Miracle-dz/UniFAR-FTUs huggingface dataset:
Renaissance of Bernal's random close packing and hypercritical line in the theory of liquids

We review the scientific history of random close packing (RCP) of equal spheres, advocated by J D Bernal as a more plausible alternative to the non-ideal gas or imperfect crystal as a structural model of simple liquids. After decades of neglect, computer experiments are revealing a central role for RCP in the theory of liquids. These demonstrate that the RCP amorphous state of hard spheres can be well defined, is reproducible, and has the thermodynamic status of a metastable ground state. Further evidence from simulations of square-well model liquids indicates an extended role of RCP as an amorphous ground state that terminates a supercooled liquid coexistence line, suggesting likewise for real liquids. A phase diagram involving percolation boundaries has been proposed in which there is no merging of liquid and gas phases, and no critical singularity as assumed by van der Waals. Rather, the liquid phase continuously spans all temperatures, but above a critical dividing line on the Gibbs density surface, it is bounded by a percolation transition and separated from the gas phase by a colloidal supercritical mesophase. The colloidal-like inversion in the mesophase as it changes from gas-in-liquid to liquid-in-gas can be identified with the hypercritical line of Bernal. We therefore argue that the statistical theory of simple liquids should start from the RCP reference state rather than the ideal gas. Future experimental priorities are to (i) find evidence for an amorphous ground state in real supercooled liquids, (ii) explore the microscopic structures of the supercritical mesophase, and (iii) determine how these change from gas to liquid, especially across Bernal's hypercritical line. The theoretical priority is a statistical geometrical theory of RCP. Only then might we explain the coincident values of the RCP packing fraction with Buffon's constant, and the RCP residual entropy with Boltzmann's ideal gas constant.
Elevated Ribonucleotide Reductase Levels Associate With Suppressed Radiochemotherapy Response in Human Cervical Cancers

Objective Ribonucleotide reductase (RNR) supplies deoxyribonucleotide diphosphates demanded by cells to repair radiation-induced DNA damage. Here, we investigate the impact of pretherapy RNR M1, M2, and M2b (p53R3) subunit level upon human cervical cancer radiochemosensitivity. Materials/Methods Immunohistochemistry was performed on a tissue array comprised of 18 paired benign uterine cervix and stage IB2 cervical cancers to evaluate the relationship between cytosolic RNR M1, M2, and M2b staining intensity and radiochemotherapy cancer response. Patients underwent surgical hysterectomy (n = 8), or daily radiation (45 Gy), coadministered once-weekly cisplatin (40 mg/m2), then low–dose rate brachytherapy (30 Gy) followed by adjuvant hysterectomy (n = 10). Radiochemotherapy response was determined by Response Evaluation Criteria In Solid Tumors version 1.0 criteria during brachytherapy. Cancer relapse rates and disease-free survival were calculated. Results M1, M2, and M2b antibody staining intensity was low (0–1+) in benign uterine cervical tissue. M1 and M2b immunoreactivity was 2+ or 3+ in most (13/18) cervical cancers. M2 immunoreactivity was 3+ in nearly all (16/18) cervical cancers. Cervical cancers overexpressing M1 and M2b had an increased hazard for incomplete radiochemotherapy response, relapse, and shortened disease-free survival. Conclusions Ribonucleotide reductase subunit levels may predict human cervical cancer radiochemosensitivity and subsequent posttherapy cancer outcome. Further validation testing of RNR subunits as biomarkers for radiochemotherapy response is warranted.
Cortical activity elicited by changes in auditory stimuli: different sources for the magnetic N100m and mismatch responses.

Magnetic responses to frequent and infrequent auditory stimuli, all presented in the same stimulus block in randomized order, were recorded. The standard stimuli, comprising 90% of all the stimuli, were 100-ms, 1000 Hz, 90dB sinusoidal tone bursts. There were three deviant tones, each presented at a probability of 3.3%, which differed from the standard tone on one dimension only: frequency deviant (1500 Hz), intensity deviant (67dB SPL), or duration deviant (50 ms). All mismatch fields, i.e., responses elicited by different deviants, as well as N100m to the standards and deviants, could be explained by neural activity in the supratemporal auditory cortex. The source of N100m to standards and deviants was significantly posterior to the sources for the three different mismatch fields. The mean locations of the equivalent dipoles for the different mismatch fields did not differ significantly from each other, but some differences were found for individual subjects.
Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience

AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. METHODS We performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent’s Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time. RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBeAg positive status (OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-naïve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of non-compliance. Tenofovir therapy was well tolerated. CONCLUSION Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials.
Applying IJTAG-compatible embedded instruments for lifetime enhancement of analog front-ends of cyber-physical systems

