cssi/SciSciGPT-SciSciNet huggingface dataset:
The chromosomes and causation of human cancer and leukemia. XIX. Common markers in various tumors.

Most human cancers are associated with abnormal (marker) chromosomes. In past and present studies banding analyses have uncovered a much larger number of markers in cancer cells than was seen with standard (Giemsa) staining. Furthermore, common markers of identical morphology and origin were found in tumors of related or unrelated tissues or organs, suggesting that in all probability such markers, although present in cancers of diverse nature, may indicate a common etiology, either related to the causation of the cancers, to the progression of the tumors, or to the predilection of certain chromosomes to undergo morphologic changes leading to marker formation. Even though some markers were common to different tumors, the bulk of the markers in the cancers studied could not be identified with certainty and their nature varied from tumor to tumor.
Ewing's sarcoma of a lower extremity in an infant. A therapeutic dilemma.

A 5.5-month-old infant with Ewing's sarcoma of the left femur is described. The clinical and the pathologic features in this infant are presented in detail, and the dilemma faced in diagnosis and therapy of Ewing's sarcoma in infants is discussed. It is suggested that Ewing's sarcoma in an infant with a lower extremity lesion may be adequately managed without primary amputation. Cancer 58:187–189, 1986.
The perception of speaking rate using visual information from a talker's face.

It has been well documented that listeners are able to estimate speaking rate when listening to a talker, but almost no work has been done on perception of rate information provided by looking at a talker’s face. In the present study, the method of magnitude estimation was used to collect estimates of the rate at which a talker was speaking. The estimates were collected under four experimental conditions: auditory only, visual only, combined auditory-visual, and inverted visual only. The results showed no difference in the slope of the functions relating perceived rate to physical rate for the auditory only, visual only, and combined auditory-visual presentations. There was, however, a significant difference between the normal visual-only and the inverted-visual presentations. These results indicate that there is visual rate information available on a talker’s face and, more importantly, suggest that there is a correspondence between the auditory and visual modalities for the perception of speaking rate, but only when the visual information is presented in its normal orientation.
Phase Representation and High-Energy Behavior of the Forward Scattering Amplitude

By making use of the phase representation, the relation between the high-energy behavior of the symmetric forward scattering amplitude $F(x)$ and the asymptotic properties of the ratio $cot\ensuremath{\delta}=\frac{\mathrm{Re}F}{\mathrm{Im} F}$ is discussed. Starting assumptions are dispersion relations and the Greenberg-Low bound. Lower bounds as well as upper bounds are derived. Under the assumption of the Froissart bound, it is shown that $cot\ensuremath{\delta}$ cannot stay indefinitely greater than an arbitrarily small positive number. Also if the total cross section decreases steadily to a finite limit, but slower than $\frac{\mathrm{const}}{E}$ the real part must tend to $\ensuremath{-}\ensuremath{\infty}$. The results are discussed in connection with those of Khuri and Kinoshita. The unsymmetric case is also treated by the same methods.
Failure of Nielsen's theorem in higher dimensions

The following is known for closed orientable surfaces. If H: ii/l -+ &! is a map whose n-th power is homotopic to the identity, then H is homotopic to a homeomorphism K with Kqa = identity. The result is known as Nielsen’s Theorem on finite mapping classes. There are doubts (see [S]) as to the correctness of all parts of Nielsen’s arguments in [6]. Different (using complex analysis and the Smith theorems) and valid proofs have been given independently by Fenchel and Macbeath. Because we are dealing with surfaces, each self homotopy equivalence is homotopic to a diffeomorphism, and homotopic diffeomorphisms are diffeotopic. Consequently, Nielsen’s theorem may be equivalently stated as follows: If H: ii + ill is a diffeomorphism whose n-th power is homotopic to the identity then H is diffeotopic to a diffeomorphism K with Km = identity. The theorem is extremely useful in studying periodic maps on 3-manifolds, and there are obvious applications in surface theory. The question has been raised as to what extent Nielsen’s theorem holds for aspherical manifolds of dimensions greater than 2. An aspherical manifold is a closed manifold whose universal covering is contractible. Aspherical manifolds are therefore closed manifolds which are also K(n, 1)‘s. An important and interesting class of aspherical manifolds (generalizing the tori) are the nil-manifolds. A nil-manifold is simply the quotient of a connected contractible nilpotent Lie group by a uniform discrete subgroup. We shall show that in dimensions greater than 2 there exist closed nil-manifolds for which Nielsen’s theorem fails in a very strong sense. Specifically
Sodium glucose co-transporter 2 (SGLT2) inhibitors as potential antidiabetic agents

Sodium glucose co-transporter 2 (SGLT2) plays a key role in maintaining glucose equilibrium in the human body. SGLT2 is a kidney transporter that reabsorbs glucose from the renal filtrate and preve...
Breathing easier – good news from air medicine

Safety in transport is a major concern. Air medical crashes are in the public eye, but a greater risk of transport may be in the clinical care provided along the way. While the media focuses on the drama of helicopters landing on scene, the greatest and most common risk actually occurs during inter-hospital transport. For too long, transport has been a black hole in clinical medicine and the real rate of adverse events is unknown. New work from the University of Pennsylvania should make us all breathe a little easier.
A left preauricular mass.

