Elasticity is concerned with determining the strength and load carrying ability of engineering structures including buildings, bridges, cars, planes, and thousands of machine parts that most of us ...never see. It is especially important in the fields of mechanical, civil, aeronautical and materials engineering. This book provides a concise and organized presentation and development of the theory of elasticity, moving from solution methodologies, formulations and strategies into applications of contemporary interest, including fracture mechanics, anisotropic/composite materials, micromechanics and computational methods. Developed as a text for a one or two-semester graduate elasticity course, this new Second Edition is the only elasticity text to provide coverage in the new area of non-homogenous, or graded, material behavior. End of chapter exercises throughout the book are fully incorporated with the use of MATLAB software.
Background
Childhood maltreatment is the most important preventable cause of psychopathology accounting for about 45% of the population attributable risk for childhood onset psychiatric disorders. A ...key breakthrough has been the discovery that maltreatment alters trajectories of brain development.
Methods
This review aims to synthesize neuroimaging findings in children who experienced caregiver neglect as well as from studies in children, adolescents and adults who experienced physical, sexual and emotional abuse. In doing so, we provide preliminary answers to questions regarding the importance of type and timing of exposure, gender differences, reversibility and the relationship between brain changes and psychopathology. We also discuss whether these changes represent adaptive modifications or stress‐induced damage.
Results
Parental verbal abuse, witnessing domestic violence and sexual abuse appear to specifically target brain regions (auditory, visual and somatosensory cortex) and pathways that process and convey the aversive experience. Maltreatment is associated with reliable morphological alterations in anterior cingulate, dorsal lateral prefrontal and orbitofrontal cortex, corpus callosum and adult hippocampus, and with enhanced amygdala response to emotional faces and diminished striatal response to anticipated rewards. Evidence is emerging that these regions and interconnecting pathways have sensitive exposure periods when they are most vulnerable.
Conclusions
Early deprivation and later abuse may have opposite effects on amygdala volume. Structural and functional abnormalities initially attributed to psychiatric illness may be a more direct consequence of abuse. Childhood maltreatment exerts a prepotent influence on brain development and has been an unrecognized confound in almost all psychiatric neuroimaging studies. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex as they are discernible in both susceptible and resilient individuals with maltreatment histories. Mechanisms fostering resilience will need to be a primary focus of future studies.
Childhood maltreatment is the most important preventable cause of psychopathology, accounting for about almost half of the risk for childhood onset psychiatric disorders. A key discovery is that maltreatment alters trajectories of brain development. This review synthesizes neuroimaging findings in children who experienced caregiver neglect, as well as from studies in young people and adults who experienced physical, sexual and emotional abuse. Key findings are that childhood maltreatment is associated with consistent alterations in key regions of the brain and maltreatment is consistently associated with enhanced amygdala response to threatening stimuli and diminished striatal response to anticipated reward. Brain regions and pathways affected are predominantly part of circuits regulating threat detection and reward anticipation, with exposure to single types of abuse associated with specific alterations that convey the aversive experience. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex, however, as they are discernible in both susceptible and resilient individuals with maltreatment histories. Future studies will need to focus on mechanisms fostering resilience.
Read the Commentary on this article at doi: 10.1111/jcpp.12540
The formation of temporal dissipative Kerr solitons in microresonators driven by a continuous-wave laser enables the generation of coherent, broadband, and spectrally smooth optical frequency combs ...as well as femtosecond pulse sources with compact form factors. Here we report the observation of a Raman-induced soliton self-frequency shift for a microresonator dissipative Kerr soliton also referred to as the frequency-locked Raman soliton. In amorphous silicon nitride microresonator-based single soliton states the Raman effect manifests itself by a spectrum that is sech^{2} in shape and whose center is spectrally redshifted from the continuous wave pump laser. The shift is theoretically described by the first-order shock term of the material's Raman response, and we infer a Raman shock time of ∼20 fs for amorphous silicon nitride. Moreover, we observe that the Raman-induced frequency shift can lead to a cancellation or overcompensation of the soliton recoil caused by the formation of a coherent dispersive wave. The observations are in agreement with numerical simulations based on the Lugiato-Lefever equation with a Raman shock term. Our results contribute to the understanding of Kerr frequency combs in the soliton regime, enable one to substantially improve the accuracy of modeling, and are relevant to the understanding of the fundamental timing jitter of microresonator solitons.
