cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia (TACL) consortium

Background Outcomes remain poor for children after relapse of acute lymphoblastic leukemia (ALL), especially after early marrow relapse. Bortezomib is a proteasome inhibitor with in vitro synergy with corticosteroids and clinical activity in human lymphoid malignancies. Procedure This is a Phase I study of escalating doses bortezomib administered days 1, 4, 8, and 11, added to 4-drug induction chemotherapy with vincristine, dexamethasone, pegylated L-asparaginase, and doxorubicin (VXLD) in children with relapsed ALL. Results Ten patients were enrolled, five in first marrow relapse, and five in second relapse. Four patients were enrolled at dose level 1 (bortezomib 1 mg/m2). One patient was not evaluable for toxicity because of omitted dexamethasone doses. No dose-limiting toxicity (DLT) was observed. Six patients were enrolled at dose level 2 (bortezomib 1.3 mg/m2). One patient had dose-limiting hypophosphatemia and rhabdomyolysis after 1 dose of bortezomib, and died from a diffuse zygomyces infection on day 17. Five additional patients were enrolled with no subsequent DLTs. As planned, no further dose escalation was pursued. The regimen had predictable toxicity related to the chemotherapy drugs. Two patients had mild peripheral neuropathy (grades 1 and 2). Six of nine evaluable patients (67%) achieved a complete response (CR), and one had a bone marrow CR with persistent central nervous system leukemia. Conclusions The combination of bortezomib (1.3 mg/m2) with VXLD is active with acceptable toxicity in pretreated pediatric patients with relapsed ALL. We are expanding the 1.3 mg/m2 cohort for a phase II estimate of response. Study registered at ClinicalTrials.gov (http://clinicaltrials.gov/ct2/show/NCT00440726). Pediatr Blood Cancer 2010;55:254–259. © 2010 Wiley-Liss, Inc.
Spin-lattice relaxation in HD-He gaseous mixtures

NMR spin-lattice relaxation times have been measured for HD gas, both pure and in mixtures with He, in the range 28–100 K. The results for HD/He mixtures, extrapolated to 0% HD, have been analysed to give the collisional rate for de-excitation of HD from the rotational state J = 1 to J = 0. These results are compared with a quantum-mechanical scattering calculation of the thermally averaged cross section <υθ(1 a 0; υ)#62, using a “loaded sphere” model for HD.
Revision of the Genus Hirschmanniella Luc & Goodey, 1963 (Nematoda: Tylenchoidea)

The genus Hirschmanniella is diagnosed. Six nominal species are redescribed from type material [H. spinicaudata (Sch. Stek., 1944), H. gracilis (de Man, 1880), H. oryzae (Soltwedel, 1889), H. behningi (Micoletzky, 1923), H. mexicana (Chitwood, 1951) n. comb. and H. mucronata (Das, 1960)]. H. zostericola (Allgen, 1934) is considered a valid species. Eight new species and two new synonyms (H. nana Siddiqi, 1966 and H. magna Siddiqi, 1966) are proposed. A key to the species and illustrations is presented.
Customization: optimizing compiler technology for SELF, a dynamically-typed object-oriented programming language

Dynamically-typed object-oriented languages please programmers, but their lack of static type information penalizes performance. Our new implementation techniques extract static type information from declaration-free programs. Our system compiles several copies of a given procedure, each customized for one receiver type, so that the type of the receiver is bound at compile time. The compiler predicts types that are statically unknown but likely, and inserts run-time type tests to verify its predictions. It splits calls, compiling a copy on each control path, optimized to the specific types on that path. Coupling these new techniques with compile-time message lookup, aggressive procedure inlining, and traditional optimizations has doubled the performance of dynamically-typed object-oriented languages.
Kappa opiate receptors inhibit release of oxytocin from the magnocellular system during dehydration.

Magnocellular neurons synthesize vasopressin (VP) or oxytocin (OT) and release these hormones preferentially from the neural lobe during physiological stimulation. In the rat, VP is secreted preferent
Characterization of thin film composite mixtures of Y/sub 1/Ba/sub 2/Cu/sub 3/O/sub 7-/spl delta// and Y/sub 2/O/sub 3/

In our studies of the behavior of materials forming thin film composites with Y/sub 1/Ba/sub 2/Cu/sub 3/O/sub 7-/spl delta// (YBCO), we have characterized thin film composite mixtures of YBCO and Y/sub 2/O/sub 3/ (yttria) grown onto (100) MgO and (100) SrTiO/sub 3/ substrates by off-axis sputtering. We have examined the transport properties of the films, in particular the critical current density, J/sub c/. The temperature dependence of J/sub c/ for composites on SrTiO/sub 3/ is identical to that of our pure YBCO films, while for composites on MgO the J/sub c/ is similar to measurements on our earlier composites of YBCO and Y/sub 2/Ba/sub 1/Cu/sub 1/O/sub 5/ ("211"). The field dependence of J/sub c/ for the YBCO/yttria composites is different from our pure YBCO films, and from our earlier composites, but the magnitude of the flux pinning is similar. >
Extracellular lactate cooperates with limited glucose and glutamine to sustain breast cancer cell survival by providing ATP, NADPH, amino acids, and glutathione