A teenage boy presented with a 3-month history of a left preauricular mass. His medical history was notable for an atypical teratoid rhabdoid tumor of the left temporoparietal lobe diagnosed at age 3 years, which had been resected and treated with chemoradiation. Physical examination demonstrated a 2-cm firm, nontender, mobile mass without overlying skin invlvement. There was no palpable lymphadenopathy, butweakness of the frontal branch of the left facial nervewasnoted.Magnetic resonance imaging (MRI) of the neck revealed a 1.0 × 1.7 × 1.9-cmmildly enhancingmass lateral to the left subcondylar mandible, which was inseparable from the anterior parotid gland (Figure, A). A superficial parotidectomy was performed. The superior division of the facial nerve was intimately associated with the parotid mass, and sacrifice of the upper division of the facial nerve branches with a cable nerve graft was required. The cut surface of the surgical resection specimen of the superior parotid revealed a 1.7-cm reddish tan variegated mass. Microscopic sections showed a circumscribed tumor with microcystic architecture (Figure, B). The tumor was composed of monotonous amphophilic cells with granular cytoplasm and round to ovoid nuclei (Figure, B and C). An immunohistochemical panel showed notably positive tumoral staining for the proteins S-100 and vimentin and negative staining for DOG1 and p63 antibodies. Special stains for mucicarmine and periodic acid–Schiff diastase (PASD) were performed. Mucicarmine highlighted abundant extracellular (luminal) mucin, but intracellular mucin was absent. PASD confirmed the absence of zymogen granule formation. Fluorescence in situ hybridization (FISH) was positive for translocation of the ETV6 gene. What is your diagnosis? A B
Regularity estimates up to the boundary for elliptic systems of difference equations

Regularity estimates up to the boundary for solutions of elliptic systems of finite difference equations were proved. The regularity estimates, obtained for boundary fitted coordinate systems on domains with smooth boundary, involve discrete Sobolev norms and are proved using pseudo-difference operators to treat systems with variable coefficients. The elliptic systems of difference equations and the boundary conditions which are considered are very general in form. The regularity of a regular elliptic system of difference equations was proved equivalent to the nonexistence of eigensolutions. The regularity estimates obtained are analogous to those in the theory of elliptic systems of partial differential equations, and to the results of Gustafsson, Kreiss, and Sundstrom (1972) and others for hyperbolic difference equations.
Copper-induced release of immunoreactive α-melanotropin from isolated hypothalamic granules

Abstract Previously, we demonstrated that copper chelates stimulate the release of luteinizing hormone releasing hormone (LHRH) from isolated hypothalamic granules. To assess the generality of the copper-stimulated release process, we determined the effects of copper on the release of immunoreactive α-melanotropin (α-MSH 1 ) from isolated granules. When granules were incubated with various copper complexes, CuATP stimulated α-MSH 1 release by 54 ± 6% ( mean ± S . E .), Cu tartarate by 56 ± 4%, CuBSA by 32 ± 5% and Cu histidine by 29 ± 2%. CuATP-stimulated α-MSH 1 release from granules incubated under N 2 was 57% of that incubated under air. Furthermore, the reducing agent dithiothreitol (DTT) inhibited CuATP-stimulated α-MSH 1 release ( p 1 release by 52 ± 3 and 38 ± 4%, respectively. Thus, chelated copper, rather than ionic copper, is the active form of the metal and the action of copper involves the oxidation of thiols. These data are similar to those previously observed for the copper-stimulated release of LHRH. Hence, the effects of copper on the permeability of granule membranes may be a generalized phenomenon which underlies susceptibility of storage granules to the reduction-oxidation status of the cellular milieu.
Reverse Shoulder Arthroplasty: A Role Defined

The recent resurgence in interest in reverse shoulder replacement catalyzed by innovations in prosthetic design over the last two decades in Europe has now reached North America. In a short period of time, the concept has emerged from relative obscurity to preeminence as one of the hot topics at orthopedic and shoulder specialty meetings worldwide. However, cautionary data have emerged from highly respected centers and surgeons regarding a relatively high complication and reoperation rate. It is important to critically examine our reaction to and use of such a new and complicated technology as reverse shoulder replacement. This submission provides a detailed look at the advantages and shortcomings of this technology, focusing on the indications and contraindications with the concept that these are the most important factors to consider. When performed cautiously in the patient with ideal indications, this prosthesis offers the potential of an excellent result where previously there was none. The reverse shoulder replacement should be saved for patients for whom there is no reasonable alternative.
Multifunctional thiols as additives in UV-cured PEG-diacrylate membranes for CO2 separation

