Miracle-dz/UniFAR-FTUs huggingface dataset:
Ageing and the resting state: is cognition obsolete?

ABSTRACT Recent years have seen the rise in popularity of the resting-state approach to neurocognitive ageing, with many studies examining age differences in functional connectivity at rest and relating these differences to cognitive performance outside the scanner. There are many advantages to the resting state that likely contribute to its popularity and indeed, many insights have been gained from this work. However, there are also several limitations of the resting-state approach that restrict its ability to contribute to the study of neurocognitive ageing. In this opinion piece, we consider some of those limitations and argue that task-based studies are still essential to developing a mechanistic understanding of how age affects the brain in a cognitively relevant manner – a fundamental goal of neuroscientific research into ageing.
A sensitivity trade-off arising in small-gain design for nonlinear systems: An iISS framework

This note investigates the trade-off arising in disturbance attenuation for nonlinear feedback systems in the framework of integral input-to-state stability. Similarly to the linear case, we show that if a gain tuning on one subsystem is used to drastically reduce the effect of its exogenous disturbances, then the other subsystem's disturbance attenuation is qualitatively the same as in open loop.
Convergence of linear functionals of the Grenander estimator under misspecification

Under the assumption that the true density is decreasing, it is well known that the Grenander estimator converges at rate $n^{1/3}$ if the true density is curved [Sankhy\={a} Ser. A 31 (1969) 23-36] and at rate $n^{1/2}$ if the density is flat [Ann. Probab. 11 (1983) 328-345; Canad. J. Statist. 27 (1999) 557-566]. In the case that the true density is misspecified, the results of Patilea [Ann. Statist. 29 (2001) 94-123] tell us that the global convergence rate is of order $n^{1/3}$ in Hellinger distance. Here, we show that the local convergence rate is $n^{1/2}$ at a point where the density is misspecified. This is not in contradiction with the results of Patilea [Ann. Statist. 29 (2001) 94-123]: the global convergence rate simply comes from locally curved well-specified regions. Furthermore, we study global convergence under misspecification by considering linear functionals. The rate of convergence is $n^{1/2}$ and we show that the limit is made up of two independent terms: a mean-zero Gaussian term and a second term (with nonzero mean) which is present only if the density has well-specified locally flat regions.
PURE , ISAKSON , KAPPLER , MARRACK , KRAMMER , AND VITETTA 601 Materials and Methods Animals

B cells are the precursors of an t ibody-secre t ing cells. Since the f requency of B cells with receptors for a pa r t i cu la r an t igen is low, polyclonal s t imuli have been used to s tudy B cell act ivat ion. These st imuli inc lude mitogens, such as l ipopolysacchar ide (LPS) 1, ant ibodies specific for surface immunog lobu l in (sIg), and soluble factors from T cells. T h e results of studies wi th polyclonal act ivators suggest tha t ac t iva t ion of B cells from adul t mice occurs in two stages: (a) the induct ion of prol i fera t ion by ant i Ig and T cel l-derived B cell growth factor(s) (BCGF) (1-3), and (b) d i f ferent ia t ion to Ig secretion by T cel l -derived di f ferent ia t ion factors (BCDF) (4-8). D e p e n d i n g on the source of T cel l-derived factors, the induct ion of IgM secretion m a y require concomi tant cross-linking of Ig receptors by ant i Ig (7, 8) or can occur in the absence of ant i Ig (8-11). The lymphokine(s) in T cell superna tan t s (SN) tha t induces B cells to secrete I g M has been te rmed B cell d i f ferent ia t ion factor(s) for I g M or BCDFu (8, 12). In add i t ion to BCDF~, we have defined a second lymphok ine (BCDFy) tha t induces IgGa secretion by LPS-s t imula ted B cells (13). In the present s tudy we have dis t inguished BCDF~, BCDFv, and B C G F by their molecular weights, ab i l i ty to ac t ivate neona ta l B cells, and presence or absence in a panel of T cell SN. Fur thermore , we have Shown tha t BCDF~ and BCDFv s t imula te B cells from both neona ta l and adul t mice, whereas B C G F acts only on the latter. This f inding might par t i a l ly expla in the relat ive immuno inc ompe te nc e of i m m a t u r e B cells.
Implementing strategies to reduce singly housed male mice

