Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemistry of matrix metalloproteinases and their inhibitors in thoracic aortic aneurysms and aortic valves of patients with Marfan's syndrome.

BACKGROUND Thoracic aortic aneurysms (TAAs) and valvular insufficiency, the main cardiovascular lesions in Marfan's syndrome, are associated with destruction of connective tissue; however, their pathogenesis remains unclear. METHODS AND RESULTS To test the hypothesis that changes in the activity of the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are responsible for the damage to connective tissue in these lesions, histochemical studies of the immunoreactivity (IR) for MMPs and their tissue TIMPs (MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2) were made in TAAs (n = 7) and aortic valves (n = 5) from 7 patients with Marfan's syndrome. All TAAs showed cystic medial necrosis (CMN), with loss of elastic fibers and smooth muscle cells. Extensive areas of myxoid change were found in all aortic valves. Areas of CMN showed no IR for any MMPs or TIMPs. The IR of smooth muscle cells at the borders of areas of CMN was stronger for all MMPs, especially MMP-2 and MMP-9, than in other regions. The surfaces of disrupted elastic fibers showed IR for MMP-2 and MMP-9. Areas of myxoid change showed similar but less pronounced alterations. CONCLUSIONS We hypothesize that the defect in fibrillin-1 in Marfan's syndrome leads to (1) formation of elastin that is abnormally aggregated and more easily degraded by MMPs than is normal elastin, (2) upregulation of the synthesis of MMPs, (3) progressive destruction of connective tissue by these enzymes, and (4) development of TAAs and valvular lesions.
Molecular Functional Interaction between T 2 R Taste Receptors and G-Protein Subunits Expressed in Taste Receptor Cells

Bitter taste perception is a conserved chemical sense against the ingestion of poisonous substances in mammals. A multigene family of G-protein-coupled receptors, T2R (so-called TAS2R or TRB) receptors and a G-protein subunit (G ), gustducin, are believed to be key molecules for its perception, but little is known about the molecular basis for its interaction. Here, we use a heterologous expression system to determine a specific domain of gustducin necessary for T2R coupling. Two chimeric G 16 proteins harboring 37 and 44 gustducin-specific sequences at their C termini (G16/gust37 and G16/gust44) responded to different T2R receptors with known ligands, but G16/gust 23, G16/gust11, and G16/gust5 did not. The former two chimeras contained a predicted 6 sheet, an 5 helix, and an extreme C terminus of gustducin, and all the domains were indispensable to the expression of T2R activity. We also expressed G16 protein chimeras with the corresponding domain from other G i proteins, cone-transducin (G t2), G i2, and G z (G16/t2, G16/i2, and G16/z). As a result, G16/t2 and G16/i2 produced specific responses of T2Rs, but G16/z did not. Because G t2 and G i2 are expressed in the taste receptor cells, these G-protein i subunits may also be involved in bitter taste perception via T2R receptors. The present G 16-based chimeras could be useful tools to analyze the functions of many orphan G-protein-coupled taste receptors.
Productivity gains decomposition and distribution of the price effects among stakeholders

La performance financiere d'une firme depend a la fois de son efficacite productive et de l'environnement economique dans lequel cette firme exerce son activite. Cette these enrichit cette litterature en developpant de nouveaux liens entre l’efficacite productive, la performance financiere et la distribution des gains de productivite. Trois contributions principales y sont developpees. Premierement, nous proposons une maniere originale de decomposer les ecarts de profit entre les firmes au niveau spatial en tenant compte de leur inefficacite productive et en reliant ensuite ces ecarts aux avantages/desavantages prix des parties prenantes de la firme. Deuxiemement, nous definissons, d’un point de vue methodologique, un indicateur de l'environnement prix pour une firme en comparant sa distance a la frontiere d'efficacite estimee, d’une part, avec des volumes et, d’autre part, avec des valeurs. Cet effet d'environnement prix a ete ensuite applique pour l’ensemble des industries americaines sur la periode 1987-2014. Troisiemement, nous developpons une approche methodologique pour decomposer l'inefficience technique globale des firmes a un niveau agrege tel que le secteur ou l’economie en deux composantes : l’inefficacite technique individuelle et l’inefficacite structurelle. Au final, ce travail de these tend a montrer que la generation des gains de productivite et leur distribution entre les parties prenantes d’une firme sont les deux facettes d'une meme piece. La premiere est liee a l'analyse economique de la PGF basee sur l'estimation d'une technologie de production tandis que la seconde traite d'une approche comptable et manageriale de la performance des firmes.
Phthalate Risks, Phthalate Regulation, and Public Health: A Review

