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Globally, over half of the estimated new HIV infections now occur among key populations, including men who have sex with men, sex workers, people who inject drugs, transgender individuals, and people in prisons and other closed settings, and their sexual partners. Reaching epidemic control will, for many countries, increasingly require intensified programming and targeted resource allocation to meet the needs of key populations and their sexual partners. However, insufficient funding, both in terms of overall amounts and the way the funding is spent, contributes to the systematic marginalization of key populations from needed HIV services.The Joint United Nations Programme on HIV/AIDS (UNAIDS) has recently highlighted the urgent need to take action to end inequalities, including those faced by key populations, which have only been exacerbated by the COVID-19 pandemic. To address these inequalities and improve health outcomes, key population programs must expand the use of a trusted access platform, scale up differentiated service delivery models tailored to the needs of key populations, rollout structural interventions and ensure service integration. These critical program elements are often considered "extras," not necessities, and consequently costing studies of key population programs systematically underestimate the total and unitary costs of services for key populations. Findings from a recent costing study from the LINKAGES project suggest that adequate funding for these four program elements can yield benefits in program performance. Despite this and other evidence, the lack of data on the true costs of these elements and the costs of failing to provide them prevents sufficient investment in these critical elements.As nations strive to reach the 2030 UNAIDS goals, donors, governments and implementers should reconsider the true, but often hidden costs in future healthcare dollars and in lives if they fail to invest in the community-based and community-driven key population programs that address structural inequities. Supporting these efforts contributes to closing the remaining gaps in the 95-95-95 goals. The financial and opportunity cost of perpetuating inequities and missing those who must be reached in the last mile of HIV epidemic control must be considered.

Halophilic and osmotolerant yeast Debaryomyces hansenii has a high potential for cell factory applications due to its resistance to harsh environmental factors and compatibility with a wide substrate range. However, currently available genetic techniques do not allow the full potential of D. hansenii as a cell factory to be harnessed. Moreover, most of the currently available tools rely on the use of auxotrophic markers that are not suitable in wild-type prototrophic strains. In addition, the preferred non-homologous end-joining (NHEJ) DNA damage repair mechanism poses further challenges when precise gene targeting is required. In this study, we present a novel plasmid-based CRISPRCUG/Cas9 method for easy and efficient gene editing of the prototrophic strains of D. hansenii. Our toolset design is based on a dominant marker and facilitates quick assembly of the vectors expressing Cas9 and single or multiple single-guide RNAs (sgRNAs) that provide the possibility for multiplex gene engineering even in prototrophic strains. Moreover, we have constructed NHEJ-deficient D. hansenii that enable our CRISPRCUG/Cas9 tools to support the highly efficient introduction of point mutations and single/double gene deletions. Importantly, we also demonstrate that 90-nt single-stranded DNA oligonucleotides are sufficient for direct repair of DNA breaks induced by sgRNA-Cas9, resulting in precise edits reaching 100% efficiencies. In conclusion, tools developed in this study will greatly advance basic and applied research in D. hansenii. In addition, we envision that our tools can be rapidly adapted for gene editing of other non-conventional yeast species including the ones belonging to the CUG clade.

Supplemental material, MDM-18-418.R2_Appendix1_online_supp for Use of Lotteries for the Promotion of Voluntary Medical Male Circumcision Service: A Discrete-Choice Experiment among Adult Men in Tanzania by Jason J. Ong, Nyasule Neke, Mwita Wambura, Evodius Kuringe, Jonathan M. Grund, Marya Plotkin, Marc d’Elbée, Sergio Torres-Rueda, Hally R. Mahler, Helen A. Weiss and Fern Terris-Prestholt in Medical Decision Making

Feasible bioprocessing of lignocellulosic biomass requires the use of microbial strains with tolerance to inhibitor compounds and osmotic pressure, able to provide high product yield and productivity. In this sense, this study evaluated the potential of two non-conventional yeasts, Hansenula polymorpha CBS 4732 and Debaryomyces hansenii CBS 767, for use on biomass conversion in a biorefinery perspective. The ability of the strains to consume pentose and hexose sugars, to resist the toxic compounds present in hydrolysates, as well as to produce sugar alcohols and ethanol, was investigated. H. polymorpha showed highlighted resistance to toxic compounds and relevant ability to consume xylose and produce xylitol and ethanol under these conditions, at 37 °C. D. hansenii was a great producer of arabitol from glucose. The implications for sustainability due to the use of these yeasts in biorefineries was discussed. These results open up new perspectives for the development of the biorefinery sector.

