains the sequence IxxFF whereas box 2 is rich in positively charged residues. N‐terminal fragments of DNA ligase I and the RF‐C large subunit that contain the RFTS both interact with proliferating cell nuclear antigen (PCNA) in vitro. Moreover, the RFTS of DNA ligase I and of the RF‐C large subunit is necessary and sufficient for the interaction with PCNA. Both subnuclear targeting and PCNA binding by the DNA ligase I RFTS are abolished by replacement of the adjacent phenylalanine residues within box 1. Since sequences similar to the RFTS/PCNA‐binding motif have been identified in other DNA replication enzymes and in p21CIP1/WAF1, we propose that, in addition to functioning as a DNA polymerase processivity factor, PCNA plays a central role in the recruitment and stable association of DNA replication proteins at replication factories.
Survey and Analysis of Chaotic Image Encryption Schemes

Digital images play an important role in our daily lives and are used in many applications. Hence, there is a need to protect them from unauthorized access and modification. During the past years, several image encryption algorithms have been proposed. Image encryption techniques jumble the pixels of the plain image and reduce the association among the pixels, such that any adversary cannot modify the encrypted image. Chaotic encryption method seems to be much better day by day. The chaos based cryptographic algorithms are one of the emerging and efficient ways to develop secure image encryption techniques. Several schemes have been proposed and analyzed in the past decade based on chaotic maps. Chaotic maps require initial conditions to start iterations and usually initial conditions are derived using the external secret key by providing different weightage to all its bits. A comparative analysis and behavior of the chaotic image encryption schemes proposed in the past decade is presented in this paper such that further enhances in the field of image security can be explored.
Binary s-extremal self-dual codes of length 68 do exist 1

We study binary self-dual codes with an automorphism of order 7 and minimum distance 12 or 14 for lengths 64 ≤ n ≤ 70. A classification of all codes of length 9 over the set P of all even-weight polynomials in F2[x]/〈x − 1〉 such that the minimum distance of the binary projection is at least 12, is proven. Using one particular such code we have constructed six inequivalent s-extremal binary self-dual [68, 34, 12] codes the existence of which was not known before.
Peri‐operative warming devices: performance and clinical application

Since the adverse consequences of accidental peri‐operative hypothermia have been recognised, there has been a rapid expansion in the development of new warming equipment designed to prevent it. This is a review of peri‐operative warming devices and a critique of the evidence assessing their performance. Forced‐air warming is a common and extensively tested warming modality that outperforms passive insulation and water mattresses, and is at least as effective as resistive heating. More recently developed devices include circulating water garments, which have shown promising results due to their ability to cover large surface areas, and negative pressure devices aimed at improving subcutaneous perfusion for warming. We also discuss the challenge of fluid warming, looking particularly at how devices’ performance varies according to flow rate. Our ultimate aim is to provide a guide through the bewildering array of devices on the market so that clinicians can make informed and accurate choices for their particular hospital environment.
Linking integrin conformation to function

Integrins are αβ heterodimeric adhesion receptors that relay signals bidirectionally across the plasma membrane between the extracellular matrix and cell-surface ligands, and cytoskeletal and signalling effectors. The physical and chemical signals that are controlled by integrins are essential for intercellular communication and underpin all aspects of metazoan existence. To mediate such diverse functions, integrins exhibit structural diversity, flexibility and dynamism. Conformational changes, as opposed to surface expression or clustering, are central to the regulation of receptor function. In recent years, there has been intense interest in determining the three-dimensional structure of integrins, and analysing the shape changes that underpin the interconversion between functional states. Considering the central importance of the integrin signalling nexus, it is perhaps no surprise that obtaining this information has been difficult, and the answers gained so far have been complicated. In this Commentary, we pose some of the key remaining questions that surround integrin structure-function relationships and review the evidence that supports the current models.
Tomatoes, lysophosphatidic acid, and the small intestine: new pieces in the puzzle of apolipoprotein mimetic peptides?1

In this issue of the Journal of Lipid Research, M. Navab and colleagues describe their latest findings on the mechanism of action for apolipoprotein mimetic peptides. Besides having important implications in the design of future therapeutic peptides for the treatment of cardiovascular disease, this paper also adds to the growing evidence for the role of lysophosphatidic acid (LPA) in the pathogenesis of dyslipidemia and atherosclerosis (1).
Apolipoprotein E‐derived peptides reduce CNS inflammation: implications for therapy of neurological disease

The apolipoprotein E4 isoform (apoE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, and has also recently been associated with poor outcome after acute traumatic and ischemic brain injury. One mechanism by which apoE may influence outcome in acute and chronic neurological disease is by downregulating glial activation and the neuroinflammatory response. Because it does not readily cross the blood‐brain barrier (BBB), the apoE holoprotein has limited therapeutic potential. However, smaller peptides derived from the receptor binding region of apoE have been developed that mimic the functional anti‐inflammatory and neuroprotective effects of the intact apoE protein. These apoE‐derived therapeutic peptides cross the BBB and have been demonstrated to improve functional and histological outcomes in murine models of brain injury. Thus, the development of apoE‐derived peptides represent a novel therapeutic strategy for the treatment of acute and chronic neurological disease.
Childhood antecedents of personality disorder: An alternative perspective

Abstract One of the fundamental limitations of the Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition, Text Revision (DSM-IV-TR) categorical model of personality disorder classification has been the lack of a strong scientific foundation, including an understanding of childhood antecedents. The DSM-IV-TR personality disorders, however, do appear to be well understood as maladaptive variants of the domains and facets of the general personality structure as conceptualized within the five-factor model (FFM). Integrating the classification of personality disorder with the FFM brings to an understanding of the personality disorders a considerable body of scientific research on childhood antecedents. The temperaments and traits of childhood do appear to be antecedent to the FFM of adult personality structure, and these temperament and traits of childhood and adolescence are the likely antecedents for adult personality disorder, providing further support for the conceptualization of the adult personality disorders as maladaptive variants of the domains and facets of the FFM. Conceptualizing personality disorders in terms of the FFM thereby provides a basis for integrating the classification of abnormal and normal personality functioning across the life span.
Reductase inhibitor therapy of hypercholesterolemia.