Abstract The utility of incorporating only 20 mol% of multifunctional thiols into UV-cured poly(ethyleneglycol)diacrylate (PEGDA) membranes for CO2 separation is presented. Five different multifunctional thiols were investigated, spanning a range of functionalities from 2 to 4 and also different rigidities. All thiol-modified networks exhibited lower modulus values according to both small-strain and large-strain mechanical testing. This decrease in modulus was primarily attributed to a decrease in crosslink density via the step-growth thiol–acrylate reaction. Decreased crosslink density was more pronounced for dithiol additives which formed a “train-like” topology of connected PEGDA segments. Because of this more linear topology, dithiol-modified networks exhibited increases in gas permeability and strain at break. CO2 selectivity of each thiol-modified network was nearly comparable to the unmodified PEGDA network. Each network rapidly reached 100% conversion under a nitrogen atmosphere. However in air, the pure acrylate network reached negligible conversion while the networks modified with tri and tetrathiols reached noticeably higher conversions. Outdoor sunlight curing revealed that all thiol-modified networks were tack-free after only several minutes depending on thiol functionality. In contrast, the pure acrylate membrane remained tacky and uncured on the surface indefinitely. This study emphasizes the importance of thiol monomer selection in diminishing oxygen inhibition in UV-initiated acrylate polymerization as well as marked improvement in permeability for this specific PEGDA network via the incorporation of dithiols.
169: Effect of Intracorporeal Ventricular Assist Devices on the Risk of Mortality or Retransplantation Following Cardiac Transplantation – An Analysis of the United Network for Organ Sharing (UNOS) Registry

Purpose: To explore the effect of intracorporeal ventricular assist devices (VAD) on mortality or retransplantation (ReTx) following cardiac transplantation. Methods and Materials: Data from UNOS registry of patients aged 18 years who underwent first time single organ heart transplant in the US between 1/1/95-12/31/2004 were analyzed. UNOS status 1 patients supported with a Novacor or Heartmate VAD (group 1) were compared with UNOS status 1 patients without VAD support (group 2). A Cox model was used to compare the risk of death or ReTx between the groups. Since proportional hazards assumption was not met, hazard ratios (HR) are presented for different time periods. Analysis was adjusted for variables known to affect post-transplant outcome. Results: There were 1,433 patients in group 1 and 9,455 patients in group 2. 394(27%) patients died and 8(1%) were retransplanted in group 1. 3,077(33%) patients died and 106(1%) were retransplanted in group 2. The HR for death or ReTx as a function of time after transplant is presented in the table. There was no significant difference in the risk of death or ReTx between the groups in the first 60 months after transplant. Group 1 had a HR of 1.95 (95%CI: 1.42-2.67) beyond 60 months. Conclusions: There is no increase in risk of death or ReTx with the use of intracorporeal VADs during the first 60 months post-transplant. However, these data suggest an increase in the risk of these outcomes after 60 months. The reasons for this increase in late mortality will require further investigation.
Animalism and the varieties of conjoined twinning

We defend the view that we are not identical to organisms against the objection that it implies that there are two subjects of every conscious state one experiences: oneself and one’s organism. We then criticize animalism—the view that each of us is identical to a human organism—by showing that it has unacceptable implications for a range of actual and hypothetical cases of conjoined twinning: dicephalus, craniopagus parasiticus, and cephalopagus.
Leadership Functions and Instructional Effectiveness

This article describes what in structional leaders should be doing in light of recent re search on teacher and school effee tiveness.
Pharmacological Management of Chronic Viral Hepatitis

Chronic viral hepatitis is a worldwide health problem. Complications associated with chronic viral hepatitis include liver failure, cirrhosis and hepatocellular carcinoma. The disease often is asymptomatic, but malaise, weakness and fatigue can occur. Alfa-inter-feron (α-IFN) is the only treatment with proven benefit in chronic viral hepatitis. Common adverse physical and psychiatric effects of therapy are described. The efficacy, however, varies widely. In chronic hepatitis B, α-IFN improves liver aminotransferases and histology, and leads to loss of viral replication in 25–40% of patients. Nucleoside analogues are being evaluated as an alternative treatment. In chronic hepatitis C, α-IFN leads to improvement in liver aminotransferases and histology, and clearance of HCV RNA in 10–25% of patients. The new treatment under investigation is a combination of α-IFN and ribavirin. In chronic hepatitis D, prolonged treatment using similar dosing regimens of α-IFN in chronic hepatitis B result in clearance of HD...
Community Revitalization in Post-Katrina New Orleans: A Critical Analysis of Social Capital in an African American Neighborhood

ABSTRACT This research explored the role of social capital, particularly civic engagement and social trust, in community revitalization efforts in a primarily African American post-Katrina neighborhood (n = 153). Findings reveal high levels of participation in neighborhood and political activities but low levels of social trust. Eighty-four percent of this primarily African American sample reported that they do not trust people of other races as compared to 23 to 32% of African American respondents in the national study. Drawing from critical theoretical perspectives, we offer a critique of the limits of social capital theory as well as a discussion of the importance of building social and racial trust as central components of community development practice. Implications include emphasizing organizational capacity-building activities, community organizing training, and racial reconciliation efforts in post-disaster environments.
Processing-structure-functional property relationship in organic-inorganic nanostructured scaffolds for bone-tissue engineering: the response of preosteoblasts.

