Miracle-dz/UniFAR-FTUs huggingface dataset:
User experience experiments with mobile devices in outdoors activities: Use case: cycling and mountain biking

This paper discusses our experiences in our last user experience experiment. The purpose of the experiment was to obtain qualitative and quantitative data about the user experience of modern mobile devices like smartwatches and smartphones in outdoor activities like mountain biking. We describe a specific method of running that kind of field experiments. The use of various evaluation measures, mobile devices and tools is discussed, based on our experiences. As a result of that experiment, we discuss the convenience of using mobile devices in outdoor activities like mountain biking and which were the benefits and inconveniences found by the participants.
p53-dependent Down-regulation of Telomerase Is Mediated by p21waf1*

Inactivation of p53 and activation of telomerase occur in the majority of human cancers, raising the possibility of a link between these two pathways. Overexpression of wild-type p53 down-regulates the enzymatic activity of telomerase in various cancer cell lines through transcriptional repression of its catalytic subunit, human telomerase reverse transcriptase (hTERT). In this study, we re-evaluated the role of p53 in telomerase regulation using isogenic cell lines expressing physiological levels of p53. We demonstrate that endogenous wild-type p53 was able to down-regulate telomerase activity, hTERT mRNA levels, and promoter activity; however, the ability to repress hTERT expression was found to be cell type-specific. The integrity of the DNA-binding core domain, the N-terminal transactivation domain, and the C-terminal oligomerization domains of p53 was essential for hTERT promoter repression, whereas the proline-rich domain and the extreme C terminus were not required. Southwestern and chromatin immunoprecipitation experiments demonstrated lack of p53 binding to the hTERT promoter, raising the possibility of an indirect repressive mechanism. The down-regulation of hTERT promoter activity was abolished by a dominant-negative E2F1 mutant. Mutational analysis identified a specific E2F site responsible for p53-mediated repression. Knockdown of the key p53 transcriptional target, p21, was sufficient to eliminate the p53-dependent repression of hTERT. Inactivation of the Rb family using either viral oncoproteins or RNA interference attenuated the repression. Inhibition of histone deacetylases also interfered with the repression of hTERT by p53. Therefore, our results suggest that repression of hTERT by endogenous p53 is mediated by p21 and E2F.
PERITONEAL DIALYSIS AFTER NONRENAL SOLID ORGAN TRANSPLANTATION: CLINICAL OUTCOMES AND PRACTICAL CONSIDERATIONS

The incidence of end-stage renal disease following nonrenal solid organ transplantation (NRSOT) is increasing and is associated with a poor prognosis. The etiology of end-stage renal disease is multifactorial, with calcineurin inhibitor (CNI) nephrotoxicity being primarily responsible. The impact of dialysis modality on the survival of these patients remains unclear. Peritoneal dialysis appears to be a feasible and safe option for renal replacement therapy in NRSOT patients. Concerns that NRSOT patients are at a higher risk of infectious and noninfectious complications necessitate practical considerations when prescribing and planning for peritoneal dialysis in these patients. While nephrotoxicity is a well-recognized complication of long-term CNI use, “peritoneotoxic” effects with significant alterations in peritoneal membrane structure and function have recently been described. Further study including the role of CNI-free immunotherapy protocols to optimize the outcomes of NRSOT recipients is needed.
Stim1 Regulates Enamel Mineralization and Ameloblast Modulation

Loss-of-function mutations in the Ca2+ release-activated Ca2+ channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE) and result in ectodermal dysplasia with amelogenesis imperfecta. However, because of the limited availability of patient tissue, analyses of enamel mineralization or possible changes in ameloblast function or morphology have not been possible. Here, we generated mice with ectodermal tissue-specific deletion of Stim1 (Stim1 cKO [conditional knockout]), Stim2 (Stim2 cKO), and Stim1 and Stim2 (Stim1/2 cKO) and analyzed their enamel phenotypes as compared with those of control (Stim1/2fl/fl) animals. Ablation of Stim1 and Stim1/2 but not Stim2 expression resulted in chalky enamel and severe attrition at the incisor tips and molar cusps. Stim1 and Stim1/2 cKO, but not Stim2 cKO, demonstrated inferior enamel mineralization with impaired structural integrity, whereas the shape of the teeth and enamel thickness appeared to be normal in all animals. The gene expression levels of the enamel matrix proteins Amelx and Ambn and the enamel matrix proteases Mmp20 and Klk4 were not altered by the abrogation of SOCE in Stim1/2 cKO mice. The morphology of ameloblasts during the secretory and maturation stages was not significantly altered in either the incisors or molars of the cKO animals. However, in Stim1 and Stim1/2 cKO incisors, the alternating modulation of maturation-stage ameloblasts between the smooth- and ruffle-ended cell types continued beyond the regular cycle and extended to the areas corresponding to the zone of postmodulation ameloblasts in the teeth of control animals. These results indicate that SOCE is essential for proper enamel mineralization, in which Stim1 plays a critical role during the maturation process.
Comparative Experiments on Disambiguating Word Senses: An Illustration of the Role of Bias in Machine Learning