There are different husbandry situations that lead to social isolation of male mice. Besides legal considerations, single housing has a negative impact on behavioural and molecular studies. We have implemented two strategies, the ‘companion mouse’ and just-weaned male grouping, to reduce the number of male mice housed singly in our facility. We have achieved a progressive reduction (42% in three years) without an increase in aggression.
Edge behaviour in the glass sheet redraw process

Thin glass sheets may be manufactured using a two-part process in which a sheet is first cast and then subsequently reheated and drawn to a required thickness. The latter redrawing process typically results in a sheet with non-uniform thickness and with smaller width than the cast glass block. Experiments suggest that the loss of width can be minimized and the non-uniformities can be essentially confined to thickening at the sheet edges if the heater zone through which the glass is drawn is made very short. We present a three-dimensional mathematical model for the redraw process and consider the limits in which (i) the heater zone is short compared with the sheet width, and (ii) the sheet thickness is small compared with both of these length scales. We show that, in the majority of the sheet, the properties vary only in the direction of drawing and the sheet motion is one-dimensional, with two-dimensional behaviour and the corresponding thick edges confined to boundary layers at the sheet extremities. We present numerical solutions to this boundary-layer problem and demonstrate good agreement with experiment, as well as with numerical solutions to the full three-dimensional problem. We show that the final thickness at the sheet edge scales with the inverse square root of the draw ratio, and explore the effect of tapering of the ends to identify a shape for the initial preform that results in a uniform rectangular final product.
Predictive Value of Capnography for Suspected Diabetic Ketoacidosis in the Emergency Department

Introduction: Metabolic acidosis confirmed by arterial blood gas (ABG) analysis is one of the diagnostic criteria for diabetic ketoacidosis (DKA). Given the direct relationship between end-tidal carbon dioxide (ETCO2), arterial carbon dioxide (PaCO2), and metabolic acidosis, measuring ETCO2 may serve as a surrogate for ABG in the assessment of possible DKA. The current study focuses on the predictive value of capnography in diagnosing DKA in patients referring to the emergency department (ED) with increased blood sugar levels and probable diagnosis of DKA. Methods: In a cross-sectional prospective descriptive-analytic study carried out in an ED, we studied 181 patients older than 18 years old with blood sugar levels of higher than 250 mg/dl and probable DKA. ABG and capnography were obtained from all patients. To determine predictive value, sensitivity, specificity and cut-off points, we developed receiver operating characteristic curves. Results: Sixty-two of 181 patients suffered from DKA. We observed significant differences between both groups (DKA and non-DKA) regarding age, pH, blood bicarbonate, PaCO2 and ETco2 values (p≤0.001). Finally, capnography values more than 24.5 mmHg could rule out the DKA diagnosis with a sensitivity and specificity of 0.90. Conclusion: Capnography values greater than 24.5 mmHg accurately allow the exclusion of DKA in ED patients suspected of that diagnosis. Capnography levels lower that 24.5 mmHg were unable to differentiate between DKA and other disease entities.
Difference in blister fluid penetration after single and multiple doses of ceftriaxone

