bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Control During Erythroid and Megakaryocytic Development
Authors: Orkin Stuart H 
Published: November 2023

Abstract
Establishing a functioning hematopoietic system is the end result of a series of developmental decisions, each executed in large part by transcriptional mechanisms (Orkin, 1996). Following the commitment of mesoderm to an hemangioblast fate, the first hematopoietic progenitors are produced. At the yolk-sac stage of development, only primitive (or embryonic) red blood cells are produced. Within the embryo proper, hematopoietic stem cells (HSCs) ultimately generate progenitors that are heterogeneous with respect to their lineage options. Subsequently, single (or bi-or tri-) potent precursors develop. Cellular differentiation completes the formation of terminally mature blood cells. In this chapter, attention is directed to the roles of particular transcription factors involved in specifying aspects of erythroid and megakaryocytic development. The erythroid and megakaryocytic lineages are of special interest in that they appear to be derived from common bipotential progenitors and share several critical transcriptional components, yet ultimately they serve very different biological functions.
Ets Transcription Factor Mutations and Hematopoiesis
Authors: Dahl Richard , Hackenmiller, Renee D , Simon M Celeste 
Published: November 2023

Abstract
The Ets family of transcription factors consists of a large number of winged helix-loop-helix DNA-binding proteins. Members of the Ets family are related by a high degree of sequence identity within the DNA-binding domain (ETS domain), which recognizes purine-rich DNA motifs centered around the core nucleotides GGAA/T (Karim et al., 1990). The Ets proteins are highly conserved through evolution and are important regulators of development in flies, worms, and mammals. At least eight Ets proteins, including PU. I, Spi-B, Ets-1, Ets-2, Elf-1, Fli-1, TEL, and GABPcx are expressed in hematopoietic cells (see Table 35.1), and binding sites for these Ets proteins have been described in a large number of genes thought to be involved in hematopoietic differentiation and immune system function (reviewed in Bassuk and Leiden, 1997).
The Role of the Thrombopoietin Receptor in Megakaryopoiesis
Authors: Drachman Jonathan G , Kaushansky Kenneth 
Published: November 2023

Abstract
Occasionally, in science, findings from one area of researchinsightful and important for that discipline-exert a profound, catalytic influence on what was previously thought to be a completely unrelated field of study. The discovery of the oncogene v-mpl was such an event, initiating a new chapter in the study of hematopoietic growth factors in general, and thrombopoiesis, in particular.
The Role of Osteoblasts in Hematopoietic Stem Cell Biology
Authors: Emerson Stephen G , Taichman, Russell S , Adams Scott 
Published: November 2023

Abstract
After birth, blood cells are produced in the bone marrow. The development of the bone marrow cavity is a coordinated process in which blood precursors migrate and colonize spaces carved out of embryonic bone and cartilage. The physical proclivity and localization of hematopoietic precursors to the marrow space suggests that either cells or matrix molecules in the acellular bone microenvironment control homing and/or proliferation of hematopoietic stem cells. The key role of extracellular matrix (ECM) proteins, such as fibronectin and laminin, and glycoconjugates such as heparan sulfates, has been amply demonstrated by elegant co-culture studies. More recently, it has become clear that osteoblasts themselves directly influence and regulate hematopoiesis. This chapter will describe our current understanding of the role of osteoblasts in hematopoiesis, and suggest likely directions for critical experiments in the near future.
Transcriptional Regulation of T Cell Development and Activation
Authors: Kuo Chay T , Leiden Jeffrey M 
Published: November 2023

Abstract
The T lymphocytes are important mediators of mammalian immune responses to viral, bacterial, and parasitic pathogens, as well as to tumor cells. They have also been implicated in the etiology of allergic and autoimmune diseases, including asthma, diabetes mellitus, and multiple sclerosis. Thus, in addition to its basic scientific significance, a molecular understanding of T cell development and activation will have important implications for understanding and treating a wide variety of human diseases.
Lineage Commitment of CD4+ T Helper Lymphocytes
Authors: Glimcher Laurie H , Ranger Ann M , Ho I-Cheng 
Published: November 2023

