bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treaties in US Domestic Law: Medellín v. Texas in Context
Authors: Reed Lucy , Granoff Ilmi 
Published: May 2009

AbstractIn Medellín v. Texas, a Texas death penalty case, the United States Supreme Court decided that it could not enforce what it acknowledged to be an international legal obligation to comply with the Avena judgment of the International Court of Justice. The Supreme Court's judgment in Medellín has put our understanding of the domestic treatment of US treaty law in a state of flux. Under the Supremacy Clause of the US Constitution, treaties are the supreme law of the land: binding, equivalent to federal statutes and enforceable by judges. After Medellín, treaties may not necessarily be enforceable federal law, depending on whether they are self-executing without additional legislation. The Supreme Court's decision depends upon the dramatic expansion of a narrow but necessary exception to the Supremacy Clause provided in an 1829 Supreme Court precedent. The consequence of that expansion is to put the US historical approach to treaty-making in question. This article provides (a) a brief overview of treaty law in the United States, including the law before Medellín regarding the domestic effect of treaty law, (b) an overview of Medellín, (c) a critique of the Court's reasoning in Medellín and (d) a discussion of its consequences.
The Authority of Peremptory Norms in International Law: State Consent or Natural Law?
Authors: Dubois Dan 
Published: May 2009

AbstractPeremptory norms, or norms jus cogens, hold a unique position in the hierarchy of international law. Unlike customary international law and treaty law, peremptory norms abide no derivation and are binding on all states regardless of their willingness to be bound by them. As a result, the authority of peremptory norms, it is argued, cannot be adequately explained by current positivist and voluntarist explanations of their authority. This article discusses the inadequacies of the positivist explanation and puts forward an alternative natural law explanation for the authority of peremptory norms which avoids the conceptual difficulties found in the positivist account. Finally, in the concluding section I address a number of potential realist and post-modernist counter arguments to my position and dismiss them as unconvincing.
A Novel Magnetic Resonance Imaging Classification of Discoid Lateral Meniscus Based on Peripheral Attachment
Authors: Ahn Jin Hwan , Lee Yong Seuk , Ha Hae Chan , Shim Jong Sup , Lim Kyung Sub 
Published: May 2009

Background In the symptomatic discoid lateral meniscus, the effectiveness of preoperative magnetic resonance imaging (MRI) is not well documented. Hypothesis Magnetic resonance imaging classification will provide more information to the surgeon in choosing the appropriate treatment methods with the help of arthroscopic findings. Study design Cohort study (diagnosis); Level of evidence, 2. Methods Sixty-seven patients (82 knees) were reviewed. The preoperative MRI was checked in 76 of 82 knees. The Lysholm and Ikeuchi grading scales were evaluated. Images were analyzed from MRI, and findings were classified into 4 categories: no shift, anterocentral shift, posterocentral shift, and central shift. Tear pattern classifications were based on arthroscopic findings: horizontal tear, peripheral tear, horizontal and peripheral tear, posterolateral corner loss, and others. The correlations between MRI classification tear patterns and surgical methods were analyzed using the chi-square test or the Fisher exact test. The sensitivity, specificity, and accuracy of shift in preoperative MRI–according to the existence of peripheral tear when corroborated with arthroscopy–were also analyzed with the chi-square test. Inter- and intraobserver reliability was statistically analyzed by producing the inter- and intraclass correlation coefficient. Results The mean preoperative Lysholm score was 77.3 (range, 43-97), and the last follow-up Lysholm score had increased to 96.8 (range, 84-100; P <. 001). At last follow-up (100% follow-up), the Ikeuchi grading scale scored 48 knees as excellent, 30 as good, and 4 as fair. According to the MRI classification, 43 knees were no shift; 6, anterocentral shift; 15, posterocentral shift; and 12, central shift. Shift-type knees had a significantly larger number of peripheral tears, and repairs were performed in the shift-type knees (55%) more frequently than in the no-shift-type knees (28%). Among 82 knees, 31 were repaired simultaneously after a central partial meniscectomy. Conclusion Magnetic resonance imaging classification provides more information to surgeons in choosing the appropriate treatment methods, although the final decision regarding procedure is made during arthroscopy after thorough analysis of the tear.
The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease
Authors: Hercus Timothy R. , Thomas Daniel , Guthridge Mark A. , Ekert Paul G. , King-Scott Jack , Parker Michael W. , Lopez Angel F. 
Published: May 2009

