bluuebunny/crossref_metadata_2025 huggingface dataset:
Design strategies for self-assembly of discrete targets
Authors: Madge Jim , Miller Mark A.
Published: July 2015

Both biological and artificial self-assembly processes can take place by a range of different schemes, from the successive addition of identical building blocks to hierarchical sequences of intermediates, all the way to the fully addressable limit in which each component is unique. In this paper, we introduce an idealized model of cubic particles with patterned faces that allows self-assembly strategies to be compared and tested. We consider a simple octameric target, starting with the minimal requirements for successful self-assembly and comparing the benefits and limitations of more sophisticated hierarchical and addressable schemes. Simulations are performed using a hybrid dynamical Monte Carlo protocol that allows self-assembling clusters to rearrange internally while still providing Stokes-Einstein-like diffusion of aggregates of different sizes. Our simulations explicitly capture the thermodynamic, dynamic, and steric challenges typically faced by self-assembly processes, including competition between multiple partially completed structures. Self-assembly pathways are extracted from the simulation trajectories by a fully extendable scheme for identifying structural fragments, which are then assembled into history diagrams for successfully completed target structures. For the simple target, a one-component assembly scheme is most efficient and robust overall, but hierarchical and addressable strategies can have an advantage under some conditions if high yield is a priority.
Density of organic thin films in organic photovoltaics
Authors: Zhao Cindy X. , Xiao Steven , Xu Gu
Published: July 2015

A practical parameter, the volume density of organic thin films, found to affect the electronic properties and in turn the performance of organic photovoltaics (OPVs), is investigated in order to benefit the polymer synthesis and thin film preparation in OPVs. To establish the correlation between film density and device performance, the density of organic thin films with various treatments was obtained, by two-dimensional X-ray diffraction measurement using the density mapping with respect to the crystallinity of thin films. Our results suggest that the OPV of higher performance has a denser photoactive layer, which may hopefully provide a solution to the question of whether the film density matters in organic electronics, and help to benefit the OPV industry in terms of better polymer design, standardized production, and quality control with less expenditure.
Charge transport studies in donor-acceptor block copolymer PDPP-TNT and PC71BM based inverted organic photovoltaic devices processed in room conditions
Authors: Srivastava Shashi B. , Sonar Prashant , Singh Samarendra P.
Published: July 2015

Diketopyrrolopyrole-naphthalene polymer (PDPP-TNT), a donor-acceptor co-polymer, has shown versatile behavior demonstrating high performances in organic field-effect transistors (OFETs) and organic photovoltaic (OPV) devices. In this paper we report investigation of charge carrier dynamics in PDPP-TNT, and [6,6]-phenyl C71 butyric acid methyl ester (PC71BM) bulk-heterojunction based inverted OPV devices using current density-voltage (J-V) characteristics, space charge limited current (SCLC) measurements, capacitance-voltage (C-V) characteristics, and impedance spectroscopy (IS). OPV devices in inverted architecture, ITO/ZnO/PDPP-TNT:PC71BM/MoO3/Ag, are processed and characterized at room conditions. The power conversion efficiency (PCE) of these devices are measured ∼3.8%, with reasonably good fill-factor 54.6%. The analysis of impedance spectra exhibits electron’s mobility ∼2 × 10−3 cm2V−1s−1, and lifetime in the range of 0.03-0.23 ms. SCLC measurements give hole mobility of 1.12 × 10−5 cm2V−1s−1, and electron mobility of 8.7 × 10−4 cm2V−1s−1.
Teeter-totter effect of terahertz dual modes in C-shaped complementary split-ring resonators
Authors: Song Zhiqiang , Zhao Zhenyu , Zhao Hongwei , Peng Wei , He Xiaoyong , Shi Wangzhou
Published: July 2015

A teeter-totter effect of terahertz (THz) resonant modes in C-shaped complementary split-ring resonators (CSRRs) is observed. The dual resonant mode transmission enhancement was investigated using THz time-domain spectroscopy. The intensity of the lower-frequency resonance modes increases monotonically with the CSSR gap width, which is accompanied by a monotonic decrease in the intensity of the higher-frequency resonance modes. The origin of the dual resonant modes is numerically explained by the electromagnetic energy density distribution and surface current analysis. The inductive-capacitive resonance dominates the lower frequency mode, while the dipole oscillation dominates the higher frequency mode. By tuning the gap of the CSRR, an equilibrant transmittance of above dual resonance modes can be designed. This teeter-totter effect promises a possible application of CSSRs as potential dual-bandpass filters in the THz-region.
Atmospheric nonequilibrium mini-plasma jet created by a 3D printer
Authors: Takamatsu Toshihiro , Kawano Hiroaki , Miyahara Hidekazu , Azuma Takeshi , Okino Akitoshi
Published: July 2015

