The Dynamics of a Small Model Glass Former as Viewed from Its Potential Energy Landscape

Despite intensive research during the last decades, thetheoreticalunderstanding of supercooled liquids and the glasstransition is stillfar from being complete. Besides analytical investigations,theso-called energy-landscape approach has turned out to beveryfruitful. In the literature, many numerical studies havedemonstratedthat, at sufficiently low temperatures, all thermodynamicquantities can be predicted with the help of the propertiesof localminima in the potential-energy-landscape (PEL). The main purpose of this thesis is to strive for anunderstanding ofdynamics in terms of the potential energy landscape. Incontrast to the study of static quantities, this requirestheknowledge of barriers separating the minima.Up to now, it has been the general viewpoint that thermallyactivatedprocesses ('hopping') determine the dynamics only belowTc(the critical temperature of mode-coupling theory), in thesense that relaxation rates follow from local energybarriers.As we show here, this viewpoint should be revisedsince the temperature dependence of dynamics is governed byhoppingprocesses already below 1.5Tc.At the example of a binary mixture of Lennard-Jonesparticles (BMLJ),we establish a quantitative link from the diffusioncoefficient,D(T), to the PEL topology. This is achieved in three steps:First, we show that it is essential to consider wholesuperstructuresof many PEL minima, called metabasins, rather than singleminima. Thisis a consequence of strong correlations within groups of PELminima.Second, we show that D(T) is inversely proportional to theaverageresidence time in these metabasins. Third, the temperaturedependenceof the residence times is related to the depths of themetabasins, asgiven by the surrounding energy barriers. We further discuss that the study of small (but not toosmall) systemsis essential, in that one deals with a less complex energylandscapethan in large systems. In a detailed analysis of differentsystemsizes, we show that the small BMLJ system consideredthroughout thethesis is free of major finite-size-related artifacts.

The Small Project Observatory: Visualizing Software Ecosystems

Software evolution research has focused mostly on analyzing the evolution of single software systems. However, it is rarely the case that a project exists as standalone, independent of others. Rather, projects exist in parallel within larger contexts in companies, research groups or even the open-source communities. We call these contexts software ecosystems, and on this paper we present The Small Project Observatory, a prototype tool which aims to support the analysis of project ecosystems through interactive visualization and exploration. We present a case-study of exploring an ecosystem using our tool, we describe about the architecture of the tool, and we distill the lessons learned during the tool-building experience.

Vulnerability to risk among small farmers in Tajikistan: results of a 2011 survey

Tajikistan is judged to be highly vulnerable to risk, including food insecurity risks and climate change risks. By some vulnerability measures it is the most vulnerable among all 28 countries in the World Bank’s Europe and Central Asia Region – ECA (World Bank 2009). The rural population, with its relatively high incidence of poverty, is particularly vulnerable. The Pilot Program for Climate Resilience (PPCR) in Tajikistan (2011) provided an opportunity to conduct a farm-level survey with the objective of assessing various dimensions of rural population’s vulnerability to risk and their perception of constraints to farming operations and livelihoods. The survey should be accordingly referred to as the 2011 PPCR survey. The rural population in Tajikistan is highly agrarian, with about 50% of family income deriving from agriculture (see Figure 4.1; also LSMS 2007 – own calculations). Tajikistan’s agriculture basically consists of two groups of producers: small household plots – the successors of Soviet “private agriculture” – and dehkan (or “peasant”) farms – new family farming structures that began to be created under relevant legislation passed after 1992 (Lerman and Sedik, 2008). The household plots manage 20% of arable land and produce 65% of gross agricultural output (GAO). Dehkan farms manage 65% of arable land and produce close to 30% of GAO. The remaining 15% of arable land is held in agricultural enterprises – the rapidly shrinking sector of corporate farms that succeeded the Soviet kolkhozes and sovkhozes and today produces less than 10% of GAO (TajStat 2011) The survey conducted in May 2011 focused on dehkan farms, as budgetary constraints precluded the inclusion of household plots. A total of 142 dehkan farms were surveyed in face-to-face interviews. They were sampled from 17 districts across all four regions – Sughd, Khatlon, RRP, and GBAO. The districts were selected so as to represent different agro-climatic zones, different vulnerability zones (based on the World Bank (2011) vulnerability assessment), and different food-insecurity zones (based on WFP/IPC assessments). Within each district, 3-4 jamoats were chosen at random and 2-3 farms were selected in each jamoat from lists provided by jamoat administration so as to maximize the variability by farm characteristics. The sample design by region/district is presented in Table A, which also shows the agro-climatic zone and the food security phase for each district. The sample districts are superimposed on a map of food security phases based on IPC April 2011.