This paper describes an experimental comparison of seven different learning algorithms on the problem of learning to disambiguate the meaning of a word from context. The algorithms tested include statistical, neural-network, decision-tree, rule-based, and case-based classification techniques. The specific problem tested involves disambiguating six senses of the word ``line'' using the words in the current and proceeding sentence as context. The statistical and neural-network methods perform the best on this particular problem and we discuss a potential reason for this observed difference. We also discuss the role of bias in machine learning and its importance in explaining performance differences observed on specific problems.
Type 7 Adenylyl Cyclase is Involved in the Ethanol and CRF Sensitivity of GABAergic Synapses in Mouse Central Amygdala

The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and in the anxiogenic response to ethanol withdrawal. Previously, we found that both ethanol and corticotropin releasing factor (CRF) increase GABAergic transmission in mouse and rat CeA neurons, in part by enhancing the release of GABA via activation of presynaptic CRF1 receptors. CRF1 receptors are coupled to the enzyme adenylyl cyclase (AC), which produces the second messenger cyclic AMP. There are nine isoforms of AC, but we recently found that CRF1 receptors in the pituitary were coupled to the Type 7 AC (AC7). Therefore, using an in vitro electrophysiological approach in brain slices, here we have investigated a possible role of the AC7 signaling pathway in ethanol and CRF effects on CeA GABAergic synapses of genetically modified mice with diminished brain Adcy7 activity (HET) compared to their littermate male wild-type (WT) mice. We found no significant differences in basal membrane properties, mean baseline amplitude of evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs), or paired-pulse facilitation (PPF) of GABAA-IPSPs between HET and WT mice. In CeA neurons of WT mice, ethanol superfusion significantly augmented (by 39%) GABAA-IPSPs and decreased PPF (by 25%), suggesting increased presynaptic GABA release. However, these effects were absent in HET mice. CRF superfusion also significantly augmented IPSPs (by 38%) and decreased PPF (by 23%) in WT CeA neurons, and still elicited a significant but smaller (by 13%) increase of IPSP amplitude, but no effect on PPF, in HET mice. These electrophysiological data suggest that AC7 plays an important role in ethanol and CRF modulation of presynaptic GABA release in CeA and thus may underlie ethanol-related behaviors such as anxiety and dependence.
Expression of Autophagy-Related Proteins According to Androgen Receptor and HER-2 Status in Estrogen Receptor-Negative Breast Cancer

Purpose The purpose of this study was to investigate the expression of autophagy-related proteins in relation to androgen receptor (AR) status in estrogen receptor (ER)-negative breast cancers. Methods We extracted 334 ER-negative breast cancer samples to construct tissue microarrays (TMAs), which were immunohistochemically stained for autophagy-related proteins (beclin-1, LC3A, LC3B, p62) and for AR and HER-2. Results There were 127 AR-positive cases and 207 AR-negative cases, and 140 HER-2-positive cases and 194 HER-2 negative cases. The AR-negative group was associated with tumoral LC3A expression (P<0.001), while the AR-positive group was associated with tumoral BNIP3 expression (P<0.001). Tumoral LC3A was most highly expressed in the AR-negative and HER-2 negative group, while stromal LC3A showed the highest expression in the AR-negative and HER-2-positive group. Tumoral BNIP3 and stromal BNIP3 were highest in the AR-positive and HER-2-negative group. In the AR-positive and HER-2-negative group, stromal p62 positivity was an independent factor that was statistically significant in its association with shorter disease-free survival (DFS) (Hazard ratio: 10.21, 95% CI: 1.130–92.31, P = 0.039). Shorter DFS was associated with tumoral LC3A positivity (Hazard ratio: 10.28, 95% CI: 2.068–51.19, P = 0.004) in the AR-negative and HER-2-positive group. Conclusion In ER-negative breast cancers, AR status was associated with expression of different types of autophagy-related proteins. Tumoral LC3A was most highly expressed in AR-negative breast cancers, while tumor BNIP3 was highest in AR-positive breast cancers.
ISAC: Integrated Space-and-Time-Adaptive Chip-Package Thermal Analysis