Background Cancer progression occurs upon mutations on regulatory genes that control biological functions including cellular bioenergetics. Such perturbations lead to a metabolic switch that favors aerobic glycolysis and lactate production over oxidative phosphorylation. This process is known as the Warburg effect and results in a lactate-rich tumor microenvironment. The apparently wasteful mechanism has raised the question of why cancer cells switch from the high ATP producing TCA cycle/OXPHOS to glycolysis; and whether lactate serves a biological function in energy metabolism since a high lactate environment correlates with worse patient prognosis in several malignancies including breast cancer. Our goals were to first, determine the fate of carbons from lactate in breast cancer cells; and second, determine the mechanism of lactate metabolism.
Preferential CO oxidation in a two-stage packed-bed reactor: Optimization of oxygen split ratio and evaluation of system robustness

Abstract This study investigates the performance of a preferential CO oxidation reactor operating in two modes – single and two-stage. Preferential CO oxidation in excess H 2 was carried out on a Pt/γ-Al 2 O 3 catalyst in a packed-bed microreactor system consisting of two cascaded stages. Oxygen split ratio between the two stages was optimized to obtain best performance. The optimal split ratio was observed to be around 60:40. System robustness was evaluated by analyzing the system’s response to step changes in inlet conditions. The two-stage mode operating with a 60:40 oxygen split ratio was more robust in handling step changes than the single-stage mode.
Disruption of Retinogeniculate Pattern Formation by Inhibition of Soluble Guanylyl Cyclase

During development of the visual system of the ferret, the terminals of retinal ganglion cell axons first segregate to form eye-specific layers and subsequently On-center and Off-center sublayers within the dorsal lateral geniculate nucleus (dLGN). Sublamination requires the activity of the afferent fibers, NMDA receptors, and nitric oxide synthase (NOS). We here report that soluble guanylyl cyclase (sGC), which in turn produces cGMP, is critically involved in the process of sublamination. cGMP expression is upregulated in both retinal terminals and postsynaptic dLGN cells during sublamination, and this expression is controlled by the activity of both NMDA receptors and NOS. Furthermore, the infusion of specific inhibitors of sGC or protein kinase G (PKG), a target of cGMP, prevents sublamination in vivo. We conclude that the sGC-cGMP-PKG pathway acts downstream of NMDA receptors and nitric oxide as an effector of the activity-dependent refinement of connections at this level of the mammalian visual system.
Controlled comparison of original vented aerobic fan medium with new nonvented BacT/ALERT FA medium for culturing blood.

To evaluate the performance of BacT/ALERT FA (FA) medium, a new aerobic BacT/ALERT FAN (FAN) medium (Organon Teknika Corporation, Durham, N.C.) that does not require the added cost and inconvenience of a venting unit, we inoculated blood specimens from adult patients with suspected sepsis into an original FAN aerobic culture bottle and an FA bottle. Of 7,745 blood culture sets containing both bottles, 5,256 (68%) met the criteria for adequacy of filling. A total of 466 isolates judged to represent the causes of true infections were recovered from 276 patients; 271 isolates were recovered from both bottles, 82 were recovered from the FAN bottle only, and 113 were recovered from the FA bottle only (P < 0.05). More Burkholderia cepacia isolates (P < 0.01), Candida albicans isolates (P < 0.001), Cryptococcus neoformans isolates (P < 0.01), yeasts overall (P < 0.001), and total microorganisms (P < 0.05) were recovered from FA bottles. Of cultures found to be positive within the first 72 h of incubation, the mean times to detection were almost identical for FAN (20.4 h) and FA (20.7 h) bottles. Of 263 isolates that caused monomicrobic episodes of bloodstream infections, 180 were detected in both bottles, 32 were detected in FAN bottles only, and 51 were detected in FA bottles only (P < 0.05). Of 186 isolates considered to be contaminants, 63 were detected in both media, 64 were detected in FAN bottles only, and 59 were detected in FA bottles only (P was not significant). The number of false-positive results were comparable: 69 (1.3%) in FAN bottles and 56 (1.1%) in FA bottles. However, there were 14 isolates with false-negative results (6 yeasts, 6 nonfermenters, and 1 isolate each of Propionibacterium acnes and coagulase-negative staphylococci) in FAN bottles, whereas there were none in FA bottles. On the basis of these results, we conclude that the new nonvented FA bottle is superior to the original vented FAN medium for the recovery of B. cepacia and yeasts, especially C. albicans and C. neoformans, and is comparable to FAN medium for other microorganisms.
Recurrent Pulmonary Embolus after Insertion of Intracaval Prosthesis

A patient is described with recurrent pulmonary embolus following combined therapy of placement of a caval umbrella device for caval interruption and anticoagulation. The source of this embolus was felt to be from a thrombus located on the proximal portion of the umbrella. This is the first reported instance of this complication.
The Relationship Between Varicoceles and Obesity

