Miracle-dz/UniFAR-FTUs huggingface dataset:
Macrolide antibiotics block autophagy flux and sensitize to bortezomib via endoplasmic reticulum stress-mediated CHOP induction in myeloma cells

The specific 26S proteasome inhibitor bortezomib (BZ) potently induces autophagy, endoplasmic reticulum (ER) stress and apoptosis in multiple myeloma (MM) cell lines (U266, IM-9 and RPMI8226). The macrolide antibiotics including concanamycin A, erythromycin (EM), clarithromycin (CAM) and azithromycin (AZM) all blocked autophagy flux, as assessed by intracellular accumulation of LC3B-II and p62. Combined treatment of BZ and CAM or AZM enhanced cytotoxicity in MM cell lines, although treatment with either CAM or AZM alone exhibited almost no cytotoxicity. This combination also substantially enhanced aggresome formation, intracellular ubiquitinated proteins and induced the proapoptotic transcription factor CHOP (CADD153). Expression levels of the proapoptotic genes transcriptionally regulated by CHOP (BIM, BAX, DR5 and TRB3) were all enhanced by combined treatment with BZ plus CAM, compared with treatment with each reagent alone. Like the MM cell lines, the CHOP+/+ murine embryonic fibroblast (MEF) cell line exhibited enhanced cytotoxicity and upregulation of CHOP and its transcriptional targets with a combination of BZ and one of the macrolides. In contrast, CHOP−/− MEF cells exhibited resistance against BZ and almost completely canceled enhanced cytotoxicity with a combination of BZ and a macrolide. These data suggest that ER stress-mediated CHOP induction is involved in pronounced cytotoxicity. Simultaneously targeting two major intracellular protein degradation systems such as the ubiquitin-proteasome system by BZ and the autophagy-lysosome system by a macrolide antibiotic enhances ER stress-mediated apoptosis in MM cells. This result suggests the therapeutic possibility of using a macrolide antibiotic with a proteasome inhibitor for MM therapy.
Ly Antigens Associated with T Cell Recognition and Effector Function

The mechanisms involved in acquisition and expression of T cell immunity are being extensively investigated in many laboratories. Monoclonal antibodies occupy a central role in the study of T cell immunity at both cellular and molecular levels and have facilitated the identification of the elements which figure in and result from the process of T cell differentiation. The purpose of this review is to identify key structures known to participate in T cell effector function and to describe some of our structural studies on 3 of these antigens, Ly-2/3, T8 and Ly-15.
The role of 3-D seismic in a world-class turnaround

Amoco has achieved a major turnaround in exploration performance in the mid-1990s. Production replacement improved from 60% in 1992 to 179% in 1996 (Figure 1); cost of finding dropped from $8/bl in 1991 to under $1/bl in 1996; new resources found improved from 200 million barrels of oil equivalent (boe) in 1991 to 1000 million boe in 1994 and 1996; and exploration drilled success rate jumped from 13% in 1991 to 44% in 1996.
The design and evaluation of an auditory-enhanced scrollbar

A structured method is described for the analysis of interactions to identify situations where hidden information may exist and where non-speech sound might be used to overcome the associated problems. Interactions are considered in terms of events, status and modes to find any hidden information. This is then categorised in terms of the feedback needed to present it. An auditory-enhanced scrollbar, based on the method described, was then experimentally tested. Timing and error rates were used along with subjective measures of workload. Results from the experiment show a significant reduction in time to complete one task, a decrease in the mental effort required and an overall preference for the auditory-enhanced scrollbar.
Transmitted cardiovascular pulsations on high resolution esophageal impedance manometry, and their significance in dysphagia