Ewing sarcoma usually expresses the EWS/FLI fusion transcription factor oncoprotein. EWS/FLI regulates myriad genes required for Ewing sarcoma development. EWS/FLI binds GGAA-microsatellite sequences in vivo and in vitro. These sequences provide EWS/FLI-mediated activation to reporter constructs, suggesting that they function as EWS/FLI-response elements. We now demonstrate the critical role of an EWS/FLI-bound GGAA-microsatellite in regulation of the NR0B1 gene as well as for Ewing sarcoma proliferation and anchorage-independent growth. Clinically, genomic GGAA-microsatellites are highly variable and polymorphic. Current data suggest that there is an optimal “sweet-spot” GGAA-microsatellite length (of 18–26 GGAA repeats) that confers maximal EWS/FLI-responsiveness to target genes, but the mechanistic basis for this remains unknown. Our biochemical studies, using recombinant Δ22 (a version of EWS/FLI containing only the FLI portion), demonstrate a stoichiometry of one Δ22-monomer binding to every two consecutive GGAA-repeats on shorter microsatellite sequences. Surprisingly, the affinity for Δ22 binding to GGAA-microsatellites significantly decreased, and ultimately became unmeasureable, when the size of the microsatellite was increased to the sweet-spot length. In contrast, a fully functional EWS/FLI mutant (Mut9, which retains approximately half of the EWS portion of the fusion) showed low affinity for smaller GGAA-microsatellites but instead significantly increased its affinity at sweet-spot microsatellite lengths. Single-gene ChIP and genome-wide ChIP-sequencing (ChIP-seq) and RNA-seq studies extended these findings to the in vivo setting. Together, these data demonstrate the critical requirement of GGAA-microsatellites as EWS/FLI activating response elements in vivo and reveal an unexpected role for the EWS portion of the EWS/FLI fusion in binding to sweet-spot GGAA-microsatellites.

Information concerning the secondary isotope rate effect caused by deuterium substitution on the carbon atom next to the reaction center in carbonium ion type reactions is reviewed, and then some other examples of secondary deuterium isotope effects in organic chemistry are summarized. Some new results on isotope effects in some enzyme-catalyzed hydrogen-transfer reactions are also given. (P.C.H.)

Rapid expansion of renewable energy is occurring throughout the world due to national government financial incentives, state government mandates, and public perceptions regarding green energy. In the United States, wind power is the predominant source of renewable energy with cumulative installed capacity of over 60,000 MW as of 2012. However, integration of renewable into existing grids or proposed micro- and smart- grids is expensive with the US National Renewable Energy Laboratory estimating costs to range from US $3.5 to $5.0/MWh particularly since the unreliable nature of wind does not increase reliable generation capacity. Conventional generation facilities are therefore still needed to ensure demands can be met at all times. Storage represents one of the grand challenges facing areas with large seasonal variations in energy supply and demand. Although a number of studies suggest that grid systems in large balancing areas could handle up to 20% renewable penetration without additional storage, recent evidence suggests the lack of storage requires negative pricing at the wholesale level during periods of high power, low demand. Furthermore, smaller micro- and smart- grids will benefit from improved flexibility brought on by increased storage. While numerous studies and installations of large pump storage projects exist globally, the availability of large off-channel reservoir sites in the US is relatively limited. Investigation of smaller facilities (

