Miracle-dz/UniFAR-FTUs huggingface dataset:
Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC

The prognosis for patients with advanced esophageal or head-and-neck squamous cell carcinoma (ESCC or HNSCC) remains poor, and the identification of additional oncogenes and their inhibitors is needed. In this study, we evaluated the sensitivities of several ESCC and HNSCC cell lines to HER inhibitors (cetuximab, erlotinib, and afatinib) in vitro and found two cell lines that were hypersensitive to afatinib. Sequence analyses for the afatinib-targeted HER family genes in the two cell lines revealed that one cell line had a previously reported activating EGFR L861Q mutation, whereas the other had an HER4 G1109C mutation of unknown function. No amplification of HER family genes was found in either of the two cell lines. The phosphorylation level of HER4 was elevated in the HER4 G1109C mutation-overexpressed HEK293 cell line, and the mutation had a transforming potential and exhibited tumorigenicity in an NIH3T3 cell line, indicating that this HER4 mutation was an activating oncogenic mutation. Afatinib dramatically reduced the phosphorylation level of EGFR or HER4 and induced apoptosis in the two cell lines. In vivo, tumor growth was also dramatically decreased by afatinib. In a database, the frequencies of HER family gene mutations in ESCC or HNSCC ranged from 0% to 5%. In particular, HER4 mutations have been found relatively frequently in HNSCC. Considering the addiction of cancer cells to activating oncogenic EGFR or HER4 mutations for proliferation, HNSCC or ESCC with such oncogenic mutations might be suitable for targeted therapy with afatinib. Mol Cancer Ther; 15(8); 1988–97. ©2016 AACR.
A Non-Search Optimal Control Solution for a Team of MUAVS in a Reconnaissance Mission

We consider a team of miniature unmanned air vehicles (MUAVs) in a multi-static radar scenario. Time delay and Doppler measurements made at the UAVs are transmitted to a base station which is tracking a target. The base then transmits heading commands to the MUAVs to reduce the tracking error. Optimal solutions that attempt to minimise a function of the error covariance or maximize the observability of the system are computationally difficult to implement. We present a simpler approximate method that yields a closed-form solution and performs comparably to the optimal approaches
Motion classification for cross traffic in urban environments using laser and radar

In this paper, an approach for motion classification for laser sensors is presented concentrating on urban environments. In these complex environments the algorithm has to match both cross traffic and structures in parallel to the road, as well as objects starting and stopping moving. The requirements on sensors and algorithms for handling urban traffic are specified and some basic definitions in the context of motion classification are introduced in this paper. Our new approach extends the limits of a consistency-based motion classification with a laser sensor by a track-before-detect approach in a first step and, in a second step, by an additional source. This additional source is a radar sensor whose data is treated in a special way to be able to deal with cross traffic without any tracking. This approach runs online and has been validated in crowded urban environment.
Imagery Deficits in Nonverbal Learning Disabilities

This study reports the observations gathered from 11 children referred to consulting services because of learning difficulties at school and diagnosed with nonverbal learning disabilities (NVLD). These children had an average verbal IQ, but a WISC-R performance IQ lower than the verbal IQ by at least 15 points and experienced difficulties especially in mathematics and drawing. The children completed a battery of four tasks requiring visuospatial working memory and visual imagery: a memory task composed of pictures and their positions (Pictures task), a task that required them to memorize the positions filled in a matrix (Passive Matrix task), a task that required them to imagine a pathway along a matrix (Active Matrix task) and a task that required them to learn groups made up of three words, using a visual interactive imagery strategy (TV task). In comparison to a control group of 49 children, children with NVLD scored lower in all the tasks, showing deficits in the use of visuospatial working memory and visual imagery. By contrasting subgroups of children of different ages in the control group, it was possible to show that some tasks did not show a clear developmental trend. Thus the deficits shown by the children with NVLD cannot simply be attributed to a developmental delay of these children, but seem to reflect a more severe disability.
Genetic Variations in the Sonic Hedgehog Pathway Affect Clinical Outcomes in Non–Muscle-Invasive Bladder Cancer

