Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors

This study identifies HLA-A11*01–restricted T-cell receptors (TCRs) that specifically target mutated KRAS, which is an oncogenic driver mutation found in many types of cancers. These TCRs have antitumor activity and thus show potential for clinical use in multiple cancers. KRAS is one of the most frequently mutated proto-oncogenes in human cancers. The dominant oncogenic mutations of KRAS are single amino acid substitutions at codon 12, in particular G12D and G12V present in 60% to 70% of pancreatic cancers and 20% to 30% of colorectal cancers. The consistency, frequency, and tumor specificity of these “neoantigens” make them attractive therapeutic targets. Recent data associate T cells that target mutated antigens with clinical immunotherapy responses in patients with metastatic melanoma, lung cancer, or cholangiocarcinoma. Using HLA-peptide prediction algorithms, we noted that HLA-A*11:01 could potentially present mutated KRAS variants. By immunizing HLA-A*11:01 transgenic mice, we generated murine T cells and subsequently isolated T-cell receptors (TCR) highly reactive to the mutated KRAS variants G12V and G12D. Peripheral blood lymphocytes (PBL) transduced with these TCRs could recognize multiple HLA-A*11:01+ tumor lines bearing the appropriate KRAS mutations. In a xenograft model of large established tumor, adoptive transfer of these transduced PBLs reactive with an HLA-A*11:01, G12D-mutated pancreatic cell line could significantly reduce its growth in NSG mice (P = 0.002). The success of adoptive transfer of TCR-engineered T cells against melanoma and other cancers supports clinical trials with these T cells that recognize mutated KRAS in patients with a variety of common cancer types. Cancer Immunol Res; 4(3); 204–14. ©2015 AACR.
Interactive self-regulation during mate searching: Reciprocal romantic interest increases attention allocation to opposite-sex others.

The present research analyzed automatic self-regulation during mate searching. Specifically, we tested the hypothesis that in a dating context, individuals who are currently looking for a mate show increased automatic attention allocation (focusing effect) to faces of opposite-sex others who display signs of reciprocal romantic interest. We tested this hypothesis in a longitudinal dating study by analyzing intra-individual change in attention allocation to romantic reciprocators and non-reciprocators. Attention allocation was assessed using a visual cueing paradigm prior to and after the announcement of mutual interest in a date between two participants of the study. In line with our hypothesis, focusing effects were obtained selectively for romantic reciprocators. This focusing effect was restricted to participants with a secure attachment style, indicating interindividual differences in adaptive automatic self-regulation processes during mate searching.
Temporal expression of calcium/calmodulin‐dependent adenylyl cyclase isoforms in rat articular chondrocytes: RT‐PCR and immunohistochemical localization

A multitude of signalling cascades are implicated in the homeostasis of articular chondrocytes. However, the identity of these signalling pathways is not fully established. The 3, 5′‐cyclic AMP‐mediated signalling system is considered to be a prototype. Adenylyl cyclase (AC) is an effector enzyme responsible for the synthesis of cAMP. There are 10 mammalian AC isoforms and some of these are differentially regulated by calcium/calmodulin (Ca2+/CaM). Ca2+ is known to play an important role in the development and maintenance of skeletal tissues. Ca2+/CaM‐dependent AC isoforms and their temporal expression in articular chondrocytes in rats were identified using RT‐PCR and immunohistochemistry techniques. All Ca2+/CaM‐dependent AC isoforms were expressed in chondrocytes from all age groups examined. Each isoform was differentially expressed in developing and adult articular chondrocytes. Generally, expression of AC isoforms was observed to increase with age, but the increase was not uniform for all Ca2+/CaM‐dependent AC isoforms. Expression of Ca2+/CaM‐dependent AC isoforms along with other signalling molecules known to be present in articular chondrocytes indicate complicated and multifactorial signalling cascades involved in the development and homeostasis of articular cartilage. The significance of these findings in terms of articular chondrocyte physiology is discussed.
Reducing Truancy in Students with Mild Handicaps

The purpose of the present study was to investigate the effects of an intervention that combined contingency contracting with group counseling on rates of unexcused absences from school, academic grade point average, and rates of grade retention for students with mild handicaps. The subjects were 26 students with high rates of truancy from a comprehensive middle school in an urban school system. Data on rates of truancy and academic performance were collected at three 10-week intervals: pretreatment, posttreatment, and 10 weeks after treatment procedures were concluded. Rates of truancy for students in the experimental condition were significantly reduced at the conclusion of the 10-week treatment period. Unfortunately, gains in attendance for the experimental group did not maintain at posttreatment levels when assessed at follow-up. However, experimental group students' rates of truancy at follow-up did not approach the levels demonstrated by students assigned to the control condition. Measures of academic performance were inconclusive. Results of the study are analyzed and recommendations for future research and practice are offered.
How globalisation improves governance

