cssi/SciSciGPT-SciSciNet huggingface dataset:
Unbiased Proteomic and Phosphoproteomic Analysis Identifies Response Signatures and Novel Susceptibilities After Combined MEK and mTOR Inhibition in BRAFV600E Mutant Glioma.

Abstract The mitogen-activated protein kinase pathway is one of the most frequently altered pathways in cancer. It is involved in the control of cell proliferation, invasion, and metabolism, and can cause resistance to therapy. A number of aggressive malignancies, including melanoma, colon cancer, and glioma, are driven by a constitutively activating missense mutation (V600E) in the v-Raf murine sarcoma viral oncogene homolog B (BRAF) component of the pathway. Mitogen-activated protein kinase kinase (MEK) inhibition is initially effective in targeting these cancers, but reflexive activation of mammalian target of rapamycin (mTOR) signaling contributes to frequent therapy resistance. We have previously demonstrated that combination treatment with the MEK inhibitor trametinib and the dual mammalian target of rapamycin complex 1/2 inhibitor TAK228 improves survival and decreases vascularization in a BRAFV600E mutant glioma model. To elucidate the mechanism of action of this combination therapy and understand the ensuing tumor response, we performed comprehensive unbiased proteomic and phosphoproteomic characterization of BRAFV600E mutant glioma xenografts after short-course treatment with trametinib and TAK228. We identified 13,313 proteins and 30,928 localized phosphosites, of which 12,526 proteins and 17,444 phosphosites were quantified across all samples (data available via ProteomeXchange; identifier PXD022329). We identified distinct response signatures for each monotherapy and combination therapy and validated that combination treatment inhibited activation of the mitogen-activated protein kinase and mTOR pathways. Combination therapy also increased apoptotic signaling, suppressed angiogenesis signaling, and broadly suppressed the activity of the cyclin-dependent kinases. In response to combination therapy, both epidermal growth factor receptor and class 1 histone deacetylase proteins were activated. This study reports a detailed (phospho)proteomic analysis of the response of BRAFV600E mutant glioma to combined MEK and mTOR pathway inhibition and identifies new targets for the development of rational combination therapies for BRAF-driven tumors.
Integrating Transcriptomics, Genomics, and Imaging in Alzheimer’s Disease: A Federated Model

Alzheimer9s disease (AD) affects more than 1 in 9 people age 65 and older and becomes an urgent public health concern as the global population ages. In clinical practice, structural magnetic resonance imaging (sMRI) is the most accessible and widely used diagnostic imaging modality. Additionally, genome-wide association studies (GWAS) and transcriptomic, the study of gene expression, also play an important role in understanding AD etiology and progression. Sophisticated imaging genetics systems have been developed to discover genetic factors that consistently affect brain function and structure. However, most studies to date focused on the relationships between brain sMRI and GWAS or brain sMRI and transcriptomics. To our knowledge, few methods have been developed to discover and infer multimodal relationships among sMRI, GWAS, and transcriptomics. To address this, we propose a novel federated model, Genotype-Expression-Imaging Data Integration (GEIDI), to identify genetic and transcriptomic influences on brain sMRI measures. The relationships between brain imaging measures and gene expression are allowed to depend on a person9s genotype at the single-nucleotide polymorphism (SNP) level, making the inferences adaptive and personalized. We performed extensive experiments on publicly available Alzheimer9s Disease Neuroimaging Initiative (ADNI) dataset. Experimental results demonstrated our proposed method outperformed state-of-the-art expression quantitative trait loci (eQTL) methods for detecting genetic and transcriptomic factors related to AD and has stable performance when data are integrated from multiple sites. Our GEIDI approach may offer novel insights into the relationship among image biomarkers, genotypes, and gene expression and help discover novel genetic targets for potential AD drug treatments.
Non-Destructive Inspection of Adhesively Bonded Joints using Amplitude Modulated Thermography

The goal of this work is to design thermal waves specifically for pulsed-phase infrared thermography (PPT) of bonded joints and to test their effectiveness on adhesive lap joints in carbon-fiber reinforced polymers structures. The method was applied to both single and double lap joint specimens to test different defect depths and multiple lap joint interfaces. An optimal thermal wave was designed for each specimen type based on the blind frequency information obtained from square pulse thermal wave excitation of the lap joint specimens. Modifications to the optimal thermal wave were then implemented based on the physical limitations of the lamp systems and different threshold settings for the blind frequency calculation. Thermal input waves based on the linear combination of discrete frequency waves were also implemented. The discrete frequency waves improved the defect image contrast in both the single and double lap joint specimens, while the optimal thermal input wave had the opposite effect and instead highlighted surface features. The difference in performance between the two thermal input waves is presumed to be due to the ability to separate frequency components in the transformation of data and not due to a critical thermal energy input threshold.
Chapter 10. Emerging Opportunities in the Treatment of Atherosclerosis