Abstract
Cells of the immune system interact with each other and undergo a complex pattern of gene expression in response to extracellular and intracellular signals. Among the most important of external signals for immune system cells are a set of polypeptides, designated cytokines or lymphokines, that possess a diversity of biological activities in several cell types.
Signal Transduction and Regulation of Antigen Receptor Gene Rearrangement During Early Lymphocyte Development
Authors: Shaw Albert C , Bassing Craig H , Swat Wojciech , Alt Frederick W 
Published: November 2023

Abstract
Immunoglobulin (lg) and T cell receptor (TCR) proteins, as crucial elements in the humoral and cell-mediated immune responses, are synthesized in B and T lymphocytes, respectively, in the context of complex, precisely regulated de elopmental pathways.
The Phylogenetic Development of the Cells That Express, and the Mechanisms That Diversify, lmmunoglobulins and T Cell Antigen Receptors
Authors: Miracle Ann L , Hawke Noel A , Anderson, Michele K , Litman Gary W 
Published: November 2023

Abstract
Specific immune-type recogmt10n has been identified throughout the extant vertebrate taxa, which include the jawless vertebrates (e.g., lamprey and hagfish). However, immunoglobulin (lg) and T cell antigen receptor (TCR) genes are confined only to the radiations of the jawed vertebrates, which are represented by the cartilaginous, ray-finned, and fleshy-finned fishes, as well as amphibians, reptiles, avians, and mammals. The basic processes of genetic reorganization and secondary diversification of lg genes has been demonstrated in all species of jawed vertebrates studied to date. Remarkable variation in the organization of lg genes has been recognized in a large number of species, representing critical points in the phylogeny of jawed vertebrates. Although the mechanisms underlying the rearrangement of antigen-binding receptor genes have been characterized in great depth only in mammals (see Chapter 48, this volume), all observations to date suggest that the basic mechanism of DNA-mediated segmental rearrangement of both lg and TCR genes has been conserved throughout the jawed vertebrates.
Regulation of Hematopoiesis by Bone Marrow Microvascular Endothelium
Authors: Rafii Shahin 
Published: November 2023

Abstract
Both hematopoietic stem cells and endothelial progenitor cells (angioblasts) are believed to originate from the same mesenchymal cell referred to as a hemangioblast (Risau et al., 1988; Coffin et al., 1991; Auerbach et al., 1996; Caprioli et al., 1998; Choi et al., 1998). Hemangioblasts give rise to blood islands, which are composed of primitive hematopoietic stem cells residing in close cellular contact with angioblasts. This close interaction between hematopoietic stem cells and endothelial cells persists as the site of hematopoiesis shifts from the yolk sac or aorta-gonad-mesonephros (AGM) region to the fetal liver, and then ultimately to the spleen and adult bone marrow. Within the bone marrow microenvironment, bone marrow endothelial cells (BMEC) form a complex network of sinusoids where hematopoiesis takes place.
The Angiopoietins, and How They Act Coordinately with Vascular Endothelial Growth Factor During Normal and Pathologic Angiogenesis
Authors: Davis Samuel , Holash Jocelyn , Suri Chitra , Maisonpierre Peter C , Wiegand Stanley J , Yancopoulos George D 
Published: November 2023

Abstract
Embryonic vascular development involves a complex series of events during which endothelial cells differentiate, proliferate, migrate, and undergo profound morphological changes (Risau, 1995, 1997). These processes are generally divided into two successive stages. The first, known as vasculogenesis, refers to the processes whereby newly differentiated endothelial cells spontaneously coalesce into tubes to form a rather homogeneous and primitive primary vasculature. The second stage, during which this primary vascular network is remodeled into large and small vessels, is termed angiogenesis. Embryonic angiogenesis also encompasses sprouting into previously avascular organs, such as the brain. Recent findings, to be discussed in detail below, suggest that vascular development culminates with the maturation and stabilization of developing vessels into quiescent vessels in which the endothelium is well integrated with surrounding matrix and support cells, allowing it to serve an important barrier function.
Introduction
Authors: Costa João 
Published: November 2023