Solitons are waveforms that preserve their shape while propagating, as a result of a balance of dispersion and nonlinearity. Soliton-based data transmission schemes were investigated in the 1980s and ...showed promise as a way of overcoming the limitations imposed by dispersion of optical fibres. However, these approaches were later abandoned in favour of wavelength-division multiplexing schemes, which are easier to implement and offer improved scalability to higher data rates. Here we show that solitons could make a comeback in optical communications, not as a competitor but as a key element of massively parallel wavelength-division multiplexing. Instead of encoding data on the soliton pulse train itself, we use continuous-wave tones of the associated frequency comb as carriers for communication. Dissipative Kerr solitons (DKSs) (solitons that rely on a double balance of parametric gain and cavity loss, as well as dispersion and nonlinearity) are generated as continuously circulating pulses in an integrated silicon nitride microresonator via four-photon interactions mediated by the Kerr nonlinearity, leading to low-noise, spectrally smooth, broadband optical frequency combs. We use two interleaved DKS frequency combs to transmit a data stream of more than 50 terabits per second on 179 individual optical carriers that span the entire telecommunication C and L bands (centred around infrared telecommunication wavelengths of 1.55 micrometres). We also demonstrate coherent detection of a wavelength-division multiplexing data stream by using a pair of DKS frequency combs-one as a multi-wavelength light source at the transmitter and the other as the corresponding local oscillator at the receiver. This approach exploits the scalability of microresonator-based DKS frequency comb sources for massively parallel optical communications at both the transmitter and the receiver. Our results demonstrate the potential of these sources to replace the arrays of continuous-wave lasers that are currently used in high-speed communications. In combination with advanced spatial multiplexing schemes and highly integrated silicon photonic circuits, DKS frequency combs could bring chip-scale petabit-per-second transceivers into reach.
Fetal hemoglobin (HbF) can blunt the pathophysiology, temper the clinical course, and offer prospects for curative therapy of sickle cell disease. This review focuses on (1) HbF quantitative trait ...loci and the geography of β-globin gene haplotypes, especially those found in the Middle East; (2) how HbF might differentially impact the pathophysiology and many subphenotypes of sickle cell disease; (3) clinical implications of person-to-person variation in the distribution of HbF among HbF-containing erythrocytes; and (4) reactivation of HbF gene expression using both pharmacologic and cell-based therapeutic approaches. A confluence of detailed understanding of the molecular basis of HbF gene expression, coupled with the ability to precisely target by genomic editing most areas of the genome, is producing important preliminary therapeutic results that could provide new options for cell-based therapeutics with curative intent.
Sickle Cell Disease Piel, Frédéric B; Steinberg, Martin H; Rees, David C
The New England journal of medicine,
04/2017, Letnik:
376, Številka:
16
Journal Article
Childhood maltreatment increases risk for psychopathology. For some highly prevalent disorders (major depression, substance abuse, anxiety disorders, and posttraumatic stress disorder) a substantial ...subset of individuals have a history of maltreatment and a substantial subset do not. The authors examined the evidence to assess whether those with a history of maltreatment represent a clinically and biologically distinct subtype.
The authors reviewed the literature on maltreatment as a risk factor for these disorders and on the clinical differences between individuals with and without a history of maltreatment who share the same diagnoses. Neurobiological findings in maltreated individuals were reviewed and compared with findings reported for these disorders.