Publisher Summary Atherosclerosis, characterized by the deposition of lipids and fibrotic material in the arterial wall, is recognized as the leading contributor to cardiovascular disease, such as coronary heart disease (CHD). High levels of low density lipoprotein cholesterol (LDL-C), is a well established risk factor for CHD. Significant effort and progress have been made in recent years in the development of agents that lower LDL-C. Clinical trials with HMG-CoA reductase inhibitors (statins), the most commonly prescribed LDL-C lowering therapy. It has demonstrated a decrease in cardiovascular morbidity and mortality in patients with and without pre-existing CHD. It is generally accepted that the low levels of high density lipoprotein cholesterol (HDL-C) and high levels of triglycerides are also important risk factors, resulting in a growing emphasis to treat low HDL-C and high triglycerides. In addition to the conventional lipid therapies, modification of the underlying mechanisms of plaque formation and stabilization within the arterial wall presents an alternative potential therapy for the treatment of atherosclerosis. This chapter discusses some of the recent developments in LDL-C lowering and HDL-C elevation approaches, as well as approaches targeting the atherosclerotic plaque, focusing primarily on the programs in preclinical or early clinical development.
Aster Formation in Sea Urchin Eggs Induced by the injection of Enzyme-Treated Sperm Centrioles. (aster/centriole/enzymatic treatment/microinjection/sea urchin)

To determine the responsible components of isolated sperm centrioles for the aster induction in sea urchin eggs, the sperm centriolar fraction was treated with various enzymes and was injected into the unfertilized eggs, then the aster formation in first division was observed after fertilization. Treatment with 1 μg/ml or higher concentration of trypsin inhibited the centriolar activity for aster induction, whereas the treatment with 50 μg/ml of DNase 1, 80 μg/ml of RNase A, 40 μg/ml of RNase T1, or 0.1 μg/ml of trypsin had no inhibitory effect to induce asters. Injection of 0.5 μg/ml of RNase A or 1 mUg/ml of RNase T1 into the egg caused the detention of mitosis at the streak stage. To examine the temperature effect for aster induction, the centriolar fraction was pre-treated with boiling temperature, and it was found that the fraction became incapable to induce any aster. Results obtained suggest that the effective components of the sperm centriolar fraction to induce asters in the fertilized sea urchin eggs are the proteins but not the nucleic acids. The aster inducing activity is destroyed by heat treatment.
Determination of Impurity and Carrier Concentrations

When impurities such as donors and acceptors are introduced into a semiconductor, they produce levels within the energy gap. The energy of a level with respect to the edge of the conduction band in the case of donors, and the valence band in the case of acceptors is called the ionization energy. The simplest calculation of an impurity energy level is based on the hydrogenic model.
Vestibular rehabilitation following mild traumatic brain injury.

INTRODUCTION: Vertigo, dizziness, and imbalance are a symptom complex that is commonly found following concussion. Early metabolic changes following concussion may lead to worsening of the injury and symptoms in individuals not properly managed from the outset. When symptoms do not recover spontaneously, skilled vestibular rehabilitation can be an effective modality in an attempt to normalize the individual's vestibular responses. PURPOSE: The purpose of this review is to appraise the current and accepted methods available to the skilled clinician in quantifying and treating vestibular dysfunction following concussion. Incidence and prognostic indicators will be reviewed along with common barriers to recovery. SUMMARY: Vestibular Rehabilitation following concussion utilizes similar tools and techniques employed when treating those solely with peripheral pathology. The clinician must not only have a solid understanding of when and why certain exercises are required, but also be willing to accept that less exercise may be indicated in this population. As injury to the system following mild traumatic brain injury can include both peripheral and central structures, the duration of therapy and the time to recovery may be prolonged. Co-morbidities including cognitive and behavioral issues, visual-perceptual dysfunction, metabolic dysfunction, and autonomic dysfunction may hamper the effectiveness of the traditional Vestibular Rehabilitation approach. As successful treatment does not occur in a vacuum, working closely with other disciplines well versed in treating these co-morbid issues will help the individual to obtain optimal recovery. CONCLUSION: Vestibular Rehabilitation is an effective modality for managing dizziness, vertigo, and imbalance following concussion. Careful consideration of the acuity of the injury, along with effective management of co-morbid conditions will optimize the result. Language: en
Waveform design for compressive radar sensing

Wideband multi-frequency chirp waveforms combined with stretch processing on receive provides a way to obtain linear projection of range profiles at sub-Nyquist sampling rates. Stable recovery of high resolution range profiles from these projections is guaranteed only if the mutual coherence between the columns of the sensing matrix is sufficiently small. In this note, we derive the sensing matrix for the compressive radar sensor with multi-frequency chirp waveforms and analyze its coherence structure. We show that for suitable choice of system parameters the inter-column coherence of unstructured random sensing matrices is achieved.
Use of Skin Stretchers to Elongate a Peninsular Thoracodorsal Axial Pattern Flap for Antebrachial Wound Closure in a Dog

Objective: To describe preoperative use of skin stretchers to elongate a peninsular thoracodorsal axial pattern flap to close a large antebrachial wound on a dog. Study Design: Case report. Animals: A 21 kg, 7-year-old, male intact mixed breed dog. Methods: Two skin stretchers were applied to the site of the thoracodorsal axial pattern flap 4 days before surgery. The elastic cables connecting the adhesive pads were tightened daily to increase the skin available for a peninsular thoracodorsal axial pattern flap, which was created and rotated 180° to cover an antebrachial defect to a level 2 cm proximal to the carpus. Results: The entire flap survived; there was a small amount of incisional separation at the distal margin of the flap that healed without further treatment. Conclusion: Preoperative skin stretching provided additional skin for the axial pattern flap used.
Serum LH, FSH and prolactin levels during the estrous cycle in the hamster.