We elucidate here for the first time the structure–processing–functional property relationship in chitosan (CS)-based scaffolds, where molecular machinery governing proliferation and growth of osteoblasts is mediated by nanostructured carbon. The interconnected network structure of organic–inorganic scaffolds was obtained by covalent linkage of carboxyl group of functionalized single-walled carbon nanohorn with the amine group of CS. The molecular-scale dispersibility of functionalized nanostructured carbon was an important physicochemical factor influencing cellular interactions and biological response. Furthermore, it was beneficial in promoting the biocompatibility and the degradation product of the scaffolds. The hydrophilicity, good water retention ability, and interconnected porous structure of organic–inorganic scaffolds enabled pronounced cell attachment and proliferation and enhanced the stability toward enzymatic degradation. The infiltration of cells and colonization of the pores of the scaffolds and cellular interactions were promoted due to covalent linkage of nanostructured carbon with CS. Additionally, the interconnectivity of porous scaffolds facilitated cells to infiltrate inside the pores of CS-nanostructured scaffolds, implying that nanostructured carbon merits consideration in tissue engineering. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3080–3091, 2012.
Solid-state structure of bis(2,3,4-trimethylpentadienyl)iron

Abstract The solid-state structure of bis(2,3,4-trimethylpentadienyl)iron, Fe(2,3,4-C8H13)2, has been determined by single crystal X-ray diffraction. The space group is Ci1-P 1 (No. 2) with unit cell parameters being a 9.442(3), b 11.212(3), c 7.743(3) A, α 101.38(3), β 116.29(3), γ 89.77(2)°, and V 717.3(4) A3 for Z = 2. Final agreement indices of R = 0.046 and Rw = 0.051 were obtained for the 1998 unique reflections judged to be above background. Even with substantially increased ligand-ligand repulsions relative to its isomorphous ruthenium analog, the complex has also been found to exist in a distorted gauche-eclipsed structure. The average FeC bond distance of 2.087(1) A compares well with the value of 2.089(3) A in Fe(2,4-C7H11).
Remyelination within the CNS: Do Schwann Cells Pave the Way for Oligodendrocytes?

Schwann cells that have myelinated the CNS can be replaced by myelinating oligodendrocytes. It is unclear, however, why oligodendrocyte remyelination would occur for axons that are already myelinated. The Schwann cells might signal their own replacement by oligodendrocytes, but more probably a third player, the reactive astrocyte, is essential to this phenomenon. We propose that as long as reactive astrocytes do not form fibrous gliosis, they are beneficial to oligodendrocyte remyelination. Unknown is whether reactive astrocytes induce oligodendrocyte progenitor (NG2 immunopositive cells) cells to differentiate, a phenomenon that is absent in multiple sclerosis. So what role do Schwann cells play in CNS remyelination? They appear to serve to protect central axons and might coincidentally prevent reactive astrocytes from laying down scar tissue that impedes oligodendrocyte remyelination.
Serum steroid hormones including 11-ketotestosterone, 11-ketoandrostenedione, and dihydroprogesterone in juvenile and adult bonnethead sharks, Sphyrna tiburo.

Previous studies in the placental viviparous bonnethead shark, Sphyrna tiburo, have correlated 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone with reproductive events in both males and females. However, several key reproductive events, including implantation, maintenance of pregnancy, and parturition, did not correlate with these four steroid hormones. Therefore, the present study investigated three steroid hormones, 11-ketotestosterone, 11-ketoandrostenedione, and dihydroprogesterone, which have demonstrably important roles in the reproductive cycles of teleosts. It was hypothesized that one or more of these three hormones would correlate with specific reproductive events in S. tiburo. Concurrently, developmental (growth and/or maturation) analyses of these three steroids plus 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone were investigated in juvenile bonnethead sharks. Serum dihydroprogesterone concentrations were highest in mature females and 11-ketotestosterone concentrations were highest in mature males. In mature females, 11-ketoandrostenedione levels were elevated from the time of mating, through six months of sperm storage and another four months of gestation. At parturition concentrations became significantly lower and remained lower until mating occurred again in another two to three months. Serum 11-ketotestosterone concentrations were the highest at implantation though not significant. In mature males, significantly elevated serum levels of dihydroprogesterone occurred in April and May, near the start of annual testicular development. During growth in males, testosterone and dihydrotestosterone increased progressively and in females, testosterone increased progressively. At maturity in males, significant increases occurred in testosterone and 11-ketotestosterone concentrations while, in females, dihydroprogesterone, 11-ketotestosterone, 17 beta-estradiol, progesterone, testosterone, and dihydrotestosterone concentrations increased. This study shows that although testosterone may be the primary androgen in the bonnethead shark, other derived androgens may have important functions in growth, maturation, and reproduction. J. Exp. Zool. 284:595-603, 1999.
Response feedback triggers long-term consolidation of perceptual learning independently of performance gains