AIM To investigate the behavior of pulsatile pressure zones (PPZ’s) as noted on high resolution esophageal impedance manometry (HREIM), and determine their association with dysphagia. METHODS Retrospective, single center case control design screening HREIM studies for cases (dysphagia) and controls (no dysphagia). Thoracic radiology studies were reviewed further in cases for (thoracic cardiovascular) thoracic cardiovascular (TCV) structures in esophageal proximity to compare with HREIM findings. Manometric data was collected for number, location, axial length, PPZ pressure and esophageal clearance function (impedance). RESULTS Among 317 screened patients, 56% cases and 64% controls had PPZ’s. Fifty cases had an available thoracic radiology comparison. The distribution of PPZ’s in these 50 cases and 59 controls was similar (average 1.4 PPZ/patient). Controls (mean 31.2 ± SD 12 years) were a significantly younger population than cases (mean 67.3 ± SD 14.9 years) with P < 0.0001. The upright posture PPZ pressure was higher in controls (15.7 ± 10.0 mmHg) than cases (10.8 ± 9.7 mmHg). Although statistically significant (P = 0.005), it was a weak predictor using logistic regression and ROC model (AUC = 0.65). Three dysphagia patients had partial compression from external TCV on radiology (1 aberrant subclavian artery, 2 dilated left atrium). The posture (supine vs upright) with more prominent PPZ’s impaired bolus clearance in 9 additional cases by > 20%. CONCLUSION Transmitted TCV pulsations observed in HREIM bear no significant impact on swallowing. However, in older adults with dysphagia, evidence of impaired bolus clearance on impedance should be evaluated for external TCV compression. These associations have never been explored previously in literature, and are novel.
Atlas de la flora del Pirineo aragonés

2 vol.-Vol. I: Introduccion. Lycopodiaceae-Umbelliferae. -- XCI, 648 p. : il. col. Vol. II: Pyrolaceae-Orchidaceae. Sintesis -- XXII, 790 p. : il. ,[8] h. de lam.
Patient Satisfaction and Information Gain After the Preanesthetic Visit: A Comparison of Face-to-Face Interview, Brochure, and Video

In this study we compared 3 methods of conducting the preanesthetic visit. We prospectively studied 197 consecutive surgical patients who were to undergo general anesthesia. The patients were randomized to a routine preanesthetic interview, a brochure plus an interview, or a self-made documentary video plus an interview. After the preanesthetic visit, the degree of patient satisfaction and information gain was quantified by a questionnaire for each method. The questions on patient satisfaction were assessed on a six-point scale, and those on information gain were assessed on a multiple-choice basis. The video plus interview group showed the highest point scores (98% of the possible maximum sum point score in patient satisfaction and 93% of the maximum sum score in information gain). In contrast, the patients of the brochure plus interview group revealed 93% for patient satisfaction and 80% for information gain, and in the standard interview group, the corresponding figures were 91% and 72%, respectively. The maximum sum scores in patient satisfaction and information gain were significantly different between the interview and the video groups, but not between the interview and the brochure groups. Therefore, these data suggest that the use of a documentary video to supplement a preoperative interview may enhance patient satisfaction and maximize information gain.
Effects of Contact Placement and Intra/Interlayer Interaction in Current Distribution of Black Phosphorus Sub-10-nm FET

Black phosphorus (BP) has been proposed as the channel material in the next generation ultrascaled CMOS devices. In order to gain insight into the current characteristics in 2-D layered materials, the current distribution of a few-layer BP Schottky barrier FET is investigated via state-of-the-art quantum device simulations. Approximately 40% of the total current was found to be concentrated in the top layer when the device was switched on, with the remaining current distributed among the other layers. In comparison, ~80% of the current concentrated below the surface in a Si device with the same structure. These features are related to the strength of the intra/interlayer interaction in few-layer BP and are unique to 2-D layered materials. Moreover, the current distribution and the device performance were different for the top- and side-contacted devices, with the side-contacted devices yielding lower resistance compared with the top-contacted devices.
Changing medication use in managed care: a critical review of the available evidence.

