Miracle-dz/UniFAR-FTUs huggingface dataset:
Preclinical Development Drug Resistance to Inhibitors of the Human Double Minute-2 E 3 Ligase Is Mediated by Point Mutations of p 53 , but Can Be Overcome with the p 53 Targeting Agent RITA

The human double minute (HDM)-2 E3 ubiquitin ligase plays a key role in p53 turnover and has been validated preclinically as a target in multiple myeloma (MM) and mantle cell lymphoma (MCL). HDM-2 inhibitors are entering clinical trials, andwe therefore sought to understandpotentialmechanisms of resistance in lymphoid models. Wild-type p53 H929 MM and Granta-519 MCL cells resistant to MI-63 or Nutlin were generated by exposing them to increasingdrug concentrations.MI-63-resistantH929 andGranta-519 cellswere resistant to Nutlin, whereas Nutlin-resistant cells displayed cross-resistance toMI-63. These cells also showed cross-resistance to bortezomib, doxorubicin, cisplatin, and melphalan, but remained sensitive to the small molecule inhibitor RITA (reactivation of p53 and induction of tumor cell apoptosis). HDM-2 inhibitor-resistant cells harbored increasedp53 levels, but neither genotoxic nor nongenotoxic approaches to activate p53 induced HDM-2 or p21. Resequencing revealed wild-type HDM-2, but mutations were found in the p53 DNA binding and dimerization domains. In resistant cells, RITA induced aG2–M arrest, upregulation of p53 targets HDM-2, PUMA, and NOXA, and PARP cleavage. Combination regimens with RITA and MI-63 resulted in enhanced cell death compared with RITA alone. These findings support the possibility that p53 mutation could be a primary mechanism of acquired resistance to HDM-2 inhibitors in MCL and MM. Furthermore, they suggest that simultaneous restoration of p53 function and HDM-2 inhibition is a rational strategy for clinical translation. Mol Cancer Ther; 11(10); 2243–53. 2012 AACR.
Comparative analysis of breast cancer mortality following mammography screening in Denmark and Norway.

BACKGROUND Denmark and Norway are the best countries to study effects of mammography screening, because they are the only countries with stepwise introduction of nationwide mammography screening, enabling comparative effectiveness studies of high quality. Although Denmark and Norway are countries with similar populations and health care systems, reported reductions in breast cancer mortality (incidence-based) caused by screening differed vastly; 25% in Denmark versus 10% in Norway. This study explores reasons for this difference. PATIENTS AND METHODS We compared two published studies from the Danish and Norwegian screening programs (Olsen et al., 2005; Kalager et al., 2010) investigating biennial mammography screening for women age 50-69 years. Four comparison groups of women were constructed ('current' and 'historical screening groups'; 'current' and 'historical nonscreening groups') based on county of residence. We calculated incidence-based breast cancer mortality in the current versus the historical period for screening and nonscreening groups, using mortality rate ratios (MRR) in the two countries, accounting for concomitant changes in breast cancer mortality. RESULTS In the screening groups, similar reductions in breast cancer mortality were found when periods preceding and following start of screening were compared, in Denmark [25%; MRR 0.75; 95% confidence interval (CI) 0.64% to 0.88%] and in Norway (28%; MRR 0.72; 95% CI 0.63% to 0.81%). However, mortality increased in Denmark in the current nonscreening group compared with the historical nonscreening group; for women >59 years, breast cancer mortality increased by 14% (MRR 1.14, 95% CI 1.07-1.22), whereas in Norway a 19% reduction was seen (MRR 0.81, 95% CI 0.72-0.92). This increase accounts for the different relative effect of screening in Denmark and Norway; 25% breast cancer mortality reduction in Denmark, 10% in Norway. CONCLUSIONS The seemingly larger effect of screening in Denmark may not be solely attributable to screening itself, but to increased breast cancer mortality in women older than 59 years not invited to screening.
Performance benefits of resource-constrained adaptive filtering

In this paper we study the convergence performance of partial-update adaptive filters in a systems identification context, which has several applications in signal processing and communications. We show that a certain class of data-dependent partial-update adaptive filter algorithms can achieve improved convergence performance with respect to their full-update counterparts for highly correlated input signals. The findings of the paper are illustrated with simulation examples.
Voluminious Object Recognition & Spatial Reallocation Into a Containing Medium ( VORSRICM )