SummarySerum LH, FSH and prolactin was measured by radioimmunoassays in 21 mature female golden hamsters at 9 am on each morning of the 4-day estrous cycle and also at 6 pm on the day of proestrus. All 3 hormones showed peak values at 6 pm on proestrous day, and by the following morning (estrus) LH and prolactin had returned to basal levels. Serum FSH remained as high on the morning of estrus as on the afternoon of proestrus, and although it fell on the morning of metestrus it was still higher than on the mornings of diestrus and proestrus. The persistence of high FSH release on the mornings of estrus and metestrus may be related to the luteotropic function ascribed to FSH in the hamster. The peak rise in all 3 hormones on the afternoon of proestrus in the hamster is similar to that observed for these 3 hormones in the serum of cycling female rats.
Conservative intellectuals and the Reagan–Gorbachev summits

Ronald Reagan's 1980 election represented the apex of the conservative intellectual movement's political success in America. While historians have thoroughly examined the movement's effect on domestic American politics, international historians have been more reluctant to evaluate conservative intellectuals’ influence on Reagan's foreign policy. This essay seeks to determine what can be better understood about America's foreign affairs by examining Reagan's reaction to the conservative intellectual movement's views on the Reagan–Gorbachev summits.
Correlates of glycemic control and quality of life outcomes in adolescents with type 1 diabetes

Ingerski LM, Laffel L, Drotar D, Repaske D, Hood KK. Correlates of glycemic control and quality of life outcomes in adolescents with type 1 diabetes. Background: A major focus of pediatric multidisciplinary diabetes care is promoting glycemic control (A1c) while ensuring high quality of life (QOL). The current study investigated factors associated with A1c and QOL using a methodology that considered these variables as simultaneous outcomes. Method: A total of 261 adolescents (aged 13–18) with type 1 diabetes completed measures of blood glucose monitoring (BGM) frequency, diabetes-specific QOL, negative affect, and depression. Caregivers completed measures of demographic and disease characteristics, depression, and family conflict. Results: A1c was negatively correlated with QOL (r = −0.18 to −0.29, p < 0.01) across all subscales. Based on clinical A1c goals and median QOL scores, adolescents fell into four glycemic control–QOL groups. Multinomial logistic regression determined correlates of group membership utilizing adolescents with suboptimal glycemic control–low QOL as the referent group. Adolescents with optimal glycemic control–high QOL reported increased BGM frequency (OR = 1.87), less negative affect (OR = 1.32), and were more likely to use CSII (OR = 5.41). Adolescents with optimal A1c–low QOL reported greater BGM frequency (OR = 1.91) and shorter disease duration (OR = 1.09). Adolescents with suboptimal glycemic control–high QOL reported greater BGM frequency (OR = 1.41), fewer depressive symptoms (OR = 1.13), and less negative affect (OR = 1.31). Conclusions: Results reveal disease, management, and psychosocial characteristics that differentiate glycemic control–QOL outcome groups and identify risk factors related to this relationship. Further appreciation of these characteristics may increase clinicians' understanding and attention to these important clinical outcomes and help tailor the most appropriate interventions (e.g., individual psychotherapy vs. family problem-solving interventions) to help adolescents achieve glycemic control without sacrificing QOL.
Generalized Worpitzky Identities with Applications to Permutation Enumeration

The enumeration of permutations by inversions often leads to a q -analog of the usual generating function. In this paper, two generalizations of the Worpitzky identity for the Eulerian numbers are obtained and used to enumerate permutations by the descent number and the major index of their inverses. The resulting ( t , q )-generating series do in fact generalize the q -series obtained when counting by inversions.
Adsorption of phenol and benzoic acid from dilute aqueous solution onto a macroreticular resin

Abstract Radiolabeled solutes were used to obtain equilibrium adsorption data for the uptake of benzoic acid and phenol by a macroreticular resin (Amberlite XAD-8) from dilute aqueous solutions. Phenol was studied at 0, 25, and 70°C, and benzoic acid was studied at 25°C. The phenol data, which covered a wide concentration range, was modeled with less than 5% error using a three parameter adsorption equation.
Laissez-Faire: Fully Asymmetric Backscatter Communication