Globalization, governance and economic performance affect each other in very complex mutual relationships. In this Paper, we establish a clear and well-circumscribed hypothesis: ‘Is there an effect of globalization on governance? ’ To test this hypothesis or, even more specifically, to test how openness can affect the quality of domestic institutions, we survey available theoretical explanations of causal relationships between globalization and governance. Microeconomic theory helps us identify trade policy, competition by foreign producers and international investors, and openness-related differences in institution building costs and benefits, as three major transmission mechanisms through which openness affects a country’s corruption levels. Examining a large sample of countries covering a 20-year long period, we found robust empirical support for the fact that increases in import openness do indeed cause reductions in corruption, a crucial aspect of governance. The magnitude of the effect is also quite strong. After controlling for many cross-country differences, openness’ influence on corruption is close to one third of that exercised by the level of development. Some cautious policy conclusions are derived.
Effects of Summer Break on Math and Spelling Performance as a Function of Grade Level

The effects of a 12-week summer break on the math and spelling performance of 275 second-through fifth-grade students in 2 rural schools in 1 cooperative were assessed by comparing students' aggregated scores on curriculum-based measurement tests administered in the spring and fall. Results indicated that students in grades 2 and 3 regressed significantly in spelling but not in math. The reverse was true for students in grades 4 and 5. Implications regarding curriculum are discussed.
Light and feeding entrainment of the molecular circadian clock in a marine teleost (Sparus aurata)

Daily light and feeding cycles act as powerful synchronizers of circadian rhythmicity. Ultimately, these external cues entrain the expression of clock genes, which generate daily rhythmic behavioral and physiological responses in vertebrates. In the present study, we investigated clock genes in a marine teleost (gilthead sea bream). Partial cDNA sequences of key elements from both positive (Bmal1, Clock) and negative (Per2, Cry1) regulatory loops were cloned before studying how feeding time affects the daily rhythms of locomotor activity and clock gene expression in the central (brain) and peripheral (liver) oscillators. To this end, all fish were kept under a light-dark (LD) cycle and were divided into three experimental groups, depending on the time of their daily meal: mid-light (ML), mid-darkness (MD), or at random (RD) times. Finally, the existence of circadian control on gene expression was investigated in the absence of external cues (DD + RD). The behavioral results showed that seabream fed at ML or RD displayed a diurnal activity pattern (>91% of activity during the day), whereas fish fed at MD were nocturnal (89% of activity during the night). Moreover, seabream subjected to regular feeding cycles (ML and MD groups) showed food-anticipatory activity (FAA). Regardless of the mealtime, the daily rhythm of clock gene expression in the brain peaked close to the light-dark transition in the case of Bmal1 and Clock, and at the beginning of the light phase in the case of Per2 and Cry1, showing the existence of phase delay between the positive and negative elements of the molecular clock. In the liver, however, the acrophases of the daily rhythms differed depending on the feeding regime: the maximum expression of Bmal1 and Clock in the ML and RD groups was in antiphase to the expression pattern observed in the fish fed at MD. Under constant conditions (DD + RD), Per2 and Cry1 showed circadian rhythmicity in the brain, whereas Bmal1, Clock, and Per2 did in the liver. Our results indicate that the seabream clock gene expression is endogenously controlled and in liver it is strongly entrained by food signals, rather than by the LD cycle, and that scheduled feeding can shift the phase of the daily rhythm of clock gene expression in a peripheral organ (liver) without changing the phase of these rhythms in a central oscillator (brain), suggesting uncoupling of the light-entrainable oscillator (LEO) from the food-entrainable oscillator (FEO). These findings provide the basis and new tools for improving our knowledge of the circadian system and entraining pathways of this fish species, which is of great interest for the Mediterranean aquaculture. (Author correspondence: javisan@um.es).
Cycling Off and On Welfare in Canada

Abstract Internationally, traditional approaches to social assistance (welfare) have increasingly been replaced with ‘active’ labour market policies. Alongside other industrialised countries, Canada embraced this shift, with its emphasis on the ‘shortest route’ to paid employment. There has been little research on the outcomes of these dramatic changes in Canada, especially longer term. This article explores the post-welfare labour market experiences of people who were on social assistance in Canada in 1996. It uses the longitudinal micro-data files of the Survey of Labour and Income Dynamics (SLID) from Statistics Canada, which tracks a panel of recipients over five years. We examine the mixing of work and welfare, the transition from welfare to work, and selected labour market indicators – primarily hours of work and wages – that those in receipt of social assistance face in assuming paid work. Those leaving welfare for work face precarious employment opportunities. Leavers earn lower wages, work fewer hours and consequently have lower annual earnings than non-recipients. Over time the gap narrows but remains significant, even after six years. Returns to welfare are frequent. Overall, even after six years most social assistance recipients remained marginalised in the periphery of the labour market.
Pancreatic cancer cachexia: a review of mechanisms and therapeutics

Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions.
Taxation and the Intergenerational Transmission of Human Capital

Abstract How do taxes affect human capital accumulation? This question has been studied extensively in the context of two model classes: overlapping generations (OLG) and infinite horizon (IH) models. These embody very different assumptions about the intergenerational transmission of physical and human capital. OLG models typically abstract from intergenerational linkages, while IH models implicitly assume that new agents inherit human and physical capital from their parents. This paper investigates how such differences in intercohort persistence affect the responsiveness of human capital to taxation. A model is developed that nests OLG and IH models as special cases. Analytical expressions for the steady state tax elasticities of human capital are derived for versions of the model with varying degrees of persistence. The main finding is that higher persistence increases the responsiveness of human capital to both wage and capital income taxes. As a result, IH models generate larger tax elasticities than do OLG models with incomplete persistence, even if cohorts are altruistically linked. In a calibrated version of the model, moving from no persistence to complete persistence increases the tax elasticity of human capital by a factor between two and three.
Domestic dinner

The purpose of this article is to explore contemporary representations and practices of the domestic dinner in the context of households in the process of establishing themselves and families in suburban Norway. The concept of a ‘proper dinner’ is the result of complex social and cultural processes. Cooking dinner is not only an act of caring for others, preparing a proper meal is also an act of positioning oneself. Cooking dinner is an important part of the symbolic production of socially and culturally acceptable feminine subject positions. The empirical analysis is based on in-depth interviews with 25 mothers of young children about how they think and act in their everyday dinner practice. The material shows clear limitations on individuality when it comes to dinner patterns. There is a network of social and cultural conventions that frame eating practices and distinguish between different dishes. These distinctions follow a clear temporal and spatial order. Dishes prepared from a common Norwegian ingredient, minced-meat, are used as an example of how dishes carry quite different social and cultural meanings.While there are several discourses surrounding dinner that offer different possibilities for action, some representations and practices are more ‘proper’ than others. Three distinct dinner models for proper meals are identified: the traditional, the trendy and the therapeutic.
Illusory Arm Movements Activate Cortical Motor Areas: A Positron Emission Tomography Study

Vibration at ∼70 Hz on the biceps tendon elicits a vivid illusory arm extension. Nobody has examined which areas in the brain are activated when subjects perceive this kinesthetic illusion. The illusion was hypothesized to originate from activations of somatosensory areas normally engaged in kinesthesia. The locations of the microstructurally defined cytoarchitectonic areas of the primary motor (4a and 4p) and primary somatosensory cortex (3a, 3b, and 1) were obtained from population maps of these areas in standard anatomical format. The regional cerebral blood flow (rCBF) was measured with15O-butanol and positron emission tomography in nine subjects. The left biceps tendon was vibrated at 10 Hz (LOW), at 70 or 80 Hz (ILLUSION), or at 220 or 240 Hz (HIGH). A REST condition with eyes closed was included in addition. Only the 70 and 80 Hz vibrations elicited strong illusory arm extensions in all subjects without any electromyographic activity in the arm muscles. When the rCBF of the ILLUSION condition was contrasted to the LOW and HIGH conditions, we found two clusters of activations, one in the supplementary motor area (SMA) extending into the caudal cingulate motor area (CMAc) and the other in area 4a extending into the dorsal premotor cortex (PMd) and area 4p. When LOW, HIGH, and ILLUSION were contrasted to REST, giving the main effect of vibration, areas 4p, 3b, and 1, the frontal and parietal operculum, and the insular cortex were activated. Thus, with the exception of area 4p, the effects of vibration and illusion were associated with disparate cortical areas. This indicates that the SMA, CMAc, PMd, and area 4a were activated associated with the kinesthetic illusion. Thus, against our expectations, motor areas rather than somatosensory areas seem to convey the illusion of limb movement.
Subnanosecond spectral diffusion of a single quantum dot in a nanowire

We have studied spectral diffusion of the photoluminescence of a single CdSe quantum dot inserted in a ZnSe nanowire. We have measured the characteristic diffusion time as a function of pumping power and temperature using a recently developed technique [G. Sallen et al., Nat. Photon. 4, 696 (2010)] that offers subnanosecond resolution. These data are consistent with a model where only a single carrier wanders around in traps located in the vicinity of the quantum dot.
Unravelling the role of drinking motives in the relationship between stress and alcohol use and its related problems

