Miracle-dz/UniFAR-FTUs huggingface dataset:
Threshold-dependent transcriptional discrimination underlies stem cell homeostasis

Significance Various mechanisms have been proposed to explain dose-dependent transcriptional regulation mediated by morphogen gradients in animal development. In plant development, on the other hand, transcriptional mechanisms that underlie dose-dependent modulation of gene expression have not been discovered, despite the well-documented importance of positional signals in cell-fate specification. Here we show that the stem cell-promoting transcription factor WUSCHEL (WUS) regulates transcription in a concentration-dependent manner, activating transcription at a lower level and repressing transcription at a higher level, thus leading to the transcriptional control of its own negative regulator. Our work also shows that WUS binds a group of tightly clustered cis elements, each with different affinities; this binding suggests a buffering mechanism in maintaining a stable CLAVATA3 (CLV3) expression. Transcriptional mechanisms that underlie the dose-dependent regulation of gene expression in animal development have been studied extensively. However, the mechanisms of dose-dependent transcriptional regulation in plant development have not been understood. In Arabidopsis shoot apical meristems, WUSCHEL (WUS), a stem cell-promoting transcription factor, accumulates at a higher level in the rib meristem and at a lower level in the central zone where it activates its own negative regulator, CLAVATA3 (CLV3). How WUS regulates CLV3 levels has not been understood. Here we show that WUS binds a group of cis-elements, cis- regulatory module, in the CLV3-regulatory region, with different affinities and conformations, consisting of monomers at lower concentration and as dimers at a higher level. By deleting cis elements, manipulating the WUS-binding affinity and the homodimerization threshold of cis elements, and manipulating WUS levels, we show that the same cis elements mediate both the activation and repression of CLV3 at lower and higher WUS levels, respectively. The concentration-dependent transcriptional discrimination provides a mechanistic framework to explain the regulation of CLV3 levels that is critical for stem cell homeostasis.
Reduction of selection bias in primary prevention of cardiovascular disease through involvement of primary health care.

OBJECTIVE To examine selection bias in social and health factors in a community intervention programme for the prevention of cardiovascular disease by comparing programme data with both census data and a random sample of the same population. DESIGN Cross sectional studies. SETTING All 35 primary health care centres in Västerbotten County, Sweden. SUBJECTS 24,870 individuals who during 1992 and 1993 became 30, 40, 50 or 60 years of age. MAIN OUTCOME MEASURES Total income, socio-economic group, employment, education, body mass index (BMI), total cholesterol, systolic and diastolic blood pressure, and daily smoking. RESULTS The differences in social characteristics between participants and non-participants were marginal, indicating that the social selection bias was small. However, unemployment, low income, and younger age tended to be associated with somewhat lower preference to participate. The overall pattern of health status, as measured by risk factors, was similar rather than dissimilar. While the participants in the intervention health survey had lower mean total cholesterol, their blood pressure was generally higher compared with the reference random sample. CONCLUSIONS The primary health care system in Sweden might serve as a useful base for educational health counselling, at least within a community intervention programme, for all levels of society.
Comparison of Pedobarographic Profile in Young Males with Left and Right Scoliotic Posture

