Miracle-dz/UniFAR-FTUs huggingface dataset:
Genesis of tramsmissible protein states via deformed templating

Prion replication occurs via a template-assisted mechanism, which postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a template. The concept of prion-like template-assisted propagation of an abnormal protein conformation has been expanded to amyloidogenic proteins associated with Alzheimer, Parkinson, Huntington diseases, amyotrophic lateral sclerosis and others. Recent studies demonstrated that authentic PrPSc and transmissible prion disease could be generated in wild type animals by inoculation of recombinant prion protein amyloid fibrils, which are structurally different from PrPSc and lack any detectable PrPSc particles. Here we discuss a new replication mechanism designated as “deformed templating,” according to which fibrils with one cross-β folding pattern can seed formation of fibrils or particles with a fundamentally different cross-β folding pattern. Transformation of cross-β folding pattern via deformed templating provides a mechanistic explanation behind genesis of transmissible protein states induced by amyloid fibrils that are considered to be non-infectious. We postulate that deformed templating is responsible for generating conformationally diverse amyloid populations, from which conformers that are fit to replicate in a particular cellular environment are selected. We propose that deformed templating represents an essential step in the evolution of transmissible protein states.
Thermodynamic Temperatures of the Triple Points of Mercury and Gallium and in the Interval 217 K to 303 K

We measured the acoustic resonance frequencies of an argon-filled spherical cavity and the microwave resonance frequencies of the same cavity when evacuated. The microwave data were used to deduce the thermal expansion of the cavity and the acoustic data were fitted to a temperature-pressure surface to deduce zero-pressure speed-of-sound ratios. The ratios determine (T–T90), the difference between the Kelvin thermodynamic temperature T and the temperature on the International Temperature Scale of 1990 (ITS-90). The acoustic data fall on six isotherms: 217.0950 K, 234.3156 K, 253.1500 K, 273.1600 K, 293.1300 K, and 302.9166 K and the standard uncertainties of (T−T90) average 0.6 mK, depending mostly upon the model fitted to the acoustic data. Without reference to ITS-90, the data redetermine the triple point of gallium Tg and the mercury point Tm with the results: Tg/Tw = (1.108 951 6 ± 0.000 002 6) and Tm/Tw= (0.857 785 5 ± 0.000 002 0), where Tw = 273.16 K exactly. (All uncertainties are expressed as standard uncertainties.) The resonator was the same one that had been used to redetermine both the universal gas constant R, and Tg. However, the present value of Tg is (4.3 ± 0.8) mK larger than that reported earlier. We suggest that the earlier redetermination of Tg was erroneous because a virtual leak within the resonator contaminated the argon used at Tg in that work. This suggestion is supported by new acoustic data taken when the resonator was filled with xenon. Fortunately, the virtual leak did not affect the redetermination of R. The present work results in many suggestions for improving primary acoustic thermometry to achieve sub-millikelvin uncertainties over a wide temperature range.
Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression

Purpose: Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Experimental Design: Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab, or the combination. Results: Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Conclusions: Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. Clin Cancer Res; 21(12); 2780–91. ©2015 AACR.
Human Neuroscience

interest in the development of the functional organization of VTC and the role of experience in shaping it (Kanwisher, 2000; Tarr and Gauthier, 2000). Recent studies indicate that some category selective regions in the VTC undergo a prolonged development that continues at least through the fi rst decade of life (Gathers et al. Accumulating evidence suggests that the volume of the right FFA (rFFA) is substantially larger in adults compared to children, but not the overlapping object selective (lateral occipital complex) region (Golarai et al., 2007; Scherf et al., 2007) or the body-part selective extra-striate region (Peelen et al., 2009; Pelphrey et al., 2009)]. rFFA volume also correlates with behavioral improvements in recognition memory for faces (Golarai et al., 2007). However, the endpoint of this development is not known, as previous fMRI studies report inconclusive results. For example, one study reported no difference between adolescents' (ages 11–14 years) and adults' FFA volume based on group analyses (Scherf et al., 2007). Another study reported larger FFA size in adults compared to the combined data from both children and adolescents (Peelen et al., 2009). A third study found that adolescents' FFA size was at an intermediate level between children and adults, but these between group differences did not reach statistical signifi cance (Golarai et al., 2007). Nevertheless, behavioral studies suggest a prolonged development of face recognition memory profi ciency, consistently reporting
Transmission Line Model for Folded Waveguide Circuits

