Miracle-dz/UniFAR-FTUs huggingface dataset:
Trace Fear Conditioning Differentially Modulates Intrinsic Excitability of Medial Prefrontal Cortex–Basolateral Complex of Amygdala Projection Neurons in Infralimbic and Prelimbic Cortices

Neuronal activity in medial prefrontal cortex (mPFC) is critical for the formation of trace fear memory, yet the cellular mechanisms underlying these memories remain unclear. One possibility involves the modulation of intrinsic excitability within mPFC neurons that project to the basolateral complex of amygdala (BLA). The current study used a combination of retrograde labeling and in vitro whole-cell patch-clamp recordings to examine the effect of trace fear conditioning on the intrinsic excitability of layer 5 mPFC–BLA projection neurons in adult rats. Trace fear conditioning significantly enhanced the intrinsic excitability of regular spiking infralimbic (IL) projection neurons, as evidenced by an increase in the number of action potentials after current injection. These changes were also associated with a reduction in spike threshold and an increase in h current. In contrast, trace fear conditioning reduced the excitability of regular spiking prelimbic (PL) projection neurons, through a learning-related decrease of input resistance. Interestingly, the amount of conditioned freezing was (1) positively correlated with excitability of IL-BLA projection neurons after conditioning and (2) negatively correlated with excitability of PL-BLA projection neurons after extinction. Trace fear conditioning also significantly enhanced the excitability of burst spiking PL-BLA projection neurons. In both regions, conditioning-induced plasticity was learning specific (observed in conditioned but not in pseudoconditioned rats), flexible (reversed by extinction), and transient (lasted <10 d). Together, these data suggest that intrinsic plasticity within mPFC–BLA projection neurons occurs in a subregion- and cell-type-specific manner during acquisition, consolidation, and extinction of trace fear conditioning. SIGNIFICANCE STATEMENT Frontal lobe-related function is vital for a variety of important behaviors, some of which decline during aging. This study involves a novel combination of electrophysiological recordings from fluorescently labeled mPFC-to-amygdala projection neurons in rats with acquisition and extinction of trace fear conditioning to determine how specific neurons change during behavior. This is the first study to demonstrate that trace fear conditioning significantly alters the intrinsic excitability of mPFC-to-amygdala projection neurons in a subregion- and cell-type-specific manner, which is also transient and reversed by extinction. These data are of broad interest to the neuroscientific community, and the results will inspire additional studies investigating the cellular mechanisms underlying circuit-specific changes within the brain as a result of associative learning and memory.
Measuring supreme audit institutions’ outcomes: current literature and future insights

ABSTRACT Supreme audit institutions (SAIs) oversee the use of public resources and ensure accountability and, as such, they are very important for public sector reform. The author reviews the recent academic literature on how to measure SAIs’ results. Prior research was found to focus on performance auditing, rather than financial auditing. The authors rarely used quantitative indicators, but rather descriptive indicators or even anecdotes. Ways forward for researchers and SAIs are recommended. IMPACT This paper makes recommendations on how to measure the outcomes of SAI audits. The author also has important advice on how SAIs might improve the results of their audits: most importantly setting up follow-up procedures to monitor the effects of their audit recommendations. The paper highlights proposals (for example using a Likert scale of SAI’s audit activity, rate of SAI’s recommendations implemented), that public auditors can use to get a comprehensive picture of outcome measures to improve accountability.
Students and ICT: an analysis of student reaction to the use of computer technology in language learning

Thispaperdiscussesthereactionofstudentsinthreeuniversities to the use of information and communications technology (ICT) in their language learning experience. Although the findings apply to the language-learning context, there are more generic implications for the wider area of computer enhanced learning. The study uses qualitative and quantitative data collected as part of a doctoral investigation into computerbased language-learning environments. The paper considers one main research question: are students resistant, radical or reluctant users of the technology, and why? It examines how and why students use the Web, e-mail and CALL packages to enhance their learning. This study shows that students are generally not unsympathetic towards it, although some of the factors that affectthe level of student use of the technology, such as course relevance and access of computers, are often outside their control.
Preliminary Measurement Results of a 650 GHz Planar Circuit Balanced SIS Mixer