Purpose: To determine if a relationship between weight and varicocele occurrence exists, the prevalence of varicoceles was determined in a population of patients presenting with infertility.Materials and Methods: Records of 3,213 males presenting with infertility were examined. Patients underwent physical examinations for varicocele presence and grade. Body mass index was calculated. Patients were categorized as normal weight, overweight and obese using National Institutes of Health criteria. Means were compared with Student’s t test. Frequencies were compared by chi-square analysis and statistical significance was considered at p <0.05.Results: A total of 1,093 (34%) patients had varicoceles. The mean body mass index of those without varicoceles was 28.5 (±5.6) kg/cm2, which was greater than the body mass index of those with varicoceles (26.7 [±4.0] kg/cm2) (p <0.001). Varicocele frequency was calculated for each body mass index group. In the normal weight group (body mass index less than 25) 378 of 884 ...
A New Scheie for Subsynchronous Resonance Damping of Torsional Oscillations and Transient Torque - Part I

Series capacitor compensation of long and medium lines offers convincing advantages of optimum use of transmission lines. Technical problems with series capacitor protection and, more recently, the problems of subsynchronous resonance, resulting in high stresses on the turbogenerator shafts, have been a deterrent to widespread use of series compensation. Some generally complementary solutions to these problems have emerged, but further advances are needed.
Feedback regulation of the Bradyrhizobium japonicum nodulation genes.

Lipochitin Nod signals are produced by rhizobia and are required for the establishment of a nitrogen-fixing symbiosis with a legume host. The nodulation genes encode products required for the synthesis of this signal and are induced in response to plant-produced flavonoid compounds. The addition of chitin and lipo-chitin oligomers to Bradyrhizobium japonicum cultures resulted in a significant reduction in the expression of a nod–lacZ fusion. Intracellular expression of NodC, encoding a chitin synthase, also reduced nod gene expression. In contrast, expression of the ChiB chitinase increased nod gene expression. The chain length of the oligosaccharide was important in feedback regulation, with chitotetraose molecules the best modulators of nod gene expression. Feedback regulation is mediated by the induction of nolA by chitin, resulting in elevated levels of the repressor protein, NodD2.
Arginine Methylation of the ICP27 RGG Box Regulates ICP27 Export and Is Required for Efficient Herpes Simplex Virus 1 Replication

The herpes simplex virus 1 (HSV-1) multifunctional regulatory protein ICP27 shuttles between the nucleus and cytoplasm in its role as a viral mRNA export factor. Arginine methylation on glycine- and arginine-rich motifs has been shown to regulate protein export. ICP27 contains an RGG box and has been shown to be methylated during viral infection. We found by mass spectrometric analysis that three arginine residues within the RGG box were methylated. Viral mutants with substitutions of lysine for arginine residues were created as single, double, and triple mutants. Growth of these mutants was impaired and the viral replication cycle was delayed compared to wild-type HSV-1. Most striking was the finding that under conditions of hypomethylation resulting from infection with arginine substitution mutants or treatment of wild-type HSV-1-infected cells with the methylation inhibitor adenosine dialdehyde, ICP27 export to the cytoplasm occurred earlier and was more rapid than wild-type ICP27 export. We conclude that arginine methylation of the ICP27 RGG box regulates its export activity and that early export of ICP27 interferes with the performance of its nuclear functions.
TURBULENT HEAT TRANSFER AND TEMPERATURE FLUCTUATIONS IN A FIELD WITH UNIFORM VELOCITY AND TEMPERATURE GRADIENTS

Turbulent heat and momentum transfer for uniform velocity and temperature gradients in a flow field
Polarimetric Detection of Enantioselective Adsorption by Chiral Au Nanoparticles – Effects of Temperature, Wavelength and Size

R- and S-propylene oxide (PO) have been shown to interact enantiospecifically with the chiral surfaces of Au nanoparticles (NPs) modified with D- or L-cysteine (cys). This enantiospecific interaction has been detected using optical polarimetry measurements made on solutions of the D- or L-cys modified Au (cys/Au) NPs during addition of racemic PO. The selective adsorption of one enantiomer of the PO onto the cys/Au NP surfaces results in a net rotation of light during addition of the racemic PO to the solution. In order to optimize the conditions used for making these measurements and to quantify enantiospecific adsorption onto chiral NPs, this work has measured the effect of temperature, wavelength and Au NP size on optical rotation by solutions containing D- or L-cys/Au NPs and racemic PO. Increasing temperature, decreasing wavelength and decreasing NP size result in larger optical rotations.
Desferrioxamine-induced alterations in hepatic iron distribution, DNA damage and lipid peroxidation in control and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.

Desferrioxamine (DFX), an iron chelator, has been used to inhibit in vitro redox cycling of the transition iron ions that may interfere with free-radical formation, and is used clinically to treat conditions associated with iron overload. The effect of DFX on hepatic iron distribution has not been examined. Therefore, we have examined the effect of DFX on iron content and distribution, lipid peroxidation and DNA single-strand breaks in liver. Since 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances hepatic lipid peroxidation and induces DNA damage, the ability of DFX to modulate these effects was also examined. Female Sprague-Dawley rats received 200 mg DFX kg−1 i.p. every 12 h for 10 days and 50 μg TCDD kg−1 p.o. on Day 4 as a single dose. All animals were killed 7 days after TCDD administration. The results demonstrate that DFX alone did not decrease hepatic iron content, but enhanced the iron distribution in mitochondria, microsomes and nuclei. A 10-day administration of DFX resulted in enhanced hepatic lipid peroxidation and DNA single-strand breaks, consistent with the alterations in iron distribution. TCDD administration produced large increases in lipid peroxidation in microsomes, nuclei and whole-liver homogenates, as well as enhanced DNA damage. However, the marked increases in lipid peroxidation produced by TCDD were attenuated by DFX, while the DNA damaging effects of TCDD and DFX were additive. The results clearly demonstrate that a 10-day administration of DFX does not result in hepatic iron depletion and the DFX-associated increases in hepatic lipid peroxidation and DNA single-strand breaks may reflect altered iron distribution or the formation of an iron-catalysed nitroxide free-radical of DFX.
Semi-implicit surface tension formulation with a Lagrangian surface mesh on an Eulerian simulation grid

