Miracle-dz/UniFAR-FTUs huggingface dataset:
Using computational models to relate structural and functional brain connectivity

Modern imaging methods allow a non‐invasive assessment of both structural and functional brain connectivity. This has lead to the identification of disease‐related alterations affecting functional connectivity. The mechanism of how such alterations in functional connectivity arise in a structured network of interacting neural populations is as yet poorly understood. Here we use a modeling approach to explore the way in which this can arise and to highlight the important role that local population dynamics can have in shaping emergent spatial functional connectivity patterns. The local dynamics for a neural population is taken to be of the Wilson–Cowan type, whilst the structural connectivity patterns used, describing long‐range anatomical connections, cover both realistic scenarios (from the CoComac database) and idealized ones that allow for more detailed theoretical study. We have calculated graph–theoretic measures of functional network topology from numerical simulations of model networks. The effect of the form of local dynamics on the observed network state is quantified by examining the correlation between structural and functional connectivity. We document a profound and systematic dependence of the simulated functional connectivity patterns on the parameters controlling the dynamics. Importantly, we show that a weakly coupled oscillator theory explaining these correlations and their variation across parameter space can be developed. This theoretical development provides a novel way to characterize the mechanisms for the breakdown of functional connectivity in diseases through changes in local dynamics.
“Expectation as etiology” versus “the good old days”: Postconcussion syndrome symptom reporting in athletes, headache sufferers, and depressed individuals

The present study explored the explanatory power of Mittenberg's “expectation as etiology” theory for the persistence of postconcussion syndrome (PCS) complaints. One hundred forty-one participants completed a PCS symptom checklist under 2 conditions. Normal controls, healthy athletes and depressed individuals reported current symptoms and symptoms expected following a hypothetical mild head injury. Head-injured athletes, chronic headache sufferers, and a 2nd sample of normal controls reported current symptoms and retrospective symptoms (prior to their injury/illness or from some point in the past). Depressed individuals reported more current symptoms than normal controls and healthy athletes, demonstrating that “PCS” symptoms are not specific to PCS. All groups expected more symptoms following mild head injury than currently experienced, supporting the idea that individuals expect negative consequences following head injury. However, healthy athletes expected fewer symptoms than normals or depressed individuals, possibly due to preexisting expectations for speedy recovery. Both head-injured athletes and headache sufferers reported more current symptoms than the past, but not at a rate lower than baseline of normal controls. Results suggest that the “expectation as etiology” hypothesis may be too specific, and that, following any negative event, people may attribute all symptoms to that negative event (the “good old days” hypothesis). (JINS, 2001, 7, 323–333.)
An industry perspective on the use of “atoxigenic” strains of Aspergillus flavus as biological control agents and the significance of cyclopiazonic acid

Several nonaflatoxigenic strains of Aspergillus flavus have been registered in the United States to reduce aflatoxin accumulation in maize and other crops, but there may be unintended negative consequences if these strains produce cyclopiazonic acid (CPA). AF36, a nonaflatoxigenic, CPA-producing strain has been shown to produce CPA in treated maize and peanuts. Alternative strains, including Afla-Guard® brand biocontrol agent and K49, do not produce CPA and can reduce both aflatoxin and CPA in treated crops. Chronic toxicity of CPA has not been studied, and recent animal studies show significant harmful effects from short-term exposure to CPA at low doses. Grower and industry confidence in this approach must be preserved through transparency.
Topical Imiquimod 5% Cream in External Anogenital Warts: A Randomized, Double‐Blind, Placebo‐Controlled Study

The complete treatment of anogenital warts has not been obtained with any combination of methods; therefore, new methods are still under investigation. In this study the activity and side effects of imiquimod 5% cream were investigated. The study group consisted of 23 male and 11 female volunteers and the control group of 9 male and 2 female volunteers. Patients applied the cream three times a week, every other day in the evenings for a period of 12 weeks. After the treatment, patients were regularly monitored for six months for recurrences. At the end of the study, 23 (69.7%) patients (all of females and 54.5% of males) in the study group displayed a complete clearance, 9 patients displayed 50–90% clearance and 1 patient displayed less than 50% clearance. In the control group, only 1 patient displayed a complete clearance, 1 patient displayed 50–90% clearance, and the other 8 patients showed no alteration in the lesions. These results were statistically significantly different (p<0.01). In 15 patients in the study group, no side effects were reported; the most frequently seen side effects were erythema and erosion. In six patients that were observed for a period of six months, recurrences occurred. Imiquimod 5% cream is a topically applied medicament that should be considered as an effective and reliable medical option in the treatment of anogenital warts.
The Csr/Rsm system of Yersinia and related pathogens