As a result of concerns about the toxicity of phthalates to humans, several expert panels were convened toward the end of the 1990s to evaluate the implications of the scientific evidence for the risks of phthalates to humans of all ages. These panels concluded that the risks were low although they had concerns about specific applications of some phthalates, e.g., in medical devices. These groups identified data gaps and recommended additional studies on exposure and toxicity be conducted. In light of the additional data, reevaluations of the risks of phthalates were conducted. While these assessments were being undertaken, U.S. state governments and European authorities proposed and promulgated regulations to limit the use of certain phthalates, i.e., di-n-octyl phthalate (DnOP), di-isodecyl phthalate (DIDP), di-isononyl phthalate (DINP), butylbenzyl phthalate (BBP), dibutyl phthalate (DBP), and diethylhexyl phthalate (DEHP), especially in consumer products to which children are exposed. Very recently, similar regulations were promulgated in the United States under the Consumer Product Safety Improvement Act of 2008. This article summarizes recent evaluations of the risks of these phthalates, and addresses the public health implications of the regulations that were enacted. The analysis considers biomonitoring studies and epidemiological research in addition to laboratory animal evidence. Analysis of all of the available data leads to the conclusion that the risks are low, even lower than originally thought, and that there is no convincing evidence of adverse effects on humans. Since the scientific evidence strongly suggests that risks to humans are low, phthalate regulations that have been enacted are unlikely to lead to any marked improvement in public health.
A national study of the effect of chronic pain on the use of health care by depressed persons.

OBJECTIVE The objective of this study was to provide national estimates of the impact of common pain conditions such as back pain, chronic headache, self-reported arthritis, and unspecified chronic pain on the use of health services and quality of care among persons with depression. METHODS This was a cross-sectional study of data from a U.S. national household survey conducted in 1997-1998. The participants were 1,486 community-dwelling adults who met criteria for major depression or dysthymia according to the Composite International Diagnostic Interview Short-Form. RESULTS Depressed persons with comorbid pain (N=938) were older, had lower incomes, and reported more severe psychiatric distress than depressed persons who did not have pain. When sociodemographic characteristics and severity of psychological distress were adjusted for, comorbid pain was associated with about 20 percent more visits to medical providers by patients who made at least one visit during a year. However, the patients with comorbid pain were about 20 percent less likely to see a mental health specialist than patients without pain. Pain was also shown to be associated with greater use of complementary or alternative medicine but not with differences in the use of antidepressants. CONCLUSION Comorbid pain among persons with depression is associated with more intensive use of general medical services but lower rates of use of mental health services.
High frequencies of circulating melanoma‐reactive CD8+ T cells in patients with advanced melanoma