Placing objects in the fridge, like many tasks, is simple for humans and complex for robots. A necessary component of loading a refrigerator is to stack any items such that they are available and in the most space-efficient locations. We consider optimal packing as a refrigerator that has the smallest amount of unoccupied space between items and has the most items in view. Because of this, rotating objects and placing them on top of one another becomes important, meaning the stackability of each object’s sides is crucial for packing a fridge. Assuming a simple rectangular prism model for each object, we propose a learning approach to determine the stackability of each object’s faces. Training a support vector machine on point cloud data of food and kitchen related objects, we determine which sides are suitable for objects to be placed on top of. This information then is incorporated into our bin-packing algorithm, allowing the PR2 to stack items with less initial information about its environment.
Forwarding in opportunistic networks with resource constraints

Effective forwarding in mobile opportunistic networks is a challenge, given the unpredictable mobility of nodes, short contact durations between nodes, wireless interference and limited buffer sizes. Most forwarding algorithms aim at decreasing costs (relative to flooding the network) by forwarding only to nodes which are likely to be good relays. While it is non-trivial to decide if an encountered node is a good relay or not at the moment of encounter, it is harder still to prioritize which messages to transmit under the presence of short contact durations and which messages to drop when buffers become full. The main objective of this paper is to study different message prioritization schemes using real measurements. Such schemes can be broadly divided into two categories - schemes which do not use any network information, and schemes which do. Examples of the former set of schemes include FIFO/LIFO etc. For the latter set of schemes, there is a key design choice: On one hand, we have the following scheme: when a forwarding opportunity presents itself, assign high priorities to messages which are relatively close to their intended destination. On the other hand, we can assign high priorities to messages which are farther away from their destination than closer messages. In order to decide if messages are close to their destination or not, we have to rely on a forwarding algorithm. For this, we use delegation forwarding schemes which have been shown to be efficient in terms of cost incurred in the network. We develop a new set of prioritization schemes based on delegation schemes. We consider these schemes in our empirical study.
Maximum kurtosis beamforming with a subspace filter for distant speech recognition

This paper presents a new beamforming method for distant speech recognition (DSR). The dominant mode subspace is considered in order to efficiently estimate the active weight vectors for maximum kurtosis (MK) beamforming with the generalized sidelobe canceler (GSC). We demonstrated in [1], [2], [3] that the beamforming method based on the maximum kurtosis criterion can remove reverberant and noise effects without signal cancellation encountered in the conventional beamforming algorithms. The MK beamforming algorithm, however, required a relatively large amount of data for reliably estimating the active weight vector because it relies on a numerical optimization algorithm. In order to achieve efficient estimation, we propose to cascade the subspace (eigenspace) filter [4, §6.8] with the active weight vector. The subspace filter can decompose the output of the blocking matrix into directional signals and ambient noise components. Then, the ambient noise components are averaged and would be subtracted from the beamformer's output, which leads to reliable estimation as well as significant computational reduction. We show the effectiveness of our method through a set of distant speech recognition experiments on real microphone array data captured in the real environment. Our new beamforming algorithm provided the best recognition performance among conventional beamforming techniques, a word error rate (WER) of 5.3 %, which is comparable to the WER of 4.2 % obtained with a close-talking microphone. Moreover, it achieved better recognition performance with a fewer amounts of adaptation data than the conventional MK beamformer.
Sharp-switching Z2-FET device in 14 nm FDSOI technology

Z2-FET (Zero Impact Ionization and Zero Subthreshold Slope FET) is a very recent sharp switching device which achieves remarkable performance in terms of leakage current and triggering control. The device is fabricated with Ultra-Thin Body and Buried Oxide (UTBB) Silicon-On-Insulator (SOI) technology, features an extremely sharp on-switch, an adjustable triggering voltage (VON), and can be considered for Electro-Static Discharge (ESD). The operation of our device relies on the modulation of electrons and holes injection barriers. In this paper, we show, for the first time, experimental data obtained on the 14 nm FDSOI (Fully Depleted SOI) node.
Reliability of cardiovascular reactivity to stress: internal consistency.