This review emphasizes the function and regulation of the Csr regulatory system in the human enteropathogen Yersinia pseudotuberculosis and compares its features with the homologous Csr/Rsm systems of related pathogens. The Csr/Rsm systems of eubacteria form a complex regulatory network in which redundant non-translated Csr/Rsm-RNAs bind the RNA-binding protein CsrA/RsmA, thereby preventing its interaction with mRNA targets. The Csr system is controlled by the BarA/UvrY-type of two-component sensor-regulator systems. Apart from that, common or pathogen-specific regulators control the abundance of the Csr components. The coordinate control of virulence factors and infection-linked physiological traits by the Csr/Rsm systems helps the pathogens to adapt individually to rapidly changing conditions to which they are exposed during the different stages of an infection. As Csr/Rsm function is relevant for full virulence, it represents a target suitable for antimicrobial drug development.
Automatic code generation for cross-platform, multi-device mobile apps: some reflections from an industrial experience

With the continuously increasing adoption of mobile devices, software development companies have new business opportunities through direct sales in app stores and delivery of business to employee (B2E) and business to business (B2B) solutions. However, cross-platform and multi-device development is a barrier for today's IT solution providers, especially small and medium enterprises (SMEs), due to the high cost and technical complexity of targeting development to a wide spectrum of devices, which differ in format, interaction paradigm, and software architecture. So far, several authors have proposed the application of model driven approaches to mobile apps development following a variety of strategies. In this paper we present the results of a research study conducted to find the best strategy for WebRatio, a software development company, interested in producing a MDD tool for designing and developing mobile apps to enter the mobile apps market. We report on a comparative study conducted to identify the best trade-offs between various automatic code generation approaches.
Molecular medicine: a clinician's primer on microarrays

Cancer medicine is poised on the cusp of long-awaited change. For example, cancer taxonomy remains based on histopathological and anatomical principles, originating in concepts established prior to 1900. This classification has proven useful, but imperfect. Often, two histologically identical tumours frustratingly behave quite differently. Similarly, our current treatment strategies were established in the 1950s. Although great progress has been made in optimizing the use of cytotoxic therapies, these treatments by and large are nonspecifically targeted to all dividing cells. The toxicities associated with palliative treatments conferring a routine response rate of 25% have generated understandable cynicism, even (or especially) in the medical fraternity. Novel treatment and prognostic paradigms are needed, which we assume will be based on a molecular understanding of cancer. After some years of expectancy, recent proofs-of-principle suggest that molecular biology is generating effective and specific treatments. For example, a monoclonal antibody-based treatment for breast cancer, trastuzumab, was developed because molecular studies had identified a critical oncogenic role for amplified epidermal growth factor signalling 1 . Imatinib mesylate has provided important options for the treatment of chronic myeloid leukaemia 2 and gastrointestinal stromal tumours 3 by targeting specific molecular aberrations. The remarkable aspect of these treatments is not simply that they work, but their relative lack of toxicity. The recent development of robust, affordable and high-throughput methods of molecular analysis in the past decade promise to radically accelerate the pace at which new potential targets are identified. These technical developments have been based on the following achievements (in historical order): 1 Acceptance that cancer is a genetic disease, caused by somatic or germline mutations. This was predicted in 1914 by Theodor Boveri 4 but not proven until the 1980s with cloning of the first human oncogene ( ras ) 5 and tumour suppressor gene (the retinoblastoma tumour suppressor). 6
Tracking dynamic sparse signals using Hierarchical Bayesian Kalman filters

In this work we are interested in the problem of reconstructing time-varying signals for which the support is assumed to be sparse. For a single time instance it is possible to reconstruct the original signal efficiently by employing a suitable algorithm for sparse signal recovery, given the sparsity level of the signal. In the case of time-varying sparse signals the sparsity level is not necessarily known a-priori. Furthermore conventional tracking by Kalman filtering fails to promote sparsity. Instead, a hierarchical Bayesian model is used in the tracking process which succeeds in modelling sparsity. One theorem is provided that extends previous work by providing some more general results. A second theorem gives the conditions under which all sparse signals are recovered exactly. It is demonstrated that the proposed method succeeds in recovering time-varying sparse signals with greater accuracy than the classic Kalman filter approach.
The pericentriolar material in Chinese hamster ovary cells nucleates microtubule formation