In this study, a small-sized plasma jet source with a 3.7 mm head diameter was created via a 3D printer. The jet’s emission properties and OH radical concentrations (generated by argon, helium, and nitrogen plasmas) were investigated using optical emission spectrometry (OES) and electron spin resonance (ESR). As such, for OES, each individual gas plasma propagates emission lines that derive from gases and ambient air inserted into the measurement system. For the case of ESR, a spin adduct of the OH radical is typically observed for all gas plasma treatment scenarios with a 10 s treatment by helium plasma generating the largest amount of OH radicals at 110 μM. Therefore, it was confirmed that a plasma jet source made by a 3D printer can generate stable plasmas using each of the aforementioned three gases.
Energy harvesting from vibration with cross-linked polypropylene piezoelectrets
Authors: Zhang Xiaoqing , Wu Liming , Sessler Gerhard M.
Published: July 2015

Piezoelectret films are prepared by modification of the microstructure of polypropylene foam sheets cross-linked by electronic irradiation (IXPP), followed by proper corona charging. Young’s modulus, relative permittivity, and electromechanical coupling coefficient of the fabricated films, determined by dielectric resonance spectra, are about 0.7 MPa, 1.6, and 0.08, respectively. Dynamic piezoelectric d33 coefficients up to 650 pC/N at 200 Hz are achieved. The figure of merit (FOM, d33 ⋅ g33) for a more typical d33 value of 400 pC/N is about 11.2 GPa−1. Vibration-based energy harvesting with one-layer and two-layer stacks of these films is investigated at various frequencies and load resistances. At an optimum load resistance of 9 MΩ and a resonance frequency of 800 Hz, a maximum output power of 120 μW, referred to the acceleration g due to gravity, is obtained for an energy harvester consisting of a one-layer IXPP film with an area of 3.14 cm2 and a seismic mass of 33.7 g. The output power can be further improved by using two-layer stacks of IXPP films in electric series. IXPP energy harvesters could be used to energize low-power electronic devices, such as wireless sensors and LED lights.
Electronic and magnetic properties of N-N split substitution in GaAs: A hybrid density functional study
Authors: Huang Ruiqi , Wang Sanjun , Wang Qingxia , Cai Xiaolin , Li Chong , Jia Yu , Wang Fei
Published: July 2015

Employing the first-principles combined with hybrid functional calculations, the electronic and magnetic properties of GaAs doped with a N2 molecule are investigated in this work. We find that in Ga32As31(N2)As the N-N split is able to saturate the dangling bond of Ga atom ,form sp3-like hybridization, and simultaneously supply an extra localized electron, leading to a magnetic ground state with a magnetic moment of ∼1μB. This magnetic ground state is different from previously nonmagnetic results predicted by PBE functional, which results from the self-interaction error inherent in semi-local density functional theory. Moreover, the band gap of magnetic ground state of Ga32As31(N2)As alloy decreases, which is relative to GaAs . Finally we discuss and explain why the magnetism is not discovered in previous experiments and theories.
Structural phase transition in La2/3Ba1/3MnO3 perovskite: Elastic, magnetic, and lattice anomalies and microscopic mechanism
Authors: Fertman E. , Syrkin E. , Lykah V. , Desnenko V. , Beznosov A. , Pal-Val P. , Pal-Val L. , Fedorchenko A. , Khalyavin D. , Feher A.
Published: July 2015

The temperature dependences of the elastic and magnetic properties of polycrystalline perovskite manganite La2/3Ba1/3MnO3 were studied using ultrasonic and SQUID magnetometer techniques. The minimum of the temperature-dependent sound velocity v(T) and corresponding maximum of the decrement δ(T) were found in the vicinity of the structural phase transition R3̄c↔Imma at Ts ∼ 200 K. Large alterations of v and δ indicate a structural phase transition of the soft mode type. A high sensitivity of dc magnetization to a low uniaxial pressure caused by the softening was found in the Ts region. A negative value of the linear thermal expansion coefficient along one of the crystallographic axis was found in the Imma phase near Ts. The proposed microscopic mechanism explains the appearance of the soft mode in the vicinity of the structural phase transition temperature associated with the displacement of the manganese atom from the center of the oxygen octahedron.
Phosphate response of Trifolium uniflorum compared with T. repens and some T. repens×T. uniflorum hybrids
Authors: Nichols S. N. , Crush J. R.
Published: July 2015

