Expression of the GABAA receptor associated protein Gec1 is circadian and dependent upon the cellular clock machinery in GnRH secreting GnV-3 cells.

The timely regulation of gonadotropin-releasing hormone (GnRH) secretion requires a GABAergic signal. We hypothesized that GEC1, a protein promoting the transport of GABA(A) receptors, could represent a circadian effector in GnRH neurons. First, we demonstrated that gec1 is co-expressed with the GABA(A) receptor in hypothalamic rat GnRH neurons. We also confirmed that the clock genes per1, cry1 and bmal1 are expressed and oscillate in GnRH secreting GnV-3 cells. Then we could show that gec1 is expressed in GnV-3 cells, and oscillates in a manner temporally related to the oscillations of the clock transcription factors. Furthermore, we could demonstrate that these oscillations depend upon Per1 expression. Finally, we observed that GABA(A) receptor levels at the GnV-3 cell membrane are timely modulated following serum shock. Together, these data demonstrate that gec1 expression is dependent upon the circadian clock machinery in GnRH-expressing neurons, and suggest for the first time that the level of GABA(A) receptor at the cell membrane may be under timely regulation. Overall, they provide a potential mechanism for the circadian regulation of GnRH secretion by GABA, and may also be relevant to the general understanding of circadian rhythms.

Perspectives for Forensic Intelligence in anti-doping: Thinking outside of the box.

Today's approach to anti-doping is mostly centered on the judicial process, despite pursuing a further goal in the detection, reduction, solving and/or prevention of doping. Similarly to decision-making in the area of law enforcement feeding on Forensic Intelligence, anti-doping might significantly benefit from a more extensive gathering of knowledge. Forensic Intelligence might bring a broader logical dimension to the interpretation of data on doping activities for a more future-oriented and comprehensive approach instead of the traditional case-based and reactive process. Information coming from a variety of sources related to doping, whether directly or potentially, would feed an organized memory to provide real time intelligence on the size, seriousness and evolution of the phenomenon. Due to the complexity of doping, integrating analytical chemical results and longitudinal monitoring of biomarkers with physiological, epidemiological, sociological or circumstantial information might provide a logical framework enabling fit for purpose decision-making. Therefore, Anti-Doping Intelligence might prove efficient at providing a more proactive response to any potential or emerging doping phenomenon or to address existing problems with innovative actions or/and policies. This approach might prove useful to detect, neutralize, disrupt and/or prevent organized doping or the trafficking of doping agents, as well as helping to refine the targeting of athletes or teams. In addition, such an intelligence-led methodology would serve to address doping offenses in the absence of adverse analytical chemical evidence.

SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools.

BACKGROUND: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing. RESULTS: We present the Systems Biology Markup Language (SBML) Qualitative Models Package ("qual"), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models. CONCLUSIONS: SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks.

Involvement of gap junctional intercellular communication in the pathophysiology of inflammation

SUMMARY Inflammation has evolved as a mechanism to defend the body against invading microorganisms and to respond to injury. It requires the coordinated response of a large number of cell types from the whole organism in a time- and space-dependent fashion. This coordination involves several cell-cell communication mechanisms. Exchange of humoral mediators such as cytokines is a major one. Moreover, direct contact between cells happens and plays a primordial role, for example when macrophages present antigens to lymphocytes. Contact between endothelial cells and leucocytes occurs when the latter cross the blood vessel barrier and transmigrate to the inflammatory site. A particular way by which cells communicate with each other in the course of inflammation, which at this time starts to gain attention, is the intercellular communication mediated by gap junctions. Gap junctions are channels providing a direct pathway (i.e. without transit through the extracellular space) for the diffusion of small molecules between adjacent cells. This process is known as gap junctional intercellular communication (GJIC). The general aim of this thesis was to study a possible involvement of GJIC in the pathophysiology of inflammation. A first part of the work was dedicated to study the implication of GJIC in the modification of vascular endothelial function by inflammation. In a second part, we were interested in the possible role of GJIC in the transmigration of neutrophil polymorphonuclear leucocytes through the endothelium. The main positive finding of this work is that acute inflammation preferentially modulates the expression of connexin 40 (Cx40), a gap junction protein specifically expressed in vascular endothelium. The modulation could be towards overexpression (aortic endothelium of septic rats) or towards downregulation (acutely inflamed mouse lung). We put a lot of efforts in search of possible functions of these modulations, in two directions: a potential protective role of Cx40 increased expression against sepsis-induced endothelial dysfunction, and a facilitating role of Cx40 decreased expression in neutrophil transmigration. To pursue both directions, it seemed logical to study the impact of Cx40 deletion using knock-out mice. Concerning the potential protective role of Cx40 overexpression we encountered a roadblock as we observed, in the aorta, a Cx40 downregulation in wild type mouse whereas Cx40 was upregulated in the rat. Regarding the second direction and using an in vivo approach, we observed that pulmonary neutrophil transmigration was not affected by the genetic deletion of Cx40. In spite of their negative nature, these results are the very first ones regarding the potential implication of GJIC concerning leucocyte transmigration in vivo. Because this process involves such tight cell-cell physical contacts, the hypothesis for a role of GJIC remains attractive.

