Theory of Handwriting

Handwriting production is viewed as a constrained modulation of an underlying oscillatory process. Coupled oscillations in horizontal and vertical directions produce letter forms, and when superimposed on a rightward constant velocity horizontal sweep result in spatially separated letters. Modulation of the vertical oscillation is responsible for control of letter height, either through altering the frequency or altering the acceleration amplitude. Modulation of the horizontal oscillation is responsible for control of corner shape through altering phase or amplitude. The vertical velocity zero crossing in the velocity space diagram is important from the standpoint of control. Changing the horizontal velocity value at this zero crossing controls corner shape, and such changes can be effected through modifying the horizontal oscillation amplitude and phase. Changing the slope at this zero crossing controls writing slant; this slope depends on the horizontal and vertical velocity zero amplitudes and on the relative phase difference. Letter height modulation is also best applied at the vertical velocity zero crossing to preserve an even baseline. The corner shape and slant constraints completely determine the amplitude and phase relations between the two oscillations. Under these constraints interletter separation is not an independent parameter. This theory applies generally to a number of acceleration oscillation patterns such as sinusoidal, rectangular and trapezoidal oscillations. The oscillation theory also provides an explanation for how handwriting might degenerate with speed. An implementation of the theory in the context of the spring muscle model is developed. Here sinusoidal oscillations arise from a purely mechanical sources; orthogonal antagonistic spring pairs generate particular cycloids depending on the initial conditions. Modulating between cycloids can be achieved by changing the spring zero settings at the appropriate times. Frequency can be modulated either by shifting between coactivation and alternating activation of the antagonistic springs or by presuming variable spring constant springs. An acceleration and position measuring apparatus was developed for measurements of human handwriting. Measurements of human writing are consistent with the oscillation theory. It is shown that the minimum energy movement for the spring muscle is bang-coast-bang. For certain parameter values a singular arc solution can be shown to be minimizing. Experimental measurements however indicate that handwriting is not a minimum energy movement.

Description and Theoretical Analysis (Using Schemata) of Planner: A Language for Proving Theorems and Manipulating Models in a Robot

Planner is a formalism for proving theorems and manipulating models in a robot. The formalism is built out of a number of problem-solving primitives together with a hierarchical multiprocess backtrack control structure. Statements can be asserted and perhaps later withdrawn as the state of the world changes. Under BACKTRACK control structure, the hierarchy of activations of functions previously executed is maintained so that it is possible to revert to any previous state. Thus programs can easily manipulate elaborate hypothetical tentative states. In addition PLANNER uses multiprocessing so that there can be multiple loci of changes in state. Goals can be established and dismissed when they are satisfied. The deductive system of PLANNER is subordinate to the hierarchical control structure in order to maintain the desired degree of control. The use of a general-purpose matching language as the basis of the deductive system increases the flexibility of the system. Instead of explicitly naming procedures in calls, procedures can be invoked implicitly by patterns of what the procedure is supposed to accomplish. The language is being applied to solve problems faced by a robot, to write special purpose routines from goal oriented language, to express and prove properties of procedures, to abstract procedures from protocols of their actions, and as a semantic base for English.

Process control in agile supply chain network.

The work comprises a new theoretical development applied to aid decision making in an increasingly important commercial sector. Agile supply, where small volumes of high margin, short life cycle innovative products are offered, is increasingly carried out through a complex global supply chain network. We outline an equilibrium solution in such a supply chain network, which works through limited cooperation and coordination along edges (links) in the network. The links constitute the stochastic modelling entities rather than the nodes of the network. We utilise newly developed phase plane analysis to identify, model and predict characteristic behaviour in supply chain networks. The phase plane charts profile the flow of inventory and identify out of control conditions. They maintain quality within the network, as well as intelligently track the way the network evolves in conditions of changing variability. The methodology is essentially distribution free, relying as it does on the study of forecasting errors, and can be used to examine contractual details as well as strategic and game theoretical concepts between decision-making components (agents) of a network. We illustrate with typical data drawn from supply chain agile fashion products.

