Alleviation of severe chronic arthritic pain using polyvalent immunoglobulins (KMP01): Two case reports.

BACKGROUND: Treatment of arthritis is carried out using corticosteroids, methotrexate, sulfasalazine-like agents, and TNF-α-blocking agents such as infliximab and adalimumab. The disadvantages of these agents are high-cost, severe side effects including leucopenia, and in some cases the necessity of administration by injection. Polyvalent immunoglobulin formulations derived from bovine colostrum and marketed as a standardized formulation for oral application, are reported to be efficacious in chronic pain syndromes but are rarely, if ever, used as an alternative medication in such patients. AIMS: To treat arthritis in a real-world setting using polyvalent immunoglobulins in 2 patients, in one case where no alternative treatment modality was available and in another patient in whom the use of polyvalent immunoglobulins appeared to be a suitable option. MATERIALS AND METHODS: Two male subjects aged 46 and 82 years with confirmed diagnosis but not well-controlled arthritis/polyarthritis receiving either high-dose NSAIDS, corticosteroids, methotrexate injections, with previous use of, or recommendations for treatment with monoclonal antibodies (etanercept and adalimumab) were treated with oral polyvalent immunoglobulins (KMP01; dose range 10 - 20 g daily) in real-world settings, in one case during a field excursion in Peru. RESULTS: The treatment produced a rapid alleviation of pain in both patients, in one patient where the symptoms were severe and debilitating. In the second patient methotrexate SC injections could be discontinued, and there was a progressive reversal of leucopenia (leucocyte count 3.9 × 103/µL) over a period of ~ 3 months. DISCUSSION: Polyvalent immunoglobulins have been shown previously to reduce the expression of interleukin-6 and C-reactive protein in peripheral blood monocytes, events attributed to the neutralization of gut-derived endotoxin ligands lipopolysaccharides (LPS) driving the basal immune response. The mode of action of KMP01 on cytokine expression is therefore similar to the TNF-α-blocking agents etanercept and adalimumab. CONCLUSION: Findings from two case reports support the rationale for using polyvalent immunoglobulins as an effective and safe alternative in arthritis patients receiving standard treatments, in particular, methotrexate and TNF-α-blocking agents.

Reoccurring Bovine Anthrax in Germany on the Same Pasture after 12 Years.

The zoonotic disease anthrax, caused by the endospore-forming bacterium Bacillus anthracis, is very rare in Germany. In the state of Bavaria, the last case occurred in July of 2009, resulting in four dead cows. In August of 2021, the disease reemerged after heavy rains, killing one gestating cow. Notably, both outbreaks affected the same pasture, suggesting a close epidemiological connection. B. anthracis could be grown from blood culture, and the presence of both virulence plasmids (pXO1 and pXO2) was confirmed by PCR. Also, recently developed diagnostic tools enabled rapid detection of B. anthracis cells and nucleic acids directly in clinical samples. The complete genome of the strain isolated from blood, designated BF-5, was DNA sequenced and phylogenetically grouped within the B.Br.CNEVA clade, which is typical for European B. anthracis strains. The genome was almost identical to BF-1, the isolate from 2009, separated only by three single nucleotide polymorphisms (SNPs) on the chromosome, one on plasmid pXO2 and three indel regions. Further, B. anthracis DNA was detected by PCR from soil samples taken from spots in the pasture where the cow had fallen. New tools based on phage receptor-binding proteins enabled the microscopic detection and isolation of B. anthracis directly from soil samples. These environmental isolates were genotyped and found to be identical to BF-5 in terms of SNPs. Therefore, it seems that the BF-5 genotype is currently the prevalent one at the affected premises. The area contaminated by the cadaver was subsequently disinfected with formaldehyde.

Effect of lockdown and vaccination on the course of the COVID-19 pandemic in Germany.