Mourning becomes Electra d'Eugene O'Neill: Èsquil i Plató per a crear un drama fosc?

The fundamental debt of E. O'Neill's Mourning Becomes Electra to Aeschylus, and to a lesser degree to Sophocles and Euripides, has been always recognised but, according to the author's hypothesis, O'Neill might have taken advantage of the Platonic image of the cave in order to magnify his both Greek and American drama. It is certainly a risky hypothesis that stricto sensu cannot be proved, but it is also reader's right to evaluate the plausibility and the possible dramatic benefit derived from such a reading. Besides indicating to what degree some of the essential themes of Platonic philosophy concerning darkness, light or the flight from the prison of the material world are not extraneous to O'Neill's work, the author proves he was aware of the Platonic image of the cave thanks to its capital importance in the work of some of his intellectual mentors such as F. Nietzsche or Oscar Wilde. Nevertheless, the most significant aim of the author's article is to emphasize both the dramatic benefits and the logical reflections derived, as said before, from reading little by little O'Neill's drama bearing in mind the above mentioned Platonic parameter.

Mourning becomes Electra de Eugene O'Neill: ¿Esquilo y la caverna de Platón para crear un drama oscuro?

The fundamental debt of E. O'Neill's Mourning Becomes Electra to Aeschylus, and to a lesser degree to Sophocles and Euripides, has been always recognised but, according to the author's hypothesis, O'Neill might have taken advantage of the Platonic image of the cave in order to magnify his both Greek and American drama. It is certainly a risky hypothesis that stricto sensu cannot be proved, but it is also reader's right to evaluate the plausibility and the possible dramatic benefit derived from such a reading. Besides indicating to what degree some of the essential themes of Platonic philosophy concerning darkness, light or the flight from the prison of the material world are not extraneous to O'Neill's work, the author proves he was aware of the Platonic image of the cave thanks to its capital importance in the work of some of his intellectual mentors such as F. Nietzsche or Oscar Wilde. Nevertheless, the most significant aim of the author's article is to emphasize both the dramatic benefits and the logical reflections derived, as said before, from reading little by little O'Neill's drama bearing in mind the above mentioned Platonic parameter.

Greek misogynist tradition in Andreas Capellanus's De amore

The title of this brief article quite clearly illustrates its aims and evident limitations. In principle, a search for a Greek basis of the misogynist content of Andreas Capellanus's De amore is likely to lead researchers to focus on analysis of the sources -Greek sources, of course. However, there is no doubt that Ovid, the most frequently quoted ancient author, in this case the structural source, above all his Ars Amatoria, Remedia Amoris and Heroides, which is quite logical in light of the remarkable presence and influence of Ovid's works throughout that time. There was also a good knowledge of the works of Cicero, Virgil, Horace and Juvenal. However, other classical authors, even the Greeks -those who were known then-, were undoubtedly read in the schools, but the knowledge of their works was certainly superficial. Furthermore, given the scholastic method followed in De amore, it would be absurd not to consider the use of many quotations that appeared in the Compendia and in handbooks of religious instruction.

Interpretation: Printed Document Examination and Evidence

The literature dealing with the interpretation of results of examinations performed on "printed" documents is very limited. The absence of published literature reflects the absence of formal guidelines to help scientists assess the relationship between a questioned document and a particular printing technology. Generally, every printout, independent of the printing technology, may bear traces induced by characteristics of manufacture and/or acquired features of the printing device. A logical approach to help the scientist in the formal interpretation of such findings involves the consideration of a likelihood ratio. Three examples aim to show the application of this approach.