We present a method for applying semi-implicit forces on a Lagrangian mesh to an Eulerian discretization of the Navier Stokes equations in a way that produces a sparse symmetric positive definite system. The resulting method has semi-implicit and fully-coupled viscosity, pressure, and Lagrangian forces. We apply our new framework for forces on a Lagrangian mesh to the case of a surface tension force, which when treated explicitly leads to a tight time step restriction. By applying surface tension as a semi-implicit Lagrangian force, the resulting method benefits from improved stability and the ability to take larger time steps. The resulting discretization is also able to maintain parasitic currents at low levels.
BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak

The BH3-only proteins Bim and Bad bind to the antiapoptotic Bcl-2 proteins and induce apoptosis in wild-type cells and cells from either bax−/− or bak−/− animals. In contrast, constitutively active forms of Bim and Bad failed to induce apoptosis in bax−/−bak−/− cells. Expression of Bax restored susceptibility of the cells to Bim and Bad. In addition, Bax but not Bim or Bad sensitized the bax−/−bak−/− cells to a wide variety of cell death stimuli including UV irradiation, chemotherapeutic agents, and ER stress. These results suggest that neither activation of BH3-only proteins nor suppression of pro-survival Bcl-2 proteins is sufficient to kill cells in the absence of both Bax and Bak. Furthermore, whereas mouse embryo fibroblasts (MEF) expressing only Bax or Bak displayed resistance to transformation, bax−/−bak−/− MEF were nearly as prone to oncogenic transformation as p53−/− MEF. Thus, the function of either Bax or Bak appears required to initiate most forms of apoptosis and to suppress oncogenic transformation.
Progression of Aflatoxicosis in Broiler Chickens

The progression of aflatoxicosis was evaluated in young broiler chickens (Hubbard X Hubbard). The experimental design consisted of four dietary treatments of aflatoxin (0, 1.25, 2.5, and 5.0 micrograms of aflatoxin/g of feed, ppm) and 11 replicates of 10 broilers/replicate. The broilers were maintained in electrically heated batteries with feed and water available ad libitum from hatching to 3 weeks of age. The broilers were weighed, bled, killed by cervical dislocation, and necropzied at 3, 6, 9, 12, 15, 17, and 21 days of age. Body weights were significantly decreased by 5.0 ppm aflatoxin at 6 days of age and by 2.5 ppm at 17 days of age. Aflatoxin induced a significant increase in the relative weight of the proventriculus, gizzard, spleen, and kidney. Liver atrophy was indicated in the early stages of aflatoxicosis by a decrease in the relative weight of this organ. As aflatoxicosis progressed, hepatomegaly became apparent due to lipid accumulation in the liver. Packed-cell volume and hemoglobin levels were significantly decreased by 5.0 ppm aflatoxin at 12 days and by 2.5 ppm aflatoxin at 21 days of age. Serum levels of albumin and total protein were significantly reduced at 5.0 and 2.5 ppm aflatoxin by 3 and 6 days of age, respectively. Serum levels of uric acid, triglycerides, and cholesterol were significantly decreased from control values from 12 through 21 days of age by 5.0 ppm aflatoxin and, to a lesser extent, by 2.5 ppm aflatoxin. The activity of serum lactic dehydrogenase was significantly decreased at all aflatoxin treatment levels from 12 through 21 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Chromosomal instability in mammalian pre-implantation embryos: potential causes, detection methods, and clinical consequences

Formation of a totipotent blastocyst capable of implantation is one of the first major milestones in early mammalian embryogenesis, but less than half of in vitro fertilized embryos from most mammals will progress to this stage of development. Whole chromosomal abnormalities, or aneuploidy, are key determinants of whether human embryos will arrest or reach the blastocyst stage. Depending on the type of chromosomal abnormality, however, certain embryos still form blastocysts and may be morphologically indistinguishable from chromosomally normal embryos. Despite the implementation of pre-implantation genetic screening and other advanced in vitro fertilization (IVF) techniques, the identification of aneuploid embryos remains complicated by high rates of mosaicism, atypical cell division, cellular fragmentation, sub-chromosomal instability, and micro-/multi-nucleation. Moreover, several of these processes occur in vivo following natural human conception, suggesting that they are not simply a consequence of culture conditions. Recent technological achievements in genetic, epigenetic, chromosomal, and non-invasive imaging have provided additional embryo assessment approaches, particularly at the single-cell level, and clinical trials investigating their efficacy are continuing to emerge. In this review, we summarize the potential mechanisms by which aneuploidy may arise, the various detection methods, and the technical advances (such as time-lapse imaging, “-omic” profiling, and next-generation sequencing) that have assisted in obtaining this data. We also discuss the possibility of aneuploidy resolution in embryos via various corrective mechanisms, including multi-polar divisions, fragment resorption, endoreduplication, and blastomere exclusion, and conclude by examining the potential implications of these findings for IVF success and human fecundity.
The role of diuretics and inotropic therapy in failure associated with myocardial infarction.