Power and control in international retail franchising

Alexander, Nicholas, Doherty, Anne Marie, 'Power and control in international retail franchising', European Journal of Marketing (2006) 40(11-12) pp.1292-1316 RAE2008

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.

Hematopoietic gene promoters subjected to a group-combinatorial study of DNA samples: identification of a megakaryocytic selective DNA signature

Identification of common sub-sequences for a group of functionally related DNA sequences can shed light on the role of such elements in cell-specific gene expression. In the megakaryocytic lineage, no one single unique transcription factor was described as linage specific, raising the possibility that a cluster of gene promoter sequences presents a unique signature. Here, the megakaryocytic gene promoter group, which consists of both human and mouse 5' non-coding regions, served as a case study. A methodology for group-combinatorial search has been implemented as a customized software platform. It extracts the longest common sequences for a group of related DNA sequences and allows for single gaps of varying length, as well as double- and multiple-gap sequences. The results point to common DNA sequences in a group of genes that is selectively expressed in megakaryocytes, and which does not appear in a large group of control, random and specific sequences. This suggests a role for a combination of these sequences in cell-specific gene expression in the megakaryocytic lineage. The data also point to an intrinsic cross-species difference in the organization of 5' non-coding sequences within the mammalian genomes. This methodology may be used for the identification of regulatory sequences in other lineages.

Practices of Ministerial Leadership of Korean-American United Methodist Clergywomen; Toward a Wesleyan Ecclesiology in a Global Context

This study documents, analyzes, and interprets Korean American United Methodist (KAUM) clergywomen‘s experiences in and understandings of the church. It examines contributions these (and potentially, other) clergywomen might make to Wesleyan ecclesiology generally, and particular ways United Methodists live out their faith in transitional, diverse, and global contexts. The project attempts to re-vision existing Wesleyan ecclesial discourse in the United Methodist Church (UMC) by recognizing and incorporating the contributions of racial-ethnic clergy as expressed through their leadership and practices of faith. A "practice-theory-practice" model of practical theology was used to pay systematic attention to the practical locus of the inquiries. Twenty Korean American United Methodist clergywomen were interviewed by telephone, using a voluntary sampling technique to ascertain how they both experienced the church and understood and lived out various practices of faith, including preaching, participation in and administration of the sacraments, preparation for ordained ministry, and other spiritual practices such as prayer, worship, retreats, and journaling. The dissertation summarizes those findings, provides contextual and historical interpretation, and then analyzes their responses in relation to Wesleyan theology, MinJung (mass of people) theology, and the theology of YeoSung (women who display dignity and honor as human beings). This study identifies the extraordinary call of the KAUM clergywomen interviewees to be bridge builders, strong nurturers, wounded healers, committed educators, breakers of old stereotypes, persistent seekers to fulfill God‘s call, and ecclesial leaders with ―tragic consciousness‖ who can disrupt marginality and facilitate the creative transformation of Han (a deep experience of suffering and oppression) into a constructive energy capable of shaping a new reality. According to this study, KAUM clergywomen‘s experiences and practices of faith as ecclesial leaders strengthen Wesleyan ecclesiology in terms of the UMC‘s efforts to be an inclusive church through connectionalism, and its commitment to social justice. MinJung theology and the theology of YeoSung, in their respective understandings of the church, broaden Wesleyan ecclesiology and enable the Church to be more relevant in a global context by embracing those who have not been normative theological subjects.

The impact of learning context on the acquisition of sociopragmatic variation patterns in non-native speaker teachers of English