Introgression of genes from Trifolium uniflorum L. into T. repens L. (white clover) is being investigated as a method to improve phosphorus (P) use efficiency in white clover; however, little is known about the edaphic adaptations or P physiology of T. uniflorum. Growth responses to added P of T. uniflorum, T. repens and some T. repens × T. uniflorum hybrids were determined in a glasshouse experiment in pots of soil. Trifolium uniflorum showed traits consistent with adaptation to low-P soils: slow growth rate, small leaves, relatively high leaf-tissue P concentrations, and sequestration of P in its roots when soil P levels were increased. The response of Kopu II, one of the hybrid backcross parents, was quite different; it showed high growth rate, large leaves, much lower leaf P concentrations, and a large decrease in root : shoot P allocation as soil P increased. Tahora, the other backcross parent, exhibited several characteristics that were intermediate between Kopu II and T. uniflorum, probably reflecting its breeding origins from New Zealand hill-country ecotypes. This study confirms the potential for interspecific hybridisation with T. uniflorum to increase the tolerance of white clover to low soil P levels, through incorporation of traits related to edaphic adaptations. Variation among the hybrid families in their response to changing soil P confirmed previously published conclusions about the need to screen widely in hybrid material.
An inhibitor persistently decreased enteric methane emission from dairy cows with no negative effect on milk production
Authors: Hristov Alexander N. , Oh Joonpyo , Giallongo Fabio , Frederick Tyler W. , Harper Michael T. , Weeks Holley L. , Branco Antonio F. , Moate Peter J. , Deighton Matthew H. , Williams S. Richard O. , Kindermann Maik , Duval Stephane
Published: July 2015

Significance

Methane from enteric fermentation in the ruminant digestive system is a major contributor to anthropogenic greenhouse gas emissions in the United States and worldwide. Methane is also a net loss of feed energy to the animal. This study was undertaken to investigate the effect of a methane inhibitor on enteric methane emissions from lactating dairy cows. The experiment demonstrated that, under industry-relevant conditions, the inhibitor persistently decreased by 30% enteric methane emissions, without negatively affecting animal productivity. The spared methane energy was partially used for tissue synthesis, which led to a greater body weight gain by the inhibitor-treated cows. If adopted, this mitigation practice could lead to a substantial reduction of greenhouse gas emissions from the ruminant livestock sector.
The development of lexical complexity in second language acquisition
Authors: De Clercq Bastien
Published: July 2015

The development of lexical complexity in second language acquisition has received a considerable amount of attention in applied linguistics research. Many studies have examined the role of lexical diversity, sophistication and density as indicators of L2 proficiency. Few studies, though, have considered the development of lexical complexity from an explicitly cross-linguistic perspective. This article reports on an explorative, cross-linguistic study on the development of lexical diversity, sophistication and density in L2 French and English at four levels of linguistic proficiency. Additionally, the study proposes a number of alternative measures tapping into collocational knowledge and lexical sophistication. The analyses were carried out on a cross-sectional, multilingual corpus of L2 French and English consisting of oral narrative data. The results show a similar development of lexical diversity in L2 French and English, but considerably different developmental tendencies in terms of sophistication and density. The concluding sections discuss possible explanations for these differences and consequences for the measurement of linguistic proficiency.
The triumph of neoliberalism and the world dominance of capitalism
Authors: Senker Peter
Published: July 2015

Neoclassical economics dominates modern economics and provides an important theoretical basis for neoliberalism. Among its inadequacies are failure to take sufficient account either of technological change or of marketing activities, both of which are central features of modern capitalism. Neoliberals believe that the state should be confined to safeguarding individual and commercial liberty and strong property rights. But in practice, corporations’ dependence on states has been pervasive for at least 100 years. Corporations aim to secure higher profits. They lobby international organizations, as well as states, both to create conditions more favourable to their own individual interests, and also to increase the proportion of economies in which private corporations are allowed to operate. This may apply, for example, to privatization of health and education services which is not always in the public interest. This paper outlines several examples of interactions among corporations, technological change, marketing, state support and international organizations. Examples include huge state support for road construction, which facilitated the domination of cars over land transport; the role of marketing and technological change in the food and agricultural industries; and state support for scientific and technological change in semiconductors and the Internet, and for the development of biotechnology. In conclusion, the paper suggests an alternative approach to studying the dynamics of the modern world economy, viewing it as complex networks of interlocking systems. This might produce more useful analyses than those based on obsolete theories.
Meninges and Ventricles
Authors: Laughlin Ruple S. , Flemming Kelly D.
Published: July 2015

Knowledge of the normal structure and function of the meninges and ventricular system can aid in recognizing and understanding pathologic states. This chapter reviews the meninges, ventricular system, and cerebrospinal fluid production.
Peripheral and Central Pain Pathways and Pathophysiology
Authors: Benarroch Eduardo E. , Watson James C. , Flemming Kelly D.
Published: July 2015

Pain is an unpleasant sensory experience that may be associated with actual or potential tissue damage. Perception of pain includes the sensory-discriminative (intensity and location), cognitive (bodily sensation), and affective-emotional (suffering) aspects. Pain is a complex integration of anatomic pathways, including dorsal root ganglion (DRG) nociceptive neurons, dorsal horn neurons, spinothalamic and spinobulbar pathways, the thalamus, the cortex, and local modulation. Peripheral and central sensitization may occur after tissue injury. This chapter reviews the peripheral and central processing of pain and concludes with discussion of pain pathophysiology.
Peripheral Nerve, Neuromuscular Junction, and Muscle Anatomy
Authors: Tracy Jennifer A.
Published: July 2015