Backscatter provides dual-benefits of energy harvesting and low-power communication, making it attractive to a broad class of wireless sensors. But the design of a protocol that enables extremely power-efficient radios for harvesting-based sensors as well as high-rate data transfer for data-rich sensors presents a conundrum. In this paper, we present a new {\em fully asymmetric} backscatter communication protocol where nodes blindly transmit data as and when they sense. This model enables fully flexible node designs, from extraordinarily power-efficient backscatter radios that consume barely a few micro-watts to high-throughput radios that can stream at hundreds of Kbps while consuming a paltry tens of micro-watts. The challenge, however, lies in decoding concurrent streams at the reader, which we achieve using a novel combination of time-domain separation of interleaved signal edges, and phase-domain separation of colliding transmissions. We provide an implementation of our protocol, LF-Backscatter, and show that it can achieve an order of magnitude or more improvement in throughput, latency and power over state-of-art alternatives.
Emergence of film-thickness- and grain-size-dependent elastic properties in nanocrystalline thin films

Molecular dynamics simulations of nanocrystalline Ni revealed that the in-plane Young’s modulus of 2.2 nm grained Ni film with ∼10 grains across its thickness was only 0.64% smaller than that of bulk, while it dropped to 24.1% below bulk value for ∼1 grain across film. This size dependence arises from the increased number of more compliant grains adjacent to the free surface. Simulations of nanocrystalline diamond revealed that the anharmonicity of the potential curve determined the sensitivity of the Young’s modulus to variations in the sample size.
Elevated Donor Troponin Levels Are Associated with a Lower Frequency of Allograft Vasculopathy

Background Cardiac allograft vasculopathy (CAV) is considered a major cause of morbidity and mortality in transplant recipients and may reflect immune-mediated endothelial injury in response to the donor heart. Elevated troponin levels in the donor serum might provide a marker for this phenomenon; therefore, we evaluated the relationship of donor troponin levels to the development of CAV. Methods A retrospective analysis of troponin levels was undertaken from cardiac donor patients, and transplant recipients were monitored for the development of vasculopathy by angiography (N = 171). Results Angiographically significant CAV developed in 6% of transplantation patients and troponin levels were inversely related to the severity of CAV. Conclusions Elevated donor troponin levels are not associated with the development of CAV but rather with a significantly reduced long-term risk of developing CAV, suggesting a possible protective effect of donor released protein.
Gender differences in smoking behavior and cessation

Objective: Many women want to quit smoking, but have lower abstinent rates than men. The gender differences in smoking behaviors and cessation in adults were explored through qualitative analyses of individual interviews with male and female smokers. Methods: Sixty-one participants (34 men and 27 women), who reported using tobacco within the last year, completed open-ended phone interviews concerning barriers faced during smoking cessation. Participants reported smoking for an average of 23.0 ( SD = 11.3) years and making an average of 2.41 ( SD = 2.6) prior quit attempts. The interviews were transcribed and analyzed using qualitative content analysis procedures. An investigator external to the study independently analyzed qualitative interview data to increase the trustworthiness of results. Results: Barriers relating to stress-mood regulation and social factors ( e.g. , others smoking) were most commonly reported in both genders (72% & 41% respectively). However, women tended to report a greater number of distinct barriers (Cohen's d = 0.4) and a great frequency of stress-related factors and anxiety. Factors related to the sensory aspects of smoking were more common among women and only women noted the lack of social support as a barrier. Other barriers included use of alcohol and factors related to the addictive nature of tobacco use ( e.g. , cravings). Abrupt cessation, or “cold-turkey”, was most common cessation method for both genders. However, both men and women reported using a variety of smoking cessation methods including nicotine replacement, cessation medications, electronic cigarettes, and behavior strategies. Conclusions: The results showed that barriers to smoking cessation differed between the genders. Implications for smoking cessation programs include gender specific interventions.
Incremental clustering applied to radar deinterleaving: a parameterized FPGA implementation

ICED (Incremental Clustering of Evolving Data) is a novel incremental clustering algorithm designed for data whose characteristics change over time. ICED is an unsupervised clustering technique that assumes no prior knowledge of the incoming data, and supports removing clusters that contain stale data. The user controls the FPGA implementation through a combination of compile time parameters (number of clusters) and run time parameters (distance threshold, fade cycle length). ICED has been applied to a radar application: pulse deinterleaving. ICED is the first implementation of incremental clustering on an FPGA of which we are aware. The implementation runs 39 times faster than an equivalent C implementation on a 3GHz Intel Xeon processor, and is capable of processing radar data in real time.
Katul receives 2002 James B. Macelwane Medal

Gabriel George Katul was awarded the James B. Macelwane Medal at the AGU Spring Meeting Honors Ceremony, which was held on 29 May 2002, in Washington, D. C. The medal recognizes significant contributions to the sciences by a young scientist of outstanding ability.
Chronic liver disease in murine hereditary tyrosinemia type 1 induces resistance to cell death