Visual perceptual learning (VPL) is defined as a long-term performance enhancement on a visual task, and is typically thought of as a manifestation of plasticity in visual processing. It is thought that neural representations relevant to a recently learned task are consolidated over the course of hours or days and made robust against the effects of deterioration and interference. However, recent work has shown that when these representations are reactivated by further task exposure, they become plastic again and are vulnerable to deterioration effects. Here we used a perceptual learning paradigm in combination with performance feedback (knowledge of task accuracy provided to the observer in real-time) to investigate behavioral factors that influence consolidation. Subjects were trained to detect two coherent motion directions embedded in noise over several days. It was found that without feedback, performance improvements accrued during training rapidly deteriorated upon exposure to novel, neighboring motion directions. However, when one of the two directions was consistently paired with feedback during training, the paired direction was resilient against the effects of deterioration. This benefit coincides with a gradual inhibition of learning for the unpaired stimuli. Furthermore, this stabilizing effect operates independently of the magnitude of performance gains during training and suggests a useful behavioral marker for the study of consolidation processes.
Reproductive coercion and co-occurring intimate partner violence in obstetrics and gynecology patients.

Objective Reproductive coercion is male behavior to control contraception and pregnancy outcomes of female partners. We examined the prevalence of reproductive coercion and co-occurring intimate partner violence among women presenting for routine care at a large, urban obstetrics and gynecology clinic. Study Design Women aged 18-44 years completed a self-administered, anonymous survey. Reproductive coercion was defined as a positive response to at least 1 of 14 questions derived from previously published studies. Women who experienced reproductive coercion were also assessed for intimate partner violence in the relationship where reproductive coercion occurred. Results Of 641 women who completed the survey, 16% reported reproductive coercion currently or in the past. Among women who experienced reproductive coercion, 32% reported that intimate partner violence occurred in the same relationship. Single women were more likely to experience reproductive coercion as well as co-occurring intimate partner violence. Conclusion Reproductive coercion with co-occurring intimate partner violence is prevalent among women seeking general obstetrics and gynecology care. Health care providers should routinely assess reproductive-age women for reproductive coercion and intimate partner violence and tailor their family planning discussions and recommendations accordingly.
Information as a National Resource

“For national decision makers, no better alternative is at hand than to accept the unifying concept of information and to undertake the planning of communications policies by doing resource analysis.”
Full Size Fatigue Crack-Growth Testing for Girth Welds

Fatigue crack-growth modeling has a significant impact in establishing defect acceptance criteria for the inspection of fracture-critical, girth-welded components, such as risers and tendons. ExxonMobil has developed an experimental technique to generate crack-growth data, in actual welded tubulars, that account for the particular material properties, geometry, and residual stresses. The technique is fully compatible with conventional fracture mechanics models. It uses a series of pre-designed notches made around the welds on a production quality, full-scale specimen that is tested efficiently in a resonant fatigue setup. The crack development from notches is monitored during testing and evaluated post-mortem. Given its simplicity and high loading frequency, the technique provides growth data germane to the component at hand at a lower cost and faster than standard, small-scale tests.Copyright © 2004 by ASME
Emotional considerations in familial polyposis.

A LTHOUGH a great deal of literature covers the genetics, diagnosis, and treatment of familial multiple polyposis, there are no reports of concurrent emotional difficulties. The following is a summary of the diagnostic and treatment considerations of this disease, followed by a case study of an unusual young man with depression, bisexuality, and familial polyposis. The conflict between the definitive surgical treatment and the patient’s opposition is then considered. This patient is a caricature of the emotional difficulties that all patients with familial polyposis face. Familial polyposis is a rare hereditary disease characterized by varying numbers of adenomatous polyps originating from the mucosa of the colon and rectum. The disease has an estimated frequency of one in 8300 births’ and is transmitted as an autosomal dominate trait.2 In the majority of cases, the onset of the disease is between the ages of 10 and 40. If untreated, the polyps undergo carcinogenic degeneration and death ensues.3 The disease must be differentiated from the pseudopolyposis accompanying ulcerative colitis and the other forms of hereditary polyposis which do not necessarily have the same premalignant disposition.p These other genetically distinct syndromes include: (A) Gardner’s Syndrome (premalignant polyposis of the colon associated with skin tumors and osteomata); (B) Turcot’s Syndrome (colonic polyposis associated with brain tumor); and (C) Peutz-Jegher’s Syndrome (nonpremalignant polyposis mainly of, but not limited to, the small intestine and associated with melanotic spots of the hands and buccal mucosa).5 Once the diagnosis has been confirmed by barium enema, sigmoidoscopy, and biopsy, the question of treatment arises. Historically, there have been two schools of thought regarding the optimal therapy of this disorder. Members of the more conservative school recommend colectomy, ileoproctostomy, and frequent follow-up to guard against carcinogenic degeneration in the remaining terminal segment.6*7 Adherents of the other school recommend total proctocolectomy and ileostomy to ensure the removal of all polyp-forming mucosa.“pg Recent studies support the latter school in that approximately 5% of the patients treated by the first method go on to develop carcinoma of the terminal segment.7*10-12 In addition, a significant number of patients are lost to follow-up over the years.‘O Thus, total extirpation with ileostomy is the treatment of choice and especially in any patient thought to be unreliable for follow-up.‘3,‘” Familial polyposis is a potentially fatal disease that is curable though the use of
Partitioning-defective Protein 6 (Par-6) Activates Atypical Protein Kinase C (aPKC) by Pseudosubstrate Displacement