After exiting the spinal cord, individual nerve roots coalesce to form plexi and peripheral nerves. These nerves innervate muscle and skin. Clinical localization requires a working knowledge of this anatomy. By evaluating the distribution of muscle weakness, sensory loss, and reflexes, it is often possible to localize lesions and focus a differential diagnosis. This chapter reviews the anatomy of the peripheral nerves, neuromuscular junction, and muscle.
Spinal Cord Anatomy
Authors: Tracy Jennifer A.
Published: July 2015

The spinal cord begins as the cervical cord, which is just below the medulla and extends downward through the spinal canal. It then becomes the thoracic, lumbar, sacral, and coccygeal parts of the cord. The spinal cord proper ends at the lower portion of the first lumbar vertebral body in most persons where it forms the conus medullaris, followed by the filum terminale. There are enlargements at both the cervical and lumbar cord levels, which represent the innervation pathways of the upper and lower limbs, respectively. A number of ascending and descending pathways travel in the spinal cord. These are reviewed in this chapter.
Brainstem and Cranial Nerves:
Authors: Flemming Kelly D. , Brazis Paul W.
Published: July 2015

The pons extends from the pontomedullary junction to an imaginary line drawn from the exit of cranial nerve IV. Dorsal to the pons lies the cerebellum. The cerebellum receives information and projects information back to the brainstem through the inferior, middle, and superior cerebellar peduncles. Important structures at this level include corticospinal tracts, corticopontocerebellar fibers travelling through the middle cerebellar peduncle, the cerebellum, and cranial nerves V through VIII.
Thalamus
Authors: Flemming Kelly D. , Benarroch Eduardo E.
Published: July 2015

The diencephalon is composed of 4 components: 1) the epithalamus, which includes the pineal body; 2) the dorsal thalamus, which is commonly considered to be the thalamus proper; 3) the ventral thalamus, consisting of the reticular nucleus and subthalamic nucleus; and 4) the hypothalamus. This chapter focuses on the dorsal thalamus and the ventral thalamus. The thalamus has 3 main functions: 1) relay input from subcortical structures to the cortex, 2) control (gate) which sensory information reaches the cortex, and 3) synchronize cortical activity that relates to consciousness.
Principles of Neuroendocrinology and Hypothalamic Function
Authors: Coon Elizabeth A. , Benarroch Eduardo E.
Published: July 2015

The hypothalamus is the neural center of the endocrine system, the regulator of the autonomic nervous system, and the circadian and seasonal clock for behavioral and sleep-wake functions. The hypothalamus maintains homeostasis by integrating cortical, limbic, and spinal inputs and by affecting hormone release, temperature regulation, intake of food and water, sexual behavior and reproduction, emotional responses, and diurnal rhythms. As the link from the nervous system to the endocrine system, the hypothalamus synthesizes and secretes neurohormones that stimulate or inhibit the secretion of pituitary hormones. This chapter reviews the basic neuroanatomy and function of the hypothalamus.
Basal Ganglia
Authors: Graff-Radford Jonathan , Nelson Alex J. , Benarroch Eduardo E.
Published: July 2015

The basal ganglia are a group of nuclei connected by circuits that help select appropriate actions and other behaviors. They promote the sequential activation of movements or behaviors in response to stimuli. These movements become reinforced over time, eventually becoming habits. The anatomy and circuitry of the basal ganglia are reviewed in this chapter.
Neuropharmacology
Authors: Amy Z. Crepeau , Jeffrey W. Britton
Published: July 2015

Medications used in the treatment of nervous system disorders typically modulate neurotransmitter function or action potential propagation to result in alterations in neurologic function. This chapter begins with a discussion of principles of pharmacokinetics. Targets for drug action and a basis for understanding how medications exert their action are also discussed. Finally, disease-specific treatments are detailed.

Pharmacokinetic principles of neurologic medications are important to understand for the purposes of medication prescribing and ordering. Multiple routes of administration—intravenous, sublingual, intramuscular, subcutaneous, rectal, oral, and transdermal—are available for neurologic therapeutic agents.
Sleep Pathophysiology
Authors: Michael F. Presti
Published: July 2015

Sleep is a natural, reversible, and periodic behavioral state characterized by perceptual inattention and decreased responsiveness to external stimuli. The processes governing sleep, sleep-wake transitions, and maintenance of wakefulness are mediated via complex physiologic mechanisms, the primary neurobiological substrates of which include the neocortex, basal forebrain, thalamus, hypothalamus, pontine tegmentum, and brainstem monoaminergic nuclei. Moreover, the integrity of brainstem autonomic respiratory control networks becomes critical in the maintenance of ventilation during sleep. Pathologic insults to these systems may result in a broad constellation of clinical deficits. This chapter reviews the normal stages of sleep, age-related changes in sleep composition, physiologic mechanisms mediating the generation and maintenance of sleep and wakeful states, and homeostatic and circadian control of sleep.
Patterns of Inheritance in Neurogenetic Disease
Authors: Ralitza H. Gavrilova , Virginia V. Michels
Published: July 2015

