Miracle-dz/UniFAR-FTUs huggingface dataset:
Absence of Resistance Mutations in Antiretroviral-Naive Patients Treated with Ritonavir-Boosted Saquinavir

Background There are few data on the selection of resistance by ritonavir-boosted saquinavir (SQV/r), particularly in antiretroviral (ARV)-naive patients. Objective To assess the incidence of virological failure and evolution of resistance in ARV-naive individuals receiving SQV/r in the induction phase of the Staccato trial. Methods ARV-naive subjects (n=272) received SQV/r 1,600/100 mg once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) for at least 24 weeks. Patients were defined as having virological failure (VF) when there were two consecutive HIV-1 RNA measurements >500 copies/ml after week 12. Viral genotypes (reverse transcriptase [RT] and protease [PRO]) were determined at baseline in all patients and as close as possible to the time of initial failure in patients experiencing VF. Results VF was observed in 9/272 patients receiving SQV/r 1,600/100 mg once daily with two NRTIs (3.3%) and occurred 19–48 weeks after treatment initiation. Eight of these patients were evaluable at failure. No major PRO mutations were detected, but 2/8 displayed single new minor PRO substitutions (M36I, L10I) at VF that were known or suspected not to have been present at baseline; both these substitutions exist as natural polymorphisms. A third patient displayed a single new RT mutation (M184I). Conclusions SQV/r plus two NRTIs (1,600/100 mg once daily) is an effective initial treatment option for ARV-naive patients, resulting in a low rate of viral rebound (3.3%). Furthermore, no major protease mutations were detected following VF, suggesting that future treatment options are preserved.
Noise Attenuation for Seismic Data by Hyperbolic-Trace Time-Frequency Peak Filtering

Time-frequency peak filtering (TFPF) is a method commonly used for seismic random noise attenuation due to its excellent practical application. However, a conventional TFPF often produces significant deviations at the peak or valley of the signal where the linearity is poor. Here, we propose a novel hyperbolic-trace TFPF (HT-TFPF) approach to reduce these deviations and recover the effective signal more completely. In this method, a hyperbolic trace with a certain curvature is ascertained by fitting the reflection event to scan the seismic record. Data sequences are extracted from the seismic record along these hyperbolic traces, and their linearity is greatly improved. Then, they are taken as a new input for TFPF. HT-TFPF can preserve the signal amplitude while achieving an excellent performance of noise suppression with a long unbias window length. Tests on both synthetic records and common shot point data indicate that the HT-TFPF method can attenuate more random noise and recover events more clearly and continuously than the conventional TFPF.
Do Voters Discount Political Scandals over Time?

This paper explores how political scandals are discounted over time. Previous research has shown that voters respond disproportionately to recent economic conditions when evaluating incumbents. We argue that voters discount not only the performance of incumbents in office but also information about their personal character, largely due to accessibility biases. Building on a comprehensive database of congressional scandals covering the last four decades, we show that the electoral consequences of political scandals fade fairly quickly. Only cases emerging in the election-year systematically affect the vote share of incumbents. Moral scandals are the exception, with negative effects persisting over the entire term. In line with the mechanism proposed, additional analyses suggest this pattern results from disproportional levels of media attention, making moral scandals more easily retrieved from memory. The results broaden our understanding of the nature of myopic voting and provide an explanation for the increasing reliance on negative campaigning.
A Compact First-Order $\Sigma\Delta $ Modulator for Analog High-Volume Testing of Complex System-on-Chips in a 14 nm Tri-Gate Digital CMOS Process

On complex system-on-chips (SOCs), a compact on-die analog-to-digital converter (ADC) is required in high-volume testing, in order to reduce the test time and improve the test coverage of on-die analog intellectual properties (IPs). This paper presents a compact first-order ΣΔ modulator for on-die voltage measurements in such applications. The primary design focus is to achieve a highly compact area so that many instances can be integrated to cover the testing of multiple analog IPs on a single chip die. The proposed modulator deploys an inverter-based architecture which enables the aggressive area reduction. There are two new additional enhancements: 1) hardware dithering to minimize the limit-cycling effect and 2) time-multiplexed pseudodifferential operation for common mode rejection. The modulator exhibits a figure of merit (FOM) of 554.7 fJ/conv-step, in spite of the compact area of only 0.00023 mm2.
Effects of signal-to-noise ratio, signal periodicity, and degree of hearing impairment on the performance of voice-separation algorithms.

