Miracle-dz/UniFAR-FTUs huggingface dataset:
Valproic Acid for the Treatment of Myeloid Malignancies

W e read with interest Drs. Kuendgen and Gattermann’s recent review on valproic acid (VPA) for the treatment of myeloid malignancies. We suggest that response to VPA in myelodysplastic syndrome (MDS) patients may be underestimated in current literature because of relatively short durations of treatment in published studies. At our institution, we conducted a pilot study of VPA monotherapy in MDS. Patient response was assessed after 4–6 weeks of VPA at serum concentrations of 50–100 mg/mL. Of evaluable patients (n 1⁄4 15), 4 (27%) showed hematologic improvement (HI) per International Working Group criteria, with responses seen only in patients with low-risk disease, consistent with results of Kuendgen et al. One such subject, a 38-year-old female with no significant past medical history, presented with a 50-lb weight loss and symptomatic anemia. A diagnostic bone marrow revealed myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDSRCMD). Her International Prognostic Scoring System (IPSS) score was 0 (3% blasts on aspirate; normal female karyotype; Hg, 9.3). She required red cell (PRBC) transfusions every 3 weeks. During Months 1–7 of VPA therapy, her median Hg rose to 9.8; she received 1 PRBC transfusion. Between Months 7–12 of therapy, her hemoglobin improved by an additional 3.1 g/dL. She reported increased energy and appetite and demonstrated a 23-lb weight gain. Her response at 4–6 weeks was characterized as HI-erythroid. Her best response to VPA, a complete peripheral blood remission, occurred, however, after 7.5 months of continuous therapy and is sustained, now 32 months after initiation of therapy, with a median Hg of 13.2 during the last 2 years. Our experience with VPA suggests that sustained responses to VPA monotherapy are possible; furthermore, similar to other epigenetic agents used in MDS, responses to VPA may not be apparent for months. Patients with stable disease and minor responses may need treatment for longer durations before a final assessment is made. This observation may be important in designing future VPA and other HDAC-I studies for low-risk MDS patients.
O poder da reputação: evidências do efeito big four sobre a opinião do auditor

O presente trabalho analisou o efeito das Big Four sobre o tipo de opinião dos auditores. O estudo, descritivo, documental e quantitativo, analisou relatórios anuais de 504 empresas listadas na [B]³ no período de 2002-2012 através de estatística descritiva e regressão com dados em painel. Observou-se existir uma concentração do mercado de auditoria, pois as Big Four chegaram a auditar 75% das empresas, o que pode prejudicar a independência do auditor. Em média, a probabilidade de uma empresa listada receber um relatório modificado é 6,20%. Verificou-se ainda que ser auditado por uma Big Four e possuir Níveis Diferenciados de Governança reduzem a probabilidade de se receber uma opinião modificada. Por sua vez, empresas que apresentam prejuízos e a adoção do IFRS Parcial aumentaram a probabilidade de receberem uma opinião modificada. Estes resultados contribuem com os reguladores, investidores e auditores na sinalização dos fatores que afetam o tipo de opinião do auditor.
A new ALU architecture design using reversible logic

A new ALU design scheme using reversible logic has been reported in this paper. In digital calculators, mathematical computations like addition, subtraction, different logic operations are frequently used. Here our intention is to use reversible logic to produce outputs of different arithmetic and logic operations on the same line which is a new idea. In this paper the proposed ALU design is based on two different addition methodologies. At first the technique has been verified using FPGA and then implemented using reversible logic. In contrast with the recently reported architectures, our design offers better performance in respect of area, delay and power as well as line count and quantum cost also. The quantum cost optimization for the proposed structure has been performed using well known NCV and NCV-|v1 > libraries.
The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse.