BACKGROUND: Incidence(t), derived from observational data published by the Robert Koch Institute, Berlin, Germany, is a commonly used parameter to illustrate the course of the COVID-19 pandemic in Germany. The parameter tα(t), equivalent to the doubling-time of the virus described by our research group, has also been useful in this regard. AIMS: To identify and compare parameters suitable for monitoring the course of the pandemic and to evaluate the extent to which these reflect qualitatively and quantitatively the effects of interventional measures introduced to control the pandemic. MATERIALS AND METHODS: Parameters potentially useful for monitoring the course of the pandemic were obtained empirically or derived using the Bateman SIZ model and observational data for the daily increase in the number of new infections. The doubling-time in the number of infections, tα(t) was obtained by curve-fitting observational data for the previous 14-day interval and a fixed value for tbeta (half-life for rate of recovery = 6.24 days). The effects of the interventional measures on the course of the pandemic as reflected in the modulation of the identified parameters were evaluated. RESULTS: A total of 5 different parameters (Incidence(t), R9(t), tα_stable(S), Incidencecalc(t+14), tα(t)) of potential value in monitoring the course of the pandemic were identified. Lockdown measures altered Incidence(t), and these effects could be quantitated from alterations in the reproduction factor, R9(t), a parameter with prognostic value reflecting the consequences of non-intervention. The parameter tα_stable(S) is a function of the proportion of susceptible persons and therefore reflects the effects of vaccination. Although vaccination was in progress, together with lockdown and restrictions associated with the Recovered-Vaccinated-tested rule, R9(t) remained above 1.0 apparently due to the emergence of the more virulent Mδ variant (4th wave of the pandemic in Germany). CONCLUSION: i) The newly identified parameters provide qualitative and quantitative information on the course of the COVID-19 pandemic in Germany. ii) R9(t) is a suitable parameter for assessing the effects of interventional measures and may have prognostic value. iii) The parameter tα_stable(S), a function of the proportion of susceptible persons, reflects the effects of vaccination. iv) Incidencecalc(t+14) provides prognostic information on the projected course of the pandemic with the assumption that the factors driving the pandemic do not change and is recommended as a suitable parameter for making decisions in real-time, with minimum delay, whether lockdown measures should be implemented.

COVID 19: Pandemic assessment and management using Incidencecalc(t+14) and herd immunity - Habere nos alia modum?

The course of the COVID-19 pandemic is commonly evaluated using the 7-day Incidence. We propose using 1) Incidencecalc(t+14), an index for the theoretical course of the pandemic in the absence of lockdown, as a basis for making real-time interventions. 2) The derived parameters tα(t) and tα_stable(S), obtained with the SIZ algorithm and the Bateman function, for estimating of the required degree of herd immunity to stop the pandemic. The current value of tα(t) for Germany is ~ 1.8 days, indicating that the percentage herd immunity required to halt the pandemic, assuming an efficacy of vaccination of 90%, is at least 87%.

Evidence that oral immunoglobulins (KMP01) suppress pro-tumor inflammation in rectal carcinoma: Case report and treatment concept.

BACKGROUND: A female patient aged 49 years with a rectal adenocarcinoma underwent tumor resection and multiple follow-up surgical operations whilst receiving compassionate therapy with polyvalent immunoglobulins derived from bovine colostrum (KMP01), a potential modulator of the pro-tumor inflammatory response. AIMS: Assessment of safety of the treatment, effect on tumor recurrence, and effect on parameters associated with the pro-tumor inflammatory response. MATERIALS AND METHODS: The dose of KMP01 varied from 72 g daily in the perioperative period to 12 - 24 g daily thereafter. The pro-tumor inflammatory response was measured using changes in C-reactive protein (CRP) and the lymphocyte-monocyte ratio (LMR). RESULTS: Surgical intervention caused large increases in CRP (up to 400 mg/L) and decreases in the LMR (below target levels of 2.83). However, such changes rapidly returned to normal, where they remained during prolonged treatment with immunoglobulins. Despite the generally poor prognosis associated with a stenotic tumor, cachexia, and multiple surgery, there was no tumor recurrence during the 3-year follow-up. The condition of the patient is good, albeit with a reduced quality of life due to the stoma. CONCLUSION: Polyvalent immunoglobulins constitute a potential and safe prophylactic agent against the pro-tumor inflammatory response. This is the first time that polyvalent immunoglobulins have been used in a colorectal carcinoma patient. The findings can be a basis for further investigations.

COVID-19: Effect-modelling of vaccination in Germany with regard to the mutant strain B.1.1.7 and occupancy of ICU facilities.