We describe an equivalent circuit model for traveling wave structures based on folded or serpentine waveguides (F/SWs), including a beam tunnel. The model consists of a combination of transmission line segments and lumped electrical elements. Values of the five parameters that characterize the model are found by minimizing the differences between the dispersion and coupling impedance as calculated by the model and those obtained from a 3-D finite element code. We find that the model reproduces the dispersion to better than 0.1% and the coupling impedance to better than 1% over a broad frequency range in different examples in which the dependence of the impedance on frequency tends either to zero or to infinity near the band edge at 2π. The model is also able to capture the effects of asymmetric fields and misalignment of the beam tunnel. We conclude that the model can be used with confidence in codes that simulate the beam-wave interaction in FW and SW traveling wave tubes.
Brief Report: IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross‐Disease Meta‐Analysis of Genome‐Wide Association Studies

Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc–RA loci through an interdisease meta–genome‐wide association (meta‐GWAS) strategy.
Patients' Expectations and Satisfaction in Lumbar Spine Surgery

Study Design. Prospective consecutive series. Objective. To determine patient expectations in lumbar spine surgery and assess the level of fulfillment of those expectations. Summary of Background Data. Little has been offered in the literature in specific regards to lumbar spine surgery. Methods. Ninety-eight patients, 49 patients who underwent discectomy for lumbar disc herniation (Group 1) and 49 patients who underwent laminotomy for lumbar spinal stenosis (Group 2), completed the self-report questionnaire. Preoperative expectations, reasons for surgery, and expected postoperative status were inquired before surgery and the satisfaction at 2 years after surgery. Results. Concerning patients' expectations, half of the patients expected to become completely leg pain free, and more than three fourths of the patients expected to become unlimited in their walking ability in both groups. More than half of the patients expected to have a 90% or greater chance of complete success of surgery. With regard to satisfaction, 42 of the 49 patients (86%) in Group 1 and 35 of the 49 patients (71%) in Group 2 chose “Surgery met my expectations” at the follow-up. The remaining patients selected “I did not improve as much as I had hoped. ” Positive expectations were associated with better satisfaction in Group 1 only. Of the patients who had achieved the expected postoperative status with respect to their no.1 reason for surgery, 2 of 34 patients in Group 1 (6%) and 5 of the 26 patients in Group 2 (19%) nonetheless reported “unfulfilled expectations. ” In patients whose no. 1 concern was further progression, 3 (38%) of the 8 patients in Group 1 and 2 (40%) of the 5 patients in Group 2 demonstrated unfulfilled expectations. Conclusions. Even if the clinical expectations were met, some patients were still dissatisfied. Patients with spinal stenosis (Group 2) seem to have more unrealistic expectations than patients with disc herniation (Group 1).
Analysis of Multi-Strain Pathogens – Species or Minor Genetic Variants ?

Modern advances in genetic analysis have made it feasible to ascertain the variant type of a pathogen infecting a host. Classification of pathogen variant is commonly performed by clustering analysis of the observed genetic divergence between the variants. A natural question arises as to whether the genetically distinct variants are epidemiologically distinct. A broader question is whether the different variants constitute separate microbial species or represent minor variations of the same species. We developed new statistical methodologies for addressing these important issues, in the context of classifying genetically distinct variants of bartonella bacteria found in a rodent species based on marked capture-recapture trapping data of a rodent ∗Author for correspondence (kung-sik-chan@uiowa.edu)
Residual strength and crack propagation tests on C-130 airplane center wings with service-imposed fatigue damage

Fourteen C-130 airplane center wings, each containing service-imposed fatigue damage resulting from 4000 to 13,000 accumulated flight hours, were tested to determine their fatigue crack propagation and static residual strength characteristics. Eight wings were subjected to a two-step constant amplitude fatigue test prior to static testing. Cracks up to 30 inches long were generated in these tests. Residual static strengths of these wings ranged from 56 to 87 percent of limit load. The remaining six wings containing cracks up to 4 inches long were statically tested as received from field service. Residual static strengths of these wings ranged from 98 to 117 percent of limit load. Damage-tolerant structural design features such as fastener holes, stringers, doublers around door cutouts, and spanwise panel splices proved to be effective in retarding crack propagation.
Female Gender Attenuates Cytokine and Chemokine Expression and Leukocyte Recruitment in Experimental Rodent Abdominal Aortic Aneurysms