AbstractThe stimulus for the studies I shall describe came from the realization that conventional therapy for the treatment of cardiac failure, namely, digitalis and diuretics, may not be appropriate for failure occurring with acute infarction. This combination of therapy was developed for patients who had chronic cardiac failure primarily from rheumatic valvular disease and cardiac myopathies. These patients had low cardiac output and hypervolemia; thus, diuretics and digitalis were appropriate therapy. In the 1960s, with the introduction of the coronary care unit, failure occurring during the acute phase of myocardial infarction was recognized to be quite frequent, and therapy was instituted similar to that for chronic failure. Yet, it is somewhat obvious that a person with a normal blood volume who has a myocardial infarction and within a few hours develops pulmonary oedema does not necessarily need a diuretic. A patient with clinically recognizable acute pulmonary oedema has lost between 500 and 700 c...
The Puzzling Case of the FCC’S Broadband Plan

As part of its effort to save an ailing economy from a deeper recession, Congress, in the American Recovery and Reinvestment Act of 2009 (the “Recovery Act”), charged the Federal Communications Commission (FCC) with preparing a national broadband plan to ensure that “all the people of the United States have access to broadband capability.” A bit over a year later, “Connecting America: The National Broadband Plan” has been submitted to Congress as the FCC’s plan for ensuring broadband availability across the land. The National Broadband Plan takes a holistic look at the role of broadband Internet investment, deployment, competition and adoption in our society and economy. The Plan looks at policies and actions in three categories: fostering innovation and competition in networks, devices and applications; redirecting assets that government controls or influences in order to spur investment and inclusion; and optimizing the use of broadband to help achieve national priorities. It was a monumental undertaking for the FCC, the process used to generate its data and recommendations was open and participatory, and the Plan is impressive in the depth and breadth. A comprehensive assessment of the Plan is well beyond the scope of this piece, which focuses primarily on those pieces of the Plan in Part I, addressing broadband competition and innovation policy.
Probabilities of conditionals in context

Khoos argument in favor of his theory (hereafter, simply the theory) starts by accepting the judgments in the two cases outlined above, and offers the theory as the best explanation of the data. I will have nothing to say about this argument. I think the argument is convincing but of limited value: rst, because the number of competing explanations is small Kaufmanns (2004) theory, and the possible range of explanations not fully explored; second, because there will certainly be many readers who do not accept the data, or in any case many who will not feel sufciently strongly about their judgments in the Hospital and Oracle to run an inference to the best explanation argument on them. For this group of readers, it is of interest, rst, to ask what motivation independent of our judgments in the Hospital and Oracle cases could be given for the theory. Second, it is of interest to ask whether the plausibility of the theory can be gauged by applying the theory to other, less puzzling cases. On the rst question, I think we are not given anything in the article, and perhaps it will be said that it is not a fair question to ask to begin with. So let me focus on the second question.
Spectroscopic studies of potential energy constants, root-mean-square amplitudes, coriolis coupling coefficients and shrinkages of chemical bonds in mercurous halides

A brief vibrational and structural analysis of mercurous halides possessing a linear symmetrical configuration with the symmetry point groupD∞h has been made. On the basis of group theoretical considerations, potential energy constants have been evaluated by employing a five-constant valence force field. Mean-square amplitudes and root-mean-square amplitudes for both bonded and nonbonded atom pairs have been computed at the temperatures 298 °K and 500 °K. The Coriolis coupling coefficients have been, in terms of the symmetrized force constants, computed. The generalized mean-square amplitudes (mean-square parallel amplitudes, mean-square perpendicular amplitudes, and mean cross products) have been evaluated from the symmetrized mean-square amplitudes, and used to calculate the shrinkages of chemical bonds. The results have been discussed in relation to the nature of the two characteristic bonds of these three molecular systems.
Charge origin and localization at the n -type SrTiO 3 / LaAlO 3 interface

We report a first-principles study of ${({\text{LaAlO}}_{3})}_{m}/{({\text{SrTiO}}_{3})}_{n}$ heterostructures using density-functional theory at the $\text{LDA}+U$ level. Our results support the original explanation of Ohtomo and Hwang [Nature (London) 427, 423 (2004)] that the charge at the $n$-type interface may be due to electrostatic doping. The internal electric field in the ${\text{LaAlO}}_{3}$ layer is calculated to be $0.24\text{ }\text{V}/\text{\AA{}}$. Though it is not sufficient to cause the dielectric breakdown in a wide band-gap La aluminate, it causes charge transfer into the adjacent narrower gap ${\text{SrTiO}}_{3}$ layer. The quasi-two-dimensional nature of the charge distribution is caused by a combination of the crystal-field effect, pseudo-Jahn-Teller distortion, and interface chemistry. Our theoretical estimate suggests that the interfacial carrier density of about $2\ifmmode\times\else\texttimes\fi{}{10}^{13}\text{ }{\text{cm}}^{\ensuremath{-}2}$ can be easily achieved.
Sex Hormones and Prognosis of Neonatal Seizures

The influence of testosterone on the development of the substantia nigra pars reticulata (SNR), a brain region involved in the control of seizures, was investigated in male rats castrated at birth, in experiments at Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY.
Influence of short-term maternal zinc deficiency on the in vitro development of preimplantation mouse embryos.