Plasma and suction skin blister fluid concentrations of ceftriaxone were studied in 12 subjects after intravenous administration of 1 g of ceftriaxone every 12 h (q12h) and 2 g every 24 h (q24h) after single and multiple doses. Ceftriaxone concentrations were determined by high-pressure liquid chromatography. Mean peak plasma concentrations (at the end of the 5-min infusion) were 254.0 and 374.8 micrograms/ml after administration of 1 g q12h after single and multiple doses, respectively. Similarly, with 2 g q24h, maximum levels were 409.6 and 443.5 micrograms/ml. Forty-eight hours after the last dose of ceftriaxone, plasma concentrations were still detectable: 1.2 micrograms/ml after 1 g q12h and 3.0 micrograms/ml after 2 g q24h. Higher ceftriaxone concentrations were observed in blister fluid after multiple doses than after a single dose. Peak concentrations almost doubled in the blister fluid after multiple doses: 36.0 versus 67.0 micrograms/ml and 38.6 versus 68.9 micrograms/ml for 1 g q12h and 2 g q24h, respectively. Elimination half-life of ceftriaxone in the blister (8.3 and 11.5 h) was longer than plasma half-life (6.3 h). With the area under the concentration-time curve ratio, a 113% increase in tissue penetration was observed after multiple doses for the 1 g q12h regimen. The free plasma and blister fluid ceftriaxone concentrations observed at the end of the dosing interval of the 2 g q24h regimen were higher than the MIC for 90% of the susceptible microorganisms and justified the once-a-day use of ceftriaxone.
In Vitro Function of Chronic Myelocytic Leukemia Granulocytes. Effects of Irradiation and Storage

Granulocyte function was studied in 9 patients with untreated, Ph1-positive chronic myelocytic leukemia (CML). The nitroblue tetrazolium reduction by stimulated granulocytes was impaired in all patients; 4 patients also had diminished phagocytosis and 2 others defective Chemotaxis. In spite of this variety of polymorphonuclear (PMN) functional impairments, there is little evidence of increased susceptibility to infections in CML patients. This suggests that CML-PMN leucocytes (PMNs) may be successfully used for transfusion into neutropenic recipients, as previously reported. To evaluate the effects of irradiation and liquid storage on CML-PMNs, 5 of our patients were subjected to leukapheresis by continuous-flow centrifugation in the Aminco Celltrifuge, and granulocyte functional capacities were also evaluated on the cell-rich plasma immediately after collection and after short-term storage at 4°C with or without irradiation (1500 rads). As evaluated by in vitro studies, granulocytes maintained, even after irradiation, functional activities similar to those found immediately after collection up to 24 h of storage at 4°C and presented a moderate loss of function after 48 h. Chemotaxis appeared to be the most sensitive detector for cellular damage of stored leucocytes, irradiated and non-irradiated, so that it might be used for assessment of leucocyte function before transfusion.
Interpersonal Distance in Schizophrenic Patients: Relationship to Negative Syndrome

Background: Personal space is the area individuals maintain around themselves into which others cannot intrude without arousing discomfort. Objective: We tested the hypotheses that psychological distancing of patients with schizophrenia would be a characteristic of 1) diagnosis and/or 2) syndrome. Methods: For this aim, 30 schizophrenic and 30 age matching normal males established comfortable interpersonal distances for 20 word-stimuli representing family members, significant others, self-images, emotionally neutral and threatening surroundings. The distances were assessed by a paper-and-pencil projective measure, the Comfortable Interpersonal Distance scale and the patients' psycho-pathological symptoms were quantified by the Positive and Negative Syndrome Scale. t-tests and correlational analyses were employed to examine the relation-ships between the parameters of interest. Results: The rank order (hierarchy) of preferable interpersonal distances of patients with schizophrenia was similar to that of normal subjects. At the same time, psychological distance from family members and themselves was substantially larger among the patients. There were no significant correlations between any kind of interpersonal distance and positive syndrome of schizophrenia, while negative syndrome showed significant inverse association with distances from emotionally neutral and threatening figures and positive correlation with family member and self-image distances. Conclusion: The results suggest that the negative syndrome of schizophrenia attenuates the differences between interpersonal distances from generally close and distant persons.
Space Pseudorandom Generators by Communication Complexity Lower Bounds