After intravenous (i.v.) injection, acepromazine was distributed widely in the horse (Vd = 6.6 litres/kg) and bound extensively (greater than 99%) plasma proteins. Plasma levels of drug declined with an alpha half-life of 4.2 min, while the beta phase or elimination half-life was 184.8 min. At a dosage level of 0.3 mg/kg acepromazine was detectable in the plasma for 8 h post dosing. The whole blood partitioning of acepromazine was 46% in the plasma phase and 54% in the erythrocyte phase. Penile prolapse was clearly evident at doses from 0.01 mg/kg to 0.4 mg/kg i.v. , and the duration and extent of protrusion were dose related. Hematocrit levels were significantly lowered by administration of 0.002 mg/kg i.v. (about 1 mg to a 500 kg horse) and increasing dosages resulted in greater than 20% lowering of the hematocrit from control levels. Pretreatment of horses with acepromazine also reduced the variable interval (VI 60) responding rate in all horses tested. These data show that hematocrit changes are the most sensitive pharmacological responses to acepromazine, followed by changes in penile extension, respiratory rate, VI responding and locomotor responses. Acepromazine is difficult to detect in plasma at normal clinical doses. However, because of its large volume of distribution, its urinary elimination is likely prolonged, and further work on its elimination in equine urine is required.
Neurocognitive outcomes among children who experienced seizures during treatment for acute lymphoblastic leukemia

Limited information is available regarding neurocognitive outcomes of children who experience seizures during treatment for acute lymphoblastic leukemia (ALL). Accordingly, the main objectives of this study were to determine the incidence and risk factors for treatment‐related seizures among children with ALL, and the neurocognitive outcomes associated with treatment‐related seizures.
A new experimental in vitro culture medium for cultivation of Leishmania species

A new liquid culture medium prepared with chemicals that can be obtained economically and commercially was tested in in vitro cultivation of Leishmania promastigotes to obtain a large number of organisms to use in serological studies. The number of Leishmania infantum and Leishmania tropica promastigotes taken from Novy-MacNeal-Nicolle (NNN) medium reached 1 x 10(7)/ml at the end of the 8th day in our new medium, though in NNN medium the number of organisms reached only 5 x 10(6)/ml. After 10 subsequent passages, the culture medium prepared was evaluated as being quite inexpensive, simple, and successful compared with other commercially available liquid culture media.
Seed Transcriptomics Analysis in Camellia oleifera Uncovers Genes Associated with Oil Content and Fatty Acid Composition

Camellia oleifera is a major tree species for producing edible oil. Its seed oil is well known for the high level of oleic acids; however, little is known regarding the molecular mechanism of lipid biosynthesis in C. oleifera. Here, we measured the oil contents and fatty acid (FA) compositions at four developmental stages and investigated the global gene expression profiles through transcriptomics sequencing. We identified differentially-expressed genes (DEGs) among the developmental stages and found that the distribution of numbers of DEGs was associated with the accumulation pattern of seed oil. Gene Ontology (GO) enrichment analysis revealed some critical biological processes related to oil accumulation, including lipid metabolism and phosphatidylcholine metabolism. Furthermore, we investigated the expression patterns of lipid biosynthesis genes. We showed that most of the genes were identified with single or multiple copies, and some had correlated profiles along oil accumulation. We proposed that the higher levels of stearoyl-ACP desaturases (SADs) coupled with lower activities of fatty acid desaturase 2 (FAD2) might be responsive to the boost of oleic acid at the late stage of C. oleifera seeds’ development. This work presents a comprehensive transcriptomics study of C. oleifera seeds and uncovers valuable DEGs that are associated with the seed oil accumulation.
Current carrying ground state in a bilayer model of strongly correlated systems