The sexually dimorphic cremaster nucleus contains motoneurons that project via the genitofemoral nerve and theoretically direct androgen dependent testicular descent. The effects of flutamide on descent and masculinization of the cremaster nucleus were studied in the rat and pig.Flutamide was given to pregnant rats and pigs on days 16 to 22 and 65 to 113 of gestation, respectively. Tissues were perfused and examined at birth (pigs) or at age 30 days (rats). Spinal cords were removed, sectioned and immunohistochemically stained for serotonin (rats) or substance P (pigs) to demarcate the position of the cremaster nucleus and allow the determination of cremaster motoneuron number.After exposure to flutamide testes were undescended in 6 of 9 rats and 7 of 10 pigs. Cremaster motoneuron number per nucleus were 288 +/- 22 in control versus 250 +/- 27 in flutamide treated rats, and 165 +/- 28 in control versus 148 +/- 24 in flutamide treated pigs. The decrease in motoneuron number by flutamide was significant in both species (p0.02) but it did not approach the levels in female rats (93 +/- 11) and pigs (57 +/- 12). Cremaster motoneuron number did not correlate with testicular position. Porcine undescended testes were associated with a significant increase in mean gubernacular volume.Unlike other sexually dimorphic spinal cord nuclei masculinization of the cremaster nucleus appears to be largely androgen independent and it does not correlate with ipsilateral testicular descent. These data suggest that androgens do not mediate descent of the testes via the efferent limb of the genitofemoral nerve.

Androgens may control rat testicular descent via effects on the genitofemoral nerve or cranial gonadal ligaments. Androgen-mediated release of calcitonin gene-related peptide from the genito-femoral nerve (whose motoneuron cell bodies reside in the sexually dimorphic cremaster nucleus) may stimulate cremaster sac formation and testicular descent. Alternatively, androgens may cause regression of cranial gonadal ligaments and thereby allow the testes to descend. To evaluate these theories testicular position, and the cremaster sac and nucleus were studied in Tfm (androgen insensitive) rats. Testes were abdominal, inguinal and scrotal in 20%, 67% and 13% of Tfm male rats, respectively, and cranial ligaments were present in all cases. Mean cremaster nucleus motoneuron number was lower in female rats (70 +/- 14) but not significantly different between normal male (256 +/- 44) and Tfm male (231 +/- 42) rats, and it correlated poorly with testicular position. Calcitonin gene-related peptide immunoreactivity was rarely observed in cremaster motoneurons. These data suggest that the cremaster nucleus is not androgen-dependent, calcitonin gene-related peptide release from cremaster motoneurons is not the likely mechanism of testicular descent and persistent cranial ligaments may cause cryptorchidism in the Tfm rat.

Much research has been devoted to work-family relationships, but almost none has focused on single working parents. The present research compared a volunteer sample of single and married working parents of both sexes. Solo parents were found to engage in more agentic behavior than their married counterparts, but were only marginally more agentic in their self-concept. However, unlike married parents, agentic behavior had no relationship with well-being. Although analysis of variance showed they valued extrinsic rewards from work more than married parents, covariance analysis revealed that this was associated with their relative economic deprivation.

Multitarget detection and tracking algorithms typically presume that sensors are spatially registered-i.e., that all sensor states are precisely specified with respect to some common coordinate system. In actuality, sensor observations may be contaminated by unknown spatial misregistration biases. This paper demonstrates that these biases can be estimated by exploiting the data collected from a sufficiently large number of unknown targets, in a unified methodology in which sensor registration and multitarget tracking are performed jointly in a fully unified fashion. We show how to (1) model single-sensor bias, (2) integrate the biased sensors into a single probabilistic multiplatform-multisensor-multitarget system, (3) construct the optimal solution to the joint registration/tracking problem, and (4) devise a principled computational approximation of this optimal solution. The approach does not presume the availability of GPS or other inertial information.

This paper describes the efforts of a psychologist to use word processing, spreadsheet, and graphics programs as psycho-therapeutic aids with chronic psychiatric patients. The basic goal was to enhance users' feelings of mastery and self-esteem. Individual and group interventions are briefly described as well as positive responses and resistances to computer use. No differences in computer utilization were found based on diagnosis, age, or educational level. Future areas of research are delineated.