To determine whether circulating tumor‐reactive T cells are present in melanoma patients, unstimulated T cells from peripheral blood were tested for recognition of HLA‐A2‐ or HLA‐A1‐matched melanoma cell lines using the ELISPOT assay. Eleven out of 19 patients with metastatic melanoma had a T‐cell response with up to 0.81%, 0.78%, 0.53%, 0.12%, 0.10%, 0.09%, 0.07%, 0.06%, 0.06%, 0.04%, and 0.04% of peripheral blood mononuclear cells (PBMC) secreting IFNγ upon exposure to various HLA‐A2‐ or HLA‐A1‐matched melanoma cell lines. These T‐cell responses were mediated by CD8+ T cells and could specifically be blocked by an anti‐HLA‐A2 antibody in HLA‐A2‐positive patients. Separation experiments performed in one melanoma patient showed tumor‐reactive T cells in both the CD8+ effector T cell (CD45RA+/IFNγ+) as well as the CD8+ memory T‐cell compartment (CD45RO+/IFNγ+). In 3 out of 5 patients, in whom autologous cell lines were available, similar frequencies of T cells in response to HLA‐A1‐ or HLA‐A2‐matched allogeneic and autologous tumor cells were observed, while 2 patients had a T‐cell response restricted to either the autologous or the allogeneic cell lines. These results give evidence for the presence of tumor‐reactive CD8+ T cells in more than half of melanoma patients tested. Although some of these patients have clinical evidence for an immunological‐mediated tumor control, several patients have growing tumors suggesting presence of escape mechanisms. Int. J. Cancer 87:659–664, 2000. © 2000 Wiley‐Liss, Inc.
Biochemical and biophysical features of both oligomer/fibril and cell membrane in amyloid cytotoxicity

A great deal must still be learnt on the structural features of amyloid assemblies, particularly prefibrillar aggregates, and the relationship of the latter with amyloid cytotoxicity. Presently, it is recognized that the population of unstable, heterogeneous amyloid oligomers and protofibrils is mainly responsible for amyloid cytotoxicity. Conversely, mature fibrils are considered stable, harmless reservoirs of molecular species devoid of toxicity in the polymerized state. This view has been modified by recent reports showing that mature fibrils grown at different conditions can display different structural features and stabilities, possibly leading them to undergo disassembly with the leak of toxic oligomers. Fibril polymorphism is paralleled by oligomer polymorphism and both can be traced back to amyloid growth from differently destabilized monomers with distinct structural features at differing conditions. Recent research has started to unravel oligomer structural and biophysical features and the relationship between the latter and oligomer cytotoxicity. These data have led to the proposal that, together, both oligomer and membrane physical features determine the extent of oligomer–membrane interaction with the resulting disruption of membrane integrity and cell impairment. Such a view can help to explain the variable vulnerability of different cell types to the same amyloids and the lack of relationship between amyloid load and the severity of clinical symptoms. It also stresses the importance, for cell/tissue impairment, of the presence, in tissue, in addition to toxic oligomers, of fibrils conformers of reduced stability as a possible source of toxic oligomers, whose leakage can be favoured upon interaction with suitable surfaces or by other environmental conditions.
A 4.0 GHz 291 Mb Voltage-Scalable SRAM Design in a 32 nm High-k + Metal-Gate CMOS Technology With Integrated Power Management

This paper introduces a high-performance voltage-scalable SRAM design in a 32 nm strain-enhanced high-k + metal-gate logic CMOS technology. The 291 Mb SRAM design features a 0.171 ¿m2 six-transistor bitcell that supports a broad range of operating voltages for low-power and high-frequency embedded applications. The tileable 128 kb SRAM subarray achieves 72% array efficiency with 4.2 Mb/mm2 bit density, and consumes 5 mW of leakage power at the supply voltage of 1 V. The design provides 4 GHz and 2 GHz of operating frequencies at the supply voltages of 1.0 V and 0.8 V, respectively. The integrated power management scheme features close-loop memory array leakage control, floating bitline, and wordline driver sleep transistor, resulting in a 58% reduction in subarray leakage power consumption.
Variable selection in monotone single‐index models via the adaptive LASSO

We consider the problem of variable selection for monotone single‐index models. A single‐index model assumes that the expectation of the outcome is an unknown function of a linear combination of covariates. Assuming monotonicity of the unknown function is often reasonable and allows for more straightforward inference. We present an adaptive LASSO penalized least squares approach to estimating the index parameter and the unknown function in these models for continuous outcome. Monotone function estimates are achieved using the pooled adjacent violators algorithm, followed by kernel regression. In the iterative estimation process, a linear approximation to the unknown function is used, therefore reducing the situation to that of linear regression and allowing for the use of standard LASSO algorithms, such as coordinate descent. Results of a simulation study indicate that the proposed methods perform well under a variety of circumstances and that an assumption of monotonicity, when appropriate, noticeably improves performance. The proposed methods are applied to data from a randomized clinical trial for the treatment of a critical illness in the intensive care unit. Copyright © 2013 John Wiley & Sons, Ltd.
Periodontal characteristics in individuals with varying form of the upper central incisors.

