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The article explores an ethical dilemma faced by a quality manager at a mid-sized company that produces eco-friendly cleaning products. It mentions that during a routine audit, the manager discovers that a key ingredient in the company's popular product line is not fully biodegradable and contains a harmful synthetic additive, despite marketing claims of all-natural ingredients.

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex (TSC), and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, permits the formation of tumors that can lead to developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro.Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that total Tuberin levels are tightly regulated through developmental stages in the embryonic brain. At a cell biology level, we show that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. This functional data supports the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

OBJECTIVE--In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) study, the safety and efficacy of 30 weeks of treatment [...]

OBJECTIVE--To compare the efficacy and safety of adding mealtime pramlintide or rapid-acting insulin analogs (RAIAs) to basal insulin for patients with inadequately controlled type 2 diabetes. RESEARCH DESIGN AND METHODS--In [...]

Fully differentiated cells can be reprogrammed through ectopic expression of key transcription factors to create induced pluripotent stem cells. These cells share many characteristics of normal embryonic stem cells and have great promise in disease modeling and regenerative medicine. The process of remodeling has its limitations, including a very low efficiency due to the upregulation of many antiproliferative genes, including cyclin dependent kinase inhibitors CDKN1Aand CDKN2A, which serve to protect the cell by inducing apoptotic and senescent programs. Our data reveals a unique cell cycle mechanism enabling mouse fibroblasts to repress cyclin dependent kinase inhibitors through the activation of the epigenetic regulator EZH2 by a cyclin‐like protein SPY1. This data reveals that the SPY1 protein is required for reprogramming to a pluripotent state and is capable of increasing reprogramming efficiency. Reprogramming of normal fibroblasts to induced pluripotent stem cells is characterized by low efficiency due to the upregulation of tumor suppressors and reprogramming‐induced senescence (RIS). Spy1 can be combined with classical pluripotency factors to override RIS through activation of EZH2 followed by an increase in trimethylation of histone H3 at the lysine 27 residue.

Purpose: Power, policy and politics set the landscape for technocratic approaches in the educational system. Efficiency and money-saving initiatives that adhere to a one-size-fits-all approach drive the response to complex and multifaceted challenges within education. This has been made apparent through the COVID-19 pandemic and its aftermath. This paper aims to explore one of the most pronounced and gaping realities that became evident during this crisis in how the system dehumanizes those in the margins. By not centralizing the biographies of families served in the schools, particularly culturally and linguistically diverse families, the system has failed to capitalize on the assets and affirm their wisdom. Design/methodology/approach: This conceptual paper juxtaposes the technocratic and humanistic approaches of family engagement and provides alternative narratives rooted in authentic cariño (Bartolomé, 2008; Herrera et al., 2020; Valenzuela, 1999) and radical kinship (Boyle, 2017). Findings: Currently, the educational system has sought to address complex issues by attending to the structures (i.e. plexiglass) and instructions (i.e. technology) as a way of responding to life-altering events that are in need of humanistic approaches. Originality/value: The authors ask educators to reflect on the ways that power, policy and politics often stifle opportunities to move outside what is known to transform educational contexts. The authors conclude with critical questions to create new pathways guided by empathy and hope.

My wife and I recently experienced an unusual springtime birding adventure on board a cruise ship in the Atlantic Ocean between the Bahamas and Port Canaveral, Florida. While on an […]

The article focuses on the artist William Blake. Topics discussed include his painting "Newton" held in the Tate collection in London, Great Britain in which Blake positions Newton at the bottom of the ocean, turning his back to the beauty and mystery of nature that surrounds him, and Leach’s life and creative practice were heavily influenced by Japanese peers and Eastern spiritual and metaphysical principals.