Ever-increasing integrated circuit (IC) power densities and peak temperatures threaten reliability, performance, and economical cooling. To address these challenges, thermal analysis must be embedded within IC synthesis. However, this requires accurate three-dimensional chip-package heat flow analysis. This has typically been based on numerical methods that are too computationally intensive for numerous repeated applications during synthesis or design. Thermal analysis techniques must be both accurate and fast for use in IC synthesis. This paper presents a novel accurate incremental spatially and temporally adaptive chip-package thermal analysis technique called ISAC for use in IC synthesis and design. It is common for IC temperature variation to strongly depend on position and time. ISAC dynamically adapts spatial- and temporal-modeling granularities to achieve high efficiency while maintaining accuracy. Both steady-state and dynamic thermal analyses are accelerated by the proposed heterogeneous spatial-resolution adaptation and asynchronous thermal-element time-marching techniques. Each technique enables orders-of-magnitude improvement in performance while preserving accuracy when compared with other state-of-the-art adaptive steady-state and dynamic IC thermal analysis techniques. Experimental results indicate that these improvements are sufficient to make accurate dynamic and steady-state thermal analysis practical within the inner loops of IC synthesis algorithms. ISAC has been validated against reliable commercial thermal analysis tools using industrial and academic synthesis test cases and chip designs. It has been implemented as a software package suitable for integration in IC synthesis and design flows and has been publicly released
Autophagy induction causes a synthetic lethal sensitization to ribonucleotide reductase inhibition in breast cancer cells

Macroautophagy can promote cellular survival or death depending on the cellular context and its extent. We hypothesized that autophagy induction would synergize with a therapeutic agent targeting the autophagic cargo. To test this hypothesis, we treated breast cancer MDA-MB-231 cells with tamoxifen (TMX), which induces autophagy through an estrogen receptor-independent pathway. Induction of autophagy reduced cellular levels of RRM2, a subunit of ribonucleotide reductase (RR), the rate limiting enzyme in the production of deoxyribonucleotide triphosphates (dNTPs). This autophagy inducer was combined with COH29, an inhibitor developed in our laboratory that targets RR through a novel mechanism. The combination therapy showed synergistic effects on cytotoxicity in vitro and in an in vivo xenograft model. This cytotoxicity was blocked by knockdown of the autophagy protein ATG5 or addition of chloroquine, an autophagy inhibitor. The combined therapy also induced dNTP depletion and massive genomic instability, leading us to hypothesize that combining autophagy induction with RR inhibition can lead to mitotic catastrophe in rapidly dividing cells. We propose that this TMX + COH29 combined therapy may have clinical benefit. Furthermore, autophagy induction may be a general mechanism for augmenting the effects of chemotherapeutic agents
Efficient Quantum Algorithms for (Gapped) Group Testing and Junta Testing

In the k-junta testing problem, a tester has to efficiently decide whether a given function f: {0, 1}n → {0, 1} is a k-junta (i.e., depends on at most fc of its input bits) or is e-far from any k-junta. Our main result is a quantum algorithm for this problem with query complexity O([EQUATION]) and time complexity O(n[EQUATION]). This quadratically improves over the query complexity of the previous best quantum junta tester, due to Atici and Servedio. Our tester is based on a new quantum algorithm for a gapped version of the combinatorial group testing problem, with an up to quartic improvement over the query complexity of the best classical algorithm. For our upper bound on the time complexity we give a near-linear time implementation of a shallow variant of the quantum Fourier transform over the symmetric group, similar to the Schur-Weyl transform. We also prove a lower bound of Ω(k1/3) queries for junta-testing (for constant e).
Tuning afferent synapses of hippocampal interneurons by neuropeptide Y

