Miracle-dz/UniFAR-FTUs huggingface dataset:
Hippocampal participation in navigational map learning in young homing pigeons is dependent on training experience

The homing pigeon navigational map is perhaps one of the most striking examples of a naturally occurring spatial representation of the environment used to guide navigation. In a previous study, it was found that hippocampal lesions thoroughly disrupt the ability of young homing pigeons held in an outdoor aviary to learn a navigational map. However, since that study an accumulation of anecdotal data has hinted that hippocampal‐lesioned young pigeons allowed to fly during their first summer could learn a navigational map. In the present study, young control and hippocampal‐lesioned homing pigeons were either held in an outdoor aviary or allowed to fly during the time of navigational map learning. At the end of their first summer, the birds were experimentally released to test for navigational map learning. Independent of training experience, control pigeons oriented homeward during the experimental releases demonstrating that they learned a navigational map. Surprisingly, while the aviary‐held hippocampal‐lesioned pigeons failed to learn a navigational map as reported previously, hippocampal‐lesioned birds allowed flight experience learned a navigational map indistinguishable from the two control groups. A subsequent experiment revealed that the navigational map learned by the three groups was based on atmospheric odours. The results demonstrate that hippocampal participation in navigational map learning depends on the type of experience a young bird pigeon has, and presumably, the type of navigational map learned.
Low temperature blocks transport and sorting of cathepsin D in fibroblasts.

The transport of newly synthesized cathepsin D in fibroblasts at 16-28 degrees C was compared to that at 37 degrees C. At 37 degrees C newly synthesized cathepsin D passes the trans Golgi within 30-60 min, becomes segregated from the secretory route into prelysosomal organelles within 1-2 h and processed to mature forms in dense lysosomes within 1.5-3 h after synthesis. The small fraction of cathepsin D that escapes transport into lysosomes is secreted within less than 2 h. At 16-28 degrees C the transport of cathepsin D to lysosomes is inhibited in a temperature-dependent manner. At 16-28 degrees C cathepsin D precursors are slowly transported to the trans Golgi. The cathepsin D precursors accumulate at a site that is in continuity with the secretory pathway and located within or distal of the trans Golgi and proximal to the site where cathepsin D precursors leave the secretory pathway as complexes with mannose 6-phosphate receptors. The arrest at this site is not complete. The receptor-dependent segregation of the cathepsin D precursors released from the block is impaired at less than or equal to 26 degrees C. The inhibition of segregation results in an increased, albeit retarded secretion of cathepsin D. The fraction of cathepsin D precursors that is segregated from the secretory pathway encounters a further low temperature block in prelysosomal organelles. There cathepsin D precursors are proteolytically processed to an intermediate form, which accumulates transiently. (ABSTRACT TRUNCATED AT 250 WORDS)
Memory SEU simulations using 2-D transport calculations

An advance in the simulation of a single event upset (SEU) of a static memory is achieved by combining transport and circuit effects in a single calculation. The program SIFCOD [4] is applied to the four transistors of a CMOS SRAM cell to determine its transient circuit response following a very high energy ion hit. Results unique to this type of calculation include determination of relative upset sensitivites and different upset mechanisms for specific area hits, i.e., the OFF p-channel drain, the OFF or ON n-channel drain, etc. The calculation determines the transport variables as a function of time in two-space dimensions for each of the four transistors and provides the nodal voltage and current responses for assessing memory upset conditions.
Severe head injury in children: emergency access to neurosurgery in the United Kingdom

