bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socrates’ New Aitia:Causal and Metaphysical Explanations in plato’s Phaedo
Authors: Sharma Ravi 
Published: November 2023

Abstract
The section of the Phaedo that recounts Socrates’ intellectual ‘autobiography’ and culminates in his turn to the theory of Forms (95 e“102 b) has long been considered a key passage for understanding Plato’s mature philosophy. Besides offering explicit commentary on various themes of Presocratic thought, it is one of the few Platonic texts purporting to explain some of the considerations that motivate the theory of Forms.
What is lung cancer?
Authors: Falk Stephen , Williams Chris 
Published: November 2023

Abstract
Lung cancer is the most common cancer in the Western world. Cancer is defined as an abnormal growth of cells which tend to divide and grow in an uncontrolled way and, in some cases, to metastasize (spread). Treatment is determined by which of the two commonest types of lung cancer is present: small cell lung cancer or non-small cell lung cancer.
Treatment of non-small cell lung cancer
Authors: Falk Stephen , Williams Chris 
Published: November 2023

Abstract
The treatment is planned according to the extent of the disease and general fitness. The major curative treatment is surgery. Radiotherapy can cure lung cancer and also help the common symptoms. Chemotherapy either adds to radiotherapy or surgery for cure or is used to prolong the quantity and quality of life. Newer targeted treatments offer the hope of improving treatment outcomes with fewer side-effects.
‘Type 2’ myotonic dystrophy
Authors: Harper Peter S 
Published: November 2023

Abstract
The gene for ‘type 2’ myotonic dystrophy was discovered in 2000, and this has proved very important for our understanding of myotonic dystrophy as a whole. This condition is often relatively mild and only slowly progressive. In particular, it rarely occurs in childhood and never in a severe congenital form as may happen in type 1 myotonic dystrophy.
Family aspects and genetic risks
Authors: Harper Peter S 
Published: November 2023

Abstract
In type 1 myotonic dystrophy (the usual form), just one specific gene is altered. In the much less frequent type 2 myotonic dystrophy, a different gene is altered. The genes that cause myotonic dystrophy can be detected by a genetic test. Both type 1 and type 2 myotonic dystrophy are inherited. Therefore, a number of family members are likely to be affected. There is a 50% chance that a child will inherit myotonic dystrophy from an affected parent.
Divine Will Theory: Intentions or Desires?
Authors: Miller Christian 
Published: November 2023

Abstract
Due largely to the work of Mark Murphy and Philip Quinn, divine will theory has emerged as a legitimate alternative to divine command theory in recent years.¹ As an initial characterization, divine will theory is a view of deontological properties according to which, for instance, an agent S’s obligation to perform action A in circumstances C is grounded in God’s will that S A in C. Characterizing this abstractly, divine will theory does not specify which kind of mental state is supposed to ground S’s obligation; it could be God’s desires, beliefs, intentions, or emotions. My purpose here is not to challenge this view. Rather, I want to examine the decision by Murphy and Quinn to base their version of divine will theory on God’s intentions, and argue that this may have been an unwise move. As an alternative, I suggest that those who are initially attracted to divine will theory would be better served to develop the view with a focus on God’s desires rather than intentions.
Summary of Legislation in Radiological Protection in the United Kingdom
Authors: Prime David 
Published: November 2023

Abstract
The use of equipment or materials which emit radiations is governed by two pieces of legislation: the Radioactive Substances Act (1960) and the Ionizing Radiations Regulations (1985). This legislation imposes a system of radio logical protection which is more or less the same in all premises using radio active materials or radiation emitting equipment. This system will be outlined in two sections dealing with the respective items of legislation.
The use of the Filtration Technique in in Vitro Radioligand Binding Assays for Membrane-Bound and Solubilized Receptors
Authors: Wang Jian-xin , Yamamura Henry I , Wang Wan , Roeske william R 
Published: November 2023

