This book serves as an introduction to the ongoing
political debate about the relationship of capitalism and
democracy. In recent years, the ideological battles
between advocates of free markets and ...minimal government, on the
one hand, and adherents of greater democratic equality and some
form of the welfare state, on the other hand, have returned in full
force. Anyone who wants to make sense of contemporary American
politics and policy battles needs to have some understanding of the
divergent beliefs and goals that animate this debate. In
Capitalism and Democracy , Thomas A. Spragens, Jr.,
examines the opposing sides of the free market versus welfare state
debate through the lenses of political economy, moral philosophy,
and political theory. He asks: Do unchecked markets maximize
prosperity, or do they at times produce wasteful and damaging
outcomes? Are market distributions morally appropriate, or does
fairness require some form of redistribution? Would a society of
free markets and minimal government be the best kind of society
possible, or would it have serious problems? After leading the
reader through a series of thought experiments designed to compare
and clarify the thought processes and beliefs held by supporters of
each side, Spragens explains why there are no definitive answers to
these questions. He concludes, however, that some answers are
better than others, and he explains why his own judgement is that a
vigorous free marketplace provides great benefits to a democratic
society, both economically and politically, but that it also
requires regulation and supplementation by collective action for a
society to maximize prosperity, to mitigate some of the unfairness
of the human condition, and to be faithful to important democratic
purposes and ideals. This engaging and accessible book will
interest students and scholars of political economy, democratic
theory, and theories of social justice. It will also appeal to
general readers who are seeking greater clarity and understanding
of contemporary debates about government's role in the economy.
The epidemic of opioid abuse is related in part to incomplete understanding of pain-relief management, opioid tolerance, and opioid addiction. Among the prevention strategies are more widespread ...sharing of data about opioid neuropharmacology and opioid-use patterns.
Chronic pain not caused by cancer is among the most prevalent and debilitating medical conditions but also among the most controversial and complex to manage. The urgency of patients’ needs, the demonstrated effectiveness of opioid analgesics for the management of acute pain, and the limited therapeutic alternatives for chronic pain have combined to produce an overreliance on opioid medications in the United States, with associated alarming increases in diversion, overdose, and addiction. Given the lack of clinical consensus and research-supported guidance, physicians understandably have questions about whether, when, and how to prescribe opioid analgesics for chronic pain without increasing public . . .
In contrast to the traditional mechanism of drug action that relies on the reversible, noncovalent interaction of a ligand with its biological target, a targeted covalent inhibitor (TCI) is designed ...such that the initial, reversible association is followed by the formation of a covalent bond between an electrophile on the ligand and a nucleophilic center in the protein. Although this approach offers a variety of potential benefits (high potency and extended duration of action), concerns over the possible toxicological consequences of protein haptenization have hindered the development of the TCI concept. Recently, approaches to mitigate the risk of serious adverse reactions to this new class of agent have emerged, thus stimulating interest in the field and leading to authorization of the first cadre of TCIs to be marketed. The covalent inhibitor approach is rapidly gaining acceptance as a valuable tool in drug discovery, and is poised to make a major impact on the design of enzyme inhibitors and receptor modulators.
In a bind: Targeted covalent inhibitors (TCIs), such as HKI‐272 (shown in the picture in complex with a protein), first form a reversible association and then a covalent bond between an electrophile on the ligand and a nucleophilic center in the protein. This can offer benefits such as high potency and extended duration of action, and new approaches can limit the risk of serious adverse reactions.
The neurobiology of addiction is pointing the way to potential methods of disrupting the neurocircuitry with both pharmaceutical and behavioral tools. Altering the reward and emotional circuits may ...prevent and treat the problem.
This article reviews scientific advances in the prevention and treatment of substance-use disorder and related developments in public policy. In the past two decades, research has increasingly supported the view that addiction is a disease of the brain. Although the brain disease model of addiction has yielded effective preventive measures, treatment interventions, and public health policies to address substance-use disorders, the underlying concept of substance abuse as a brain disease continues to be questioned, perhaps because the aberrant, impulsive, and compulsive behaviors that are characteristic of addiction have not been clearly tied to neurobiology. Here we review recent advances in . . .