Improved neo-endothelialization of small diameter ePTFEgrafts with titanium coating

BACKGROUND: Patency of small synthetic bypass grafts is inferior compared to autologous grafts for revascularization procedures. Titanium coating of foreign surfaces has shown to decrease thrombogenicity, enhance biocompatibility and promote adhesion of endothelial cells. The aim of this study was to test the effect of titanium coating of small diameter ePTFE grafts on short term patency, neo-endothelialization and neointimal proliferation. METHODS: Bilateral carotid graft interposition was performed in 5 pigs with uncoated (n=5) and titanium-coated (n=5) ePTFE grafts (internal diameter=4 mm, length=5 cm), thus each pig served as its own control. At the end of the study (30 +/- 3 days), patency and stenosis severity was assessed by carotid angiography. Animals were sacrificed and grafts were excised for histology and scanning electron microscopy. Morphometry of histologic sections was carried out to determine neointimal proliferation and percentage of neo-endothelial coverage. RESULTS: Patency rate was 80% for uncoated and titanium-coated grafts. Quantitative angiography did not show any significant difference in lumen size between two groups. Morphometry revealed a significantly higher cellular coverage with CD31 positive endothelial cells for titanium-coated (84 +/- 19%) than uncoated grafts (48 +/- 26%, p<0.001). There was a non significant trend (p=0.112) towards increased neointimal proliferation in titanium-coated (94 +/- 61 micron2/micron) compared to uncoated grafts (60 +/- 57 micron2/micron). CONCLUSIONS: Patency rate in uncoated and titanium-coated ePTFE grafts is similar at one month. However, titanium coated grafts show a significant improvement in neo-endothelialization compared to uncoated grafts.

Sirolimus-eluting coronary stents in small vessels

BACKGROUND: This prospective multicenter study compared angiographic in-lesion late lumen loss in de novo native coronary artery lesions (vessel diameter range 2.25-2.75 mm, length range > or = 15 to < or = 30 mm) 8 months after the implantation of a sirolimus-eluting stent with that of similar vessels with the same drug-eluting stent or a bare stent of the SIRIUS study (historical controls). METHODS AND RESULTS: One hundred one patients (study group) were matched and compared with 323 patients receiving the bare stent (bare control group) and with 350 receiving the Cypher stent (Cypher control group) in the SIRIUS trial. Mean in-lesion late loss in the study group was lower than that in the bare control group (0.20 versus 0.76 mm, P < .0001) and not inferior to that in the Cypher control group (0.27 mm, P = .3). Adverse event rates (death and myocardial infarction) were similar between groups. At 8 months, target lesion revascularization rates were 0% in the study group, 13.2% in the bare control group (P < .001), and 4.6% in the Cypher control group (P = .03). CONCLUSIONS: The Cypher Bx Velocity stent was confirmed to be superior to the bare Bx Velocity stent in small coronary vessels in terms of in-lesion late loss 8 months after implantation.

Perioperative fluid management: comparison of high, medium and low fluid volume on tissue oxygen pressure in the small bowel and colon