Strongly interacting systems have been conjectured to spontaneously develop current carrying ground states under certain conditions. We demonstrate the existence of a commensurate staggered interlayer current phase in a bilayer model by using the recently discovered quantum Monte Carlo algorithm without the sign problem for fermionic systems. A pseudospin $\mathit{SU}(2)$ algebra and the corresponding anisotropic spin-1 Heisenberg model are constructed to show the competition among the staggered interlayer current, rung singlet, and charge density wave phases.
A fully human monoclonal antibody with novel binding epitope and excellent neutralizing activity to multiple human IFN-α subtypes: A candidate therapy for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease short of effective therapeutic agents. A multitude of studies of SLE in the last decade have accentuated a central role of the interferon alpha (IFN-α) pathway in SLE pathogenesis. We report here a candidate therapeutic neutralizing antibody, AIA22, with a different binding epitope and discrepant neutralizing profile from the anti-multiple IFN-α subtype antibodies currently in clinical trials. AIA22 specifically interacts with multiple IFN-α subtypes, binds to the type I IFN receptor 2 (IFNAR2) recognition region of IFN-α (considered a novel antigen epitope), and effectively neutralizes the activity of almost all of the IFN-α subtypes (with the exception of IFN-α7) both in vitro and in vivo. Concurrently, structural modeling and computational design yielded a mutational antibody of AIA22, AIAmut, which exhibited substantially improved neutralizing activity to multiple IFN-α subtypes.
Interleukin-10 gene rs1800896 polymorphism increases risk of acute pancreatitis

Background: The association between interleukin-10 (IL-10) gene rs1800896 polymorphism and susceptibility to acute pancreatitis (AP) has been investigated in several studies, but with contradictory findings. Therefore, a comprehensive meta-analysis is needed to assess the strength of such association. Methods: Literatures on PubMed, EMBASE, and CNKI were searched to identify relevant studies. The strength of association between IL-10 gene rs1800896 polymorphism and AP risk was assessed using pooled odds ratios and 95% confidence intervals. Results: Totally 7 case–control studies involving 1527 cases and 1511 controls were identified. Analyses proved that IL-10 gene rs1800896 polymorphism was significantly associated with an increased risk of AP. Stratification analysis of ethnicity found such significant association only among Asians, but not Caucasians. Conclusion: IL-10 gene rs1800896 polymorphism increases the risk of AP.
Dynamic admittance of mesoscopic conductors: Discrete-potential model.

We present a discussion of the low-frequency admittance of mesoscopic conductors in close analogy with the scattering approach to dc conductance. The mesoscopic conductor is coupled via contacts and gates to a macroscopic circuit which contains ac-current sources or ac-voltage sources. We find the admittance matrix which relates the currents at the contacts of the mesoscopic sample and of nearby gates to the voltages at these contacts. The problem is solved in two steps: we first evaluate the currents at the sample contacts in response to the oscillating voltages at the contacts, keeping the internal electrostatic potential fixed. In a second stage an internal response due to the potential induced by the injected charges is evaluated. The self-consistent calculation is carried out for the simple limit in which each conductor is characterized by a single induced potential. Our discussion treats the conductor and the gates on equal footing. Since our approach includes all conductors on which induced fields can change the charge distribution, the admittance of the total response is current conserving, and the current response depends only on ac-voltage differences. We apply our approach to a mesoscopic capacitor for which each capacitor plate is coupled via a lead to an electron reservoir. We find an electrochemical capacitance with density-of-state contributions in series with the geometrical capacitance. The dissipative part of the admittance is governed by a charge-relaxation resistance which is a consequence of the dynamics of the charge pileup on the capacitor plates. We specialize on a geometry displaying an Aharonov-Bohm effect only at nonzero frequencies. For a double barrier with a well coupled capacitively to a gate the low-frequency admittance terms may have either sign, reflecting either a capacitive or a kinetic-inductive behavior. The validity of a second-quantization-current-operator expression which neglects spatial information is examined for perfect leads in both the frequency and the magnetic-field domain. \textcopyright{} 1996 The American Physical Society.
What is the evidence to support acetabular dysplasia as a cause of osteoarthritis?