The murine model of hereditary tyrosinemia type 1 (HT1) was used to analyze the relationship between chronic liver disease and programmed cell death in vivo. In healthy fumarylacetoacetate hydrolase deficient mice (Fah(-/-)), protected from liver injury by the drug 2-(2- nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), the tyrosine metabolite homogentisic acid (HGA) caused rapid hepatocyte death. In contrast, all mice survived the same otherwise lethal dose of HGA if they had preexisting liver damage induced by NTBC withdrawal. Similarly, Fah(-/-) animals with liver injury were also resistant to apoptosis induced by the Fas ligand Jo-2 and to necrosis-like cell death induced by acetaminophen (APAP). Molecular studies revealed a marked up-regulation of the antiapoptotic heat shock proteins (Hsp) 27, 32, and 70 and of c-Jun in hepatocytes of stressed mice. In addition, the p38 and Jun N-terminal kinase (JNK) stress-activated kinase pathways were markedly impaired in the cell-death resistant liver. In conclusion, these results provide evidence that chronic liver disease can paradoxically result in cell death resistance in vivo. Stress-induced failure of cell death programs may lead to an accumulation of damaged cells and therefore enhance the risk for cancer as observed in HT1 and other chronic liver diseases.
Hierarchical molecular modelling with ellipsoids

Protein and DNA structures are represented at varying levels of details using ellipsoidal RGBA textured splats. The splat texture at each level is generated by rendering its children in a hierarchical model, from a distribution of viewing directions, and averaging the result. For rendering, the ellipsoids to be used are chosen adaptively, depending on the distance to the viewpoint. This technique is applied to visualize DNA coiling around nucleosomes in chromosomes.
Sex steroid hormones in natural populations of a sexual whiptail lizard Cnemidophorus inornatus, a direct evolutionary ancestor of a unisexual parthenogen

The lizard genus Cnemidophorus consists of both sexual species and unisexual, all-female species. We characterized changes in circulating levels of gonadal sex steroid hormones in males and females in one of the sexual species, C. inornatus, to compare them to previously measured levels in a unisexual, parthenogenetic species, C. uniporens. Reproductively active male C. inornatus have high levels of dihydrotestosterone and somewhat lower levels of testosterone. These levels are highest immediately after females become sexually receptive and decrease later at the onset of testicular regression. Female C. inornatus have high levels of estradiol and low levels of progesterone during the previtellogenic and vitellogenic phases of the ovarian cycle. During the postovulatory phase, they have low levels of estradiol and high levels of progesterone. We could not detect circulating levels of androgen at any phase of the ovarian cycle. The patterns of hormone secretion in the female C. inornatus are virtually identical to those of its direct evolutionary descendant, C. uniparens. This confirms our previous conclusion that the evolution of the parthenogenetic mode of reproduction and expression of male-like pseudosexual behavior that are characteristic of the unisexual C. uniparens has not been accomplished by evolutionary modifications in the pattern of sex steroid hormone secretion. Rather it is the response to this pattern of secretion that has been modified.
An experimental testbed for investigating nonsmooth bifurcations in an electromechanical system

In this paper we detail the design, construction, experimental investigation, theoretical modeling, and numerical exploration of a laboratory-scale electromechanical device, which includes the possibility of recurrent mechanical contact and exploitable multidomain signal transduction. In particular, we illustrate the use of inductive coupling between electrical and mechanical degrees of freedom to actuate and interrogate changes in the mechanical response due to the onset of contact through the coupled behavior of the device current. It is shown that nonsmooth bifurcations associated with a transition from nonimpacting to impacting dynamics, induced by changes in critical parameter values, may result in detectable changes in the current amplitude and, significantly, frequency content. The device design and the observed results are argued to support a similar functionality in microscale devices, where multidomain coupling is common.
Frequency judgments of nonretarded and retarded individuals.

rived from an extended version of frequency theory that: retarded individuals relative to MA-matched normals are not as accurate in their ability to detect differences in frequency. The method of constant stimuli w3s used to obtain an estimate of the difference thresholds based on normative word frequency in Exp. 1 and experimentally manipulated trigram frequency in Exp. 2. The results from Exp. 1 supported the notion that retarded individuals are not as sensitive to differences in frequency as MA-matched normals. However, in Exp. 2 the differences in performance berween the two MA-matched groups disappeared. The results were interpreted as indicating that the retarded individual can use the frequency cue as effectively as the normal individual and that the differences reported in Exp. 1 simply reflected the inadequacy of the Thorndike and Lorge (1944) word frequency norms for normal and retarded children. The results were also discussed within the context of a frequency theory analysis of discrimination learning by the retarded.
Aroma chemicals isolated and identified from leaves of Aloe arborescens Mill. Var. Natalensis Berger.