Background: A widely held assumption is that one way in which people can cope with stress is by drinking alcohol. Aims: To investigate to what extent drinking motives moderate the possible effect of stress on alcohol use and its related problems, that is, circumstances under which stress is more likely to lead to alcohol use and its related problems. Method: Multiple regression analyses on cross-sectional data of a convenience sample of 179 Dutch students. Results: The role of drinking motives is non-existent in the stress–alcohol relationship. Conclusion: There is limited evidence-based support for the widely held assumption that people cope with stress by drinking alcohol, and drinking motives cannot be used as an alternative explanation to account for stress-related effects on alcohol use and its related problems.
Birth Weight and Its Relationship with the Cardiac Autonomic Balance in Healthy Children

Several studies indicate that the fetal environment plays a significant role in the development of cardiometabolic disease later in life. However, a few studies present conflicting data about the correlation between birth weight and the impairment of cardiac autonomic modulation. The purpose of the present study was to provide further knowledge to elucidate this contradictory relationship. One hundred children aged 5 and 14 years had anthropometric parameters, body composition and blood pressure levels determined. Heart rate variability (HRV) was evaluated by heart rate monitoring, including measurements of both the time and frequency domains. The results showed inverse correlation between the HRV parameters with BMI (RMSSD: P = 0.047; PNN50: P = 0.021; HF: P = 0.041), systolic (RMSSD: P = 0.023; PNN50: P = 0.032) and diastolic (PNN50: P = 0.030) blood pressure levels. On the other hand, there were consistent positive correlations between the HRV parameters and birth weight (RMSSD: P = 0.001; PNN50: P = 0.001; HF: P = 0.002). To determine the effect of birth weight on HRV parameters, we perform multivariate linear regression analysis adjusted for potentially confounding factors (prematurity, gender, age, BMI, physical activity index and SBP levels). These findings were preserved even after adjusting for these confounders. Our results suggested that impaired cardiac autonomic modulation characterized by a reduction in the parasympathetic activity occurs in children with low birth weight. One possible interpretation for these data is that a vagal withdrawal, rather than a sympathetic overactivity, could precede the development of hypertension and other cardiometabolic diseases in children with low birth weight. However, long-term studies should be performed to investigate this possibility.
Compact Inband Full-Duplex Relays With Beyond 100 dB Self-Interference Suppression: Enabling Techniques and Field Measurements

In this communication, the self-interference (SI) channel and the novel enabling techniques for a compact inband full-duplex relay are described and characterized in different operating environments. The full-duplex operation is based on a novel antenna design that uses wavetraps to provide passive isolation of up to 70 dB between the transmit and receive antenna ports. The passive isolation is complemented with novel active RF and digital cancellation stages that further suppress the residual SI to the receiver noise floor. Measurement results of a complete prototype implementation show that the proposed design can achieve an overall SI cancellation performance of over 100 dB even with an ambitious instantaneous bandwidth of 80 MHz. Similar results are obtained both in an anechoic chamber as well as in realistic multipath indoor environments.
Learning to Teach in the Figured World of Reform Mathematics: Negotiating New Models of Identity

Starting from the assertion that traditional and reform mathematics pedagogy constitute two distinct figured worlds of teaching and learning, the authors explore the initiation of prospective teachers into the figured world of reform mathematics pedagogy. To become successful teachers in reform-oriented classrooms, prospective teachers must learn more than pedagogical tools and moves: They must understand what it is to participate in the figured world of reform pedagogy, develop models of identities for participants in this world, and negotiate new constructions of mathematics. In this article the authors present three episodes from an elementary mathematics teacher education class where positions of “teacher” and “child” were offered by instructors in activities designed to approximate practice in the reform figured world. Students negotiated new models of identity and conceptions of mathematics as they took up these positions in varying ways.
Phonological Representations Are Unconsciously Used when Processing Complex, Non-Speech Signals

Neuroimaging studies of speech processing increasingly rely on artificial speech-like sounds whose perceptual status as speech or non-speech is assigned by simple subjective judgments; brain activation patterns are interpreted according to these status assignments. The naïve perceptual status of one such stimulus, spectrally-rotated speech (not consciously perceived as speech by naïve subjects), was evaluated in discrimination and forced identification experiments. Discrimination of variation in spectrally-rotated syllables in one group of naïve subjects was strongly related to the pattern of similarities in phonological identification of the same stimuli provided by a second, independent group of naïve subjects, suggesting either that (1) naïve rotated syllable perception involves phonetic-like processing, or (2) that perception is solely based on physical acoustic similarity, and similar sounds are provided with similar phonetic identities. Analysis of acoustic (Euclidean distances of center frequency values of formants) and phonetic similarities in the perception of the vowel portions of the rotated syllables revealed that discrimination was significantly and independently influenced by both acoustic and phonological information. We conclude that simple subjective assessments of artificial speech-like sounds can be misleading, as perception of such sounds may initially and unconsciously utilize speech-like, phonological processing.