Cholecystokinin (CCK)‐expressing basket cells encompass a subclass of inhibitory GABAergic interneurons that regulate memory‐forming oscillatory network activity of the hippocampal formation in accordance to the emotional and motivational state of the animal, conveyed onto these cells by respective extrahippocampal afferents. Various excitatory and inhibitory afferent and efferent synapses of the hippocampal CCK basket cells express serotoninergic, cholinergic, cannabinoid, and benzodiazepine sensitive receptors, all contributing to their functional plasticity. We explored whether CCK basket cells are modulated by neuropeptide Y (NPY), one of the major local neuropeptides that strongly inhibits hippocampal excitability and has significant effect on its memory function. Here, using GAD65‐GFP transgenic mice for prospective identification of CCK basket cells and whole‐cell patch‐clamp recordings, we show for the first time that excitatory and inhibitory inputs onto CCK basket cells in the dentate gyrus of the hippocampus are modulated by NPY through activation of NPY Y2 receptors. The frequency of spontaneous and miniature EPSCs, as well as the amplitudes of stimulation‐evoked EPSCs were decreased. Similarly, the frequency of both spontaneous and miniature IPSCs, and the amplitudes of stimulation‐evoked IPSCs were decreased after NPY application. Most of the effects of NPY could be attributed to a presynaptic site of action. Our data provide the first evidence that the excitatory and inhibitory inputs onto the CCK basket cells could be modulated by local levels of NPY, and may change the way these cells process extrahippocampal afferent information, influencing hippocampal function and its network excitability during normal and pathological oscillatory activities. © 2009 Wiley‐Liss, Inc.
Star Formation in Sculptor Group Dwarf Irregular Galaxies and the Nature of “Transition” Galaxies

We present new Hα narrowband imaging of the H II regions in eight Sculptor group dwarf irregular (dI) galaxies. The Hα luminosities of the detected H II regions range from some of the faintest detected in extragalactic H II regions (∼1035 ergs s-1 in SC 24) to some of the most luminous (∼1040 ergs s-1 in NGC 625). The total Hα luminosities are converted into current star formation rates (SFRs). Comparing the Sculptor group dI's to the Local Group dI's, we find that the Sculptor group dI's have, on average, lower values of SFR when normalized to either galaxy luminosity or gas mass (although there is considerable overlap between the two samples). The range for both the Sculptor group and Local Group samples is large when compared with that seen for the sample of gas-rich, quiescent, low surface brightness (LSB) dI's from van Zee et al. (published in 1997) and the sample of isolated dI's from van Zee (from 2000 and 2001). This is probably best understood as a selection effect since the nearby group samples have a much larger fraction of extremely low luminosity galaxies and the smaller galaxies are much more liable to large relative variations in current SFRs. The Sculptor group and LSB samples are very similar with regard to mean values of both τgas and τform, and the Local Group and isolated dI samples are also similar to each other in these two quantities. Currently, the Sculptor group lacks dI galaxies with elevated normalized current SFRs as high as the Local Group dI's IC 10 and GR 8. The properties of "transition" (dSph/dIrr) galaxies in Sculptor and the Local Group are also compared and found to be similar. The transition galaxies are typically among the lowest luminosities of the gas-rich dwarf galaxies. Relative to the dwarf irregular galaxies, the transition galaxies are found preferentially nearer to spiral galaxies and are found nearer to the center of the mass distribution in the local cloud. While most of these systems are consistent with normal dI galaxies, exhibiting temporarily interrupted star formation, the observed density-morphology relationship (which is weaker than that observed for the dwarf spheroidal galaxies) indicates that environmental processes such as "tidal stirring" may play a role in causing their lower SFRs.
Challenges in the Evaluation of Urinary Iodine Status in Pregnancy: The Importance of Iodine Supplement Intake and Time of Sampling