In this study, electrical properties of four metals (W, Mo, Au, Ni) as Schottky contacts on n-type (100)-oriented b-Ga2O3 substrates grown by the Czochralski method are reported. The Schottky barrier heights for each metal contact were calculated from I-V and/or C-V measurements. Two methods were used to cross check the Schottky barrier heights (phB) and ideality factors (n) calculated from I-V measurements. The Schottky barrier height values calculated from C-V and I-V measurements showed excellent agreement with each other and increased with an increase in the metal work functions. Some anomalous behavior of Au contacts, which is similar to behavior reported on (010)-oriented b-Ga2O3, is also described.

Disproportionate proinsulinemia, manifest as an increased proinsulin (PI) to immunoreactive insulin (IRI) ratio, has been observed in type 2 diabetes and is inversely related to [Beta]-cell function and positively related [...]

Rosiglitazone (RSG), a potent thiazolidinedione, reduces insulin resistance and improves glycemic control when used alone or in combination with sulfonylureas or metformin. This study tested the hypothesis that agents such [...]

When smoke cleared on the Lake Tahoe Angora fire that destroyed 255 homes this summer, Sukut Construction joined forces with California's EPA team to safely remove the remains. [ILLUSTRATION OMITTED] [...]

This study reports on the growth and characterization of three different phases - a, b, and e - of Ga2O3 epitaxial layers grown on (001) sapphire substrates at 650 degC. The stable b-phase was observed for films grown using metalorganic chemical vapor deposition with trimethygallium and oxygen as source gases. In contrast, the a- and/or e-phase(s) were observed for films grown by halide vapor phase epitaxy with gallium chloride and oxygen as source gases. Orientation relationships from x-ray diffraction measurements are reported, along with transmission electron microscopy images of the interfacial microstructure and optical transmittance measurements of the different phases.

The artificial nanostructures such as nanoparticles and natural nanostructures such as secreted nanosized extracellular vesicles known as exosomes are promising tools for the realization of personalized medicine. Radionanomedicine is a recently coined term for the simultaneous application of either radiation technology or nuclear medicine with nanomedicine. In addition, radioexosomics is our suggested term for the study of exosomes functions, cytotoxicity, cancerogenicity, and biodistribution using radiation technology and nuclear medicine tracing technology. Prostate cancer (PCa) is the most commonly diagnosed cancer in males and a big majority of patients with PC progress to castration-resistant prostate cancer (CRPC) mostly. The mechanisms leading to development of CRPC remain poorly understood and there is still a need to improve the therapeutic options available for PCa. In this review, a wide variety of nanostructure-based prostate cancer research using radiation technology and nuclear medicine is discussed. In addition, we will present what is currently known about the function of exosomes in PCa. The review concludes by summarizing the current status and future perspectives of radionanomedicine and radioexosomics for understanding PCa biology, as well as PCa enhancement of targeting strategies, drug delivery, molecular imaging and therapy.

ABSTRACTFamilies of cyclin-like proteins have emerged that bind and activate cyclin dependent kinases (Cdk)s, directing the phosphorylation of noncanonical Cdk substrates. One of these proteins, Spy1, has demonstrated the unique ability to directly bind and activate both Cdk1 and Cdk2, as well as binding and promoting the degradation of at least one Cdk inhibitor, p27Kip1. Spy1 accelerates somatic cell growth and proliferation and is implicated in a number of human cancers including the breast, brain and liver. Herein we isolate key residues mediating the direct interaction with p27. We use mutants of Spy1 to determine the physiological role of direct interactions with distinct binding partners Cdk2 and p27. We demonstrate that disrupting the direct interaction with either Spy1 binding partner decreased endogenous activity of Cdk2, as well as Spy1-mediated proliferation. However, only the direct interaction with p27 was essential for Spy1-mediated effects on p27 stability. In vivoneither mutation completely prevented tumorigenesis, although each mutation slowed the rate of Spy1-mediated tumorigenesis and decreased overall tumor volumes. This work supports the conclusion that direct interaction with both p27 and Cdk2 contribute to Spy1-mediated effects on cell growth. It is important to elucidate the dynamics of these interactions and to consider these data when assessing functional outcomes.