OBJECTIVE To review the effectiveness of strategies to improve the quality and efficiency of medication use in managed care organizations (MCOs). STUDY DESIGN Systematic review of published intervention studies. METHODS Studies were identified by using computerized and manual literature searches and personal contacts, and were categorized by intervention type and adequacy of research design according to commonly accepted criteria. Reported significance and magnitude of the changes in key outcomes were used to summarize the effects of studies with adequate research designs. RESULTS The searches identified 105 studies, 70 of which were reported since 1996. Overall, 46% of the studies met the minimum criteria for methodologic adequacy (n = 48). Consistently effective interventions included dissemination of educational materials with drug samples, participatory clinical guideline development, group or one-to-one educational outreach, and enhanced patient-specific feedback. Disease management (primarily for depression and diabetes) showed promise in improving short-term outcomes. Dissemination of educational materials and aggregated feedback alone were ineffective. Interventions in staff-model health maintenance organizations were more effective than those conducted in group-model health maintenance organizations. CONCLUSION High-quality studies of interventions to improve drug use in MCOs are increasing in frequency. There is evidence for the effectiveness of several strategies to change drug use, but little is known about longer-term clinical outcomes. Few well-designed, published studies have assessed the efficacy or safety of financial incentives for physicians, tiered copayments for patients, or formularies--despite their widespread use.
Sustained and transient attentional processes modulate neural predictors of memory encoding in consecutive time periods

Memory formation is commonly thought to rely on brain activity following an event. Yet, recent research has shown that even brain activity previous to an event can predict later recollection (subsequent memory effect, SME). In order to investigate the attentional sources of the SME, event‐related potentials (ERPs) elicited by task cues preceding target words were recorded in a switched task paradigm that was followed by a surprise recognition test. Stay trials, that is, those with the same task as the previous trial, were contrasted with switch trials, which included a task switch compared to the previous trial. The underlying assumption was that sustained attention would be dominant in stay trials and that transient attentional reconfiguration processes would be dominant in switch trials. To determine the SME, local and global statistics of scalp electric fields were used to identify differences between subsequently remembered and forgotten items. Results showed that the SME in stay trials occurred in a time window from 2 to 1 sec before target onset, whereas the SME in switch trials occurred subsequently, in a time window from 1 to 0 sec before target onset. Both SMEs showed a frontal negativity resembling the topography of previously reported effects, which suggests that sustained and transient attentional processes contribute to the prestimulus SME in consecutive time periods.
Lily Results for OAEI 2019

This paper presents the results of Lily in the ontology alignment contest OAEI 2019. As a comprehensive ontology matching system, Lily is intended to participate in three tracks of the contest: anatomy, conference, and spimbench. The speciﬁc techniques used by Lily will be introduced brieﬂy. The strengths and weaknesses of Lily will also be discussed.
Exercise test on the patients with normokalaemic periodic paralysis from a Chinese family with a mutation in the SCN4A gene.

BACKGROUND Normokalaemic periodic paralysis (normoKPP) is characterized by transient and recurrent myoasthenia, and some patients also show muscle stiffness induced by cold exposure (paramyotonia congenita, PMC). It is caused by a mutation in the muscle voltage gated sodium channel alpha subunit (SCN4A) gene. Due to the diversity of the clinical manifestations of patients, it is difficult for clinicians to differentiate some of patients with atypical normoKPP from those who suffer from other periodic paralysis and nondystrophic myotonia. So far, for normoKPP there are almost no ways to assist definite diagnosis besides genetic screening. This research was designed to evaluate an exercise test (ET) in confirming the diagnosis of normoKPP and in assessing the therapeutic effectiveness of some drugs on this disease. METHODS ET, described by McMains, was performed on six subjects from a Chinese family, including four patients with overlapping disease of normoKPP and PMC caused by a mutation of SCN4A Met1592Val that is identified by genetic analysis and two normal control members. The change of compound muscle action potential (CMAP) was recorded. Besides the family, two patients were also tested during treatments with acetazolamide. RESULTS All patients showed a slight increase in CMAP immediately after exercise, followed by an abnormal gradual decline, which reached its nadir 25-30 minutes after exercise. CMAP amplitude dropped by more than 40% in patients but less than 23% in controls. In the patients who received treatment with acetazolamide, the change of CMAP amplitude was less than 28% and, at any fixed times, less than pretreatment values. CONCLUSIONS The ET may be used as a predictive, easy and reliable method of diagnosing normoKPP under conditions without genetic screening help, and is an objective way to evaluate the therapeutic effectiveness. According to different response patterns, the ET may also be helpful in reducing the scope of genetic screening.
Insertion of a New Transcriptional Unit into the Genome of Mouse Hepatitis Virus