Objective: To determine the scale of acute neurosurgery for severe traumatic brain injury (TBI) in childhood, and whether surgical evacuation for haematoma is achieved within four hours of presentation to an emergency department. Methods: A 12 month audit of emergency access to all specialist neurosurgical and intensive care services in the UK. Severe TBI in a child was defined as that necessitating admission to intensive care. Results: Of 448 children with severe head injuries, 91 (20.3%) underwent emergency neurosurgery, and 37% of these surgical patients had at least one non-reactive and dilated pupil. An acute subdural or epidural haematoma was present in 143/448 (31.9%) children, of whom 66 (46.2%) underwent surgery. Children needing surgical evacuation of haematoma were at a median distance of 29 km (interquartile range (IQR) 11.8–45.7) from their neurosurgical centre. One in four children took longer than one hour to reach hospital after injury. Once in an accident and emergency department, 41% took longer than fours hours to arrive at the regional centre. The median interval between time of accident and arrival at the surgical centre was 4.5 hours (IQR 2.23–7.73), and 79% of inter-hospital transfers were undertaken by the referring hospital rather than the regional centre. In cases where the regional centre undertook the transfer, none were completed within four hours of presentation—the median interval was 6.3 hours (IQR 5.1–8.12). Conclusions: The system of care for severely head injured children in the UK does not achieve surgical evacuation of a significant haematoma within four hours. The recommendation to use specialist regional paediatric transfer teams delays rather than expedites the emergency service.
Functional Effects of a Tissue‐Engineered Cardiac Patch From Human Induced Pluripotent Stem Cell‐Derived Cardiomyocytes in a Rat Infarct Model

A tissue‐engineered cardiac patch provides a method to deliver cardiomyoctes to the injured myocardium with high cell retention and large, controlled infarct coverage, enhancing the ability of cells to limit remodeling after infarction. The patch environment can also yield increased survival. In the present study, we sought to assess the efficacy of a cardiac patch made from human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) to engraft and limit left ventricular (LV) remodeling acutely after infarction. Cardiac patches were created from hiPSC‐CMs and human pericytes (PCs) entrapped in a fibrin gel and implanted acutely onto athymic rat hearts. hiPSC‐CMs not only remained viable after in vivo culture, but also increased in number by as much as twofold, consistent with colocalization of human nuclear antigen, cardiac troponin T, and Ki‐67 staining. CM+PC patches led to reduced infarct sizes compared with myocardial infarction‐only controls at week 4, and CM+PC patch recipient hearts exhibited greater fractional shortening over all groups at both 1 and 4 weeks after transplantation. However, a decline occurred in fractional shortening for all groups over 4 weeks, and LV thinning was not mitigated. CM+PC patches became vascularized in vivo, and microvessels were more abundant in the host myocardium border zone, suggesting a paracrine mechanism for the improved cardiac function. PCs in a PC‐only control patch did not survive 4 weeks in vivo. Our results indicate that cardiac patches containing hiPSC‐CMs engraft onto acute infarcts, and the hiPSC‐CMs survive, proliferate, and contribute to a reduction in infarct size and improvements in cardiac function.
Transcapillary fluid balance in pre‐eclampsia

Summary. The fluid transport between the plasma and interstitial fluid compartment is governed by the Starling forces, i.e. the capillary pressure (Pc), interstitial fluid hydrostatic pressure (Pi) and colloid osmotic pressure in plasma (COPp) and interstitial fluid (COPi). Interstitial fluid was collected from subcutaneous tissue on the thorax and ankle by implanted wicks and Pi was measured using the ‘wick‐in‐needle’ technique. In pre‐eclampsia, COPp, is reduced due to hypoproteinaemia and this predisposes towards loss of fluid from the vascular compartment. An important oedema‐preventing mechanism is reduction of COPi, which serves as a homeostatic buffer against increased capillary filtra‐tion. This mechanism works in moderate, but not in severe preeclampsia. A higher COPi was found both at the thorax (8·3 vs 7·0 mmHg) and ankle (5·9 vs 3·9 mmHg) in the group with severe pre‐eclampsia compared with the group moderate pre‐eclampsia, in spite of a significant reduction in COPp (15·5 vs 19·9 mmHg). These findings suggest that an increased microvascular permeability of plasma proteins to subcutaneous tissue contributes to COPp reduction in severe pre‐eclampsia.
JUVENILE IDIOPATHIC ARTHRITIS AND HLA CLASS I AND CLASS II INTERACTION AND AGE OF ONSET EFFECTS