Maltreated individuals with depressive, anxiety, and substance use disorders have an earlier age at onset, greater symptom severity, more comorbidity, a greater risk for suicide, and poorer treatment response than nonmaltreated individuals with the same diagnoses. Imaging findings associated with these disorders, such as reduced hippocampal volume and amygdala hyperreactivity, are more consistently observed in maltreated individuals and may represent a maltreatment-related risk factor. Maltreated individuals also differ from others as a result of epigenetic modifications and genetic polymorphisms that interact with experience to increase risk for psychopathology.
Phenotypic expression of psychopathology may be strongly influenced by exposure to maltreatment, leading to a constellation of ecophenotypes. While these ecophenotypes fit within conventional diagnostic boundaries, they likely represent distinct subtypes. Recognition of this distinction may be essential in determining the biological bases of these disorders. Treatment guidelines and algorithms may be enhanced if maltreated and nonmaltreated individuals with the same diagnostic labels are differentiated.
Ecological networks depict the interactions between species, mainly based on observations in the field. The information contained in such interaction matrices depends on the sampling design, and ...typically, compounds preferences (specialization) and abundances (activity). Null models are the primary vehicles to disentangle the effects of specialization from those of sampling and abundance, but they ignore the feedback of network structure on abundances. Hence, network structure, as exemplified here by modularity, is difficult to link to specific causes. Indeed, various processes lead to modularity and to specific interaction patterns more generally. Inferring (co)evolutionary dynamics is even more challenging, as competition and trait matching yield identical patterns of interactions. A satisfactory resolution of the underlying factors determining network structure will require substantial additional information, not only on independently assessed abundances, but also on traits, and ideally on fitness consequences as measured in experimental setups.
There is increasing interest in childhood maltreatment as a potent stimulus that may alter trajectories of brain development, induce epigenetic modifications and enhance risk for medical and ...psychiatric disorders. Although a number of useful scales exist for retrospective assessment of abuse and neglect they have significant limitations. Moreover, they fail to provide detailed information on timing of exposure, which is critical for delineation of sensitive periods. The Maltreatment and Abuse Chronology of Exposure (MACE) scale was developed in a sample of 1051 participants using item response theory to gauge severity of exposure to ten types of maltreatment (emotional neglect, non-verbal emotional abuse, parental physical maltreatment, parental verbal abuse, peer emotional abuse, peer physical bullying, physical neglect, sexual abuse, witnessing interparental violence and witnessing violence to siblings) during each year of childhood. Items included in the subscales had acceptable psychometric properties based on infit and outfit mean square statistics, and each subscale passed Andersen's Likelihood ratio test. The MACE provides an overall severity score and multiplicity score (number of types of maltreatment experienced) with excellent test-retest reliability. Each type of maltreatment showed good reliability as did severity of exposure across each year of childhood. MACE Severity correlated 0.738 with Childhood Trauma Questionnaire (CTQ) score and MACE Multiplicity correlated 0.698 with the Adverse Childhood Experiences scale (ACE). However, MACE accounted for 2.00- and 2.07-fold more of the variance, on average, in psychiatric symptom ratings than CTQ or ACE, respectively, based on variance decomposition. Different types of maltreatment had distinct and often unique developmental patterns. The 52-item MACE, a simpler Maltreatment Abuse and Exposure Scale (MAES) that only assesses overall exposure and the original test instrument (MACE-X) with several additional items plus spreadsheets and R code for scoring are provided to facilitate use and to spur further development.
Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, ...and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non-oxygen-binding form of hemoglobin that readily loses heme. Circulating hemoglobin and heme represent erythrocytic danger-associated molecular pattern (eDAMP) molecules, which activate the innate immune system and endothelium to an inflammatory, proadhesive state that promotes sickle vaso-occlusion and acute lung injury in murine models of sickle cell disease. Intravascular hemolysis can impair NO bioavailability and cause oxidative stress, altering redox balance and amplifying physiological processes that govern blood flow, hemostasis, inflammation, and angiogenesis. These pathological responses promote regional vasoconstriction and subsequent blood vessel remodeling. Thus, intravascular hemolysis represents an intrinsic mechanism for human vascular disease that manifests clinical complications in sickle cell disease and other chronic hereditary or acquired hemolytic anemias.
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