BACKGROUND AND OBJECTIVE: Insufficient blood flow and oxygenation in the intestinal tract is associated with increased incidence of postoperative complications after bowel surgery. High fluid volume administration may prevent occult regional hypoperfusion and intestinal tissue hypoxia. We tested the hypothesis that high intraoperative fluid volume administration increases intestinal wall tissue oxygen pressure during laparotomy. METHODS: In all, 27 pigs were anaesthetized, ventilated and randomly assigned to one of the three treatment groups (n = 9 in each) receiving low (3 mL kg-1 h-1), medium (7 mL kg-1 h-1) or high (20 mL kg-1 h-1) fluid volume treatment with lactated Ringer's solution. All animals received 30% and 100% inspired oxygen in random order. Cardiac index was measured with thermodilution and tissue oxygen pressure with a micro-oximetry system in the jejunum and colon wall and subcutaneous tissue. RESULTS: Groups receiving low and medium fluid volume treatment had similar systemic haemodynamics. The high fluid volume group had significantly higher mean arterial pressure, cardiac index and subcutaneous tissue oxygenation. Tissue oxygen pressures in the jejunum and colon were comparable in all three groups. CONCLUSIONS: The three different fluid volume regimens tested did not affect tissue oxygen pressure in the jejunum and colon, suggesting efficient autoregulation of intestinal blood flow in healthy subjects undergoing uncomplicated abdominal surgery.

Role of beta1-, beta2-, and beta3-adrenoceptors in contractile hypersensitivity in a model of small bowel transplantation

BACKGROUND: Chronic extrinsic denervation induced by small bowel transplantation (SBT) results in adrenergic hypersensitivity in rat ileum. This study evaluated the role of neuronal and/or muscular beta1-, beta2-, and beta3-adrenoceptor (AR) mechanisms on contractility. METHODS: Ileal longitudinal muscle strips from Lewis rats (n = 6 rats per group, 8 strips per rat): naive controls (NC), 4 months after sham operation (SC) or after syngeneic orthotopic SBT were studied in vitro. Spontaneous contractile activity and dose responses (10(-8)-10(-4) mol) to isoprenaline (IP), a nonspecific beta-AR agonist were studied with or without selective antagonists (10(-5) mol), for beta1- (atenolol), beta2- (ICI 118551), or beta3- (SR 59230A) AR subtypes in the presence or absence of tetrodotoxin (TTX; 10(-6) mol; nerve blocker). RESULTS: pEC50 (neg log of EC50, which is the concentration where 50% of inhibition was observed) of IP was 7.2 +/- 0.2 (mean value +/- SEM) in SBT vs 6.3 +/- 0.1 in SC and 6.3 +/- 0.2 in NC (both P < .05 vs SBT), reflecting adrenergic hypersensitivity. Beta1- and beta2-AR blockade induced a TTX-sensitive right shift of the curve only in SBT and normalized pEC50 values from 7.2 +/- 0.2 to 6.4 +/- 0.1 and 7.2 +/- 0.2 to 6.6 +/- 0.1, respectively (P < .05). Beta3-AR blockade shifted the curve independent of the presence of TTX to the right in all groups (all P < .05). CONCLUSIONS: In rat ileum, adrenergic inhibition of contractility was dependent on muscular beta3-AR pathways, whereas posttransplant hypersensitivity was due to upregulated neuronal beta1- and beta2-AR mechanisms that were inactive before SBT.

Granulocyte colony stimulating factor supports liver regeneration in a surgical small for size liver remnant mouse model

ntense liver regeneration and almost 100% survival follows partial hepatectomy of up to 70% of liver mass in rodents. More extensive resections of 70 to 80% have an increased mortality and partial hepatectomies of >80% constantly lead to acute hepatic failure and death in mice. The aim of the study was to determine the effect of systemically administered granulocyte colony stimulating factor (G-CSF) on animal survival and liver regeneration in a small for size liver remnant mouse model after 83% partial hepatectomy (liver weight <0.8% of mouse body weight). Methods: Male Balb C mice (n=80, 20-24g) were preconditioned daily for five days with 5μg G-CSF subcutaneously or sham injected (aqua ad inj). Subsequently 83% hepatic resection was performed and daily sham or G-CSF injection continued. Survival was determined in both groups (G-CSF n=35; Sham: n=33). In a second series BrdU was injected (50mg/kg Body weight) two hours prior to tissue harvest and animals euthanized 36 and 48 hours after 83% liver resection (n=3 each group). To measure hepatic regeneration the BrdU labeling index and Ki67 expression were determined by immunohistochemistry by two independent observers. Harvested liver tissue was dried to constant weight at 65 deg C for 48 hours. Results: Survival was 0% in the sham group on day 3 postoperatively and significantly better (26.2% on day 7 and thereafter) in the G-CSF group (Log rank test: p<0.0001). Dry liver weight was increased in the G-CSF group (T-test: p<0.05) 36 hours after 83% partial hepatectomy. Ki67 expression was elevated in the G-CSF group at 36 hours (2.8±2.6% (Standard deviation) vs 0.03±0.2%; Rank sum test: p<0.0001) and at 48 hours (45.1±34.6% vs 0.7±1.0%; Rank sum test: p<0.0001) after 83% liver resection. BrdU labeling at 48 hours was 0.1±0.3% in the sham and 35.2±34.2% in the G-CSF group (Rank sum test: p<0.0001) Conclusions: The surgical 83% resection mouse model is suitable to test hepatic supportive regimens in the setting of small for size liver remnants. Administration of G-CSF supports hepatic regeneration after microsurgical 83% partial hepatectomy and leads to improved long-term survival in the mouse. G-CSF might prove to be a clinically valuable supportive substance in small for size liver remnants in humans after major hepatic resections due to primary or secondary liver tumors or in the setting of living related liver donation.

Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma: a cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance? A study of 136 cases

Patients with skin nodules characterized by the infiltrate of pleomorphic small/medium T lymphocytes are currently classified as "primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma" (SMPTCL) or as T-cell pseudolymphoma. The distinction is often arbitrary, and patients with similar clinicopathologic features have been included in both groups. We studied 136 patients (male:female = 1:1; median age: 53 years, age range: 3-90 years) with cutaneous lesions that could be classified as small-/medium-sized pleomorphic T-cell lymphoma according to current diagnostic criteria. All but 3 patients presented with solitary nodules located mostly on the head and neck area (75%). Histopathologic features were characterized by nonepidermotropic, nodular, or diffuse infiltrates of small- to medium-sized pleomorphic T lymphocytes. A monoclonal rearrangement of the T-cell receptor-gamma gene was found in 60% of tested cases. Follow-up data available for 45 patients revealed that 41 of them were alive without lymphoma after a median time of 63 months (range: 1-357 months), whereas 4 were alive with cutaneous disease (range: 2-16 months). The incongruity between the indolent clinical course and the worrying histopathologic and molecular features poses difficulties in classifying these cases unambiguously as benign or malignant, and it may be better to refer to them with a descriptive term such as "cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance," rather than forcing them into one or the other category. On the other hand, irrespective of the name given to these equivocal cutaneous lymphoid proliferations, published data support a nonaggressive therapeutic strategy, particularly for patients presenting with solitary lesions.

Preserving middle lobe to improve lung function in non-small-cell lung cancer

When a lung tumor arises in segment 6, the close anatomical relationship to the middle lobe bronchus may make a lower bilobectomy necessary. Sleeve lobectomy may be an alternative. These procedures were compared retrospectively in 36 patients operated on between January 2005 and December 2006 with non-small-cell lung cancer (stage I-IIIB) of the right lower lobe. Sleeve lobectomy was performed in 21 patients and bilobectomy in 15 (41%). Preoperative lung function was comparable in both groups. Radical resection was achieved in 34/36 patients. Operation time was 121 min for sleeve lobectomy and 144 min for bilobectomy. Chest tubes were removed after 5 days in both groups. Postoperative lung function was better after sleeve lobectomy than bilobectomy (forced expiratory volume in 1st sec: 78% vs. 69%). Preservation of the middle lobe by sleeve lobectomy is feasible. There was no evidence that this resection was less radical, and complication rates were similar in both groups.