In 1989, Babai, Nisan and Szegedy [BNS92] gave a construction of a pseudorandom generator for logspace, based on lower bounds for multiparty communication complexity. The seed length of their pseudorandom generator was 2 ( p log n) , because the best lower bounds for multiparty communication complexity are relatively weak. Subsequently, pseudorandom generators for logspace with seed length O(log 2 n) were given by [N92] and [INW94]. In this paper, we show how to use the pseudorandom generator construction of [BNS92] to obtain a third construction of a pseudorandom generator with seed length O(log 2 n), achieving the same parameters as [N92] and [INW94]. We achieve this by concentrating on protocols in a restricted model of multiparty communication complexity that we call the conservative one-way unicast model and is based on the conservative one-way model of [DJS98]. We observe that bounds in the conservative one-way unicast model (rather than the standard Number On the Forehead model) are sufficient for the pseudorandom generator construction of [BNS92] to work. Roughly speaking, in a conservative one-way unicast communication protocol, the players speak in turns, one after the other in a fixed order, and every message is visible only to the next player. Moreover, before the beginning of the protocol, each player only knows the inputs of the players that speak after she does and a certain function of the inputs of the players that speak before she does. We prove a lower bound for the communication complexity of conservative one-way unicast communication protocols that compute a family of functions obtained by compositions of strong extractors. Our final pseudorandom generator construction is related to, but different from the constructions of [N92] and [INW94].
Potent Anti-R5 Human Immunodeficiency Virus Type 1 Effects of a CCR5 Antagonist, AK602/ONO4128/GW873140, in a Novel Human Peripheral Blood Mononuclear Cell Nonobese Diabetic-SCID, Interleukin-2 Receptor γ-Chain-Knocked-Out AIDS Mouse Model

ABSTRACT We established human peripheral blood mononuclear cell (PBMC)-transplanted R5 human immunodeficiency virus type 1 isolate JR-FL (HIV-1JR-FL)-infected, nonobese diabetic-SCID, interleukin 2 receptor γ-chain-knocked-out (NOG) mice, in which massive and systemic HIV-1 infection occurred. The susceptibility of the implanted PBMC to the infectivity and cytopathic effect of R5 HIV-1 appeared to stem from hyperactivation of the PBMC, which rapidly proliferated and expressed high levels of CCR5. When a novel spirodiketopiperazine-containing CCR5 inhibitor, AK602/ONO4128/GW873140 (molecular weight, 614), was administered to the NOG mice 1 day after R5 HIV-1 inoculation, the replication and cytopathic effects of R5 HIV-1 were significantly suppressed. In saline-treated mice (n = 7), the mean human CD4+/CD8+ cell ratio was 0.1 on day 16 after inoculation, while levels in mice (n = 8) administered AK602 had a mean value of 0.92, comparable to levels in uninfected mice (n = 7). The mean number of HIV-RNA copies in plasma in saline-treated mice were ∼106/ml on day 16, while levels in AK602-treated mice were 1.27 × 103/ml (P = 0.001). AK602 also significantly suppressed the number of proviral DNA copies and serum p24 levels (P = 0.001). These data suggest that the present NOG mouse system should serve as a small-animal AIDS model and warrant that AK602 be further developed as a potential therapeutic for HIV-1 infection.
An explosive innovation: Phylogenetic relationships of Solanum section Gonatotrichum (Solanaceae)

Abstract Solanum is one of the largest plant genera and exhibits a wide range of morphological diversity. Solanum section Gonatotrichum, the focus of this study, is unique within the genus because of its fruits that swell with turgor pressure and explosively dehisce to disperse the seeds. We infer phylogenetic relationships within section Gonatotrichum using DNA sequence data from two nuclear regions (ITS and the granule-bound starch synthase gene [GBSSI or waxy]) and the chloroplast region trnT-F. The resulting phylogenetic trees support the monophyly of the section with the inclusion of Solanum lignescens, a species not previously thought to belong to the group due to the presence of stellate hairs. This inclusion of this species in section Gonatotrichum suggests that the simple, often geniculate hairs of species in the group may represent reduced stellate hairs. The presence of heterantherous flowers appears to be derived in the section, but this character is largely lost in Solanum parcistrigosum.
ANTIBIOTIC RESISTANCE AND β-LACTAMASES OF YERSINIA ENTEROCOLITICA ISOLATED FROM PIGS IN POLAND