Background: Scoliosis alters both posture and gait. Pedobarography is a biomechanical method for assessing gait that has been rarely used in scoliosis-specific gait research. Objective: To determine differences between left and right scoliotic posture in plantar pressure and force gait profile among young males. Methods: Twenty-one young, trained males assigned to one of two groups: left scoliotic posture (LSP ; N=12) and right scoliotic posture (RSP ; N=9) group. Subjects were assigned to a group based on forward-bending test and controlled for age, height, weight, body mass index (BMI), right and left leg length. All subjects were blinded for group they were assigned and study outcomes. Examiners were blinded for study outcomes. Subjects walked at self-selected speed along the 9, 5-meter-long walkway for 2 minutes. Plantar pressures and forces were measured using pedobarographic device Zebris medical FDM 1.5. Measured outcomes during gait included: Maximum force right foot (N), Maximum force left foot (N), Maximum force at first contact right foot (N), Maximum force at first contact left foot (N), Maximum force at take-off right foot (N), Maximum force at take-off left foot (N), Maximum forefoot force right foot (N), Maximum forefoot force left foot (N), Maximum midfoot force right foot (N), Maximum midfoot force left foot (N), Maximum heel force right foot (N), Maximum heel force left foot (N), Maximum forefoot pressure right foot (N/cm2), Maximum forefoot pressure left foot (N/cm2), Maximum midfoot pressure right foot (N/cm2), Maximum midfoot pressure left foot (N/cm2), Maximum heel pressure right foot (N/cm2), Maximum heel pressure left foot (N/cm2). Results: There were no significant differences in any observed foot pressure or force gait parameter between left and right scoliotic posture group (p<0, 05). Conclusion: Plantar pressure and force gait parameters seems to have no diagnostic value in determining scoliosis-specific gait. Focus should be shifted to other pedobarographic gait parameters (e.g. center of pressure, time-force parameters, etc.). Future research should investigate relationships between biomechanical movement compensation and neuromuscular, musculo- skeletal and genetic factors that may initiate scoliosis.
Vaccination of Mice with an Antigenic Serine Protease-Like Protein Elicits a Protective Immune Response Against Trichinella spiralis Infection

Abstract: Trichinellosis has major economic impacts on animal husbandry and food safety, and the control and elimination of trichinellosis is a major objective of veterinary medicine. A gene encoding serine protease of Trichinella spiralis (Ts-Adsp) was identified by immunoscreening an adult T. spiralis cDNA library. In this study, the recombinant Ts-Adsp protein (rTs-Adsp) was cloned and expressed in a prokaryotic expression system and purified by Ni-affinity chromatography. To determine whether the purified rTs-Adsp is a potential vaccine candidate for the control of T. spiralis infection, we immunized BALB/c mice with this protein in combination with an alum adjuvant and subsequently challenged with T. spiralis larvae. The results showed that mice vaccinated with rTs-Adsp exhibited an average reduction in the muscle larvae burden of 46.5% relative to the control group. Immunization with the rTs-Adsp antigen induced both humoral and cellular immune responses, which manifested as elevated specific anti–rTs-Adsp IgG and IgE antibodies and a mixed Th1–Th2 response, as determined by Th1 (IFN-γ and IL-2) and Th2 (IL-4, IL-10, and IL-13) cytokine profiling, with the Th2 predominant. Thus, purified rTs-Adsp is able to limit the invasion of T. spiralis, and this protein could be an effective vaccine candidate for trichinellosis.
Bandwidth allocation and preemption for supporting differentiated-service-aware traffic engineering in multi-service networks

We present a bandwidth management algorithm for supporting differentiated-service-aware traffic engineering. The algorithm contains both bandwidth allocation and preemption schemes, in which the link bandwidth is managed in two dimensions: class type and preemption priority. For the purpose of achieving simple, effective and non-fragmentation bandwidth allocation, we establish a novel "use it or lend it" bandwidth management model, which is implemented by an innovative technique of separating the reserved bandwidth information into three colored matrices. A new bandwidth preemption rule is proposed by extending the basic preemption rule in the standard. Our algorithm has been prototyped in the C programming language, and experimental results are presented to demonstrate the effectiveness of our algorithm.
Microcirculation Inflammation Associates With Outcome in Renal Transplant Patients With De Novo Donor‐Specific Antibodies

