Policy for Accommodating and Adjustment of Utilities on the Primary Road System, 2005

This chapter covers initial placement, adjustment, and maintenance of utility facilities in, on, above or below the right-of-way of primary highways, including attachments to primary highway structures. It embodies the basic specifications and standards needed, to ensure the safety of the highway user and the integrity of the highway. (2005 revision to 1992 policy.)

Emergence of novel domains in proteins

Proteins are composed of a combination of discrete, well-defined, sequence domains, associated with specific functions that have arisen at different times during evolutionary history. The emergence of novel domains is related to protein functional diversification and adaptation. But currently little is known about how novel domains arise and how they subsequently evolve. To gain insights into the impact of recently emerged domains in protein evolution we have identified all human young protein domains that have emerged in approximately the past 550 million years. We have classified them into vertebrate-specific and mammalian-specific groups, and compared them to older domains. We have found 426 different annotated young domains, totalling 995 domain occurrences, which represent about 12.3% of all human domains. We have observed that 61.3% of them arose in newly formed genes, while the remaining 38.7% are found combined with older domains, and have very likely emerged in the context of a previously existing protein. Young domains are preferentially located at the N-terminus of the protein, indicating that, at least in vertebrates, novel functional sequences often emerge there. Furthermore, young domains show significantly higher non-synonymous to synonymous substitution rates than older domains using human and mouse orthologous sequence comparisons. This is also true when we compare young and old domains located in the same protein, suggesting that recently arisen domains tend to evolve in a less constrained manner than older domains. We conclude that proteins tend to gain domains over time, becoming progressively longer. We show that many proteins are made of domains of different age, and that the fastest evolving parts correspond to the domains that have been acquired more recently.

Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene.

Mutations in the FGD1 gene have been shown to cause Aarskog-Scott syndrome (AAS), or facio-digito-genital dysplasia (OMIM#305400), an X-linked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed AAS. In the present study, we report on our experience of screening for mutations in the FGD1 gene in a cohort of 60 European patients with a clinically suspected diagnosis of AAS. We identified nine novel mutations in 11 patients (detection rate of 18.33%), including three missense mutations (p.R402Q; p.S558W; p.K748E), four truncating mutations (p.Y530X; p.R656X; c.806delC; c.1620delC), one in-frame deletion (c.2020_2022delGAG) and the first reported splice site mutation (c.1935+3A>C). A recurrent mutation (p.R656X) was detected in three independent families. We did not find any evidence for phenotype-genotype correlations between type and position of mutations and clinical features. In addition to the well-established phenotypic features of AAS, other clinical features are also reported and discussed.

The effect of mountain bike suspensions on vibrations and off-road uphill performance.

AIM: This study evaluates the effect of front suspension (FS) and dual suspension (DS) mountain-bike on performance and vibrations during off-road uphill riding. METHODS: Thirteen male cyclists (27+/-5 years, 70+/-6 kg, VO(2max)59+/-6 mL.kg(-1).min(-1), mean+/-SD) performed, in a random sequence, at their lactate threshold, an off-road uphill course (1.69 km, 212 m elevation gain) with both type of bicycles. Variable measured: a) VO(2) consumption (K4b2 analyzer, Cosmed), b) power output (SRM) c) gain in altitude and d) 3-D accelerations under the saddle and at the wheel (Physilog, EPFL, Switzerland). Power spectral analy- sis (Fourier) was performed from the vertical acceleration data. RESULTS: Respectively for the FS and DS mountain bike: speed amounted to 7.5+/-0.7 km.h(-1) and 7.4+/-0.8 km.h(-1), (NS), energy expenditure 1.39+/-0.16 kW and 1.38+/-0.18, (NS), gross efficiency 0.161+/-0.013 and 0.159+/-0.013, (NS), peak frequency of vibration under the saddle 4.78+/-2.85 Hz and 2.27+/-0.2 Hz (P<0.01) and median-frequency of vertical displacements of the saddle 9.41+/-1.47 Hz and 5.78+/-2.27 Hz (P<0.01). CONCLUSION: Vibrations at the saddle level of the DS bike are of low frequencies whereas those of the FS bike are mostly of high frequencies. In the DS bike, the torque produced by the cyclist at the pedal level may generate low frequency vibrations. We conclude that the DS bike absorbs more high frequency vibrations, is more comfortable and performs as well as the FS bicycle.