In safety-critical cyber-physical systems, analog front-ends combined with many-processors are being increasingly employed. An example is an imminent collision detection chip for cars. Such a complex system requires zero downtime and a very high dependability despite aging issues under harsh environmental conditions. By on-line monitoring the health status of the processor cores and taking appropriate counteractions if required, we have accomplished this goal in the past via IJTAG compatible embedded instruments and appropriate embedded software. This paper extends this approach to the analog / mixed-signal frontends of these systems, thereby creating a new uniform approach in design & test methodology, as well as a streamlined fault management. An IJTAG-compatible voltage monitor is introduced, for measuring aging-generated offset in OpAmps and SAR ADCs, as well as a delay-monitoring embedded instrument for detecting timing issues in ADCs. In addition, two-stage counter measures, like digitized recalibration and subsequent replacement, are presented to increase the lifetime by factors of the analog front-end of Cyber-Physical Systems-on-Chips.
Widespread crown condition decline, food web disruption, and amplified tree mortality with increased climate change-type drought

Climate change is progressively increasing severe drought events in the Northern Hemisphere, causing regional tree die-off events and contributing to the global reduction of the carbon sink efficiency of forests. There is a critical lack of integrated community-wide assessments of drought-induced responses in forests at the macroecological scale, including defoliation, mortality, and food web responses. Here we report a generalized increase in crown defoliation in southern European forests occurring during 1987–2007. Forest tree species have consistently and significantly altered their crown leaf structures, with increased percentages of defoliation in the drier parts of their distributions in response to increased water deficit. We assessed the demographic responses of trees associated with increased defoliation in southern European forests, specifically in the Iberian Peninsula region. We found that defoliation trends are paralleled by significant increases in tree mortality rates in drier areas that are related to tree density and temperature effects. Furthermore, we show that severe drought impacts are associated with sudden changes in insect and fungal defoliation dynamics, creating long-term disruptive effects of drought on food webs. Our results reveal a complex geographical mosaic of species-specific responses to climate change–driven drought pressures on the Iberian Peninsula, with an overwhelmingly predominant trend toward increased drought damage.
Maximum Likelihood Sequence Estimation of Quadrature Pulse-Overlapping Modulated Signals for Portable/Mobile Satellite Communications

A maximum-likelihood sequence estimation (MLSE) receiver structure for constant-envelope quadrature pulse-overlapping modulated (QPOM) signals in fading channels is presented. QPOM is first decomposed into a liner encoder followed by a memoryless modulator. The trellis diagram representing this inherent nonredundant coding structure is then used to construct its MLSE receiver. The upper bounds on the average bit error probability in both AWGN and Rayleigh fading channels are derived. Computer simulations are also used to verify the analytical results. In fast-fading shadowed mobile satellite channels the scheme is shown to outperform conventional QPSK techniques. It maintains the low complexity of 4PSK, but its performance is comparable to that of four-state 8PSK TCM schemes. The constant envelope, compact spectrum, superior performance, and low complexity enable QPOM to meet the requirements of low cost, small size, and high power and bandwidth efficiencies for portable/mobile satellite systems. >
Pharmacological Modulation of Mucosa-Related Impairment of β-Adrenoceptor-Mediated Relaxation in Human Detrusor

Objectives: The mucosa of human detrusor strips impairs catecholamine-induced relaxation. In order to elucidate which signal transduction pathways are involved in this cross talk between the mucosa and detrusor, we have studied the effects of several pharmacological agonists and antagonists on noradrenaline-mediated relaxation in intact and mucosa-denuded detrusor strips. Patients and Methods: Strips of detrusor tissue were obtained from patients who had undergone cystectomy for bladder cancer and were set up for force measurement. KCl- or carbachol-precontracted strips were relaxed with increasing concentrations of noradrenaline in the absence and in the presence of nitric oxide synthase inhibitor, L-NAME; P2X-receptor antagonist, PPADS; ETA-receptor antagonist, BQ-123; ETB-receptor antagonist, BQ-788; cyclooxygenase inhibitor, diclofenac; AT1-receptor antagonist, candesartan; and NK1-receptor antagonist, L-703,606. Results: In intact strips, KCl-stimulated force was enhanced by all blockers; carbachol-stimulated force increased with L-703,606. In denuded strips, only L-NAME augmented the KCl-stimulated contraction. Noradrenaline relaxed the precontracted detrusor strips to a significantly larger extent and at lower concentrations in denuded than in intact strips. L-NAME, PPADS and BQ-123/BQ-788 had little effect on noradrenaline-induced relaxation, whereas diclofenac, candesartan and L-703,606 sensitized intact carbachol-stimulated detrusor strips to noradrenaline-induced relaxation. Conclusion: Inhibition of the noradrenaline-induced relaxation of precontracted human detrusor strips by the mucosa is attenuated by diclofenac, candesartan and L-703,606 suggesting the involvement of prostanoids, angiotensin and neurokinin pathways. Further experiments are required to unravel the exact mechanisms.
Thinking about thinking: changes in first-year medical students’ metacognition and its relation to performance

