Miracle-dz/UniFAR-FTUs huggingface dataset:
CI‐977, a novel and selective agonist for the κ‐opioid receptor

1 CI‐977 is a new, nonpeptide κ‐opioid compound that has been synthesized and its pharmacological properties determined in a series of in vitro and in vivo rodent models. 2 In radioligand binding studies, with guinea‐pig forebrain homogenates, CI‐977 bound with high affinity to [3H]‐U69593‐labelled κ‐sites (Ki = 0.11 nm) but with low affinity to [3H]‐[d‐Ala2, MePhe4, Glyol5] enkephalin (DAMGO) labelled μ‐sites (Ki = 99nm) and [3H]‐[d‐Pen2,5]enkephalin (DPDPE) labelled δ‐sites (Ki = 1.04 μm). CI‐977 also bound with negligible affinity to [3H]‐(+)‐3‐(1‐propyl‐3‐piperidinyl)phenol (3‐PPP) labelled σ‐sites (Ki = 1.9 μm) and [3H]‐1‐(1‐[2‐thienyl]cyclohexyl)piperidine (TCP) labelled PCP sites (Ki > 10 μm). 3 CI‐977 produced a potent inhibition of the electrically‐evoked contractions of the guinea‐pig ileum and rabbit vas deferens with IC50 values of 0.087 nM and 3.3 nM, respectively. The pKB values for the opioid antagonists naloxone (7.6) and norbinaltorphimine (10.5) supported the κ nature of the CI‐977‐mediated effects in the smooth muscle assays. 4 CI‐977 was a potent antinociceptive agent against a mechanical noxious stimulus in rats following intravenous, intramuscular, subcutaneous and oral administration. CI‐977 was also effective against mechanical and chemical noxious stimuli in the mouse but ineffective against a thermal stimulus. The antinociceptive effects produced by CI‐977 were completely reversed by naloxone (1 mg kg−1, s.c.). 5 At doses close to those required to produce antinociception, CI‐977 also caused a naloxone‐reversible diuresis and inhibition of locomotor activity. 6 The in vitro and in vivo pharmacological profile of CI‐977 demonstrates that it is a potent and selective agonist at the κ‐opioid receptor.
Recurrent convolutional neural network for object recognition

In recent years, the convolutional neural network (CNN) has achieved great success in many computer vision tasks. Partially inspired by neuroscience, CNN shares many properties with the visual system of the brain. A prominent difference is that CNN is typically a feed-forward architecture while in the visual system recurrent connections are abundant. Inspired by this fact, we propose a recurrent CNN (RCNN) for object recognition by incorporating recurrent connections into each convolutional layer. Though the input is static, the activities of RCNN units evolve over time so that the activity of each unit is modulated by the activities of its neighboring units. This property enhances the ability of the model to integrate the context information, which is important for object recognition. Like other recurrent neural networks, unfolding the RCNN through time can result in an arbitrarily deep network with a fixed number of parameters. Furthermore, the unfolded network has multiple paths, which can facilitate the learning process. The model is tested on four benchmark object recognition datasets: CIFAR-10, CIFAR-100, MNIST and SVHN. With fewer trainable parameters, RCNN outperforms the state-of-the-art models on all of these datasets. Increasing the number of parameters leads to even better performance. These results demonstrate the advantage of the recurrent structure over purely feed-forward structure for object recognition.
Translate of horospheres and counting problems

Let G be a semisimple Lie group without compact factors, \Gamma be an irreducible lattice in G. In the first part of the article we give the necessary and sufficient condition under which a sequence of translates of probability "horospherical measures" is convergent. And the limiting measure is also determined when it is convergent (see Theorems 1 and 2 for the precise statements). In the second part, two applications are presented. The first one is of geometric nature and the second one gives an alternative way to count the number of rational points on a flag variety.
Knowledge, Reservations, or Promise?