Sonic hedgehog (Shh) pathway genetic variations may affect bladder cancer risk and clinical outcomes. Therefore, we genotyped 177 single-nucleotide polymorphisms (SNP) in 11 Shh pathway genes in a study including 803 bladder cancer cases and 803 controls. We assessed SNP associations with cancer risk and clinical outcomes in 419 cases of non–muscle-invasive bladder cancer (NMIBC) and 318 cases of muscle-invasive and metastatic bladder cancer (MiMBC). Only three SNPs (GLI3 rs3823720, rs3735361, and rs10951671) reached nominal significance in association with risk (P ≤ 0.05), which became nonsignificant after adjusting for multiple comparisons. Nine SNPs reached a nominally significant individual association with recurrence of NMIBC in patients who received transurethral resection (TUR) only (P ≤ 0.05), of which two (SHH rs1233560 and GLI2 rs11685068) were replicated independently in 356 TUR-only NMIBC patients, with P values of 1.0 × 10−3 (SHH rs1233560) and 1.3 × 10−3 (GLI2 rs11685068). Nine SNPs also reached a nominally significant individual association with clinical outcome of NMIBC patients who received Bacillus Calmette-Guérin (BCG; P ≤ 0.05), of which two, the independent GLI3 variants rs6463089 and rs3801192, remained significant after adjusting for multiple comparisons (P = 2 × 10−4 and 9 × 10−4, respectively). The wild-type genotype of either of these SNPs was associated with a lower recurrence rate and longer recurrence-free survival (versus the variants). Although three SNPs (GLI2 rs735557, GLI2 rs4848632, and SHH rs208684) showed nominal significance in association with overall survival in MiMBC patients (P ≤ 0.05), none remained significant after multiple-comparison adjustments. Germ-line genetic variations in the Shh pathway predicted clinical outcomes of TUR and BCG for NMIBC patients. Cancer Prev Res; 3(10); 1235–45. ©2010 AACR.
Persuasive Effects of Point of View, Protagonist Competence, and Similarity in a Health Narrative About Type 2 Diabetes

We examined the persuasive effects of three narrative features in a message about type 2 diabetes: narrative point of view (first- vs. third-person perspective), protagonist competence (positive role model who prevents diabetes vs. negative role model who develops diabetes), and protagonist-reader similarity (demographically similar vs. dissimilar). We posited that a first-person point of view would elevate people’s identification levels more than a third-person point of view, especially when the protagonist was depicted as a positive role model. We also expected a similar protagonist to foster greater levels of identification than a dissimilar one. In addition, the positive effect of a competent role model on identification was expected to be enhanced under the condition of reader-protagonist similarity. Finally, we hypothesized that the effects of identification on persuasion would be mediated by self-referencing. Participants 30 years of age or younger (N = 489) were randomly assigned to read a story about a person with a family history of type 2 diabetes that was altered with regard to the experimental factors. Thereafter they completed a questionnaire incorporating measures of study variables. Greater levels of identification were found to foster self-referencing, leading to persuasion. Identification was strongest with a first-person point of view and when the narrator was a positive role model. The effect of identification on persuasion was mediated by self-referencing. Contrary to expectations, protagonist-reader demographic similarity did not affect identification or self-referencing. There was no support for the two moderation hypotheses.
Modeling and analysis of the role of fast-response energy storage in the smart grid

The large short time-scale variability of renewable energy resources presents significant challenges to the reliable operation of power systems. This variability can be mitigated by deploying fast-ramping generators. However, these generators are costly to operate and produce environmentally harmful emissions. Fast-response energy storage devices, such as batteries and flywheels, provide an environmentally friendly alternative, but are expensive and have limited capacity. To study the environmental benefits of storage, we introduce a slotted-time dynamic residual dc power flow model with the prediction error of the difference between the generation (including renewables) and the load as input and the fast-ramping generation and the storage (charging/discharging) operation as the control variables used to ensure that the demand is satisfied (as much as possible) in each time slot. We assume the input prediction error sequence to be i.i. d. zero-mean random variables. The optimal power flow problem is then formulated as an infinite horizon average-cost dynamic program with the cost function taken as a weighted sum of the average fast-ramping generation and the loss of load probability. We find the optimal policies at the two extremes of the cost function weights and propose a two-threshold policy for the general case. We also obtain refined analytical results under the assumption of Laplace distributed prediction error and corroborate this assumption using simulated wind power generation data from NREL.
Cannabinoid WIN 55,212-2 Regulates TRPV1 Phosphorylation in Sensory Neurons*

