The photo-Dember effect is a source of pulsed THz emission following femtosecond pulsed optical excitation. The emission results from the ultrafast spatial separation of electron-hole pairs in ...carrier gradients due to their different diffusion coefficients. The associated time dependent polarization of the photo-carriers within the photo-Dember emitters is oriented perpendicular to the excited surface. THz emission under photo-excitation can also be due to the surface field effect or optical rectification. We review the studies that attempt to understand surge current and study the surface emission of different semiconductor materials. We also review the work that has been done on increasing the efficiency of THz surface emitters using plasmonic interactions and other resonant effects. We later focus on a new THz emission mechanism called lateral photo-Dember which proposes a scheme for generating strong carrier current parallel to the excited surface, using the Dember field as well as dipole quenching effect. Because the resulting currents are oriented parallel to the surface and the THz radiation is emitted collinearly to the optical excitation. Surprisingly, the lateral photo-Dember THz emitters provide a higher bandwidth than photoconductive emitters. The theory for the mechanism of emission is reviewed and the parameters that affect the performance of the lateral photo-Dember emitters, namely fluence and polarization, are summarized. Finally we review multiplexing geometries with periodically tailored photo-excited spatial carrier distributions that create phase coherent photo-Dember and surface field currents which enhance the THz emission. These multiple emitters can reach electric field amplitudes comparable to a high-efficiency externally biased photoconductive emitter.
New perspectives on osteogenesis imperfecta Forlino, Antonella; Cabral, Wayne A; Barnes, Aileen M ...
Nature reviews. Endocrinology,
09/2011, Letnik:
7, Številka:
9
Journal Article
Recenzirano
Odprti dostop
A new paradigm has emerged for osteogenesis imperfecta as a collagen-related disorder. The more prevalent autosomal dominant forms of osteogenesis imperfecta are caused by primary defects in type I ...collagen, whereas autosomal recessive forms are caused by deficiency of proteins which interact with type I procollagen for post-translational modification and/or folding. Factors that contribute to the mechanism of dominant osteogenesis imperfecta include intracellular stress, disruption of interactions between collagen and noncollagenous proteins, compromised matrix structure, abnormal cell-cell and cell-matrix interactions and tissue mineralization. Recessive osteogenesis imperfecta is caused by deficiency of any of the three components of the collagen prolyl 3-hydroxylation complex. Absence of 3-hydroxylation is associated with increased modification of the collagen helix, consistent with delayed collagen folding. Other causes of recessive osteogenesis imperfecta include deficiency of the collagen chaperones FKBP10 or Serpin H1. Murine models are crucial to uncovering the common pathways in dominant and recessive osteogenesis imperfecta bone dysplasia. Clinical management of osteogenesis imperfecta is multidisciplinary, encompassing substantial progress in physical rehabilitation and surgical procedures, management of hearing, dental and pulmonary abnormalities, as well as drugs, such as bisphosphonates and recombinant human growth hormone. Novel treatments using cell therapy or new drug regimens hold promise for the future.
Amyotrophic lateral sclerosis (ALS) is an invariably lethal progressive disease, causing degeneration of neurons and muscle. No current treatment halts or reverses disease advance. This single arm, ...open label, clinical trial in patients with ALS investigated the safety and tolerability of a novel modified low molecular weight dextran sulphate (LMW-DS, named ILB®) previously proven safe for use in healthy volunteers and shown to exert potent neurotrophic effects in pre-clinical studies. Secondary endpoints relate to efficacy and exploratory biomarkers.
Thirteen patients with ALS were treated with 5 weekly subcutaneous injections of ILB®. Safety and efficacy outcome measures were recorded weekly during treatment and at regular intervals for a further 70 days. Functional and laboratory biomarkers were assessed before, during and after treatment.
No deaths, serious adverse events or participant withdrawals occurred during or after ILB® treatment and no significant drug-related changes in blood safety markers were evident, demonstrating safety and tolerability of the drug in this cohort of patients with ALS. The PK of ILB® in patients with ALS was similar to that seen in healthy controls. The ILB® injection elicited a transient elevation of plasma Hepatocyte Growth Factor, a neurotrophic and myogenic growth factor. Following the ILB® injections patients reported increased vitality, decreased spasticity and increased mobility. The ALSFRS-R rating improved from 36.31 ± 6.66 to 38.77 ± 6.44 and the Norris rating also improved from 70.61 ± 13.91 to 77.85 ± 14.24 by Day 36. The improvement of functions was associated with a decrease in muscle atrophy biomarkers. These therapeutic benefits decreased 3-4 weeks after the last dosage.