The gastrointestinal (GI) tract is the predominant site for primary extranodal non-Hodgkin lymphomas (NHL), accounting for 5–10% of all extranodal disease. A 74-year-old man underwent colonoscopy for a positive fecal occult blood test. Colonoscopy revealed a 3.5-cm polyp in the descending colon and was removed by snare cautery polypectomy. Post-polypectomy site showed a 0.3–0.5-cm mucosal defect. Five endoclips were applied to close the mucosal defect. The patient remained stable during subsequent intensive monitoring and never required surgical intervention. Pathology of the polyp revealed follicular lymphoma (FL) involving the lamina propria of the mucosa with extension into the submucosa. The patient had no systemic symptoms, and staging for NHL with contrast computerized tomography of the chest, abdomen, and pelvis revealed no evidence suggestive of lymphoma. Approximately 6–20% of all primary GI-NHL are in the colon. The frequency of GI-FL accounts for 1–3.6% of all GI-NHL. After a search of the current literature, there have been no cases of a follicular lymphoma presenting solely as an isolated colon polyp. Likewise, bowel perforation due to polypectomy of such polyps has never been cited. Retrospectively, the diagnosis and extent of the polyp could have been established using endoscopic end-to-end forceps biopsy and/or endoscopic ultrasound with a radial scanning catheter probe and fine-needle aspiration of the lesion. Such a diagnosis could have changed the strategy for endoscopic removal of the polyp. Our case is interesting because it is the first report of a follicular lymphoma presenting as a single isolated colon polyp involving all layers of the colonic mucosa.

In recent years the first author has developed a unified, computationally tractable approach to multisensor-multitarget sensor management. This approach consists of closed-loop recursion of a PHD or CPHD filter with maximization of a "natural" sensor management objective function called PENT (posterior expected number of targets). In this paper we extend this approach so that it can be used in unknown, dynamic clutter backgrounds.

Joint search and sensor management for space situational awareness presents daunting scientific and practical challenges as it requires a simultaneous search for new, and the catalog update of the current space objects. We demonstrate a new approach to joint search and sensor management by utilizing the Posterior Expected Number of Targets (PENT) as the objective function, an observation model for a space-based EO/IR sensor, and a Probability Hypothesis Density Particle Filter (PHD-PF) tracker. Simulation and results using actual Geosynchronous Satellites are presented.

Dynamic sensor management of dispersed and disparate sensors for space situational awareness presents daunting scientific and practical challenges as it requires optimal and accurate maintenance of all Resident Space Objects (RSOs) of interest. We demonstrate an approach to the space-based sensor management problem by extending a previously developed and tested sensor management objective function, the Posterior Expected Number of Targets (PENT), to disparate and dispersed sensors. This PENT extension together with observation models for various sensor platforms, and a Probability Hypothesis Density Particle Filter (PHD-PF) tracker provide a powerful tool for tackling this challenging problem. We demonstrate the approach using simulations for tracking RSOs by a Space Based Visible (SBV) sensor and ground based radars.

Summary Clostridia rarely cause pleuropulmonary infections in the absence of trauma. We report a case of intermittent bowel obstruction, clostridial bacteraemia and pneumonia with a fatal outcome. Only 16 cases have previously been reported. Clostridial infection of the lung has many features of an acute pneumonia and is almost always associated with a pleural effusion. Most cases are caused by Clostridium perfringens , though infections with other species have been reported. The prognosis is generally more favourable than in clostridial infection secondary to aspiration pneumonia or complicating empyema.

The PHD filter propagates a multitarget statistical first moment, the probability hypothesis density (PHD), in place of the full multitarget posterior distribution. It has been the basis of a systematic approach to multisensor, multitarget sensor management based on the posterior expected number of targets (PENT) objective function. The PHD filter has since been generalized to the cardinalized PHD (CPHD) filter, which propagates not only the PHD but also the full probability distribution on target number. The CPHD filter provides more accurate estimates of target number and target states. This paper shows how PENT-based objective functions can be naturally extended for use with the CPHD filter.

Sensor management for space situational awareness presents a daunting theoretical and practical challenge as it requires the use of multiple types of sensors on a variety of platforms to ensure that the space environment is continuously monitored. We demonstrate a new approach utilizing the Posterior Expected Number of Targets (PENT) as the sensor management objective function, an observation model for a space-based EO/IR sensor platform, and a Probability Hypothesis Density Particle Filter (PHD-PF) tracker. Simulation and results using actual Geostationary Satellites are presented. We also demonstrate enhanced performance by applying the ProgressiveWeighting Correction (PWC) method for regularization in the implementation of the PHD-PF tracker.