The structure and function of the centrosomes from Chinese hamster ovary (CHO) cells were investigated by electron microscopy of negatively stained wholemount preparations of cell lysates. Cells were trypsinized from culture dishes, lysed with Triton X-100, sedimented onto ionized, carbon-coated grids, and negatively stained with phosphotungstate. The centrosomes from both interphase and dividing cells consisted of pairs of centrioles, a fibrous pericentriolar material, and a group of virus-like particles which were characteristic of the CHO cells and which served as markers for the pericentriolar material. Interphase centrosomes anchored up to two dozen microtubules when cells were lysed under conditions which preserved native microtubules. When Colcemid-blocked mitotic cells, initially devoid of microtubules, were allowed to recover for 10 min, microtubules formed at the pericentriolar material, but not at the centrioles. When lysates of Colcemid-blocked cells were incubated in vitro with micotubule protein purified from porcine brain tissue, up to 250 microtubules assembled at the centrosomes, similar to the number of microtubules that would normally form at the centrosome during cell division. A few microtubules could also be assembled in vitro onto the ends of isolated centrioles from which the pericentriolar material had been removed, forming characteristic axoneme- like bundles. In addition, microtubules; were assembled onto fragments of densely staining, fibrous material which was tentatively identified as periocentriolar material by its association of CHO can initiate and anchor microtubules both in vivo and in vitro.
Gender and Uveitis in Patients with Multiple Sclerosis

Multiple sclerosis (MS), a demyelinating disease of the central nervous system, is more commonly seen in women. It has been associated with both anterior and intermediate uveitis as well as retinal vasculitis. Ocular inflammation may develop concurrent with, prior to, or after the development of neurologic signs and symptoms. Patients with MS have an approximately 1% chance of developing intraocular inflammation. Patients with intermediate uveitis have an 8–12% risk of being diagnosed with MS. This risk is higher in females and in those with bilateral disease. This should be kept in mind when evaluating patients with uveitis, particularly in those patients for whom TNF inhibitor therapy is being considered, as these agents may worsen demyelinating disease.
Lipid- and sugar-modified endomorphins: novel targets for the treatment of neuropathic pain

Endomorphins are endogenous opioid peptides that cause potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, endomorphins are poorly suited to clinical applications because of low membrane permeability and a susceptibility to enzymatic degradation. Glycosylation and lipidation have proven to be two of the most robust approaches for the generation of new therapeutic endomorphin derivatives. Conjugation with lipoamino acids (LAA) confers an amphipathic character to the peptide, which improved interaction between the peptide and the lipid bilayer of the cell membranes, increasing permeability. Glycosylation can also improve peptide stability and blood brain barrier (BBB) transport. It is believed that an endocytotic mechanism (transcytosis) is responsible for the systemic delivery of water-soluble glycopeptides. This review discusses the application of glycosylation and lipidation strategies to improve the drug-like properties of endomorphins. Pharmacologically active endomorphin analogs with less adverse effects are also discussed.
Model predictive control using segregated disturbance feedback

This paper proposes a new control parametrization under Model Predictive Controller (MPC) framework for constrained linear discrete time systems with bounded additive disturbances. The parametrization takes the form of a piecewise affine disturbance feedback and is a generalization of the linear disturbance feedback proposed in the literature. Thus, performance of the resultant MPC controller may be improved. Properties and the numerical computations of the parametrization are discussed. Under mild assumptions of the disturbance set, the associated finite-horizon optimization can be computed efficiently. Stability of the closed-loop system with the proposed parametrization is also ensured.
Quantitative Sensory Testing Predicts Pregabalin Efficacy in Painful Chronic Pancreatitis

Background A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. Methods Sixty-four patients with painful chronic pancreatitis received pregabalin (150–300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. Results The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9–1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5–2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. Conclusions The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient’s individual sensory profile and thus comprises a significant step towards personalized pain medicine.
Mortality and cancer incidence among secondary lead smelter workers.

