Miracle-dz/UniFAR-FTUs huggingface dataset:
What is the best approach to glycaemic control in patients with type 2 diabetes?

Recent studies have suggested that there is more than one pharmacological approach to glycaemic control in patients with type 2 diabetes and that insulin may not always be the best approach to achieve control in such patients. Conventional wisdom has always held that insulin, owing to its unlimited potential for lowering blood sugar in patients with severe hyperglycaemia, was a superior therapeutic agent compared with other agents with more limited glycaemic efficacy. Insulin was therefore the accepted, and often the preferred, agent for patients with poorly controlled diabetes. This conclusion, however, overlooks two major characteristics regarding all injectable insulins, even modern insulin analogues. First, analogues do not exactly match the physiology of insulin secretion by the non-diabetic pancreas. As a result, their pharmacodynamic action profiles do not match prandial glucose excursions in patients and thus create an excess risk of hypoglycaemia. Human insulin and older types of animal insulin have a far greater potential for hypoglycaemic reactions than do modern insulin analogues, but even the latter clearly have residual hypoglycaemic potential [1]. Excess hypoglycaemia leads to undesirable outcomes, such as poor glycaemic control, weight gain from defensive eating and a greater number of emergency room visits and hospitalizations for treatment [2]. Second, in the presence of well defined standards for glycaemic control, attempts to achieve those targets in clinical practice with commercially available insulins typically incur excess rates of hypoglycaemia, which are intolerable to patients and which therefore limit the degree of glycaemic control attainable. Such limitations may be the result of actual experience in any given patient, or they may result from fear of hypoglycaemia on the part of the patient or the physician, or both. As a result, in almost all modern trials, even with the newest injectable insulin analogues, the majority of patients with type 2 diabetes fail to achieve the modest goals for glycaemic control of the American Diabetes Association [glycated haemoglogin (HbA1c) <7.0%]. Owing to the lack of alternative therapies that are effective in helping more advanced degrees of pancreatic insufficiency and hyperglycaemia, injectable basal insulin was often used in patients failing one or more oral agents and its adverse reactions tolerated, despite its many failings and inadequacies. Within the last decade, several new classes of antidiabetic therapies have appeared that produce superior glycaemic
Advanced Simulation and Emulation Techniques for Fault Injection

The environment can produce transient faults in digital circuits, especially nowadays with the new technology development. Fault injection has been widely used to evaluate the hardness degree of circuits in which fault tolerance is a requirement, like aerospace or automotive applications. The magnitude of the fault effects evaluation problem is computationally unaffordable, if an exhaustive test must be performed on a circuit. Several solutions have been proposed to improve the performance of the process. Simulation based fault injection offers slower execution speed, but a great flexibility in the fault injection campaign. Emulation based solution are much faster, but not so flexible. In this paper, the fault injection problem is analysed from a performance point of view, and some optimized solutions are proposed.
Inhibitory interactions in the human vision system revealed in pattern‐evoked potentials.

1. Visual evoked potentials (v.e.p.s) were recorded from human adults to investigate orientation‐specific neural interactions. The stimuli were the sum of two gratings, sinusoidally modulated in space and time at different frequencies. Recordings were made for one grating (test) alone, and with another superimposed grating (mask), oriented parallel or orthogonal to the test. The amplitude and phase of the v.e. p.s at twice the test modulation frequency (second harmonic) was measured as a function of test contrast to produce contrast‐response curves. 2. Orthogonal masks attenuated considerably the amplitude of v.e. p.s. The attenuation at any given contrast was approximately proportional, or multiplicative, lowering the slope of the contrast‐response curve, without affecting significantly the extrapolated threshold. Parallel masks also attenuated v.e. p. amplitudes but in a different way, leaving the slope of the contrast‐response curves unchanged, while elevating threshold. 3. The attenuation by orthogonal masks occurred over a wide range of test spatial frequencies, from 0.8 to 8 cycles/deg. For any given test spatial frequency, the most effective masks were those of spatial frequency similar to or lower than the test. Masks of spatial frequency 1.5 octaves higher than the test did not attenuate v.e. p. amplitudes. 4. The mask temporal frequency for maximal attenuation of v.e. p. amplitude was around 12 Hz, with stationary masks having little effect. 5. Under most conditions, the phase of the second harmonic of the v.e. p., increased with increasing contrast (phase advance). Superimposition of a parallel mask abolished phase advance, while orthogonal masks increased it. 6. Comparisons with single cortical unit and evoked potential recordings in cats suggest that the attenuation by orthogonal masks reflects intracortical inhibitory interactions between cell populations of different orientation preference.
Estradiol and Testosterone Levels Are Lower after Oophorectomy than after Natural Menopause