A theoretical formulation for mission based sensor management and information fusion using advanced tools of probability theory and stochastic processes is presented. We apply Bayes' Belief Network methods to fuse features and determine a tactical significant function which is used by the sensor management objective function. The estimated multi-sensor multi-target posterior that results reflects tactical significant, and is used to determine the course of action for the given mission. We demonstrate the performance of the algorithm using the simple mission of reaching a pre-specified location while avoiding threatening targets, and discuss the results.

In last year's conference we demonstrated new results using a foundational, joint control-theoretic approach to situation assessment (SA) and SA sensor management that is based on a "dynamic situational significance map", the maximization of the expected number of targets of tactical interest, and approximate multitarget filters (specifically, first-order multitarget moment filters and multi-hypothesis correlator (MHC) engines). This year we report on the following new developments and extensions: (1) a tactical significance function based on the fusion of different ambiguous attributes from several different sources; (2) a Bayes' belief network formulation for multi-target tracking and information fusion; and (3) a recursive closed form expression for the posterior expected number of targets of interests (PENTIs) for ANY number of sources. Results of testing this sensor management algorithm with significance maps defined in terms of targets/attributes interrelationships using simplified battlefield situations demonstrate that these new advancements allow for a better SA, and a more efficient SA sensor management.

The ambiguousness of human information sources and of a PRIORI human context would seem to automatically preclude the feasibility of a Bayesian approach to information fusion. We show that this is not necessarily the case, and that one can model the ambiguities associated with defining a “ state” or “ states of interest” of an entity. We show likewise that we can model information such as natural-language statements, and hedge against the uncertainties associated with the modeling process. Likewise a likelihood can be created that hedges against the inherent uncertainties in information generation and collection including the uncertainties created by the passage of time between information collections. As with the processing of conventional sensor information, we use the Bayes filter to produce posterior distributions from which we could extract estimates not only of the states, but also estimates of the reliability of those state-estimates. Results of testing this novel Bayes-filter information-fusion approach against simulated data are presented.

Sensor management in support of situation assessment (SA) presents a daunting theoretical and practical challenge. We demonstrate new results using a foundational, joint control-theoretic approach to SA and SA sensor management that is based on three concepts: (1) a “ dynamic situational significance map” that mathematically specifies the meaning of tactical significance for a given theater of interest at a given moment ; (2) an intuitively meaningful and potentially computationally tractable objective function for SA, namely maximization of the expected number of targets of tactical interest ; and (3) integration of these two concepts with approximate multitarget filters (specifically, first-order multitarget moment filters and multi-hypothesis correlator (MHC) engines). Under this approach, sensors will be directed to preferentially collect observations from targets of actual or potential tactical significance, according to an adaptively modified definition of tactical significance. Result of testing this sensor management algorithm with significance maps defined in terms of target’ s location, speed, and heading will be presented. Testing is performed against simulated data, and different sensor management algorithms including the proposed are compared.

This paper describes a unified approach to the problem of estimating the states of one or more targets, based on fusion of accumulating multisource information which can take one of two forms: ambiguous measurements or ambiguous state-estimates. We show that, as most commonly employed, Dempster-Shafer (DS) fusion methods can be subsumed within the Bayesian theory. Specifically, we show that the following are equivalent to fusion using Bayes' rule: (I) fusion of ambiguous measurements using Dempster's combination rule; and (2) fusion of ambiguous state-estimates using the Fixsen-Mahler "modified" combination. We show that the Voorbraak and pignistic transforms can be understood as posterior probability densities conditioned on, respectively, ambiguous measurements and ambiguous state-estimates. Our approach is based on natural extensions of the recursive Bayes filter. We also derive closed-form formulas for one type of single-target "evidential filter" and briefly show how it can be incorporated into multi-hypothesis multitarget tracker techniques.

Multisensor-multitarget sensor management is viewed as a problem in nonlinear control theory. This paper applies newly developed theories for sensor management based on a Bayesian control-theoretic foundation. Finite-Set-Statistics (FISST) and the Bayes recursive filter for the entire multisensor-multitarget system are used with information-theoretic objective functions in the development of the sensor management algorithms. The theoretical analysis indicate that some of these objective functions lead to potentially tractable sensor management algorithms when used in conjunction with MHC (multi-hypothesis correlator)-like algorithms. We show examples of such algorithms, and present an evaluation of their performance against multisensor-multitarget scenarios. This sensor management formulation also allows for the incorporation of target preference, and experiments demonstrating the performance of sensor management with target preference will be presented.