Interest in identifying and treating patients with hypercholesterolemia has reached a high level of intensity and efforts in this area continue to expand. Epidemiologic studies demonstrate that cholesterol is a risk factor for CHD in women and in the elderly, suggesting that these unique populations may benefit from cholesterol reduction (1, 2, 3). There now is little doubt that cholesterol reduction prevents, slows and even causes regression of CHD in men (4, 5, 6, 7, 8). Diet is the cornerstone of therapy; however, the use of hypolipidemic drugs is justified by the absolute level of hypercholesterolemia and/or the presence of other factors that place patients at risk. The need for an effective and welltolerated pharmacologic hypolipidemic agent was recently met by the development and FDA approval of lovastatin, a new type of drug, that inhibits the rate limiting enzyme of cholesterol synthesis. These drugs are now known as reductase inhibitors (RI). Despite uncertainty about long term or delayed adverse side effects, lovastatin accounted for 29.7% of all prescriptions of cholesterol-lowering medications in the 12 months following its release and was the most frequently prescribed hypolipidemic agent (Figure 1) (9).
Deceptive vocal duets and multimodal display in a songbird

Many group-living animals cooperatively signal to defend resources, but what stops deceptive signalling to competitors about coalition strength? Cooperative-signalling species include mated pairs of birds that sing duets to defend their territory. Individuals of these species sometimes sing ‘pseudo-duets’ by mimicking their partner's contribution, but it is unknown if these songs are deceptive, or why duets are normally reliable. We studied pseudo-duets in Australian magpie-larks, Grallina cyanoleuca, and tested whether multimodal signalling constrains deception. Magpie-larks give antiphonal duets coordinated with a visual display, with each sex typically choosing a different song type within the duet. Individuals produced pseudo-duets almost exclusively during nesting when partners were apart, but the two song types were used in sequence rather than antiphonally. Strikingly, birds hid and gave no visual displays, implying deceptive suppression of information. Acoustic playbacks showed that pseudo-duets provoked the same response from residents as true duets, regardless of whether they were sequential or antiphonal, and stronger response than that to true duets consisting of a single song type. By contrast, experiments with robot models showed that songs accompanied by movements of two birds prompted stronger responses than songs accompanied by movements of one bird, irrespective of the number of song types or singers. We conclude that magpie-larks used deceptive pseudo-duets when partners were apart, and suppressed the visual display to maintain the subterfuge. We suggest that the visual component of many species' duets provides the most reliable information about the number of signallers and may have evolved to maintain honesty in duet communication.
Phosphatidylinositol 3,4,5‐trisphosphate is a substrate for the 75 kDa inositol polyphosphate 5‐phosphatase and a novel 5‐phosphatase which forms a complex with the p85/p110 form of phosphoinositide 3‐kinase.

Agonist‐stimulated production of phosphatidylinositol 3,4,5‐trisphosphate [PtdIns(3,4,5)P3], is considered the primary output signal of activated phosphoinositide (PI) 3‐kinase. The physiological targets of this novel phospholipid and the identity of enzymes involved in its metabolism have not yet been established. We report here the identification of two enzymes which hydrolyze the 5‐position phosphate of PtdIns(3,4,5)P3, forming phosphatidylinositol (3,4)‐bisphosphate. One of these enzymes is the 75 kDa inositol polyphosphate 5‐phosphatase (75 kDa 5‐phosphatase), which has previously been demonstrated to metabolize inositol 1,4,5‐trisphosphate [Ins(1,4,5)P3], inositol 1,3,4,5‐tetrakisphosphate [Ins(1,3,4,5)P4] and phosphatidylinositol 4,5‐bisphosphate [PtdIns(4,5)P2]. We have identified a second PtdIns(3,4,5)P3 5‐phosphatase in the cytosolic fraction of platelets, which forms a complex with the p85/p110 form of PI 3‐kinase. This enzyme is immunologically and chromatographically distinct from the platelet 43 kDa and 75 kDa 5‐phosphatases and is unique in that it removes the 5‐position phosphate from PtdIns(3,4,5)P3, but does not metabolize PtdIns(4,5)P2, Ins(1,4,5)P3 or Ins(1,3,4,5)P4. These studies demonstrate the existence of multiple PtdIns(3,4,5)P3 5‐phosphatases within the cell.
Single linkage region growing algorithms based on the vector degree of match

The class of the single linkage region growing (SLRG) algorithms, in which pairs of neighboring pixels are compared for merging, is one of the conceptually simplest approaches to image segmentation. A new normalized coefficient, which measures the degree of match between two multivalued vectors, termed the vector degree of match (VDM), provides the SLRG applications with the metric needed to group adjacent pixel pairs. Two new SLRG algorithms, applied to multiband images and exploiting the VDM criterion, are presented. Their major advantage, in comparison with the SLRG implementations found in the literature, is that they required only one user-defined parameter, the VDM Threshold (VDMT), which is a normalized value featuring local adaptivity and having an intuitive physical meaning. The use of an SLRG module is convenient as the first stage of a structured segmentation procedure featuring the following functional properties: (i) it is implemented sequentially; (ii) it combines single linkage, centroid linkage and hybrid linkage criteria; and (iii) its goal is the detection of image areas characterized by low contrast.