Abstract: Female gender appears to be protective in the development of abdominal aortic aneurysms (AAAs). This study sought to identify gender differences in cytokine and chemokine expression in an experimental rodent AAA model. Male and female rodent aortas were perfused with either saline (control) or elastase to induce AAA formation. Aortic diameter was determined and aortic tissue was harvested on postperfusion days 4 and 7. Cytokine and chemokine gene expression was examined using focused gene arrays. Immunohistochemistry was used to quantify aortic leukocyte infiltration. Data were analyzed by Student's t‐tests and ANOVA. Elastase‐perfused female rodents developed significantly smaller aneurysms compared to males by day 7 (93 ± 10% vs. 201 ± 25%, P= 0.003). Elastase‐perfused female aortas exhibited a fivefold decrease in expression of the BMP family and ligands of the TNF superfamily compared to males. In addition, the expression of members of the TGF β and VEGF families were three to fourfold lower in female elastase‐perfused aortas compared to males. Multiple members of the interleukin, CC chemokine receptor, and CC ligand families were detectable in only the male elastase‐perfused aortas. Female elastase‐perfused aortas demonstrated a corollary twofold lower neutrophil count (females: 17.5 ± 1.1 PMN/HPF; males: 41 ± 5.2 neutrophils/HPF, P= 0.01) and a 1.5‐fold lower macrophage count (females: 12 ± 1.1 macrophages/HPF; males: 17.5 ± 1.1 macrophages/HPF, P= 0.003) compared to male elastase‐perfused aortas. This study documents decreased expression of multiple cytokines and chemokines and diminished leukocyte trafficking in female rat aortas compared to male aortas following elastase perfusion. These genes may contribute to the gender disparity seen in AAA formation.
TRAF6 Establishes Innate Immune Responses by Activating NF-κB and IRF7 upon Sensing Cytosolic Viral RNA and DNA

Background In response to viral infection, the innate immune system recognizes viral nucleic acids and then induces production of proinflammatory cytokines and type I interferons (IFNs). Toll-like receptor 7 (TLR7) and TLR9 detect viral RNA and DNA, respectively, in endosomal compartments, leading to the activation of nuclear factor κB (NF-κB) and IFN regulatory factors (IRFs) in plasmacytoid dendritic cells. During such TLR signaling, TNF receptor-associated factor 6 (TRAF6) is essential for the activation of NF-κB and the production of type I IFN. In contrast, RIG-like helicases (RLHs), cytosolic RNA sensors, are indispensable for antiviral responses in conventional dendritic cells, macrophages, and fibroblasts. However, the contribution of TRAF6 to the detection of cytosolic viral nucleic acids has been controversial, and the involvement of TRAF6 in IRF activation has not been adequately addressed. Principal Findings Here we first show that TRAF6 plays a critical role in RLH signaling. The absence of TRAF6 resulted in enhanced viral replication and a significant reduction in the production of IL-6 and type I IFNs after infection with RNA virus. Activation of NF-κB and IRF7, but not that of IRF3, was significantly impaired during RLH signaling in the absence of TRAF6. TGFβ-activated kinase 1 (TAK1) and MEKK3, whose activation by TRAF6 during TLR signaling is involved in NF-κB activation, were not essential for RLH-mediated NF-κB activation. We also demonstrate that TRAF6-deficiency impaired cytosolic DNA-induced antiviral responses, and this impairment was due to defective activation of NF-κB and IRF7. Conclusions/Significance Thus, TRAF6 mediates antiviral responses triggered by cytosolic viral DNA and RNA in a way that differs from that associated with TLR signaling. Given its essential role in signaling by various receptors involved in the acquired immune system, TRAF6 represents a key molecule in innate and antigen-specific immune responses against viral infection.
Oral mucosal lesions in a UK HIV/AIDS oral medicine clinic. a nine year, cross-sectional, prospective study.