Abstract
It has been nearly a century since the receptor hypothesis was first proposed for the mechanism of the effects of drug and toxins on biosystems (1,2). In 1926, A. J. Clark established his receptor occupation theory (3) describing a quantitative interaction between drugs and their receptors. For a period of almost 40 years putative drug receptors were detected by measuring the functional response elicited by drugs. This method must make assumptions that relate the drug-receptor binding properties to the function measured. The first attempt to directly measure the receptors with radiolabelled ligand can be traced back to the 1960s when [3H]atropine (4) and [3H]propranolol (5) were used to label the muscarinic uptake sites in the intestinal smooth muscle and the adrenergic uptake site in atria, respectively. In 1970, radioiso tope labelled adrenocorticotropic hormone (ACTH) (6), angiotensin (7) and o.-bungarotoxin (8) were used to measure ACTH, angiotensin, and nicotinic cholinergic receptors, respectively. These pioneering experiments demon strated that radioisotopically labelled hormones or toxins could be used to study directly the interaction of hormones or toxins with their specific membrane sites. However, some of these studies were limited by technical difficulties such as a low signal-to-noise ratio.
Centrifugation Binding Assays
Authors: Hulme E C 
Published: November 2023

Abstract
Centrifugation assays are best applied to assaying the labelling of receptors in membrane preparations using radioligands. The principle is elementary. At the end of the assay period, the membranes bearing the labelled receptors are sedimented, and thus physically removed from the supernatant, containing the bulk of the unbound radioligand. After pouring off the supernatant, and subjecting the pellet to washing procedures of greater or less rigour, the amount of bound ligand is assayed, typically by liquid scintillation spectroscopy, or γ-counting.
Purification of Nicotinic Acetylcholine Receptors
Authors: Weed Sigrid Hertling-Ja , Bandini Giampiero , Hucho Ferdinand 
Published: November 2023

Abstract
Receptors are membrane proteins receiving extracellular signals-hormones, growth factors, neurotransmitters-and transducing them to the interior of receiving cells (1). Despite their diversity they have many properties in common, some of which have been discovered through pioneering work on the nicotinic acetylcholine receptor (nAChR), which therefore has become a model for much of the present-day receptor research (2). All membrane-bound receptors are glycoproteins embedded in and partially protruding from the plasma membrane. All are composed of one or several polypeptide chains threaded through the lipid bilayer of the membrane by means of one, four, or seven possibly α-helical hydrophobic sequences. The growth-factor receptors have one membrane-spanning helix; receptors rigidly coupled to ion channels have four, and the receptors transiently coupled to effector enzymes via G-proteins have seven putative transmembrane helices. Most, if not all, receptors can be phosphorylated at sites located on sequences oriented towards the cytoplasm. Receptors exist in inter convertible functional states. They can be considered to be allosterically regulated proteins (3).
Interactions of muscarinic acetylcholine receptors (mAChRs) with G-proteins
Authors: Haga T , Haga k. 
Published: November 2023

Abstract
The responses induced by mAChRs are considered to occur in the following order (for a review, see reference 1):
(a) the binding of acetylcholine (ACh) to mAChRs:
(b) the activation by the ACh-mAChR complex of G-proteins (G), i.e. facilitation of the dissociation of GDP from G and the subsequent association of GTP with G;
(c) the activation or inhibition by G-GTP of effectors, which include adenylate cyclase (inhibition), polyphosphoinositide phosphodiesterase, and ion channels.
Evidence for a direct interaction between mAChRs and G-proteins has been provided by reconstituting purified mAChRs and purified G-proteins into phospholipid vesicles, and then observing the effect of guanine nucleotides on acetylcholine binding and the effect of acetylcholine on guanine nucleotide binding (2-6).
Mechanism of action of hormone antagonists
Authors: Dauvois S , Parker M G 
Published: November 2023

Abstract
Steroid hormone antagonists are compounds that compete with steroid hormones for receptor binding but fail to trigger the normal response and thereby inhibit the action of the hormone. They have a number of important clinical applications, particularly in the control of fertility and for the treatment of hormone-dependent cancer, and are also useful for elucidating the role of steroid hormones in the regulation of a wide range of physiological responses. The advantage of using anti-hormones to suppress hormone action compared with other approaches such as endocrine gland ablation is their greater degree of specificity: in general, their effects are restricted to target tissues for the hormone. Thus, while endocrine gland ablation is being used successfully to treat a number of clinical syndromes, specific hormone antagonists are now available which in certain circumstances are used as the preferred treatment.
Mutations in steroid hormone receptors causing clinical disease
Authors: Mcphaul Michael J 
Published: November 2023