BACKGROUND: The characteristics of the COVID-19 pandemic in Europe have changed since the initial outbreak in 2019 due to the emergence of more contagious mutant strains, notably the B.1.1.7 variant. This has resulted in the rapid implementation of vaccination programs in an effort to control the spread of the disease. AIMS: To model the effect of vaccination on the course of the pandemic in Germany taking into account observational data and the appearance of viral mutant B.1.1.7. MATERIALS AND METHODS: An effect model based on the Batman-SIZ algorithm was developed, taking into account both the parent and the B.1.1.7 mutant strains of the SARS-CoV-2 coronavirus and using input parameters obtained from observational data for January - March 2021. RESULTS: Effect-modelling using 3 different vaccination scenarios with different rates of vaccination involving 67 million persons (priority groups 1 - 5) and completed within 134 days compared to 318 days beginning February 24, 2021, showed a reduction in the number of infected persons from ca. 12.5 million to ca. 4.5 million with quantitively similar benefits regarding the occupancy and a critical burden on ICU facilities. CONCLUSION: The effect of vaccination in reducing the daily number of new infections, the total number of infections and the occupancy of intensive-care facilities in hospitals is proportional to the speed with which the target population are vaccinated.

COVID-19: Predictions for SARS-CoV-2 vaccination on the course of the pandemic and critical occupancy of intensive-care facilities in Germany.

AIMS OF THE STUDY: To obtain predictions using the Modified Bateman SIZ Model for the effects of vaccination on the course of the COVID-19 pandemic in Germany. MATERIALS AND METHODS: Start parameters for the model were obtained from observational data after data-smoothing to reduce between-day variation. Three scenarios, 1) no vaccination, 2) vaccination of 60% of the population over 12 months, 3) vaccination of 60% of the population over 7 months were examined. The effects of changes in tα (doubling-time for the spread of infection, known to be slower in the summer months) and tß (half-life of recovery from infection) on the daily number of infectious persons, the cumulative number of infected persons, and the duration of critical occupancy of intensive-care units were also determined. RESULTS: Vaccination produced a marked and rapid reduction in the number of infectious persons (up to -60%) and the total number of infected persons (up to -70%). A 7-month vaccination strategy was significantly more effective than a 12-month strategy. The summer effect came too late to have an additional effect on the spread of infection. Vaccination was predicted to reduce the duration of critical occupancy of intensive-care facilities by ~ 70%. DISCUSSION: The predictions are based on the assumptions that lockdown conditions are maintained and vaccine availability is not limiting. CONCLUSION: Predictions made using the model show that vaccination with a SARS-CoV-2 vaccine can markedly reduce the spread of the COVID-19 disease and the period of critical occupancy of intensive-care facilities in Germany.

Forensic mental health in Europe: some key figures.

PURPOSE: While the number of forensic beds and the duration of psychiatric forensic psychiatric treatment have increased in several European Union (EU) states, this is not observed in others. Patient demographics, average lengths of stay and legal frameworks also differ substantially. The lack of basic epidemiological information on forensic patients and of shared indicators on forensic care within Europe is an obstacle to comparative research. The reasons for such variation are not well understood. METHODS: Experts from seventeen EU states submitted data on forensic bed prevalence rates, gender distributions and average length of stay in forensic in-patient facilities. Average length of stay and bed prevalence rates were examined for associations with country-level variables including Gross Domestic Product (GDP), expenditure on healthcare, prison population, general psychiatric bed prevalence rates and democracy index scores. RESULTS: The data demonstrated substantial differences between states. Average length of stay was approximately ten times greater in the Netherlands than Slovenia. In England and Wales, 18% of patients were female compared to 5% in Slovenia. There was a 17-fold difference in forensic bed rates per 100,000 between the Netherlands and Spain. Exploratory analyses suggested average length of stay was associated with GDP, expenditure on healthcare and democracy index scores. CONCLUSION: The data presented in this study represent the most recent overview of key epidemiological data in forensic services across seventeen EU states. However, systematically collected epidemiological data of good quality remain elusive in forensic psychiatry. States need to develop common definitions and recording practices and contribute to a publicly available database of such epidemiological indicators.

Ultrasensitive Detection of Bacillus anthracis by Real-Time PCR Targeting a Polymorphism in Multi-Copy 16S rRNA Genes and Their Transcripts.

