Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation and use of sediment toxicity reference sites for statistical comparisons in regional assessments

Sediment reference sites were used to establish toxicity standards against which to compare results from sites investigated in San Francisco Bay (California, USA) monitoring programs. The reference sites were selected on the basis of low concentrations of anthropogenic chemicals, distance from active contaminant sources, location in representative hydrographic areas of the Bay, and physical features characteristic of depositional areas (e.g., fine grain size and medium total organic carbon [TOC]). Five field‐replicated sites in San Francisco Bay were evaluated over three seasons. Samples from each site were tested with nine toxicity test protocols and were analyzed for sediment grain size and concentrations of trace metals, trace organics, ammonia, hydrogen sulfide, and TOC. The candidate sites were found to have relatively low concentrations of measured chemicals and generally exhibited low toxicity. Toxicity data from the reference sites were then used to calculate numerical tolerance limits to be used as threshold values to determine which test sites had significantly higher toxicity than reference sites. Tolerance limits are presented for four standard test protocols, including solid‐phase sediment tests with the amphipods Ampelisca abdita and Eohaustorius estuarius and sea urchin Strong ylocentrotus purpuratus embryo/larval development tests in pore water and at the sediment‐water interface (SWI). Tolerance limits delineating the lowest 10th percentile (0.10 quantile) of the reference site data distribution were 71% of the control response for Ampelisca, 70% for Eohaustorius, 94% for sea urchin embryos in pore water, and 87% for sea urchins embryos exposed at the SWI. The tolerance limits are discussed in terms of the critical values governing their calculation and the management implications arising from their use in determining elevated toxicity relative to reference conditions.
Total-body irradiation and melphalan is a safe and effective conditioning regimen for autologous bone marrow transplantation in children with acute myeloid leukemia in first remission. The Italian Association for Pediatric Hematology and Oncology-Bone Marrow Transplantation Group.

PURPOSE To evaluate the safety and efficacy of a preparative regimen consisting of fractionated total-body radiation (9.9 to 12 Gy) and melphalan (140 mg/m(2) in a single dose) in children with acute myeloid leukemia in first complete remission (CR) given autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS Fifty-three children (30 males and 23 females; age range, 1.5 to 18 years) were enrolled onto the study. The median time from first CR to ABMT was 3.5 months (range, 1.4 to 13 months), with 45 patients (85%) undergoing transplantation within 6 months from the diagnosis. Forty-five patients received in vitro marrow purging with standard-dose mafosfamide (100 microg/mL), seven patients were treated with interleukin-2 before marrow collection, and in the remaining child, the marrow was unmanipulated. The median infused cell dose was 1.8 x 10(8)/kg (range, 0.4 to 5.8 x 10(8)/kg). RESULTS All patients but one achieved hematopoietic engraftment, with a median time to neutrophil recovery of 24 days (range,11 to 66 days). Treatment-related toxicity was moderate and consisted mainly of mucositis. One patient died from cytomegalovirus interstitial pneumonia, and one died from pulmonary hemorrhage. Fourteen patients (26%) relapsed at a median time of 6 months after ABMT (range, 2 to 17 months), with a cumulative relapse probability of 29% (95% confidence interval, 16% to 42%). The 5-year Kaplan-Meier estimate of survival for all 53 patients was 78% (range, 65% to 90%), whereas the overall 5-year disease-free survival was 68% (range, 55% to 81%), with a median follow-up duration of 40 months (range, 7 to 130 months). CONCLUSIONS These data suggest that, in our cohort of patients, the combination of total-body irradiation and melphalan is safe and associated with good antileukemia activity, making ABMT an appealing alternative for postremission therapy in children with acute myeloid leukemia in first CR.
Chimeric G proteins allow a high-throughput signaling assay of Gi-coupled receptors.