This study introduces a media effects model specific to public perceptions of science and technology. Analysis of the National Science Board's Science and Engineering Indicators Survey provides evidence that different media—newspapers, general television, science television, and science magazines—do affect perceptions differently. These media effects are direct but also indirect, as mediated through effects on science knowledge. Although newspaper reading, science television viewing, and science magazine reading all promote positive perceptions of science, given the relative size of its audience, the impact of general television viewing remains the most compelling finding. The negative images of science on television appear to cultivate scientific reservations, whereas television's portrayal of science as sometimes omnipotent, and offering hope for the future, appears to also promote a competing schema related to the promise of science. Television's direct effect on reservations is reinforced through the medium's negative relationship with science knowledge.
Association of Gene Polymorphisms With Intervertebral Disc Degeneration and Vertebral Osteophyte Formation

Study Design. Cross-sectional cohort study of elderly people. Objectives. To examine the factors influencing osteophyte formation without lumbar disc degeneration and to estimate the implications of osteophytes from the viewpoint of low back pain and gene polymorphisms. Summary of Background Data. The degenerative changes that occur in the intervertebral discs are the point of departure of osteophyte formation. Several studies on factors associated with genetic susceptibility to spinal osteophyte formation, such as VDR and TGF-β1. However, there are no detailed studies concerning osteophytes not accompanied with disc degeneration. Methods. A total of 387 elderly persons were recruited, and disc degeneration and osteophyte formation were evaluated. The cases with osteophyte formation were classified into 3 groups: osteophyte formation with disc height narrowing (n = 217), osteophyte formation without disc height narrowing (n = 99), and control group defined as the cases without osteophyte formation (n = 71). Twelve genotypes were characterized. Correlations between these degenerative factors and the polymorphisms were analyzed. Results. The prevalence of low back pain was significantly greater in the group of osteophyte formation with disc height narrowing than the other 2 groups. In the polymorphism of alcohol dehydrogenase (ADH2), prevalence of osteophyte formation without disc height narrowing was less in His/Arg (odds ratio = 0.57, P = 0.041) and Arg/Arg (odds ratio = 0.41, P = 0.18) than His/His. Conclusions. Patients with osteophyte formation preceding intervertebral disc narrowing had a lower risk of low back pain compared with those without osteophytes. The 47Arg polymorphism in the ADH2 may act to suppress osteophyte formation unaffected by disc degeneration.
Mitotic Transcription Repression in Vivo in the Absence of Nucleosomal Chromatin Condensation

All nuclear RNA synthesis is repressed during the mitotic phase of the cell cycle. In addition, RNA polymerase II (RNAP II), nascent RNA and many transcription factors disengage from DNA during mitosis. It has been proposed that mitotic transcription repression and disengagement of factors are due to either mitotic chromatin condensation or biochemical modifications to the transcription machinery. In this study, we investigate the requirement for chromatin condensation in establishing mitotic transcription repression and factor loss, by analyzing transcription and RNAP II localization in mitotic cells infected with herpes simplex virus type 1. We find that virus-infected cells enter mitosis and that mitotic viral DNA is maintained in a nucleosome-free and noncondensed state. Our data show that RNAP II transcription is repressed on cellular genes that are condensed into mitotic chromosomes and on viral genes that remain nucleosome free and noncondensed. Although RNAP II may interact indirectly with viral DNA during mitosis, it remains transcriptionally unengaged. This study demonstrates that mitotic repression of transcription and loss of transcription factors from mitotic DNA can occur independently of nucleosomal chromatin condensation.
Quality of life and economic impact of switching from established infliximab therapy to adalimumab in patients with rheumatoid arthritis.

OBJECTIVE To evaluate the quality of life and economic impact of switching therapy from infliximab to adalimumab in patients with rheumatoid arthritis (RA). METHODS In this open-label study, patients demonstrating a clinical response to infliximab were switched to treatment with adalimumab and followed for 16 weeks. Both generic (Health Assessment Questionnaire and Short Form 36 Physical Component Summary and Mental Component Summary) and specific (Rheumatoid Arthritis Quality of Life questionnaire) assessment instruments of physical function and of quality of life were employed. An economic analysis of treatment-related costs was also performed. Disease activity was assessed by the composite 28-joint count Disease Activity Score (DAS28). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured as acute phase markers. RESULTS Nineteen patients were enrolled and completed the study. No changes in functional and quality-of-life measures were observed. One-year extrapolation data showed potential reductions in costs following switching to adalimumab that could be attributed primarily to reductions in patient- and staff-related costs. Safety and tolerability were similar for both treatments. Although there was a significant reduction in DAS28 (P < 0.005) and CRP (P < 0.001) after switching to adalimumab, there were no significant changes in individual DAS28 components, including swollen and tender joint counts and ESR. CONCLUSIONS A switch from infliximab to adalimumab in patients with RA who have responded to infliximab is a feasible, well-tolerated treatment option, with the potential for direct and indirect economic advantages.
Prevalence of and Risk Factors for Colonization With Methicillin-Resistant Staphylococcus aureus at the Time of Hospital Admission