The anthrax pathogen Bacillus anthracis poses a significant threat to human health. Identification of B. anthracis is challenging because of the bacterium's close genetic relationship to other Bacillus cereus group species. Thus, molecular detection is founded on species-specific PCR targeting single-copy genes. Here, we validated a previously recognized multi-copy target, a species-specific single nucleotide polymorphism (SNP) present in 2-5 copies in every B. anthracis genome analyzed. For this, a hydrolysis probe-based real-time PCR assay was developed and rigorously tested. The assay was specific as only B. anthracis DNA yielded positive results, was linear over 9 log10 units, and was sensitive with a limit of detection (LoD) of 2.9 copies/reaction. Though not exhibiting a lower LoD than established single-copy PCR targets (dhp61 or PL3), the higher copy number of the B. anthracis-specific 16S rRNA gene alleles afforded ≤2 unit lower threshold (Ct) values. To push the detection limit even further, the assay was adapted for reverse transcription PCR on 16S rRNA transcripts. This RT-PCR assay was also linear over 9 log10 units and was sensitive with an LoD of 6.3 copies/reaction. In a dilution series of experiments, the 16S RT-PCR assay achieved a thousand-fold higher sensitivity than the DNA-targeting assays. For molecular diagnostics, we recommend a real-time RT-PCR assay variant in which both DNA and RNA serve as templates (thus, no requirement for DNase treatment). This can at least provide results equaling the DNA-based implementation if no RNA is present but is superior even at the lowest residual rRNA concentrations.

COVID-19 pandemic predictions using the modified Bateman SIZ model and observational data for Heidelberg, Germany: Effect of vaccination with a SARS-CoV-2 vaccine, coronavirus testing and application of the Corona-Warn-App.

AIMS OF THE STUDY: Published data show that the current progression of the COVID-19 pandemic in Heidelberg, Germany, despite the current lockdown, could continue into 2021 and become more severe. We have used the modified Bateman SIZ algorithm to predict the effects of interventional measures to control the COVID-19 pandemic. MATERIALS AND METHODS: Model parameters, e.g., doubling time and rate of decrease in the number of infectious persons were obtained from published reports. Predictions were made for the status quo on June 1, 2020, and for interventional measures obtained for 4 scenarios. These included vaccination of the whole population using a SARS-CoV-2 vaccine having an efficacy of 50% and 100%, mass-testing for COVID-19 coronavirus and application of the Corona-Warn-App. RESULTS: The principle findings were 1) without new measures to control the pandemic, the daily number of infectious persons could reach a peak of > 4,500 daily within 18 months when > 67,000 persons would have been infected. This could be prevented by using a vaccine with 50% efficacy which was almost equally effective as a vaccine with 100% efficacy. Application of the Corona-Warn-App was the most effective method and more effective than testing for COVID-19. The methodology used has been described in detail to enable other researchers to apply the modified Bateman SIZ model to obtain predictions for COVID-19 outbreaks in other regions. Application of the model has been verified by independent investigators using different commercial software packages. CONCLUSION: The modified Bateman SIZ model has been verified and used to predict the course of the COVID-19 pandemic in Heidelberg. Lockdown measures alone are insufficient to control the pandemic during 2021. Vaccination, diagnostic tests, and use of the Corona-Warn-App with quarantine could successfully control the spread of the coronavirus infection in the community. The Corona-Warn-App applied correctly may be the most effective. The model showed that vaccination with 50% efficacy is almost as effective as vaccination with 100% efficacy.

Predictions for the COVID-19 pandemic in Germany using the modified Bateman SIZ model.