In renal transplant patients with de novo donor‐specific antibodies (dnDSA) we studied the value of microcirculation inflammation (MI; defined by the addition of glomerulitis (g) and peritubular capillaritis (ptc) scores) to assess long‐term graft survival in a retrospective cohort study. Out of all transplant patients with standard immunological risk (n = 638), 79 (12.4%) developed dnDSA and 58/79 (73%) had an indication biopsy at or after dnDSA development. Based on the MI score on that indication biopsy patients were categorized, MI0 (n = 26), MI1 + 2 (n = 21) and MI ≥ 3 (n = 11). The MI groups did not differ significantly pretransplantation, whereas posttransplantation higher MI scores developed more anti‐HLA class I + II DSA (p = 0.011), showed more TCMR (p < 0.001) and showed a trend to C4d‐positive staining (p = 0.059). Four‐year graft survival estimates from time of indication biopsy were MI0 96.1%, MI1 + 2 76.1% and MI ≥ 3 17.1%; resulting in a 24‐fold increased risk of graft failure in the MI ≥ 3 compared to the MI0 group (p = 0.003; 95% CI [3.0–196.0]). When adjusted for C4d, MI ≥ 3 still had a 21‐fold increased risk of graft failure (p = 0.005; 95% CI [2.5–180.0]), while C4d positivity on indication biopsy lost significance. In renal transplant patients with de novo DSA, microcirculation inflammation, defined by g + ptc, associates with graft survival.
Functional interaction between transcriptional elements in the long terminal repeat of reticuloendotheliosis virus: cooperative DNA binding of promoter- and enhancer-specific factors

Transcription from reticuloenodotheliosis virus strain T (REV-T), an avian retrovirus unrelated to avian leukosis and sarcoma viruses, is modulated by sequences in at least five functional domains. A promoter containing a TATA and multiple CCAAT motifs in U3 of the long terminal repeat was absolutely required for transcription. Transcriptional efficiency was greatly augmented by an enhancer immediately upstream, which contained a 22-base-pair repeated sequence. Transcription was further influenced by a negative-acting domain in the 5' region of U3 and two downstream domains in the transcribed non-protein-coding region. One of these latter domains contained a consensus enhancer core sequence and positively affected transcription in both mammalian and avian cells; the other acted negatively in a dog cell line. Transcription from REV-T in vivo required cellular factors which could be competed for specifically by the promoter or enhancer domain. The downstream domains competed with reporter genes containing these domains, but not directly with the U3 sequences. The promoter, enhancer, and the positive-acting downstream domains formed multiple complexes with distinct classes of cellular factors in both avian and mammalian cell extracts. Binding of factors to the promoter and enhancer domains was cooperative when these domains were joined in cis.
Measuring return on investment of outreach by Community Health Workers

Community health workers (CHWs) are effective in improving access to health care, promoting client knowledge and behavior change, and contributing to improved health status of individuals. However, few outreach programs have evaluated the financial impact of CHWs on health care systems and policies. A longitudinal repeated measures design was used to assess the return on investment (ROI) of outreach by CHWs employed by Denver Health Community Voices. Service utilization, charges and reimbursements for 590 underserved men were analyzed 9 months before and after interaction with a CHW. Primary and specialty care visits increased and urgent care, inpatient, and outpatient behavioral health care utilization decreased, resulting in a reduction of monthly uncompensated costs by $14,244. Program costs were $6,229 per month and the ROI was 2.28:1.00, a savings of $95,941 annually. These data provide evidence of economic contributions that CHWs make to a public safety net system and inform policy making regarding program sustainability.
Tying Free Cash Flows To Market Valuations

Last month, in this magazine, this author argued in Fixing Financial Statements: Financial Statement Overhaul that the traditional formats of the primary financial statements—income statement, balance sheet, and cash flow statement—need major redesign to again be useful for meaningful financial analysis, decision-making and value creation. Since the fundamental objective of a business is to increase real shareholder value, this means increasing the net present value (NPV) of the future stream of cash flows. Financial statements must, therefore, put much more emphasis on the free cash flows that a business generates. A vivid example of the different impressions one can get from focusing on profits and cash flows is Xerox Corp. (see page 18). Focusing on profits could suggest Xerox is doing well; free cash flows tell another story.
Quantitative assessment of human beta-globin gene expression in vitro by TaqMan real-time reverse transcription-PCR: comparison with competitive reverse transcription-PCR and application to mutations or deletions in noncoding regions.