Abstract
This collection of essays brings together a number of studies dealing with aspects of Portuguese syntax within the Principles and Parameters framework (Chomsky and Lasnik 1993) and its extension known as the Minimalist Program (Chomsky 1995). According to this framework, explanatory adequacy in the description of languages may be attained by determining the universal language-independent principles that govern the shape of natural languages rather than by postulating language-specific and construction-specific rules for describing isolated phenomena. Language variation is explained by a minimal set of parameters, with different values specified for different languages. Under the Minimalist Program, it is explicitly proposed that language-specific variation may be a consequence of morphological variation reflected in the syntax.1
A Minimalist Approach to Clitic Climbing
Authors: Martins Ana Maria 
Published: November 2023

Abstract
In the Minimalist framework (Chomsky 1993, 1994), movement is driven by morphological necessity, that is, movement is possible only for the purposes of morphological feature checking. In Kayne’s (1989) account of clitic climbing (CC), languages displaying this phenomenon are showed to have certain properties, induced by the nature of INFL, which make clitic extraction out of an infinitival clause available. A minimalist approach to this subject, however, will have to show that clitics must move out of the infinitival clause, not that they can move, since the principles of economy would preclude movement if it were not necessary to satisfy morphological requirements. Postulating a restructuring rule (which maps a biclausal structure into a monoclausal one), applying optionally in some languages as in Rizzi’s account (1982) and several others, does not hold water on minimalist assumptions either. My goal in this chapter is to show why movement of the clitic out of an infinitival clause is in certain instances needed. I will restrict my attention to Romance.
Viral Infections and Prion Diseases of the Central Nervous System (Excluding Retroviral Diseases)
Authors: Rushing Elisabeth J 
Published: November 2023

Abstract
The past decade has witnessed a rapid growth in our knowledge of how to diagnose and treat viral diseases. In particular, the advent of effective antiviral treatment options has focused new attention on the prompt and accurate diagnosis of nervous system viral infections. The routine availability of antibody testing of the cerebrospinal fluid (CSF) and more recently, of polymerase chain reaction (PCR) analysis has facilitated early detection of many viral infections (DiBiasi and Tyler, 1999). Despite these advances, viral infections of the nervous system remain an important source of global morbidity and mortality. In general, most acute viral infections are benign and self-limited and clinically significant central nervous system (CNS) disease is an uncommon complication of systemic viral infection. In other instances, as exemplified by the notorious 1918–1919 influenza pandemic, the tragic aftermath included worldwide outbreaks of viral encephalitis with debilitating morbidity and over 25 million deaths (Reid et al., 2001). Furthermore, in a variety of diseases including multiple sclerosis and schizophrenia, viruses are once again under scrutiny as potential pathogens (Johnston et al., 2001; Stohlman and Hinton, 2001; Pearce, 2001). What role will the pathologist play in the investigation and diagnosis of CNS viral diseases? In the future, pathologists will probably rely less on their knowledge of morphology and will instead be called upon to integrate molecular diagnostic tools with traditional histopathologic methods (Gressens et al., 1993). The reasons are twofold: the lack of diagnostic specificity of morphologic features in most viral infections, and secondly, the fact that the presence of a viral agent in infected tissue is not always coupled with specific pathologic change. Nonetheless, classic histopathologic study will continue to complement newer molecular diagnostic methods and provide useful insight into both the recognition and pathogenesis of viral diseases. The present review focuses on the basic patterns of disease and selected advances regarding the most common agents, as well as a brief survey of important emerging causes of viral infections of the nervous system. In addition, special consideration will be given to a discussion of the so-called “slow virus infections” or prion diseases.
Neuropathology of Acquired Immunodeficiency Syndrome
Authors: Petito Carol K 
Published: November 2023