Objectives: Median urinary iodine concentration (UIC) is the recommended method to evaluate iodine status in pregnancy, but several factors may challenge the interpretation of the results. We evaluated UIC in pregnant women according to (1) sampling in the hospital versus at home, (2) time of the most recent iodine supplement intake prior to sampling, and (3) members of their household. Study Design: Danish cross-sectional study in the year 2012. Pregnant women (n = 158), their male partners (n = 157) and children (n = 51) provided a questionnaire with detailed information on iodine supplement intake and a spot urine sample obtained in the hospital and/or at home for measurement of UIC and urinary creatinine concentration. Results: In the pregnant women providing a urine sample both in the hospital and at home (n = 66), individual UIC (p = 0.002) and urinary creatinine concentration (p = 0.042), but not estimated 24-hour urinary iodine excretion (p = 0.79), were higher when sampling was at home. Median UIC was dependent on the time of the most recent iodine supplement intake prior to sampling [same day (n = 79): 150 µg/l (95% CI 131-181 µg/l), the day before (n = 51): 105 µg/l (78-131 µg/l), several days ago/non-user (n = 28): 70 µg/l (56-94 µg/l), p < 0.001]. The pattern was similar in the male partners. Apart from a more frequent iodine supplement intake in pregnancy (87.3% vs. partners 15.9%), no systematic differences were observed in urinary measurements between the pregnant women and their partners. Conclusions: Time of spot urine sampling and time span from iodine supplement intake to spot urine sampling should be considered when evaluating urinary iodine status in pregnancy.
The Plant Vacuolar Sorting Receptor Atelp Is Involved in Transport of Nh2-Terminal Propeptide-Containing Vacuolar Proteins in Arabidopsis thaliana

Many soluble plant vacuolar proteins are sorted away from secreted proteins into small vesicles at the trans-Golgi network by transmembrane cargo receptors. Cleavable vacuolar sorting signals include the NH2-terminal propeptide (NTPP) present in sweet potato sporamin (Spo) and the COOH-terminal propeptide (CTPP) present in barley lectin (BL). These two proteins have been found to be transported by different mechanisms to the vacuole. We examined the ability of the vacuolar cargo receptor AtELP to interact with the sorting signals of heterologous and endogenous plant vacuolar proteins in mediating vacuolar transport in Arabidopsis thaliana. AtELP extracted from microsomes was found to interact with the NTPPs of barley aleurain and Spo, but not with the CTPPs of BL or tobacco chitinase, in a pH-dependent and sequence-specific manner. In addition, EM studies revealed the colocalization of AtELP with NTPP-Spo at the Golgi apparatus, but not with BL-CTPP in roots of transgenic Arabidopsis plants. Further, we found that AtELP interacts in a similar manner with the NTPP of the endogenous vacuolar protein AtALEU (Arabidopsis thaliana Aleu), a protein highly homologous to barley aleurain. We hypothesize that AtELP functions as a vacuolar sorting receptor involved in the targeting of NTPP-, but not CTPP-containing proteins in Arabidopsis.
Emerging Roles for Long Non-Coding RNAs in Cancer and Neurological Disorders

The recent discovery of thousands of long non-coding (lnc)RNAs in the human genome has prompted investigation of the potential roles of these molecules in human biology and medicine. Indeed, it is now well documented that many lncRNAs are involved in key biological processes, including dosage compensation, genomic imprinting, chromatin regulation, alternative splicing of pre-mRNA, nuclear organization; and potentially many other biological processes, which are yet to be elucidated. Recently, a number of studies have also reported that lncRNAs are dysregulated in a number of human diseases, including several cancers and neurological disorders. Although many of these studies have fallen short of implicating lncRNAs as causative, they suggest potential roles that warrant further in depth investigations. In this review, we discuss the current state of knowledge regarding the roles of lncRNAs in cancer and neurological disorders, and suggest potential future directions in this rapidly emerging field.
Electrophysiologic Studies in Patients with Persistent Atrial Tachycardia

Clinical and electrophysiologic studies in two patients with chronic persistent atrial tachycardia unresponsive to drug or electroconversion therapy are reported. In both, exercise increased the atrial rate and decreased the atrioventricular nodal conduction time. The opposite effect occurred after &bgr;-adrenergic blockade. Single electrically-induced atrial depolarizations (A2) at progressively premature times resulted in a linear increase in the return cycle (A2A3) until plateau levels were achieved but failed to produce sinus rhythm. Abrupt cessation of continuous atrial pacing at rates up to 600 beats/min in one patient and up to 300 beats/min in the other resulted in a pause that was similar to the plateau levels of A2A3 achieved during atrial scanning with single impulses. Our findings suggest that an ectopic atrial focus is responsible for this arrhythmia. The electrophysiologic properties of the ectopic pacemaker appear to be similar to the sinoatrial node in some respects but to differ in terms of spontaneous rate and in relative immunity from the effects of overdrive pacing.