Abstract Objectives: To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization among patients presenting for hospital admission and to identify risk factors for MRSA colonization. Design: Surveillance cultures were performed at the time of hospital admission to identify patients colonized with S. aureus. A case-control study was performed to identify risk factors for MRSA colonization. Setting: A tertiary-care academic medical center. Patients: Adults presenting for hospital admission (N = 974). Results: S. aureus was isolated from 205 (21%) of the patients for whom cultures were performed. Methicillin-sensitive S. aureus was isolated from 179 (18.4%) of the patients, and MRSA was isolated from 26 (2.7%) of the patients. All 26 MRSA-colonized patients had been admitted to a healthcare facility in the preceding year, had at least one chronic illness, or both. In multivariate analyses comparing MRSA-colonized patients with control-patients, admission to a nursing home (odds ratio [OR], 16.5; 95% confidence interval [CI95], 1.4 to 192.1; P = .025) or a hospitalization of 5 days or longer during the preceding year (OR, 3.91; CI95, 1.1 to 13.9; P = .035) were independent predictors of MRSA colonization. Conclusions: Patients colonized with MRSA admitted to this hospital likely acquired the organism during previous encounters with healthcare facilities. There was no evidence that MRSA colonization occurs commonly among low-risk individuals in this community. These data suggest that evaluation of recent healthcare exposures is essential if true community acquisition of MRSA is to be confirmed.
Participatory Sensing: Crowdsourcing Data from Mobile Smartphones in Urban Spaces

The recent wave of sensor-rich, Internet-enabled, smart mobile devices such as the Apple iPhone has opened the door for a novel paradigm for monitoring the urban landscape known as participatory sensing. Using this paradigm, ordinary citizens can collect multi-modal data streams from the surrounding environment using their mobile devices and share the same using existing communication infrastructure (e.g., 3G service or WiFi access points). The data contributed from multiple participants can be combined to build a spatiotemporal view of the phenomenon of interest and also to extract important community statistics. Given the ubiquity of mobile phones and the high density of people in metropolitan areas, participatory sensing can achieve an unprecedented level of coverage in both space and time for observing events of interest in urban spaces. Several exciting participatory sensing applications have emerged in recent years. For example, GPS traces uploaded by drivers and passengers can be used to generate real time traffic statistics. Similarly, street-level audio samples collected by pedestrians can be aggregated to create a citywide noise map. In this advanced seminar, we will provide a comprehensive overview of this new and exciting paradigm and outline the major research challenges.
A multi-data source surveillance system to detect a bioterrorism attack during the G8 Summit in Scotland

SUMMARY In 18 weeks, Health Protection Scotland (HPS) deployed a syndromic surveillance system to early-detect natural or intentional disease outbreaks during the G8 Summit 2005 at Gleneagles, Scotland. The system integrated clinical and non-clinical datasets. Clinical datasets included Accident & Emergency (A&E) syndromes, and General Practice (GPs) codes grouped into syndromes. Non-clinical data included telephone calls to a nurse helpline, laboratory test orders, and hotel staff absenteeism. A cumulative sum-based detection algorithm and a log-linear regression model identified signals in the data. The system had a fax-based track for real-time identification of unusual presentations. Ninety-five signals were triggered by the detection algorithms and four forms were faxed to HPS. Thirteen signals were investigated. The system successfully complemented a traditional surveillance system in identifying a small cluster of gastroenteritis among the police force and triggered interventions to prevent further cases.
Validation and Use of an Instrument to Measure the Learning Environment as Perceived by Medical Students