AIMS OF THE STUDY: To obtain predictions for the course of the COVID-19 pandemic in Germany using the modified Bateman SIZ model and input variables based on the status quo in July 2020. To predict the effect of a change in tα on the course of the pandemic. To evaluate the robustness and sensitivity of the model in response to a change in the input parameters. MATERIALS AND METHODS: Start parameters for the modified Bateman SIZ model were obtained from observational data published by the Robert-Koch-Institute in Berlin for the period June 1 to July 13, 2020. The robustness and sensitivity of the model were determined by changing the input parameter for the doubling-time (tα) by ± 5% and ± 10%. RESULTS: The predictions show that small changes, ± 5%, in the doubling-time, tα for the rate of increase in the number of new infections, can have a major effect, both positive and negative, on the course of the pandemic. The model predicted that the number of persons infected with the virus would reach 1 million within 8 years. A 5% longer tα would reduce the number of infected persons by ~ 75%. In contrast, a 5% shorter doubling-time would increase the number of infections over 8 years to ~ 9 million when the number of infectious persons would exceed 100,000 at the end of 2022. The pandemic is predicted to have disappeared by the end of 2024. DISCUSSION: Predictions for the course of the COVID-19 pandemic in Germany based on the status quo up to July 13, 2020 have been obtained using the modified Bateman SIZ model. There are several important assumptions necessary to apply the model and thus the results must be interpreted with caution. The model, previously used to predict the course of the COVID-19 pandemic in the city of Heidelberg (pop. 166,000) gives comparable predictive data for the whole of Germany (pop. 83 million) and thus appears to be both sensitive and robust. CONCLUSION: Since a shorter doubling-time for the number of infectious persons by only 5% would result in a major clinical emergency, interventional measures such as vaccination are urgently needed. Taking into consideration that a SARS-CoV-2 vaccine is not yet available and the efficacy of the Corona-Warn-App has yet to be shown, a relaxation in the lockdown conditions in Germany in 2020 appears premature.

COVID-19: Cytokine storm modulation/blockade with oral polyvalent immunoglobulins (PVIG, KMP01D): A potential and safe therapeutic agent (Primum nil nocere).

Although medication treatment in COVID-19 patients would have no direct effect on the spread of the disease, a shortening of the period of hospitalization by only a few days would release 25 - 30% of critical-care resources. However, there appears to be no well-established medication treatment available that can do this reliably at the present time. Anti-malarials currently being evaluated, i.e., chloroquine and hydroxychloroquine, are not yet established as effective medications, and antiviral agents, including remdesivir, are only weakly active. This position paper report is focused on the modulation of the cytokine storm since it appears to be a major cause of the multi-organ failure in COVID-19. Whereas corticosteroids are not recommended in patients not on mechanical ventilation, immunotherapy with convalescent plasma and intravenous immunoglobulin (IVIG) have been used with some success in COVID-19. There is emerging new evidence that polyvalent immunoglobulins (PVIG) from bovine colostrum given orally can also modulate the immune response. Research using lipopolysaccharide-stimulated peripheral blood mononuclear cells from colorectal cancer patients (a so called micro-cytokine storm) has shown that PVIG block the expression of pro-inflammatory cytokines and stimulate the expression of anti-inflammatory cytokines. We have been able to confirm these results in a similar model using mononuclear cells from healthy subjects and could demonstrate that the modulations produced by PVIG are quantitatively and qualitatively similar to those obtained using human immunoglobulin (IVIG). Both immunoglobulins reduce the lipopolysaccharide-induced increase in inflammatory cytokines, interleukin (IL-) 12/23p40 (-90%), IL-6 (-75%) and TNF-α (-60%) and increased the levels of the anti-inflammatory cytokine, IL-10 (+75%). Evidence is presented that PVIG can produce anti-inflammatory effects similar to these after oral application in patients. Its use is contraindicated in patients with lactose intolerance but is otherwise safe and free of complications in clinical studies including the treatment of infants with gastrointestinal disorders. Conclusion: PVIG appears to be a potential and safe anti-inflammatory agent and can be recommended as a candidate medication for studies in COVID-19 patients.

Evaluation of the COVID-19 pandemic using an algorithm based on the Bateman function: Prediction of disease progression using observational data for the city of Heidelberg, Germany
.

