The Swiss-Austrian Alliance for Mountain Research

Switzerland and Austria are committed to addressing sustainable mountain development in Europe through a joint effort. In June 2013, more than 140 researchers as well as representatives of the 2 countries' funding ministries participated in the “Mountain Days” event in Mittersill, Austria, thereby marking the official launch of the Swiss-Austrian Alliance. The resulting Mittersill Commitment Paper highlights 8 research areas and calls for international cooperation between mountain researchers, institutions, and governments.

How can computer simulations produce new knowledge?

It is often claimed that scientists can obtain new knowledge about nature by running computer simulations. How is this possible? I answer this question by arguing that computer simulations are arguments. This view parallels Norton’s argument view about thought experiments. I show that computer simulations can be reconstructed as arguments that fully capture the epistemic power of the simulations. Assuming the extended mind hypothesis, I furthermore argue that running the computer simulation is to execute the reconstructing argument. I discuss some objections and reject the view that computer simulations produce knowledge because they are experiments. I conclude by comparing thought experiments and computer simulations, assuming that both are arguments.

"Fascinating Voids: Alexander von Humboldt and the Myth of Chimborazo"

When Alexander von Humboldt reached the village of Calpi in the Andes on 22 June 1802, he was greeted with reverence and enthusiasm. Triumphal arches adorned with cotton, cloth, and silver decorated his path. The natives performed a dance in festive dress. A singer praised the explorer's expedition, which had departed three years earlier from the Spanish port of La Coruña. Like Odysseus on the isle of the Phaeacians, the traveler listened to a local rhapsodist singing about his heroic deeds. Before his adventure ended, it had already spun a popular myth. This episode, which Humboldt recorded in his diary, occurred at a significant moment. One day later, the “Second Discoverer of America” rose to even greater fame on an excursion marking in more ways than one the climax of his enterprise. Humboldt set out to climb Chimborazo (6,310 m/20,702 ft.), the mountain then thought to be the highest in the world. He was accompanied by the French botanist Aimé Bonpland (1773–1858) and the Creole nobleman and future activist Carlos Montúfar (1780–1816), as well as native guides and assistants. They climbed to heights never reached before, setting a new record and catapulting Humboldt to fame on both continents.

Accumulating mutations in series of haplotypes at the KIT and MITF loci are major determinants of white markings in Franches-Montagnes horses.

Coat color and pattern variations in domestic animals are frequently inherited as simple monogenic traits, but a number are known to have a complex genetic basis. While the analysis of complex trait data remains a challenge in all species, we can use the reduced haplotypic diversity in domestic animal populations to gain insight into the genomic interactions underlying complex phenotypes. White face and leg markings are examples of complex traits in horses where little is known of the underlying genetics. In this study, Franches-Montagnes (FM) horses were scored for the occurrence of white facial and leg markings using a standardized scoring system. A genome-wide association study (GWAS) was performed for several white patterning traits in 1,077 FM horses. Seven quantitative trait loci (QTL) affecting the white marking score with p-values p≤10(-4) were identified. Three loci, MC1R and the known white spotting genes, KIT and MITF, were identified as the major loci underlying the extent of white patterning in this breed. Together, the seven loci explain 54% of the genetic variance in total white marking score, while MITF and KIT alone account for 26%. Although MITF and KIT are the major loci controlling white patterning, their influence varies according to the basic coat color of the horse and the specific body location of the white patterning. Fine mapping across the MITF and KIT loci was used to characterize haplotypes present. Phylogenetic relationships among haplotypes were calculated to assess their selective and evolutionary influences on the extent of white patterning. This novel approach shows that KIT and MITF act in an additive manner and that accumulating mutations at these loci progressively increase the extent of white markings.

Why Monte Carlo Simulations are Inferences and not Experiments

Monte Carlo simulations arrive at their results by introducing randomness, sometimes derived from a physical randomizing device. Nonetheless, we argue, they open no new epistemic channels beyond that already employed by traditional simulations: the inference by ordinary argumentation of conclusions from assumptions built into the simulations. We show that Monte Carlo simulations cannot produce knowledge other than by inference, and that they resemble other computer simulations in the manner in which they derive their conclusions. Simple examples of Monte Carlo simulations are analysed to identify the underlying inferences.

Gene therapy of cancer: Mechanisms of ``bystander effect'' killing in cells expressing the herpes simplex virus-thymidine kinase gene and its potential clinical applications