Background: Aiming to inform curriculum changes in medical school, we developed, administered, and validated a 31-question survey to measure the learning environment as perceived by medical students. Description: We administered the survey annually in 4 medical school classes in a Southeastern medical school from May 1994 through May 1997 (N = 619). Evaluation: The survey responses reflected 3 dimensions of the medical school learning environment: the teacher-learner relationship (T-L R), the physician-patient relationship (Phys-Pt R), and self-efficacy. We found that the 3 dimensions are equally valid and reliable for all students, but that the mean values on all 3 dimensions differed by year in school and number of survey responses. Conclusions: As students progress through school, they perceive deteriorating T-L Rs, feel diminishing self-efficacy, and accord less value to the Phys-Pt R. Based on these results, we developed training programs for faculty members to promote teaching attributes known to facilitate relationship formation between teacher and learner, and learner-centered and self-directed learning.
Re‐immunisation schedule in leukaemic children after intensive chemotherapy: a possible strategy

Abstract: The aim of this retrospective study was to test the residual humoral immunity to compulsory vaccines after the end of chemotherapy for acute lymphoblastic leukaemia in a cohort of 70 Italian children. All the patients, who had been immunised according to the Italian schedule prior to the disease, were tested for antibody levels against tetanus and hepatitis B at a median of 10 months after the end of therapy. Median age at diagnosis of leukaemia was 48 months, and median age at vaccine titration was 84 months. The protective level of antibodies for tetanus and hepatitis B was shown in 83% and 81% of patients, respectively; the remaining 17% and 19% were not protected against the two pathogens. Double negativity was observed in only four of 62 (6%) patients in the cohort. These data were comparable with published data regarding healthy children of the same age and from the same geographical areas. Therefore, given the direct and indirect costs of performing laboratory tests, as well as the cost of revaccination, our proposal is to continue the vaccination schedule according to the child's age without any titration screening 6 months after the end of therapy. Larger studies are needed to confirm these observations.
Weakly Supervised Open-Set Domain Adaptation by Dual-Domain Collaboration

In conventional domain adaptation, a critical assumption is that there exists a fully labeled domain (source) that contains the same label space as another unlabeled or scarcely labeled domain (target). However, in the real world, there often exist application scenarios in which both domains are partially labeled and not all classes are shared between these two domains. Thus, it is meaningful to let partially labeled domains learn from each other to classify all the unlabeled samples in each domain under an open-set setting. We consider this problem as weakly supervised open-set domain adaptation. To address this practical setting, we propose the Collaborative Distribution Alignment (CDA) method, which performs knowledge transfer bilaterally and works collaboratively to classify unlabeled data and identify outlier samples. Extensive experiments on the Office benchmark and an application on person reidentification show that our method achieves state-of-the-art performance.
A Highly Elastic and Rapidly Crosslinkable Elastin‐Like Polypeptide‐Based Hydrogel for Biomedical Applications

Elastin‐like polypeptides (ELPs) are promising for biomedical applications due to their unique thermoresponsive and elastic properties. ELP‐based hydrogels have been produced through chemical and enzymatic crosslinking or photocrosslinking of modified ELPs. Herein, a photocrosslinked ELP gel using only canonical amino acids is presented. The inclusion of thiols from a pair of cysteine residues in the ELP sequence allows disulfide bond formation upon exposure to UV light, leading to the formation of a highly elastic hydrogel. The physical properties of the resulting hydrogel such as mechanical properties and swelling behavior can be easily tuned by controlling ELP concentrations. The biocompatibility of the engineered ELP hydrogels is shown in vitro as well as corroborated in vivo with subcutaneous implantation of hydrogels in rats. ELP constructs demonstrate long‐term structural stability in vivo, and early and progressive host integration with no immune response, suggesting their potential for supporting wound repair. Ultimately, functionalized ELPs demonstrate the ability to function as an in vivo hemostatic material over bleeding wounds.
Structural Response of Polyethylene Foam-Based Sandwich Panels Subjected to Edgewise Compression