PURPOSE To investigate changes in presentation of oral mucosal lesions in patients with HIV/AIDS attending a dedicated oral medicine clinic over a nine year period. MATERIALS AND METHODS 358 Patients with HIV/AIDS attending a dedicated oral medicine clinic, contained within a genitourinary medicine clinic. Data was collected prospectively for all patients attending the oral medicine clinic, and entered into a database. Lesions were recorded according to the EEC-WHO diagnostic criteria 1991/1993. RESULTS In 358 patients with 542 lesions, over 54% of the lesions belong within one of the five categories of ulcers, warts, candidiasis, OHL and Kaposi's sarcoma. The major differences in the presentation of the lesions over time were between the ulcers and the warts, but in this series the introduction of HAART did not make a statistical difference. CONCLUSIONS There has been a large reduction in the presentation of oral ulcers, and there appears to be a relative increase in viral papillomata, and a decrease of other mucosal diseases over the period of study. Many of the warts biopsied showed dysplastic changes, and continued follow-up of these patients will be important to determine whether these patients are at increased risk for developing oral squamous carcinoma. Also, proposals are put forward suggesting a need for alteration of the three groups of HIV/AIDS lesions classification suggested by the EEC-WHO consensus.
Increased presentations to emergency departments for asthma associated with rye grass pollen season in inland NSW.

AIM This study measured the frequency and geographical extent of peaks in asthma presentations to emergency departments in inland NSW; it assessed the characteristics of patients who presented at peak presentation times during the rye grass pollination season (October-November) and at other times of the year. METHODS Data describing over 13 years of daily emergency department presentations with a provisional diagnosis of asthma at nine inland NSW base hospitals were assembled. Days of counts in the top 0.1 percentile for each emergency department were classified as peak asthma count days. RESULTS While the rye grass pollen season accounts for only 17% of days in the year, 53% of peak asthma count days fell within that period. Patients aged over 14 years represented 74% of visits on peak asthma count days during the pollen season and 50% on peak days at other times of the year. DISCUSSION Under the right climatic conditions, rye grass pollen may be responsible for presentations for acute asthma to emergency departments in inland NSW.
Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

Circulating tumor cell (CTC) count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.
Understanding the Challenges of Mobile Phone Usage Data

Driven by curiosity and our own three diverse smartphone application usage datasets, we sought to unpack the nuances of mobile device use by revisiting two recent Mobile HCI studies [1, 17]. Our goal was to add to our broader understanding of smartphone usage by investigating if differences in mobile device usage occurred not only across our three datasets, but also in relation to prior work. We found differences in the top-10 apps in each dataset, in the durations and types of interactions as well as in micro-usage patterns. However, it proved very challenging to attribute such differences to a specific factor or set of factors: was it the time frame in which the studies were executed? The recruitment procedure? The experimental method? Using our somewhat troubled analysis, we discuss the challenges and issues of conducting mobile research of this nature and reflect on caveats related to the replicability and generalizability of such work.
On “Visual Prosthesis” by Schiller and Tehovnik (2008)

The first sentence in this extract is inaccurate and misleading because, in fact, we carried out many years of primate experiments before the Clinical Center and the Director of NIH approved our project for a temporary human implant. The second sentence is completely false. Our experiment did not end abruptly and there were no such c̀omplications'. Drs Schiller and Tehovnik base their statement on an unpublished and non-peer-reviewed term paper done in 2004 for a course at the California Institute of Technology (Wagenaar 2004). The statements made in that term paper with respect to our work are totally false. We strenuously reject this mischaracterization of our work and write to set the record straight. Before explaining our approach and what happened after our short-term human experiment, some background information is necessary. The pioneering work of Brindley and Lewin (1968), later confirmed by Dobelle and Mladejovsky (1974), demonstrated that surface stimulation of the human visual cortex produced small spots of light called phosphenes. The current required to produce phosphenes with surface electrodes is in the milliampere range. The results from these studies indicated that a prosthesis based on cortical surface stimulation would have limited usefulness. By implanting floating microelectrodes within the visual cortex, with exposed tip sizes the same order of magnitude as the excited neurons, much more selective stimulation can, in principle, be achieved. In 1976 Salcman and Bak described a new microelectrode developed at NIH. Initially the electrode was used for recording from cat motor cortex. A new way of insulating the microelectrode with Parylene-C was then developed (Loeb et al 1977) and numerous implants were made in the motor cortex of primates to establish safety. The major goal of these studies was to record single-unit neural activity that could be used for controlling artificial limbs and neuromuscular stimulators. The microelectrodes were also used for microstimulation of cortical neurons. The longest implant of a primate was three years (Schmidt et al 1976). Over a 12-year period, the microelectrodes have proven to be safe in primate cortex (Schmidt et al 1988). With these background studies, we believed these microelectrodes would be safe for implantation in the human cortex. LETTER TO THE EDITOR