Research on the reliability of cardiovascular reactivity has focused on temporal stability and intertask consistency with only modest results. The present study evaluated the internal consistency reliability of cardiovascular reactivity in three large samples of adolescents and young adults (N=326, 136, and 142). Impedance cardiographic and blood pressure measures were recorded at rest and during standard laboratory stress tasks (math, video game, cold pressor). The reliability of cardiovascular reactivity within tasks, as assessed by Cronbach's alpha coefficient of internal consistency, ranged from alpha=. 83 to . 96 for 4-min to 5-min math tasks, and alpha=. 65 to . 94 for 3-min video game and cold pressor tasks. Although highly reliable within tasks, cardiovascular reactivity was less reliable across tasks, even within a single testing session. Possible reasons for the discrepancy between internal consistency and intertask consistency are discussed.
Toward Optogenetic Control of Neural Synchrony : Experimental Results from the Hippocampal Slice Model of Gamma Oscillations and Computational Modeling OF TECHNOLOGY by OCT 2 6 2009

Ever since Hans Berger recorded the first human EEGs in humans and observed large, rhythmic 8 Hz field oscillations, neuroscientists have been intrigued by the pervasive presence of synchronized, regular patterns of the activity in the brain. A number of frequency bands, spanning from 0.1 to several hundred hertz have been described, and associated with particular functions and brain states. Not surprisingly, disruptions in such patterns have been postulated to be the mechanistic basis of a number of disorders, from schizophrenia to Parkinson's disease, to Alzheimer. Until now, however, virtually all evidence on the role of synchronous oscillations in brain functions has been merely correlative, that is, it has never been possible to selectively manipulate neural synchrony without altering other fundamental properties of the system and observing the functional outcome. This limit may now be overcome with the introduction of genetically targeted light-activeatable means of controlling neural activity, which allows spatially and temporally precise control of the activity of determined classes of neurons. Although the ultimate goal is to observe the functional, behavioral outcomes of modulating synchrony in awake animals, it's necessary first to develop such techniques in vitro, if we are to be able (given the current technological limitations) to extract useful "design principles" that can meaningfully generalize. A particularly well-studied, reliable and yet relevant in vitro model, is the hippocampal slice gamma oscillations model, so we have been focusing on those as a testbed, integrating experimental work with computational modeling. Among the previously undescribed capabilities we have gained in the process are: precisely resetting the phase of an ongoing gamma oscillation, altering its frequency, and modulating its amplitude.
Cataract surgery in posterior polymorphous corneal dystrophy

Posterior polymorphous corneal dystrophy (PPCD) is a dominantly inherited, commonly non-progressive condition featuring metaplasia (with epithelial features) and overgrowth of corneal endothelial cells and defects in the Descemet membrane.1 Slit-lamp biomicroscopy shows isolated or coalescent vescicles and/or band-shaped lesions.2 Patients are usually asymptomatic, although more severe cases may develop corneal oedema.2 3 The outcomes of modern cataract surgery in eyes with asymptomatic PPCD have never been reported (one case of a patient who developed corneal oedema is cited, but no details are given). 4 Hence, we aimed to describe two patients with PPCD who successfully underwent phacoemulsification and intraocular lens (IOL) implantation. Two men with PPCD, aged 71 and 75, had been scheduled for cataract surgery on the same day. On slit-lamp biomicroscopy, a vertical paracentral band-shaped lesion was preset in patient 1 (figure 1) and a horizontal band-shaped lesion in patient 2 (figure …
Cost-Effective Enhancement on Both Yield and Reliability for Cache Designs Based on Performance Degradation Tolerance

Guaranteeing functional correctness of cache memories is crucial for computer designs. In the literature, there have been several works addressing this issue. However, fault tolerability of these methods may be limited. In this paper, we present a new cache architecture that has flexible tolerability. Moreover, by using the proposed architecture, both yield and reliability of the cache can be enhanced simultaneously. In our cache, a particular type of cache blocks called tolerable block is further identified among the faulty ones. Such blocks can still be used during cache access in our architecture, while accessing to intolerable blocks will result in additional cache misses, and therefore performance degradation. The number of tolerable cache blocks is thus critical for the achievable yield and reliability enhancement, as well as the incurred cost on performance. In this work, error correcting code (ECC) methods are employed to increase the number of tolerable blocks. In particular, we propose to embed the required check bits in one of the cache ways. Analysis results show that this embedding method only incurs minor performance degradation, while the incurred area overhead due to ECC can thus be significantly reduced from 5.92% to only 0.92%. General applicability of the embedding method to ordinary ECC methods is also investigated. Experimental results show that the performance degradation can be reduced from 16% to only 1.53% by using the proposed cache. This leads to great tolerability improvement, and thus the yield and reliability are enhanced very significantly when compared with the previous work.
Gust of me: reconnecting mother and son