Cannabinoids are known to have multiple sites of action in the nociceptive system, leading to reduced pain sensation. However, the peripheral mechanism(s) by which this phenomenon occurs remains an issue that has yet to be resolved. Because phosphorylation of TRPV1 (transient receptor potential subtype V1) plays a key role in the induction of thermal hyperalgesia in inflammatory pain models, we evaluated whether the cannabinoid agonist WIN 55,212-2 (WIN) regulates the phosphorylation state of TRPV1. Here, we show that treatment of primary rat trigeminal ganglion cultures with WIN led to dephosphorylation of TRPV1, specifically at threonine residues. Utilizing Chinese hamster ovary cell lines, we demonstrate that Thr144 and Thr370 were dephosphorylated, leading to desensitization of the TRPV1 receptor. This post-translational modification occurred through activation of the phosphatase calcineurin (protein phosphatase 2B) following WIN treatment. Furthermore, knockdown of TRPA1 (transient receptor potential subtype A1) expression in sensory neurons by specific small interfering RNA abolished the WIN effect on TRPV1 dephosphorylation, suggesting that WIN acts through TRPA1. We also confirm the importance of TRPA1 in WIN-induced dephosphorylation of TRPV1 in Chinese hamster ovary cells through targeted expression of one or both receptor channels. These results imply that the cannabinoid WIN modulates the sensitivity of sensory neurons to TRPV1 activation by altering receptor phosphorylation. In addition, our data could serve as a useful strategy in determining the potential use of certain cannabinoids as peripheral analgesics.
Better Than Advertised: Improved Collision-Resistance Guarantees for MD-Based Hash Functions

The MD transform that underlies the MD and SHA families iterates a compression function h to get a hash function H. The question we ask is, what property X of h guarantees collision resistance (CR) of H? The classical answer is that X itself be CR. We show that weaker conditions X, in particular forms of what we call constrained-CR, suffice. This reduces demands on compression functions, to the benefit of security, and also, forensically, explains why collision-finding attacks on compression functions have not, historically, lead to immediate breaks of the corresponding hash functions. We obtain our results via a definitional framework called RS security, and a parameterized treatment of MD, that also serve to unify prior work and variants of the transform.
Role of microtubules in the organization and localization of the Golgi apparatus

Normal interphase PtK2 and A549 cells display long microtubules radiating from the microtubule-organizing center (MTOC) to the plasma membrane. Both MTOC and Golgi apparatus are contained in the same perinuclear area. Treatment of cells with 1 microM colcemid for 2 h results in microtubule depolymerization and fragmentation of the Golgi apparatus into elements scattered throughout the cytoplasm. Both normal microtubules and the Golgi apparatus assemble again following removal of colcemid. Injection of the alpha, beta-nonhydrolyzable GTP analog, guanosine 5'(alpha, beta-methylene)diphosphate [pp(CH2)pG], into interphase cells growing in normal medium results in the formation of microtubule bundles resistant to colcemid and prevents the fragmentation of the Golgi apparatus. Injection of pp(CH2)pG into cells incubated with colcemid results in substitution of tubulin ribbons for microtubules and has no effect on the Golgi-derived elements scattered throughout the cytoplasm. Removal of colcemid 1 h after the injection of pp(CH2)pG results in polymerization of large numbers of short, single randomly oriented microtubules, whereas the Golgi apparatus remains fragmented. Treatment of cells with 10 microM taxol for 3 h results both in polymerization of microtubule bundles without relation to the MTOC in the cell periphery and fragmentation of the Golgi apparatus. The Golgi-derived fragments are present exclusively in regions of the peripheral cytoplasm enriched in microtubules. The codistribution of microtubules and Golgi elements can be reversed in taxol-treated cells by injection of a monoclonal (YL 1/2) antibody reacting specifically with the tyrosylated form of alpha-tubulin. Cells incubated with colcemid after treatment with taxol have large numbers of Golgi-derived elements in close association with colcemid-resistant microtubule bundles. Incubation of cells with 50 microM vinblastine for 90 min results in microtubule dissembly, formation of tubulin paracrystals, and fragmentation of the Golgi apparatus into elements without relation to the tubulin paracrystals.
Personal messages reduce vandalism and theft of unattended scientific equipment