The study is a cross-linguistic, cross-sectional investigation of the impact of learning contexts on the acquisition of sociopragmatic variation patterns and the subsequent enactment of compound identities. The informants are 20 non-native speaker teachers of English from a range of 10 European countries. They are all primarily mono-contextual foreign language learners/users of English: however, they differ with respect to the length of time accumulated in a target language environment. This allows for three groups to be established – those who have accumulated 60 days or less; those with between 90 days and one year and the final group, all of whom have accumulated in excess of one year. In order to foster the dismantling of the monolith of learning context, both learning contexts under consideration – i.e. the foreign language context and submersion context are broken down into micro-contexts which I refer to as loci of learning. For the purpose of this study, two loci are considered: the institutional and the conversational locus. In order to make a correlation between the impact of learning contexts and loci of learning on the acquisition of sociopragmatic variation patterns, a two-fold study is conducted. The first stage is the completion of a highly detailed language contact profile (LCP) questionnaire. This provides extensive biographical information regarding language learning history and is a powerful tool in illuminating the intensity of contact with the L2 that learners experience in both contexts as well as shedding light on the loci of learning to which learners are exposed in both contexts. Following the completion of the LCP, the informants take part in two role plays which require the enactment of differential identities when engaged in a speech event of asking for advice. The enactment of identities then undergoes a strategic and linguistic analysis in order to investigate if and how differences in the enactment of compound identities are indexed in language. Results indicate that learning context has a considerable impact not only on how identity is indexed in language, but also on the nature of identities enacted. Informants with very low levels of crosscontextuality index identity through strategic means – i.e. levels of directness and conventionality; however greater degrees of cross-contextuality give rise to the indexing of differential identities linguistically by means of speaker/hearer orientation and (non-) solidary moves. When it comes to the nature of identity enacted, it seems that more time spent in intense contact with native speakers in a range of loci of learning allows learners to enact their core identity; whereas low levels of contact with over-exposure to the institutional locus of learning fosters the enactment of generic identities.

Investigation of global regulators influencing styrene metabolism and bioplastic synthesis in Pseudomonas putida CA-3

The genetics and biochemistry involved in the biodegradation of styrene and the production of polyhydroxyalkanoates in Pseudomonas putida CA-3 have been well characterised to date. Knowledge of the role played by global regulators in controlling these pathways currently represents a critical knowledge gap in this area. Here we report on our efforts to identify such regulators using mini-Tn5 transposon mutagenesis of the P. putida CA-3 genome. The library generated was subjected to phenotypic screening to identify mutants exhibiting a reduced sensitivity to the effects of carbon catabolite repression of aromatic pathway activity. Our efforts identified a clpX disrupted mutant which exhibited wild-type levels of growth on styrene but significantly reduced growth on phenylacetic acid. RT-PCR analysis of key PACoA catabolon genes necessary for phenylacetic acid metabolism, and SDS-PAGE protein profile analyses suggest that no direct alteration of PACoA pathway transcriptional or translational activity was involved. The influence of global regulators affecting the accumulation of PHAs in P. putida CA-3 was also studied. Phenotypic screening of the mini-Tn5 library revealed a gacS sensor kinase gene disruption resulting in the loss of PHA accumulation capacity in P. putida CA-3. Subsequent SDS-PAGE protein analyses of the wild type and gacS mutant strains identified post-transcriptional control of phaC1 synthase as a key point of control of PHA synthesis in P. putida CA-3. Disruption of the gacS gene in another PHA accumulating organism, P. putida S12, also demonstrated a reduction of PHA accumulation capacity. PHA accumulation was observed to be disrupted in the CA-3 gacS mutant under phosphorus limited growth conditions. Over-expression studies in both wild type CA-3 and gacS mutant demonstrated that rsmY over-expression in gacS disrupted P. putida CA-3 is insufficient to restore PHA accumulation in the cell however in wild type cells, over-expression of rsmY results in an altered PHA monomer compositions.