Procedures for enhancing the intelligibility of a target talker in the presence of a co-channel competing talker were evaluated in tests involving (i) continuously voiced sentences spoken on a monotone, (ii) continuously voiced sentences with time-varying intonation, and (iii) noncontinuously voiced sentences produced with natural intonation. The procedures were based on the methods of harmonic selection and cepstral filtering [R.J. Stubbs and Q. Summerfield, J. Acoust. Soc. Am. 87, 359-372 (1990)]. Target and competing voices were combined at signal-to-noise ratios (SNRs) between -10 dB and +10 dB. Subjects were a group with normal hearing and a heterogeneous group with mild-moderate cochlear hearing impairments. Processing enhanced the target voice over a range of SNRs for each type of sentence and for most listeners. Enhancement was greatest at negative SNRs. Among the impaired listeners, benefit was generally greater for those with milder losses. These results consolidate and extend previous demonstrations that voice-separation algorithms that exploit the harmonic structure of the voiced portions of speech can enhance intelligibility. However, practical application of such algorithms depends on a solution to the problem of tracking the fundamental-frequency contour of one voice in the presence of a competing voice.
In vivo expression of proinflammatory cytokines in HIV encephalitis: an analysis of 11 autopsy cases

As the pathogenesis of AIDS dementia complex (ADC), cytokines such as TNF‐α and IL‐1β have been thought to have toxic effects on CNS cells and induce neuronal cell death. However, many of the discussions have been based on the studies done by in vitro experiments. There are only a few reports which demonstrate proinflammatory cytokines directly in vivo in HIV encephalitis (HIVE) brains, and roles of these cytokines with relation to HIV‐1 infection are not yet clarified. In the present study, we examined 11 autopsy cases of HIVE using immunohistochemistry, and explored which cell types expressed these cytokines and whether expression of cytokines was related to viral infection. IL‐1β was detected in the frontal white matter of all 11 cases where microglial nodules were observed to varying degrees, whereas TNF‐α was detected in seven cases. IL‐1β− or TNF‐α‐positive cells were almost restricted to CD68‐positive macrophages/microglia and mild expression of these cytokines by astrocytes was observed in two cases with severe HIVE. IL‐1β was detected in some HIVp24‐positive multinucleated giant cells. However, we could not detect TNF‐α expression in the HIVp24‐positive cells, which indicates that IL‐1β is induced by HIV‐1 infection. In conclusion, a macrophage/microglia lineage is the main cell type to release cytokines in HIVE, and IL‐1β expression by HIV‐1‐infected cells may be one of the important factors for induction of HIVE. In addition, many non‐infected macrophages/microglia as well as some astrocytes express IL‐1β and TNF‐α, which might contribute to pathogenesis of ADC.
Effect of salts on the structural behavior of hPrP α2‐helix‐derived analogues: the counterion perspective

Both theoretical studies and direct experimental evidence have emphasized the importance of electrostatic interactions in the general phenomenon of spontaneous amyloid fibril formation. A number of observations have recently spurred interest in the contribution of these interactions to the conformational behavior of the prion protein. In this paper, we show how salt addition and pH change can modify the conformation of two peptide analogues derived from the human prion protein helix 2 according to a Hofmeister‐series‐type dependence. Employment of various sodium salts allowed us to highlight the fact that chaotropic anions favor unstructured conformation, whereas kosmotropic anions promote the formation of compact structures like α‐helix and β‐sheet, which may ultimately facilitate fibril formation. This finding should warn people engaged in ion‐based research on prion and derived peptides about cation‐bound effects, which have been almost exclusively investigated to date, being easily confounded with modifications that are actually caused by anion activity, thus leading researchers into misunderstand ion‐specific effects. To avoid the common complication of ion confounding, it is highly desirable that experiments be designed so that the species causing the modification can be unequivocally perceived. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.
Need for a paradigm shift in cancer prevention and clinical oncology