Scientific equipment, such as animal traps and autonomous data collection systems, is regularly left in the field unattended, making it an easy target for vandalism or theft. We tested the effectiveness of three label types, which differed in their information content and tone of the message, that is, personal, neutral or threatening, for reducing incidents of vandalism and theft of unattended scientific field equipment. The three label types were attached to 20 scientific equipment dummies each, which were placed semi‐hidden and evenly distributed in four public parks in Munich, Germany. While the label type had no effect on the severity of the interactions with our equipment dummies, the personal label reduced the overall number of interactions by c. 40–60%, compared with the dummies showing the neutral or threatening label type. We suggest that researchers, in addition to securing their field equipment, label it with personal and polite messages that inform about the ongoing research and directly appeal to the public not to disturb the equipment. Further studies should extend these results to areas with different socio‐economic structure.
New TA Index-Based Rollover Prevention System for Electric Vehicles

In addition to clean transportation and energy savings, electric vehicles can inherently offer better performance in the field of active safety and dynamic stability control, thanks to the superior fast and accurate control characteristics of electric motors. With the novel wheel status parameter TA for electric vehicles proposed by the authors in an earlier publication, a new TA index (TAI)-based rollover prevention method is presented in this paper to improve the driving performance of EVs equipped with in-wheel motors. A three-level electric vehicle control structure is used to analyze the effective control steps for rollover prevention with the newly proposed TAI method. The simulation is conducted using an in-house developed electric vehicle dynamic model. The simulation results prove the feasibility of using TAI to detect rollover. The experiment uses an electric vehicle equipped with four in-wheel motors in the authors’ research lab. The vehicle parameter and performance data are imported to CarSim, which is industrial standard vehicle dynamic analysis software to run the rollover test. The experimental results also demonstrate that TAI is an effective method of rollover prevention.
Music Training Enhances Rapid Neural Plasticity of N1 and P2 Source Activation for Unattended Sounds

Neurocognitive studies have demonstrated that long-term music training enhances the processing of unattended sounds. It is not clear, however, whether music training also modulates rapid (within tens of minutes) neural plasticity for sound encoding. To study this phenomenon, we examined whether adult musicians display enhanced rapid neural plasticity compared to non-musicians. More specifically, we compared the modulation of P1, N1, and P2 responses to standard sounds between four unattended passive blocks. Among the standard sounds, infrequently presented deviant sounds were presented (the so-called oddball paradigm). In the middle of the experiment (after two blocks), an active task was presented. Source analysis for event-related potentials (ERPs) showed that N1 and P2 source activation was selectively decreased in musicians after 15 min of passive exposure to sounds and that P2 source activation was found to be re-enhanced after the active task in musicians. Additionally, ERP analysis revealed that in both musicians and non-musicians, P2 ERP amplitude was enhanced after 15 min of passive exposure but only at the frontal electrodes. Furthermore, in musicians, the N1 ERP was enhanced after the active discrimination task but only at the parietal electrodes. Musical training modulates the rapid neural plasticity reflected in N1 and P2 source activation for unattended regular standard sounds. Enhanced rapid plasticity of N1 and P2 is likely to reflect faster auditory perceptual learning in musicians.
High-throughput chromatin information enables accurate tissue-specific prediction of transcription factor binding sites