Solution-processed silver nanowire (Ag-NW) network structures are candidate materials for application as flexible transparent conductors in a wide range of flexible electronics. However, challenges remain in fabricating these materials in an efficient and scalable manner in addition to making them mechanically robust. Here, a method based on the direct processing of Ag-NW network structures from aqueous polymer solutions is presented that significantly increases the uniformity of the NW networks and lowers the percolation threshold, thus resulting in an increased figure of merit (percolative FoM P > 40) of Ag-NW based transparent conductors. Direct polymer solution processing also reduces the batch-to-batch variability of optical and electrical properties of the NW networks to <5% of the mean (as compared to 10-20% variability for pristine Ag-NW networks), and significantly improves their resistance to mechanical deformation. Our results further indicate that semicrystalline polymers such as poly (vinyl alcohol) (PVA) could serve as viable and benign alternatives to conducting polymer matrices (such as PEDOT:PSS) that pose a challenge to device fabrication due to their corrosive properties.

Suitable design of periodic metal/polymer composite materials is shown to facilitate resonant tunneling of light at absorbing wavelengths and to provide a means to significantly reduce optical absorption losses in polymer-based metallodielectric composite structures. The conditions for resonant tunneling are established based on the concept of “photonic band edge alignment” in 1D-periodic systems. For the particular case of a four-layer gold/polystyrene laminate structure, it is shown that the matching of the lower band edge of the 1D-periodic structure with the plasma frequency of the metal component facilitates the increase of optical transmission by about 500% as compared to monolithic film structures of equal total thickness. The effect of sheet thickness on the optical properties of thin metal films is determined and shown to be an important prerequisite for the reliable prediction of resonant metallodielectric structures. The resonant 1D-periodic metal/polymer heterostructures are shown to retain the flexural stability of the polymer matrix and thus could find application as flexible transparent conductors in areas such as “plastic electronics”.

Glucagon-like peptide-1 receptor agonists exenatide and liraglutide have been shown to improve glycaemic control and reduce bodyweight in patients with type 2 diabetes. We compared the efficacy and safety of exenatide once weekly with liraglutide once daily in patients with type 2 diabetes.

Tuberous sclerosis is a multi-organ disorder characterized by the formation of benign tumors, called hamartomas, which affects more than 1 million people worldwide. The syndrome is initiated by a mutation in one of two tumor suppressor genes, TSC1 or TSC2, that encode for the proteins hamartin and tuberin, respectively. Herein, we demonstrate that tuberin binds and regulates the G2/M cyclin, cyclin B1. We have determined that this binding region encompasses a mutational hotspot within tuberin that is implicated in some of the most severe cases of TS. Mimicking a mutation found in a subset of patients with tuberous sclerosis, we found a significant reduction in the binding between tuberin and cyclin B1. Functionally, our data supports that tuberin plays a role in regulating the cellular localization of cyclin B1. These results demonstrate a novel and clinically relevant mechanism, where tuberin functions in mitotic onset.

Most patients with type 2 diabetes begin pharmacotherapy with metformin, but eventually need additional treatment. We assessed the safety and efficacy of once weekly exenatide, a glucagon-like peptide 1 receptor agonist, versus maximum approved doses of the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the thiazolidinedione, pioglitazone, in patients treated with metformin.