Application of signal detection methods to fisheries management

The abundance of many commercially important fish stocks are declining and this has led to widespread concern on the performance of traditional approach in fisheries management. Quantitative models are used for obtaining estimates of population abundance and the management advice is based on annual harvest levels (TAC), where only a certain amount of catch is allowed from specific fish stocks. However, these models are data intensive and less useful when stocks have limited historical information. This study examined whether empirical stock indicators can be used to manage fisheries. The relationship between indicators and the underlying stock abundance is not direct and hence can be affected by disturbances that may account for both transient and persistent effects. Methods from Statistical Process Control (SPC) theory such as the Cumulative Sum (CUSUM) control charts are useful in classifying these effects and hence they can be used to trigger management response only when a significant impact occurs to the stock biomass. This thesis explores how empirical indicators along with CUSUM can be used for monitoring, assessment and management of fish stocks. I begin my thesis by exploring various age based catch indicators, to identify those which are potentially useful in tracking the state of fish stocks. The sensitivity and response of these indicators towards changes in Spawning Stock Biomass (SSB) showed that indicators based on age groups that are fully selected to the fishing gear or Large Fish Indicators (LFIs) are most useful and robust across the range of scenarios considered. The Decision-Interval (DI-CUSUM) and Self-Starting (SS-CUSUM) forms are the two types of control charts used in this study. In contrast to the DI-CUSUM, the SS-CUSUM can be initiated without specifying a target reference point (‘control mean’) to detect out-of-control (significant impact) situations. The sensitivity and specificity of SS-CUSUM showed that the performances are robust when LFIs are used. Once an out-of-control situation is detected, the next step is to determine how much shift has occurred in the underlying stock biomass. If an estimate of this shift is available, they can be used to update TAC by incorporation into Harvest Control Rules (HCRs). Various methods from Engineering Process Control (EPC) theory were tested to determine which method can measure the shift size in stock biomass with the highest accuracy. Results showed that methods based on Grubb’s harmonic rule gave reliable shift size estimates. The accuracy of these estimates can be improved by monitoring a combined indicator metric of stock-recruitment and LFI because this may account for impacts independent of fishing. The procedure of integrating both SPC and EPC is known as Statistical Process Adjustment (SPA). A HCR based on SPA was designed for DI-CUSUM and the scheme was successful in bringing out-of-control fish stocks back to its in-control state. The HCR was also tested using SS-CUSUM in the context of data poor fish stocks. Results showed that the scheme will be useful for sustaining the initial in-control state of the fish stock until more observations become available for quantitative assessments.

Prostate cancer treatment as an embodied rite of passage: impotence and incontinence as challenges to status reversal and reintegration

Introduction and Rationale: A central argument in the thesis is that performative acts of control, sexual potency and spontaneity are central to the continuous construction of embodied masculine identities. The acts of control, and particularly issues of spontaneity, are central to understandings and addressing the difficulties men face at varying levels of embodied identity. Using Watson’s (2000) ‘Male body schema’, I will explore the challenges and opportunities men face when negotiating normative, pragmatic, and experiential embodiment. I will later then explore the importance of these levels of embodiment to achieving visceral embodiment; or what I would define as a renewed unconscious satisfaction and ability to achieve and maintain normative, pragmatic and experiential forms of embodiment. Purpose and Objectives: Using the concept of liminality, and permanent liminality, the thesis explores how we can interpret and understand men’s experience of prostate cancer diagnosis and treatment, and their struggle to regain power and control in the context of diagnosis, and also the side effects to treatment. The strategies men adopt in seeking out personalised medical programmes of treatment with their doctors are explored in detail. The power and control that can be exercised over medical professionals and treatment options is demonstrated. Method: Collecting responses online from prostate specific discussion boards via gatekeepers, and from interviews on the ‘health talk’ online database, three intersecting conceptual categories - liminality, masculinity and the body/embodiment - are combined in this research. Liminality and ‘time’ are directly linked to notions of ‘success’ and ‘outcome’ during the treatment process, and mark distinct points at which men, and their families, expect measures or limits to have been reached. Exploring liminality within the context of Turner’s ‘rites of passage’, I explore the difficulty men face in concluding the third stage of the rites; reintegration. Results: Prostate cancer diagnosis and treatment, impotence and incontinence, in particular, have profound implications for the continuous construction of embodied masculine identities, and thus identity in general, making the construction of hegemonic ideals in the context of a highly ‘performative’ society highly troublesome. The issue of ‘spontaneity’ in the construction of various forms of embodied identities is of particular concern for men who contributed to this study.

What is the effect of systemic anticancer treatment on cognitive function?