Atypical protein kinase C (aPKC) controls cell polarity by modulating substrate cortical localization. Aberrant aPKC activity disrupts polarity, yet the mechanisms that control aPKC remain poorly understood. We used a reconstituted system with purified components and a cultured cell cortical displacement assay to investigate aPKC regulation. We find that aPKC is autoinhibited by two domains within its NH2-terminal regulatory half, a pseudosubstrate motif that occupies the kinase active site, and a C1 domain that assists in this process. The Par complex member Par-6, previously thought to inhibit aPKC, is a potent activator of aPKC in our assays. Par-6 and aPKC interact via PB1 domain heterodimerization, and this interaction activates aPKC by displacing the pseudosubstrate, although full activity requires the Par-6 CRIB-PDZ domains. We propose that, along with its previously described roles in controlling aPKC localization, Par-6 allosterically activates aPKC to allow for high spatial and temporal control of substrate phosphorylation and polarization.
Microbiologic and pharmacodynamic principals applied to the antimicrobial susceptibility testing of ampicillin/sulbactam: Analysis of the correlations between in vitro test results and clinical response

The correlation between various ampicillin/sulbactam in vitro antimicrobial susceptibility test results and the clinical outcome of patients treated with this agent have been examined. A survey of over 29,000 clinical isolates of the family Enterobacteriaceae found that the proportion of susceptible pathogens as assessed by current susceptibility testing interpretive guidelines (NCCLS) for disk diffusion and dilution (MIC) assays was significantly less than the proportion of patients cured or clinically improved in ampicillin/sulbactam clinical trials. Also, the results of two NCCLS methods differ greatly in the perceived percentages of susceptible strains (63.9% versus 72.2%; unacceptable variation). Furthermore, the current interpretive criteria resulted in high false-susceptible (4.2%) and total (19.7%) error rates. When proposed interpretive guidelines were applied, approximately 73 to 87% of the Enterobacteriaceae strains were observed to be susceptible, the variation between methods was minimized, and the error rates were reduced. A retrospective analysis of data from clinical trials with ampicillin/sulbactam indicated that the proportion of patients who were cured or clinically improved and bacterially eradicated was not appreciably different in patients having baseline Enterobacteriaceae pathogens with MICs of 16 or 32 micrograms/ml (ampicillin MIC component) as compared to those with pathogens having MICs of or = 14 mm) as susceptible and > or = 64/32 micrograms/ml ( or = 18 mm) as susceptible and > or = 32/32 micrograms/ml ( or = 14 mm) as susceptible and > or = 64/64 micrograms/ml (< or = 10 mm) as resistant; e.g., 84.7 to 86.9% spectrum and 1.3% false-susceptible error. Data from a comprehensive in vitro survey of clinical isolates, retrospective analyses of clinical trials, and studies of animal models support the modification of contemporary interpretive guidelines for ampicillin/sulbactam antimicrobial susceptibility tests. The best short-term criteria would apply current in vitro diagnostic reagents and a modified susceptible breakpoint (< or = 16/8 micrograms/ml as susceptible; option 1 above) until new diagnostic reagents can be qualified by means of studies needed for quality assurance of standardized methods (NCCLS M23-A and FDA procedures). These changes would provide a better in vitro prediction of ampicillin/sulbactam efficacy in clinical practice.
Th2 Cytokines in Skin Draining Lymph Nodes and Serum IgE Do Not Predict Airway Hypersensitivity to Intranasal Isocyanate Exposure in Mice

Isocyanate exposure in the workplace has been linked to asthma and allergic rhinitis. Recently, investigators have proposed that Th2 cytokine responses in lymph nodes draining the site of dermal application of chemicals including isocyanates may be used to identify sensitizers that cause asthma-like responses. The purpose of this study was to determine if the cytokine profile induced after dermal sensitization with isocyanates and serum IgE predict immediate (IHS) and methacholine-induced late (LHS) respiratory hypersensitivity responses after intranasal challenge. Dermal application of hexylmethane diisocyanate (HMDI), toluene diisocyanate (TDI), or methylene diisocyanate (MDI) significantly increased interleukin-4 (IL-4), IL-5, and IL-13 secretion in parotid lymph node cells. Isophorone diisocyanate (IPDI) increased IL-4 and IL-13, but not IL-5. Tolyl(mono)isocyanate (TMI), tetramethylene xylene diisocyanate (TMXDI), or the contact sensitizer dinitrochlorobenzene (DNCB), only induced minor increases in some of the Th2 cytokines. HMDI, TDI, MDI, and IPDI elicited greater increases in total serum IgE than DNCB, TMI, and TMXDI. All chemicals except TMXDI caused IHS after intranasal challenge of sensitized female BALB/c mice. Only HMDI-, TMI-, or TMXDI-sensitized and challenged mice had increases in LHS. All chemicals elicited epithelial cytotoxicity indicative of nasal airway irritation. The discordance between dermal cytokine profiles and respiratory responses suggests that dermal responses do not necessarily predict respiratory responses. Serum IgE also was not predictive of the respiratory responses to the isocyanates, suggesting that other unknown mechanisms may be involved.
Agency Problems and Endogenous Investment Fluctuations