ABSTRACT The subgenomic mRNAs of the coronavirus mouse hepatitis virus (MHV) are composed of a leader sequence, identical to the 5′ 70 nucleotides of the genome, joined at distant downstream sites to a stretch of sequence that is identical to the 3′ end of the genome. The points of fusion occur at intergenic sequences (IGSs), loci on the genome that contain a tract of sequence homologous to the 3′ end of the leader RNA. We have constructed a mutant of MHV-A59 containing an extra IGS inserted into the genome immediately downstream of the 3′-most gene, that encoding the nucleocapsid (N) protein. We show that in cells infected with the mutant, there is synthesis of an additional leader-containing subgenomic RNA of the predicted size. Our study demonstrates that (i) an IGS can be a sufficient cis-acting element to dictate MHV transcription, (ii) the relative efficiency of an IGS must be influenced by factors other than the nucleotides immediately adjacent to the 5′AAUCUAAAC3′ core consensus sequence or its position relative to the 3′ end of the genome, (iii) a downstream IGS can exert a polar attenuating effect on upstream IGSs, and (iv) unknown factors prevent the insertion of large exogenous elements between the N gene and the 3′ untranslated region of MHV. These results confirm and extend conclusions previously derived from the analysis of defective interfering RNAs.
Intelligibility Enhancement of Telephone Speech Using Gaussian Process Regression for Normal-to-Lombard Spectral Tilt Conversion

Noise in the environment can decrease the quality and intelligibility of a telephone conversation. This study focuses on the intelligibility enhancement of narrowband telephone speech in a near-end noise scenario using a postprocessing method based on normal-to-Lombard spectral tilt conversion. The proposed technique uses nonparallel, conversational normal, and Lombard speech together with Gaussian process regression in order to mimic the flattening of the spectral tilt that occurs in the production of natural speech in noisy conditions. The performance of the proposed method was evaluated in comparison to two reference methods, a fixed high-pass filter, and a baseline spectral tilt conversion, as well as in comparison to unprocessed speech in terms of intelligibility and listening preference in noisy conditions and in terms of pressedness in silent conditions. The results indicate that while the proposed technique provides a similar benefit in terms of intelligibility as fixed high-pass filtering, it is also able to produce a notable increase in pressedness. This suggests that the developed processing of the spectral tilt can compete with fixed high-pass filtering in intelligibility enhancement, but it is also able to convert speech to become perceptually closer to natural Lombard speech.
All Numbers Are Not Equal: An Electrophysiological Investigation of Small and Large Number Representations

Behavioral and brain imaging research indicates that human infants, humans adults, and many nonhuman animals represent large nonsymbolic numbers approximately, discriminating between sets with a ratio limit on accuracy. Some behavioral evidence, especially with human infants, suggests that these representations differ from representations of small numbers of objects. To investigate neural signatures of this distinction, event-related potentials were recorded as adult humans passively viewed the sequential presentation of dot arrays in an adaptation paradigm. In two studies, subjects viewed successive arrays of a single number of dots interspersed with test arrays presenting the same or a different number; numerical range (small numerical quantities 1–3 vs. large numerical quantities 8–24) and ratio difference varied across blocks as continuous variables were controlled. An early-evoked component (N1), observed over widespread posterior scalp locations, was modulated by absolute number with small, but not large, number arrays. In contrast, a later component (P2p), observed over the same scalp locations, was modulated by the ratio difference between arrays for large, but not small, numbers. Despite many years of experience with symbolic systems that apply equally to all numbers, adults spontaneously process small and large numbers differently. They appear to treat small-number arrays as individual objects to be tracked through space and time, and large-number arrays as cardinal values to be compared and manipulated.
Carbon isotopic signatures of methanol and acetaldehyde emitted from biomass burning source