This pilot clinical study demonstrates safety and tolerability of ILB® in patients with ALS. The exploratory biomarker and functional measures must be cautiously interpreted but suggest clinical benefit and have a bearing on the mechanism of action of ILB®. The results support the drug's potential as the first disease modifying treatment for patients with ALS.
EudraCT 2017-005065-47.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Although US cancer survival rates have increased over time, disparities by race/ethnicity remain, including for children and adolescents. OBJECTIVE: To examine whether racial/ethnic ...disparities in childhood and adolescent cancer survival vary by cancer type according to relative survival rates (RSRs), a marker for amenability to medical intervention. DESIGN, SETTING, AND PARTICIPANTS: In a retrospective cohort study using US Surveillance, Epidemiology, and End Results data, 67 061 children and adolescents diagnosed at ages 0 to 19 years with a first primary malignant cancer from January 1, 2000, to December 31, 2016, were evaluated. Data analysis was performed from June 19 to November 3, 2019. Participants were followed up from the dates of diagnosis to cancer death or the end of the follow-up period, whichever came first. EXPOSURES: Race/ethnicity defined as non-Hispanic white, non-Hispanic black, non-Hispanic American Indian/Alaskan Native, non-Hispanic Asian or Pacific Islander, or Hispanic (any race). MAIN OUTCOMES AND MEASURES: Cancer amenability was defined using 5-year RSRs for 103 cancer types. Cox proportional hazards regression was used to compute adjusted hazard ratios (aHRs) and 95% CIs for the association between race/ethnicity and cancer survival for high (>85% RSR), medium (70%-85% RSR), and low (<70% RSR) amenability categories. RESULTS: Among 67 061 cancer cases, 36 064 were male (53.8%); most individuals were non-Hispanic white (35 186 52.5%) followed by Hispanic of any race (19 220 28.7%), non-Hispanic black (7100 10.6%), non-Hispanic Asian or Pacific Islander (4981 7.4%), and non-Hispanic American Indian/Alaskan Native (574 0.9%). Mean (SD) age at diagnosis was 9.66 (6.41) years. Compared with non-Hispanic white children and adolescents, a higher aHR of death was observed for high- than low-amenability cancers for non-Hispanic black patients (high: aHR, 1.59; 95% CI, 1.41-1.80 vs low: aHR, 1.35; 95% CI, 1.24-1.47; P = .002 for interaction) and Hispanic (any race) patients (high: aHR, 1.63; 95% CI, 1.50-1.78 vs low: aHR, 1.16; 95% CI, 1.08-1.25; P < .001 for interaction). Results for other race/ethnicities showed similar patterns but were not statistically significant. CONCLUSIONS AND RELEVANCE: Racial/ethnic minority children and adolescents were observed to have a higher risk of death than non-Hispanic white children and adolescents, with more amenable cancers having larger relative survival differences. This disparity may be associated with a combination of factors, including differences in access to health care resources.
Understanding nanoparticle uptake by biological cells is fundamentally important to wide-ranging fields from nanotoxicology to drug delivery. It is now accepted that the arrival of nanoparticles at ...the cell is an extremely complicated process, shaped by many factors including unique nanoparticle physico-chemical characteristics, protein-particle interactions and subsequent agglomeration, diffusion and sedimentation. Sequentially, the nanoparticle internalisation process itself is also complex, and controlled by multiple aspects of a cell's state. Despite this multitude of factors, here we demonstrate that the statistical distribution of the nanoparticle dose per endosome is independent of the initial administered dose and exposure duration. Rather, it is the number of nanoparticle containing endosomes that are dependent on these initial dosing conditions. These observations explain the heterogeneity of nanoparticle delivery at the cellular level and allow the derivation of simple, yet powerful probabilistic distributions that accurately predict the nanoparticle dose delivered to individual cells across a population.