At the fore-front of cancer research, gene therapy offers the potential to either promote cell death or alter the behavior of tumor-cells. One example makes use of a toxic phenotype generated by the prodrug metabolizing gene, thymidine kinase (HSVtk) from the Herpes Simplex Virus. This gene confers selective toxicity to a relatively nontoxic prodrug, ganciclovir (GCV). Tumor cells transduced with the HSVtk gene are sensitive to 1-50 $\mu$M GCV; normal tissue is insensitive up to 150-250 $\mu$M GCV. Utilizing these different sensitivities, it is possible to selectively ablate tumor cells expressing this gene. Interestingly, if a HSVtk$\sp+$ expressing population is mixed with a HSVtk$\sp-$ population at high density, all the cells are killed after GCV administration. This phenomenon for killing all neighboring cells is termed the "bystander effect", which is well documented in HSVtk$\sp-$ GCV systems, though its exact mechanism of action is unclear.^ Using the mouse colon carcinoma cell line CT26, data are presented supporting possible mechanisms of "bystander effect" killing of neighboring CT26-tk$\sp-$cells. A major requirement for bystander killing is the prodrug GCV: as dead or dying CT26tk$\sp+$ cells have no toxic effect on neighboring cells in its absence. In vitro, it appears the bystander effect is due to transfer of toxic GCV-metabolites, through verapamil sensitive intracellular-junctions. Additionally, possible transfer of the HSVtk enzyme to bystander cells after GCV addition, may play a role in bystander killing. A nude mouse model suggests that in a 50/50 (tk$\sp+$/tk$\sp-$) mixture of CT26 cells the bystander eradication of tumors does not involve an immune component. Additionally in a possible clinical application, the "bystander effect" can be directly exploited to eradicate preexisting CT26 colon carcinomas in mice by intratumoral implantation of viable or lethally irradiated CT26tk$\sp+$ cells and subsequent GCV administration. Lastly, an application of this toxic phenotype gene to a clinical marking protocol utilizing a recombinant adenoviral vector carrying the bifunctional protein GAL-TEK to eradicate spontaneously-arisen or vaccine-induced fibrosarcomas in cats is demonstrated. ^

Faith as a Mustard Seed

Abstract: This investigation of the concept of faith is divided into two parts. Part One evaluates a topical philosophical interpretation of faith as irreducibly disjunctive, collecting the best fragmented ideas as to what constitutes faith in a recent family resemblance exposition as an objective for an adequate essentialist analysis of the concept of faith to achieve. Part Two offers a more extended essentialist analysis of the concept of faith as unconditional patience in the eventuality of a positive future state, and a detailed reduction of six supposedly disparate family resemblance senses of faith to this single definition. Criteria for a satisfactory analysis of faithfulness are considered and defended. In contrast with what has become a standard doxastic-epistemic interpretation of faith as persistent unjustified or even unjustifiable belief, a concept of faith is advanced that appears to satisfy the necessary and sufficient criteria identified. Systematic comparison with a variety of usages of the word “faith” suggests that the analysis agrees with many and arguably most applications of this sometimes loosely understood term. Implications of the analysis of the concept of faith are considered and defended against anticipated objections. Pascal’s wager is critically examined in relation to matters of religious faith, along with positivist meaningfulness requirements that seem to conflict especially with epistemically ungrounded belief, the power of faith, and the metaphorical size of mustard seeds. The inquiry concludes with a synthesis of five aspects of six supposedly distinct senses of faith under the single essentialist reductive umbrella of unconditional patience in the eventuality of a positive future state.

Universal ontology: attentive tracking of objects and substances across languages and over development

Previous research has demonstrated that adults are successful at visually tracking rigidly moving items, but experience great difficulties when tracking substance-like ‘‘pouring’’ items. Using a comparative approach, we investigated whether the presence/absence of the grammatical count–mass distinction influences adults and children’s ability to attentively track objects versus substances. More specifically, we aimed to explore whether the higher success at tracking rigid over substance-like items appears universally or whether speakers of classifier languages (like Japanese, not marking the object–substance distinction) are advantaged at tracking substances as compared to speakers of non-classifier languages (like Swiss German, marking the object–substance distinction). Our results supported the idea that language has no effect on low-level cognitive processes such as the attentive visual processing of objects and substances. We concluded arguing that the tendency to prioritize objects is universal and independent of specific characteristics of the language spoken.

Volcanostratigraphic Controls on the Occurrence of Massive Sulfide (VMS) Deposits in the Semail Ophiolite, Oman

The Semail ophiolite in Oman is capped by up to 2 km of basaltic-andesitic lavas that host copper-dominant, Cyprus-type, volcanogenic massive sulfide (VMS) deposits. This study identifies multiple volcanostratigraphic horizons on which the deposits are situated, based on characterization of footwall and hanging-wall lavas from 16 deposits or deposit clusters. Comparison of field and petrographic features, compositions of igneous clinopyroxenes, and whole-rock geochemical signatures permits classification of the lavas within a modified version of the established regional volcanostratigraphy. Four extrusive units host deposits: Geotimes (earliest), Lasail, Alley, and Boninitic Alley (latest). The latter was previously known only at few localities, but this study reveals its regional extent and significance as a host for VMS deposits. The Geotimes and Lasail units represent Late Cretaceous, ocean spreading ridge and related off-axis volcanic environments, respectively. The Alley and Boninitic Alley units represent younger, subduction-related volcanism prior to Coniacian-Santonian obduction of the ophiolite. Our results show that VMS deposits occur on or near the Geotimes/Lasail and Geotimes/Alley contacts as well as entirely within the Geotimes, Lasail, Alley, and Boninitic Alley units. Highest Cu grades tend to occur in deposits lying on or within the Geotimes, whereas highest Au grades occur in deposits within the Boninitic Alley. In contrast to earlier studies, we conclude that essentially every horizon marking a hiatus in lava deposition in the Semail ophiolite, i.e., contacts between the four major eruptive units, and umbers and sedimentary chert layers within the units, has exploration potential for Cu-Au VMS deposits.