This article proposes a theory of investment fluctuations in which the source of the oscillating dynamics is an agency problem between financiers and entrepreneurs. In the model, investment decisions depend on entrepreneurs' initiative to select investment projects ex ante, and financiers' incentive to control entrepreneurs ex post. Too much control discourages entrepreneurial incentive to initiate new investment, whereas too little control jeopardizes its productivity. This initiative-control trade-off is capable of generating endogenous reversal of investment booms, induced by an ongoing deterioration of project profitability. Investment fluctuations may arise even though no external shocks hit the economy and agents are perfectly rational. The Author 2012. Published by Oxford University Press on behalf of The Society for Financial Studies. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com., Oxford University Press.
The source of dual-task limitations: Serial or parallel processing of multiple response selections?

Although it is generally recognized that the concurrent performance of two tasks incurs costs, the sources of these dual-task costs remain controversial. The serial bottleneck model suggests that serial postponement of task performance in dual-task conditions results from a central stage of response selection that can only process one task at a time. Cognitive-control models, by contrast, propose that multiple response selections can proceed in parallel, but that serial processing of task performance is predominantly adopted because its processing efficiency is higher than that of parallel processing. In the present study, we empirically tested this proposition by examining whether parallel processing would occur when it was more efficient and financially rewarded. The results indicated that even when parallel processing was more efficient and was incentivized by financial reward, participants still failed to process tasks in parallel. We conclude that central information processing is limited by a serial bottleneck.
ECOLOGICAL RESISTANCE TO BIOLOGICAL INVASION OVERWHELMED BY PROPAGULE PRESSURE

Models and observational studies have sought patterns of predictability for invasion of natural areas by nonindigenous species, but with limited success. In a field experiment using forest understory plants, we jointly manipulated three hypothesized determinants of biological invasion outcome: resident diversity, physical disturbance and abiotic conditions, and propagule pressure. The foremost constraints on net habitat invasibility were the number of propagules that arrived at a site and naturally varying resident plant density. The physical environment (flooding regime) and the number of established resident species had negligible impact on habitat invasibility as compared to propagule pressure, despite manipulations that forced a significant reduction in resident richness, and a gradient in flooding from no flooding to annual flooding. This is the first experimental study to demonstrate the primacy of propagule pressure as a determinant of habitat invasibility in comparison with other candidate controlling factors.
The Design and Implementation of a Smart Building Control System

A significant proportion of total worldwide energy is consumed by buildings. For example, buildings in the US account for about 40 percent of total energy consumption and greenhouse gas emission. Making buildings more energy-efficient is an important step to reduce our energy consumption and carbon emission in the combat with global climate change. Broad participation by consumers, business owners, and governments is required to continuously improve on energy efficiency for new and existing buildings and to achieve the global greenhouse gas emission reduction objectives. This paper provides a software system perspective of improving energy efficiency for buildings. It proposes an architecture that allows for phased investments in technologies to capture the returns from energy savings in various use cases. In addition, it addresses the needs and objectives of different stakeholders, including owners, operators, users, and utility providers. A proof-of-concept implementation of the architecture is used to demonstrate the support for building-wide energy conservation policies using real-time energy pricing and individual occupants’ locations and preferences. It shows that the proposed architecture enables fine-grained building control and reduces energy consumption while maximizing its occupants’ comfort.
Effect of DOCA/salt hypertension on CRF expression in the amygdala and the autonomic stress response in conscious rats.

Abstract The effects of DOCA/salt treatment on amygdala-area CRF gene expression and the autonomic response to air jet stress (AJS) were evaluated in conscious male Sprague Dawley (SD) rats. Fifteen days of DOCA/salt treatment significantly increased resting arterial pressure (AP), decreased resting heart rate (HR) and significantly reduced regional CRF mRNA compared to controls (23 ± 7% vs. 100 ± 26%) independent of changes in regional CRF receptor expression. Twenty min of AJS elicited a rise in AP (~ 15 mm Hg) that was similar in both DOCA/salt animals (n = 11) and controls (n = 6). Alternatively, increases in HR were significantly different in the DOCA/salt animals compared to controls; including one group of DOCA/salt animals (n = 5) which responded with an attenuated HR response at the onset of AJS (low-responders) and a second group (n = 6) which demonstrated an elevated HR response to AJS (high-responders), specifically during the last 10 min of AJS. The divergent HR responses to AJS in the DOCA/salt animals were linked to differences in resting heart rate variability. During recovery HR returned to baseline within 10 min in both control and the low responder DOCA group but indicators of spontaneous baroreflex gain only increased significantly in controls. HR in the high-responder DOCA animals did not return to baseline during the same period. These results show that DOCA/salt treatment triggers downregulation of CRF gene expression in the region of the amygdala and significantly alters the HR response to acute stress but does not alter the pressor response to stress compared to normotensive controls.
Nucleic acid testing for tuberculosis at the point-of-care in high-burden countries