Objective— To quantitate risk and study heterogeneity at high resolution for HLA in the most common JIA subtypes, IgM RF negative polyarticular and oligoarticular. Four digit comprehensive HLA typing enabled great precision and a large cohort allowed for consideration of both age of onset and subtype. Methods— PCR-based high resolution HLA typing for Class I and Class II loci was accomplished for 802 JIA patients and 273 controls. Specific HLA epitopes, potential interactions of alleles at specific loci and between loci, (accounting for linkage disequilibrium and haplotypic associations), and an assessment of the current ILAR classification were considered. Results— An HLA DRB1-DQB1 effect was shown to be exclusively due to DRB1 and showed similarity between oligoarticular patients and a younger subgroup of polyarticular patients. Furthermore, polyarticular patients showed age-specific related effects with susceptibility in the >6 year group limited to the HLA–DRB1*08 haplotype, a marked distinction from the additional susceptibility haplotypes, HLA-DRB1*1103/1104, found in the oligoarticular cohort and the younger polyarticular group. Also in contrast to findings for oligoarticular JIA, polyarticular patients had no evidence of an HLA class I effect. Markers associated with reduced risk for disease include DRB1*1501, DRB1*0401 and DRB1*0701. The DRB1*1501 effect was shown to reduce risk across the whole cohort, whereas DRB1*0401 and DRB1*0701 were protective for selected subtypes. Surprisingly, the susceptibility mediated by DPB1*0201, even in the absence of DR susceptibility haplotypes, overcame the protective effect of DRB1*1501. Conclusions— Inherited HLA factors in JIA show similarities overall as well as differences between subtypes.
Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA

Significance Consumption of palatable food or food-related advertising can prime increased food intake, potentially leading to overeating. We show that short-term exposure to palatable foods induces long-lasting synaptic plasticity in mesolimbic dopamine neurons. Furthermore, short-term exposure to sweetened high-fat food can drive food approach behaviors and consumption days after the initial exposure. Suppressing excitatory synaptic transmission in the ventral tegmental area can reverse increased food approach behaviors and consumption. Targeting this circuit with brain-delivered insulin may provide a strategy to suppress food cravings. In an environment with easy access to highly palatable and energy-dense food, food-related cues drive food-seeking regardless of satiety, an effect that can lead to obesity. The ventral tegmental area (VTA) and its mesolimbic projections are critical structures involved in the learning of environmental cues used to predict motivationally relevant outcomes. Priming effects of food-related advertising and consumption of palatable food can drive food intake. However, the mechanism by which this effect occurs, and whether these priming effects last days after consumption, is unknown. Here, we demonstrate that short-term consumption of palatable food can prime future food approach behaviors and food intake. This effect is mediated by the strengthening of excitatory synaptic transmission onto dopamine neurons that is initially offset by a transient increase in endocannabinoid tone, but lasts days after an initial 24-h exposure to sweetened high-fat food (SHF). This enhanced synaptic strength is mediated by a long-lasting increase in excitatory synaptic density onto VTA dopamine neurons. Administration of insulin into the VTA, which suppresses excitatory synaptic transmission onto dopamine neurons, can abolish food approach behaviors and food intake observed days after 24-h access to SHF. These results suggest that even a short-term exposure to palatable foods can drive future feeding behavior by “rewiring” mesolimbic dopamine neurons.
Multivariable self-tuning regulators

This paper describes a design method of multivariable self-tuning regulators. The controller is developed to minimize a quadratic cost function which penalizes the control signals as well as the output deviations from time varying reference signals. This gives an extension of the minimum variance strategy [1] to handle non-minimum phase systems using a different approach than [2]. One of the advantages is that the number of inputs does not have to be the same as the number of outputs. A simulation example is presented to illustrate the efficiency and the usefulness of this approach.
Cyclooxygenase-2 Inhibitor Decreases Extracellular Matrix Synthesis in Stretched Renal Fibroblasts

