Miracle-dz/UniFAR-FTUs huggingface dataset:
Absolute Quantitation of Human Milk Oligosaccharides Reveals Phenotypic Variations during Lactation.

BACKGROUND The quantitation of human milk oligosaccharides (HMOs) is challenging because of the structural complexity and lack of standards. OBJECTIVE The objective of our study was to rapidly measure the absolute concentrations of HMOs in milk using LC-mass spectrometry (MS) and to determine the phenotypic secretor status of the mothers. METHODS This quantitative method for measuring HMO concentration was developed by using ultraperformance LC multiple reaction monitoring MS. It was validated and applied to milk samples from Malawi (88 individuals; 88 samples from postnatal month 6) and the United States (Davis, California; 45 individuals, mean age: 32 y; 103 samples collected on postnatal days 10, 26, 71, or 120, repeated measures included). The concentrations of α(1,2)-fucosylated HMOs were used to determine the mothers' phenotypic secretor status with high sensitivity and specificity. We used Friedman's test and Wilcoxon's signed rank test to evaluate the change in HMO concentration during the course of lactation, and Student's t test was used to compare secretors and nonsecretors. RESULTS A decrease (P < 0.05) in HMO concentration was observed during the course of lactation for the US mothers, corresponding to 19.3 ± 2.9 g/L for milk collected on postnatal day 10, decreasing to 8.53 ± 1.18 g/L on day 120 (repeated measures; n = 14). On postnatal day 180, the total concentration of HMOs in Malawi milk samples from secretors (6.46 ± 1.74 mg/mL) was higher (P < 0.05) than that in samples from nonsecretors (5.25 ± 2.55 mg/mL ). The same trend was observed for fucosylated species; the concentration was higher in Malawi milk samples from secretors (4.91 ± 1.22 mg/mL) than from nonsecretors (3.42 ± 2.27 mg/mL) (P < 0.05). CONCLUSIONS HMOs significantly decrease during the course of lactation. Secretor milk contains higher concentrations of total and fucosylated HMOs than does nonsecretor milk. These HMO concentrations can be correlated to the health of breastfed infants in order to investigate the protective effects of milk components. The trials were registered at clinicaltrials.gov as NCT01817127 and NCT00524446.
Perceptual Lateralization of Coda Rhotic Production in Puerto Rican Spanish

When speakers of Puerto Rican Spanish (PRS) produce phonemic coda taps, Spanish-speakers of other dialects often perceive these as laterals. We observed production of phonemic coda laterals and taps by a male PRS speaker in real-time MRI. Temporal and spatial characteristics of tongue tip movements during coda liquid production are inconsistent with accounts positing a categorical change from rhotic to lateral in coda for this speaker. Perceptual coding of coda tap production by naïve listeners suggests that both preceding vowel type and the relative strength of a proximal prosodic boundary may impact the proportion of the subject’s phonemic taps that received a lateral percept. Results are discussed in the context of persistent difficulties in modeling the gestural representation of liquid consonants.
On the Gibbs phenomenon IV: recovering exponential accuracy in a subinterval from a Gegenbauer partial sum of a piecewise analytic function

We continue the investigation of overcoming Gibbs phenomenon, i.e., obtaining exponential accuracy at all points including at the discontinuities themselves, from the knowledge of a spectral partial sum of a discontinuous but piecewise analytic function. We show that if we are given the first N expansion coefficients of an L_2 function f(x) in terms of either the trigonometrical polynomials or the Chebyshev or Legendre polynomials, we can construct an exponentially convergent approximation to the point values of f(x) in any sub-interval in which it is analytic.
Fundamentally Distributed Information Processing Integrates the Motor Network into the Mental Workspace during Mental Rotation

The manipulation of mental representations in the human brain appears to share similarities with the physical manipulation of real-world objects. In particular, some neuroimaging studies have found increased activity in motor regions during mental rotation, suggesting that mental and physical operations may involve overlapping neural populations. Does the motor network contribute information processing to mental rotation? If so, does it play a similar computational role in both mental and manual rotation, and how does it communicate with the wider network of areas involved in the mental workspace? Here we used multivariate methods and fMRI to study 24 participants as they mentally rotated 3-D objects or manually rotated their hands in one of four directions. We find that information processing related to mental rotations is distributed widely among many cortical and subcortical regions, that the motor network becomes tightly integrated into a wider mental workspace network during mental rotation, and that motor network activity during mental rotation only partially resembles that involved in manual rotation. Additionally, these findings provide evidence that the mental workspace is organized as a distributed core network that dynamically recruits specialized subnetworks for specific tasks as needed.
Erythropoietin promotes survival of retinal ganglion cells in DBA/2J glaucoma mice.