β-Thalassemia is a genetic hemolytic disorder characterized by diminished production of β-globin chains, attributable to alterations within coding and noncoding sequences of the β-globin gene (1). Whether noncoding mutations are involved in the decrease of β-globin chain production or are simple polymorphisms remains a difficult issue (2). Although stable transfection with constructs bearing key regulatory β-locus control region elements upstream of the promoter are commonly used to assess the transcriptional effect of noncoding mutations in β-globin (3)(4)(5)(6)(7), discrepant results are still reported, as evidenced recently by the research team that used Northern blotting or ribonuclease protection assay to assess the functional impact of the +10 (-T) deletion (3)(5)(8). Although highly accurate, the competitive reverse transcription-PCR (RT-PCR) technique that we recently developed to quantify the transcriptional effect of genetic alterations in any part of the human β-globin gene is tedious and time-consuming (6). There is a need, therefore, for an expression method that is accurate, rapid, easier to perform, and well controlled quantitatively. In our current study, we developed a TaqMan® real-time quantitative RT-PCR assay (QRT-PCR), using the same in vitro expression model and the following human β-globin variants: −223T→C, −101C→T, −30T→A, +20C→T, IVS-I-108T→C, +10 (-T), and +15653→1577 (6). An additional …
Association between a High BK Virus Load in Urine Samples of Patients with Graft-Versus-Host Disease and Development of Hemorrhagic Cystitis after Hematopoietic Stem Cell Transplantation

ABSTRACT BK virus (BKV) load in urine alone or in combination with acute graft-versus-host disease (GVHD) was correlated to development of hemorrhagic cystitis (HC). BKV load in combination with acute GVHD discriminated the best, while BKV and viral load alone, but not GVHD, still showed predictive ability for HC.
Adaptive extremum seeking of nonisothermal tubular reactor

In this paper, we extend recent results of adaptive extremum seeking control to a class of nonlinear distributed parameter system. We address the real-time optimization of a chemical reaction that occurs in a tubular reactor described by a hyperbolic set of partial differential equations. An estimation and a control algorithm that take into account temperature constraints are developed based on a Lyapunov functional. The result of this algorithm is a late-lumping feedback profile control that steers the system to its optimum.
Retinal vascular calibre and the risk of coronary heart disease-related death

Objective: To examine whether retinal vascular calibre independently predicts risk of coronary heart disease (CHD) -related death. Methods: In a population-based cohort study of 3654 Australians aged ⩾ 49 years, retinal arteriolar and venular calibres were measured from baseline retinal photographs and the arteriole to venule ratio (AVR) was calculated. CHD-related death was confirmed from the Australian National Death Index. Results: Over nine years, 78 women (4.1%) and 114 men (7.8%) had incident CHD-related deaths. In people aged 49–75 years, wider venules were associated with CHD death, with relative risk (RR) 1.8 (95% confidence interval (CI) 1.1 to 2.7) and RR 2.0 (95% CI 1.1 to 3.6) per standard deviation (SD) increase in venular calibre for men and women, respectively, after adjustment for traditional risk factors. Additionally, in women aged 49–75 years, smaller AVR and narrower arterioles were associated with CHD death (RR 1.5, 95% CI 1.1 to 2.2, and RR 1.9, 95% CI 1.0 to 3.5 per SD decrease in AVR and arteriolar calibre, respectively, after adjustment). These associations were not observed in people aged > 75 years. Conclusions: These findings suggest that microvascular disease processes may have a role in CHD development in middle-aged people, particularly in women. Retinal photography may be useful in cardiovascular risk prediction.
Action Recognition Based on Local Fisher Discriminant Analysis and Mix Encoding

Action recognition has been one of the most popular fields of computer vision. This paper presents a novel approach to action recognition problem using the dimension reduction method, local fisher discriminant analysis, to reduce the dimension of feature descriptors as the preprocessing step after feature extraction. We propose to use sparse matrix and randomized kd-tree to modify and accelerate the standard local fisher discriminant analysis and propose the modified local fisher discriminant analysis. We also propose an effective feature encoding called mix encoding to combine fisher vector encoding and locality-constrained linear coding to obtain video representations. The experiments show the methods clearly improve the recognition accuracy. Experimental results show our method outperforms our baseline method and can be the state of the art in the KTH dataset.
Trends in the use of gastrostomies at a tertiary paediatric referral centre