Extracts from leaves of aloe (Aloe arborescens Mill. var. natalensis Berger) were obtained using two methods: steam distillation under reduced pressure followed by dichloromethane extraction (DRP) and simultaneous purging and extraction (SPE). A total of 123 aroma chemicals were identified in the extracts obtained by both methods using gas chromatography and gas chromatography/mass spectrometry. There were 42 alcohols, 23 terpenoids, 21 aldehydes, 9 esters, 8 ketones, 6 acids, 5 phenols, and 9 miscellaneous compounds. The major aroma constituents of this extract by DRP were (Z)-3-hexenol (29.89%), (Z)-3-hexenal (18.86%), (E)-hexenal (7.31%), 4-methyl-3-pentenol (5.66%), and butanol (4.29%). The major aroma constituents of this extract by SPE were (E)-2-hexenal (45.46%), (Z)-3-hexenal (32.12%), hexanal (9.14%), (Z)-3-hexenol (1.60%), and 3-pentanone (1.41%). Terpenoids were also found as one of the major constituents. The fresh green note of aloe leaves is due to the presence of these C6 alcohols and alde...
α2A-adrenoceptors enhance the serotonergic effects of fluoxetine

Abstract The ability of subtype-preferring α2-adrenoceptor antagonists to enhance the neurochemical effects of the antidepressant, fluoxetine, was evaluated by in vivo microdialysis. Combining the selective α2A-adrenoceptor antagonist, BRL-44408 (10 mg/kg, s.c.), with fluoxetine (30 mg/kg, s.c.) elevated the extracellullar levels of serotonin (5-HT) and noradrenaline in the rat frontal cortex, an effect not observed following antidepressant treatment alone. In contrast, combining fluoxetine with the α2B- or α2C-adrenoceptor antagonists, imiloxan (10 mg/kg, s.c.) or rauwolscine (10 mg/kg, s.c.), respectively, did not similarly alter biogenic amine levels. Collectively, these results reveal a specific role for the α2A-adrenoceptor subtype in augmenting the neurochemical effects of antidepressants.
Techniques to improve the CLEAN deconvolution algorithm

Abstract The CLEAN algorithm was introduced in radio astronomy as a means to overcome the shadowing of small targets by the sidelobes of the point spread function (PSF) of a strong target. The idea was further used in microwave imaging where the concept of coherent CLEAN was introduced. The classical CLEAN algorithm is limited to a case where the targets are isolated. Techniques to overcome this limitation are presented in this paper. These techniques include PSF correlation to improve the estimation of target locations and intensities, sequence CLEAN (S-CLEAN) which improves the detection of true targets and suppresses the detection of false ones, and iterative CLEAN (ICLEAN) which uses knowledge about a target to improve the estimation of other targets' parameters. Emulation, using real experimental data, shows that a significant improvement can be achieved using these techniques.
Depressive symptoms in the immediate postpartum period among Hispanic women in three U.S. cities.

The aim of this was to examine rates and determinants of depressive symptomatology in the immediate postpartum period among Hispanic women in the United States. A total of 3952 Hispanic women who had delivered infants (parturients) were interviewed in postpartum wards in Miami, New York City and San Francisco. Symptoms of depression were regressed onto a series of social, psychological, and socioeconomic variables. Results showed that 42.6% of participants were probable cases of depression (CES-D ≥ 16). Depression was negatively associated with perceived level of social support (adjusted OR = 0.59, 95% CI: 0.53–0.67) and health insurance coverage (adjusted OR = 0.68, 95% CI: 0.49–0.95), but not with the degree of acculturation or immigration status. It was found that depressive symptoms are common among Hispanic parturients. Pregnant Hispanic women should be carefully monitored for signs of depression and appropriate preventive measures are needed.
Optimizing target-organ protection in patients with renal impairment

Abstract Key Words: combination antihypertensive therapy, diabetes, African-Americans, Lotrel, amlodipine, benazepril, SHIELD, LEAAD *This activity is supported by an unrestricted educational grant from Novartis Pharmaceuticals Corporation.
Biology of cancer and aging

The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development.
Limb neurovascular control during altered otolithic input in humans

Head-down rotation (HDR), which activates the vestibulosympathetic reflex, increases leg muscle sympathetic nerve activity (MSNA) and produces calf vasoconstriction with no change in either cardiac output or arterial blood pressure. Based on animal studies, it was hypothesized that differential control of arm and leg MSNA explains why HDR does not alter arterial blood pressure. Fifteen healthy subjects were studied. Heart rate, arterial blood pressure, forearm and calf blood flow, and leg MSNA responses were measured during HDR in these subjects. Simultaneous recordings of arm and leg MSNA were obtained from five of the subjects. Forearm and calf blood flow, vascular conductances, and vascular resistances were similar before HDR, as were arm and leg MSNA. HDR elicited similar significant increases in leg (Delta 6 +/- 1 bursts min(-1); 59 +/- 16 % from baseline) and arm MSNA (Delta 5 +/- 1 bursts min(-1); 80 +/- 28 % from baseline). HDR significantly decreased calf (-19 +/- 2 %) and forearm vascular conductance (-12 +/- 2 %) and significantly increased calf (25 +/- 4 %) and forearm vascular resistance (15 +/- 2 %), with ~60 % greater vasoconstriction in the calf than in the forearm. Arterial blood pressure and heart rate were not altered by HDR. These results indicate that there is no differential control of MSNA in the arm and leg during altered feedback from the otolith organs in humans, but that greater vasoconstriction occurs in the calf than in the forearm. These findings indicate that vasodilatation occurs in other vascular bed(s) to account for the lack of increase in arterial blood pressure during HDR.
On the structure of vector quantizers