The fact that evidence can take highly disparate forms has been a major stumbling block in multisource-multitarget data fusion. Evidence can have at least three forms: unambiguous data (easily amenable to probabilistic analysis); ambiguously-generated data (difficult to characterize probabilistically); and ambiguous data (difficult to even model mathematically). We summarize a unified, systematic, and fully probabilistic methodology for fusing all three data types with the aim of detecting, tracking, and identifying multiple targets. The basic tool is the generalized likelihood function, which hedges against the inherent uncertainties associated with ambiguous and ambiguously-generated data.

Multisensor-multitarget sensor management is at root a problem in nonlinear control theory. We apply newly developed theories for sensor management based on a Bayesian control-theoretic foundation. Finite-Set-Statistics (FISST) and the Bayes recursive filter for the entire multisensor-multitarget system are used with information-theoretic objective functions in the development of the sensor management algorithms. The theoretical analysis indicates that some of these objective functions are geometric, and lead to potentially tractable sensor management algorithms when used in conjunction with MHC (multihypothesis correlator)-like algorithms. We show examples of such algorithms, and present a preliminary evaluation of their performance against simulated scenarios.

In this paper we consider the problem of autonomously improving upon a sensor management algorithm for better tracking performance. Since various Performance Metrics have been proposed and studied for monitoring a tracking system's behavior, the problem is solvable by first parameterizing a sensor management algorithm and then searching the parameter space for a (sub-)optimal solution. Genetic Algorithms (GA) are ideally suited for this optimization task. In our GA approach, the sensor management algorithm is driven by "rules" that has a "condition" part to specify track locations and uncertainties, and an "action" part to specify where the Field of Views (FoVs) of the sensors should be directed. Initial simulation studies using a Multi-Hypothesis Tracker and the Kullback-Leibler metric (as a basis for the GA fitness function) are presented. They indicate that the method proposed is feasible and promising.© (2003) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Information fusion is the name given to military expert-systems problems. In this paper we summarize recent work proposing a fully probabilistic theoretical unification for much of information fusion based on the theory of random sets. Our approach unifies detection, localization, classification, and prior knowledge with respect to these. It also unifies precise data together with imprecise data and propositional or vague/fuzzy evidence, as well as certain associated methodologies (e.g., fuzzy logic, rules). Underlying our approach is the discovery that classical single-sensor, single-target point-variate statistics can be directly generalized to a multisensor, multitarget statistics of finite-set variates. We describe "finite-set statistics" and its application to multisensor estimation using diverse data forms. We also point out relationships with current theoretical statistics.

Progress in single-sensor, single-object tracking has been greatly facilitated by the existence of a systematic, rigorous, and yet practical engineering statistics that supports the development of new concepts. Surprisingly, until recently no similar engineering statistics has been available for multi-sensor, multi-object tracking. The author describes the Bayes filtering equations (the theoretical basis for all optimal single-sensor, single-object tracking) and explain why their generalization to multisensor-multitarget problems requires systematic engineering statistics-i.e., finite-set statistics (FISST). He concludes by summarising the main concepts of FISST-in particular, the multisensor-multitarget differential and integral calculus that is its core.

In multi-hypothesis target tracking, given the time-predicted tracks, we consider the sensor management problem of directing the sensors' Field of View (FOV) in such a way that the targets detection rate is improved. Defining a (squared) distance between a sensor and a track as the (squared) Euclidean distance between the centers of their respective Gaussian distributions, weighted by the sum of the covariance matrices, the problem is formulated as the minimization of the Hausdorff distance from the set of tracks to the set of sensors. An analytical solution for the single sensor case is obtained, and is extended to the multiple sensors case. This extension is achieved by performing the following: (1) It is first proved that for an optimal solution, there exists a partition of the set of tracks into subsets, and an association of each subset with a sensor, such that each subset-sensor pair is optimal in the Hausdorff distance sense; (2) a brute force search is then conducted to check all possible subset-partitions of the tracks as well as the permutations of sensors; (3) for each subset-sensor pair, the optimal solution is obtained analytically; and (4) the configuration with the smallest Hausdorff distance is declared as the optimal solution for the given multi-target multi-sensor problem. Some well established loopless algorithms for generating set partitions and permutations are implemented to reduce the computational complexity. A simulation result demonstrating the proposed sensor management algorithm is also presented.