AbstractIn this study, we evaluated the use of mouse preimplantation embryos as a model to study zinc deficiency-induced abnormal development. In Experiment 1, the effect of culture medium Zn concentrations on blastocyst development was studied. Preimplantation embryos (2 and 4 cells) obtained from superovulated females developed normally in media containing 0.7–30 μM Zn for up to 72 hr; higher levels of medium Zn resulted in abnormal development. In Experiment 2A, females were fed diets containing 50 (+Zn) or 0.4 (-Zn) μg Zn/g (760 vs 6 nmol/g, respectively) from 1 day before to 1 day after mating (3 days total). Preimplantation embryos were removed from the dams and cultured for 72 hr in 0.7 μM Zn medium. Embryos from the –Zn dams were morphologically normal at time zero; however, over the 72-hr period, these embryos tended to develop at a slower rate than controls, although compaction and cavitation frequency were similar. By the end of the 72-hr culture period, embryos from –Zn dams had significantly ...
Social mobility in contemporary Japan

One of the important questions in industrial societies is how people attain their socioeconomic position. It is a question of who gets ahead, and what determines individual success in industrial societies. It is also a question of social mobility. If fathers simply hand over their position to their sons and the allocation of social position is determined by social origin, there will be no mobility between generations. In contrast, a society is relatively ‘open’ and ‘mobile’ when social position is allocated independent of social origin, and people can attain positions regardless of their background characteristics. This study attempts to understand the process through which individuals attain socioeconomic status and to examine the pattern of change in class position between generations in Japan through a cross-national comparison with the United States and Britain.
Planning for Density in a Driverless World

Automobile-centered, low-density development was the defining feature of population growth in the United States for decades. This development pattern displaced wildlife, destroyed habitat, and contributed to a national loss of biodiversity. It also meant, eventually, that commutes and air quality worsened, a sense of local character was lost in many places, and the negative consequences of sprawl impacted an increasing percentage of the population. Those impacts led to something of a shift in the national attitude toward sprawl. More people than ever are fluent in concepts of “smart growth,” “new urbanism,” and “green building,” and with these tools and others, municipalities across the country are working to redevelop a central core, rethink failing transit systems, and promote pockets of density. Changing technology may disrupt this trend. Self-driving vehicles are expected to be widespread within the next several decades. Those vehicles will likely reduce congestion, air pollution, and deaths, and free up huge amounts of productive time in the car. These benefits may also eliminate much of the conventional motivation and rationale behind sprawl reduction. As the time-cost of driving falls, driverless cars have the potential to incentivize human development of land that, by virtue of its distance from settled metropolitan areas, had been previously untouched. From the broader ecological perspective, each human surge into undeveloped land results in habitat destruction and fragmentation, and additional loss of biological diversity. New automobile technology may therefore usher in better air quality, increased safety, and a significant threat to ecosystem health. Our urban and suburban environments have been molded for centuries to the needs of various forms of transportation. The same result appears likely to occur in response to autonomous vehicles, if proactive steps are not taken to address their likely impacts. Currently, little planning is being done to prepare for driverless technology. Actors at multiple levels, however, have tools at their disposal to help ensure that new technology does not come at the expense of the nation’s remaining natural habitats. This Article advocates for a shift in paradigm from policies that are merely anti-car to those that are pro-density, and provides suggestions for both cities and suburban areas for how harness the positive aspects of driverless cars while trying to stem the negative. Planning for density regardless of technology will help to ensure that, for the world of the future, there is actually a world.
Subtherapeutic voriconazole concentrations associated with concomitant dexamethasone: case report and review of the literature.

Summary What is known and objective Voriconazole has significant drug interactions due to metabolism by CYP enzymes. Subtherapeutic voriconazole concentrations associated with concomitant dexamethasone are not well described. Case description An 84-year-old male was started on voriconazole for a fungal brain abscess. He was readmitted due to clinical failure thought to be the result of subtherapeutic voriconazole concentrations. Dexamethasone was identified as a potential cause due to its induction of CYP enzymes. This interaction was substantiated by sequential troughs that demonstrated a rise in voriconazole concentrations as dexamethasone was tapered off. What is new and conclusion Therapeutic drug monitoring for patients on voriconazole and dexamethasone is essential to prevent suboptimal clinical outcomes.
Total en bloc spondylectomy for locally aggressive and primary malignant tumors of the lumbar spine

