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The IRE1α-XBP1 arm of the unfolded protein response (UPR) has been associated with immunosuppression and cancer progression. Here the authors show that IRE1α-XBP1 activation is associated with poor overall survival in patients with non-small cell lung cancer and that IRE1α loss in cancer cells promotes anti-tumor immune responses in lung cancer preclinical models.

Summary: Infants and children infected with human immunodeficiency virus (HIV)-1 have been shown to develop neutralizing antibodies (nAbs) against heterologous HIV-1 strains, characteristic of broadly nAbs (bnAbs). Thus, having a neonatal model for the induction of heterologous HIV-1 nAbs may provide insights into the mechanisms of neonatal bnAb development. Here, we describe a neonatal model for heterologous HIV-1 nAb induction in pathogenic simian-HIV (SHIV)-infected rhesus macaques (RMs). Viral envelope (env) evolution showed mutations at multiple sites, including nAb epitopes. All 13 RMs generated plasma autologous HIV-1 nAbs. However, 8/13 (62%) RMs generated heterologous HIV-1 nAbs with increasing potency over time, albeit with limited breadth, and mapped to multiple nAb epitopes, suggestive of a polyclonal response. Moreover, plasma heterologous HIV-1 nAb development was associated with antigen-specific, lymph-node-derived germinal center activity. We define a neonatal model for heterologous HIV-1 nAb induction that may inform future pediatric HIV-1 vaccines for bnAb induction in infants and children.

Physical Unclonable Functions (PUFs) are primitives that are designed to leverage naturally occurring variations to produce a random bitstring. Current PUF designs are typically implemented in silicon or utilize variations found in commercial off-the-shelf (COTS) parts. Because of this, existing designs are insufficient for the authentication of Printed Circuit Boards (PCBs). In this paper, we propose a novel PUF design that leverages board variations in a manufactured PCB to generate unique and stable IDs for each PCB. In particular, a single copper trace is used as a source of randomness for bitstring generation. The trace connects three notch filter structures in series, each of which is designed to reject specific but separate frequencies. The bitstrings generated using data measured from a set of PCBs are analyzed using statistical tests to illustrate that high levels of uniqueness and randomness are achievable.

BackgroundPrevious studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts.Methodology/principal findingsFive single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034Conclusions/significanceCommon variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals.

The understanding of maps drawn or significantly influenced by American Indians fosters critical thinking, cultural diversity, and awareness of a much-neglected topic in cartography. Line styles, scale depiction, and the sizing of individual entities are discussed in the context of applying principles from mental maps to American Indian maps and early European maps of North America possessing significant American Indian input.

Professionals in education, treatment, social services, and juvenile justice are bombarded by messages promoting virtually every method as an "evidence-based practice" (EBP). After years of debating EBP, research is turning toward "practice-based evidence" (PBE). The focus shifts from arguing about what practice works best to delivering practices that best meet a person's needs. With so many competing ideas, how do we identify evidence-based principles to guide effective practice? The answer is a little-known term called "consilience," first coined in 1847 by British philosopher of science, William Whewell. He proposed that the ultimate test for any important truth was that it could be supported by knowledge from different fields. Today, consilience finds new importance as researchers toil in specialized silos to churn out millions of disconnected factoids (Cory, 2000; Wilson, 1998). Consilience cuts through complexity by tapping data from diverse sources to identify powerful simple truths. Key sources of knowledge include "natural science," "social science," "experience," and "values." In this article, the authors discuss the new science of "epigenetics," bio-ecological research and interplay, and the dramatic turn from deficit-based to strength-based perspectives in the new millennium. They conclude with a description of the Circle of Courage and its origins.

In the behavioral science literature, successful childhood socialization is termed Positive Youth Development (PYD). Young people themselves are active agents in charting their own life course (Jackson, in press). However, the responsibility for socialization begins with families and is shared by neighbors, faith communities, educators, youth professionals, policy leaders, and all who impact young lives (Eccles & Appleton, 2002). development, simpler principles are needed to make sense of this mass of information (Small & Memmo, 2004). The most parsimonious paradigm is the Circle of Courage (Heck & Subramaniam, 2009) which integrates evidence from positive psychology and neuroscience with child care philosophies from traditional Native "cultures of respect" (Bolin, 2010; Brendtro, Brokenleg, & Van Bockern, 1990). The Circle of Courage applies across all settings including the family (Brokenleg, 2012a), school (Van Bockern & McDonald, 2012), peer group treatment (Quigley, 2004; Steinebach, Jungo, & Zihlmann, 2012), mental health and juvenile justice (Brendtro & Shahbazian, 2004), and faith-based programs (Larson & Brendtro, 2000). Since the Circle of Courage incorporates research from Native cultures, it has particular relevance with indigenous populations worldwide (DeJong & Hall, 2006; James & Lunday, 2014). Herein, the authors describe four evidence-based principles identified by the Circle of Courage model of Positive Youth Development that are essential for young people to succeed and thrive in any setting.