AbstractAlready 20 years have passed since the cloning of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor α-chain, the first member of the GM-CSF/interleukin (IL)–3/IL-5 family of hemopoietic cytokine receptors to be molecularly characterized. The intervening 2 decades have uncovered a plethora of biologic functions transduced by the GM-CSF receptor (pleiotropy) and revealed distinct signaling networks that couple the receptor to biologic outcomes. Unlike other hemopoietin receptors, the GM-CSF receptor has a significant nonredundant role in myeloid hematologic malignancies, macrophage-mediated acute and chronic inflammation, pulmonary homeostasis, and allergic disease. The molecular mechanisms underlying GM-CSF receptor activation have recently been revealed by the crystal structure of the GM-CSF receptor complexed to GM-CSF, which shows an unexpected higher order assembly. Emerging evidence also suggests the existence of intracellular signosomes that are recruited in a concentration-dependent fashion to selectively control cell survival, proliferation, and differentiation by GM-CSF. These findings begin to unravel the mystery of cytokine receptor pleiotropy and are likely to also apply to the related IL-3 and IL-5 receptors as well as other heterodimeric cytokine receptors. The new insights in GM-CSF receptor activation have clinical significance as the structural and signaling nuances can be harnessed for the development of new treatments for malignant and inflammatory diseases.
Platelet membrane proteomics: a novel repository for functional research
Authors: Lewandrowski Urs , Wortelkamp Stefanie , Lohrig Katharina , Zahedi René P. , Wolters Dirk A. , Walter Ulrich , Sickmann Albert 
Published: May 2009

AbstractBeing central players in thrombosis and hemostasis, platelets react in manifold and complex ways to extracellular stimuli. Cell-matrix and cell-cell interactions are mandatory for initial adhesion as well as for final development of stable plugs. Primary interfaces for interactions are plasma membrane proteins, of which many have been identified over the past decades in individual studies. However, due to their enucleate structure, platelets are not accessible to large-scale genomic screens and thus a comprehensive inventory of membrane proteins is still missing. For this reason, we here present an advanced proteomic setup for the detailed analysis of enriched platelet plasma membranes and the so far most complete collection of platelet membrane proteins. In summary, 1282 proteins were identified, of which more than half are termed to be of membrane origin. This study provides a brief overview of gene ontology subcellular and functional classification, as well as interaction network analysis. In addition, the mass spectrometric data were used to assemble a first tentative relative quantification of large-scale data on the protein level. We therefore estimate the presented data to be of major interest to the platelet research field and to support rational design of functional studies.
A single nucleotide polymorphism determines protein isoform production of the human c-FLIP protein
Authors: Ueffing Nana , Singh Kusum K. , Christians Andrea , Thorns Christoph , Feller Alfred C. , Nagl Florian , Fend Falko , Heikaus Sebastian , Marx Alexander , Zotz Rainer B. , Brade Joachim , Schulz Wolfgang A. , Schulze-Osthoff Klaus , Schmitz Ingo , Schwerk Christian 
Published: May 2009

Abstract
The cellular FLICE-inhibitory protein (c-FLIP) is a modulator of death receptor-mediated apoptosis and plays a major role in T- and B-cell homeostasis. Three different isoforms have been described on the protein level, including the long form c-FLIPL as well as 2 short forms, c-FLIPS and the recently identified c-FLIPR. The mechanisms controlling c-FLIP isoform production are largely unknown. Here, we identified by sequence comparison in several mammals that c-FLIPR and not the widely studied c-FLIPS is the evolutionary ancestral short c-FLIP protein. Unexpectedly, the decision for production of either c-FLIPS or c-FLIPR in humans is defined by a single nucleotide polymorphism in a 3′ splice site of the c-FLIP gene (rs10190751A/G). Whereas an intact splice site directs production of c-FLIPS, the splice-dead variant causes production of c-FLIPR. Interestingly, due to differences in protein translation rates, higher amounts of c-FLIPS protein compared with c-FLIPR are produced. Investigation of diverse human cell lines points to an increased frequency of c-FLIPR in transformed B-cell lines. A comparison of 183 patients with follicular lymphoma and 233 population controls revealed an increased lymphoma risk associated with the rs10190751 A genotype causing c-FLIPR expression.
Molecular identification of differentially regulated genes in the hydrothermal-vent species Bathymodiolus thermophilus and Paralvinella pandorae in response to temperature
Authors: Boutet Isabelle , Jollivet Didier , Shillito Bruce , Moraga Dario , Tanguy Arnaud 
Published: May 2009