Background/Aims: Both TGF-β and cyclooxygenase-2 have been implicated in the pathogenesis of interstitial fibrosis in unilateral ureteral obstruction (UUO). Cyclic tensile stretch has been used in vitro to mimic the changes in intrarenal pressure in UUO. We sought to determine the effect of meloxicam (a selective cyclooxygenase-2 inhibitor) on extracellular matrix and TGF-β synthesis in stretched renal fibroblasts (NRK-49F). Methods: NRK-49F cells were subject to cyclic stretch (6 cycles/min, 15% elongation) using a Flexcell apparatus. Cells were stretched in the absence or presence of meloxicam for 48 h, and then cells and supernatants were isolated. Collagen was quantified by the Sircol assay; fibronectin and laminin were visualized using immunofluorescence. TGF-β was quantified by ELISA, and protease activity determined by a colorimetric assay. Results: Bothcollagen and TGF-β synthesis were increased following a 48-hour stretch of NRK-49F. Meloxicam significantly decreased the collagen and TGF-β response to stretch. Stretch-induced fibronectin and laminin synthesis was also decreased by meloxicam. NRK-49F protease activity was decreased by stretch; this was unaffected by meloxicam. Conclusions: Stretch of NRK-49F results in extracellular matrix synthesis, a process which may be activated in UUO and contribute to interstitial fibrosis. Inhibition of cyclooxygenase-2 may reduce fibrosis through a TGF-β-dependent process.
A Multiple Logistic Regression Analysis of the Risk and Relative Odds of Temporomandibular Disorders as a Function of Common Occlusal Features

A multiple logistic regression analysis was used to compute the odds ratios for 11 common occlusal features for asymptomatic controls (n = 147) us. five temporomandibular disorder groups: Disc Displacement with Reduction (n = 81), Disc Displacement without Reduction (n = 48), Osteoarthrosis with Disc Displacement History (n = 75), Primary Osteoarthrosis (n = 85), and Myalgia Only (n = 124). Features that did not contribute included: retruded contact position (RCP) to intercuspal position (ICP) occlusal slides < 2 mm, slide asymmetry, unilateral RCP contacts, deep overbite, minimal overjet, dental midline discrepancies, ≤ 4 missing teeth, and maxillo-mandibular first molar relationship or cross-arch asymmetry. Groupings of a minimum of two to at most five occlusal variables contributed to the TMD patient groups. Significant increases in risk occurred selectively with anterior open bite (p < 0.01), unilateral maxillary lingual crossbite (p < 0.05 to p < 0.01), overjets > 6-7 mm (p < 0.05 to p < 0.01), ≥5-6 missing posterior teeth (p < 0.05 to p < 0.01), and RCP-ICP slides > 2 mm (p < 0.05 to p < 0.01). While the contribution of occlusion to the disease groups was not zero, most of the variation in each disease population was not explained by occlusal parameters. Thus, occlusion cannot be considered the unique or dominant factor in defining TMD populations. Certain features such as anterior open bite in osteoarthrosis patients were considered to be a consequence of rather than etiological factors for the disorder.
The epithelium in acute lung injury/acute respiratory distress syndrome

Purpose of reviewThe mechanisms of epithelial injury in acute lung injury/acute respiratory distress syndrome have been of interest since the syndrome was first described. Cell therapies to replace injured epithelium are a futuristic dream; however, there is ongoing research to achieve this goal. We review research regarding the function of the epithelium in acute lung injury/acute respiratory distress syndrome, including potential novel therapies. Relevant findingsAltered fluid clearance from the injured lungs in acute lung injury/acute respiratory distress syndrome patients has been consistently found and is an important prognostic finding. New research suggests that neutrophils that enter the lung late and which are enticed into the lung through a specific chemokine system may be important for causing lung injury. If this is the case, then blockers of this system could be a possible therapy. The role of fibrinolysis and coagulation abnormalities in lung injury due to infection and other perturbations is examined. These abnormal findings may be useful diagnostic tools for prognostication as well as targets for future therapies. SummaryEpithelial damage is a hallmark of acute lung injury/acute respiratory distress syndrome. An increased understanding of the function of these cells and of the abnormalities that occur when these lung cells are injured should allow the development of novel therapies and, perhaps, lead to replacement therapies.
Immune-Induced Fever Is Dependent on Local But Not Generalized Prostaglandin E2 Synthesis in the Brain