In silico prediction of transcription factor binding sites (TFBSs) is central to the task of gene regulatory network elucidation. Genomic DNA sequence information provides a basis for these predictions, due to the sequence specificity of TF-binding events. However, DNA sequence alone is an impoverished source of information for the task of TFBS prediction in eukaryotes, as additional factors, such as chromatin structure regulate binding events. We show that incorporating high-throughput chromatin modification estimates can greatly improve the accuracy of in silico prediction of in vivo binding for a wide range of TFs in human and mouse. This improvement is superior to the improvement gained by equivalent use of either transcription start site proximity or phylogenetic conservation information. Importantly, predictions made with the use of chromatin structure information are tissue specific. This result supports the biological hypothesis that chromatin modulates TF binding to produce tissue-specific binding profiles in higher eukaryotes, and suggests that the use of chromatin modification information can lead to accurate tissue-specific transcriptional regulatory network elucidation.
Detection of a carrier state in Theileria parva-infected cattle by the polymerase chain reaction

SUMMARY Two sets of oligonucleotide primers, one derived from a repetitive sequence and the other from the gene encoding a 67 kDa sporozoite antigen of Theileria parva, were used to amplify parasite DNA from the blood of T. parva-infected carrier cattle using the polymerase chain reaction (PCR). PCR amplification products were obtained from 15 carrier cattle infected with one of 4 different T. parva stocks. Successful amplifications were performed using DNA from 2 cattle infected with T. p. parva Pemba Mnarani, 10 cattle infected with T. p. parva Marikebuni, 2 cattle infected with T. p. bovis Boleni and 1 animal infected with T. p. lawrencei 7014. No amplification products were obtained from any of 7 cattle which had been infected with the T. p. parva Muguga stock. A synthetic oligonucleotide, which hybridized specifically to T. p. parva Marikebuni DNA among 6 T. parva stocks tested, was designed using sequence data from within the region of the T. parva genome amplified by the repetitive sequence primers. The oligonucleotide was used to probe PCR products and to increase the sensitivity and specificity of carrier animal detection. Southern blot analysis using a T. parva repetitive sequence probe demonstrated the existence of restriction fragment length polymorphisms between parasites isolated from T. p. parva Marikebuni-infected carrier cattle. The use of the PCR and other methods of carrier animal detection are discussed.
Eigenvalue Bounds, Spectral Partitioning, and Metrical Deformations via Flows

We present a new method for upper bounding the second eigenvalue of theLaplacian of graphs. Our approach uses multi-commodity flows to deform the geometry of the graph; we embed the resulting metric into Euclidean space to recover a bound on the Rayleigh quotient. Using this, we show that every n-vertex graph of genus g and maximum degree d satisfies lambda2(G) = O((g+1)3d/n). This recovers the O(d/n) bound of Spielman and Teng for planar graphs, and compares to Kelner's bound of O((g+1)poly(d)/n), but our proof does not make use of conformal mappings or circle packings. We are thus able to extend this to resolve positively a conjecture of Spielman and Teng, by proving that lambda2(G) = O(dh6log h/n) whenever G is Kh-minor free. This shows, in particular, that spectral partitioning can be used to recover O(radicn)-sized separators in bounded degree graphs that exclude a fixed minor. We extend this further by obtaining nearly optimal bounds on lambda2 for graphs which exclude small-depth minors in the sense of Plotkin, Rao, and Smith. Consequently, we show that spectral algorithms find small separators in a general class of geometric graphs. Moreover, while the standard "sweep'' algorithm applied to the second eigenvector may fail to find good quotient cuts in graphs of unbounded degree, our approach produces a vector that works for arbitrary graphs. This yields an alternate proof of the result of Alon, Seymour, and Thomas that every excluded-minor family of graphs has O(radicn)-node balanced separators.
La identificación de los alumnos rechazados. Comparación de métodos sociométricos de nominaciones bidimensionales

Resumen Se revisa la historia, los procedimientos y las cuestiones básicas del método sociométrico de nominaciones directas (procedimientos estandarizados y de probabilidad, número de dimensiones, número de elecciones, población elegible, elecciones intra y entregéneros). Los objetivos son establecer una terminología compartida y facilitar la comparación de los estudios. Con una muestra de 121 alumnos de 5 aulas de cuarto de educación primaria se comparan diferentes sistemas de clasificación sociométrica y se valida un procedimiento, basado en la distribución binomial continua, que asegura una precisa identificación de todos los tipos sociométricos, es exhaustiva y presenta una excelente validez discriminante.