Vector quantization is intrinsically superior to predictive coding, transform coding, and other suboptimal and {\em ad hoc} procedures since it achieves optimal rate distortion performance subject only to a constraint on memory or block length of the observable signal segment being encoded. The key limitation of existing techniques is the very large randomly generated code books which must be stored, and the computational complexity of the associated encoding procedures. The quantization operation is decomposed into its rudimentary structural components. This leads to a simple and elegant approach to derive analytical properties of optimal quantizers. Some useful properties of quantizers and algorithmic approaches are given, which are relevant to the complexity of both storage and processing in the encoding operation. Highly disordered quantizers, which have been designed using a clustering algorithm, are considered. Finally, lattice quantizers are examined which circumvent the need for a code book by using a highly structured code based on lattices. The code vectors are algorithmically generated in a simple manner rather than stored in a code book, and fast algorithms perform the encoding algorithm with negligible complexity.
Evoked gamma band response in male adolescent subjects at high risk for alcoholism during a visual oddball task

This study investigates early evoked gamma band activity in male adolescent subjects at high risk for alcoholism (HR; n=68) and normal controls (LR; n=27) during a visual oddball task. A time-frequency representation method was applied to EEG data in order to obtain stimulus related early evoked (phase-locked) gamma band activity (29-45 Hz) and was analyzed within a 0-150 ms time window range. Significant reduction of the early evoked gamma band response in the frontal and parietal regions during target stimulus processing was observed in HR subjects compared to LR subjects. Additionally, the HR group showed less differentiation between target and non-target stimuli in both frontal and parietal regions compared to the LR group, indicating difficulty in early stimulus processing, probably due to a dysfunctional frontoparietal attentional network. The results indicate that the deficient early evoked gamma band response may precede the development of alcoholism and could be a potential endophenotypic marker of alcoholism risk.
Coupled heat and multicomponent mass transfer in particulate systems with residence time and size distributions

Abstract A theory is presented for the general case of coupled heat and multicomponent mass transfer in dispersions and suspensions with residence time and particle size distributions. The general formulations describe the behavior of industrial or biological particulate systems in terms of equations familiar from non-equilibrium thermodynamics and transport phenomena. Using matrix notation and appropriate transformations the resulting partial differential equations are first decoupled and then transformed into ordinary differential equations by employing an integral operator whose kernel takes into account the particle size and residence time distributions. Moment equations of the size distribution are formulated and used to evaluate general interrelationships among average sizes, interfacial surface area, dispersed-phase holdup fraction, and total average rates of transfer from the particle population. The total average heat- and mass-transfer rates in multiphase particulate systems are evaluated in terms of a general normalized size distribution and the expected values of the various fluxes involved. The properties of a proposed general normalized size distribution are discussed and compared with experimental results of bubble size distributions in a gas-liquid dispersion.
Mating Pair Formation Homologue TraG Is a Variable Membrane Protein Essential for Contact-Independent Type IV Secretion of Chromosomal DNA by Neisseria gonorrhoeae

Neisseria gonorrhoeae uses a type IV secretion system (T4SS) to secrete chromosomal DNA into the surrounding milieu. The DNA is effective in transforming gonococci in the population, and this mechanism of DNA donation may contribute to the high degree of genetic diversity in this species. Similar to other F-like T4SSs, the gonococcal T4SS requires a putative membrane protein, TraG, for DNA transfer. In F-plasmid and related systems, the homologous protein acts in pilus production, mating pair stabilization, and entry exclusion. We characterized the localization, membrane topology, and variation of TraG in N. gonorrhoeae. TraG was found to be an inner-membrane protein with one large periplasmic region and one large cytoplasmic region. Each gonococcal strain carried one of three different alleles of traG. Strains that carried the smallest allele of traG were found to lack the peptidoglycanase gene atlA but carried a peptidoglycan endopeptidase gene in place of atlA. The purified endopeptidase degraded gonococcal peptidoglycan in vitro, cutting the peptide cross-links. Although the other two traG alleles functioned for DNA secretion in strain MS11, the smallest traG did not support DNA secretion. Despite the requirement for a mating pair stabilization homologue, static coculture transformation experiments demonstrated that DNA transfer was nuclease sensitive and required active uptake by the recipient, thus demonstrating that transfer occurred by transformation and not conjugation. Together, these results demonstrate the TraG acts in a process of DNA export not specific to conjugation and that different forms of TraG affect what substrates can be transported.
A note on the diffusion drag forces

A formal derivation of the expression for the diffusion drag force is given. The expression involves the coefficient of diffusion of the solute through the solvent and the coefficient of diffusion which the solute would posses if it diffused through itself in the form of a gas, in the absence of the solvent.
The diphasic action of halothane on the oxidative metabolism of drugs by the liver. An in-vitro study in the rat.