This study analyzes the mechanical behavior of low density polyethylene foam core sandwich panels subjected to edgewise compression. In order to monitor panel response to buckling, strains generated in the facesheets and overall out-of-plane deformations are measured with strain gages and projection moiré, respectively. A finite element (FE) model simulating the experimental test is developed. Numerical results are compared with moiré measurements. After having been validated against experimental evidence, the FE model is parameterized, and a trade study is carried out to investigate to what extent the structural response of the panel depends on the sandwich wall construction and facesheet/core interface defects. The projection moiré set-up utilized in this research is able to capture the sudden and very localized buckling phenomena occurring under edgewise compression of foam-based sandwich panels. Results of parametric FE analyses indicate that, if the total thickness of the sandwich wall is fixed, including thicker facesheets in the laminate yields a larger deflection of the panel that becomes more sensitive to buckling. Furthermore, the mechanical response of the foam sandwich panel is found to be rather insensitive to the level of waviness of core-facesheet interfaces.
Crystal structural analysis of protein–protein interactions drastically destabilized by a single mutation

The complex of barnase (bn) and barstar (bs), which has been widely studied as a model for quantitative analysis of protein–protein interactions, is significantly destabilized by a single mutation, namely, bs Asp39 → Ala, which corresponds to a change of 7.7 kcal·mol−1 in the free energy of binding. However, there has been no structural information available to explain such a drastic destabilization. In the present study, we determined the structure of the mutant complex at 1.58 Å resolution by X‐ray crystallography. The complex was similar to the wild‐type complex in terms of overall and interface structures; however, the hydrogen bond network mediated by water molecules at the interface was significantly different. Several water molecules filled the cavity created by the mutation and consequently caused rearrangement of the hydrated water molecules at the interface. The water molecules were redistributed into a channel‐like structure that penetrated into the complex. Furthermore, molecular dynamics simulations showed that the mutation increased the mobility of water molecules at the interface. Since such a drastic change in hydration was not observed in other mutant complexes of bn and bs, the significant destabilization of the interaction may be due to this channel‐like structure of hydrated water molecules.
Regulation of antibody response in vitro. IX. Induction of secondary anti-hapten IgG antibody response by anti-immunoglobulin and enhancing soluble factor.

Attempts were made to induce antibody response of hapten-primed cells by stimulation with anti-immunoglobulin (Ig) antibody and cellfree supernatant (CFS) which contained nonspecific enhancing factor. Mesenteric lymph node cells were obtained from rabbits which were primed with dinitrophenylated ragweed antigen (DNP-Rag), and the primed cells were incubated in vitro with either anti-rabbit gamma-chain or anti-Fab antibody for 24 hr. After washing, the cells were cultured in CFS which was obtained from the culture of DNP-Ascaris (DNP-Asc)-primed lymph node cells with free carrier (Asc). The results showed that hapten-primed cells were triggered for IgG anti-DNP antibody response by the two reagents, i.e., anti-Ig antibody and CFS, both which did not share any antigenic specificity with the priming antigen (DNP-Rag). Neither anti-Ig alone nor CFS alone induced anti-hapten antibody response. Anti-Ig and CFS triggered not only hapten-primed B cells but also the other IgG-bearing (B) cells for IgG synthesis. Lymph node cells of umprimed animals were activated for IgG synthesis by the stimulation with anti-Ig followed by culture in CFS. Evidence was obtained that anti-Ig antibody has to be divalent for the activation of B cells. Stimulation of DNP-primed cells with the F(ab')2 fragment of the antibody and CFS-induced anti-hapten antibody response, whereas the Fag' fragment of the anti-Ig plus CFS failed to do so. The results suggested that bridging of cell-surface Ig receptors by multivalent ligand is the initial step of B cell activation. Another evidence for the activation of hapten-primed B cells by anti-Ig was obtained by supplemental immunization of DNP-Asc-primed animals with the Fc fragment of goat IgG. Stimulation of mesenteric lymph node cells from these animals with goat anti-rabbit-Ig alone (no CFS) resulted in the formation of anti-DNP IgG antibody. The results indicated that lymphocytes primed for goat IgG collaborated with DNP-primed IgG-B cells when the lymph node cells were stimulated with goat anti-Ig.