The term "acetabular dysplasia" suggests a smaller than normal acetabulum or one that is abnormally vertical. Acetabular dysplasia has been linked to the development of hip osteoarthritis over the last 90 years in 3 ways. First, it has been linked through the concept that biomechanical forces can cause osteoarthritis. A smaller than normal acetabulum will result in a smaller than normal contact surface between the femoral head and the acetabulum. This will generate increased pressure per unit of area, which will precipitate articular cartilage failure when the pressure reaches a critical point. Osteoarthritis will ensue in response to this cartilage failure. A more vertical than normal acetabulum will be associated with increased shear. When that shear reaches a critical level, articular cartilage will fail, leading that to osteoarthritis. This critical level, for a small or a steep acetabulum, may differ between individuals, based on their biology and their life styles. Second, it has been linked by multiple empirical studies. One of these is Wiberg's 1939 thesis entitled "Studies on Dysplastic Acetabula and Congenital Subluxation of the Hip Joint with Special reference to the Complication of Osteoarthritis. " It is among the most quoted and most powerful works in the Orthopaedic literature connecting a disease entity with an antecedent. Third, the linkage is reenforced by an absence of glaring exceptions to the hypothesis that acetabular dysplasia causes osteoarthritis. Orthopaedic surgeons just do not report on dysplastic hips in the arthritis-free elderly. The inability of the Orthopaedic community to identify even 1 elderly, arthritis-free individual with significant hip dysplasia should not carry weight in establishing the concept that acetabular dysplasia causes osteoarthritis. However, the longer this case report goes unpublished, the more certain orthopaedic surgeons will be that the 2 are linked.
Ghrelin concentrations in healthy children and adolescents

objective In addition to its regulation by GH releasing hormone (GHRH) and somatostatin, release of GH from the pituitary is modulated by a third factor, ghrelin, which is expressed in high concentration in the stomach and is present in the circulation. Ghrelin has also been shown to cause weight gain by increasing food intake and decreasing fat utilization. Ghrelin is a potential candidate hormone to influence nutrient intake and growth. Its role through normal childhood and adolescence has not been fully defined.
Identification and Quantification of Intrinsic Optical Contrast for Near‐infrared Mammography

Near‐infrared spectroscopy has been used to quantify the composition of healthy female breast tissue in vivo. By collecting transillumination spectra in the wavelength range 680–1100 nm at 7–9 positions on the breasts of five female volunteers, an attempt was made to quantify the intra‐ and intersubject variability of breast composition. The dominant absorbers are water, lipids and hemoglobin. Hemoglobin concentration in the breast is substantially lower than that in the brain or muscle (less than 10 μM). The measured deoxyhemoglobin concentration can vary by up to 100% between different positions on the same breast. Water and lipid concentrations can show similar variability. Phantom and simulation studies demonstrate that this variability is not due to the effects of tissue boundaries on the measurements. The low hemoglobin concentration implies that optical breast imaging should be performed at wavelengths below about 850 nm to ensure that the image contrast comes predominantly from hemoglobin. Intrasubject variability could have implications for the ability of optical imaging to discern tumors from background contrast variations.
Fat frogs, mobile genes: unexpected phylogeographic patterns for the ornate chorus frog (Pseudacris ornata)

The southeastern coastal plain of the United States is a region marked by extraordinary phylogeographic congruence that is frequently attributed to the changing sea levels that occurred during the glacial‐interglacial cycles of the Pleistocene epoch. A phylogeographic break corresponding to the Apalachicola River has been suggested for many species studied to date that are endemic to this region. Here, we used this pattern of phylogeographic congruence to develop and test explicit hypotheses about the genetic structure in the ornate chorus frog (Pseudacris ornata). Using 1299 bp of mtDNA sequence and seven nuclear microsatellite markers in 13 natural populations of P. ornata, we found three clades corresponding to geographically distinct regions; one spans the Apalachicola River (Southern Clade), one encompasses Georgia and South Carolina (Central Clade) and a third comprises more northerly individuals (Northern Clade). However, it does not appear that typical phylogeographic barriers demarcate these clades. Instead, isolation by distance across the range of the entire species explained the pattern of genetic variation that we observed. We propose that P. ornata was historically widespread in the southeastern United States, and that a balance between genetic drift and migration was the root of the genetic divergence among populations. Additionally, we investigated fine‐scale patterns of genetic structure and found the spatial scale at which there was significant genetic structure varied among the regions studied. Furthermore, we discuss our results in light of other phylogeographic studies of southeastern coastal plain organisms and in relation to amphibian conservation and management.
The peptide encoded by angiotensin II complementary RNA does not interfere with angiotensin II action.