AbstractBackgroundHydrothermal vents and cold seeps represent oases of life in the deep-sea environment, but are also characterized by challenging physical and chemical conditions. The effect of temperature fluctuations on vent organisms in their habitat has not been well explored, in particular at a molecular level, most gene expression studies being conducted on coastal marine species. In order to better understand the response of hydrothermal organisms to different temperature regimes, differentially expressed genes (obtained by a subtractive suppression hybridization approach) were identified in the musselBathymodiolus thermophilusand the annelidParalvinella pandorae irlandeito characterize the physiological processes involved when animals are subjected to long term exposure (2 days) at two contrasting temperatures (10° versus 20°C), while maintained atin situpressures. To avoid a potential effect of pressure, the experimental animals were initially thermally acclimated for 24 hours in a pressurized vessel.ResultsFor each species, we produced two subtractive cDNA libraries (forward and reverse) from sets of deep-sea mussels and annelids exposed together to a thermal challenge under pressure. RNA extracted from the gills, adductor muscle, mantle and foot tissue were used forB. thermophilus. For the annelid model, whole animals (small individuals) were used. For each of the four libraries, we sequenced 200 clones, resulting in 78 and 83 unique sequences in mussels and annelids (about 20% of the sequencing effort), respectively, with only half of them corresponding to known genes. Real-time PCR was used to validate differentially expressed genes identified in the corresponding libraries. Strong expression variations have been observed for some specific genes such as the intracellular hemoglobin, the nidogen protein, and Rab7 inP. pandorae, and the SPARC protein, cyclophilin, foot protein and adhesive plaque protein inB. thermophilus.ConclusionOur results indicate that mussels and worms are not responding in the same way to temperature variations. While the results obtained for the musselB. thermophilusseem to indicate a metabolic depression (strong decrease in the level of mRNA expression of numerous genes) when temperature increased, the annelidP. pandoraemainly displayed a strong regulation of the mRNA encoding subunits and linkers of respiratory pigments and some proteins involved in membrane structure. In both cases, these regulations seem to be partly due to a possible cellular oxidative stress induced by the simulated thermal environment (10°C to 20°C). This work will serve as a starting point for studying the transcriptomic response of hydrothermal mussels and annelids in future experiments in response to thermal stress at various conditions of duration and temperature challenge.
Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies
Authors: Solares Ana M , Santana Agueda , Baladrón Idania , Valenzuela Carmen , González Carlos A , Díaz Alina , Castillo Dagnelia , Ramos Thelvia , Gómez Roberto , Alonso Daniel F , Herrera Luis , Sigman Hugo , Perea Silvio E , Acevedo Boris E , López-Saura Pedro 
Published: May 2009

Abstract

Background
Cervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL), the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV) has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2) phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies.

Methods
Thirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 – 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated.

Results
No maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression. HPV DNA was negative in 48% of the previously positive patients. Long term follow-up did not reveal recurrences or adverse events.

Conclusion
CIGB 300 was safe and well tolerated. This is the first clinical trial where a drug has been used to target the CK2 phosphoaceptor domain providing an early proof-of-principle of a possible clinical benefit.
Use of television, videogames, and computer among children and adolescents in Italy
Authors: Patriarca Alessandro , Di Giuseppe Gabriella , Albano Luciana , Marinelli Paolo , Angelillo Italo F 
Published: May 2009

Abstract

Background
This survey determined the practices about television (video inclusive), videogames, and computer use in children and adolescents in Italy.

Methods
A self-administered anonymous questionnaire covered socio-demographics; behaviour about television, videogames, computer, and sports; parental control over television, videogames, and computer.

Results
Overall, 54.1% and 61% always ate lunch or dinner in front of the television, 89.5% had a television in the bedroom while 52.5% of them always watched television there, and 49% indicated that parents controlled the content of what was watched on television. The overall mean length of time daily spent on television viewing (2.8 hours) and the frequency of watching for at least two hours per day (74.9%) were significantly associated with older age, always ate lunch or dinner while watching television, spent more time playing videogames and using computer. Those with parents from a lower socio-economic level were also more likely to spend more minutes viewing television. Two-thirds played videogames for 1.6 daily hours and more time was spent by those younger, males, with parents that do not control them, who watched more television, and who spent more time at the computer. The computer was used by 85% of the sample for 1.6 daily hours and those older, with a computer in the bedroom, with a higher number of computers in home, who view more television and play videogames were more likely to use the computer.