The human genome consists of approximately 25,000 genes that are encoded within the nuclear DNA and embedded in the chromosome. Mitochondria are the only cytoplasmic organelles that have their own DNA. Nuclear gene and mitochondrial inheritance are discussed in this chapter. Basic genetic terms are defined.
Chromosomal Syndromes
Authors: Ralitza H. Gavrilova , Virginia V. Michels
Published: July 2015

The chromosomal syndromes are due to numerical, structural, or functional abnormalities of chromosomes. These include numerary changes of chromosomes in some or all cells, structural rearrangements, deletions or duplications of parts of chromosomes, and, in some cases, changes in small segments of the chromosomes as in fragile X syndrome. The most common chromosomal syndromes are discussed in this chapter.
Cerebrospinal Fluid
Authors: Laughlin Ruple S.
Published: July 2015

This chapter focuses on the utility of spinal fluid evaluation and on the aspects of CSF evaluation that are useful clinically. The anatomy and physiologic aspects of the ventricles and spinal fluid are discussed elsewhere. The total volume of cerebrospinal fluid (CSF) within ventricles and subarachnoid space is about 150 mL. The absorption of CSF is directly linked to intracranial pressure.
Personality and Illness
Authors: Palmer Brian A.
Published: July 2015

A personality disorder (PD), as defined in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-V), is “an enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture, is pervasive and inflexible, has an onset in adolescence or early adulthood, is stable over time, and leads to distress or impairment.” The PDs are divided into 3 clusters by their descriptive similarities. Cluster A reflects odd or eccentric character structure; Cluster B reflects dramatic, emotional, or erratic character structure; and Cluster C reflects anxious or fearful character structure. Further details on diagnosis, etiology, and treatment issues follow. Accurate identification and optimal treatment of PDs can help improve outcomes of other psychiatric and medical illness.
Breast cancer and neutropenic sepsis
Authors: Rigg Anne , Patel Gargi
Published: July 2015

Treatment of breast cancer in the adjuvant setting to reduce the risk of recurrence of breast cancer takes into consideration prognostic factors, the risks of relapse, and the role of biological, hormonal, and cytotoxic therapies, as well as radiotherapy. This case presents a scenario when a patient has declined the recommended adjuvant strategy, subsequently presenting with complications arising from metastatic breast cancer and from chemotherapy treatment for this disease, including neutropenic sepsis. The role of bisphosphonates in metastatic bone disease, the management of neutropenic sepsis, and adjuvant hormonal treatments for pre-, peri-, and post-menopausal women and familial breast cancer are discussed.
Mesothelioma and chemotherapy-induced vomiting
Authors: Steele Jeremy , Payne Sarah
Published: July 2015

Malignant mesothelioma, a tumour of the pleura or peritoneum, is associated with previous asbestos exposure. It frequently presents with diffuse disease, which is not amenable to surgery. Chemotherapy in advanced disease has been shown to increase the time to disease progression and overall survival. Second-line treatment is ideally offered within a clinical trial. Radiotherapy offers good, but short-lived, symptomatic relief for chest pain. This case illustrates the management of a patient with inoperable mesothelioma, receiving chemotherapy and developing the complication of chemotherapy-induced vomiting (CINV). This is thought to be triggered by the activation of the chemoreceptor trigger zone, as well as the direct irritation of the gastrointestinal tract. Neurokinin-1 inhibitors, substance P inhibitors, and glucocorticoids represent the most effective groups of drugs to manage CINV in the prophylactic and refractory setting.
Endometrial cancer and treatment complications
Authors: Sadozye Azmat , Manetta Caroline
Published: July 2015

This case highlights some of the issues surrounding the management of endometrial cancer. The management of stage I disease is contentious, and the roles of chemotherapy and radiotherapy, as well as optimal surgical management, are discussed. Pelvic lymphadenectomy for early-stage disease has been debated strongly. Risk group stratification plays a key role in the decision making for adjuvant treatment. Adjuvant radiotherapy is well established in advanced disease. Its role in early disease is less clear, with a definite move towards more brachytherapy and less external beam radiotherapy. Chemotherapy has a definite role in metastatic disease. Hormonal therapy is useful, particularly in frailer patients. The use of novel agents is being explored.
Oesophageal cancer and dysphagia
Authors: Remer Marcus , Propper David
Published: July 2015