Fever occurs upon binding of prostaglandin E2 (PGE2) to EP3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE2 has not been clearly determined. Here, using mice of both sexes, we examined the role of local versus generalized PGE2 production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreERT2 under the Slco1c1 promoter, PGE2 levels in the CSF were only weakly related to the magnitude of the febrile response, whereas the PGE2 synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever. Histological analysis showed that the deletion of cyclooxygenase-2 in brain endothelial cells occurred preferentially in small- and medium-sized vessels deep in the brain parenchyma, such as in the hypothalamus, whereas larger vessels, and particularly those close to the neocortical surface and in the meninges, were left unaffected, hence leaving PGE2 synthesis largely intact in major parts of the brain while significantly reducing it in the region critical for the febrile response. Furthermore, injection of a virus vector expressing microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevation in response to LPS. We conclude that the febrile response is dependent on local release of PGE2 onto its target neurons and not on the overall PGE2 production in the brain. SIGNIFICANCE STATEMENT By using mice with selective deletion of prostaglandin synthesis in brain endothelial cells, we demonstrate that local prostaglandin E2 (PGE2) production in deep brain areas, such as the hypothalamus, which is the site of thermoregulatory neurons, is critical for the febrile response to peripheral inflammation. In contrast, PGE2 production in other brain areas and the overall PGE2 level in the brain do not influence the febrile response. Furthermore, partly restoring the PGE2 synthesizing capacity in the anterior hypothalamus of mice lacking such capacity with a lentiviral vector resulted in a temperature elevation in response to LPS. These data imply that the febrile response is dependent on the local release of PGE2 onto its target neurons, possibly by a paracrine mechanism.
Performance and Variability Analysis of SiNW 6T-SRAM Cell Using Compact Model With Parasitics

In this paper, we analyze stability metrics [e.g., read, write noise margins (WNM), and access time], geometrical variability, and layout area optimization of silicon nanowire field effect transistor (SiNW FET) based 6T SRAM with multiwire sizing technique. The SRAM cell analyzed in this paper is based on the TCAD and experimentally verified SiNW FET Verilog-A compact model with parasitics. The different NW SRAM design configurations (e.g., <inline-formula> <tex-math notation="LaTeX">$\boldsymbol{C}\_111$</tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">$\boldsymbol{C}\_123$</tex-math></inline-formula>, etc., <inline-formula> <tex-math notation="LaTeX">${{\mathbf where}}\,\boldsymbol{C}\_111$</tex-math></inline-formula> denotes the number of wires in pull-up, access, and pull-down transistors, respectively) are investigated. The read static noise margin and read access time (RAT) are improved up to ∼38% and ∼18% with little pay of WNM by ∼9% (↓), write access time (WAT) ∼33% (↑) in <inline-formula><tex-math notation="LaTeX"> $\boldsymbol{C}\_112$</tex-math></inline-formula> configuration compared to <inline-formula><tex-math notation="LaTeX"> $\boldsymbol{C}\_111$</tex-math></inline-formula>. Other configuration such as <inline-formula> <tex-math notation="LaTeX">$\boldsymbol{C}\_113$</tex-math></inline-formula> possess more improvements upto ∼55%, ∼20% in RNM, RAT with WNM (↓∼21%), and WAT (∼44%↑) compare to <inline-formula><tex-math notation="LaTeX">$\boldsymbol{C}\_111$</tex-math></inline-formula> at the expense of more layout area. Finally, the impact of geometrical variability including length, radius, and oxide thickness on the read and write stability using <italic>N</italic>-curve is examined. It is found that the static read and write stability is less susceptible to variability at nominal supply voltage. However, it is very sensitive to the voltage scaling in which read (write) voltage margin varies upto ∼2–3% (∼2.5–4.5%) and read (write) current margin varies upto ∼18% (∼35%) depending upon the design configurations. Among all design configurations, <inline-formula><tex-math notation="LaTeX">$\boldsymbol{C}\_112$</tex-math></inline-formula> is the better configuration for considering overall performances such as write stability, speed, layout area, and variability tolerance.