Improving Global Flow with the Known-New Contract

Large-scale flow of ideas is the key to effective scientific and argumentative writing. This tutor’s column discusses the Known-New Contract as a teaching tool for global flow. It also discusses the outlining and discussion techniques that can be practically used in appointments with students who struggle with the structure of their papers

Phenomena Conflict, Anxiety, and Depression for Cancer Survivor One Year and After Have Therapy in General Hospital

Introduction. Psychosocial distress emerges in cancer disease. This research explores experience of conflict, anxiety, and depression in one year cancer survivor. Methods. Data were collected through in-depth semi structured interviews with fifteen participants when seeking treatment at a public hospital in Bandung. Result. There nine themes emerge: anxiety about cancer\u27s spread and recurrence, changing relationships with a partner, \u27labeling\u27 from oneself and others, physical discomfort along treatment, psychological discomfort along treatment, self-concept, religious/spiritual, hiding diagnose and complain, and deficit information about cancer. But, four themes among were not characterized with conflict, anxiety, and depression. Conflict, anxiety, and depression impact condition of the client cancer. Discussion. Experience of conflict, anxiety, and depression became the basis for the development of management system service and provision of facilities for integrated mental health nursing therapy

Oligonucleotide-assisted cleavage and ligation: a novel directional DNA cloning technology to capture cDNAs. Application in the construction of a human immune antibody phage-display library

The use of oligonucleotide-assisted cleavage and ligation (ONCL), a novel approach to the capture of gene repertoires, in the construction of a phage-display immune antibody library is described. ONCL begins with rapid amplification of cDNA ends to amplify all members equally. A single, specific cut near 5′ and/or 3′ end of each gene fragment (in single stranded form) is facilitated by hybridization with an appropriate oligonucleotide adapter. Directional cloning of targeted DNA is accomplished by ligation of a partially duplex DNA molecule (containing suitable restriction sites) and amplification with primers in constant regions. To demonstrate utility and reliability of ONCL, a human antibody repertoire was cloned from IgG mRNA extracted from human B-lymphocytes engrafted in Trimera mice. These mice were transplanted with peripheral blood lymphocytes from Candida albicans infected individuals and subsequently immunized with C.albicans glyceraldehyde-3-phosphate dehydrogenase (GAPDH). DNA sequencing showed that ONCL resulted in efficient capture of gene repertoires. Indeed, full representation of all V(H) families/segments was observed showing that ONCL did not introduce cloning biases for or against any V(H) family. We validated the efficiency of ONCL by creating a functional Fab phage-display library with a size of 3.3 × 10(10) and by selecting five unique Fabs against GAPDH antigen

The Computational Complexity of Generating Random Fractals

In this paper we examine a number of models that generate random fractals. The models are studied using the tools of computational complexity theory from the perspective of parallel computation. Diffusion limited aggregation and several widely used algorithms for equilibrating the Ising model are shown to be highly sequential; it is unlikely they can be simulated efficiently in parallel. This is in contrast to Mandelbrot percolation that can be simulated in constant parallel time. Our research helps shed light on the intrinsic complexity of these models relative to each other and to different growth processes that have been recently studied using complexity theory. In addition, the results may serve as a guide to simulation physics.Comment: 28 pages, LATEX, 8 Postscript figures available from [email protected]

A Complete Axiom System for Propositional Interval Temporal Logic with Infinite Time

Interval Temporal Logic (ITL) is an established temporal formalism for reasoning about time periods. For over 25 years, it has been applied in a number of ways and several ITL variants, axiom systems and tools have been investigated. We solve the longstanding open problem of finding a complete axiom system for basic quantifier-free propositional ITL (PITL) with infinite time for analysing nonterminating computational systems. Our completeness proof uses a reduction to completeness for PITL with finite time and conventional propositional linear-time temporal logic. Unlike completeness proofs of equally expressive logics with nonelementary computational complexity, our semantic approach does not use tableaux, subformula closures or explicit deductions involving encodings of omega automata and nontrivial techniques for complementing them. We believe that our result also provides evidence of the naturalness of interval-based reasoning

Calpain-Catalyzed Proteolysis of Human dUTPase Specifically Removes the Nuclear Localization Signal Peptide