G-protein-coupled receptors are a major target for potential therapeutics; yet, a large number of these receptors couple to the Gi pathway, generating signals that are difficult to detect. We have combined chimeric G proteins, automated sample handling, and simultaneous 96-well fluorometric imaging to develop a high-throughput assay system for Gi signaling. The chimeric G proteins alter receptor coupling so that signaling can occur through Gq and result in mobilization of intracellular calcium stores. An automated signaling assay device, the fluorometric imaging plate reader (FLIPR), can simultaneously measure this response in real time in 96-well microplates, allowing two people to process more than 10,000 points per day. We used the chimeric G protein/FLIPR system to characterize signaling by the Gi-coupled human opioid receptors. We show that the mu, delta, and kappa opioid receptors and the related nociceptin receptor, ORL1, each couple to Galphaqi5, Galphaqo5, and Galpha16 (Galphaqi5 and Galphaqo5 refer to Galphaq proteins containing the five carboxyl-terminal amino acids from Galphai and Galphao, respectively) and that different receptor/G protein combinations show different levels of maximal activation. We tested 31 opioid ligands for agonist activity at the opioid receptors (124 ligand-receptor combinations); all 31 activated at least one receptor type, and several activated multiple receptors with differing potencies. This high-throughput assay could be useful for dissecting the complex ligand-receptor relationships that are common in nature.
Technologies for genomic and epigenomic analysis: a new frontier for micro- and nano-fluidics

Les sciences de la vie et de la sante sont aujourd'hui au centre d'interets scientifiques et economiques. Les aspects economiques sont presides par le developpement de nouveaux outils de diagnostic fiables, reposant sur des mesures parallelisees d'interaction moleculaires au niveau de l'ADN ou des proteines. L'interet scientifique est tres pluridisciplinaire, car les mecanismes de la vie impliquent des reactions physico-physiques multiples, que l'on aborde avec des technologies nouvelles et des approches de modelisation encore a developper. Dans ce panorama, les micro- et nano-technologies sont appelees a apporter de nouvelles solutions car elles permettent de manipuler des cellules ou des molecules avec une grande precision temporelle et spatiale. Elles sont en outre complementaires avec les outils classiques de la biologie cellulaire et moleculaire, qui permettent des analyses sur des echantillons de grande dimension. Pourtant les exemples de succes scientifiques a l'interface des sciences de la vie et de la biologie restent plutot rares. Dans ce manuscrit, nous faisons un tour d'horizon sur l'emergence de nouvelles technologies dediees a l'analyse du genome. Nous presentons certaines de nos contributions, et proposons quelques pistes pour de futures recherches, principalement focalisees sur l'etude des mecanismes d'instabilite du genome realisee dans des populations contenant seulement quelques cellules.
Does Legal Doctrine Matter? Unpacking Law and Policy Preferences on the U.S. Supreme Court

Judicial scholars often struggle to disentangle the effects of law and policy preferences on U.S. Supreme Court decision making. We employ a new approach to measuring the effect—if any—of the law on justices' decisions. We use positions taken on Supreme Court cases by members of Congress and presidents to identify policy components of voting. Doing so enables us to isolate the effects of three legal doctrines: adherence to precedent, judicial restraint, and a strict interpretation of the First Amendment's protection of speech clause. We find considerable evidence that legal factors play an important role in Supreme Court decision making. We also find that the effect of legal factors varies across justices.
Influence of transcriptional and translational control sequences on the expression of foreign genes in Caulobacter crescentus

The influence of expression control sequences (ECSs; promoters and ribosome-binding sites [RBSs]), transcriptional terminators, and gene orientation on the expression of the Escherichia coli lacZ gene in the gram-negative microorganisms Caulobacter crescentus and E. coli was investigated. A series of broad-host-range expression vectors, based on the RK2 plasmid derivative pRK248, were constructed. The ECSs included the tac promoter, the promoter for the surface layer protein of C. crescentus, and promoters from a number of gram-positive bacteria together with their associated RBSs. In addition, synthetic ECSs were constructed by using different combinations of promoters and RBSs. lacZ expression was found to be dependent on the nature of the promoter and RBS and, to a lesser extent, on the presence of a transcriptional terminator and the orientation of the promoter-lacZ construct in pRK248. The relative efficiencies of the various ECSs in driving lacZ expression differed markedly in C. crescentus and E. coli. In C. crescentus, the ECS ptac1 (tac promoter and consensus RBS for C. crescentus mRNAs) appeared to be the most efficient, producing 12-fold-higher activity than did pSL (promoter for the surface layer protein of C. crescentus and its putative RBS). pSL was not transcribed in E. coli, whereas various promoters from gram-positive microorganisms were transcribed in both C. crescentus and E. coli. A number of ECSs were also used to drive mosquitocidal toxin gene expression in C. crescentus, and a correlation between toxin expression and lacZ expression was observed.
Bedside Ultrasound‐Guided Celiac Plexus Neurolysis in Upper Abdominal Cancer Patients: A Randomized, Prospective Study for Comparison of Percutaneous Bilateral Paramedian vs. Unilateral Paramedian Needle‐Insertion Technique