Sixty-two isolates of pig-derived Yersinia enterocolitica belonging to 1A and 4 biotypes and non-typeable isolates were subjected to antimicrobial resistance testing by the disc diffusion method. The presence of β-lactamase A (Bla-A) and B (Bla-B) was detected by the double disc diffusion test, and the β-lactamase genes blaA and blaB in these isolates were detected by PCR. The isolates were resistant or moderately susceptible mostly to penicillins (except piperacillin) and first-generation cephalosporins. The majority of the isolates of biotype 1A were resistant or moderately susceptible to amoxicillin/clavulanic acid. Three isolates of biotype 4 were also resistant to amoxicillin/clavulanic acid. Most of Y. enterocolitica isolates were resistant or intermediately susceptible to second-generation cephalosporins. Cefotaxime was the most active third-generation cefalosporin against the tested Y. enterocolitica. No isolate was resistant to imipenem. Tetracyclines, aminoglycosides, and quinolones showed high activity against Y. enterocolitica. The presence of the Bla-A enzyme was found in 27/31 isolates of biotype 1A, 22/28 isolates of biotype 4, and in all untypeable isolates. In these isolates the blaA gene was detected by PCR amplification. In all Y. enterocolitica isolates blaB gene was detected but not all isolates of biotype 4 showed the presence of Bla-B.
Symptoms and impact of symptoms on function and health in patients with chronic obstructive pulmonary disease and chronic heart failure in primary health care

Background Patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) seem to have several symptoms in common that impact health. However, methodological differences make this difficult to compare. Aim Comparisons of symptoms, impact of symptoms on function and health between patients with COPD and CHF in primary health care (PHC). Method The study is cross sectional, including patients with COPD (n=437) and CHF (n=388), registered in the patient administrative systems of PHC. The patients received specific questionnaires – the Memorial Symptom Assessment Scale, the Medical Research Council dyspnea scale, and the Fatigue Impact Scale – by mail and additional questions about psychological and physical health. Results The mean age was 70±10 years and 78±10 years for patients with COPD and CHF respectively (P=0.001). Patients with COPD (n=273) experienced more symptoms (11±7.5) than the CHF patients (n=211) (10±7.6). The most prevalent symptoms for patients with COPD were dyspnea, cough, and lack of energy. For patients with CHF, the most prevalent symptoms were dyspnea, lack of energy, and difficulty sleeping. Experience of dyspnea, cough, dry mouth, feeling irritable, worrying, and problems with sexual interest or activity were more common in patients with COPD while the experience of swelling of arms or legs was more common among patients with CHF. When controlling for background characteristics, there were no differences regarding feeling irritable, worrying, and sexual problems. There were no differences in impact of symptoms or health. Conclusion Patients with COPD and CHF seem to experience similar symptoms. There were no differences in how the patients perceived their functioning according to their cardinal symptoms; dyspnea and fatigue, and health. An intervention for both groups of patients to optimize the management of symptoms and improve function is probably more relevant in PHC than focusing on separate diagnosis groups.
Methamphetamine Regulation of Firing Activity of Dopamine Neurons

Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca2+ homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca2+-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane. SIGNIFICANCE STATEMENT Methamphetamine (METH) competes with dopamine uptake, increases dopamine efflux via the dopamine transporter, and affects the excitability of dopamine neurons. Here, we identified an unexpected property of METH on dopamine neuron firing activity. METH transiently increased the spontaneous spike activity of dopamine neurons followed by a progressive reduction of the spontaneous spike activity. METH broadened the action potentials, increased coefficients of variation of the interspike interval, and decreased the amplitude of afterhyperpolarization, which are consistent with changes in the activity of Ca2+-activated potassium (BK) channels. We found that METH decreased the activity of BK channels by stimulating BK-α subunit trafficking. Thus, METH modulation of dopamine neurotransmission and resulting behavioral responses is, in part, due to METH regulation of BK channel activity.