A novel approach to reducing number of sensing units for wearable gait analysis systems.

Gait analysis methods to estimate spatiotemporal measures, based on two, three or four gyroscopes attached on lower limbs have been discussed in the literature. The most common approach to reduce the number of sensing units is to simplify the underlying biomechanical gait model. In this study, we propose a novel method based on prediction of movements of thighs from movements of shanks. Datasets from three previous studies were used. Data from the first study (ten healthy subjects and ten with Parkinson's disease) were used to develop and calibrate a system with only two gyroscopes attached on shanks. Data from two other studies (36 subjects with hip replacement, seven subjects with coxarthrosis, and eight control subjects) were used for comparison with the other methods and for assessment of error compared to a motion capture system. Results show that the error of estimation of stride length compared to motion capture with the system with four gyroscopes and our new method based on two gyroscopes was close ( -0.8 ±6.6 versus 3.8 ±6.6 cm). An alternative with three sensing units did not show better results (error: -0.2 ±8.4 cm). Finally, a fourth that also used two units but with a simpler gait model had the highest bias compared to the reference (error: -25.6 ±7.6 cm). We concluded that it is feasible to estimate movements of thighs from movements of shanks to reduce number of needed sensing units from 4 to 2 in context of ambulatory gait analysis.

Optimization of Snow Drifting Mitigation and Control Methods for Iowa Conditions Part II, TR-626, 2015

Blowing and drifting of snow is a major concern for transportation efficiency and road safety in regions where their development is common. One common way to mitigate snow drift on roadways is to install plastic snow fences. Correct design of snow fences is critical for road safety and maintaining the roads open during winter in the US Midwest and other states affected by large snow events during the winter season and to maintain costs related to accumulation of snow on the roads and repair of roads to minimum levels. Of critical importance for road safety is the protection against snow drifting in regions with narrow rights of way, where standard fences cannot be deployed at the recommended distance from the road. Designing snow fences requires sound engineering judgment and a thorough evaluation of the potential for snow blowing and drifting at the construction site. The evaluation includes site-specific design parameters typically obtained with semi-empirical relations characterizing the local transport conditions. Among the critical parameters involved in fence design and assessment of their post-construction efficiency is the quantification of the snow accumulation at fence sites. The present study proposes a joint experimental and numerical approach to monitor snow deposits around snow fences, quantitatively estimate snow deposits in the field, asses the efficiency and improve the design of snow fences. Snow deposit profiles were mapped using GPS based real-time kinematic surveys (RTK) conducted at the monitored field site during and after snow storms. The monitored site allowed testing different snow fence designs under close to identical conditions over four winter seasons. The study also discusses the detailed monitoring system and analysis of weather forecast and meteorological conditions at the monitored sites. A main goal of the present study was to assess the performance of lightweight plastic snow fences with a lower porosity than the typical 50% porosity used in standard designs of such fences. The field data collected during the first winter was used to identify the best design for snow fences with a porosity of 50%. Flow fields obtained from numerical simulations showed that the fence design that worked the best during the first winter induced the formation of an elongated area of small velocity magnitude close to the ground. This information was used to identify other candidates for optimum design of fences with a lower porosity. Two of the designs with a fence porosity of 30% that were found to perform well based on results of numerical simulations were tested in the field during the second winter along with the best performing design for fences with a porosity of 50%. Field data showed that the length of the snow deposit away from the fence was reduced by about 30% for the two proposed lower-porosity (30%) fence designs compared to the best design identified for fences with a porosity of 50%. Moreover, one of the lower-porosity designs tested in the field showed no significant snow deposition within the bottom gap region beneath the fence. Thus, a major outcome of this study is to recommend using plastic snow fences with a porosity of 30%. It is expected that this lower-porosity design will continue to work well for even more severe snow events or for successive snow events occurring during the same winter. The approach advocated in the present study allowed making general recommendations for optimizing the design of lower-porosity plastic snow fences. This approach can be extended to improve the design of other types of snow fences. Some preliminary work for living snow fences is also discussed. Another major contribution of this study is to propose, develop protocols and test a novel technique based on close range photogrammetry (CRP) to quantify the snow deposits trapped snow fences. As image data can be acquired continuously, the time evolution of the volume of snow retained by a snow fence during a storm or during a whole winter season can, in principle, be obtained. Moreover, CRP is a non-intrusive method that eliminates the need to perform man-made measurements during the storms, which are difficult and sometimes dangerous to perform. Presently, there is lots of empiricism in the design of snow fences due to lack of data on fence storage capacity on how snow deposits change with the fence design and snow storm characteristics and in the estimation of the main parameters used by the state DOTs to design snow fences at a given site. The availability of such information from CRP measurements should provide critical data for the evaluation of the performance of a certain snow fence design that is tested by the IDOT. As part of the present study, the novel CRP method is tested at several sites. The present study also discusses some attempts and preliminary work to determine the snow relocation coefficient which is one of the main variables that has to be estimated by IDOT engineers when using the standard snow fence design software (Snow Drift Profiler, Tabler, 2006). Our analysis showed that standard empirical formulas did not produce reasonable values when applied at the Iowa test sites monitored as part of the present study and that simple methods to estimate this variable are not reliable. The present study makes recommendations for the development of a new methodology based on Large Scale Particle Image Velocimetry that can directly measure the snow drift fluxes and the amount of snow relocated by the fence.