The planarization of bottom‐contact organic field‐effect transistors (OFETs) resulting in dramatic improvement in the nanomorphology and an associated enhancement in charge injection and transport is reported. Planar OFETs based on regioregular poly(3‐hexylthiophene) (rr‐P3HT) are fabricated wherein the Au bottom‐contacts are recessed completely in the gate‐dielectric. Normal OFETs having a conventional bottom‐contact configuration with 50‐nm‐high contacts are used for comparison purpose. A modified solvent‐assisted drop‐casting process is utilized to form extremely thin rr‐P3HT films. This process is critical for direct visualization of the effect of planarization on the polymer morphology. Atomic force micrographs (AFM) show that in a normal OFET the step between the surface of the contacts and the gate dielectric disrupts the self‐assembly of the rr‐P3HT film, resulting in poor morphology at the contact edges. The planarization of contacts results in notable improvement of the nanomorphology of rr‐P3HT, resulting in lower resistance to charge injection. However, an improvement in field‐effect mobility is observed only at short channel lengths. AFM shows the presence of well‐ordered nanofibrils extending over short channel lengths. At longer channel lengths the presence of grain boundaries significantly minimizes the effect of improvement in contact geometry as the charge transport becomes channel‐limited.

The cyclin dependent kinase inhibitor (CKI) p27Kip1 binds to cyclin E/CDK2 complexes and prevents premature S-phase entry. During late G1and throughout S phase, p27 phosphorylation at T187 leads to its subsequent degradation, which relieves CDK2 inhibition to promote cell cycle progression. However, critical events that trigger CDK2 complexes to phosphorylate p27 remain unclear. Utilizing recombinant proteins, we demonstrate that human Speedy (Spy1) activates CDK2 to phosphorylate p27 at T187 in vitro. Addition of Spy1 or Spy1/CDK2 to a preformed, inhibited cyclin E/CDK2/p27 complex also promoted this phosphorylation. Furthermore, Spy1 protected cyclin E/CDK2 from p27 inhibition toward histone H1, in vitro. Inducible Spy1 expression in U2OS cells reduced levels of endogenous p27 and exogenous p27WT, but not a p27T187A mutant. Additionally, Spy1 expression in synchronized HeLa cells enhanced T187 phosphorylation and degradation of endogenous p27 in late G1and throughout S phase. Our studies provide evidence that Spy1 expression enhances CDK2-dependent p27 degradation during late G1and throughout S phase.

To test the hypothesis that rosiglitazone combined with metformin provides a greater reduction in microalbuminuria and blood pressure than metformin and glyburide at comparable levels of glycemic control.

Progression through the G1/S transition commits cells to synthesize DNA. Cyclin dependent kinase 2 (CDK2) is the major kinase that allows progression through G1/S phase and subsequent replication events. p27 is a CDK inhibitor (CKI) that binds to CDK2 to prevent premature activation of this kinase. Speedy (Spy1), a novel cell cycle regulatory protein, has been found to prematurely activate CDK2 when microinjected into Xenopusoocytes and when expressed in mammalian cells. To determine the mechanism underlying Spy1-induced proliferation in mammalian cell cycle regulation, we used human Spy1 as bait in a yeast two-hybrid screen to identify interacting proteins. One of the proteins isolated was p27; this novel interaction was confirmed both in vitro, using bacterially expressed and in vitro translated proteins, and in vivo, through the examination of endogenous and transfected proteins in mammalian cells. We demonstrate that Spy1 expression can overcome a p27-induced cell cycle arrest to allow for DNA synthesis and CDK2 histone H1 kinase activity. In addition, we utilized p27-null cells to demonstrate that the proliferative effect of Spy1 depends on the presence of endogenous p27. Our data suggest that Spy1 associates with p27 to promote cell cycle progression through the G1/S transition.