Abstract
The syndromes of hormone resistance have been of interest to scientists for decades. Following the detection of specific receptors for thyroid hormone, vitamin D, and steroid hormones, substantial effort was made to study patients affected with these disorders using assays of hormone binding. Although interesting patterns often emerged from such studies, the pathogenesis of the diseases remained obscure.
Techniques For Studying Mitosis In Drosophila
Authors: Gonzalez Cayetano , Glover David M 
Published: November 2023

Abstract
Of all mctazoans, Drosophila melanogaster is perhaps best suited for a genetic analysis of cell division. In this chapter, we cannot hope to cover all the experimental techniques needed to study Drosophila. However, we aim to supplement existing texts by concentrating on techniques to characterize mitotic mutants. Ashburner has recently undertaken the Herculean task of producing an excellent laboratory handbook (1) which together with a laboratory manual (2) provide an essential reference guide for Drosophila research. In addition, we refer to another volume in this series Drosophila: a practical approach, edited by David Roberts (3).
Prediction and experitnental investigation of RNA secondary and tertiary foldings
Authors: Westhof Eric , Michel Francois 
Published: November 2023

Abstract
Through folding of the polynucleotide sugar-phosphate backbone, the ribonucleic acid bases interact and form hydrogen-bonded double-stranded helices separated by single-stranded regions forming hairpin loops, bulges, and internal or multiple loops (Figure 1). The main secondary structural element, the antiparallel double stranded helix, is maintained via hydrogen bonds involving atoms of the bases, that is, atoms of the side chains and not of the polynucleotide backbone (in contrast to proteins where secondary structure elements such as sheets or helices are held through hydrogen bonds involving atoms of the polypeptide backbone). The establishment of the secondary structure of an RNA molecule is thus feasible either directly from its base sequence on the basis of solution data (chemical and enzymatic probing) coupled with theoretical free energy minimizations or by sequence comparisons of functionally similar molecules across phylogeny.
PFGE in physical mapping
Authors: Ho M F , Monaco A P 
Published: November 2023

Abstract
The development of pulsed field gel electrophoresis (PFGE), which allows the separation of DNA molecules as large as 10 Mb, has enabled large regions of genomic DNA to be mapped and analysed without cloning the DNA (1–3). Its wide separation range has bridged the size gap between cytogenetic methods (&gt;5 Mb) and conventional gel electrophoresis (up to 50 kb). Prior to this, genetic mapping has been the primary method for mapping genes responsible for inherited disorders. Genetic maps relate the apparent distance between genes or other detectable markers to the relative frequency of genetic events, such as recombination; hence its resolution is dependent on the number of available meiotic events and recombination frequency. The latter not only differs between male and female but varies for different regions of the genome. In contrast, physical maps reflect the actual structure of the DNA, its range as well as resolution can be adjusted within wide limits by choosing the appropriate rare-cutting restriction enzymes and electrophoretic conditions. The combination of genetic and physical mapping strategies has been essential for the isolation of genes responsible for many human genetic disorders including cystic fibrosis and Huntington’s disease.
Functional analysis of mammalian genomes using yeast artificial chromosomes
Authors: Larin Z 
Published: November 2023

Abstract
Methods for isolating genes by positional cloning have been enhanced by using yeast artificial chromosomes (YACs) as mapping tools. However, YACs may also be used to isolate genes by functional complementation of a mutant phenotype (1) following transfer of YACs containing the respective region into cultured cells (2, 3) or mice (4, 5, 6). This approach is particularly attractive for isolating murine genes where large regions containing mutant loci have been mapped by genetic markers. Once a YAC is known to encompass a particular gene, further localization of the gene can be obtained by re-introducing a series of YAC deletions, constructed by telomere fragmentation (7) (see Chapter 6), into mammalian cells, and testing for complementation of the mutant phenotype.
Concentration and purification of viruses
Authors: Minor P D 
Published: November 2023