The increasing incidence of oesophageal cancer in Western countries has been associated with a rise in adenocarcinoma arising from Barrett’s metaplasia. Tobacco and alcohol consumption remain significant risk factors for cancer development. Fewer than 30% of oesophageal cancers present at a stage suitable for radical therapy. A multidisciplinary multimodality treatment approach has improved survival outcomes for locally advanced disease. The choice and timing of treatments are highly dependent on the tumour stage and histological subtype. Accurate staging is essential to inform management decisions and optimize treatment outcome. The majority of cancers present at an advanced stage, and overall prognosis remains poor; the median overall survival for advanced oesophageal cancer treated with palliative chemotherapy is approximately 11 months. This is the discussion of a case of squamous cancer, treated with chemoradiotherapy (and not surgery), with subsequent progression and metastatic disease.
Gastric cancer and complications of relapsed disease
Authors: Petkar Imran , Bridgewater John
Published: July 2015

Gastric cancer is the fourth commonest cancer worldwide. Unfortunately, only a minority of patients present with localized operable disease. Survival rates, following surgery alone, are poor, and a number of multimodality approaches, including perioperative chemotherapy, adjuvant chemotherapy, and adjuvant chemoradiotherapy, have been adopted to improve cure rates. This case demonstrates the presentation of gastric cancer and the role of perioperative chemotherapy. The patient relapses, and the management of recurrent disease is discussed; recently, the benefits of second-line irinotecan or docetaxel for advanced disease have been established. A further improvement has been demonstrated with the addition of trastuzumab to first-line doublet chemotherapy for tumours overexpressing human epidermal receptor 2 (HER2), which is seen in about 20% of cases. Further understanding of tumour biology is fundamental to improve current outcomes from management of this aggressive disease.
Muscle-invasive transitional cell carcinoma of the bladder
Authors: Chester John , Crusz Shanthini
Published: July 2015

Transitional cell carcinoma (TCC) of the bladder is the commonest malignancy affecting the urothelium. Muscle-invasive TCC is a life-threatening, but potentially curable, cancer which presents significant challenges for the uro-oncological multidisciplinary team. Treatment options for localized muscle-invasive bladder cancer are evolving. There is solid trial-based evidence for the use of neoadjuvant systemic therapy, prior to radical treatment, with curative intent; the use of adjuvant chemotherapy is less well established. Systemic therapy treatment decisions are complicated by disease-related complications and co-morbidities, especially impaired renal function. This chapter explores a typical bladder cancer patient journey, from presentation with a new diagnosis of muscle-invasive disease to the failure of first-line palliative chemotherapy. The chapter illustrates potential problems that can arise in routine clinical practice, suggests some solutions to commonly encountered difficulties, and reviews the evidence base for the range of treatment approaches.
Glioblastoma multiforme (GBM)
Authors: Sims Eliot , Tarver Kathryn
Published: July 2015

Central nervous system (CNS) malignancies vary widely in their morphological and clinical characteristics, the varying patient groups affected, as well as in terms of outcome. Of all the CNS malignancies, glioblastoma multiforme (GBM) is arguably the most devastating. In spite of practice-changing studies in recent years that have impacted favourably on the outcome in GBM, the prognosis remains limited. This chapter focusses on a typical case of a previously fit and well middle-aged patient presenting with symptoms of raised intracranial pressure (ICP) who is found to have GBM. Building on the case and management of this patient, it details standard first-line management of the condition with surgery, chemoradiation, and chemotherapy, exploring the evidence behind current clinical practice. Additional information is given on subtopics such as the management of seizures and raised ICP, the clinical and radiological phenomenon of pseudoprogression, as well as MGMT promoter methylation and its significance in the management of patients with GBM.
Thyroid cancer and radioiodine therapy
Authors: Dallas Nicola , Woolf David
Published: July 2015

Thyroid cancer is the commonest malignancy to affect the endocrine system, with 80% of lesions being papillary. The incidence rates of this malignancy continue to rise significantly, whilst cure rates are increasing and relapse-free survival is amongst the highest of any solid cancer. Treatment is multidisciplinary, involving thyroid surgeons, clinical oncologists, and endocrinologists. For the majority of patients, the treatment pathway will involve local surgery, with either a lobectomy or a total thyroidectomy, and radioactive iodine therapy, although significant controversies remain and prospective data are lacking. This chapter reviews a patient case history and explores aspects of the management, including: the choice of surgical approach and whether a lymph node dissection is appropriate; the role of radioactive iodine; the preparation for, and complications of, therapy; and follow-up schedules.
Cancer of unknown primary
Authors: Bhattacharyya Madhumita , Olsson-Brown Anna C
Published: July 2015