It has been suggested that the variation in the morphology of the human periodontium may be related to the shape and form of the teeth. Furthermore, the severity of symptoms of periodontal disease have been proposed to differ among these various morphologic entities or "biotypes". The aim of the present study was (i) to identify individuals with markedly different crown forms and (ii) to determine probing pocket depth, probing attachment level and amount of gingival recession that had occurred at different teeth and tooth surfaces in such individuals. Clinical photographs of the maxillary incisor tooth region of 113 subjects who had been recruited for a long-term study on periodontal disease were available. The length (CL) and width (CW) of the crowns were determined and the CW/CL ratio was calculated for each tooth. 10% in each tail, 11 subjects in each group, were arbitrarily chosen as having either a long-narrow (N) or a short-wide (W) form of the central incisors. The probing pocket depth, probing attachment level and gingival recession data available from all subjects and subjects in groups W and N were compared and analyzed using the Student t-test and multiple regression analysis. The result from the analyses demonstrated that: (1) subjects with a long-narrow form of the upper central incisors had experienced more recession of the gingival margin at buccal surfaces than subjects who had a short-wide tooth form; (2) there was a significant influence of the CW/CL-ratio on the probing attachment level (p less than 0.05) and the amount of gingival recession (p less than 0.01) on buccal tooth surfaces. (ABSTRACT TRUNCATED AT 250 WORDS)
CSP control system implementation on embedded board

Renewable power generation can help countries meet their sustainable development goals through provision of access to clean, secure, reliable and affordable energy. Concentrated Solar Power (CSP) is a power generation technology that uses mirrors or lenses to concentrate the sun's rays and, in most of today's CSP systems, to heat a fluid and produce steam. CSP technologies are not currently widely deployed. This paper present a possible solution for the implementation of the electronic control board for a CSP system.
Recombinant human thyrotropin-stimulated radioiodine therapy of large nodular goiters facilitates tracheal decompression and improves inspiration.

INTRODUCTION The impact on tracheal anatomy and respiratory function of recombinant human (rh)TSH-stimulated (131)I therapy in patients with goiter is not clarified. METHODS In a double-blinded design, patients (age 37-87 yr) with a large multinodular goiter (range, 99-440 ml) were randomized to placebo (n = 15) or 0.3 mg rhTSH (n = 14) 24 h before (131)I therapy. The smallest cross-sectional area of the trachea (SCAT; assessed by magnetic resonance imaging) and the pulmonary function were determined before, 1 wk, and 12 months after therapy. RESULTS Data on goiter reduction have been reported previously. In the placebo group, no significant changes in the lung function or SCAT were found throughout the study. In the rhTSH group, a slight decrease was observed in the forced vital capacity 1 wk after therapy, whereas the mean individual change in SCAT was significantly increased by 10.5% (95% confidence interval = 0.9-20.0%). A further increase in SCAT to 117 +/- 36 mm(2) (P = 0.005 compared with 92 +/- 38 mm(2) at baseline) was seen at 12 months, corresponding to a mean of 31.4% (95% confidence interval = 16.0-46.8%). The expiratory parameters did not change significantly, whereas forced inspiratory flow at 50% of the vital capacity (FIF50%) increased from initially 3.34 +/- 1.33 liters/sec to ultimately 4.23 +/- 1.88 liters/sec (P = 0.015) in the rhTSH group, corresponding to a median increase of 24.6%. By 12 months, the relative improvements in FIF50% and in SCAT were inversely correlated to the respective baseline values (FIF50%: r = -0.47, P = 0.012; SCAT: r = -0.57, P = 0.001). CONCLUSION On average, neither compression of the trachea nor deterioration of the pulmonary function was observed in the acute phase after rhTSH-augmented (131)I therapy. In the long term, tracheal compression is diminished, and the inspiratory capacity improved, compared with (131)I therapy alone.
Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome.