PURPOSE Retinal ganglion cell (RGC) loss occurs in response to increased intraocular pressure (IOP) and/or retinal ischemia in glaucoma and leads to impairment of vision. This study was undertaken to test the efficacy of erythropoietin (EPO) in providing neuroprotection to RGCs in vivo. METHODS The neuroprotective effects of EPO were studied in the DBA/2J mouse model of glaucoma. Mice were intraperitoneally injected with control substances or various doses of EPO, starting at the age of 6 months and continuing for an additional 2, 4, or 6 months. RGCs were labeled retrogradely by a gold tracer. IOP was measured with a microelectric-mechanical system, and EPO receptor (EPOR) expression was detected by immunohistochemistry. Axonal death in the optic nerve was quantified by para-phenylenediamine staining, and a complete blood count system was used to measure the number of erythrocytes. RESULTS In DBA/2J mice, the average number of viable RGCs significantly decreased from 4 months to 10 months, with an inverse correlation between the number of dead optic nerve axons and viable RGCs. Treatment with EPO at doses of 3000, 6000, and 12,000 U/kg body weight per week all prevented significant RGC loss, compared with untreated DBA/2J control animals. EPO effects were similar to those of memantine, a known neuroprotective agent. IOP, in contrast, was unchanged by both EPO and memantine. Finally, EPOR was expressed in the RGC layer in both DBA/2J and C57BL/6J mice. CONCLUSIONS EPO promoted RGC survival in DBA/2J glaucomatous mice without affecting IOP. These results suggest that EPO may be a potential therapeutic neuroprotectant in glaucoma.
Host specificity in vascular epiphytes: a review of methodology, empirical evidence and potential mechanisms

A considerable number of plants depend on structural support of other plants. To understand their diversity and ecology, it is essential to know how strongly potential host species differ in their suitability as hosts. This review focuses on vascular epiphytes, i.e. structurally dependent plants that do not parasitize their hosts. Despite a longstanding interest in the topic, our knowledge on the strength of their host specificity is still scanty. This is arguably due to conceptual confusion, but also because of the large complexity of the study system, which turns quantifying host specificity in the field into a challenge.
Modern Evaluation of Liquisolid Systems with Varying Amounts of Liquid Phase Prepared Using Two Different Methods

Liquisolid systems are an innovative dosage form used for enhancing dissolution rate and improving in vivo bioavailability of poorly soluble drugs. These formulations require specific evaluation methods for their quality assurance (e.g., evaluation of angle of slide, contact angle, or water absorption ratio). The presented study is focused on the preparation, modern in vitro testing, and evaluation of differences of liquisolid systems containing varying amounts of a drug in liquid state (polyethylene glycol 400 solution of rosuvastatin) in relation to an aluminometasilicate carrier (Neusilin US2). Liquisolid powders used for the formulation of final tablets were prepared using two different methods: simple blending and spraying of drug solution onto a carrier in fluid bed equipment. The obtained results imply that the amount of liquid phase in relation to carrier material had an effect on the hardness, friability, and disintegration of tablets, as well as their height. The use of spraying technique enhanced flow properties of the prepared mixtures, increased hardness values, decreased friability, and improved homogeneity of the final dosage form.
Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the PROTECT Study.

