scholarly journals Thalidomide Embryopathy: An Enigmatic Challenge

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Neil Vargesson

Thalidomide remains one of the world’s most notorious drugs due to the severe birth defects it induced in children between 1957 and 1962. Yet, to some this drug is a lifesaver, as it now enjoys renaissance in the treatment for a wide range of conditions including leprosy, multiple myeloma, Behcet’s disease, and some cancers. However, thalidomide has also been linked to causing a new generation of thalidomide survivors in Brazil, where the drug is used to treat leprosy. Surprisingly how thalidomide causes birth defects and how it acts in the treatment of clinical conditions are still far from clear. In the past decade great strides in our understanding of the actions of the drug, as well as molecular targets, have been made. The purpose of this review is to look at the recent work carried out into understanding how thalidomide causes birth defects, it’s molecular targets and the challenges that remain to be elucidated. These challenges include identifying clinically relevant but nonteratogenic forms of the drug, and the mechanisms underlying phocomelia and species specificity.

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Alessandra Romano ◽  
Concetta Conticello ◽  
Maide Cavalli ◽  
Calogero Vetro ◽  
Cosimo Di Raimondo ◽  
...  

During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.


2002 ◽  
Vol 55 (2) ◽  
pp. 39 ◽  
Author(s):  
M. Zheng ◽  
T. Endo ◽  
W. Zimmermann

Large-ring cyclodextrins (LR-CD) are cyclic α-1,4-glucans composed of nine to more than several hundred glucopyranose units. Cyclodextrins are able to form highly specific inclusion complexes with a wide range of guest molecules thereby modifying their physicochemical properties. Only in the past 10 years, LR-CD with a degree of polymerization between 9 and 32 have been isolated and characterized. The structures of these LR-CD show novel features distinct from those of the extensively studied α- β-, and γ-CD composed of six, seven, and eight glucopyranose units, respectively. Recent work on the enzymatic synthesis of LR-CD has confirmed the ability of different 4-α-glucanotransferases to form large cyclic α-1,4-glucans from amylose and amylopectin, depending on the specificity of the enzyme used and on the substrate and reaction conditions chosen. The potential of LR-CD for specific host-guest interactions and corresponding applications has been demonstrated.


2002 ◽  
Vol 55 (1) ◽  
pp. 141-154 ◽  
Author(s):  
Koen Lamberts

This article presents an overview of some recent work on the time course of perceptual categorization and recognition memory. First, The EGCM-RT, which is a feature-sampling model of the time course of categorization, is described. It is shown that the model explains a wide range of categorization data. Second, an overview is given of a feature-sampling model of the time course of recognition that is derived from the EGCM-RT. This model explains results that have been interpreted in the past as evidence for dual-process models of recognition, and it provides a single-process alternative to dual-process accounts.


Author(s):  
A. Strojnik ◽  
J.W. Scholl ◽  
V. Bevc

The electron accelerator, as inserted between the electron source (injector) and the imaging column of the HVEM, is usually a strong lens and should be optimized in order to ensure high brightness over a wide range of accelerating voltages and illuminating conditions. This is especially true in the case of the STEM where the brightness directly determines the highest resolution attainable. In the past, the optical behavior of accelerators was usually determined for a particular configuration. During the development of the accelerator for the Arizona 1 MEV STEM, systematic investigation was made of the major optical properties for a variety of electrode configurations, number of stages N, accelerating voltages, 1 and 10 MEV, and a range of injection voltages ϕ0 = 1, 3, 10, 30, 100, 300 kV).


Author(s):  
John L. Hutchison

Over the past five years or so the development of a new generation of high resolution electron microscopes operating routinely in the 300-400 kilovolt range has produced a dramatic increase in resolution, to around 1.6 Å for “structure resolution” and approaching 1.2 Å for information limits. With a large number of such instruments now in operation it is timely to assess their impact in the various areas of materials science where they are now being used. Are they falling short of the early expectations? Generally, the manufacturers’ claims regarding resolution are being met, but one unexpected factor which has emerged is the extreme sensitivity of these instruments to both floor-borne and acoustic vibrations. Successful measures to counteract these disturbances may require the use of special anti-vibration blocks, or even simple oil-filled dampers together with springs, with heavy curtaining around the microscope room to reduce noise levels. In assessing performance levels, optical diffraction analysis is becoming the accepted method, with rotational averaging useful for obtaining a good measure of information limits. It is worth noting here that microscope alignment becomes very critical for the highest resolution.In attempting an appraisal of the contributions of intermediate voltage HREMs to materials science we will outline a few of the areas where they are most widely used. These include semiconductors, oxides, and small metal particles, in addition to metals and minerals.