Background Studies have shown the importance of metacognition in medical education. Metacognitive skills consist of two dimensions: knowledge of metacognition and regulation of metacognition. Aim This study hypothesizes that the knowledge and regulation of metacognition is significantly different at the beginning and end of the academic year, and a correlation exists between the two dimensions of metacognitive skills with academic performance. Methods The Metacognitive Skills Inventory comprising 52 Likert-scale items was administered to 159 first-year medical students at the University of Malaya. Students’ year-end results were used to measure their academic performance. Results A paired sample t-test indicated no significant difference for knowledge of metacognition at the beginning and end of the academic year. A paired sample t-test revealed significant difference for regulation of metacognition at the beginning and end of the academic year. A very strong correlation was found between the two dimensions of metacognition. The correlation between knowledge and regulation of metacognition with students’ academic result was moderate. Conclusions The improvement in students’ metacognitive regulation and the moderate correlation between knowledge and regulation of metacognition with academic performance at the end of the academic year indicate the probable positive influence of the teaching and learning activities in the medical program.
Specificity of skin test with varicella-zoster virus antigen in varicella-zoster and herpes simplex virus infections

Specificity of the skin test with varicella-zoster virus (VZV) antigen was examined in guinea pigs infected with herpes simplex virus (HSV) type 1 or VZV and in children with a history of HSV infection who developed varicella. Infected guinea pigs responded positively only to homologous virus. No cross-reaction between HSV and VZV was detected in the skin test, as well as in the neutralization test in infected guinea pigs, suggesting that the VZV skin test is specific for immunity to VZV infection. Twelve children were infected with HSV during an HSV epidemic and subsequently developed varicella in institutional settings. During the 2.5-month period between the HSV and VZV infections, the immune status of the children to VZV was negative both in the skin test and in the antibody test, although antibody to HSV was detected by an immune adherence hemagglutination test. After VZV infection, all responded positively both in the skin test and in the antibody test (immune adherence hemagglutination test) to VZV. These results suggest that the VZV skin test is specific for immunity to VZV infection, not cross-reactive to HSV infection in humans. This specificity will be of value in screening susceptibility or immunity to VZV, irrespective of prior HSV infection.
The Impact of Contract Enforcement Costs on Outsourcing and Aggregate Productivity

Legal institutions affect economic outcomes, but how much? This paper documents how costly supplier contract enforcement shapes firm boundaries, and quantifies the impact of this transaction cost on aggregate productivity and welfare. I embed a contracting game between a buyer and a supplier in a general-equilibrium model. Contract enforcement costs lead suppliers to under produce. Thus, firms will perform more of the production process in-house instead of outsourcing it. On a macroeconomic scale, in countries with slow and costly courts, firms should buy relatively less inputs from sectors whose products are more specific to the buyer-seller relationship. I present reduced-form evidence for this hypothesis using a novel measure of relationship-specificity, which I construct from microdata on US case law. I then structurally estimate my model, and perform welfare counterfactuals. Setting enforcement costs to US levels would increase real income by an average of 7.5 percent across all countries, and by an average of 15.3 percent across low-income countries. Hence, transaction costs and the determinants of firm boundaries are important for countries' aggregate level of development.
Genetic Variation in IL 28 B and Treatment-induced Clearance of Hepatitis C Virus in HIV-Positive Patients With Acute and Chronic Hepatitis C

Jacob Nattermann,1 Martin Vogel,1 Hans Dieter Nischalke,1 Mark Danta,12 Stefan Mauss,2 Hans-Jörg Stellbrink,3 Axel Baumgarten,5 Christoph Mayr,6 Raffaele Bruno,13 Cristina Tural,14 Gerd Klausen,7 Bonaventura Clotet,14 Uwe Naumann,3 Thomas Lutz,10 Michael Rausch,8 Knud Schewe,4 Bernhard Bienek,9 Georg Haerter,11 Tilman Sauerbruch,1 Juergen K. Rockstroh,1 and Ulrich Spengler1 1Department of Internal Medicine I, University of Bonn, Bonn, 2Center for HIV and Hepatogastroenterology, Duesseldorf; 3ICH and 4Practice St. Georg, Hamburg, 5Practice Dupke/Carganico/Baumgarten, 6Practice Aerzteforum Seestraße, 7Praxiszentrum Kaiserdamm, 8Practice Freiwald/Rausch, and 9Practice Bieniek/ Cordes, Berlin; 10HIV-cohort Frankfurt, Frankfurt, and 11Division of Infectious Diseases, Department of Internal Medicine, University Hospital and Medical Center, Ulm, Germany; 12Department of Medicine UNSW, St Vincent's Clinical School, Australia; 13Division of Infectious and Tropical Diseases, Hepatology outpatients Unit, University of Pavia—IRCCS, San Matteo Hospital, Italy; 14HIV Clinical Unit Department, University Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Barcelona, Spain
The Role of Genetics in Inhibitor Formation