Every year approximately 3 million Europeans develop a cancer. Of these patients, 20–25% will suffer from cancer of the hepatogastrointestinal tract (the largest cancer group) and most of these individuals will die from the disease. Recent analysis from the American Cancer Society indicates that disease-related mortality from heart, cerebrovascular and infectious disease has decreased dramatically in the last 60 years, whereas the mortality of cancer remains unchanged. Despite recent improvements in the understanding of the biology, development and progression of human cancers, and the development of novel diagnostic and therapeutic approaches, most cancer patients are diagnosed in an advanced stage with a limited chance of cure. We hypothesize that there has been a dramatic shift in the treatment and, more importantly, prevention of heart, cerebrovascular and infectious diseases that has not yet reached oncology practice. We think that the shift from local to systemic therapy in combination with biomarker-guided detection of patients at risk leads to a reversion of current medical management: we do not treat the end-stage disease but rather follow the course of cancer development starting with risk assessment, followed by disease treatment and prevention of disease progression. Thus, we can prevent end-stage disease that cannot be treated curatively. Our two-step hypothesis should lead to a dramatic improvement of the prognosis of cancer patients.
Leptin directly acts within the hypothalamus to stimulate gonadotropin‐releasing hormone secretion in vivo in rats

It is still not known whether leptin, an adipocyte‐derived hormone, acts directly within the hypothalamus to stimulate the gonadotropin‐releasing hormone (GnRH)‐luteinizing hormone (LH) system. In order to address this question, the present study examined the effects of direct intrahypothalamic perfusions with leptin on the in vivo release of GnRH in ovarian steroid‐primed ovariectomized rats utilizing the push‐pull perfusion technique. Both α‐melanocyte‐stimulating hormone (α‐MSH) and neuropeptide Y were also measured in the hypothalamic perfusates. In normally fed animals, the leptin infusion was without effect on the release of these three hypothalamic peptides and also without effect on plasma LH and prolactin (PRL), whether leptin was infused into the medial preoptic area (where the majority of GnRH neuronal cell bodies exist) or the median eminence‐arcuate nucleus complex (where axon terminals of GnRH neurons are located). In contrast, in 3‐day fasted rats leptin was effective in stimulating the secretion of GnRH, α‐MSH, and LH, regardless of the site of perfusion. These three hormones were increased in a temporal order of α‐MSH, GnRH and LH. Irrespective of the site of perfusion, leptin was without effect on the release of neuropeptide Y. Only when leptin was infused into the median eminence‐arcuate nucleus complex was PRL secretion also stimulated, although its onset was 1 h behind that of LH. The leptin‐induced elevations of GnRH, α‐MSH, LH and PRL were all dose‐dependently stimulated by subnormal (1.0 ng ml−1) and normal (3.0 ng ml−1) concentrations of leptin, but at higher concentrations (10 ng ml−1) it did not produce additional effects. Leptin infusion into the anterior hypothalamic area, a control site equidistant from both the medial preoptic area and the median eminence‐arcuate nucleus complex, did not produce a significant change in any of the hormones in either the fed or fasted rats. These results demonstrate for the first time that leptin can act at both the cell bodies and axon terminals of GnRH neurons to stimulate the release of the neurohormone in vivo, and they also suggest that α‐MSH may play a significant intermediary role in linking leptin and GnRH secretion.
The Sojourner's Return: Risks and Challenges of the Study Abroad Experience on Re-Entry