Objective: The aim of this study was to compare hormone levels between women who became postmenopausal after a prophylactic bilateral salpingo-oophorectomy, and women who became postmenopausal in a natural way. Methods: In this cross-sectional study, we investigated estradiol, testosterone, SHBG, IGF-1 and IGFBP-3 levels in 35 surgically and 40 naturally postmenopausal women. Results: Serum samples were drawn at a mean age of 45.9 years for women with surgical menopause and at 56.5 years for women with natural menopause. Mean estradiol levels declined 1.4 pmol/l per year in both menopausal groups, however, at an 11.1 pmol/l lower level for women with surgical menopause. Testosterone levels of naturally postmenopausal women remained stable at a level of 0.89 nmol/l, while testosterone levels of the surgically postmenopausal women declined 0.04 nmol/l per year. Conclusions: For IGF-1, IGFBP-3 and SHBG, no differences were found between surgically and naturally postmenopausal women. Lower estradiol levels of surgically as compared to naturally postmenopausal women seem to be fully explained by the earlier onset of menopause in combination with the same age-related decrease. However, a decrease in testosterone levels seems to occur in oophorectomized women only, suggesting postmenopausal activity of ovaries in situ.
Na+—Ca2+ Exchange Currents in Cortical Neurons: Concomitant Forward and Reverse Operation and Effect of Glutamate

Na+‐Ca2+ exchanger‐associated membrane currents were studied in cultured murine neocortical neurons, using whole‐cell recording combined with intracellular perfusion. A net inward current specifically associated with forward (Na+o‐Ca2+i) exchange was evoked at ‐40 mV by switching external 140 mM Li+ to 140 mM Na+. The voltage dependence of this current was consistent with that predicted for 3Na+:1Ca2+ exchange. As expected, the current depended on internal Ca2+, and could be blocked by intracellular application of the exchanger inhibitory peptide, XIP. Raising internal Na+ from 3 to 20 mM or switching the external solution from 140 mM Li+ to 30 mM Na+ activated outward currents, consistent with reverse (Na+,‐Ca2+o) exchange. An external Ca2+‐sensitive current was also identified as associated with reverse Na+‐Ca2+ exchange based on its internal Na+ dependence and sensitivity to XIP. Combined application of external Na+ and Ca2+ in the absence of internal Na+ triggered a 3.3–fold larger inward current than the current activated in the presence of 3 mM internal Na+, raising the intriguing possibility that Na+‐Ca2+ exchangers might concurrently operate in both the forward and the reverse direction, perhaps in different subcellular locations. With this idea in mind, we examined the effect of excitotoxic glutamate receptor activation on exchanger operation. After 3–5 min of exposure to 100–200 μM glutamate, the forward exchanger current was significantly increased even when external Na+ was reduced to 100 mM, and the external Ca2+‐activated reverse exchanger current was eliminated.
Role of retinoids in the CNS: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid

Retinoic acid (RA), a retinoid metabolite, acts as a gene regulator via ligand‐activated transcription factors, known as retinoic acid receptors (RARs) and retinoid X receptors (RXRs), both existing in three different subtypes, α, β and γ. In the intracellular regulation of retinoids, four binding proteins have been implicated: cellular retinol binding protein (CRBP) types I and II and cellular retinoic acid binding protein (CRABP) types I and II. We have used in situ hybridization to localize mRNA species encoding CRBP‐ and CRABP I and II as well as all the different nuclear receptors in the developing and adult rat and mouse central nervous system (CNS), an assay to investigate the possible presence of RA, and immunohistochemistry to also analyse CRBP I‐ and CRABP Iimmunoreactivity (IR). RXRβ is found in most areas while RARα and ‐β and RXRα and ‐γ show much more restricted patterns of expression. RARα is found in cortex and hippocampus and RARβ and RXRγ are both highly expressed in the dopamine‐innervated areas caudate/putamen, nucleus accumbens and olfactory tubercle. RARγ could not be detected in any part of the CNS. Using an in vitro reporter assay, we found high levels of RA in the developing striatum. The caudate/putamen of the developing brain showed strong CRBP I‐IR in a compartmentalized manner, while at the same time containing many evenly distributed CRABP I‐IR neurons. The CRBP I‐ and CRABP I‐IR patterns were closely paralleled by the presence of the corresponding transcripts. The specific expression pattern of retinoid‐binding proteins and nuclear retinoid receptors as well as the presence of RA in striatum suggests that retinoids are important in many brain structures and emphasizes a role for retinoids in gene regulatory events in postnatal and adult striatum.
Impact of Education and Culture on Entrepreneurship