The COVID-19 pandemic has been evaluated using an algorithm based on the Bateman function in a modified SIR/SIZ-Model. Prediction of the number of persons carrying the live COVID-19 coronavirus (I) in a susceptible population (S) was achieved using two rate constants describing the rate of increase and decrease in the number of infectious persons on a daily basis. The model was verified using observational data for the city of Heidelberg, Germany. Three hypothetical scenarios, having their counterparts in practice were considered, namely Scenario A - No restrictions on the population; Scenario B - Assumption of a 10-fold higher number of infections than observed; Scenario C - Protective measures introduced only for elderly persons. It could be demonstrated using the model that the lockdown measures introduced prevented a major medical emergency and possibly a near catastrophe in the region. It was further demonstrated that the prospective application of the model can facilitate realtime decisions on pandemic management strategy for the population. This is achieved by curve-fitting for the rate constants, determinants for the number of infectious persons. The calculated maximum numbers of infected and infectious persons daily increased in proportion to the number of persons initially susceptible to the infection. After appearance of the first two infections in Heidelberg, the calculated maximum number of persons carrying live virus was 2,291 at Day 102 (Scenario B), 18,936 infectious persons at Day 139 (Scenario C) and 22,535 infectious at Day 142 (Scenario A). In Scenario A, high values would have persisted for 6 months during which a total of 124,301 persons would have been infected in Heidelberg. The model predicted that the virus would have disappeared within 1 year after being first detected. A disease catastrophe of this magnitude would not be expected provided the rate constant (α) for the rate of increase in the number of infectious persons remained lower than the rate constant (ß) for the fall in number of infectious persons.

In vitro compressive strength and edge stability testing of directly repaired glass-ionomer cements.

OBJECTIVE: To study the repair potential of seven commercial glass-ionomer cements (GICs) using an in vitro edge compression test model. MATERIALS AND METHODS: A total of 448 normal and 192 repaired cylindrical specimens (6 × 4 mm) were produced from 6 GICs and one resin-modified GIC. Repaired samples consisted of a base aged for 1 month before repaired by an overlying layer. All samples were matured for 1 day, 1 week, 1 month or 3 months before compression, and edge tests were performed respectively on the whole surface (compressive strength, CS) or on the edge (edge stability, ES) using a universal testing machine. RESULTS: For normal specimens, Ketac Universal (KU) illustrated a significantly higher CS than other groups at all time points (p < 0.001). ES of KU was weaker than EQUIA Forte (EQF), FIX (Fuji IX) and RSC (Riva Self Cure) after 1 day, increasing after 1 week. Repaired specimens showed CS comparable to normal specimens (p > 0.05). Repaired KU significantly improved CS compared to repaired EQF and Fuji II (FII) after 1 day. No statistical difference was found in ES among these groups (p > 0.05). CONCLUSIONS: KU provided the fastest maturation and greatest CS and ES in both normal and repair models after short-term ageing. Repair of GICs could potentially be achieved directly onto the fractured substrate and the subsequent improved mechanical performance could be maintained for at least 3 months. CLINICAL RELEVANCE: This study provides a potential alternative in-vitro method to assess GIC restoration failure as well as provide insight into the mechanisms of GIC restoration repair.

Predicting the evolutionary dynamics of seasonal adaptation to novel climates in Arabidopsis thaliana.

Predicting whether and how populations will adapt to rapid climate change is a critical goal for evolutionary biology. To examine the genetic basis of fitness and predict adaptive evolution in novel climates with seasonal variation, we grew a diverse panel of the annual plant Arabidopsis thaliana (multiparent advanced generation intercross lines) in controlled conditions simulating four climates: a present-day reference climate, an increased-temperature climate, a winter-warming only climate, and a poleward-migration climate with increased photoperiod amplitude. In each climate, four successive seasonal cohorts experienced dynamic daily temperature and photoperiod variation over a year. We measured 12 traits and developed a genomic prediction model for fitness evolution in each seasonal environment. This model was used to simulate evolutionary trajectories of the base population over 50 y in each climate, as well as 100-y scenarios of gradual climate change following adaptation to a reference climate. Patterns of plastic and evolutionary fitness response varied across seasons and climates. The increased-temperature climate promoted genetic divergence of subpopulations across seasons, whereas in the winter-warming and poleward-migration climates, seasonal genetic differentiation was reduced. In silico "resurrection experiments" showed limited evolutionary rescue compared with the plastic response of fitness to seasonal climate change. The genetic basis of adaptation and, consequently, the dynamics of evolutionary change differed qualitatively among scenarios. Populations with fewer founding genotypes and populations with genetic diversity reduced by prior selection adapted less well to novel conditions, demonstrating that adaptation to rapid climate change requires the maintenance of sufficient standing variation.

AI-Based Sensor Information Fusion for Supporting Deep Supervised Learning.