Percutaneous anterior abdominal ultrasound guidance for performing celiac plexus neurolysis is a relatively new but more economical, less time‐consuming, more comfortable bedside technique for interventional pain management. Paucity of studies evaluating the efficacy of single‐site vs. double‐site injections at celiac trunk for ultrasound‐guided celiac plexus neurolysis (USCPN) prompted us to conduct a prospective, randomized, single‐blind clinical trial to compare USCPN using bilateral paramedian (double needle) technique with unilateral paramedian (single needle) technique.
In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-β11

Down-regulation of CD4+CD25+ regulatory T (Treg) cell function might be beneficial to enhance the immunogenicity of viral and tumor vaccines or to induce breakdown of immunotolerance. Although the mechanism of suppression used by Treg cells remains controversial, it has been postulated that TGF-β1 mediates their immunosuppressive activity. In this study, we show that P17, a short synthetic peptide that inhibits TGF-β1 and TGF-β2 developed in our laboratory, is able to inhibit Treg activity in vitro and in vivo. In vitro studies demonstrate that P17 inhibits murine and human Treg-induced unresponsiveness of effector T cells to anti-CD3 stimulation, in an MLR or to a specific Ag. Moreover, administration of P17 to mice immunized with peptide vaccines containing tumor or viral Ags enhanced anti-vaccine immune responses and improved protective immunogenicity against tumor growth or viral infection or replication. When CD4+ T cells purified from OT-II transgenic mice were transferred into C57BL/6 mice bearing s.c. EG.7-OVA tumors, administration of P17 improved their proliferation, reduced the number of CD4+Foxp3+ T cells, and inhibited tumor growth. Also, P17 prevented development of immunotolerance induced by oral administration of OVA by genetically modified Lactococcus lactis in DO11.10 transgenic mice sensitized by s.c. injection of OVA. These findings demonstrate that peptide inhibitors of TGF-β may be a valuable tool to enhance vaccination efficacy and to break tolerance against pathogens or tumor Ags.
Skill premium y tipo de cambio real: El caso de las economías latinoamericanas