This paper explored the impact of secondary education level and national culture on the entrepreneurial activities. Specifically, we examine how higher education and one dimension of national culture (individualist-collectivist orientation) are related to the ratio of opportunity-entrepreneurship in a country. The research model is developed as: high education and individualism are positive determinants of the entrepreneurial activity, but only when the motivation for starting new ventures is opportunity or improvement and not when people do it for necessity. Our variables were developed with GEM data, World Economic Forum's Global Competitiveness Report and Hofstede's cultural determinants for 57 countries for the years 2009, 2010 and 2011, and we test our hypothesis empirically. In addition to our testing independent variables, we added 3more control variables, economic freedom, and perception of corruption and property rights, in order to specify our findings. Our analysis proves that higher education and individualism are determinants for superior opportunity entrepreneurial activity. Education levels and individualism, however, do not show the interaction effect. Our results show that, after controlling for other entrepreneurship determinants variables borrowed from the institutional theory of entrepreneurship, education at the tertiary level i.e., university, college, etc., positively affects the choice of individuals to pursue opportunity driven entrepreneurship. Moreover, individualism is also found to positively affect entrepreneurs' choice. We hope this research contribute in expanding our understanding on global entrepreneurship activities.
Towards parliamentarisation of foreign and security policy?

Abstract It is customary to argue that foreign policy is very much dominated by the executive, with parliaments wielding limited influence. However, with the exception of the US Congress, legislative‒executive relations in the realm of foreign and security policy have attracted remarkably little scholarly attention. Drawing on a principal‒agent framework, this collection scrutinises the conventional wisdom of ‘executive autonomy’ in foreign affairs, indicating that even though parliaments have arguably become more involved in foreign and security policy over time, any notions of parliamentarisation need to be treated with caution. While expectations of consensus in the name of the national interest continue to play an important role in foreign policy decision-making, the papers highlight the role of party-political contestation structuring parliamentary debates and votes in this increasingly politicised issue area. This introductory paper introduces the analytical framework and hypotheses guiding the contributions in this collection, summarises their main findings and suggests avenues for future research.
Designing Emotionally Expressive Robots: A Comparative Study on the Perception of Communication Modalities

Socially assistive agents, be it virtual avatars or robots, need to engage in social interactions with humans and express their internal emotional states, goals, and desires. In this work, we conducted a comparative study to investigate how humans perceive emotional cues expressed by humanoid robots through five communication modalities (face, head, body, voice, locomotion) and examined whether the degree of a robot's human-like embodiment affects this perception. In an online survey, we asked people to identify emotions communicated by Pepper - a highly human-like robot and Hobbit - a robot with abstract humanlike features. A qualitative and quantitative data analysis confirmed the expressive power of the face, but also demonstrated that body expressions or even simple head and locomotion movements could convey emotional information. These findings suggest that emotion recognition accuracy varies as a function of the modality, and a higher degree of anthropomorphism does not necessarily lead to a higher level of recognition accuracy. Our results further the understanding of how people respond to single communication modalities and have implications for designing recognizable multimodal expressions for robots.
Reduced Cβ statistical potentials can outperform all‐atom potentials in decoy identification

We developed a series of statistical potentials to recognize the native protein from decoys, particularly when using only a reduced representation in which each side chain is treated as a single Cβ atom. Beginning with a highly successful all‐atom statistical potential, the Discrete Optimized Protein Energy function (DOPE), we considered the implications of including additional information in the all‐atom statistical potential and subsequently reducing to the Cβ representation. One of the potentials includes interaction energies conditional on backbone geometries. A second potential separates sequence local from sequence nonlocal interactions and introduces a novel reference state for the sequence local interactions. The resultant potentials perform better than the original DOPE statistical potential in decoy identification. Moreover, even upon passing to a reduced Cβ representation, these statistical potentials outscore the original (all‐atom) DOPE potential in identifying native states for sets of decoys. Interestingly, the backbone‐dependent statistical potential is shown to retain nearly all of the information content of the all‐atom representation in the Cβ representation. In addition, these new statistical potentials are combined with existing potentials to model hydrogen bonding, torsion energies, and solvation energies to produce even better performing potentials. The ability of the Cβ statistical potentials to accurately represent protein interactions bodes well for computational efficiency in protein folding calculations using reduced backbone representations, while the extensions to DOPE illustrate general principles for improving knowledge‐based potentials.
The NIMH community violence project: II. Children's distress symptoms associated with violence exposure.