The Gust of Presence conceptual design lets parents and children who live apart reconnect in a more friendship-based relationship. With two Gustbowls, parents and children can communicate in a simple way that requires little effort and could subtly become a part of their daily routines. Gustbowl is designed to promote and support informal, unobtrusive interactions in families whose members live apart. The Gustbowl helps families keep in touch, rather than just exchange information, by letting members be a part of each other's daily routines. This lets them have the little encounters that are ordinary to members who live together yet are greatly missed by members who live apart. We describe how the Delft design team created the Gustbowl from user studies by developing the concept for and field-testing an experiential prototype.
Characterization of Highly Porous Materials from Cellulose Carbamate

Highly porous cellulose was formed by gelation of cellulose carbamate solutions in caustic soda. Two methods for gel preparation were optimized for the formation of beads and bulky materials - the chemical precipitation from dilute sulfuric acid and the thermal gelation by annealing at elevated temperatures. Various methods were used for characterizing of the pores of low density materials: scanning electron microscopy, small angle X-ray scattering, mercury intrusion and nitrogen sorption. These methods were optimized and used for characterizing the complete pore system from micro to macro pores. The effects of different preparation (cellulose carbamate concentration in caustic soda) and processing (precipitation, drying and pyrolysis) on the pore structure were studied by the set of complementary methods. Aerocell samples with a minimum density of 0.06 g/cm 3 were prepared from cellulose carbamate. They are characterized by a broad pore size distribution ranging from 0.5 nm to 1 mm, specific internal surfaces of up to 660 m 2 /g and total pore volumes of up to 18 cm 3 /g.
Do Structural Changes of T Cell Receptor Complex Occur in Tumor‐bearing State?

T cells in tumor‐bearing mice and cancer patients were recently shown to be devoid of CD3‐ζ chain, a signal‐transducing invariant chain in T cell receptor (TCR) complex, and p56lck tyrosine kinase. In the present study, we investigated the structure and function of TCR complex in T cells from BALB/c mice bearing CSA1M fibrosarcoma. The expressions of TCR chains and p56lck in a T cell‐enriched population from spleen were analyzed. Almost complete loss of CD3‐ζ and p56lck was observed in the preparation from tumor‐bearing mice as assessed by immunoblotting analysis using whole cell lysates, whereas the amounts of other TCR chains were relatively unchanged. However, these changes were due to the increase of contaminating Mac‐1+ cells in the spleen of tumor‐bearing mice because: 1) the removal of Mac‐1+ cells led to the restoration of CD3‐ζ and p56lck; and 2) CD3‐ζ was clearly present when the preparation was solubilized with ionic detergent. Fc receptor γ chain detected in the preparation from tumor‐bearing mice disappeared along with the removal of Mac‐1+ cells. These observations were further supported by the finding that addition of Mac‐1+ cells from tumor‐bearing mice to normal T cells resulted in loss of CD3‐ζ, leaving CD3‐ζ largely intact. When T cells from tumor‐bearing mice were highly purified by depletion of Mac‐1+ cells, these T cells contained normal amounts of CD3‐ζ at mRNA, protein, and surface levels, and expressed the properly assembled TCR complex on their cell surface. Moreover, stimulation of the TCR in these T cells by anti‐TCR antibodies resulted in a comparable Ca2+ mobilization to that observed in normal T cells. These results suggest that no structural changes occur in TCR complex in our tumor‐bearing mice, and that complete depletion of Mac‐1+ cells in important to assess the structure of TCR complex.
PGC-1α Coactivates PDK4 Gene Expression via the Orphan Nuclear Receptor ERRα: a Mechanism for Transcriptional Control of Muscle Glucose Metabolism