Abstract
Retroviruses are RNA viruses that contain a reverse transcriptase (RNA-dependent DNA polymerase) by which they replicate and persist in cells as intermediate DNA proviruses. In humans and experimental animals, infections by these viruses are associated with neoplasms and a variety of neurologic disorders resulting from direct or indirect involvement of the central nervous system (CNS) (Johnson and McArthur, 1987). Human T-cell lymphotropic virus type I (HTLV-1), the retrovirus responsible for T-cell lymphomas and leukemias, is associated with a chronic, slowly progressive myelopathy characterized by spastic paraparesis or paraplegia, extensor plantar reflexes and hyperreflexia, and urinary incontinences; sensory disturbances are infrequent (Cartier et al., 1997). HTLV-1-associated myelopathy (HAM) is endemic in certain parts of the tropics (Vemant et al., 1987) and Japan (Osame et al., 1987a). Maternal, hereditary, and transfusion-acquired transmissions may occur (Osame et al., 1987b; Gout et al., 1990). HTLV-1 antigens and DNA, as well as antiHTLV-1 antibodies, are found in patients’ sera and cerebrospinal fluid (Bhagavati et al., 1988). Pathologic studies demonstrate lymphocytic inflammation of meninges, perivascular spaces, and parenchyma of the spinal cord with loss of myelin and axons in the lateral and anterior columns (Akuzuki et al., 1988).
Central Nervous System Trauma
Authors: Case Mary E S 
Published: November 2023

Abstract
Head injuries account for half of all trauma deaths and for more cases of permanent disability than any other type of trauma (Kraus, 1993). Head injury statistics vary markedly depending upon how the head injury is defined and whether the data come from hospitals, medical examiners’ reports, or police reports; data on admissions for head injury are not collected uniformly in the United States. Many hospitalized patients who have other severe injuries in addition to their head injury do not have the diagnosis of head injury recorded in the hospital record, so those injuries are lost from the database (Moss and Wade, 1996). In a series of 49,143 patients from 95 trauma centers, the overall mortality of patients with head injury was 18.2%, three times higher than in patients with no head injury (Gennarelli et al., 1989). U.S. mortality data from 1979 to 1986 recorded 315,328 deaths associated with head injury, representing 2% of all deaths, 26% of injury deaths, and an annual death rate of 16.9 per 100,000 residents (Sosin et al., 1989). The head injury death rate varies among different population settings up to a high of about 32 per 100,000 residents, and urban populations have the higher rates. The most common causes of these head injuries are traffic accidents (~50%), gunshot wounds (20%–40%), falls (10%), and assaults (5%–10%). Head injury is a major cause of mortality and morbidity at all ages. The death rate for head injury in children is about 10 per 100,000, five times the mortality rate for leukemia, the next leading cause of death (Kraus et al., 1986). The annual head injury rate for children in San Diego was found to be 185 per 100,000. The most common causes of childhood head injury were falls (35%), recreational activities (29%), and traffic accidents (24%). The mechanism of children’s head injuries varies with the age of the child. In some series, falls account for as many as 75% of head injuries in those under the age of 3 years (Jamison and Kaye, 1974; Hanhn et al., 1988; Luerssen et al., 1988). Many studies find that children have a lower mortality rate and better outcome than adults after severe head injury, although this trend does not hold for the very young child who sustains abusive head injury (Berger et al., 1985; Alberico et al., 1987).
Introduction to Neurooncology
Authors: Nelson James S , Burger Peter 
Published: November 2023

Abstract
CNS tumors may be primary or secondary. Primary CNS tumors develop initially within the brain, spinal cord, optic nerves, cranial or spinal nerve roots, leptomeninges, and dura. Pituitary tumors are primary intracranial tumors and are sometimes classified as primary CNS tumors. Secondary tumors originate from primary neoplasms arising in organs, structures, and tissues outside the CNS and reach the CNS either by direct extension when the primary tumor is located in a contiguous structure such as the base of the skull or by metastasis, indicated by absence of continuity between the CNS tumor deposit and its primary source outside the CNS. Primary CNS tumors are generally classified according to their cellular origin (glioma, astrocytoma), their tissue of origin (meningioma, nerve sheath tumors), or their organ of origin (pinealoma). The craniopharyngioma is an exception to this scheme. Distinctive Characteristics Of CNS Tumors Although similar to systemic neoplasms in some respects, tumors involving the central nervous system have the following distinctive characteristics. • Primary central nervous system tumors rarely metastasize outside the CNS. Malignancy is indicated by rapid growth, invasion of adjacent structures, and spread to other parts of the central nervous system along anatomic pathways such as the ventricular system or subarachnoid space. Even apparently benign tumors may cause considerable morbidity or death because they involve major blood vessels or other vital structures and cannot be safely excised. Such tumors are categorized more appropriately as slowly growing rather than benign. They are sometimes described as “malignant by position.”
Non-Neoplastic Diseases of the Peripheral Nervous System
Authors: Schmidt Robert E 
Published: November 2023