Reforming the Iowa Civil Justice System, January 30, 2012

Executive Summary I. Survey The Task Force conducted a wide-ranging survey of more than 9,000 licensed Iowa attorneys and judges to obtain their input on a variety of civil justice system topics. The survey results helped inform the Task Force of problem areas in Iowa’s civil justice system. II. Two-Tier Justice System The Task Force recommends a pilot program based on a two-tier civil justice system. A two-tier system would streamline litigation processes—including rules of evidence and discovery disclosures—and reduce litigation costs of certain cases falling below a threshold dollar value. III. One Judge/One Case and Date Certain for Trial Some jurisdictions in Iowa have adopted one judge/one case and date certain for trial in certain cases. The assignment of one judge to each case for the life of the matter and the establishment of dates certain for civil trials could enhance Iowans’ access to the courts, improve judicial management, promote consistency and adherence to deadlines, and reduce discovery excesses. IV. Discovery Processes Reforms addressing inefficient discovery processes will reduce delays in and costs of litigation. Such measures include adopting an aspirational purpose for discovery rules to “secure the just, speedy, and inexpensive determination of every action,” holding discovery proportional to the size and nature of the case, requiring initial disclosures, limiting the number of expert witnesses, and enforcing existing rules. V. Expert Witness Fees The Task Force acknowledges the probable need to revisit the statutory additional daily compensation limit for expert witness fees. Leaving the compensation level to the discretion of the trial court is one potential solution. VI. Jurors Additions to the standard juror questionnaire would provide a better understanding of the potential jurors’ backgrounds and suitability for jury service. The Task Force encourages adoption of more modern juror educational materials and video. Rehabilitation of prospective jurors who express an unwillingness or inability to be fair should include a presumption of dismissal. VII. Video and Teleconferencing Options When court resources are constrained both by limited numbers of personnel and budget cuts, it is logical to look to video and teleconferencing technology to streamline the court process and reduce costs. The judicial branch should embrace technological developments in ways that will not compromise the fairness, dignity, solemnity, and decorum of judicial proceedings. VIII. Court-Annexed Alternative Dispute Resolution(ADR) Litigants and practitioners in Iowa are generally satisfied with the current use of private, voluntary ADR for civil cases. There is concern, however, that maintaining the status quo may have steep future costs. Court-annexed ADR is an important aspect of any justice system reform effort, and the Task Force perceives benefits and detriments to reforming this aspect of the Iowa civil justice system. IX. Relaxed Requirement of Findings of Fact and Conclusions of Law A rule authorizing parties to waive findings of fact and conclusions of law could expedite resolution of nonjury civil cases. X. Business (Specialty) Courts Specialty business courts have achieved widespread support across the country. In addition, specialty courts provide excellent vehicles for implementing or piloting other court innovations that may be useful in a broader court system context. A business specialty court should be and could be piloted in Iowa within the existing court system framework of the Iowa Judicial Branch. Appendix included as a separate document, is 176 pages.

Enhanced recovery after surgery: are we ready, and can we afford not to implement these pathways for patients undergoing radical cystectomy?

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes.

Adaptive tracking of EEG oscillations.

Neuronal oscillations are an important aspect of EEG recordings. These oscillations are supposed to be involved in several cognitive mechanisms. For instance, oscillatory activity is considered a key component for the top-down control of perception. However, measuring this activity and its influence requires precise extraction of frequency components. This processing is not straightforward. Particularly, difficulties with extracting oscillations arise due to their time-varying characteristics. Moreover, when phase information is needed, it is of the utmost importance to extract narrow-band signals. This paper presents a novel method using adaptive filters for tracking and extracting these time-varying oscillations. This scheme is designed to maximize the oscillatory behavior at the output of the adaptive filter. It is then capable of tracking an oscillation and describing its temporal evolution even during low amplitude time segments. Moreover, this method can be extended in order to track several oscillations simultaneously and to use multiple signals. These two extensions are particularly relevant in the framework of EEG data processing, where oscillations are active at the same time in different frequency bands and signals are recorded with multiple sensors. The presented tracking scheme is first tested with synthetic signals in order to highlight its capabilities. Then it is applied to data recorded during a visual shape discrimination experiment for assessing its usefulness during EEG processing and in detecting functionally relevant changes. This method is an interesting additional processing step for providing alternative information compared to classical time-frequency analyses and for improving the detection and analysis of cross-frequency couplings.