Abstract
Virus infectivity or its neutralization by antibodies can usually be measured on non-concentrated preparations, but for many other purposes concentration and purification are essential because of the small mass of the infectious agent. For example, 1 × 106 plaque-forming units of poliovirus may have a total mass of about 1 ng, of which 250 pg will be genomic RNA. While this is sufficient for genome amplification where the sequence is known, more concentrated and purified preparations will be required for investigations such as: physical analysis genetic analysis where the genome sequence is not known use as an antigen or immunogen Concentrated virus preparations will contain the virus at a higher concentration than in the starting material but still include substantial amounts of impurities such as components from host cells. These crude preparations can be used successfully in a variety of applications, including immunoprecipitation with specific antibodies, some routine antibody assays such as ELISA for known viruses, or as immunogens to produce neutralising antibodies. Possible adverse effects of non-viral impurities can include false-positive reactions with antibodies, the induction of antibodies to non-viral antigens, or the detection of non-viral nucleic acids, and some purification procedure is usual following concentration.
Application of the baculoviral expression system to signal transduction
Authors: Paterson Andrew 
Published: November 2023

Abstract
The Baculovirus Expression Vector System (BEYS) is an extremely versatile and powerful laboratory tool (1). In simplest terms, the BEYS allows the forced heterologous expression of recombinant protein in susceptible host strains of insect cells. Gene products from the simplest prokaryotes through to the higher eukaryotes have been expressed successfully in this system. Recombinant proteins are recovered in a folded and active form, and posttranslation modifications, such as phosphorylation, lipid acylation, and simple glycosylation are often preserved. Oligomerization is preserved also, as is the ability to form holomeric complexes. This has been demonstrated clearly with expression of the - 40 k Da G proteins in their native al3 ‘) ‘ heterotrimeric complexes (2), and extended to the activation of the kinase, c-Raf, upon coexpression with Ras and Src tyrosine kinase (3). Since the host insect cells maintain the ability to process eukaryotic pre-mRNA, heterologous expression from genomic DNA is possible. However, the most attractive facet of BEYS must be the high level of heterologous protein expression with values of between 0.1 and 30% of total cell protein being reported, and often with gene products that fail to express with activity or reasonable yield in other systems. The rationale of the BEYS is fairly simple. The baculoviral genome is engineered to incorporate the coding sequence of a foreign protein. Incorporation is directed to a position downstream, and under the control, of a strong viral promoter.
Phospholipase D and phosphatidylcholine metabolism
Authors: Meier Kathryn E , Gibbs Terra C 
Published: November 2023

Abstract
Phospholipase D (PLD) catalyses the hydrolysis of phospholipids to phosphatidic acid (PA). The preferred substrate for most PLDs is phosphatidylcholine, although utilization of other substrates (e.g. phosphatidylethanolamine) has been reported. PLDs are expressed in mammals, insects, plants, yeast, and certain bacteria. In mammalian cells, PLD is activated in response to a broad range of agonists (reviewed in refs 1-4). In general, PLD activity is increased by agonists that bind to G protein-coupled receptors (GPCRs) inducing phospholipase C (PLC) activation. Various growth factors, hormones, and cytokines can activate PLD. Phorbol-12-myristate-13-acetate (PMA), a tumour promoter that activates protein kinase C (PKC) isoforms, induces PLD activation in most mammalian cell types. The roles of PLDs in signal transduction remain of great interest, but poorly defined. The recent molecular cloning of PLD isoforms has greatly accelerated work in this research area.
Protein-ligand interactions and their analysis
Authors: Chowdhry Babur Z , Harding Stephen E 
Published: November 2023

Abstract
In each cell of an organism, a myriad of reactions, covalent and non-covalent, occur at any given point in time. These reactions are co-ordinated and regulated, both spatially and temporally. Each reaction has a specific purpose, occurs as a result of finely-tuned inter- and intramolecular recognition mechanisms, and forms part of an intricate network of interdependent multi-component linear/ non-linear reactions in interconnected compartments (organelles etc.) of the cell. Moreover the frontiers of viability of such reactions-and the living organ isms that depend on them-are marked by extreme conditions: 1-12 for pH, -5-110 °C for temperature, 0.1-120 MPa for hydrostatic pressure, and 0.6-1.0 for water activity. Amongst the many molecules that participate in such reactions in the complex-and, as yet hardly understood, milieu of the cell-are proteins.
Quantitative characterization of ligand binding by chromatography
Authors: Winzer Donald J 
Published: November 2023