Abstract Objectives The aims of this study were to describe the population of paediatric patients undergoing gastrostomy placement at a Norwegian tertiary referral centre and to investigate trends over time in patient characteristics and operative technique. Materials and methods Patients <15 years of age getting a primary gastrostomy from 1994 to 2012 were included in this retrospective observational study. Patient data were collected from medical records and the National Registry. Results Six-hundred forty-nine patients with a median age of 1.2 years [gestational week 30–14.9 years] were included. Neurological disorders (ND) was the most common underlying group of diagnosis (n = 311, 48%), followed by cardiac disease 104 (16%), congenital anomalies 85 (13%), respiratory disease 43 (7%), malignancy 29 (5%), and others 77 (12%). At follow-up, 162 (25%) patients were dead. A percutaneous endoscopic technique (PEG) was used in 401 (62%) patients, open surgery (OPEN) in 201 (31%) and laparoscopy (LAP) in 47 (7%). The number of gastrostomies per year more than doubled during the period (p < 0.001). More patients with cardiac disease and congenital anomalies were given a gastrostomy during the last years (all p < 0.05), whereas the number of patients with ND remained stable. Furthermore, there has been a decrease in median age and an increase in the number of PEG and LAP (p < 0.05). Conclusion The number of gastrostomy insertions has increased from 1994 to 2012. NDs is the most common underlying diagnosis in patients receiving a gastrostomy, PEG is the most common technique and patient characteristics have changed during the study period.
An evaluation of routing in vehicular networks using analytic hierarchy process

This paper presents a comprehensive study of the performance of routing protocols in distributed vehicular networks. We propose a novel and efficient routing protocol, namely cross-layer, weighted, position-based routing, which considers link quality, mobility and utilisation of nodes in a cross layer manner to make effective position-based forwarding decisions. An analytic hierarchy process approach is utilised to combine multiple decision criteria into a single weighting function and to perform a comparative evaluation of the effects of aforementioned criteria on forwarding decisions. Comprehensive simulations are performed in realistic representative urban scenarios with synthetic and real traffic. Insights on the effect of different communication and mobility parameters are obtained. The results demonstrate that the proposed protocol outperforms existing routing protocols for vehicular ad hoc networks, including European Telecommunications Standards Institute ETSI's proposed greedy routing protocol, greedy traffic aware routing protocol and advanced greedy forwarding in terms of combined packet delivery ratio, end-to-end delay and overhead. Copyright © 2015 John Wiley & Sons, Ltd.
Cancer incidence among European man-made vitreous fiber production workers.

OBJECTIVES This study analyzed cancer incidence among man-made vitreous fiber workers. METHODS A cancer incidence follow-up was conducted among 3685 rock-slag wool (RSW) and 2611 glass wool (GW) production workers employed for > or =1 year in Denmark, Finland, Norway, or Sweden, and the standardized incidence ratios (SIR) were calculated on the basis of national incidence rates. RESULTS Overall cancer incidence was close to expectation. Lung cancer incidence was increased among the RSW [SIR 1.08, 95% confidence interval (95% CI) 0.85-1.36] and GW (SIR 1.28, 95% CI 0.91-1.74) workers. For both subcohorts, a trend was suggested for time since first employment (P-value for linear trend 0.1 and 0.2, respectively). Neither subcohort showed an association with employment during the early technological phase, when fiber exposure was high. The incidence of oral, pharyngeal, and laryngeal cancer was increased among the RSW (SIR 1.46, 95% CI 0.99-2.07) and the GW (SIR 1.41, 95% CI 0.80-2.28) subcohorts. Despite a trend in risk for these neoplasms among the GW workers with time since first employment, the lack of a positive relation with other indirect indicators of fiber exposure points against a causal interpretation. No association between RSW or GW exposure and the risk of other neoplasms was suggested. CONCLUSIONS These lung cancer results are similar to those of a mortality study that included a larger number of factories. For other cancers there was no suggestion of an association with RSW or GW exposure.