To report outcomes after total en bloc spondylectomy (TES) for primary aggressive/malignant tumors of the lumbar spine. We performed a retrospective review of 23 neurosurgical patients operated between 2004 and 2014. Outcomes included perioperative complication rates and reoperation rates for instrumentation failure. The relationship between patient/operative parameters and complication development/instrumentation failure was investigated. There were 15 men (65.2 %) and eight women (24.8 %), with a median of 47 years. The most common tumor was chordoma in 11 patients (47.8 %), followed by sarcoma in four (17.4 %), and giant cell tumor in three (13.0 %). All patients but one underwent a two-staged operation; median total estimated blood loss was 3200 mL and median total operative time was 18.5 h. Fifteen patients developed at least one perioperative complication (65.2 %), with the most common being wound infection and ileus (26.1 % each). There was one case of intraoperative iliac vein injury (4.4 %). Instrumentation failure occurred in 9 patients (39.1 %) at a median time of 23 months after index spondylectomy. Following logistic regression, there were no factors associated with complication development. On the other hand, postoperative radiation was significantly associated with instrumentation failure (OR 7.49; 95 % CI, 1.02–54.9). Local recurrence and 5-year survival was 8.7 and 84.4 %, respectively. Median follow-up time was 50 months. Although favorable oncological outcomes after en bloc resection of spinal tumors may be achieved in terms of recurrence and survival, TES in the lumbar spine remains a challenging procedure. Future investigation into complication avoidance and reconstruction techniques is encouraged.
3D path planning for small UAS operating in low-altitude airspace

A two step path planning algorithm with collision detection logic for small UAS is proposed. The path planning approach taken in this work is carried out in two steps. In the first step, an initial suboptimal path is generated using A∗ search. In the second step, a chain of unit masses connected by springs and dampers evolves in a simulated force field, using the A∗ solution as an initial condition. The chain is described by a set of ordinary differential equations that is driven by virtual forces to find the steady-state equilibrium. A unique strength of this approach is the ability to use dynamic chain analogy to smooth path into a flyable shape while mainlining a safe distance from intruders. The simulation results show that the proposed approach produces collision-free plans while minimizing the path length.
Report of New Haplotype for ABCC2 Gene: rs17222723 and rs8187718 in cis

The ATP-binding cassette, subfamily C [CFTR/MRP], member 2 (ABCC2) gene is a member of the ATP-binding cassette transporters and is involved in the transport of molecules across cellular membranes. Substrates transported by ABCC2 include antiepileptics, statins, tenofovir, cisplatin, irinotecan, and carbamazepine. Because of the pharmacogenomics implications, we developed a clinical laboratory–developed assay to test for seven variants in the ABCC2 gene: c.3563T>A (p.V1188E, rs17222723), c.1249G>A (p.V417I, rs2273697), c.3972C>T (p.I1324I, rs3740066), c.2302C>T (p.R768W, rs56199535), c.2366C>T (p.S789F, rs56220353), c.-24C>T (5′UTR, rs717620), and c.4544G>A (p.C1515Y, rs8187710). During the validation process, we noted several DNA samples, obtained from the Coriell Cell Repository, that contained both c.3563T>A, c.4544G>A, and a third variant, suggesting that c.3563T>A and c.4544G>A are in cis on the chromosome in some individuals. We obtained DNA samples from a trio (father, mother, and child), tested their ABCC2 variants, and confirmed that c.3563T>A and c.4544G>A were in cis on the same chromosome. Here, we report a new haplotype in ABCC2.
RNA Sequencing Reveals a Role of TonEBP Transcription Factor in Regulation of Pro-inflammatory Genes in Response to Hyperosmolarity in Healthy Nucleus Pulposus Cells: A HOMEOSTATIC RESPONSE?

Transcription factor tonicity-responsive enhancer-binding protein (TonEBP/NFAT5) is critical for osmo-adaptation and extracellular matrix homeostasis of nucleus pulposus (NP) cells in their hypertonic tissue niche. Recent studies implicate TonEBP signaling in inflammatory disease and rheumatoid arthritis pathogenesis. However, broader functions of TonEBP in the disc remain unknown. RNA sequencing was performed on NP cells with TonEBP knockdown under hypertonic conditions. 1140 TonEBP-dependent genes were identified and categorized using Ingenuity Pathway Analysis. Bioinformatic analysis showed enrichment of matrix homeostasis and cytokine/chemokine signaling pathways. C-C motif chemokine ligand 2 (CCL2), interleukin 6 (IL6), tumor necrosis factor (TNF), and nitric oxide synthase 2 (NOS2) were studied further. Knockdown experiments showed that TonEBP was necessary to maintain expression levels of these genes. Gain- and loss-of-function experiments and site-directed mutagenesis demonstrated that TonEBP binding to a specific site in the CCL2 promoter is required for hypertonic inducibility. Despite inhibition by dominant-negative TonEBP, IL6 and NOS2 promoters were not hypertonicity-inducible. Whole-disc response to hypertonicity was studied in an ex vivo organ culture model, using wild-type and haploinsufficient TonEBP mice. Pro-inflammatory targets were induced by hypertonicity in discs from wild-type but not TonEBP-haploinsufficient mice. Mechanistically, NF-κB activity increased with hypertonicity and was necessary for hypertonic induction of target genes IL6, TNF, and NOS2 but not CCL2. Although TonEBP maintains transcription of genes traditionally considered pro-inflammatory, it is important to note that some of these genes also serve anabolic and pro-survival roles. Therefore, in NP cells, this phenomenon may reflect a physiological adaptation to diurnal osmotic loading of the intervertebral disc.
A phase II study of cabozantinib in metastatic castration-resistant prostate cancer (mCRPC) with visceral metastases (VM) with very small nuclear circulating tumor cell (vsnCTC) association studies.