Abstract
The power of chromatography as a means of separating molecµles on the basis of charge (ion-exchange chromatography), size (exclusion or gel chromatography), and biospecificity (affinity chromatography) is recognized universally. Less well known is the scope of the technique for the quantitative characterization of ligand binding in terms of the stoichiometry and strength of the equilibrium phenomenon.
Capillary electrophoresis
Authors: Heegaard Niels H H 
Published: November 2023

Abstract
Electrophoresis is the transport of charged molecules in solution by the action of an electrical field (1). Electrophoretic techniques are widely used to separate and characterize biomolecular mixtures and very high resolution may be achieved by the use of denaturing one- or two-dimensional gel methods. The separation efficiency in these techniques is normally achieved at the expense of analyte functions such as enzyme and ligand binding activities that are adversely affected by the denaturing conditions required. With the advent of capillary electro phoresis (CE) (2), however, it has become possible to preserve molecular function whilst still maintaining separation efficiency for the reason that extremely high resolution can be obtained in buffers that do not interfere with the native structure of the analyte. This has expanded the use of affinity electrophoresis methods considerably.
Proteins of the major histocompatibility complex and their interactions with T-cell receptors
Authors: Dafforn Tim R 
Published: November 2023

Abstract
Surgical patients, if not immunosuppressed by drugs, will reject transplanted organsunless the donor is an identical twin-because the transplant is recognized as being foreign. The immunological distinction between ‘self’ and ‘non-self’ resides in the proteins of the Major Histocompatibility Complex (MHC) and their interaction with T-cell receptors. MHC proteins bind intracellularly produced peptides and present them on cell surfaces. The triggering event in alerting the immune system to the presence of a foreign protein is the recognition, by a T-cell receptor, of a complex between an MHC protein and a peptide derived from the foreign protein.
RNA editing in kinetoplastid mitochondria
Authors: Stuart Kenneth D 
Published: November 2023

Abstract
All three major classes of RNA undergo post-transcriptional processing by nucleolytic cleavage and base modification before they become functional (1). A general theme in RNA processing is (cis or trans) RNA–RNA interactions and the association with a macromolecular complex. Ribosomal RNA precursors are processed by a series of endonucleolytic cleavages that are catalyzed by RNA or protein enzymes. The rRNA bases are modified at sites which are guided by base pairing with small nucleolar (sno) RNAs (2). Similarly, tRNAs are cleaved from precursors, and the site of the 5’ cleavage is guided by bases pairing with the RNA component of RNase P. In addition, many bases of tRNA are modified by a variety of enzymes that select the base by RNA–RNA interactions that result from the tRNA structure (3). The mRNA precursors also undergo a variety of processing reactions. These include cleavage, 5’ capping, 3’ polyadenylation and intron excision (splicing). An important aspect of RNA splicing is that it produces informationally correct mature mRNA and, indeed, the appropriate mRNA version in the case of alternative splicing. Splicing is catalyzed by the spliceosome, a ribonucleoprotein complex that is composed of numerous proteins and several small RNAs that base pair with the mRNA and guide the sites of catalysis. Indeed, spliceosome RNAs may catalyze some of the steps of splicing. More recently, it was found that mRNAs undergo other forms of RNA processing that are collectively termed RNA editing since they alter the sequence from that encoded in the structural gene (4). RNA editing falls into two categories: base modification and nucleotide insertion/deletion. The first observed, and perhaps most complex, form of RNA editing is that which occurs in the mitochondrion of kinetoplastid protozoa (trypanosomatids). This type of editing is the subject of this chapter and has been covered in several excellent previous reviews (5, 6). This type of editing inserts and deletes uridylates (Us) to produce mature mRNAs with sequences that are specified by small guide RNAs (gRNAs). The editing in trypanosomes occurs in association with a macromolecular complex. It occurs in all kinetoplastids but is most extensive in African trypanosomes. Editing in this group will be the focus of this review.