on blood vessels (vasoconstriction) and adrenal cortex (steroidogenesis) are mediated by specific receptors at the surface of its target cells. Recently it was shown that the octapeptide (IIA) specified by the RNA sequence complementary to the mRNA sequence for All could inhibit the binding of 125I-AII to its receptor present on rat adrenal particles [1]. That report together with a few others [2-8] (using different hormones) suggested that peptides encoded by complementary strands of nucleic acid (designated 'complementary peptides') have the ability to bind one another. The proposed hypothesis was that ligands and receptor binding sites can be derived from complementary sequences of nucleic acid. Since it may have important applications in the study of the mechanism of hormonal action, we decided to verify this interesting hypothesis. The octapeptide IIA, Lys-Gly-Val-Asp-Val-Tyr-AlaVal (specified by the nucleotide sequence of the rat angiotensinogen cDNA; see [1]) was synthesized by a standard solid phase method [9] and purified by h.p.l.c. The identity of the peptide was verified by FAB mass spectrometry and had a (M+ 1) = 851 mass unit. The steroidogenic action of AII is well known. In our system (for methods, see [10]), All brought the level of aldosterone secretion by bovine adrenal glomerulosa cells (400000 cells incubated for 2 h) from a basal value around 40 ng/ml to a maximal value around 200 ng/ml [EC50 (concentration producing 50 % of the maximal effect) 1.2+1.1 nm, n = 5]. The complementary peptide IIA had no effect (at concentrations as high as 10 ,tM) on the basal secretion of aldosterone. In five different experiments, the steroidogenic effect of AII (1 nM) was not inhibited by increasing concentrations of IIA (up to 10,M). The ability of AII to contract rabbit aorta strips is well documented (for methods, see [11]). In our system, IIA (up to 10 uM) had no effect on the contraction of rabbit aorta strips. Most importantly, the responses to halfmaximal doses of All (2 ng/ml) were unchanged in the presence of increasing concentrations of IIA (up to 10 uM). In some experiments, in order to facilitate a putative interaction, All and IIA were preincubated together for 15 min before addition to the baths. Despite this precaution, IIA did not modify the response of the aortae to All. Finally, the binding of 125I-AII (120000 c.p.m., 1 nM) to bovine adrenal cortex membranes (for methods,
A Climate-Oriented Approach to Support Decision-Making for Seed Provenance in Ecological Restoration

There is increasing awareness that the long-term success of ecological restoration efforts can be compromised if projected climate change is not effectively incorporated in restoration planning. We propose an approach that aims to support the decision-making process for seed provenance selection in ecological restoration when clear genetic-based guidelines for seed transfer are not available. The approach takes advantage of the increasing availability and refinement of user-friendly web-based GIS interfaces that allow non-experts to directly access biodiversity and environmental data, and build species distribution models. It offers an easily accessible desktop method that land managers and practitioners can use to gain insight: 1) on the overall spatial implications of projected climate change to their restoration project; 2) whether assisted gene flow through climate-adjusted provenance may be appropriate for a given species at a given restoration site; and 3) how far away and in which direction from the restoration site seeds should be collected from. This approach should be used in the early stages of the restoration project to help frame the decision-making process in a climate change context, and can also be used as a platform where other lines of evidence are integrated. We advocate that, in the context of rapid climate change, the climate-adjusted provenance is a promising approach to seed sourcing in ecological restoration, and we suggest its refinement in a way that hedges against uncertainty in climatic projections.