Cytokines in Cancer Immunotherapy Waldmann, Thomas A
Cold Spring Harbor perspectives in biology,
12/2018, Letnik:
10, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Cytokines that control the immune response were shown to have efficacy in preclinical murine cancer models. Interferon (IFN)-α is approved for treatment of hairy cell leukemia, and interleukin (IL)-2 ...for the treatment of advanced melanoma and metastatic renal cancer. In addition, IL-12, IL-15, IL-21, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been evaluated in clinical trials. However, the cytokines as monotherapy have not fulfilled their early promise because cytokines administered parenterally do not achieve sufficient concentrations in the tumor, are often associated with severe toxicities, and induce humoral or cellular checkpoints. To circumvent these impediments, cytokines are being investigated clinically in combination therapy with checkpoint inhibitors, anticancer monoclonal antibodies to increase the antibody-dependent cellular cytotoxicity (ADCC) of these antibodies, antibody cytokine fusion proteins, and anti-CD40 to facilitate tumor-specific immune responses.
Type 2 immune responses are defined by the cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, which can either be host protective or have pathogenic activity. Type 2 immunity promotes antihelminth ...immunity, suppresses type 1-driven autoimmune disease, neutralizes toxins, maintains metabolic homeostasis, and regulates wound repair and tissue regeneration pathways following infection or injury. Nevertheless, when type 2 responses are dysregulated, they can become important drivers of disease. Type 2 immunity induces a complex inflammatory response characterized by eosinophils, mast cells, basophils, type 2 innate lymphoid cells, IL-4-and/or IL-13-conditioned macrophages and T helper 2 (TH2) cells, which are crucial to the pathogenesis of many allergic and fibrotic disorders. As chronic type 2 immune responses promote disease, the mechanisms that regulate their maintenance are thought to function as crucial disease modifiers. This Review discusses the many endogenous negative regulatory mechanisms that antagonize type 2 immunity and highlights how therapies that target some of these pathways are being developed to treat type 2-mediated disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Pulmonary fibrosis is a highly heterogeneous and lethal pathological process with limited therapeutic options. Although research on the pathogenesis of pulmonary fibrosis has frequently focused on ...the mechanisms that regulate the proliferation, activation, and differentiation of collagen-secreting myofibroblasts, recent studies have identified new pathogenic mechanisms that are critically involved in the initiation and progression of fibrosis in a variety of settings. A more detailed and integrated understanding of the cellular and molecular mechanisms of pulmonary fibrosis could help pave the way for effective therapeutics for this devastating and complex disease.
Fibrinogen adsorption to biomaterials Horbett, Thomas A.
Journal of biomedical materials research. Part A,
October 2018, Letnik:
106, Številka:
10
Journal Article
Developing a comprehensive method to compute bond orders is a problem that has eluded chemists since Lewis's pioneering work on chemical bonding a century ago. Here, a computationally efficient ...method solving this problem is introduced and demonstrated for diverse materials including elements from each chemical group and period. The method is applied to non-magnetic, collinear magnetic, and non-collinear magnetic materials with localized or delocalized bonding electrons. Examples studied include the stretched O 2 molecule, 26 diatomic molecules, 3d and 5d transition metal solids, periodic materials with 1 to 8748 atoms per unit cell, a biomolecule, a hypercoordinate molecule, an electron deficient molecule, hydrogen bound systems, transition states, Lewis acid–base complexes, aromatic compounds, magnetic systems, ionic materials, dispersion bound systems, nanostructures, and other materials. From near-zero to high-order bonds were studied. Both the bond orders and the sum of bond orders for each atom are accurate across various bonding types: metallic, covalent, polar-covalent, ionic, aromatic, dative, hypercoordinate, electron deficient multi-centered, agostic, and hydrogen bonding. The method yields similar results for correlated wavefunction and density functional theory inputs and for different S Z values of a spin multiplet. The method requires only the electron and spin magnetization density distributions as input and has a computational cost scaling linearly with increasing number of atoms in the unit cell. No prior approach is as general. The method does not apply to electrides, highly time-dependent states, some extremely high-energy excited states, and nuclear reactions.
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