HYPOTHESIS Normal resuscitation (oxygen delivery index [DO2I] >/=500 mL/min per square meter), compared with supranormal trauma resuscitation (DO2I >/=600 mL/min per square meter), requires less crystalloid volume, thus decreasing the incidence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). DESIGN Retrospective analysis of a prospective database. SETTING Twenty-bed intensive care unit (ICU) in a regional level I trauma center. PATIENTS Patients with major trauma (injury severity score >15, initial base deficit >/=6 mEq/L, or need for >/=6 units of packed red blood cells in the first 12 hours) or age 65 years or older with any 2 of the previous criteria. INTERVENTIONS Shock/trauma resuscitation protocol: pulmonary artery catheter, gastric tonometry, urinary bladder pressure measurements, lactated Ringer infusion, packed red blood cell transfusion, and moderate inotrope support, as needed, in that sequence, to attain and maintain a DO2I greater than or equal to 600 mL/min per m2 (16 months, ending January 1, 2001, n = 85) or a DO2I greater than or equal to 500 mL/min per square meter (16 months, starting January 1, 2001, n = 71) for the first 24 hours in the ICU. MAIN OUTCOME MEASURES Lactated Ringer infusion volume (liters) at ICU admission, gastric partial carbon dioxide minus end-tidal carbon dioxide(GAPCO2), IAH (urinary bladder pressure measurements >20 mm Hg), ACS (urinary bladder pressure measurements >25 mm Hg with organ dysfunction), multiple organ failure, and mortality. RESULTS Demographics, injury severity, and shock severity parameters were similar in both groups. The supranormal resuscitation group required more lactated Ringer infusion volume in the first 24 hours in the ICU (mean +/- SD, 13 +/- 2 vs 7 +/- 1 L; P<.05) and had higher GAPCO2 (16 +/- 2 vs 7 +/- 1 mm Hg; P<.05). In the supranormal group, IAH (42% vs 20%; P<.05) and ACS (16% vs 8%; P<.05) were more frequent. The conventional trauma outcomes, such as multiple organ failure (22% vs 9%; P<.05) and mortality (27% vs 11%; P<.05) were less favorable in the supranormal resuscitation group. CONCLUSION Supranormal resuscitation, compared with normal resuscitation, was associated with more lactated Ringer infusion, decreased intestinal perfusion (higher GAPCO2), and an increased incidence of IAH, ACS, multiple organ failure, and death.
Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread

The HA of influenza virus is a receptor-binding and fusion protein that is required to initiate infection. The HA receptor-binding domain determines the species of sialyl receptors recognized by influenza viruses. Here, we demonstrate that changes in the HA receptor-binding domain alter the ability of the H5N1 virus to spread systemically in mice. The A/Vietnam/1203/04 (VN1203) and A/Hong Kong/213/03 (HK213) viruses are consistently lethal to domestic chickens but differ in their pathogenicity to mammals. Insertion of the VN1203 HA and neuraminidase (NA) genes into recombinant HK213 virus expanded its tissue tropism and increased its lethality in mice; conversely, insertion of HK213 HA and NA genes into recombinant VN1203 virus decreased its systemic spread and lethality. The VN1203 and HK213 HAs differ by 10 aa, and HK213 HA has shown greater binding affinity for synthetic α2,6-linked sialyl receptor. Introduction of an S227N change and removal of N-linked glycosylation at residue 158 increased the α2,6-binding affinity of VN1203 HA. Recombinant VN1203 virus carrying the S227N change alone or with the residue-158 glycosylation site removed showed reduced lethality and systemic spread in mice but not in domestic chickens. Wild-type VN1203 virus exhibited the greatest efficiency in systemic spread after intramuscular inoculation and in infection of mouse bone marrow-derived dendritic cells and conventional pulmonary dendritic cells. These results show that VN1203 HA glycoprotein confers pathogenicity by facilitating systemic spread in mice; they also suggest that a minor change in receptor binding domain may modulate the virulence of H5N1 viruses.