Harsh and cruel experiences have led many of our young to believe that they are alone in the world and that no one cares. In this article, Martin L Mitchell introduces us to the "National CARES Mentoring Movement" founded by Susan L.Taylor. This movement provides young people with role models who help shape their positive development. Mentoring is matter of trust, a structured supportive relationship that brings a young person together with a caring adult who offers guidance and encouragement to develop competence and character. A mentor acts in support of parents or guardians providing counsel, friendship, and constructive examples of how to make responsible life choices. Mentoring can occur in a wide array of settings: school, workplace, a faith-based organization, or even a library or bookstore. "Mentoring is all about caring," says Susan L. Taylor, founder of the National CARES Mentoring Movement. It is caring enough to commit just one hour a week to help and guide a vulnerable young person. The organization formed in 2005 was initially called "Essence CARES." Now known as the "National CARES Mentoring Movement," it has grown to influence more than 125,000 youth. A Brain Trust of leaders created a training and manual for mentors, highlighting the principles they deemed necessary to provide healing and guidance for a too large number of impoverished black youth in this country. The objective is to help African American adults adopt healthy lifestyles and to pass the same on to their children, families, and community. CARES Mentoring Circles are commonly held in faith institutions in a group-mentoring format, which addresses the imbalanced ratio of mentees in need of mentors. This exponentially increases the impact and reach of volunteer mentors and professionals. Mentors can have a profound impact and save a precious young life. Nourished are both the young person and mentor as they are transformed by a mentoring relationship

Periodic mass school shootings and the steady slaughter of youth on the streets of our cities are both products of cultures of violence. The authors highlight key factors that promote or prevent such acts, beginning with the little-known account of a young boy who perpetuated the most deadly school violence in history.

Many methods claim to be Evidence-Based Practices. Yet success comes not from a particular practice, but principles that underlie all effective helping. This article uses the principle of consilience to tap knowledge from science, values, and practical experience.

Professionals dealing with challenging behavior frequently operate detached from the other relationships in the child's life. This narrow approach has been called the unilateral strategy based on the belief that the child's outside world can be ignored and behavior can be changed by administering specific corrective interventions. In contrast, ecological treatment focuses on strengthening relationships in the life space of a child's family, school, peers, and community. No force is more powerful than parents who are the life span experts on their offspring. But in a climate that blames problems on so-called dysfunctional families, parents are often the missing team members. Parents are the best source of data on their children but are seldom enlisted as full team members in the search for solutions. Too often, schools have an uneasy relationship with parents, and residential programs try to keep them at bay. This article provides practical guidelines for building partnerships with families. (Contains 3 endnotes.)

To reach responsible independence, young people must become invested in setting their life course. A rich history of research and practice shows that democratic group climates foster autonomy and prosocial behavior. This article explores principles and practices for creating positive peer cultures to develop strengths and help youth meet their full potential. (Contains 4 endnotes.)

A flood of contradictory publications claim widely different methods to be "evidence-based." What then are the key principles for success with challenging youth? Amidst all the confusion, how do we identify powerful universal truths? The answer lies in a "consilience," which involves drawing information from multiple fields of knowledge. Consilience combines research from the natural sciences and the social sciences with wisdom from experience and values. The authors propose twenty evidence-based principles meeting this test for truth. (Contains 2 figures.)

Decades of studies show that children's behavior is shaped by relationships in the "social ecology" of family, peers, school, and community. But in recent decades the prevailing scientific dogma was that genes determine destiny. Now it is clear that experience changes genes. For better or worse, environmental experiences including nutrition, stress, emotions, and learning can modify the genes. The knowledge that experience shapes genes can also provide new hope for healing and building resilient brain pathways.

Starr Commonwealth has served troubled children and youth and their families for nearly a century. Starr's Montcalm Schools operate from campuses in Michigan and Ohio, enrolling students referred by families and educational consultants. The Montcalm Outdoor Challenge Program is a key part of Starr's network of nonprofit alternative education and treatment programs. It operates from a base camp and involves treks in wilderness settings. Positive peer cultures are created in a rich experiential learning environment. Trained staff guide students through a process of building trust, exploring problems, and creating transformational change. Families are integral partners in the Outdoor Challenge program. (Contains 1 table.)