Cancer of unknown primary origin (CUP) is classically associated with rapid progression and poor prognosis. If review of the available radiological and pathological information favours a particular tumour type, site-specific chemotherapy can be instituted; otherwise, empirical combination chemotherapy is recommended. Many patients present with advanced disease and poor performance status. The introduction of dedicated multidisciplinary team (MDT) care for CUP, including an MDT with palliative care and oncology input, is designed to diagnose patients earlier and identify patients suitable for treatment earlier in their disease pathway. Furthermore, developments in imaging, immunohistochemistry, and molecular profiling may lead to improvements in identifying the site of origin or targets suitable for treatment. This is a case of a patient who presented with a raised CA125 and multiple liver metastases and responded to chemotherapy regimens with activity in ovarian cancer. Although an unusual case of CUP, the principles of diagnosis and management of CUP are well illustrated.
Signaling in the Brain
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Neurons are the cells of the brain responsible for intracellular and intercellular information transfer, or signaling; they are asymmetrical cells with morphologically and functionally distinct regions that specialize them for signaling. This chapter focuses on the unique structural elements characteristic of neurons throughout the animal kingdom. These include the dendrite, among whose functions is the receipt of information from other neurons. The axon, in contrast, is specialized for the intracellular transfer of information over long distances. The chapter concludes with a discussion of the synapse, the highly specialized structure that mediates the transfer of information from one neuron to another. It is this intracellular and intercellular communication that is the essence of nervous system function, and that makes the brain so complex and difficult to study and yet at the same time so fascinating for students of cell and molecular biology.
Form and Function in Cells of the Brain
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

This chapter examines unique mechanisms that the neuron has evolved to establish and maintain the form required for its specialized signaling functions. Unlike some other organs, the brain contains a variety of cell types including several classes of glial cells, which play a critical role in the formation of the myelin sheath around axons and may be involved in immune responses, synaptic transmission, and long-distance calcium signaling in the brain. Neurons share many features in common with other cells (including glia), but they are distinguished by their highly asymmetrical shapes. The neuronal cytoskeleton is essential for establishing this cell shape during development and for maintaining it in adulthood. The process of axonal transport moves vesicles and other organelles to regions remote from the neuronal cell body. Proteins such as kinesin and dynein, called molecular motors, make use of the energy released by hydrolysis of ATP to drive axonal transport.
Ion Channels, Membrane Ion Currents, and the Action Potential
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

The flow of ions down their electrochemical gradients, through populations of ion channels in the neuronal plasma membrane, gives rise to transmembrane ion currents. It is the sum of the various currents flowing at any point in time that determines the neuron’s membrane potential. Thus the normal firing pattern of a neuron, and its response to different kinds of stimulation, can be seen as a play of interactions among the currents flowing through the different kinds of ion channels in its membrane. The activities of the sodium and potassium channels responsible for axonal action potentials are themselves dependent on voltage. Voltage clamp studies, which allow the measurement of the current flowing through these channels at fixed voltage, have provided a detailed understanding of the sequence of changes in sodium and potassium channel activity that give rise to action potentials.
Diversity in the Structure and Function of Ion Channels
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Voltage clamp and patch clamp techniques are used to reveal heterogeneity of ion currents carried through voltage-dependent sodium, calcium, and potassium channels. Advances in channel molecular biology have made it clear that the diversity of ion channels is even greater than was suspected from these electrophysiological measurements. This diversity is achieved by several different mechanisms, including the existence of multiple genes for the pore-forming α‎ subunits of ion channels, alternative splicing of the messenger RNA transcribed from each individual gene, formation of heterotetramers containing different α‎ subunits of potassium channels, and modulation of channel properties by auxiliary subunits that may themselves comprise a large and diverse family of proteins. Moreover, potassium channels can be further categorized into voltage-dependent, calcium-dependent, sodium-dependent, two-pore, and inward rectifier channels. Emerging evidence suggests that many human diseases are associated with dysfunction of individual classes of ion channels in neurons.
How Neurons Communicate: Gap Junctions and Neurosecretion
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Two ways that neurons communicate with one another are by direct electrical coupling and by the secretion of neurotransmitters. Electrical coupling arises from the existence of proteins, known as connexins, that form pores linking the cytoplasm of adjacent cells. Ions and small molecules can carry signals from one cell to another through these pores. Neurosecretion is a more complex process whereby different categories of molecules are sorted into cytoplasmic vesicles. Chemical processes within these vesicles ensure that they contain biologically active transmitters or hormones. SNARE complex proteins cooperate with other proteins to allow synaptic vesicles containing neurotransmitter to release their components into the external medium following calcium entry into nerve terminals. Such exocytosis of synaptic vesicles can be monitored with imaging techniques using fluorescent dyes or proteins, or by capacitance measurements. A second set of molecules retrieves the membrane of synaptic vesicles back from the plasma membrane through endocytosis.
Synaptic Release of Neurotransmitters
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Several specialized synapses, including those in squid stellate ganglion, frog neuromuscular junction, and calyx of Held, have been instrumental in advancing our understanding of the release of neurotransmitters from presynaptic terminals. Studies of rapid synaptic transmission have shown that neurotransmitters are released in packets, or quanta, which may correspond to the exocytosis of individual synaptic vesicles. Following an action potential, release is linked in space and time to the entry of calcium though voltage-dependent channels. The amount of transmitter released by a single action potential varies through depression, facilitation, or potentiation during and after repetitive stimulation of a synapse. Mechanisms that induce neurotransmitter release and proteins, such as synapsins, that modulate their release are still not completely understood. Biochemical and genetic experiments that characterize, modify, or eliminate components of synaptic vesicles and release sites, coupled with physiological experiments at specific synapses, provide further insights into the release process.
Neurotransmitters and Neurohormones
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