AIMS Dyspnoea and pulmonary and/or peripheral congestion are the most frequent manifestations of acute heart failure (AHF) and are important targets for therapy. We have assessed changes in dyspnoea, their relationship with mortality, and the effects of the adenosine A1 receptor antagonist rolofylline on these endpoints in patients enrolled in the PROTECT trial. METHODS AND RESULTS PROTECT was a prospective, double-blind, placebo-controlled study assessing the effect of rolofylline in patients hospitalized for AHF with dyspnoea, fluid overload, increased plasma natriuretic peptides, and mild-to-moderate renal dysfunction. Early dyspnoea relief, prospectively defined as moderately or markedly better dyspnoea at both 24 and 48 h after the start of study drug administration, occurred in 49.8% of the patients. Early dyspnoea relief was associated with greater weight loss and with reduced mortality at Days 14 and 30 [hazard ratio (HR) 0.28, 95% confidence interval (CI): 0.15, 0.50; and 0.35, 95% CI: 0.22, 0.55, respectively]. Rolofylline administration was associated with an increase in the proportion of patients showing early dyspnoea relief (HR 1.30; 95% CI: 1.08, 1.57) and with a numerically lower mortality at 14 and 30 days, largely driven by the mortality due to HF [at 30 days, HR (95% CI, P-value): 0.65 (0.38-1.10, P= 0.107)]. Rolofylline did not reduce episodes of in-hospital worsening HF or post-discharge re-admissions, nor did it improve survival at 60 or 180 days. CONCLUSION The present analysis from PROTECT demonstrated that more weight loss was associated with early dyspnoea relief and reduced short-term mortality.
Assessment and treatment of suicidal patients.

The assessment of suicidal thoughts or behavior and its management are topics relevant to all clinicians, not just mental health professionals. Up to two thirds of patients who commit suicide have seen a physician in the month before their death.1–5 Many patients who kill themselves do so by taking an overdose of prescribed medications, and physicians sometimes unwittingly provide the means for suicide in a single prescription.3 Few patients spontaneously report their suicidal thoughts and intentions to their physicians,4 so the clinician must be alert to signals that a patient may be at risk for suicide. Although the patient .
The Tetrameric Protein Transthyretin Dissociates to a Non-native Monomer in Solution

In amyloidosis, normally innocuous soluble proteins polymerize to form insoluble fibrils. Amyloid fibril formation and deposition have been associated with a wide range of diseases, including spongiform encephalopathies, Alzheimer's disease, and familial amyloid polyneuropathies (FAP). In certain forms of FAP, the amyloid fibrils are mostly constituted by variants of transthyretin (TTR), a homotetrameric plasma protein implicated in the transport of thyroxine and retinol. The most common amyloidogenic TTR variant is V30M-TTR, and L55P-TTR is the variant associated with the most aggressive form of FAP. Recently, we reported that TTR dissociates to a monomeric species at pH 7.0 and nearly physiological ionic strengths (Quintas, A., Saraiva, M. J., and Brito, R. M. (1997) FEBS Lett.418, 297–300). Here, we show that the tetramer dissociation is apparently irreversible; and based on intrinsic tryptophan fluorescence and fluorescence quenching experiments, we show that the monomeric species formed upon tetramer dissociation is non-native. We also show, based on 1-anilino-8-naph-thalenesulfonate binding studies, that this monomeric species appears not to behave like a molten globule. These data allowed us to propose a model for TTR amyloidogenesis based on tetramer dissociation occurring naturally under commonly observed physiological solution conditions.
Ensemble coding of context-dependent fear memory in the amygdala

After fear conditioning, presenting the conditioned stimulus (CS) alone yields a context-specific extinction memory; fear is suppressed in the extinction context, but renews in any other context. The context-dependence of extinction is mediated by a brain circuit consisting of the hippocampus, prefrontal cortex (PFC) and amygdala. In the present work, we sought to determine at what level of this circuit context-dependent representations of the CS emerge. To explore this question, we used cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH). This method exploits the intracellular expression profile of the immediate early gene (IEG), Arc, to visualize neuronal activation patterns to two different behavioral experiences. Rats were fear conditioned in one context and extinguished in another; 24 h later, they were sequentially exposed to the CS in the extinction context and another context. Control rats were also tested in each context, but were never extinguished. We assessed Arc mRNA expression within the basal amygdala (BA), lateral amygdala (LA), ventral hippocampus (VH), prelimbic cortex (PL) and infralimbic cortex (IL). We observed that the sequential retention tests induced context-dependent patterns of Arc expression in the BA, LA, and IL of extinguished rats; this was not observed in non-extinguished controls. In general, non-extinguished animals had proportionately greater numbers of non-selective (double-labeled) neurons than extinguished animals. Collectively, these findings suggest that extinction learning results in pattern separation, particularly within the BA, in which unique neuronal ensembles represent fear memories after extinction.
Role of Ca\(^{2+}\) in the Control of H\(_2\)O\(_2\)-Modulated Phosphorylation Pathways Leading to eNOS Activation in Cardiac Myocytes how this access benefits you. Your story matters

Nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ) play key roles in physiological and pathological responses in cardiac myocytes. The mechanisms whereby H 2 O 2 –modulated phosphorylation pathways regulate the endothelial isoform of nitric oxide synthase (eNOS) in these cells are incompletely understood. We show here that H 2 O 2 treatment of adult mouse cardiac myocytes leads to increases in intracellular Ca 2 + ([Ca 2 + ] i ), and document that activity of the L-type Ca 2 + channel is necessary for the H 2 O 2 -promoted increase in sarcomere shortening and of [Ca 2 + ] i . Using the chemical NO sensor Cu 2 (FL2E), we discovered that the H 2 O 2 -promoted increase in cardiac myocyte NO synthesis requires activation of the L-type Ca 2 + channel, as well as phosphorylation of the AMP-activated protein kinase (AMPK), and mitogen-activated protein kinase kinase 1/2 (MEK1/2). Moreover, H 2 O 2 -stimulated phosphorylations of eNOS, AMPK, MEK1/2, and ERK1/2 all depend on both an increase in [Ca 2 + ] i as well as the activation of protein kinase C (PKC). We also found that H 2 O 2 -promoted cardiac myocyte eNOS translocation from peripheral membranes to internal sites is abrogated by the L-type Ca 2 + channel blocker nifedipine. We have previously shown that kinase Akt is also involved in H 2 O 2 -promoted eNOS phosphorylation. Here we present evidence documenting that H 2 O 2 -promoted Akt phosphorylation is dependent on activation of the L-type Ca 2 + channel, but is independent of PKC. These studies establish key roles for Ca 2 + - and PKC-dependent signaling pathways in the modulation of cardiac myocyte eNOS activation by H 2 O 2 .
A Class of Weighted Low Rank Approximation of the Positive Semidefinite Hankel Matrix

We consider the weighted low rank approximation of the positive semidefinite Hankel matrix problem arising in signal processing. By using the Vandermonde representation, we firstly transform the problem into an unconstrained optimization problem and then use the nonlinear conjugate gradient algorithm with the Armijo line search to solve the equivalent unconstrained optimization problem. Numerical examples illustrate that the new method is feasible and effective.
Mechanisms of Orbital Floor Fractures: A Clinical, Experimental, and Theoretical Study

Purpose The purpose of this study was to investigate the two accepted mechanisms of the orbital blowout fracture (the hydraulic and the buckling theories) from a clinical, experimental, and theoretical standpoint. Methods Clinical cases in which blowout fractures resulted from both a pure hydraulic mechanism and a pure buckling mechanism are presented. Twenty-one intact orbital floors were obtained from human cadavers. A metal rod was dropped, experimentally, onto each specimen until a fracture was produced, and the energy required in each instance was calculated. A biomathematical model of the human bony orbit, depicted as a thin-walled truncated conical shell, was devised. Two previously published (by the National Aeronautics and Space Administration) theoretical structural engineering formulas for the fracture of thin-walled truncated conical shells were used to predict the energy required to fracture the bone of the orbital floor via the hydraulic and buckling mechanisms. Results Experimentally, the mean energy required to fracture the bone of the human cadaver orbital floor directly was 78 millijoules (mJ) (range, 29–127 mJ). Using the engineering formula for the hydraulic theory, the predicted theoretical energy is 71 mJ (range, 38–120 mJ); for the buckling theory, the predicted theoretical energy is 68 mJ (range, 40–106 mJ). Conclusion Through this study, we have experimentally determined the amount of energy required to fracture the bone of the human orbital floor directly and have provided support for each mechanism of the orbital blowout fracture from a clinical and theoretical basis.
Hantavirus Causing Hemorrhagic Fever with Renal Syndrome Enters from the Apical Surface and Requires Decay-Accelerating Factor (DAF/CD55)