For the last two years at this conference, we have described the implementation of a unified, scientific approach to performance measurement for data fusion algorithms based on FINITE-SET STATISTICS (FISST). FISST makes it possible to directly extend Shannon-type information metrics to multisource, multitarget problems. In previous papers we described application of information Measures of Effectiveness (MoEs) to multisource-multitarget data fusion and to non-distributed sensor management. In this follow-on paper we show how to generalize this work to DISTRIBUTED sensor management and ADAPTIVE DATA FUSION.

Last year at this conference we described initial result in the practical implementation of a unified, scientific approach to performance measurement for data fusion algorithms, The proposed approach is based on 'finite-set statistics' (FISST), a generalization of conventional statistics to multisource, multitarget problems. Finite-set statistics makes it possible to directly extend Shannon-type information metrics to multi-source, multitarget problems in such a way that 'information' can be defined and measured even though any given end-user may have conflicting or even subjective definitions of what 'informative' means. In last year's paper, we described scientific performance evaluation for Level 1 data fusion. In this follow-on paper we describe a generalization of the FISST approach to Level 4 data fusion, specifically sensor management. Our Level 4 MoEs are based on the fact that sensor management is a support function: its purpose is to redirect collection assets in order to improve the input data into- and therefore the output performance of a Level 1 fusion algorithm. Accordingly, our basic MoE is 'excess information'. By using a sensor scheduler to simulate various sensor management algorithms, we established the effectiveness and intuitiveness of two different sensor management MoEs: the multitarget Kullback-Leibler information metric, and the Hausdorff multitarget miss-distance metric.

In clinical islet transplantation to patients with type 1 diabetes mellitus, the number of isolated and purified islet has been identified as a key determinant for functional success of the islet graft [1]. With improved isolation methods based on the original procedure published by Ricordi et al. [2] yield and function of isolated islets were considerably enhanced. However, there is still a large variance in the number, purity, viability and secretory capacity of islets isolated from brain-dead human donor pancreata, significantly hampering utilization of human islet preparations derived from a single donor for one diabetic recipient. The reasons for the limited success in islet isolation and purification have not been clarified in detail yet. Recent studies have indicated, that donor preconditions, and a number of technical factors during organ procurement and the islet isolation process itself are critical to successful islet isolation [3, 4]. This study aimed at identifying distinct morphological and histopathological characteristics of the donor pancreas as determinants for the outcome of human islet isolation and purification.

OBJECTIVE: The recent EURODIAB Study has identified autonomic neuropathy as an independent risk factor for severe hypoglycemia in patients with type 1 diabetes. We tested the hypothesis that counterregulatory catecholamine responses and awareness of hypoglycemia are impaired to a greater extent in type 1 diabetic patients with autonomic neuropathy (AN+) than in those without autonomic neuropathy (AN-). RESEARCH DESIGN AND METHODS: We studied 22 type 1 diabetic patients (8 AN+, 14 AN-) matched for age, duration of diabetes, glycemic control, and history of hypoglycemic episodes. We also studied 33 nondiabetic control subjects using the stepped hypoglycemic clamp technique and determined glycemic thresholds and magnitudes of counterregulatory hormone responses and of hypoglycemia symptoms. RESULTS: Both groups of diabetic patients had reduced awareness of hypoglycemia as evidenced by an elevated glycemic threshold for autonomic symptoms > or =2 SD above normal but neither the magnitude nor thresholds for symptoms differed in AN+ patients and AN-patients. Both groups also had impaired glucagon, epinephrine, norepinephrine, growth hormone and cortisol responses to hypoglycemia. However, in AN+ patients compared with AN-patients, magnitudes of epinephrine and norepinephrine responses (194+/-49 vs. 784+/-206 pmol/l, P < 0.007, and 316+/-56 vs. 610+/-87 pmol/l, P < 0.02, respectively) and epinephrine and norepinephrine glycemic thresholds (2.33+/- 0.10 vs. 2.82+/-0.10 mmol/l, P < 0.009 and 2.34+/-0.06 vs. 2.79+/-0.10 mmol/l, P < 0.008, respectively) were impaired to a greater extent. This was associated with a 50% greater requirement of exogenous glucose to prevent more severe hypoglycemia during the 2.3 mmol/l glycemic plateau (P < 0.002). No differences were observed between other counterregulatory hormone responses in AN+ and AN- patients. CONCLUSIONS: We conclude that in patients with type 1 diabetes, autonomic neuropathy further reduces counterregulatory catecholamine responses. Since this should increase the risk for severe hypoglycemia, one might consider safer therapeutic goals in these patients.