Thousands of students are participating in study abroad programs, which is a major decision that could alter the life of a student and shape his/her future. It is important, therefore, to carefully weigh the options that come with being an international student. This chapter explores the history of study abroad, students’ study abroad experiences, and the benefits of these programs. Study abroad benefits include personal growth, intercultural development, and career attainment. Educators consistently assert that a significant part of the studying abroad experience is training future global leaders to be more effective and efficient, respecting the diversities of people and cultures, including political and economic systems, and the willingness to take a stand for the world’s welfare. Following this, the re-entry experiences of students who return to their home countries at the end of their studies are examined with respect to the physical, social, and psychological risks that student returnees are faced with. The Sojourner’s Return: Risks and Challenges of the Study Abroad Experience on Re-Entry
Potency, continence and complications in 3,477 consecutive radical retropubic prostatectomies.

PURPOSE We report results in a series of 3,477 consecutive patients treated with anatomical nerve sparing radical retropubic prostatectomy (RRP) in terms of recovery of erectile function, urinary continence and postoperative complications. MATERIALS AND METHODS From May 1983 through February 2003, 1 surgeon (WJC) performed anatomical RRP using a unilateral or bilateral nerve sparing modification when possible. Urinary continence and recovery of erections were evaluated in men with a minimum followup of 18 months. Excluded from potency analysis were men who were not reliably potent before surgery, those who did not undergo a nerve sparing procedure and those who received postoperative adjuvant radiotherapy or hormonal therapy within 18 months of surgery. Other postoperative complications in this patient population were also evaluated. RESULTS Erections sufficient for intercourse occurred in 76% of preoperatively potent men treated with bilateral (1,770) and 53% of men treated with unilateral or partial nerve sparing (64) surgery. Adequate erectile function was more common following bilateral than unilateral nerve sparing surgery in men younger than 70 years old (78% versus 53%, p = 0.001) compared with those 70 years old or older (52% versus 56%, p = 0.6). Recovery of urinary continence occurred in 93% of all men and was associated with younger age (p = 0.001) but not nerve sparing surgery, tumor stage, prostate specific antigen (PSA), Gleason grade or number of prior prostatectomies performed by the surgeon. Postoperative complications occurred in 320 (9%) of patients and were associated with older age (p <0.0001), nonnerve sparing surgery (p = 0.001), PSA era (p <0.0001) and surgeon experience. Complications were not significantly correlated with clinical stage, pathological stage, preoperative PSA or Gleason grade. There was no perioperative mortality. CONCLUSIONS Nerve sparing RRP can be performed with favorable potency and urinary continence. Better results are achieved in younger men. Other complications are reduced with increasing surgeon experience.
An optimum mapping of IPs for On-Chip Network design based on the minimum latency constraint

A new chip design paradigm, so called network on chip, has been introducing based on the demand of integration of many heterogeneous semiconductor intellectual property (IP) blocks. The network on chip design not only requires the good performance but also the minimization of several physical constraints such that the network latency, the used area as well as the power consumption of design. This paper analyzes the average latency of heterogeneous network on chip architectures in which the shortest path routing algorithm is applied. This average latency includes the queuing latency and the wire latency, and is calculated for general cases of allocating IPs onto a fixed generic switching architecture as 2-D mesh. With different allocation schemes of IPs, the network has different average latencies. Hence, this article presents an optimal search that adopts the Branch and Bound algorithm to find out the optimal mapping scheme to achieve the minimal network latency. This algorithm automatically map the desired IPs onto the target network on chip architecture with the criteria of lowest network latency. The optimal latency, as our research target, allows us to achieve the design with low power consumption as well. We also carry out the experiment for on chip multiprocessor network application. The results shows that 36.5% and 40.3% of network latency are saved with the optimized allocation scheme for the cases of 3 x 3 and 4 x 4 Mesh architectures of on chip multiprocessor network application, respectively.
Chondrosarcoma of the Skull Base: Long-Term Follow-Up