In recent years, artificial intelligence (AI) and its subarea of deep learning have drawn the attention of many researchers. At the same time, advances in technologies enable the generation or collection of large amounts of valuable data (e.g., sensor data) from various sources in different applications, such as those for the Internet of Things (IoT), which in turn aims towards the development of smart cities. With the availability of sensor data from various sources, sensor information fusion is in demand for effective integration of big data. In this article, we present an AI-based sensor-information fusion system for supporting deep supervised learning of transportation data generated and collected from various types of sensors, including remote sensed imagery for the geographic information system (GIS), accelerometers, as well as sensors for the global navigation satellite system (GNSS) and global positioning system (GPS). The discovered knowledge and information returned from our system provides analysts with a clearer understanding of trajectories or mobility of citizens, which in turn helps to develop better transportation models to achieve the ultimate goal of smarter cities. Evaluation results show the effectiveness and practicality of our AI-based sensor information fusion system for supporting deep supervised learning of big transportation data.

Interacting effects of genetic variation for seed dormancy and flowering time on phenology, life history, and fitness of experimental Arabidopsis thaliana populations over multiple generations in the field.

Major alleles for seed dormancy and flowering time are well studied, and can interact to influence seasonal timing and fitness within generations. However, little is known about how this interaction controls phenology, life history, and population fitness across multiple generations in natural seasonal environments. To examine how seed dormancy and flowering time shape annual plant life cycles over multiple generations, we established naturally dispersing populations of recombinant inbred lines of Arabidopsis thaliana segregating early and late alleles for seed dormancy and flowering time in a field experiment. We recorded seasonal phenology and fitness of each genotype over 2 yr and several generations. Strong seed dormancy suppressed mid-summer germination in both early- and late-flowering genetic backgrounds. Strong dormancy and late-flowering genotypes were both necessary to confer a winter annual life history; other genotypes were rapid-cycling. Strong dormancy increased within-season fecundity in an early-flowering background, but decreased it in a late-flowering background. However, there were no detectable differences among genotypes in population growth rates. Seasonal phenology, life history, and cohort fitness over multiple generations depend strongly upon interacting genetic variation for dormancy and flowering. However, similar population growth rates across generations suggest that different life cycle genotypes can coexist in natural populations.

The cofilin phosphatase slingshot homolog 1 (SSH1) links NOD1 signaling to actin remodeling.

NOD1 is an intracellular pathogen recognition receptor that contributes to anti-bacterial innate immune responses, adaptive immunity and tissue homeostasis. NOD1-induced signaling relies on actin remodeling, however, the details of the connection of NOD1 and the actin cytoskeleton remained elusive. Here, we identified in a druggable-genome wide siRNA screen the cofilin phosphatase SSH1 as a specific and essential component of the NOD1 pathway. We show that depletion of SSH1 impaired pathogen induced NOD1 signaling evident from diminished NF-κB activation and cytokine release. Chemical inhibition of actin polymerization using cytochalasin D rescued the loss of SSH1. We further demonstrate that NOD1 directly interacted with SSH1 at F-actin rich sites. Finally, we show that enhanced cofilin activity is intimately linked to NOD1 signaling. Our data thus provide evidence that NOD1 requires the SSH1/cofilin network for signaling and to detect bacterial induced changes in actin dynamics leading to NF-κB activation and innate immune responses.

Single-cell based high-throughput sequencing of full-length immunoglobulin heavy and light chain genes.

Single-cell PCR and sequencing of full-length Ig heavy (Igh) and Igk and Igl light chain genes is a powerful tool to measure the diversity of antibody repertoires and allows the functional assessment of B-cell responses through direct Ig gene cloning and the generation of recombinant mAbs. However, the current methodology is not high-throughput compatible. Here we developed a two-dimensional bar-coded primer matrix to combine Igh and Igk/Igl chain gene single-cell PCR with next-generation sequencing for the parallel analysis of the antibody repertoire of over 46 000 individual B cells. Our approach provides full-length Igh and corresponding Igk/Igl chain gene-sequence information and permits the accurate correction of sequencing errors by consensus building. The use of indexed cell sorting for the isolation of single B cells enables the integration of flow cytometry and Ig gene sequence information. The strategy is fully compatible with established protocols for direct antibody gene cloning and expression and therefore advances over previously described high-throughput approaches to assess antibody repertoires at the single-cell level.