We have undertaken a systematic examination of the polypeptides accumulating in thirteen (out of 23) mutants in the intron cluster box7 and its flanking clusters box2 and box9 of the cob-box (cytochrome b) region of the mitochondrial genome of Saccharomyces cerevisiae. We have subjected these polypeptides to fingerprint analysis, both sequential and in parallel, with two proteases in order to disclose sequence homologies and differences between the different novel polypeptides themselves, and between them and the wild type product of the gene, i.e. apocytochrome b. One of our aims has been to establish the existence of possible correlations between the nature of the novel polypeptides and the fine structure genetic map of that segment of the mitochondrial genome. Our results show that all box7 mutants accumulate the following set of polypeptides not seen in wild type cells: a) a characteristic set of “large” polypeptides consisting of three species: p56, p42 and p35 or p34.5; b) a polypeptide p23; c) a much shorter fragment (of which the apparent molecular weight varies from 12.5 to 13, according to the mutation) with the exception of two mutants; d) in addition, the majority accumulate in varying amounts a polypeptide p30 closely related to but not identical with apocytochrome b. Moreover only two box7 mutants accumulate a polypeptide in the range of mobilities corresponding to 25–27 Kd (referred to as class p26) while such a polypeptide is seen in all box9 and box2 mutants examined with one exception in box2. Only one mutant in box2 resembles box7 mutants with respect to criterion a), and no box2 or box9 mutants resemble box7 mutants with respect to criterion c); criteria b) and d) appear to apply equally well to mutants in all three clusters. Fingerprint analysis, carried out with polypeptides p56, p42, p35, p34.5, p30, p26, p23, discloses that a) The polypeptides belonging to the same class of mobility exhibit very similar if not identical sequences in various cases. b) These polypeptide classes, except p56, p42 and p26, share considerable sequence homologies with wild type apocytochrome b, perhaps encompassing 50% or more of the wild type sequences. b) Polypeptides belonging to the classes p42 and p26 exhibit less extensive but nevertheless significant homologies with the wild type sequence. c) Sequences in polypeptides belonging to class p56 are virtually indistinguishable from ones in cytochrome oxidase subunit I. The inferences from these findings are 1) one gene can produce a multiplicity of polypeptide products that share a common sequence at the promoter-proximal (N-terminal) portion, but diverge beyond these regions of homology. 2) Both the multiplicity of products in single mutants, and the protein structure found, argue against the divergent segments to be due to frameshift terminations, and instead suggest that the novel products are consequences of mRNA processing defects (excision and/or ligation) at and near intron regions. 3) Mutations at edges and the center of an intron can generate similar polypeptide patterns, i.e. produce analoguous mRNA processing defects. 4) Mutations in exons, at their boundary with introns, can produce polypeptide patterns indistinguishable from those at the neighbouring intron; they diverge and eventually become typically exonlike in mutants localized at increasing distances from the boundary. 5) Taken together these findings argue that pre-mRNA processing extends beyond the boundaries of the intron proper and that certain exonsequences participate in excision and ligation. 6) Accumulated pre-mRNAs, resulting from defects in splicing can be translated. 7) Product p56 is formally analogous to p23, as a faulty but highly conserved partial product of the wild type protein, the former of Cox I (oxi3 gene), the latter of the cob-box gene proper. Therefore both genes may utilize identical RNA processing elements which are affected by box7 mutations. 8) A small amount of product similar to p56 may accumulate even in some wild types but not in others. This observations suggests that in certain nuclear backgrounds RNA processing may be more error-prone than in others.