We present carbon isotopic signatures of methanol and acetaldehyde emitted from biomass burning sources using laboratory experiments. The respective δ13C of methanol and acetaldehyde emitted from burning experiments of five plant materials (three C3 and two C4 plants) were −20–−46‰ and −11–−25‰. The variation in δ13C of methanol depends on the δ13C of the fuel biomass and burning conditions, but the variation in δ13C of acetaldehyde depends on the δ13C of fuel biomass and is independent of burning conditions. Combining these observations with previously reported global distributions of fire types, burning conditions, amounts of biomass burned, vegetation types, and emission factors, we estimated the global isotopic signature for biomass burning source as −33 ± 16‰ for methanol.
Systematic Errors in the Hubble Constant Based upon Measurement of the Sunyaev-Zeldovich Effect

Values of the Hubble constant reported to date that are based upon measurement of the Sunyaev-Zeldovich (SZ) effect in clusters of galaxies are systematically lower than those derived by other methods (e.g., Cepheid variable stars or the Tully-Fisher relation). We investigate the possibility that systematic errors may be introduced into the analysis by the generally adopted assumptions that observed clusters are in hydrostatic equilibrium, are spherically symmetric, and are isothermal. We construct self-consistent theoretical models of merging clusters of galaxies, using hydrodynamic/N-body simulations. We then compute the magnitude of H0 derived from the SZ effect at different times and at different projection angles, both from first principles and by applying each of the standard assumptions used in the interpretation of observations. Our results indicate that the assumption of isothermality in the evolving clusters can result in H0 being underestimated by 10%-30%, depending upon both epoch and projection angle. Moreover, use of the projected, emission-weighted temperature profile under the assumption of spherical symmetry does not significantly improve the situation except in the case of more extreme mergers (i.e., those involving relatively gas-rich subclusters). Although less significant, we find that asphericity in the gas density can also result in a 15% error in H0. If the cluster is prolate (as is generally the case for on-axis, or nearly on-axis, mergers) and viewed along its major axis, H0 will be systematically underestimated. More extreme off-axis mergers may result in oblate merger remnants, which, when viewed nearly face-on, may result in an overestimation of H0. A similar effect is noted when viewing a prolate distribution along a line of sight that is nearly perpendicular to its major axis. In both cases the potential overestimation occurs only when the remnant is viewed within 15°-30° of face-on. Bulk gas motions and the kinematic SZ effect do not appear to be significant except for a brief period during the very early stages of a merger. Our study shows that the most meaningful SZ measurement will be accompanied by high-resolution temperature data and a detailed dynamical modeling of the observed system. In lieu of this, a large sample selected to avoid dynamically evolving systems is preferred.
Explaining opposition to refugee resettlement: The role of NIMBYism and perceived threats

Support for refugee resettlement declines when citizens consider resettlement within their communities or face threatening frames. One week after President Donald Trump signed a controversial executive order to reduce the influx of refugees to the United States, we conducted a survey experiment to understand American citizens’ attitudes toward refugee resettlement. Specifically, we evaluated whether citizens consider the geographic context of the resettlement program (that is, local versus national) and the degree to which they are swayed by media frames that increasingly associate refugees with terrorist threats. Our findings highlight a collective action problem: Participants are consistently less supportive of resettlement within their own communities than resettlement elsewhere in the country. This pattern holds across all measured demographic, political, and geographic subsamples within our data. Furthermore, our results demonstrate that threatening media frames significantly reduce support for both national and local resettlement. Conversely, media frames rebutting the threat posed by refugees have no significant effect. Finally, the results indicate that participants in refugee-dense counties are less responsive to threatening frames, suggesting that proximity to previously settled refugees may reduce the impact of perceived security threats.