Se conoce como skill premium a la brecha salarial promedio existente entre los trabajadores calificados y los no calificados. A partir de la segunda globalizacion financiera, en los paises desarrollados se ha visto un ensanchamiento de este diferencial mientras que en los paises en desarrollo el comportamiento ha sido mas volatil. Especificamente para el caso de los paises de America Latina hubo un incremento del skill premium en la decada de 1990 y una reduccion a partir del comienzo del nuevo siglo. Explicaciones basadas en el comercio internacional, el cambio tecnico sesgado, vaivenes en el marco institucional y choques macroeconomicos han sido propuestas para comprender el origen de los movimientos en la desigualdad en el mercado laboral. En este trabajo se repasan cada una de ellas y se las relaciona con el efecto particular que el tipo de cambio real puede generar en economias subdesarrolladas. Los vinculos entre ambas variables son diversos y se mueven en distintas direcciones. A priori, un incremento en el tipo de cambio real implica una mayor demanda de trabajadores calificados en el sector dinamico exportador, pero al mismo tiempo funciona como una proteccion natural para la industria manufacturera domestica intensiva en mano de obra no calificada. A su vez, encarece la importacion de capital que resulta mas complementario con el trabajo calificado. La predominancia de un efecto sobre otro esta historicamente determinada por lo que su estudio tiene un fuerte componente empirico. Con el objetivo de indagar sobre los distintos canales sobre los que el tipo de cambio real puede afectar al skill premium se construyo un panel con datos de 13 paises latinoamericanos para el periodo 1993-2011. Del analisis cuantitativo emergen dos conclusiones. Mientras que una moneda nacional debil medida en niveles parece estar asociada a una elevada brecha salarial, una depreciacion induciria una reduccion del skill premium. En esta aparente contradiccion se esconde la posibilidad de que la relacion mute a traves del tiempo. En los primeros anos posteriores a una devaluacion el efecto ingreso asociado a un encarecimiento de las importaciones produce un incremento en la demanda de trabajadores no calificados gracias a la expansion de la industria sustitutiva. A medida que el tipo de cambio real se establece en un nivel competitivo se alienta el desarrollo del sector exportador, intensivo en mano de obra calificada y toma fuerza la demanda de trabajadores calificados. Por otra parte la estructura productiva es relevante en materia distributiva. No solo afecta por si misma a la brecha salarial sino que influye significativamente reforzando o mitigando los efectos que el tipo de cambio real tiene sobre el skill premium. El resultado es consistente aun si se consideran potenciales problemas de endogeneidad.
Pluralistic ignorance and college student perceptions of gender-specific alcohol norms.

Students' perceived norms and personal concern about alcohol use were examined in 4 (N=971) experiments. Men reported that same-sex peers were less concerned about campus alcohol practices than themselves or female students; women believed that they were more concerned about campus alcohol practices than both same- and opposite-sex peers (Experiments 1 and 2). Additional evidence suggested that students were not merely engaging in impression management. Men reported more social pressure to drink and greater embarrassment about expressing drinking-related concerns; women expected more severe consequences if they drank excessively (Experiment 3). A male student (vs female student) expressing concerns about alcohol was believed to experience greater difficulties fitting in (Experiment 4). Implications for peer influence and drug use intervention are discussed.
Secretory Granule-mediated Co-secretion ofl-Glutamate and Glucagon Triggers Glutamatergic Signal Transmission in Islets of Langerhans*

l-Glutamate is believed to function as an intercellular transmitter in the islets of Langerhans. However, critical issues, i.e. where, when and howl-glutamate appears, and what happens upon stimulation of glutamate receptors in the islets, remain unresolved. Vesicular glutamate transporter 2 (VGLUT2), an isoform of the vesicular glutamate transporter essential for neuronal storage of l-glutamate, is expressed in α cells (Hayashi, M., Otsuka, M., Morimoto, R., Hirota, S., Yatsushiro, S., Takeda, J., Yamamoto, A., and Moriyama, Y. (2001) J. Biol. Chem. 276, 43400–43406). Here we show that VGLUT2 is specifically localized in glucagon-containing secretory granules but not in synaptic-like microvesicles in αTC6 cells, clonal α cells, and islet α cells. VGLUT1, another VGLUT isoform, is also expressed and localized in secretory granules in α cells. Low glucose conditions triggered co-secretion of stoichiometric amounts ofl-glutamate and glucagon from αTC6 cells and isolated islets, which is dependent on temperature and Ca2+ and inhibited by phentolamine. Similar co-secretion ofl-glutamate and glucagon from islets was observed upon stimulation of β-adrenergic receptors with isoproterenol. Under low glucose conditions, stimulation of glutamate receptors facilitates secretion of γ-aminobutyric acid from MIN6 m9, clonal β cells, and isolated islets. These results indicate that co-secretion ofl-glutamate and glucagon from α cells under low glucose conditions triggers GABA secretion from β cells and defines the mode of action of l-glutamate as a regulatory molecule for the endocrine function. To our knowledge, this is the first example of secretory granule-mediated glutamatergic signal transmission.
Decline of plasma 5α‐dihydrotestosterone (DHT) levels upon testosterone administration to elderly men with subnormal plasma testosterone and high DHT levels