We present the design and preliminary experimental results of a broadband 650 GHz balanced SIS mixer utilizing two back-to-back unilateral finline tapers. The new design employs fully integrated circuit components onto a 15 μm silicon-on-insulator (SOI) substrate, hence greatly simplifying the balanced mixer block requirements. Independent testing of the on-chip RF quadrature hybrid and the DC/IF blocks showed performances consistence with the computational predictions. The fabricated mixer chip tests have also demonstrated successful operation in balanced mixing mode as the LO noise was separated from the IF output. Preliminary tests of the device's sensitivity gave a best double sideband (DSB) noise temperature of 714 K measured at 635 GHz, and remained at a similar level throughout the operating frequency band. The higher than expected noise temperature was mainly caused by a significant shift in the junction position during fabrication, in both the longitudinal and lateral directions, resulting in substantial shift in the tuning frequency and degradation in the coupling of power to the junction.
Overlapping Population Structures of Nasal Isolates of Staphylococcus aureus from Healthy Dutch and American Individuals

ABSTRACT To understand Staphylococcus aureus nasal carriage and its relationship with subsequent disease, insight into the natural (nonclinical) bacterial population structure is essential. This study investigated whether the distributions of S. aureus genotypes that cause colonization differ by geographic locales. High-throughput amplified fragment length polymorphism (AFLP) analysis was performed on nasal isolates of S. aureus from healthy American (n = 391) and Dutch (n = 829) volunteers. In total, 164,970 binary outcomes, covering 135 different markers per isolate, were scored. Methicillin resistance was defined for all strains; pulsed-field gel electrophoresis typing was performed for the American isolates. The overall population structures of the American and Dutch S. aureus isolates were comparable. The same four major AFLP clusters (I to IV) and subclusters were identified for both collections. However, the Dutch methicillin-susceptible S. aureus (MSSA) isolates were overrepresented in AFLP cluster III (P = 0.0016). Furthermore, the majority of the American methicillin-resistant S. aureus isolates (90.5%) were located in AFLP cluster I (P < 0.0001). This result identifies differences in the local prevalence of certain S. aureus genotypes. AFLP clusters II and III, which represent multilocus sequence typing clonal complexes 30 and 45, respectively, account for 46.4% of all MSSA isolates in the study, suggesting that these two lineages have evolved as extremely successful pandemic colonizers of humans. In conclusion, the overall population structures of American and Dutch nasal carriage isolates of S. aureus are surprisingly similar, despite subtle geographic differences in the prevalence of certain S. aureus genotypes.
EGCG stabilizes growth cone filopodia and impairs retinal ganglion cell axon guidance

Background: Antioxidants such as the green tea polyphenol epigallocatechin gallate (EGCG) are neuroprotective under many conditions in mature nervous systems; however, their impact has rarely been explored in developing nervous systems, in which a critical step is the formation of connections between neurons. Axons emerge from newly formed neurons and are led by a dynamic structure found at their tip called a growth cone. Here we explore the impact of EGCG on the development of retinal ganglion cell (RGC) axons, which connect the eye to the brain. Results: EGCG acts directly on RGC axons to increase the number of growth cone filopodia, fingerlike projections that respond to extrinsic signals, in vitro and in vivo. Furthermore, EGCG exposure leads to a dramatic defect in the guided growth of RGC axons where the axons fail to make a key turn in the mid‐diencephalon required to reach their target. Intriguingly, at guidance points where RGCs do not show a change in direction, EGCG has no influence on RGC axon behavior. Conclusions: We propose that EGCG stabilizes filopodia and prevents normal filopodial dynamics required for axons to change their direction of outgrowth at guidance decision points. Developmental Dynamics 245:667–677, 2016. © 2016 Wiley Periodicals, Inc.
Cell Swelling and a Nonselective Cation Channel Regulated by Internal Ca2+ and ATP in Native Reactive Astrocytes from Adult Rat Brain