Objective: Chondrosarcoma of the skull base is an uncommon neoplasm comprising 0.15% of all intracranial tumors and 6% of skull base neoplasms. The outcome of treatment is difficult to assess because the slow growth rate means that there is a long interval before detecting the recurrence. We describe the use of lateral skull base techniques for these lesions and examine the long-term outcomes. The pathological features, radiological findings, and radiotherapy options are also discussed. Study Design: Retrospective case review with current follow-up where possible. Setting: Tertiary referral neurotologic private practice. Patients: Eight patients with histologically confirmed skull base chondrosarcoma operated on since 1979. At the time of the surgery, the five women and three men ranged in age from 31 to 63 years, with a mean of 42.9 years. The follow-up ranged from 9 months to 25 years and 5 months. Interventions: All patients underwent surgical removal; the earliest patient underwent surgical removal via transcochlear and retrosigmoid approaches, and seven via an infratemporal fossa approach, with or without exenteration of the otic capsule. Main Outcome Measures: Number of patients with residual and recurrent tumors. Results: In the patient who underwent surgery via the transcochlear approach, recurrence was noted within 3 months, and new exploration using the retrosigmoid approach was performed for the removal of the recurrent lesion. This patient showed no signs of recurrence for 25 years since last surgery. Of the seven patients who underwent surgery via the infratemporal fossa approach, one had residual tumor found at 1 year, but remained alive and well for 21 years after the surgery. The other six had gross total resection and showed no signs of recurrence at the last known follow-up. One patient died as a result of an unrelated cause 18 years after surgery for the chondrosarcoma. Conclusion: The gross total resection of these lesions is possible because of the evolution of lateral skull base techniques and can be routinely accomplished with the infratemporal fossa approach. The improved exposure afforded by this approach seems to have resulted in more complete extirpation of the tumor and a decrease in the recurrence rate.
Power Shifts Via the Judicial Arena: How Annulments Cases between EU Institutions Shape Competence Allocation

Besides infringement and preliminary ruling procedures, actions for annulment form a third important category of procedures brought before the Court of Justice of the European Union (CJEU). A subset of these actions is ‘horizontal litigation’, where EU institutions litigate against other EU institutions. Based on a new dataset covering all horizontal annulment conflicts (1957–2017), this contribution analyzes conflict patterns. I identify the most typical litigant constellations and link them to substantial battles over competences including winners and losers. Using the example of EU external affairs, I show how annulment actions have shaped the relationship between EU institutions over time, with impact as significant as treaty changes. In sum, the analysis of this so far ‘forgotten’ type of procedure furthers our systematic understanding of policy development and competence allocation in the EU system.
Quality of life and functional disability in patients with interstitial lung disease related to Systemic Sclerosis.

BACKGROUND Systemic Sclerosis (SSc) is a connective disease impairing respiratory function. SSc worsens patients' Health Assessment Questionnaire (HAQ-DI), Short Form 36 Physical and Mental Component Summary (SF36-PCS and SF36-MCS). The aim of this work is to verify whether there is correlation between quality of life and lung interstitiopathy in SSc patients. METHODS SF36 and HAQ-DI were given to each patient (48 in all). Lung involvement was evaluated with Baseline Dyspnea Index (BDI), spirometry and pulmonary fibrosis radiological assessment (PFRA). Correlations between SF36, HAQ-DI and lung involvement severity were investigated with Spearman's rank test. A p-value<0.05 was considered statistically significant. RESULTS SF36-PCS and SF36-MCS correlate with BDI (respectively rho=0.553 p=0.0001; rho=0.357 p=0.0150). The best correlating SF36 subsets are Physical Role (rho =0.566 p<0.0001) and Bodily Pain (rho=0.444 p=0.0020). BDI correlates with HAQ-DI (rho=-0.655 p<0.0001). No statistically significant correlation was found between SF36, HAQ-DI and spirometrical values nor PFRA. CONCLUSIONS The SSc patients enrolled have an impaired quality of life as widely demonstrated in literature. Quality of life reduction and functional ability decrease are only related to respiratory subjective impairment (assessed by BDI). Actually no correlation with objective lung damage (assessed by spirometry and PFRA) was detected.