OBJECTIVES--To examine the mortality pattern and the cancer incidence in a cohort of long term smelter workers exposed to lead. METHODS--The cohort consists of 664 male lead battery workers, employed for at least three months in 1942-87. From 1969 the values of all blood lead samples repeatedly obtained from these workers every two to three months, have been collected in a database. The expected mortality and morbidity 1969-89 was estimated from the county rates, specified for cause, sex, five-year age groups, and calendar year. Individual exposure matrices have been calculated and used for dose-response analyses. RESULTS--The total cohort showed an increased overall mortality (standardised mortality ratio (SMR) 1.44; 95% confidence interval (95% CI) 1.16-1.79), an increased mortality from ischaemic heart diseases (SMR 1.72; 95% CI 1.20-2.42) and all malignant neoplasms (SMR 1.65; 95% CI 1.09-2.44). These risk estimates were unaffected or slightly decreased when applying a latency period of 15 years, and no dose-response pattern was shown. The non-significantly raised cancer incidence in the gastrointestinal tract (11 malignancies) in the total cohort, increased to a barely significant level in the quartile with the highest cumulative lead exposure (standardised incidence ratio (SIR) 2.34, 95% CI 1.07-4.45). No clear dose response pattern was evident when further subdividing the data into those first employed up to 1969 v those first employed after 1969 when the blood lead monitoring programme started. The risk estimate for malignancies in the gastrointestinal tract was not related to latency time. The cancer incidence was not increased at other sites. CONCLUSIONS--A slightly increased incidence of gastrointestinal cancers was found in workers exposed to lead and employed before 1970. The lead cohort also showed an increased mortality from ischaemic heart diseases. These risk estimates did not show a dose-response pattern and were not associated with latency time. The results must also be interpreted with caution because of limited numbers, and lack of dietary and smoking data.
Effects of dietary essential oil components on growth performance, digestive enzymes and lipid metabolism in female broiler chickens

1. The present experiment was conducted to describe the effects of thymol, cinnamaldehyde and a commercial preparation of essential oil components (CRINA® Poultry), in female broilers. Feed and water were provided for ad libitum consumption. 2. Feed intake, weight gain and feed:gain ratio were not different among the treatments. Water intake was significantly lowered by cinnamaldehyde. Relative liver weight (g/100 g of body weight) was highest in birds given thymol, but this was seen only at the age of 21 d and not at 40 d. Patterns of digestive enzymes in pancreatic tissue were similar for the 4 treatments. 3. Amylase activity in intestinal digesta was highest in chickens given CRINA® Poultry for 21 d, but the effect had disappeared after 40 d. Ileal digestibility coefficients for starch and protein were high and identical for all treatments. 4. Fatty acid composition of diet was reflected in that of adipose tissue. Plasma lipid concentrations were not changed by any dietary treatment. 5. Thus, the present results show no effect of essential oil constituents on growth performance in female broiler chickens, but it cannot be excluded that positive effects would have been observed under less hygienic environmental conditions or when using a less digestible diet.
Primary Sludge Addition for Enhanced Biosludge Dewatering

Biosludge disposal is a costly challenge for pulp and paper mills. Primary sludge is often combined with biosludge, and while this is known to improve downstream dewatering, quantification of the effects of primary sludge addition is not well studied. Evaluation of sludge properties, including mechanical dewaterability, has shown that primary sludge improves biosludge dewaterability by a factor of 2-4 when combined with biosludge at levels as low as 20 wt%. The improvement follows a consistent pattern between different primary sludge types, however a model derived from filtration theory is unable to fully capture the trend. Primary sludge pretreatment is proposed as a means to improve primary sludge usage with regards to excess water and monovalent cations. Primary sludge pretreatment, particle size and nature, and field trials are areas recommended for further investigation in line with the objective of better understanding dewatering enhancement by primary sludge addition.
Nonparametric infinite horizon Kullback-Leibler stochastic control

We present two nonparametric approaches to Kullback-Leibler (KL) control, or linearly-solvable Markov decision problem (LMDP) based on Gaussian processes (GP) and Nyström approximation. Compared to recently developed parametric methods, the proposed data-driven frameworks feature accurate function approximation and efficient on-line operations. Theoretically, we derive the mathematical connection of KL control based on dynamic programming with earlier work in control theory which relies on information theoretic dualities for the infinite time horizon case. Algorithmically, we give explicit optimal control policies in nonparametric forms, and propose on-line update schemes with budgeted computational costs. Numerical results demonstrate the effectiveness and usefulness of the proposed frameworks.
Datalog expressiveness of chain queries: grammar tools and characterizations

A chain query seeks, for each input database (viewed as directed graph), all pairs of start and end nodes of paths whose labels spell words in an associated (possibly non context-free) language over some binary predicates. We study the expressive power of Datalog for chain queries. Extending context-free productions with labels, we introduce a new tool called “indexed positive programmed grammarr” (IPPG). Three variations of IPPG are introduced to characterize chain queries computable (i) by linear Datalog, (ii) by “semi-linear Datalog”, and (iii) by general Datalog, respectively, under a natural “addressable” condition.