Introduction Treatment of hemorrhages in patients with inherited severe hemophilia A is dependent on transfusion replacement therapy with either plasma-derived or recombinant factor VIII concentrates.1 Hemorrhages become very difficult to treat after inhibitors develop, resulting in significant decreases in qualityof- life and life expectancy.2-6 Strategies to treat hemorrhages in the face of an inhibitor include the use of “bypass” therapy with activated and nonactivated prothrombin complex concentrates, high-dose factor VIII, porcine factor VIII, and recombinant factor VIIa. None of these is as effective as treatment of the noninhibitor patient with factor VIII.2,6 Therefore, several strategies to induce tolerance to factor VIII administration have been attempted, including administration of daily high-dose intravenous infusions of factor VIII concentrate alone, or in combination with, immune-modulating therapy.2,6 These strategies are extraordinarily difficult and expensive and are frequently unsuccessful, particularly when the inhibitor is well established. Thus, the ability to predict which patients are at risk for inhibitor development and to identify factors that predispose to inhibitor development would allow investigation of therapies targeted to prevent the establishment of the inhibitor response or to provide the ability to initiate early and, thus, more effective, immune tolerance induction for those at risk.
Midterm Outcome of the Agility Total Ankle Arthroplasty

Background: Ankle arthritis is a debilitating condition that causes severe functional impairment. While arthrodesis has been the gold standard of surgical treatment for this condition, significant improvements in total ankle arthroplasty have made it a viable alternative. The purpose of this study was to look at the midterm follow-up of the Agility total ankle. Methods: A retrospective review of prospectively collected data was conducted on 127 consecutive Agility total ankles implanted between 2002 and 2009. Charts were reviewed to collect patient demographics. In addition, coronal alignment, overall arc of motion, tibiotalar component motion, syndesmotic fusion, zones of osteolysis, and subsidence were determined. A Kaplan-Meier survival and linear regression analysis were used to predict implant failure. A multivariate regression analysis was used to assess whether radiographic measures were predictive of patient satisfaction. Results: Ninety (78.2%) of 115 patients retained their primary implant, of which 105 were available for evaluation, with an average follow-up of 9.1 years. Twenty-five had their implant removed. The average score for the Foot and Ankle Ability Measure (FAAM) activities of daily living subscale was 82.4, FAAM sport subscale 55.3, postoperative visual analog scale (VAS) for pain 12.7, and Short Form-12 (SF-12) Health Survey physical component 45.8 and SF-12 mental component 56.1. Average arc of motion across the implant was 22.3 and 6.3 degrees in adjacent joints. Osteolysis most commonly occurred in zones 1 and 6. No statistical differences were found in the rate or location of subsidence. Linear regression analysis demonstrated that age at the time of surgery was predictive of failure (P = .036). Inflammatory and atraumatic arthritis demonstrated higher likelihoods of revision. No correlation was detected between radiographic parameters and outcomes scores (P > .05; rho >0.2). A significant reduction in mean VAS pain scores by 67.6% was maintained at an average of 8 years. Discussion: Our results were improved over the nondesigner outcomes published in the current literature. Survivorship approached 80% at 9 years, with Kaplan-Meier 14-year survival calculated at 70.4%. Patients with their original implant were functioning with a high level of satisfaction based on statistically validated outcome scores, which was independent of the radiographic appearance of their implant. Age at the time of surgery and inflammatory/atraumatic arthritis were predictive of failure. Level of Evidence: Level IV, case series.
Demonstration of Diamond-Based Schottky p-i-n Diode With Blocking Voltage > 500 V

Diamond is considered to be the ultimate semiconductor for power devices due to its high breakdown electric field, high carrier mobility, and superior thermal properties. The success of diamond-based electronic devices has been difficult due to critical challenges involved with poor doping efficiency and achievement of ohmic contacts. Achieving n-type diamond has proved to be more difficult over p-type so far. In this letter, we report the achievement of n-type doping in diamond, verified using Hall measurements, which was then used to fabricate Schottky p-i-n diodes measuring a forward current density greater than 300 A/cm2 at 4 V and breakdown voltage of over 500 V with a 3.5-μm -thick drift layer. A Silvaco simulation was performed which agreed well with the experimental data showing turn-ON voltage of 1 V and an ideality factor of 1.04, consistent with the model of a p-i-n diode with a fully depleted n-type contact.