Treatment regimens for solid tumours have been extensively investigated for their physical toxic effects, but far less is known about the potential impairment of cognitive function by anticancer treatment regimens. Here, we review published studies that examined cognitive function in adult patients receiving systemic therapy for solid tumours. Our review suggests that patients can experience cognitive changes related to their treatment. However, several studies had methodological limitations, such as use of a limited sample size, lack of baseline assessment, and lack of control for potential confounding factors. Better designed clinical trials are required so that the difficulties patients face in terms of reduced cognitive function as a result of anticancer treatment can be fully elucidated. These trials should have sufficient statistical power and, importantly, should also be prospective.

Study protocol: the Adherence and Intensification of Medications (AIM) study--a cluster randomized controlled effectiveness study.

BACKGROUND: Many patients with diabetes have poor blood pressure (BP) control. Pharmacological therapy is the cornerstone of effective BP treatment, yet there are high rates both of poor medication adherence and failure to intensify medications. Successful medication management requires an effective partnership between providers who initiate and increase doses of effective medications and patients who adhere to the regimen. METHODS: In this cluster-randomized controlled effectiveness study, primary care teams within sites were randomized to a program led by a clinical pharmacist trained in motivational interviewing-based behavioral counseling approaches and authorized to make BP medication changes or to usual care. This study involved the collection of data during a 14-month intervention period in three Department of Veterans Affairs facilities and two Kaiser Permanente Northern California facilities. The clinical pharmacist was supported by clinical information systems that enabled proactive identification of, and outreach to, eligible patients identified on the basis of poor BP control and either medication refill gaps or lack of recent medication intensification. The primary outcome is the relative change in systolic blood pressure (SBP) measurements over time. Secondary outcomes are changes in Hemoglobin A1c, low-density lipoprotein cholesterol (LDL), medication adherence determined from pharmacy refill data, and medication intensification rates. DISCUSSION: Integration of the three intervention elements--proactive identification, adherence counseling and medication intensification--is essential to achieve optimal levels of control for high-risk patients. Testing the effectiveness of this intervention at the team level allows us to study the program as it would typically be implemented within a clinic setting, including how it integrates with other elements of care. TRIAL REGISTRATION: The ClinicalTrials.gov registration number is NCT00495794.

A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency: a case report.

A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.

Morphological and genomic characterization of Filobasidiella depauperata: a homothallic sibling species of the pathogenic cryptococcus species complex.

The fungal species Cryptococcus neoformans and Cryptococcus gattii cause respiratory and neurological disease in animals and humans following inhalation of basidiospores or desiccated yeast cells from the environment. Sexual reproduction in C. neoformans and C. gattii is controlled by a bipolar system in which a single mating type locus (MAT) specifies compatibility. These two species are dimorphic, growing as yeast in the asexual stage, and producing hyphae, basidia, and basidiospores during the sexual stage. In contrast, Filobasidiella depauperata, one of the closest related species, grows exclusively as hyphae and it is found in association with decaying insects. Examination of two available strains of F. depauperata showed that the life cycle of this fungal species shares features associated with the unisexual or same-sex mating cycle in C. neoformans. Therefore, F. depauperata may represent a homothallic and possibly an obligately sexual fungal species. RAPD genotyping of 39 randomly isolated progeny from isolate CBS7855 revealed a new genotype pattern in one of the isolated basidiospores progeny, therefore suggesting that the homothallic cycle in F. depauperata could lead to the emergence of new genotypes. Phylogenetic analyses of genes linked to MAT in C. neoformans indicated that two of these genes in F. depauperata, MYO2 and STE20, appear to form a monophyletic clade with the MATa alleles of C. neoformans and C. gattii, and thus these genes may have been recruited to the MAT locus before F. depauperata diverged. Furthermore, the ancestral MATa locus may have undergone accelerated evolution prior to the divergence of the pathogenic Cryptococcus species since several of the genes linked to the MATa locus appear to have a higher number of changes and substitutions than their MATalpha counterparts. Synteny analyses between C. neoformans and F. depauperata showed that genomic regions on other chromosomes displayed conserved gene order. In contrast, the genes linked to the MAT locus of C. neoformans showed a higher number of chromosomal translocations in the genome of F. depauperata. We therefore propose that chromosomal rearrangements appear to be a major force driving speciation and sexual divergence in these closely related pathogenic and saprobic species.