Changes in species composition in alpine snowbeds with climate change inferred from small-scale spatial patterns

Alpine snowbeds are characterised by a very short growing season. However, the length of the snow-free period is increasingly prolonged due to climate change, so that snowbeds become susceptible to invasions from neighbouring alpine meadow communities. We hypothesised that spatial distribution of species generated by plant interactions may indicate whether snowbed species will coexist with or will be out-competed by invading alpine species – spatial aggregation or segregation will point to coexistence or competitive exclusion, respectively. We tested this hypothesis in snowbeds of the Swiss Alps using the variance ratio statistics. We focused on the relationships between dominant snowbed species, subordinate snowbed species, and potentially invading alpine grassland species. Subordinate snowbed species were generally spatially aggregated with each other, but were segregated from alpine grassland species. Competition between alpine grassland and subordinate snowbed species may have caused this segregation. Segregation between these species groups increased with earlier snowmelt, suggesting an increasing importance of competition with climate change. Further, a dominant snowbed species (Alchemilla pentaphyllea) was spatially aggregated with subordinate snowbed species, while two other dominants (Gnaphalium supinum and Salix herbacea) showed aggregated patterns with alpine grassland species. These dominant species are known to show distinct microhabitat preferences suggesting the existence of hidden microhabitats with different susceptibility to invaders. These results allow us to suggest that alpine snowbed areas are likely to be reduced as a consequence of climate change and that invading species from nearby alpine grasslands could outcompete subordinate snowbed species. On the other hand, microhabitats dominated by Gnaphalium or Salix seem to be particularly prone to invasions by non-snowbed species.

Differential association of MUC5AC and CLCA1 expression in small cartilaginous airways of RAO-affected and control horses

REASONS FOR PERFORMING STUDY: Airway mucus accumulation is associated with indoor irritant and allergen exposure in horses with recurrent airway obstruction (RAO). Epidermal growth factor receptor (EGFR) and a chloride channel (calcium activated, family member 1; CLCA1) are key signalling molecules involved in mucin gene expression. OBJECTIVES: We hypothesised that exposure to irritants and aeroallergens would lead to increased expression of the mucin gene eqMUC5AC and increased stored mucosubstance in the airways of RAO-affected horses, associated with increased neutrophils and CLCA1 and EGFR mRNA levels. METHODS: We performed quantitative RT-PCR of eqMUC5AC, CLCA1 and EGFR; volume density measurements of intraepithelial mucosubstances; and cytological differentiation of intraluminal inflammatory cells in small cartilaginous airways from cranial left and right and caudal left and right lung lobes of 5 clinically healthy and 5 RAO-affected horses that had been exposed to indoor stable environment for 5 days before euthanasia. RESULTS: Neutrophils were increased in RAO-affected horses compared to clinically healthy controls. EqMUC5AC mRNA levels were positively correlated with both CLCA1 and EGFR mRNA levels in RAO-affected horses but only with CLCA1 in controls. The relationship between eqMUC5AC and CLCA1 differed in the 2 groups of horses with RAO-affected animals overexpressing CLCA1 in relation to eqMUC5AC. CONCLUSIONS: These data implicate CLCA1 as a signalling molecule in the expression of eqMUC5AC in horses but also suggest differential regulation by CLCA1 and EGFR between horses with RAO and those with milder degrees of airway inflammation.

A stereological comparison of villous and microvillous surfaces in small intestines of frugivorous and entomophagous bats: species, inter-individual and craniocaudal differences

The extents of functional surfaces (villi, microvilli) have been estimated at different longitudinal sites, and in the entire small intestine, for three species of bats belonging to two feeding groups: insect- and fruit-eaters. In all species, surface areas and other structural quantities tended to be greatest at more cranial sites and to decline caudally. The entomophagous bat (Miniopterus inflatus) had a mean body mass (coefficient of variation) of 8.9 g (5%) and a mean intestinal length of 20 cm (6%). The surface area of the basic intestinal tube (primary mucosa) was 9.1 cm2 (10%) but this was amplified to 48 cm2 (13%) by villi and to 0.13 m2 (20%) by microvilli. The total number of microvilli per intestine was 4 x 10(11) (20%). The average microvillus had a diameter of 8 nm (10%), a length of 1.1 microns (22%) and a membrane surface area of 0.32 micron 2 (31%). In two species of fruit bats (Epomophorus wahlbergi and Lisonycteris angolensis), body masses were greater and intestines longer, the values being 76.0 g (18%) and 76.9 g (4%), and 73 cm (16%) and 72 cm (7%), respectively. Surface areas were also greater, amounting to 76 cm2 (26%) and 45 cm2 (8%) for the primary mucosa, 547 cm2 (29%) and 314 cm2 (16%) for villi and 2.7 m2 (23%) and 1.5 m2 (18%) for microvilli. An increase in the number of microvilli, 33 x 10(11) (19%) and 15 x 10(11) (24%) per intestine, contributed to the more extensive surface area but there were concomitant changes in the dimensions of microvilli. Mean diameters were 94 nm (8%) and 111 nm (4%), and mean lengths were 2.8 microns (12%) and 2.9 microns (10%), respectively. Thus, an increase in the surface area of the average microvillus to 0.83 micron 2 (12%) and 1.02 microns 2 (11%) also contributed to the greater total surface area of microvilli. The lifestyle-related differences in total microvillous surface areas persisted when structural quantities were normalised for the differences in body masses. The values for total microvillous surface area were 148 cm2g-1 (20%) in the entomophagous bat, 355 cm2g-1 (20%) in E. wahlbergi and 192 cm2g-1 (17%) in L. angolensis. This was true despite the fact that the insecteater possessed a greater length of intestine per unit of body mass: 22 mm g-1 (8%) versus 9-10 mm g-1 (9-10%) for the fruit-eaters.

