cssi/SciSciGPT-SciSciNet huggingface dataset:
Neuronal ion-channel dynamics in silicon

We present a simple silicon circuit for modelling voltage-dependent ion channels found within neural cells, capturing both the gating particle's sigmoidal activation (or inactivation) and the bell-shaped time constant. In its simplest form, our ion-channel analog consists of two MOS transistors and a unity-gain inverter. We present equations describing its nonlinear dynamics and measurements from a chip fabricated in a 0.25 /spl mu/m CMOS process. The channel analog's simplicity allows tens of thousands to be built on a single chip, facilitating the implementation of biologically realistic models of neural computation.
The Community of Scholars and the Culture of Silence

(1992). The Community of Scholars and the Culture of Silence. Journal of Architectural Education: Vol. 46, No. 2, pp. 124-126.
Observation of Four Age‐Related Parameters in the Red Cells of Various Disease States

Simultaneous determinations of anaerobic glycolysis, hexokinase activity (HxK), glucose-6-phosphate dehydrogenase activity (G6PD) and acetyl-cholinesterase activity (AChE) were made in the whole red cell populations of patients and of healthy subjects, and in the layers of the centrifuged cell packs of selected patients to give regression lines for each parameter plotted against each of the others. Apparently normal interrelationships were found in blood loss and in haemolytic disease of various origins. Abnormalities were revealed which would escape notice if a single parameter were assayed. These were relative, not absolute, deficiency of anaerobic glycolysis in a case of congenital nonspherocytic haemolytic disease with no deficiency of G6PD, HxK or pyruvate kinase; of HxK in a case of unexplained anaemia; and of AChE in a case of Coombs positive haemolytic disease. In a case of paroxysmal nocturnal haemoglobinuria AChE was severely deficient while glycolysis, HxK and G6PD were extraordinarily high and appeared normally interrelated. The patient had been transfused just before these studies, and calculations based on the enzyme data led to the hypothesis that in this case the donor cells were rapidly destroyed. Observations in normal blood showed that values for G6PD and AChE occur as two independent normal distributions. The same was true for glycolysis and AChE. Glycolysis and G6PD were correlated but did not approach a perfect functional relationship. There is evidence that high G6PD unrelated to red cell age occurs in malignant disease, but it is not conclusive.
Knudsen's cosine law and random billiards

This article lays the groundwork for understanding the details of gas transport in the so-called Knudsen regime, particularly during the early, nonstationary stages of the transport process. A simple mathematical model of gas–surface interaction is introduced, which is both fairly general and sufficiently explicit to permit a detailed analysis. The model, which we call a random billiard, is an example of a random dynamical system based on the idea of a billiard system with geometric microstructure. Among the main results, we show that Knudsen's cosine law is a stationary probability distribution of post-collision velocities, although not always the unique one. Through numerical experiments with a variety of microgeometries we also provide some insight concerning the approach to stationarity.
Permanent HBsAg clearance in chronic hepatitis B viral infection following acute delta superinfection.

Three patients are described with chronic hepatitis B virus infection for three to six years before hepatitis delta virus superinfection occurred. Liver biopsy performed in two patients prior to their delta illness revealed chronic persistent hepatitis and chronic active hepatitis, respectively. Within one to seven months of the acute delta event, all three patients lost their circulating hepatitis B surface antigen. Subsequently, delta antibody also cleared. Clinical well-being and normal transaminases were documented over 10–44 months of follow-up. Although most cases of delta infection in chronic hepatitis B result in severe or progressive disease, a small number of patients may develop clearance of the HBsAg with clearance of both B and delta infections.
Insertion of the Polytopic Membrane Protein MalF Is Dependent on the Bacterial Secretion Machinery

Abstract We examined the dependence of protein export and membrane protein insertion on SecE and SecA, two components of the secretion (Sec) apparatus of Escherichia coli. The magnitude of the secretion defect observed for signal sequence-containing proteins in cells depleted of SecE is larger and more general than that in many temperature- or cold-sensitive Sec mutants. In addition, we show that the proper insertion of the polytopic MalF protein (synthesized without a signal sequence) into the cytoplasmic membrane is also SecE-dependent. In contrast to an earlier study (McGovern, K., and Beckwith, J.(1991) J. Biol. Chem. 266, 20870-20876), the membrane insertion of MalF also is inhibited by treatment of cells with sodium azide, a potent inhibitor of SecA. Therefore, our data strongly suggest that the cytoplasmic membrane insertion of MalF is dependent on the same cellular machinery as is involved in the export of signal sequence-containing proteins. We propose that the mechanism of export from the cytoplasm is related for both signal sequence-containing and cytoplasmic membrane proteins, but hydrophobic membrane proteins such as MalF may have a higher affinity for the Sec apparatus.
Vasoconstrictor and norepinephrine potentiating action of 5-hydroxykynuramine in the isolated perfused rat kidney: involvement of serotonin receptors and alpha1-adrenoceptors