The rising tide of violence in American cities has placed the causes and consequences of violence squarely on the public health agenda. The U.S. Government's Year 2000 National Health Promotion and Disease Prevention Objectives includes a full chapter devoted to violence issues and delineates a number of goals and programs aimed at reducing the number of deaths and injuries associated with violence (Public Health Service 1990). Notably absent from these objectives, however, is attention to the possible adverse psychological consequences of exposure to acute or chronic violence. Nonetheless, in light of numerous media reports of children's exposure to community violence and recent reports documenting high levels of exposure even among very young children (Richters and Martinez 1993), it is reasonable to question whether the risks of exposure extend beyond death and physical injury to psychological well-being.
Control of systems with input nonlinearities and uncertainties: An adaptive approach

Although many of today's nonlinear control design algorithms assume the system dynamics to be affine in the control input, this often does not hold in practice. A remedy for this is to instead design a control law in terms of some other entity that satisfies the structural assumptions of the design method. In this contribution we discuss how to realize such a virtual control law in terms of the actual control variable. Given a nominal static invertible model of the mapping between the two, the true mapping is assumed to differ from the model by a constant bias. Two ways of how to estimate this bias on-line and use it for feedback are proposed. One of them corresponds to adaptive backstepping, the other one is an observer based approach. In both cases we investigate how to guarantee closed loop stability when the estimate is used for feedback.
Secretion of Vascular Endothelial Growth Factor by Primary Human Fibroblasts at Senescence*

Cellular senescence prevents the proliferation of cells at risk for neoplastic transformation. Nonetheless, the senescence response is thought to be antagonistically pleiotropic and thus contribute to aging phenotypes, including, ironically, late life cancers. The cancer-promoting activity of senescent cells is likely due to secreted molecules, the identity of which remains largely unknown. Here, we have shown that senescent fibroblasts, much more than presenescent fibroblasts, stimulate tumor vascularization in mice. Weakly malignant epithelial cells co-injected with senescent fibroblasts had larger and greater numbers of blood vessels compared with controls. Accordingly, increased vascular endothelial growth factor (VEGF) expression was a frequent characteristic of senescent human and mouse fibroblasts in culture. Importantly, conditioned medium from senescent fibroblasts, more than medium from presenescent cells, stimulates cultured human umbilical vein endothelial cells to invade a basement membrane, a hallmark of angiogenesis. Increased VEGF expression was specific to the senescent phenotype and increased whether senescence was induced by replicative exhaustion, overexpression of p16Ink4a, or overexpression of oncogenic RAS. The senescence-dependent increase in VEGF production was accompanied by very little increase in hypoxic-inducible (transcription) factor 1 α protein levels, and hypoxia further induced VEGF in senescent cells. This result suggests the rise in VEGF expression at senescence is not a hypoxic response. Our findings may in part explain why senescent cells stimulate tumorigenesis in vivo and support the idea that senescent cells may facilitate age-associated cancer development by secreting factors that promote malignant progression.
Research on the simulation method of an underwater target dimension characteristic based on circular arc array

The highlight structure model of underwater target echo and the model of underwater target dimension recognition based on cross-spectrum method of splitting beam are given. The generating methods of reflecting and scattering highlights digital time series are presented. We introduce a method to simulate the target dimension characteristic with a circular arc array placed in an anechoic pool. Each projector of the arc array transmits acoustic highlight simulating signals in synchronous or asynchronous mode. The transmitted signals arc transformed into element space by the time-varied matrixes, which are, used Io project the highlights on the arc array. The method is applied in the homing system simulation. The simulation results show that the methods can get better simulation effect of an underwater target dimension. The methods not only can simulate the working mode of conventional acoustic simulator, but also can simulate more complex target bearing changing, and can be applied to underwater weapon homing hardware in the loop simulation.
Taste pathways to hypothalamus and amygdala

The projections of a third order gustatory relay in the dorsal pons of rats have been traced using tritiated proline autoradiography and antidromic activation of pontine neurons from electrodes in the thalamus and amygdala. Labelled axons collect in the central tegmental tract and ascend to the thalamic taste area in the medial extension of the ventrobasal complex. The majority of the fibers remain ipsilateral, but a few cross in the rostral pons and midbrain. The largest crossing occurs at the level of the thalamic termination. Many fascicles of fibers continue rostrally by passing beneath the thalamic taste area, piercing the medial lemniscus, and spreading out along the dorsomedial corner of the internal capsule (IC). The terminal field at this level caps IC from the subthalamic nucleus down into the far‐lateral hypothalamus. Labelled axons gradually penetrate through the internal capsule, and ramify throughout the underlying substantia innominata. This terminal zone extends laterally into the rostral end of the central nucleus of the amygdala, which is densely labelled to its caudal extremity. At the caudal end of the amygdala labelled fibers are visible in one component of the stria terminalis. These fibers can be followed over the dorsal thalamus into a smaller, but equally dense terminal area in the dorsolateral bed nucleus of the stria terminalis. The electrophysiological data demonstrate that pontine gustatory units can be antidromically activated by electrodes located in or near the central nucleus of the amygdala. Since many of the same units can also be driven from the thalamic taste area, at least some of the axons traced autoradiographically probably convey gustatory information to the hypothalamus and amygdala.