ABSTRACT The transcriptional coactivator PGC-1α is a key regulator of energy metabolism, yet little is known about its role in control of substrate selection. We found that physiological stimuli known to induce PGC-1α expression in skeletal muscle coordinately upregulate the expression of pyruvate dehydrogenase kinase 4 (PDK4), a negative regulator of glucose oxidation. Forced expression of PGC-1α in C2C12 myotubes induced PDK4 mRNA and protein expression. PGC-1α-mediated activation of PDK4 expression was shown to occur at the transcriptional level and was mapped to a putative nuclear receptor binding site. Gel shift assays demonstrated that the PGC-1α-responsive element bound the estrogen-related receptor α (ERRα), a recently identified component of the PGC-1α signaling pathway. In addition, PGC-1α was shown to activate ERRα expression. Chromatin immunoprecipitation assays confirmed that PGC-1α and ERRα occupied the mPDK4 promoter in C2C12 myotubes. Additionally, transfection studies using ERRα-null primary fibroblasts demonstrated that ERRα is required for PGC-1α-mediated activation of the mPDK4 promoter. As predicted by the effects of PGC-1α on PDK4 gene transcription, overexpression of PGC-1α in C2C12 myotubes decreased glucose oxidation rates. These results identify the PDK4 gene as a new PGC-1α/ERRα target and suggest a mechanism whereby PGC-1α exerts reciprocal inhibitory influences on glucose catabolism while increasing alternate mitochondrial oxidative pathways in skeletal muscle.
Trends in Obesity Prevalence Among Children and Adolescents in the United States, 1988-1994 Through 2013-2014.

IMPORTANCE Previous analyses of obesity trends among children and adolescents showed an increase between 1988-1994 and 1999-2000, but no change between 2003-2004 and 2011-2012, except for a significant decline among children aged 2 to 5 years. OBJECTIVES To provide estimates of obesity and extreme obesity prevalence for children and adolescents for 2011-2014 and investigate trends by age between 1988-1994 and 2013-2014. DESIGN, SETTING, AND PARTICIPANTS Children and adolescents aged 2 to 19 years with measured weight and height in the 1988-1994 through 2013-2014 National Health and Nutrition Examination Surveys. EXPOSURES Survey period. MAIN OUTCOMES AND MEASURES Obesity was defined as a body mass index (BMI) at or above the sex-specific 95th percentile on the US Centers for Disease Control and Prevention (CDC) BMI-for-age growth charts. Extreme obesity was defined as a BMI at or above 120% of the sex-specific 95th percentile on the CDC BMI-for-age growth charts. Detailed estimates are presented for 2011-2014. The analyses of linear and quadratic trends in prevalence were conducted using 9 survey periods. Trend analyses between 2005-2006 and 2013-2014 also were conducted. RESULTS Measurements from 40,780 children and adolescents (mean age, 11.0 years; 48.8% female) between 1988-1994 and 2013-2014 were analyzed. Among children and adolescents aged 2 to 19 years, the prevalence of obesity in 2011-2014 was 17.0% (95% CI, 15.5%-18.6%) and extreme obesity was 5.8% (95% CI, 4.9%-6.8%). Among children aged 2 to 5 years, obesity increased from 7.2% (95% CI, 5.8%-8.8%) in 1988-1994 to 13.9% (95% CI, 10.7%-17.7%) (P < .001) in 2003-2004 and then decreased to 9.4% (95% CI, 6.8%-12.6%) (P = .03) in 2013-2014. Among children aged 6 to 11 years, obesity increased from 11.3% (95% CI, 9.4%-13.4%) in 1988-1994 to 19.6% (95% CI, 17.1%-22.4%) (P < .001) in 2007-2008, and then did not change (2013-2014: 17.4% [95% CI, 13.8%-21.4%]; P = .44). Obesity increased among adolescents aged 12 to 19 years between 1988-1994 (10.5% [95% CI, 8.8%-12.5%]) and 2013-2014 (20.6% [95% CI, 16.2%-25.6%]; P < .001) as did extreme obesity among children aged 6 to 11 years (3.6% [95% CI, 2.5%-5.0%] in 1988-1994 to 4.3% [95% CI, 3.0%-6.1%] in 2013-2014; P = .02) and adolescents aged 12 to 19 years (2.6% [95% CI, 1.7%-3.9%] in 1988-1994 to 9.1% [95% CI, 7.0%-11.5%] in 2013-2014; P < .001). No significant trends were observed between 2005-2006 and 2013-2014 (P value range, .09-.87). CONCLUSIONS AND RELEVANCE In this nationally representative study of US children and adolescents aged 2 to 19 years, the prevalence of obesity in 2011-2014 was 17.0% and extreme obesity was 5.8%. Between 1988-1994 and 2013-2014, the prevalence of obesity increased until 2003-2004 and then decreased in children aged 2 to 5 years, increased until 2007-2008 and then leveled off in children aged 6 to 11 years, and increased among adolescents aged 12 to 19 years.