Christians are one of the most underrepresented groups in science, and one potential explanation is that scientists have a bias against Christian students, which could discourage and actively prevent ...Christian students from becoming scientists. Although there is a general perception in society that there is bias against Christians in science, we do not know whether science students, who frequently interact with scientists, perceive this bias. Further, no researchers have attempted to experimentally document the existence of bias against Christians in science. To address these gaps in the literature, we designed three studies. In the first study, we found that college science students report a perceived bias against Christians in science and that evangelical Christians perceive greater bias than Catholic and non-Christian students. Then in two studies, biology professors evaluated Ph.D. program applicants and we examined whether the professors rated a student less favorably when the student revealed a Christian religious identity. We found no statistically significant differences in how biology professors rated a student who was President of the Christian Association compared to a student who was President of the Atheist Association or a student who was President of the Activities Association. However, in Study 3, biology professors did rate a Christian student who went on a mission trip with Campus Crusade for Christ as less hireable, less competent, and less likeable than a student who did not reveal a Christian identity. Taken together, these studies indicate that perceived bias against Christians in science may contribute to underrepresentation of Christians but actual bias against Christians in science may be restricted to a specific type of Christianity that scientists call fundamentalist and/or evangelical.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Removal or protection from biostratinomic agents of decomposition, such as predators and scavengers, is widely seen as a requirement for high-quality preservation of soft tissues in the fossil ...record. In this context, extremely rapid burial is an oft-cited mechanism for shielding remains from degradation, but not all fossils fit nicely into this paradigm. Dinosaurian mummies in particular seemingly require two mutually exclusive taphonomic processes to preserve under that framework: desiccation and rapid burial. Here we present a recently prepared Edmontosaurus mummy that reveals an alternate fossilization pathway for resistant soft tissues (e.g., skin and nails). While the skin on this specimen is well-preserved in three dimensions and contains biomarkers, it is deflated and marked by the first documented examples of injuries consistent with carnivore activity on dinosaurian soft tissue during the perimortem interval. Incomplete scavenging of the carcass provided a route for the gases, fluids, and microbes associated with decomposition to escape, allowing more durable soft tissues to persist through the weeks to months required for desiccation prior to entombment and fossilization. This pathway is consistent with actualistic observations and explains why dinosaurian skin, while rare, is more commonly preserved than expected if extreme circumstances were required for its preservation. More broadly, our assumptions guide specimen collection and research, and the presence of soft tissues and biomolecules in fossils that demonstrably were not rapidly buried, such as this mummy, suggests that such types of evidence may be substantially more common than previously assumed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Air pollution has become a global public health hazard leading to debilitating effects on physical, mental, and emotional health. Management research has just begun to explore the effects of air ...pollution on employees' work life. Drawing from the transactional theory of stress (Lazarus & Folkman, 1984) and crossover theory (Westman, 2001), we argue that appraisal of air pollution is an important factor that influences leaders and their behavior with subordinates. Specifically, we propose that when leaders appraise severe air pollution, they are more likely to behave abusively toward their subordinates and engage in laissez-faire leadership. We also propose that this relationship is mediated by leaders' experience of somatic complaints and negative affect. We test our model using an experience sampling study in India of leaders and followers who were located in different cities from each other. Overall, our results highlight how air pollution appraisals can harm not only the leader experiencing the pollution but also subordinates of those leaders. In other words, our counterintuitive finding is that subordinates may be harmed by air pollution to which they are not even directly exposed.
Lack of sleep and unethical conduct Barnes, Christopher M.; Schaubroeck, John; Huth, Megan ...
Organizational behavior and human decision processes,
07/2011, Letnik:
115, Številka:
2
Journal Article
Recenzirano
We draw from the Ego Depletion model and research on sleep physiology to predict a relationship between lack of sleep and individuals’ unethical behavior. Laboratory studies showed that sleep ...quantity is positively related to self-control resources and negative associated with unethical behavior. In a cross-sectional field study examining unethical behavior in a variety of work settings, low levels of sleep, and low perceived quality of sleep, were both positively related to unethical behavior as rated by the supervisor, and cognitive fatigue mediated the influence of sleep quantity. In an experience sampling field study, we found similar effects within-individuals. We discuss the role of lost sleep in better understanding unethical behavior in organizations.
AMP-activated protein kinase (AMPK) senses energetic stress and, in turn, promotes catabolic and suppresses anabolic metabolism coordinately to restore energy balance. We found that a diverse array ...of AMPK activators increased mTOR complex 2 (mTORC2) signaling in an AMPK-dependent manner in cultured cells. Activation of AMPK with the type 2 diabetes drug metformin (GlucoPhage) also increased mTORC2 signaling in liver in vivo and in primary hepatocytes in an AMPK-dependent manner. AMPK-mediated activation of mTORC2 did not result from AMPK-mediated suppression of mTORC1 and thus reduced negative feedback on PI3K flux. Rather, AMPK associated with and directly phosphorylated mTORC2 (mTOR in complex with rictor). As determined by two-stage in vitro kinase assay, phosphorylation of mTORC2 by recombinant AMPK was sufficient to increase mTORC2 catalytic activity toward Akt. Hence, AMPK phosphorylated mTORC2 components directly to increase mTORC2 activity and downstream signaling. Functionally, inactivation of AMPK, mTORC2, and Akt increased apoptosis during acute energetic stress. By showing that AMPK activates mTORC2 to increase cell survival, these data provide a potential mechanism for how AMPK paradoxically promotes tumorigenesis in certain contexts despite its tumor-suppressive function through inhibition of growth-promoting mTORC1. Collectively, these data unveil mTORC2 as a target of AMPK and the AMPK-mTORC2 axis as a promoter of cell survival during energetic stress.
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