Kynuramines are endogenously occurring diamines derived from tryptophan. In the present study, we have compared the pharmacological actions of 5-hydroxykynuramine (5-OH-K) with kynuramine and 5-hydroxytryptamine (5-HT) on vascular resistance changes and responsiveness to adrenergic stimuli in the isolated perfused rat kidney. 5-OH-K was found to mimic the actions of 5-HT in that it produced vasoconstriction, potentiation of alpha1-adrenoceptor-mediated responses to norepinephrine (NE) and periarterial nerve stimulation and displaced specific [3H]spiroperidol binding from rat cortical membranes. With regard to all parameters measured, 5-OH-K was about 15-times less active than 5-HT. Vascular responses to 5-OH-K and 5-HT were inhibited noncompetitively by ketanserin and cyproheptadine. Unlike 5-OH-K, kynuramine, failed to evoke vasoconstriction and Inhibited vascular responses to NE via alpha1-adrenoceptors. Thus, kynuramine lacks serotonin receptor agonist activity but possesses alphaI-adrenoceptor blocking properties. In contrast, 5-OH-K potentiates NE and acts as a serotonin agonist. The present results raise the possibility that kynuramine and 5-OH-K might act as endogenous modulators of serotonergic and adrenergic mechanisms in the renal vascular bed.
Pediatric response to a large-scale child protection intervention

OBJECTIVE: In a rural area of the US state of Texas, in April 2008, the Texas Department of Family and Protective Services (DFPS) responded to evidence of widespread child abuse in an isolated religious compound by removing 463 individuals into state custody. This mass child protection intervention is the largest such action that has ever occurred in the United States. The objective of this paper is to characterize the burdens placed on the area's community resources, healthcare providers, and legal system, the limitations encountered by the forensic and public health professionals, and how these might be minimized in future large-scale child protection interventions. METHODS: Drawing on publicly available information, this article describes the child abuse investigation, legal outcomes, experiences of pediatric healthcare providers directly affected by the mass removal, and the roles of regional child abuse pediatric specialists. RESULTS: Because the compound's residents refused to cooperate with the investigation and the population of the compound was eight times higher than expected, law enforcement and child protection resources were insufficient to conduct standard child abuse investigations. Local medical and public health resources were also quickly overwhelmed. Consulting child abuse pediatricians were asked to recommend laboratory and radiologic studies that could assist in identifying signs of child abuse, but the lack of cooperation from patients and parents, inadequate medical histories, and limited physical examinations precluded full implementation of the recommendations. CONCLUSIONS: Although most children in danger of abuse were removed from the high-risk environment for several months and some suspected abusers were found guilty in criminal trials, the overall success of the child protection intervention was reduced by the limitations imposed by insufficient resources and lack of cooperation from the compound's residents. PRACTICE IMPLICATIONS: Recommendations for community and child abuse pediatricians who may become involved in future large child-protection interventions are presented. Language: en
By your attributions you shall be known: Consequences of attributional accounts for professional and gender identities

We demonstrate the power of a situated identity perspective for understanding the different attributional patterns of women and men in an academic setting and their differential experiences in the workplace. Two explanations for the gender difference found in attributions of success are considered. This difference may be due either to different identities being attributed to men and women employing the same explanations for success and failure, or to the inconsistency between actions that confirm a professional (academic) identity and women's gender identity. The results of this survey of senior social science faculty men support the latter explanation but not the former. An editorial acceptance was seen as more professional but less feminine than a rejection. In the eyes of senior colleagues, the modest account of success, typical of women academics, enhances femininity but detracts from professionalism. The self-serving account typical of men makes the offerer appear less feminine but more professional. Thus in their situated identity claims, successful academic women, but not men, must choose between their professional and gender identities. Despite the movement of women into university social science positions, the role of academic has a masculine face.
Paraneoplastic T cell lymphocytosis associated with a thymoma in a dog

A four-year-old male neutered Australian shepherd dog was diagnosed with a thymoma and concurrent mature T cell lymphocytosis. The lymphocytosis consisted of a mixed population of T cells expressing either CD4 or CD8 or neither marker, and the result of polymerase chain reaction for antigen receptor rearrangement was negative. The peripheral lymphocytosis resolved within 24 hours following thoracotomy and thymectomy. Similar cases have been reported in man, but the aetiology of the increased circulating lymphocytes remains unclear. Although peripheral lymphocytosis is an uncommon paraneoplastic syndrome associated with thymomas, thymoma should be considered as a differential when the increased lymphocytes consist of a mixed population of T cells.
A comparison of treatment results in complete bilateral cleft lip and palate using a conservative approach versus millard-latham PSOT procedure