Executive Summary, Feasibility Report on Proposed Amtrak Service Quad Cities-Chicago, January 7, 2008

Since the introduction of expanded levels of intrastate service on October 30, 2006, Amtrak trains in Illinois have produced impressive gains in both ridership and ticket revenue. This success and continuing stakeholder support has given rise to a formal request from the Illinois Department of Transportation (“Ill. DOT”) to Amtrak to develop a feasibility study regarding possible service consisting of a morning and an evening train in each direction between Chicago and the Quad Cities. The area between Chicago and the Quad Cities includes many rapidly growing communities. From Chicago toward the West and South, many towns and cities have experienced double digit growth increases in population since the year 2000. Southern DuPage, Cook and Will counties have seen especially strong growth, pressuring highway infrastructure, utilities, and schools. Community development and highway congestion are readily apparent when traveling the nearly 3 hour, 175 mile route between Chicago and the Quad Cities. As information, there are only three weekday round trip bus frequencies available between Chicago and the Quad Cities. The Quad City International Airport offers a total of 10 daily scheduled round trip flights to Chicago's O'Hare International Airport via two separate carriers flying regional jets. The Quad Cities (Davenport, Moline, Rock Island, and Bettendorf) are located along the Mississippi River. Nearly 60% of its visitors are from the Chicago area. With dozens of miles of scenic riverfront, river boating, casinos, and thousands of acres of expansive public spaces, the Quad Cities area is a major draw from both Iowa and Illinois. The huge Rock Island Arsenal, one of the largest military arsenals in the country and located along the river, is transitioning to become the headquarters of the United States First Army. As will be discussed later in the report, there is only one logical rail route through the Quad Cities themselves. The Iowa Interstate Railroad operates through the Quad Cities along the river and heads west through Iowa. The Quad Cities are considering at least three potential locations for an Amtrak station. A study now underway supported by several local stakeholders will recommend a site which will then be considered, given available local and other financial support. If Amtrak service were to terminate in the Quad Cities, an overnight storage track of sufficient length along with ample parking and certain other requirements covered elsewhere in the report would be required.

Bayes factor for investigative assessment of selected handwriting features

This paper extends previous research [1] on the use of multivariate continuous data in comparative handwriting examinations, notably for gender classification. A database has been constructed by analyzing the contour shape of loop characters of type a and d by means of Fourier analysis, which allows characters to be described in a global way by a set of variables (e.g., Fourier descriptors). Sample handwritings were collected from right- and left-handed female and male writers. The results reported in this paper provide further arguments in support of the view that investigative settings in forensic science represent an area of application for which the Bayesian approach offers a logical framework. In particular, the Bayes factor is computed for settings that focus on inference of gender and handedness of the author of an incriminated handwritten text. An emphasis is placed on comparing the efficiency for investigative purposes of characters a and d.

El origen de la construcción fenomenalista: Mach, Moore y Whitehead

It's usually believed that the idea of applying logical methods to constructivist phenomenalism was, --in general- a result of Russell's originality. In this paper is argued that some important ideas were in fact due to Mach, Moore and Whitehead. According to the author, Russell got from Mach the general idea of epistemology as an analysis of scientific concepts and, specially,the idea of sensations as the building blocks for his logical construction. Moore made Russell believe that only sensations are known in a direct way, and so, the existence of external objects as the cause of our perceptions is only inferred. Moreover, according to the author, Russell's views on sense data -his sensibilia- are also due to Moore. Finally, Russell got from Whitehead the idea of the phenomenical reconstruction as an alternative to the causal theory of perception, and also how the logical construction should be done. The author undertakes also a detailed analysis of some early works of Whitehead not very well known.

Artificial-Intelligence-Based Optimization of the Management of Snow Removal Assets and Resources Final Report, October 2002

Geographic information systems (GIS) and artificial intelligence (AI) techniques were used to develop an intelligent snow removal asset management system (SRAMS). The system has been evaluated through a case study examining snow removal from the roads in Black Hawk County, Iowa, for which the Iowa Department of Transportation (Iowa DOT) is responsible. The SRAMS is comprised of an expert system that contains the logical rules and expertise of the Iowa DOT’s snow removal experts in Black Hawk County, and a geographic information system to access and manage road data. The system is implemented on a mid-range PC by integrating MapObjects 2.1 (a GIS package), Visual Rule Studio 2.2 (an AI shell), and Visual Basic 6.0 (a programming tool). The system could efficiently be used to generate prioritized snowplowing routes in visual format, to optimize the allocation of assets for plowing, and to track materials (e.g., salt and sand). A test of the system reveals an improvement in snowplowing time by 1.9 percent for moderate snowfall and 9.7 percent for snowstorm conditions over the current manual system.