Conclusion
Immediate and comprehensive actions are needed in order to diminish time spent at the television, videogames, and computer.
Will the NHS continue to function in an influenza pandemic? a survey of healthcare workers in the West Midlands, UK
Authors: Damery Sarah , Wilson Sue , Draper Heather , Gratus Christine , Greenfield Sheila , Ives Jonathan , Parry Jayne , Petts Judith , Sorell Tom 
Published: May 2009

AbstractBackgroundIf UK healthcare services are to respond effectively to pandemic influenza, levels of absenteeism amongst healthcare workers (HCWs) must be minimised. Current estimates of the likelihood that HCWs will continue to attend work during a pandemic are subject to scientific and predictive uncertainty, yet an informed evidence base is needed if contingency plans addressing the issues of HCW absenteeism are to be prepared.MethodsThis paper reports the findings of a self-completed survey of randomly selected HCWs across three purposively sampled healthcare trusts in the West Midlands. The survey aimed to identify the factors positively or negatively associated with willingness to work during an influenza pandemic, and to evaluate the acceptability of potential interventions or changes to working practice to promote the continued presence at work of those otherwise unwilling or unable to attend. 'Likelihood' and 'persuadability' scores were calculated for each respondent according to indications of whether or not they were likely to work under different circumstances. Binary logistic regression was used to compute bivariate and multivariate odds ratios to evaluate the association of demographic variables and other respondent characteristics with the self-described likelihood of reporting to work.ResultsThe survey response rate was 34.4% (n = 1032). Results suggest absenteeism may be as high as 85% at any point during a pandemic, with potential absence particularly concentrated amongst nursing and ancillary workers (OR 0.3; 95% CI 0.1 to 0.7 and 0.5; 95% CI 0.2 to 0.9 respectively).ConclusionLevels of absenteeism amongst HCWs may be considerably higher than official estimates, with potential absence concentrated amongst certain groups of employees. Although interventions designed to minimise absenteeism should target HCWs with a low stated likelihood of working, members of these groups may also be the least receptive to such interventions. Changes to working conditions which reduce barriers to theabilityto work may not address barriers linked towillingnessto work, and may fail to overcome HCWs' reluctance to work in the face of what may still be deemed unacceptable risk to self and/or family.
Interaction of perfluorooctanoic acid with human serum albumin
Authors: Wu Ling-Ling , Gao Hong-Wen , Gao Nai-Yun , Chen Fang-Fang , Chen Ling 
Published: May 2009

AbstractBackgroundRecently, perfluorooctanoic acid (PFOA) has become a significant issue in many aspects of environmental ecology, toxicology, pathology and life sciences because it may have serious effects on the endocrine, immune and nervous systems and can lead to embryonic deformities and other diseases. Human serum albumin (HSA) is the major protein component of blood plasma and is called a multifunctional plasma carrier protein because of its ability to bind an unusually broad spectrum of ligands.ResultsThe interaction of PFOA with HSA was investigated in the normal physiological condition by equilibrium dialysis, fluorospectrometry, isothermal titration calorimetry (ITC) and circular dichroism (CD). The non-covalent interaction is resulted from hydrogen bond, van der Waals force and hydrophobic stack. PFOA binding to HSA accorded with two-step binding model with the saturation binding numbers of PFOA, only 1 in the hydrophobic intracavity of HSA and 12 on the exposed outer surface. The interaction of PFOA with HSA is spontaneous and results in change of HSA conformation. The possible binding sites were speculated.ConclusionThe present work suggested a characterization method for the intermolecular weak interaction. It is potentially useful for elucidating the toxigenicity of perfluorochemicals when combined with biomolecular function effect, transmembrane transport, toxicological testing and the other experiments.
Acute myocardial infarction and pulmonary embolism in a young man with pernicious anemia-induced severe hyperhomocysteinemia
Authors: Melhem Ayyash , Desai Ankit , Hofmann Marion A 
Published: May 2009

Abstract
A 27 year-old man who presented to the hospital with progressive lower extremity weakness, developed an acute ST elevation myocardial infarction on his second hospital day. Primary angioplasty to the left anterior descending coronary artery was performed. Due to persistent dyspnea, the patient underwent a diagnostic chest computed tomography which confirmed multiple small pulmonary emboli. Laboratory analysis revealed a megaloblastic anemia with a reduced vitamin B12 level and positive titers for antibodies against intrinsic factor, establishing a diagnosis of pernicious anemia. Screening for hypercoaguable markers documented an isolated severely elevated homocysteine levels (105 μmol/l). No other significant risk factors for coronary artery disease including a family history of premature atherosclerosis were identified. This case illustrates the importance of testing for hyperhomocysteinemia as part of a workup for atherothrombotic disease, especially in patients without other significant risk factors. The severity of hyperhomocysteinemia found in our patient is unusual for patients with vitamin B12 malabsorption and raises the question of whether the widely practiced folic acid fortification in the United States may mask or even worsen vitamin B12 deficiency over time, leading to more severe cases of vitamin B12 deficiency and hyperhomocysteinemia than seen in the past.