208 Background: Cabozantinib is a multi-targeted tyrosine kinase inhibitor (TKI) that has recognized clinical activity in mCRPC. While phase 3 studies did not show a significant improvement in overall survival (OS), patients with VM had improved OS compared to those with only osseous metastases in subgroup analysis. Our group has also identified a subgroup of CTCs strongly associated with the presence of VM (Chen, Cancer 2015). We hypothesized that cabozantinib would yield clinical benefit and changes in vsnCTC counts would reflect disease behavior. Methods: This study was designed as an open label study of cabozantinib 60 mg daily, for mCRPC patients with visceral disease. The primary endpoint is clinical benefit rate (radiographic stable disease + partial response (PR) by RECIST 1.1) at 12 weeks (CBR12). Serum PSA concentrations were not used as a primary endpoint. CTCs were enumerated by NanoVelcro CTC Assay and characterized using published methods. Results: Thirteen patients have completed at least 8...
Increasing plasma parameters using sheared flow stabilization of a Z-pinch

The ZaP and ZaP-HD Flow Z-pinch experiments at the University of Washington have successfully demonstrated that sheared plasma flows can be used as a stabilization mechanism over a range of parameters that has not previously been accessible to long-lived Z-pinch configurations. The stabilization is effective even when the plasma column is compressed to small radii, producing predicted increases in magnetic field and electron temperature. The flow shear value, extent, and duration are shown to be consistent with theoretical models of the plasma viscosity, which places a design constraint on the maximum axial length of a sheared flow stabilized Z-pinch. Measurements of the magnetic field topology indicate simultaneous azimuthal symmetry and axial uniformity along the entire 100 cm length of the Z-pinch plasma. Separate control of plasma acceleration and compression has increased the accessible plasma parameters and has generated stable plasmas with radii of 0.3 cm, as measured with a high resolution digital...
Palliative Care Interventions before Left Ventricular Assist Device Implantation in Both Bridge to Transplant and Destination Therapy

Abstract Background: The optimal level of palliative care (PC) involvement in left ventricular assist device (LVAD) therapy has yet to be determined. Objective: Describe the feasibility of PC intervention to elucidate patients' goals and values in LVAD therapy in both destination therapy (DT) and bridge to transplant (BTT). Design: Single center, prospective, single-arm study. Setting/Subjects: All patients who received mandatory PC consultation, using a semistructured script, before LVAD implantation (PreVAD evaluation). Measurements: We evaluated the feasibility of PreVAD evaluation and family awareness by analyzing responses and compared it between DT and BTT. We examined the association between withdrawal of LVAD therapy and family awareness in death cases. Results: Between January 2014 and September 2016, 112 patients (DT, 75; BTT, 37) underwent PreVAD evaluation. All patients could express what makes their life meaningful, and 101 (92.0%) could discuss possible complications. Seventy-nine patients (...
Enterotomy During Hernia Repair

There is no standard approach to enterotomy management in the setting of a hernia repair. The factors affecting the treatment path include the severity and nature of the injured bowel, presence of gross spillage, and surgeon’s expertise and comfort level, which results in options for both laparoscopic and open repairs. As demonstrated in the literature, multiple options exist, and all are reasonable choices, as long as they are done safely, minimizing the risk to the patient.
Scalable Synthesis of Hydrido-Disiloxanes from Silanes: A One-Pot Preparation of 1,3-Diphenyldisiloxane from Phenylsilane

A simple, one-pot, and high-yielding synthesis of 1,3-diphenyldisiloxane is presented. The preparation of similar symmetrical disiloxane materials is also accomplished with this same protocol. This mechano-chemical procedure is efficient and highly scalable, furnishing a convenient route to hydrido-disiloxanes from widely accessible commercially available silanes.
Human Rights, Solitary Confinement, and Youth Justice in the United States

Over the last 15 years, US activists working on a range of domestic issues – from police violence and mass criminalization to reproductive rights to access to water – have incorporated human rights claims into their work. But even as it becomes more commonplace to hear activists make human rights claims, the question remains, what impact do the claims have? When are they successful in contributing to changes in attitudes, laws, and policies? For the most part, the United States’ human rights obligations cannot be directly enforced in US courts. The lack of a legally enforceable human rights charter or text leaves both the substantive rights and the forums and spaces to implement them up for grabs. Indeed, while Americans have a commitment to human rights, we often lack a common understanding of what is encompassed by the term. But the fluidity of the term also creates opportunities for social justice activists. US activists often seek to expand the public’s understanding of what can be claimed as a right beyond the confines of rights formally recognized under US law. In the United States (as in other countries), successful human rights claims can be leveraged in debates to change public attitudes on issues as long as they are accepted by American audiences as human rights. These claims may ultimately result in changes in laws, standards, and policies irrespective of whether they create legally binding obligations under international or domestic law. These claims are strengthened and legitimized when the international human rights community recognizes and prioritizes the claims as important human rights issues, but ultimately their success relies upon whether they resonate with Americans as human rights issues and inspire activism for change. Two areas where there has been increased human rights advocacy in the United States are in challenges to the use of solitary confinement and to the practice of trying and incarcerating youth (individuals under age 18 years) in the adult criminal justice system. In New York and in many other states, work around the second issue is known as “raise the age.” This chapter examines advocacy efforts around these two issues, with a particular focus on reform efforts in New York City and New York State, and considers the ways in which human rights activism and popular understandings of rights influence law and policy making.