Hypoxia–ischemia and ATP depletion are associated with glial swelling and blebbing, but mechanisms involved in these effects remain incompletely characterized. We examined morphological and electrophysiological responses of freshly isolated native reactive astrocytes (NRAs) after exposure to NaN3, which depletes cellular ATP. Here we report that NaN3 caused profound and sustained depolarization attributable to activation of a novel 35 pS Ca2+-activated, [ATP]i-sensitive nonselective cation (NCCa-ATP) channel, found in >90% of excised membrane patches. The channel was impermeable to Cl−, was nearly equally permeable to monovalent cations, with permeabilities relative to K+ being PCs+/PK+(1.06) ≈ PNa+/PK+(1.04) ≈ PRb+/PK+(1.02) ≈ PLi+/PK+(0.96), and was essentially impermeable to Ca2+ and Mg2+(PCa2+/PK+≈ PMg2+/PK+< 0.001), with intracellular Mg2+ (100 μm to 1 mm) causing inward rectification. Pore radius, estimated by fitting relative permeabilities of organic cations to the Renkin equation, was 0.41 nm. This channel exhibited significantly different properties compared with previously reported NCCa-ATP channels, including different sensitivity to block by various adenine nucleotides (EC50of 0.79 μm for [ATP]i, with no block by AMP or ADP), and activation by submicromolar [Ca]i. The apparent dissociation constant for Ca2+ was voltage dependent (0.12, 0.31, and 1.5 μm at −40, −80, and −120 mV, respectively), with a Hill coefficient of 1.5. Channel opening by [ATP]i depletion was accompanied by and appeared to precede blebbing of the cell membrane, suggesting participation of this channel in cation flux involved in cell swelling. We conclude that NRAs from adult rat brain express a 35 pS NCCa-ATP channel that may play an important role in the pathogenesis of brain swelling.
Ethnic variation in early age-related macular degeneration lesions between white Australians and Singaporean Asians.

PURPOSE We compared early age-related macular degeneration (AMD) lesion characteristics between white Australians and Singaporean Asians. METHODS Participants of the Blue Mountains Eye Study (BMES; whites, n = 3508) and the Singapore Epidemiology of Eye Disease Study (SEED; Malay, n = 3280, Indian, n = 3400, and Chinese, n = 3353) underwent examinations, including retinal photography. The AMD lesions were assessed following the Wisconsin AMD grading protocol by the same photographic grader. Prevalence and characteristics of early AMD lesions were compared between the BMES and the SEED. The associations between ethnicity and early AMD lesion types were analyzed using logistic regression models adjusting for age, sex, smoking status, lipids, and genetic polymorphisms associated with AMD. RESULTS After age-standardization to the BMES population, the prevalence of distinct soft drusen was significantly higher in Singaporeans compared to Australians (23.9%, 95% confidence interval [CI] 22.9-25.0 vs. 6.2%, 95% CI 5.3-7.0), with an adjusted odds ratio (OR) of 4.6 (95% CI 3.4-6.0). In contrast, the prevalence of indistinct soft or reticular drusen was significantly lower in Singaporeans compared to Australians (6.5%, 95% CI 5.9-7.1 vs. 8.3%, 95% CI 7.4-9.3, with nonsignificant adjusted OR of 1.2, 95% CI 0.8-1.7). Soft drusen of any type were present frequently at the inner and outer macula (within a zone ≥500 to <3000 μm radius from the foveal center) among Singaporeans, while among Australians soft drusen were present more frequently at the central macula (<500 μm radius). CONCLUSIONS Singaporean Asians had a milder spectrum of early AMD lesions and lesion characteristics (predominantly distinct soft drusen and noncentral location) compared to white Australians.
Synaptic connections involving immunoreactive glycine receptors in the turtle retina