Clinical and intravascular imaging outcomes at 1 and 2 years after implantation of absorb everolimus eluting bioresorbable vascular scaffolds in small vessels. Late lumen enlargement: does bioresorption matter with small vessel size? Insight from the ABSORB cohort B trial

BACKGROUND The long-term results after second generation everolimus eluting bioresorbable vascular scaffold (Absorb BVS) placement in small vessels are unknown. Therefore, we investigated the impact of vessel size on long-term outcomes, after Absorb BVS implantation. METHODS In ABSORB Cohort B Trial, out of the total study population (101 patients), 45 patients were assigned to undergo 6-month and 2-year angiographic follow-up (Cohort B1) and 56 patients to have angiographic follow-up at 1-year (Cohort B2). The pre-reference vessel diameter (RVD) was <2.5 mm (small-vessel group) in 41 patients (41 lesions) and ≥2.5 mm (large-vessel group) in 60 patients (61 lesions). Outcomes were compared according to pre-RVD. RESULTS At 2-year angiographic follow-up no differences in late lumen loss (0.29±0.16 mm vs 0.25±0.22 mm, p=0.4391), and in-segment binary restenosis (5.3% vs 5.3% p=1.0000) were demonstrated between groups. In the small-vessel group, intravascular ultrasound analysis showed a significant increase in vessel area (12.25±3.47 mm(2) vs 13.09±3.38 mm(2) p=0.0015), scaffold area (5.76±0.96 mm(2) vs 6.41±1.30 mm(2) p=0.0008) and lumen area (5.71±0.98 mm(2) vs 6.20±1.27 mm(2) p=0.0155) between 6-months and 2-year follow-up. No differences in plaque composition were reported between groups at either time point. At 2-year clinical follow-up, no differences in ischaemia-driven major adverse cardiac events (7.3% vs 10.2%, p=0.7335), myocardial infarction (4.9% vs 1.7%, p=0.5662) or ischaemia-driven target lesion revascularisation (2.4% vs 8.5%, p=0.3962) were reported between small and large vessels. No deaths or scaffold thrombosis were observed. CONCLUSIONS Similar clinical and angiographic outcomes at 2-year follow-up were reported in small and large vessel groups. A significant late lumen enlargement and positive vessel remodelling were observed in small vessels.

Heterotic T-folds with a small number of neutral moduli

We discuss non-geometric supersymmetric heterotic string models in D=4, in the framework of the free fermionic construction. We perform a systematic scan of models with four a priori left-right asymmetric Z2 projections and shifts. We analyze some 220 models, identifying 18 inequivalent classes and addressing variants generated by discrete torsions. They do not contain geometrical or trivial neutral moduli, apart from the dilaton. However, we show the existence of flat directions in the form of exactly marginal deformations and identify patterns of symmetry breaking where product gauge groups, realized at level one, are broken to their diagonal at higher level. We also describe an “inverse Gepner map” from Heterotic to Type II models that could be used, in certain non geometric settings, to define “effective” topological invariants.