EL Portafolio docente como estrategia formativa innovadora del profesorado novel universitario. Un estudio de casos

Este artículo sintetiza los resultados y las principales conclusiones de una investigación realizada en la Universidad de Barcelona sobre el tema del portafolio docente, un fenómeno bastante reciente en el campo de la formación del profesorado en general, y en la del docente universitario en particular. La introducción de esta herramienta en la Enseñanza universitaria se debe a la Asociación Canadiense de Profesores de Universidad (en la década de los ochenta), que la empleó para la habilitación y la evaluación de docentes. Sin embargo, en este trabajo se parte de la idea de que los portafolios docentes tienen también una vertiente formativa y resultan útiles en la mejora y el desarrollo profesional del profesorado universitario novel. Explorar este aspecto es el objetivo de nuestro estudio. Se ha elegido, como campo de aplicación, el profesorado novel de la Universidad de Barcelona, que ha elaborado un portafolio docente en los cursos de Iniciación en la Docencia Universitaria. El enfoque usado ha sido cualitativo y como estrategia metodológica hemos optado por el estudio de casos múltiple, dado que la muestra está constituida por 10 profesores universitarios noveles de diferentes áreas de conocimiento. Para recoger y registrar la información, los instrumentos empleados fueron la entrevista en profundidad y el análisis de documentos. Los resultados apuntan a que el verdadero valor del portafolio docente reside en su potencial formativo y para el desarrollo profesional del profesorado universitario novel. También revelan que el portafolio es una herramienta valiosa para un nuevo profesionalismo docente, que se orienta a la reflexión sobre la propia práctica docente y al desarrollo de una enseñanza más acorde con las exigencias de la nueva sociedad del conocimiento.

Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells.

Pluripotency in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is regulated by three transcription factors-OCT3/4, SOX2, and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behavior of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11) and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more naïve cell state compared to hESCs and how to convert primed hESCs back to the naïve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.

A novel approach to characterize clonality and differentiation of human melanoma-specific T cell responses: spontaneous priming and efficient boosting by vaccination.

Despite major progress in T lymphocyte analysis in melanoma patients, TCR repertoire selection and kinetics in response to tumor Ags remain largely unexplored. In this study, using a novel ex vivo molecular-based approach at the single-cell level, we identified a single, naturally primed T cell clone that dominated the human CD8(+) T cell response to the Melan-A/MART-1 Ag. The dominant clone expressed a high-avidity TCR to cognate tumor Ag, efficiently killed tumor cells, and prevailed in the differentiated effector-memory T lymphocyte compartment. TCR sequencing also revealed that this particular clone arose at least 1 year before vaccination, displayed long-term persistence, and efficient homing to metastases. Remarkably, during concomitant vaccination over 3.5 years, the frequency of the pre-existing clone progressively increased, reaching up to 2.5% of the circulating CD8 pool while its effector functions were enhanced. In parallel, the disease stabilized, but subsequently progressed with loss of Melan-A expression by melanoma cells. Collectively, combined ex vivo analysis of T cell differentiation and clonality revealed for the first time a strong expansion of a tumor Ag-specific human T cell clone, comparable to protective virus-specific T cells. The observed successful boosting by peptide vaccination support further development of immunotherapy by including strategies to overcome immune escape.