Abstract The distribution of glycine receptors in the turtle retina was studied with the aid of a monoclonal antibody that detects the 93-kD protein associated with the strychnine-sensitive glycine receptor. Light microscopically, receptors were found in the inner plexiform layer and, more sparsely, in the innermost parts of the inner nuclear layer. No receptors were seen to be associated with photoreceptor cells, horizontal cells, or any other structures in the distal inner nuclear layer or outer plexiform layer. Ultrastructurally, glycine receptors were found on the inner face of postsynaptic membranes of processes from amacrine and presumed ganglion cells and always involved amacrine cell processes as the presynaptic element. Such glycine receptor immunoreactive synapses onto amacrine cell processes were distributed throughout the inner plexiform layer with a peak density near the middle. On the other hand, output synapses onto ganglion cell processes displaying immunoreactive glycine receptor sites showed a bimodal distribution in the inner plexiform layer. Glycine receptor immunoreactivity was not detected on bipolar cells, but presumed glycine-utilizing processes (i.e. those presynaptic to immunoreactive glycine receptors) were occasionally found to be postsynaptic in bipolar cell dyads. The majority of the synaptic input to the presumed glycine-utilizing amacrine cell processes was from other amacrine processes, some of which were themselves glycine utilizing. The observations suggest that glycinergic synapses in the turtle retina are, to a large extent, engaged in processing interamacrine signals.
Tissue Injury from Tricyclic Antidepressants Used as Local Anesthetics

Neurotoxicity has been reported with tricyclic antidepressants (TCAs) used as local anesthetics. We examined the hypothesis that TCAs cause tissue injury, particularly myotoxicity, as occurs with many local anesthetics. Animals were given sciatic nerve injections with 0–80 mM doxepin, amitriptyline, or bupivacaine (1.5 mL for histological studies, 0.3 mL for neurobehavioral studies). Four days after injection, the TCAs caused ischemic tissue injury. Subcutaneous tissue showed expansion and hardening, with hemorrhage and adhesion to overlying skin. Muscle was diffusely pale. Histopathology showed coagulative necrosis of muscle and surrounding soft tissues, with thrombus formation in vasculature near affected areas. These findings were much reduced with bupivacaine. TCA-injected and bupivacaine-injected animals also developed characteristic local anesthetic myotoxicity. Amitriptyline proved less potent than bupivacaine as a local anesthetic: the concentrations required to provide 100 min of nerve block were 20 mM and 3 mM, respectively. Some animals receiving large concentrations of amitriptyline developed spontaneous recrudescence of nerve blockade or had irreversible nerve blockade, both of which may reflect nerve injury. Neither finding occurred in animals injected with bupivacaine. TCAs do not appear to offer any advantages over conventional local anesthetics and do appear to risk substantially increased toxicity.
Conservation of Mass‐Specific Metabolic Rate among High‐ and Low‐Elevation Populations of the Acridid Grasshopper Xanthippus corallipes

High‐elevation populations of many grasshopper species produce small adults in response to shortened growing seasons and cooler ambient temperatures. Mass‐specific metabolic rate tends to increase with elevation, and several authors have argued that this is an adaptation to accelerate development. In the present study, the relationship of thermoregulation and metabolism was investigated in adults of the acridid grasshopper Xanthippus corallipes from six populations along an elevation gradient. Thermoregulation was measured in the field, and several lines of evidence suggested that afternoon body temperatures were actively maintained within each population. Populations were found to maintain stable afternoon body temperatures that correlate negatively with elevation. Elevation had a strong negative effect on adult mass. Mass‐specific metabolic rates at 35° and 45°C correlated positively with elevation. However, population differences in mass explained most of the variation in mass‐specific metabolic rates, and when mass was used as a covariate, the effect of elevation disappeared. Mass‐specific metabolic rates at afternoon field body temperatures were estimated and found not to differ among populations. Thus, differences in thermoregulation offset the effect of mass on mass‐specific metabolic rate across populations, such that X. corallipes adults exhibited a common mass‐specific metabolic rate in the wild, independent of large population differences in mass and ambient temperatures.
Evidence for obesity paradox in patients with acute coronary syndromes: a report from the Swedish Coronary Angiography and Angioplasty Registry.