First evidence for differential and sequential efferent effects of stimulus relevance and goal conduciveness appraisal.

In the context of a memory task, participants were presented with pictures displaying biological and cultural threat stimuli or neutral stimuli (stimulus relevance manipulation) with superimposed symbols signaling monetary gains or losses (goal conduciveness manipulation). Results for heart rate and facial electromyogram show differential efferent effects of the respective appraisal outcomes and provide first evidence for sequential processing, as postulated by Scherer's component process model of emotion. Specifically, as predicted, muscle activity over the brow and cheek regions marking the process of relevance appraisal occurred significantly earlier than facial muscle activity markers of goal conduciveness appraisal. Heart rate, in contrast, was influenced by the stimulus relevance manipulation only.

Intuitionistic common knowledge or belief

Starting off from the usual language of modal logic for multi-agent systems dealing with the agents’ knowledge/belief and common knowledge/belief we define so-called epistemic Kripke structures for intu- itionistic (common) knowledge/belief. Then we introduce corresponding deductive systems and show that they are sound and complete with respect to these semantics.

Patientensicherheit in der Shuntchirurgie

Zusammenfassung Hintergrund. Hämodialysepatienten, die operativ mit einem Gefäßzugang versorgt werden müssen, sind eine vulnerable Patientengruppe, die aufgrund von Multimorbidität, der intensiven und oft fragmentierten Behandlung und vieler Schnittstellen ein erhöhtes Risiko für vermeidbare unerwünschte Ereignisse tragen. Fragestellung. Aktuelle Entwicklungen und Maßnahmen zur Förderung der Patientensicherheit mit Fokus auf die Shuntchirurgie. Material und Methoden. Auswertung und Aufarbeitung aktueller Daten zur Patientensicherheit und Instrumenten zu ihrer Förderung. Ergebnisse. Fehler im nicht operativen Management verursachen einen wesentlichen Anteil der unerwünschten Ereignisse. Checklisten, präoperative Seitenmarkierung, Zählkontrollen und interprofessionelle Teamtrainings sind wichtige Instrumente der Patientensicherheit im OP. Standardisierungen von postoperativen Übergaben durch einfache Protokolle können erheblich zur Reduktion von Fehlern und Schädigungen beitragen. Die Sicherheitskultur einer Abteilung ist ein Umgebungsfaktor, der für die Effektivität dieser Sicherheitsbarrieren wesentlich ist. Schlussfolgerungen. Es existieren wirksame Instrumente, die die Patientensicherheit in der Shuntchirurgie fördern. Gerade an den Schnittstellen zur weiteren Versorgung können durch die konsequente Implementierung und Nutzung dieser Maßnahmen und ein aktives Sicherheitsmanagement unerwünschte Ereignisse vermieden werden. Die interprofessionelle und interdisziplinäre Zusammenarbeit und der Einbezug der Patienten sind wichtige Ressource für die Behandlungssicherheit, die stärker genutzt werden sollten.

Inversion, Obviation, and Animacy in Native Languages of the Americas: Elements for a Cross-linguistic Survey

Native languages of the Americas whose predicate and clause structure reflect nominal hierarchies show an interesting range of structural diversity not only with respect to morphological makeup of their predicates and arguments but also with respect to the factors governing obviation status. The present article maps part of such diversity. The sample surveyed here includes languages with some sort of nonlocal (third person acting on third person) direction-marking system.

Proximal Femoral Osteotomies with the Paediatric Hip Plate (LCP): Valgus osteotomy.

OBJECTIVE Proximal femoral osteotomy with stable fixation and sufficient correction. Low complication rates due to exact preoperative planning. INDICATIONS Congenital or traumatic femoral neck pseudarthrosis. Coxa vara. CONTRAINDICATIONS None. In severe deformities, a single femoral osteotomy may not solve the problem; thus, additional correction, e.g., a pelvic osteotomy, is required. SURGICAL TECHNIQUE Correct planning of the correction angle. Lateral approach. Subperiosteal detachment of vastus lateralis muscle. Place guide wire on the femoral neck to judge anteversion. Insert positioning wire 5 mm distal to trochanteric physis. Insert 2.8 mm Kirschner wire in the femoral neck. Osteotomy of the femur after marking the rotation by Kirschner wires or oscillating saw. Slide LC plate over Kirschner wires. Replace Kirschner wires with screws. Reduction of the femoral shaft to the plate with bone forceps. Definitive fixation of the plate to the femoral shaft by cortex or locking screws. Readaptation of vastus lateralis muscle over the plate. POSTOPERATIVE MANAGEMENT Partial weightbearing for 4-6 weeks depending on the age of the patient without any external fixation (e. g. cast) is possible. RESULTS Recent studies support the authors' findings of sufficient correction and stable fixation after proximal femoral osteotomy with the LCP pediatric hip plate. Low complication rates and stable fixation.