Investigation of the Lane-Wells Road Logger, HR-113, 1966

The Lane-Wells Road Logger was utilized primarily to determine the feasibility of employing such a device for moisture and density control in Iowa highway construction. A secondary objective was the use of the Road Logger to obtain information concerning moisture content and density during and after construction. Correlation studies with conventional test results required a small portion of the lease period. Practically all phases of construction and most materials utilized in base and surface courses were surveyed. Results of this study were good, in general, with the Road Logger indicating dry density slightly higher and the moisture content slightly lower than conventional results in most instances. Economic feasibility seemed to pose the greatest problem for the acceptance of the Road Logger as a standard compaction control device. It would appear from the findings of this study that probably only large projects, or several smaller contracts tested simultaneously, could justify the expense of the Logger. A total of about 128 miles were surveyed with the Logger during the lease period. Approximately 16 days of downtime due to minor breakdowns were recorded. Inclement weather forcing construction delays resulted in several idle days in which the Logger's full capabilities were not realized.

Road Profile Adjustment Computer Program, HR-143, 1969

A computer program to adjust roadway profiles has been developed to serve as an aid to the county engineers of the State of Iowa. Many hours are spent reducing field notes and calculating adjusted roadway profiles to prepare an existing roadway for paving that will produce a high quality ride and be as maintenance free as possible. Since the computer is very well adapted to performing long tedious tasks; programming this work for a computer would result in freeing the engineer of these tasks. Freed from manual calculations, the engineer is able to spend more time in solving engineering problems. The type of roadway that this computer program is designed to adjust is a road that at sometime. in its history was graded to a finished subgrade. After a period of time, this road is to receive a finished paved surface. The problem then arises whether to bring the existing roadway up to the de signed grade or to make profile adjustments and comprise between the existing and the design profiles. In order to achieve the latter condition using this program, the engineer needs to give the computer only a minimum amount of information.

TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration.

Inflammation participates in tissue repair through multiple mechanisms including directly regulating the cell fate of resident progenitor cells critical for successful regeneration. Upon surveying target cell types of the TNF ligand TWEAK, we observed that TWEAK binds to all progenitor cells of the mesenchymal lineage and induces NF-kappaB activation and the expression of pro-survival, pro-proliferative and homing receptor genes in the mesenchymal stem cells, suggesting that this pro-inflammatory cytokine may play an important role in controlling progenitor cell biology. We explored this potential using both the established C2C12 cell line and primary mouse muscle myoblasts, and demonstrated that TWEAK promoted their proliferation and inhibited their terminal differentiation. By generating mice deficient in the TWEAK receptor Fn14, we further showed that Fn14-deficient primary myoblasts displayed significantly reduced proliferative capacity and altered myotube formation. Following cardiotoxin injection, a known trigger for satellite cell-driven skeletal muscle regeneration, Fn14-deficient mice exhibited reduced inflammatory response and delayed muscle fiber regeneration compared with wild-type mice. These results indicate that the TWEAK/Fn14 pathway is a novel regulator of skeletal muscle precursor cells and illustrate an important mechanism by which inflammatory cytokines influence tissue regeneration and repair. Coupled with our recent demonstration that TWEAK potentiates liver progenitor cell proliferation, the expression of Fn14 on all mesenchymal lineage progenitor cells supports a broad involvement of this pathway in other tissue injury and disease settings.

A novel cyclosporin a aqueous formulation for dry eye treatment: in vitro and in vivo evaluation.