AIMS The obesity paradox refers to the epidemiological evidence that obesity compared with normal weight is associated with counter-intuitive improved health in a variety of disease conditions. The aim of this study was to investigate the relationship between body mass index (BMI) and mortality in patients with acute coronary syndromes (ACSs). METHODS AND RESULTS We extracted data from the Swedish Coronary Angiography and Angioplasty Registry and identified 64 436 patients who underwent coronary angiography due to ACSs. In 54 419 (84.4%) patients, a significant coronary stenosis was identified, whereas 10 017 (15.6%) patients had no significant stenosis. Patients were divided into nine different BMI categories. The patients with significant stenosis were further subdivided according to treatment received such as medical therapy, percutaneous coronary intervention (PCI), or coronary artery by-pass grafting. Mortality for the different subgroups during a maximum of 3 years was compared using Cox proportional hazards regression with the lean BMI category (21.0 to <23.5 kg/m(2)) as the reference group. Regardless of angiographic findings [significant or no significant coronary artery disease (CAD)] and treatment decision, the underweight group (BMI <18.5 kg/m(2)) had the greatest risk for mortality. Medical therapy and PCI-treated patients with modest overweight (BMI category 26.5-<28 kg/m(2)) had the lowest risk of mortality [hazard ratio (HR) 0.52; 95% CI 0.34-0.80 and HR 0.64; 95% CI 0.50-0.81, respectively]. When studying BMI as a continuous variable in patients with significant CAD, the adjusted risk for mortality decreased with increasing BMI up to ~35 kg/m(2) and then increased. In patients with significant CAD undergoing coronary artery by-pass grafting and in patients with no significant CAD, there was no difference in mortality risk in the overweight groups compared with the normal weight group. CONCLUSION In this large and unselected group of patients with ACSs, the relation between BMI and mortality was U-shaped, with the nadir among overweight or obese patients and underweight and normal-weight patients having the highest risk. These data strengthen the concept of the obesity paradox substantially.
Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis.

PURPOSE A phase I trial of intrathecal (IT) topotecan was performed to determine the optimal dose, the dose-limiting toxic effects, and the incidence and severity of other toxic effects in patients 3 years and older with neoplastic meningitis. PATIENTS AND METHODS Twenty-three assessable patients received IT topotecan administered by means of either lumbar puncture or an indwelling ventricular access device (Ommaya reservoir). Intrapatient dose escalation from 0.025 mg to 0.2 mg was performed in the first cohort of patients. Subsequent cohorts of patients were treated at fixed dose levels of 0.2 mg, 0.4 mg, or 0.7 mg. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. RESULTS Arachnoiditis, characterized by fever, nausea, vomiting, headache, and back pain, was the dose-limiting toxic effect in two of four patients enrolled at the 0.7 mg dose level. The maximum-tolerated dose (MTD) was 0.4 mg. Six of the 23 assessable patients had evidence of benefit manifested as prolonged disease stabilization or response. CONCLUSION The MTD and recommended phase II dose of IT topotecan in patients who are 3 years or older is 0.4 mg. A phase II trial of IT topotecan in children with neoplastic meningitis is in progress.
From the SelectedWorks of Cécile Péraire May , 2017 Software Development Waste

Context: Since software development is a complex socio-technical activity that involves coordinating different disciplines and skill sets, it provides ample opportunities for waste to emerge. Waste is any activity that produces no value for the customer or user. Objective: The purpose of this paper is to identify and describe different types of waste in software development. Method: Following Constructivist Grounded Theory, we conducted a two-year five-month participant-observation study of eight software development projects at Pivotal, a software development consultancy. We also interviewed 33 software engineers, interaction designers, and product managers, and analyzed one year of retrospection topics. We iterated between analysis and theoretical sampling until achieving theoretical saturation. Results: This paper introduces the first empirical waste taxonomy. It identifies nine wastes and explores their causes, underlying tensions, and overall relationship to the waste taxonomy found in Lean Software Development. Limitations: Grounded Theory does not support statistical generalization. While the proposed taxonomy appears widely applicable, organizations with different software development cultures may experience different waste types. Conclusion: Software development projects manifest nine types of waste: building the wrong feature or product, mismanaging the backlog, rework, unnecessarily complex solutions, extraneous cognitive load, psychological distress, waiting/multitasking, knowledge loss, and ineffective communication. Keywords-Software engineering waste, Extreme Programming, Lean Software Development