Abstract
The most frequently sampled peripheral nerve in clinical settings is the sural nerve, a predominantly sensory nerve distributed to the lateral aspect of the foot. This entire nerve is typically sampled over the course of a few centimeters; however, in some cases fascicular biopsy is performed. The sural nerve biopsy specimen is studied using hematoxylin and eosin, trichrome (for connective tissue), and silver stains (for axons), as well as with specialized stains as needed (e.g., Congo red for amyloid or Hirsch-Peiffer acidified cresyl violet stain for metachromatic materials). A biopsy of the entire cross section of the sural nerve contains approximately 6 to 12 individual fascicles of nerve (Fig. 22.1) embedded in the epineurium, which consists of collagenous connective tissue, scattered fat cells, and blood vessels. Each fascicle is delimited from the epineurium by the perineurium (arrows, Fig. 22.1). The perineurium consists of several laminae of flattened perineurial cells (arrowheads, Fig. 22.2) with numbers of laminae decreasing proximodistally in parallel with diminishing fascicular size. Perineurial cells, the innermost layers of which are joined together by tight junctions, restrict entry of foreign materials into the endoneurium and may show minute calcifications as a nonspecific finding in various neuropathies. Several septae of perineurial cells may subdivide individual fascicles, in some cases in anticipation of branching. The endoneurial space—technically, the space inside the perineurial cell sheath and outside the axon–Schwann cell unit (arrows, Fig. 22.2)—contains collagen, a mucopolysaccharide ground substance, and small volumes of fluid, which can be sampled by micropuncture using specialized techniques. Other cellular elements within the endoneurium are small capillaries and venules, scattered fibroblasts (approximately 10 times fewer fibroblasts than Schwann cell nuclei), occasional macrophage/monocytes, which are frequently perivascular, and scattered mast cells.
The Ethical Challenges of Health Care Rationing
Authors: Fleck Leonard M 
Published: November 2023

Abstract
What does it mean to be a just and caring society when we (societal decisionmakers) have only limited resources to meet virtually unlimited health care needs? What does it mean to be a just and caring hospital or managed care organization (MCO) when administrators have only limited resources to meet the virtually unlimited health needs of the patient population for which they are responsible? What does it mean to be a just and caring physician or other health professional when only limited resources are available to meet the disproportionate health needs of the patient before that professional now? These three questions are all variants at different social levels of the problem of health care rationing, which is the central focus of this volume. ?is is what I refer to as the “Just Caring” problem, whose scope and complexity I will sketch below as the primary task of this chapter.
Lastchance Therapies
Authors: Fleck Leonard M 
Published: November 2023

Abstract
What does it mean to be a just and caring society (or a just and caring hospital or managed care plan) when we have only limited resources to meet virtually unlimited health care needs, and the need before us now is a person faced with death in the near future unless he or she has access to a very expensive medical intervention that offers only a relatively small chance of a relatively small gain in life expectancy? Such medical interventions are what Daniels and Sabin (a) refer to as “lastchance therapies” because patients who need them have no other medical options to forestall death in the foreseeable future.
Human Resource and Employment Practices in Telecommunications Services, 1980-1998
Authors: Batt Rosemary , Keefe Jeffrey 
Published: November 2023

Abstract
In the academic literature on manufacturing, much research and debate have focused on whether firms are adopting some form of “high-performance” or “high-involvement” work organization based on such practices as employee participation, teams, and increased discretion, skills, and training for frontline workers (Ichniowski et al., 1996; Kochan and Osterman, 1994; MacDuffie, 1995). Whereas many firms in the telecommunications industry flirted with these ideas in the 1980s, they did not prove to be a lasting source of inspiration for the redesign of work and employment practices. Rather, work restructuring in telecommunications services has been driven by the ability of firms to leverage net work and information technologies to reduce labour costs and create customer segmentation strategies. “Good jobs” versus “bad jobs,” or higher versus lower wage jobs, do not vary according to whether firms adopt a high-involvement model.