The study was performed to measure the impact of testosterone (T) administration on circulating levels of 5α‐dihydrotestosterone (DHT). Group 1 (32 men; mean age 61 years; mean T 6.9 ± 1.9 nmol l−1) were treated for 15 months with long‐acting T undecanoate. Group 2 (23 men, mean age 60 years, mean T 7.6 ± 2.0 nmol l−1) were treated for 9 months with T gel. Plasma T and DHT were measured before and after 9 months T administration. In the men treated with T undecanoate plasma T and DHT were also measured after 12 and 15 months. Before T administration, plasma DHT ranged from 0.39 to 1.76 nmol l−1 (0.30–1.90 nmol l−1). Mean DHT declined upon T administration from 0.95 ± 0.50 to 0.55 ± 0.30 nmol l−1 (P < 0.05). With an arbitrary cut‐off at 0.60 nmol l−1, all 21 values of DHT > 0.60 nmol l−1 had fallen from 1.29 ± 0.50 to 0.70 ± 0.60 nmol l−1 (P < 0.01). Below this cut‐off point 13 values rose and 21 fell upon T administration. Below this cut‐off point values on average declined from 0.39 ± 0.12 to 0.30 ± 0.14 nmol l−1 (P < 0.05). The study revealed that in a cohort of elderly men with subnormal plasma T levels plasma DHT levels declined upon T administration when they were in the higher range of normal (>0.6 nmol l−1), with a profound shift of DHT/T ratios presumed to be an indicator of a reduced 5α‐reductase activity. Below plasma DHT levels of 0.6 nmol l−1, responses of plasma DHT to T administration varied.
Hyperinsulinemia in African-American Adolescents Compared With Their American White Peers Despite Similar Insulin Sensitivity

OBJECTIVE—African-American (AA) children are hyperinsulinemic and insulin resistant compared with American white (AW) children. Previously, we demonstrated that insulin secretion relative to insulin sensitivity was ∼75% higher in AA compared with AW children, suggesting that hyperinsulinemia in AA children is not merely a compensatory response to lower insulin sensitivity. The aim of the present investigation was to assess whether glucose-stimulated insulin response is higher in AA versus AW adolescents who have comparable in vivo insulin sensitivity. RESEARCH DESIGN AND METHODS—The hyperinsulinemic-euglycemic and hyperglycemic clamp techniques were utilized to assess first- and second-phase insulin secretion. Insulin secretion relative to insulin sensitivity was calculated as the glucose disposition index. RESULTS—AA adolescents compared with their AW peers with comparable insulin sensitivity and body composition had higher first-phase insulin concentrations. CONCLUSIONS—The quantitative relationship between insulin sensitivity and first-phase insulin appears to differ among AA and AW adolescents.
Abnormal prion protein in the retina of the most commonly occurring subtype of sporadic Creutzfeldt-Jakob disease

Background: Involvement of the eye has been reported in patients with variant Creutzfeldt-Jakob disease (vCJD), but there is disagreement on whether retinal involvement occurs in sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Western blotting, paraffin embedded tissue blotting, and immunohistochemistry were used to test whether the abnormal form of the prion protein (PrPSc) accumulates to detectable levels in the eye in a case of the most common subtype of sCJD (MM1). Results: Low levels of PrPSc were detectable in the retina, localised to the plexiform layers of the central retina. PrPSc was not detectable in other ocular tissues. Conclusions: The abnormal form of the prion protein is present in the retina in the most common sCJD subtype (MM1), albeit at levels lower than those found previously in vCJD and in sCJD of the VV2 subtype.
Image processing strategies to accurately measure red blood cell motion in superficial capillaries

We report on the signal and image processing and initial results of an optical set-up designed to image, track and directly measure the velocity of red blood cells passing through small arterial and venous capillaries in the skin covering the proximal part of the fingernail. Due to the fact that refractive index matching oil is applied to the skin the measurement can be done transdermally. The aim of this research is in the medical field in particular in drug efficacy tests or determining the effectiveness of medical treatments of various kinds. The paper give details on the optical setup the image acquisition and the processing of the video data stream to obtain accurate velocity estimates of the blood flow in superficial capillaries.