A multitude of chemicals called neurotransmitters mediate intercellular communication in the nervous system. These include acetylcholine, the catecholamines, serotonin, glutamate, GABA, glycine, and a wide variety of neuropeptides. Although they exhibit great diversity in many of their properties, all are stored in vesicles in nerve terminals and are released to the extracellular space via a process requiring calcium ions. Their actions are terminated by reuptake into the presynaptic terminal or nearby glial cells by specific transporter proteins or by their destruction in the extracellular space. The role of neurotransmitters is to alter the properties—chemical, electrical, or both—of some target cell. With the arrival on the scene of the neuropeptides, it has become evident that signaling in the nervous system occurs through the use of rich and varied forms of chemical currency, and that some neurons use more than one type of currency simultaneously.
Neuronal Growth and Trophic Factors
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Neural development requires the participation of growth factors that regulate neuronal determination, proliferation, migration, and differentiation. Molecular genetic approaches using Drosophila, as well as other creatures whose genetics is well understood, have provided insights into the mechanisms of action of some of these developmental factors. Other factors are soluble and are secreted by nearby cells or other neurons. These include neurotrophins such as NGF and BDNF, cytokines such as CNTF, as well as GDNF and steroid hormones. Current research aims to identify key growth factors required for producing different types of neurons, and different patterns of transcription factor activated by different combinations of these factors. This knowledge may eventually allow medical therapies to convert a stem cell into a sympathetic neuron, a motor neuron, or any one of the thousands of other types of neurons that make up a mature nervous system.
Adhesion Molecules and Axon Pathfinding
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Developing neurons extend neurites, which become the axons and dendrites of the adult neuron. These neurites follow specific paths and branch in characteristic ways. The leading tip of the neurite, the growth cone, appears to sample the extracellular environment and contribute to decisions about the direction of extension. Various molecules are essential for appropriate pathfinding by growing neurites. For example, neurites grow selectively toward or away from guidance molecules such as semaphorins, netrins, slits, and ephrins. In addition, adhesion molecules such as fibronectin and laminin mediate specific adhesion of the neurite to the substrate over which it is growing, while CAMs and cadherins promote the adhesion of neurites of different cells to each other in specific patterns. Some molecules and mechanisms that regulate neuronal development and differentiation may also regulate neurite outgrowth in adult nervous systems, either during recovery from injury or in response to novel stimuli from the environment.
Intrinsic Neuronal Properties, Neural Networks, and Behavior
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Complex interactions among large numbers of neurons are required to generate most behaviors. Studies in biological model systems—such as the stomatogastric ganglion of lobsters and crabs, and neurons controlling reproduction in Aplysia—have provided insights into how the intrinsic electrical properties of neurons shape network activity and animal behavior. Some neurons can participate simultaneously in more than a single network, and the properties of a network may be modulated by the actions of neurotransmitters and hormones. Changes in the intrinsic excitability of a single command neuron or command systems of neurons can trigger a complicated and long-lasting behavior. Cellular mechanisms that regulate the accuracy of timing of action potentials, both within a network and in different parts of a dendritic tree, are also important for the interpretation of sensory information and for the ability of a neuron to modify the strength of the connections it makes with other neurons.
Self-rated health is prospectively associated with uptake of screening for the early detection of colorectal cancer, not vice versa
Authors: Neter Efrat , Stein Nili , Rennert Gad , Hagoel Lea
Published: July 2015

Self-rated health (SRH) is a consistent predictor of mortality and other health outcomes. One of the mechanisms hypothesized to explain its validity as a predictor is that SRH affects the adoption of health behaviors. The present study examined the prospective association between SRH and performance of a recommended colorectal cancer (CRC) screening test. One thousand four hundred and seventy-six men and women aged 50–74 years, eligible for CRC screening, who had undergone the test a year before were interviewed 1–2 weeks (long interview, before testing) or 2 months (short interview, after testing) following the mailing of a test kit. Test performance was ascertained using an HMO’s computerized data set. Respondents in the long interview group who rated their health as ‘higher than others’ performed the screening test 2 months following the invitation more than those who rated their health as similar to or lower than that of others (65.4, 61.6, and 49.1%, respectively, χ
2=8.02, P=0.018). At the same time, these respondents perceived the risk of CRC as significantly lower than that of those who rated their health as comparable with or lower than that of others. In a multivariate logistic regression of CRC screening behavior that included demographic and perceptual variables, age, intentions, and SRH were found to be significant predictors. Among respondents in the short interview, who tested before the interview, there was no significant association between SRH and behavior. SRH prospectively predicts uptake of CRC screening better than other perceptual variables, after accounting for demographic variables.