ABSTRACT The Old World hantaviruses, members of the family Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS). Transmission to humans occurs via inhalation of aerosols contaminated with the excreta of infected rodents. The viral antigen is detectable in dendritic cells, macrophages, lymphocytes, and, most importantly, microvascular endothelial cells. However, the site and detailed mechanism of entry of HFRS-causing hantaviruses in polarized epithelial cells have not yet been defined. Therefore, this study focused on the entry of the pathogenic hantaviruses Hantaan and Puumala into African green monkey kidney epithelial cells and primary human endothelial cells. The polarized epithelial and endothelial cells were found to be susceptible to hantavirus infection exclusively from the apical surface. Treatment with phosphatidylinositol-specific phospholipase C, which removes glycosylphosphatidylinositol (GPI)-anchored proteins from the cell surface, protects cells from infection, indicating that hantaviruses require a GPI-anchored protein as a cofactor for entry. Decay-accelerating factor (DAF)/CD55 is a GPI-anchored protein of the complement regulatory system and serves as a receptor for attachment to the apical cell surface for a number of viruses. Infection was reduced by the pretreatment of hantaviral particles with human recombinant DAF. Moreover, the treatment of permissive cells with DAF-specific antibody blocked infection. These results demonstrate that the Old World hantaviruses Hantaan and Puumala enter polarized target cells from the apical site and that DAF is a critical cofactor for infection.
Growth hormone-releasing hormone in HIV-infected men with lipodystrophy: a randomized controlled trial.

CONTEXT Reduced growth hormone (GH) concentrations are observed in men with human immunodeficiency virus (HIV) lipodystrophy. OBJECTIVE To investigate the effects of growth hormone-releasing hormone (GHRH), a GH secretagogue, in treatment of HIV lipodystrophy. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled trial conducted at a research center in the United States between October 2002 and June 2003 and enrolling 31 HIV-infected men aged 18 to 60 years with evidence of lipodystrophy. INTERVENTIONS Participants were assigned to receive GHRH (1 mg subcutaneously twice daily) or placebo for 12 weeks. MAIN OUTCOME MEASURES The primary outcome was change in concentrations of insulin-like growth factor 1 (IGF-1) to detect overall change in GH levels in response to GHRH. Secondary end points included body composition by dual-energy x-ray absorptiometry and computed tomography, lipodystrophy ratings, and levels of glucose, insulin, and lipids. RESULTS Mean (SD) IGF-1 concentrations increased significantly in the GHRH group vs the placebo group (104 [110] ng/mL vs 6 [44] ng/mL, P =.004). Lean body mass significantly increased in the GHRH group vs the placebo group (0.9 [1.3] kg vs -0.3 [1.7] kg, P =.04), trunk fat significantly decreased (-0.4 [0.7] kg vs 0.2 [0.6] kg, P =.03), and the ratio of trunk to lower extremity fat improved significantly (-0.22 [0.32] vs 0.14 [0.29], P =.005). Abdominal visceral fat was reduced (-19.2 [36.6] cm2 vs 2.3 [24.3] cm2, P =.07) and the ratio of abdominal visceral fat to abdominal subcutaneous fat improved significantly more in the GHRH group (-0.19 [0.28] vs 0.07 [0.27], P =.02). Both physician and patient rating of lipodystrophy in the arms, legs, and abdomen also improved significantly. Levels of glucose, insulin, and lipids did not change significantly. CONCLUSIONS GHRH was well tolerated and effectively increased levels of IGF-1 in HIV-infected men with lipodystrophy. Total and regional body composition improved in response to GHRH, with increased lean mass and reduced truncal and visceral fat. Use of GHRH may potentially be a beneficial treatment strategy for this population.
Air-Gap Flux Density Distortion and Iron Losses in Anisotropic Synchronous Motors

The anisotropy of the rotor of the synchronous reluctance motor (sometimes assisted by permanent magnets) causes a high content of flux density harmonics. These harmonics cause flux density fluctuations in the stator iron teeth, and thus iron losses. These losses increase with the motor speed and are independent of the main flux, that is, they exist even during the flux-weakening operations. An analytical model, validated by finite-element analysis, shows the dependence of flux density harmonic content on the rotor geometry. Therefore, this model is adopted to individuate the flux-barrier geometry so as to minimize the stator iron losses.