Progression through the G1/S transition commits cells to synthesize DNA. Cyclin dependent kinase 2 (CDK2) is the major kinase that allows progression through G1/S phase and subsequent replication events. p27 is a CDK inhibitor (CKI) that binds to CDK2 to prevent premature activation of this kinase. Speedy (Spy1), a novel cell cycle regulatory protein, has been found to prematurely activate CDK2 when microinjected into Xenopus oocytes and when expressed in mammalian cells. To determine the mechanism underlying Spy1-induced proliferation in mammalian cell cycle regulation, we used human Spy1 as bait in a yeast two-hybrid screen to identify interacting proteins. One of the proteins isolated was p27; this novel interaction was confirmed both in vitro, using bacterially expressed and in vitro translated proteins, and in vivo, through the examination of endogenous and transfected proteins in mammalian cells. We demonstrate that Spy1 expression can overcome a p27-induced cell cycle arrest to allow for DNA synthesis and CDK2 histone H1 kinase activity. In addition, we utilized p27-null cells to demonstrate that the proliferative effect of Spy1 depends on the presence of endogenous p27. Our data suggest that Spy1 associates with p27 to promote cell cycle progression through the G1/S transition.

Some cells undergo apoptosis in response to DNA damage, whereas others do not. To understand the biochemical pathways controlling this differential response, we have studied the intracellular localization of cyclin B1 in cell types sensitive or resistant to apoptosis induced by DNA damage. We found that cyclin B1 protein accumulates in the nucleus of cells that are sensitive to γ radiation–induced apoptosis (thymocytes, lymphoid cell lines), but remains cytoplasmic in apoptosis-resistant cells (primary and transformed fibroblasts). Treatment of both cell types with leptomycin B, an inhibitor of CRM1-dependent cyclin B1 nuclear export, induces apoptosis. Furthermore, ectopic expression of cyclin B1-5xE, a protein that preferentially localizes to the nucleus, is sufficient to trigger apoptosis. Conversely, expression of cyclin B1-5xA, a predominantly cytoplasmic protein, fails to induce apoptosis. This suggests that nuclear accumulation is necessary for cyclin B1–dependent apoptosis. Our observations are consistent with the idea that localization of cyclin B1 is among the factors determining the cellular decision to undergo apoptosis in response to DNA damage.

Microtubules provide structural support for a cell and play key roles in cell motility, mitosis, and meiosis. They are also the targets of several anticancer agents, indicating their importance in maintaining cell viability. We have investigated the possibility that alterations in microtubule structure and tubulin polymerization may be part of the cellular response to DNA damage. In this report, we find that γ-radiation stimulates the production and polymerization of α-, β-, and γ- tubulin in hematopoeitic cell lines (Ramos, DP16), leading to visible changes in microtubule structures. We have found that this microtubule reorganization can be prevented by caffeine, a drug that concomitantly inhibits DNA damage-induced cell cycle arrest and apoptosis. Our results support the idea that microtubule polymerization is an important facet of the mammalian response to DNA damage.

ATP-sensitive K+(KATP) channels are abundantly expressed in the heart and may be involved in the pathogenesis of myocardial ischemia. These channels are heteromultimeric, consisting of four pore-forming subunits (Kir6.1, Kir6.2) and four sulfonylurea receptor (SUR) subunits in an octameric assembly. Conventionally, the molecular composition of KATPchannels in cardiomyocytes and pancreatic β-cells is thought to include the Kir6.2 subunit and either the SUR2A or SUR1 subunits, respectively. However, Kir6.1 mRNA is abundantly expressed in the heart, suggesting that Kir6.1 and Kir6.2 subunits may co-assemble to form functional heteromeric channel complexes. Here we provide two independent lines of evidence that heteromultimerization between Kir6.1 and Kir6.2 subunits is possible in the presence of SUR2A. We generated dominant negative Kir6 subunits by mutating the GFG residues in the channel pore to a series of alanine residues. The Kir6.1-AAA pore mutant subunit suppressed both wt-Kir6.1/SUR2A and wt-Kir6.2/SUR2A currents in transfected HEK293 cells. Similarly, the dominant negative action of Kir6.2-AAA does not discriminate between either of the wild-type subunits, suggesting an interaction between Kir6.1 and Kir6.2 subunits within the same channel complex. Biochemical data support this concept: immunoprecipitation with Kir6.1 antibodies also co-precipitates Kir6.2 subunits and conversely, immunoprecipitation with Kir6.2 antibodies co-precipitates Kir6.1 subunits. Collectively, our data provide direct electrophysiological and biochemical evidence for heteromultimeric assembly between Kir6.1 and Kir6.2. This paradigm has profound implications for understanding the properties of native KATPchannels in the heart and other tissues.