2020 ◽  
Vol 04 (04) ◽  
pp. 369-372
Author(s):  
Paul B. Romesser ◽  
Christopher H. Crane

AbstractEvasion of immune recognition is a hallmark of cancer that facilitates tumorigenesis, maintenance, and progression. Systemic immune activation can incite tumor recognition and stimulate potent antitumor responses. While the concept of antitumor immunity is not new, there is renewed interest in tumor immunology given the clinical success of immune modulators in a wide range of cancer subtypes over the past decade. One particularly interesting, yet exceedingly rare phenomenon, is the abscopal response, characterized by a potent systemic antitumor response following localized tumor irradiation presumably attributed to reactivation of antitumor immunity.


2020 ◽  
Vol 1 (2) ◽  
pp. 157-172
Author(s):  
Thomas Leitch

Building on Tzvetan Todorov's observation that the detective novel ‘contains not one but two stories: the story of the crime and the story of the investigation’, this essay argues that detective novels display a remarkably wide range of attitudes toward the several pasts they represent: the pasts of the crime, the community, the criminal, the detective, and public history. It traces a series of defining shifts in these attitudes through the evolution of five distinct subgenres of detective fiction: exploits of a Great Detective like Sherlock Holmes, Golden Age whodunits that pose as intellectual puzzles to be solved, hardboiled stories that invoke a distant past that the present both breaks with and echoes, police procedurals that unfold in an indefinitely extended present, and historical mysteries that nostalgically fetishize the past. It concludes with a brief consideration of genre readers’ own ambivalent phenomenological investment in the past, present, and future each detective story projects.


What did it mean to be a man in Scotland over the past nine centuries? Scotland, with its stereotypes of the kilted warrior and the industrial ‘hard man’, has long been characterised in masculine terms, but there has been little historical exploration of masculinity in a wider context. This interdisciplinary collection examines a diverse range of the multiple and changing forms of masculinities from the late eleventh to the late twentieth century, exploring the ways in which Scottish society through the ages defined expectations for men and their behaviour. How men reacted to those expectations is examined through sources such as documentary materials, medieval seals, romances, poetry, begging letters, police reports and court records, charity records, oral histories and personal correspondence. Focusing upon the wide range of activities and roles undertaken by men – work, fatherhood and play, violence and war, sex and commerce – the book also illustrates the range of masculinities that affected or were internalised by men. Together, the chapters illustrate some of the ways Scotland’s gender expectations have changed over the centuries and how, more generally, masculinities have informed the path of Scottish history


2015 ◽  
Vol 2 (2) ◽  
pp. 85-94
Author(s):  
Christina Landman

Dullstroom-Emnotweni is the highest town in South Africa. Cold and misty, it is situated in the eastern Highveld, halfway between the capital Pretoria/Tswane and the Mozambique border. Alongside the main road of the white town, 27 restaurants provide entertainment to tourists on their way to Mozambique or the Kruger National Park. The inhabitants of the black township, Sakhelwe, are remnants of the Southern Ndebele who have lost their land a century ago in wars against the whites. They are mainly dependent on employment as cleaners and waitresses in the still predominantly white town. Three white people from the white town and three black people from the township have been interviewed on their views whether democracy has brought changes to this society during the past 20 years. Answers cover a wide range of views. Gratitude is expressed that women are now safer and HIV treatment available. However, unemployment and poverty persist in a community that nevertheless shows resilience and feeds on hope. While the first part of this article relates the interviews, the final part identifies from them the discourses that keep the black and white communities from forming a group identity that is based on equality and human dignity as the values of democracy.


2019 ◽  
Vol 20 (2) ◽  
pp. 49-54
Author(s):  
Dildora Alinazarova ◽  

In this article, based on an analysis of a wide range of sources, discusses the emergence and development of periodicals and printing house in Namangan. The activities of Ibrat- as the founder of the first printing house in Namangan are considered. In addition, it describes the functioning and development of "Matbaai Ishokia" in the past and present


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