Halothane depresses the metabolism of amobarbital, hexobarbital, pentobarbital, and aminopyrine (type I substrates) by rat hepatic microsomal enzymes. This inhibition is dose-dependent, reversible, noncompetilive, and independent of the lipid solubilities of the substrates. In contrast, the metaboli
Robust testing of CMOS logic circuits

Abstract It is well-known that two-pattern tests, which are required to detect stuck-open faults in CMOS logic circuits, can be invalidated if circuit delays have been ignored in their derivation. Furthermore, for certain CMOS circuits a robust test set, which remains valid in the presence of arbitrary circuit delays, may not exist. However, for most CMOS circuits a robust test set does exist. In this paper we present a method for obtaining a test set based on two-pattern tests to robustly test for all single stuck-open faults. If the test set is based on three-pattern tests, then we show that it can detect all multiple stuck-open faults robustly.
Abstract 3864: Blocking hypoxia-induced tumor cell migration by p16/INK4A.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC One general characteristic of fast-growing solid tumors including breast cancer is the development of intratumoral hypoxia. The activation of hypoxia-inducible factor-1α (HIF-1α) by intratumoral hypoxia stimulates a group of downstream genes including vascular endothelial growth factor (VEGF) that are responsible for tumor malignant progression. Loss of p16 expression occurs in many cancers including breast cancer. Our studies showed that, by ectopic expression via adenoviral-mediated gene transfer, p16 downregulates VEGF gene expression by neutralizing the transactivation of HIF-1α, and suppresses breast cancer angiogenesis and metastasis. To investigate whether p16 directly affects one or more aspects of the metastatic cascade, MDA-MB-231 cells infected with lentivirus expressing Tet-on inducible p16 were used to study the p16 effects on growth, adhesion and migration of the breast cancer cells. We found that p16 inhibits MDA-MB-231 cell proliferation (45.6% inhibition) and hypoxia-induced cell migration (36% inhibition), but has no apparent effect on cell adhesion. The p16-mediated inhibition of hypoxia-induced cell migration parallels with p16’s inhibition of HIF-1α transactivation activity. These results indicate that p16’s ability to suppress breast tumor metastasis may result from a combined p16-mediated actions including inhibition of cell proliferation, migration, and angiogenesis. This study suggests that p16 gene therapy may have clinical potentials to treat breast cancer due to p16’s multiple-level anti-cancer capabilities: inhibiting proliferation, inducing apoptosis, blocking tumor angiogenesis, inhibiting cell migration and suppressing metastasis. Citation Format: Yi Lu. Blocking hypoxia-induced tumor cell migration by p16/INK4A. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3864. doi:10.1158/1538-7445.AM2013-3864
Short-term streamflow forecasting with global climate change implications – A comparative study between genetic programming and neural network models

Sustainable water resources management is a critically important priority across the globe. While water scarcity limits the uses of water in many ways, floods may also result in property damages and the loss of life. To more efficiently use the limited amount of water under the changing world or to resourcefully provide adequate time for flood warning, the issues have led us to seek advanced techniques for improving streamflow forecasting on a short-term basis. This study emphasizes the inclusion of sea surface temperature (SST) in addition to the spatio-temporal rainfall distribution via the Next Generation Radar (NEXRAD), meteorological data via local weather stations, and historical stream data via USGS gage stations to collectively forecast discharges in a semi-arid watershed in south Texas. Two types of artificial intelligence models, including genetic programming (GP) and neural network (NN) models, were employed comparatively. Four numerical evaluators were used to evaluate the validity of a suite of forecasting models. Research findings indicate that GP-derived streamflow forecasting models were generally favored in the assessment in which both SST and meteorological data significantly improve the accuracy of forecasting. Among several scenarios, NEXRAD rainfall data were proven its most effectiveness for a 3-day forecast, and SST Gulf-to-Atlantic index shows larger impacts than the SST Gulf-to-Pacific index on the streamflow forecasts. The most forward looking GP-derived models can even perform a 30-day streamflow forecast ahead of time with an r-square of 0.84 and RMS error 5.4 in our study.
Improved Micro-Patterning of Soft-Polymers and Elastomers Using Conformally Coated Omni-Coat Nanofilms

This paper describes the basic Direct Polymer Patterning On Substrate Technique (DPPOST) process and a modified process currently under development to provide higher robustness in the fabrication process, with the goal of achieving near 100% patterning yields. The patterning of soft-polymers and elastomers has gained interest in the last decade as the material of choice for lab-on-the chip applications; i.e., forming micro-fluidic and bio-reactor chambers. Recently, a lithographically compatible patterning method for soft-polymers and elastomers have been demonstrated by using SU-8® hard polymer resists as robust lift-off molds. This patterning technology, DPPOST, has the ability to form a wide range of structural features found in MEMS, from tens of millimeter structures to micrometer level resolutions. It has been used to embed nano-particles, such as carbon-black (∼45nm mean radius) and metal particles, and allows lithographic alignment of electrodes on micro-fluidic channels previously not possible with soft-lithography fabricated PDMS devices. The modified-DPPOST process uses conformal coating of Omnicoat™ nano-films to provide a barrier between the SU-8® and the patterned polymer, hence reducing stiction during the release process.Copyright © 2008 by ASME