γ-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating γ-radiation–induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage. Cyclin B1 is the regulatory subunit of the cdc2 serine/threonine kinase, and accumulation of cyclin B1 in late G2 phase of the cell cycle is a prerequisite for mitotic initiation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP16, HL60, thymocytes) undergoing γ-radiation–induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibition of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expression is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for γ-radiation-induced apoptosis.

?-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating ?-radiation–induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage. Cyclin B1 is the regulatory subunit of the cdc2 serine/threonine kinase, and accumulation of cyclin B1 in late G2 phase of the cell cycle is a prerequisite for mitotic initiation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP16, HL60, thymocytes) undergoing ?-radiation–induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibition of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expression is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for ?-radiation-induced apoptosis.

Software designed for cognitively young individuals (12-30 months) relies on picture representations and contrived selection techniques such as scanning and stepping. Review of available software and accompanying documentation reveals that a number of assumptions appear to have been made regarding the cognitive/motor abilities of children. These assumptions fall into two general categories-cognitive development and specific cognitive skills required for picture recognition. This paper reviews the normal developmental literature related to these two areas and draws conclusions concerning appropriate presentation in designing software for a cognitively young population.

The article presents stories from the readers of Birder's World. Mark O'Keefe wrote that his wife and himself experienced an unusual springtime birding adventure on board a cruise ship in the Atlantic Ocean between the Bahamas and Port Canaveral, Florida. Dave Rudeen and Phyllis Rudeen wrote that in the mountains of Colorado, 7,900 feet above sea level, their bluebird box becomes a nursery every spring.

In this study, electrical properties of four metals (W, Mo, Au, Ni) as Schottky contacts on n-type (100)-oriented β-Ga2O3substrates grown by the Czochralski method are reported. The Schottky barrier heights for each metal contact were calculated from I-V and/or C-V measurements. Two methods were used to cross check the Schottky barrier heights (φB) and ideality factors (n) calculated from I-V measurements. The Schottky barrier height values calculated from C-V and I-V measurements showed excellent agreement with each other and increased with an increase in the metal work functions. Some anomalous behavior of Au contacts, which is similar to behavior reported on (010)-oriented β-Ga2O3, is also described.

This study reports on the growth and characterization of three different phases – α, β, and ε – of Ga2O3epitaxial layers grown on (001) sapphire substrates at 650 °C. The stable β-phase was observed for films grown using metalorganic chemical vapor deposition with trimethygallium and oxygen as source gases. In contrast, the α- and/or ε-phase(s) were observed for films grown by halide vapor phase epitaxy with gallium chloride and oxygen as source gases. Orientation relationships from x-ray diffraction measurements are reported, along with transmission electron microscopy images of the interfacial microstructure and optical transmittance measurements of the different phases.

Contact geometry plays an important role in charge injection and transport in organic field‐effect transistors. On page 2216, T. Kowalewski, L. M. Porter, et al. show a dramatic effect of electrode planarization on the polymer morphology at the contact edges and a resulting increase in fi eld‐effect mobility in short channel length devices, and a corresponding decrease in contact resistance. The cover image shows atomic force micrograph of individual polymer nanofi brils spanning the length of a 10 µm channel transistor with planarized contacts.

Focuses on the benefits of establishing credit unions in small business enterprises. Financial programs and services offered by credit unions; Credit union ownership; Credit unions as not-for-profit institutions.

Presents letters to the editor referencing articles and topics discussed in previous issues. "Bread and Circuses," which assessed the economy of the U.S.; "A Song to Celebrate," which focused on music; "The July 4th Maple Street Games," which tackled humanity.