Calpain proteases drive intracellular signal transduction via specific proteolysis of multiple substrates upon Ca(2+)-induced activation. Recently, dUTPase, an enzyme essential to maintain genomic integrity, was identified as a physiological calpain substrate in Drosophila cells. Here we investigate the potential structural/functional significance of calpain-activated proteolysis of human dUTPase.Limited proteolysis of human dUTPase by mammalian m-calpain was investigated in the presence and absence of cognate ligands of either calpain or dUTPase. Significant proteolysis was observed only in the presence of Ca(II) ions, inducing calpain action. The presence or absence of the dUTP-analogue α,β-imido-dUTP did not show any effect on Ca(2+)-calpain-induced cleavage of human dUTPase. The catalytic rate constant of dUTPase was unaffected by calpain cleavage. Gel electrophoretic analysis showed that Ca(2+)-calpain-induced cleavage of human dUTPase resulted in several distinctly observable dUTPase fragments. Mass spectrometric identification of the calpain-cleaved fragments identified three calpain cleavage sites (between residues (4)SE(5); (7)TP(8); and (31)LS(32)). The cleavage between the (31)LS(32) peptide bond specifically removes the flexible N-terminal nuclear localization signal, indispensable for cognate localization.Results argue for a mechanism where Ca(2+)-calpain may regulate nuclear availability and degradation of dUTPase

Partial Sums on the Ultra-Wide Word RAM

We consider the classic partial sums problem on the ultra-wide word RAM model of computation. This model extends the classic $w$-bit word RAM model with special ultrawords of length $w^2$ bits that support standard arithmetic and boolean operation and scattered memory access operations that can access $w$ (non-contiguous) locations in memory. The ultra-wide word RAM model captures (and idealizes) modern vector processor architectures. Our main result is a new in-place data structure for the partial sum problem that only stores a constant number of ultraword in addition to the input and supports operations in doubly logarithmic time. This matches the best known time bounds for the problem (among polynomial space data structures) while improving the space from superlinear to a constant number of ultrawords. Our results are based on a simple and elegant in-place word RAM data structure, known as the Fenwick tree. Our main technical contribution is a new efficient parallel ultra-wide word RAM implementation of the Fenwick tree, which is likely of independent interest.Comment: Extended abstract appeared at TAMC 202

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Treatment-seeking patterns for malaria in pharmacies in five sub-Saharan African countries

Abstract Background Artemisinin-based combination therapy (ACT) is recommended as the first-line anti-malarial treatment strategy in sub-Saharan African countries. WHO policy recommends parasitological confirmation by microscopy or rapid diagnostic test (RDT) in all cases of suspected malaria prior to treatment. Gaps remain in understanding the factors that influence patient treatment-seeking behaviour and anti-malarial drug purchase decisions in the private sector. The objective of this study was to identify patient treatment-seeking behaviour in Ghana, Kenya, Nigeria, Tanzania, and Uganda. Methods Face-to-face patient interviews were conducted at a total of 208 randomly selected retail outlets in five countries. At each outlet, exit interviews were conducted with five patients who indicated they had come seeking anti-malarial treatment. The questionnaire was anonymous and standardized in the five countries and collected data on different factors, including socio-demographic characteristics, history of illness, diagnostic practices (i.e. microscopy or RDT), prescription practices and treatment purchase. The price paid for the treatment was also collected from the outlet vendor. Results A total of 994 patients were included from the five countries. Location of malaria diagnosis was significantly different in the five countries. A total of 484 blood diagnostic tests were performed, (72.3% with microscopy and 27.7% with RDT). ACTs were purchased by 72.5% of patients who had undergone blood testing and 86.5% of patients without a blood test, regardless of whether the test result was positive or negative (p < 10−4). A total of 531 patients (53.4%) had an anti-malarial drug prescription, of which 82.9% were prescriptions for an ACT. There were significant differences in prescriptions by country. A total of 923 patients (92.9%) purchased anti-malarial drugs in an outlet, including 79.1% of patients purchasing an ACT drug: 98.0% in Ghana, 90.5% in Kenya, 80.4% in Nigeria, 69.2% in Tanzania, and 57.7% in Uganda (p < 10−4). Having a drug prescription was not a significant predictive factor associated with an ACT drug purchase (except in Kenya). The number of ACT drugs purchased with a prescription was greater than the number purchased without a prescription in Kenya, Nigeria and Tanzania. Conclusions This study highlights differences in drug prescription and purchase patterns in five sub-Saharan African countries. The private sector is playing an increasingly important role in fever case management in sub-Saharan Africa. Understanding the characteristics of private retail outlets and the role they play in providing anti-malaria drugs may support the design of effective malaria interventions

Willingness to pay for medical treatments in chronic diseases: a multicountry survey of patients and physicians

International audienc