Early diagnosis of tuberculosis (TB) facilitates appropriate treatment initiation and can limit the spread of this highly contagious disease. However, commonly used TB diagnostic methods are slow, often insensitive, cumbersome and inaccessible to most patients in TB endemic countries that lack necessary resources. This review discusses nucleic acid amplification technologies, which are being developed for rapid near patient TB diagnosis, that are in the market or undergoing clinical evaluation. They are based on PCR or isothermal methods and are implemented as manual assays or partially/fully integrated instrument systems, with associated tradeoffs between clinical performance, cost, robustness, quality assurance and usability in remote settings by minimally trained personnel. Unmet needs prevail for the identification of drug-resistant TB and for TB diagnosis in HIV-positive and pediatric patients.
Socioeconomic status and HIV seroprevalence in Tanzania: a counterintuitive relationship

Objective To examine the relationship between multiple dimensions of socioeconomic status (SES) and HIV seroprevalence in Tanzania. Methods Using a large nationally representative sample of 7515 sexually active adults drawn from the 2003–04 Tanzania HIV/AIDS Indicator Survey, we analysed the relationship between multiple SES measures and HIV seroprevalence using weighted logistic regression models. Results In adjusted models, individuals in the highest quintile of standard of living had increased odds ratio (OR) of being HIV-positive (male: OR 2.38, 95% CI 1.17–4.82; female: OR 3.74, 95% CI 2.16–6.49). Occupational status was differentially associated with HIV in men and women; women in professional jobs had higher OR of being HIV-positive (OR 1.54, 95% CI 1.02–2.38), whereas unemployed men had higher risk of being HIV-positive (OR 3.49, 95% CI 1.43–8.58). No marked association was found between increasing education and HIV seroprevalence for men (P = 0.83) and women (P = 0.87). Conclusion Contrary to the prevailing perception that low SES individuals tend to be more vulnerable to HIV-infection, we found a positive association between standard of living and HIV-infection. Strategies aimed at reducing HIV-infection needs to be cognizant of the complex social heterogeneity in the patterns of HIV-infection.
Constructive Conflict Management and Coping in Homeless Children and Adolescents.

In this largely exploratory study of the conflict management and coping behavior of homeless adolescents, the authors interviewed 176 families (mother-adolescent dyads) living in New York City welfare hotels. Results indicated that peer conflict was the “worst” problem of the previous month as reported by approximately 50% of these youth. Homeless adolescents demonstrated conflict management and coping patterns that differed in certain respects from adolescent patterns previously described in the literature. The implications of these differences as well as directions for future research are discussed.
On relaxation-spectrum estimation for decades of data: accuracy and sampling-localization considerations

In the inversion of data using the relaxation-spectrum model of electrical and rheological phenomena and processes, an important goal is to obtain a comprehensive and accurate approximation of the distribution of relaxation times (DRT) associated with the phenomenon or process under investigation. The estimation of such a DRT poses theoretical as well as experimental challenges. In the latter, it is often necessary to measure many decades of frequency-response data before sufficient information has been collected to allow an adequate estimate of the structure of the required spectrum to be calculated. At the theoretical level, among other things, one must solve the inverse problem of the relaxation-spectrum estimation, along with the frequent need to work with many decades of data. Some consequences of these two aspects of the problem are examined in this paper. In order to address this problem, accurate (or noisy), wide-range frequency-response data sets derived from the Kohlrausch-Williams-Watts (KWW) continuous DRT function (with a value of its β0 parameter of 0.5) are inverted numerically using a complex nonlinear least-squares method with variable τ free parameters and variable quadrature weighting, a method superior to Tikhonov regularization for data of the present type when inversion accuracy need not be sacrificed for increased resolution. The relative errors in the resulting DRT point estimates are investigated for various frequency ranges for both frequency-response data derived from the usual KWW DRT and from such a DRT which is abruptly cut off at its low τ end. Although the inversions are ill-posed, DRT errors were found to be very small over appreciable τ ranges, but the effects of cutoff of the range of the DRT and of a limited frequency range led to rapid relative-error increases at the ends of the DRT τ range, and allowed separation and quantification of the effects of these two limitations. Important resolution differences are illustrated between the results of inversions of accurate and of noisy data by the present method and by Tikhonov regularization. Finally, the temporal response was calculated very simply from frequency-response inversion DRT estimates and compared with exact stretched-exponential response function values associated with the KWW dispersion model. Extremely small relative errors were found, but they nevertheless showed the effects of the above limitations at short and long times. Transformation to the time domain of the kind illustrated here for wide-range data is far simpler, more accurate, and more convenient than Fourier transformation.
Computing transients on transmission lines in teaching electromagnetics

Two schemes for computing reflections and transients on transmission lines are presented. The first consists of a recursive algorithm and the second uses spreadsheets. These form suitable material for an undergraduate class and have the merit of exciting the interest of undergraduates by enhancing the role of computer-assisted instruction. >