PURPOSE: The aim of the present study was the in vitro and in vivo evaluation of a novel aqueous formulation based on polymeric micelles for the topical delivery of cyclosporine A for dry eye treatment. METHODS: In vitro experiments were carried out on primary rabbit corneal cells, which were characterized by immunocytochemistry using fluorescein-labeled lectin I/isolectin B4 for the endothelial cells and mouse monoclonal antibody to cytokeratin 3+12 for the epithelial ones. Living cells were incubated for 1 hour or 24 hours with a fluorescently labeled micelle formulation and analyzed by fluorescence microscopy. In vivo evaluations were done by Schirmer test, osmolarity measurement, CyA kinetics in tears, and CyA ocular distribution after topical instillation. A 0.05% CyA micelle formulation was compared to a marketed emulsion (Restasis). RESULTS: The in vitro experiments showed the internalization of micelles in the living cells. The Schirmer test and osmolarity measurements demonstrated that micelles did not alter the ocular surface properties. The evaluation of the tear fluid gave similar CyA kinetics values: AUC = 2339 ± 1032 min*μg/mL and 2321 ± 881.63; Cmax = 478 ± 111 μg/mL and 451 ± 74; half-life = 36 ± 9 min and 28 ± 9 for the micelle formulation and Restasis, respectively. The ocular distribution investigation revealed that the novel formulation delivered 1540 ± 400 ng CyA/g tissue to the cornea. CONCLUSIONS: The micelle formulation delivered active CyA into the cornea without evident negative influence on the ocular surface properties. This formulation could be applied for immune-related ocular surface diseases.

Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained.The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids. Copyright © 2010 John Wiley & Sons, Ltd.

Total Cost of Transportation Analysis of Road and Highway Issues, HR-388, 2002

In the administration, planning, design, and maintenance of road systems, transportation professionals often need to choose between alternatives, justify decisions, evaluate tradeoffs, determine how much to spend, set priorities, assess how well the network meets traveler needs, and communicate the basis for their actions to others. A variety of technical guidelines, tools, and methods have been developed to help with these activities. Such work aids include design criteria guidelines, design exception analysis methods, needs studies, revenue allocation schemes, regional planning guides, designation of minimum standards, sufficiency ratings, management systems, point based systems to determine eligibility for paving, functional classification, and bridge ratings. While such tools play valuable roles, they also manifest a number of deficiencies and are poorly integrated. Design guides tell what solutions MAY be used, they aren't oriented towards helping find which one SHOULD be used. Design exception methods help justify deviation from design guide requirements but omit consideration of important factors. Resource distribution is too often based on dividing up what's available rather than helping determine how much should be spent. Point systems serve well as procedural tools but are employed primarily to justify decisions that have already been made. In addition, the tools aren't very scalable: a system level method of analysis seldom works at the project level and vice versa. In conjunction with the issues cited above, the operation and financing of the road and highway system is often the subject of criticisms that raise fundamental questions: What is the best way to determine how much money should be spent on a city or a county's road network? Is the size and quality of the rural road system appropriate? Is too much or too little money spent on road work? What parts of the system should be upgraded and in what sequence? Do truckers receive a hidden subsidy from other motorists? Do transportation professions evaluate road situations from too narrow of a perspective? In considering the issues and questions the author concluded that it would be of value if one could identify and develop a new method that would overcome the shortcomings of existing methods, be scalable, be capable of being understood by the general public, and utilize a broad viewpoint. After trying out a number of concepts, it appeared that a good approach would be to view the road network as a sub-component of a much larger system that also includes vehicles, people, goods-in-transit, and all the ancillary items needed to make the system function. Highway investment decisions could then be made on the basis of how they affect the total cost of operating the total system. A concept, named the "Total Cost of Transportation" method, was then developed and tested. The concept rests on four key principles: 1) that roads are but one sub-system of a much larger 'Road Based Transportation System', 2) that the size and activity level of the overall system are determined by market forces, 3) that the sum of everything expended, consumed, given up, or permanently reserved in building the system and generating the activity that results from the market forces represents the total cost of transportation, and 4) that the economic purpose of making road improvements is to minimize that total cost. To test the practical value of the theory, a special database and spreadsheet model of Iowa's county road network was developed. This involved creating a physical model to represent the size, characteristics, activity levels, and the rates at which the activities take place, developing a companion economic cost model, then using the two in tandem to explore a variety of issues. Ultimately, the theory and model proved capable of being used in full system, partial system, single segment, project, and general design guide levels of analysis. The method appeared to be capable of remedying many of the existing work method defects and to answer society's transportation questions from a new perspective.