Conservative non—presurgical orthopedic treatment in complete bilateralcleft lip and palate (CBCLP) cases were compared with those treated will the Millard-Latham (M-L) method, which involves the presurgical mechanical retraction of the protruding premaxilla using pinned palatal appliances. In conservatively treated cases, a head bonnet with an external elastic is sometimes used before surgical lip closure to ventroflex the premaxilla thereby reducing tension at the surgical sites. The M-L method involves premaxillary bodily retraction followed by a gingivo-periosteoplasty. In both series of cases the palatal cleft (hard and soft) is closed for patients aged 18 to 30 months using a modified von Langenbeck procedure. A secondary alveolar bone graft is only performed in the conservatively treated series for patients aged 7 to 9 years. Although the premaxilla in 2 of 29 conservatively treated cases were retruded and in anterior crossbite by 10 to 12 years of age, all M-L cases were retruded by 9 years of age requiring maxillary protraction. In the M-L cases 90% showed bony bridging of the alveolar cleft with frequent loss of the lateral incisor space; surgical closure of the nasal floor is facilitated, and early aesthetic improvement is followed by midfacial retrusion.
Cyclohexanedione herbicides are inhibitors of rat heart acetyl-CoA carboxylase

Acetyl CoA carboxylase (ACC) catalyzes the carboxylation of acetyl CoA to form malonyl CoA. In skeletal muscle and heart, malonyl CoA functions to regulate lipid oxidation by inhibition of carnitine palmitoyltransferase-1, an enzyme which controls the entry of long chain fatty acids into mitochondria. We have found that several members of the cyclohexanedione class of herbicides are competitive inhibitors of rat heart ACC. These compounds constitute valuable reagents for drug development and the study of ACCβ, a validated anti-obesity target.
Crossing the blood-brain barrier: are we getting it right?

research is minimal. Therefore, even if a large pharmaceutical company wanted to start a BBB drug delivery program, there would be few, if any, BBB trained scientists to hire. The second reason for the imbalance between CNS drug discovery and drug delivery in the overall CNS drug development process is derived from current thinking within the pharmaceutical industry. It is traditionally believed that small molecules cross the BBB, and so no BBB drug delivery program is required. In fact, most small molecules do not cross the BBB1, and only small lipophilic molecules of less than 400 Da can traverse the BBB. This assumes that such molecules are neither bound by plasma proteins nor are substrates for the multiple active efflux transport systems at the BBB.
Toxicopathic hepatic lesions in subadult English sole (pleuronectes vetuls) from Puget Sound, Washington, USA: Relationships with other biomarkers of contaminant exposure

Liver neoplasms are rarely detected in young wild fish. Therefore, other lesions occurring early in the histogenesis of hepatic neoplasia need to be considered as biomarkers of chemical contaminant exposure effects in monitoring studies, especially where adult fish are not available. Moreover, exposure effects may be more reliably assessed in younger fish that have not yet migrated extensively. Accordingly, livers of subadult English sole were histologically examined from nine sites in Puget Sound, WA and the same fish were assessed for contaminant exposure by measurement of fluorescent aromatic compounds (FACs) in bile, hepatic levels of polychlorinated biphenyls (PCBs) and cytochrome P4501A (CYP1A) as catalytic activity of aryl hydrocarbon hydroxylase (AHH), and Hydrophobic DNA adducts in liver by 32P-postlabelling. Although neoplasms were rare, higher prevalences of preneoplastic, regenerative, and unique degenerative/ necrotic lesions were detected in sole from contaminated sites. Prevalences of these early histopathologic biomarkers were significantly higher at the more contaminated sites, and concentration of mean biliary FACs at each capture site was a significant risk factor for most lesions, as determined by stepwise logistic regression. By this statistical method, we also demonstrated that several measures of bioaccumulation or biochemical response to contaminants were significant and near-significant risk factors for prevalences of most hepatic lesion categories. For example, mean hepatic AHH activity was a significant risk factor for prevalence of all lesion types, except neoplasms; hepatic PCB and xenobiotic-DNA adduct concentrations were significant risk factors for the most frequently detected lesion category, hepatocellular nuclear pleomorphism/megalocytic hepatosis, and the inclusive category ‘any early toxicopathic lesion’. These findings further support the utility of certain non-neoplastic liver lesions as early indicators of biological damage in subadult as well as adult fish exposed to xenobiotics in the marine environment.
The Three-state Perfect Phylogeny Problem Reduces to 2-SAT

We extend a structural result by A. Dress and M. Steel, "Convex tree realizations of partitions," Applied Math Letters, 5 (1993), pp. 3–6., to show that the three-state Perfect Phylogeny problem reduces in polynomial time to the classic 2-SAT problem. We also give a more expanded exposition of the proof of the structural result from Dress and Steel. We hope this note will encourage additional researchers to try to solve the central open question: finding simple efficient solutions to the k-state Perfect Phylogeny problem for k > 3.
Predictors of Recurrent Instability After Acute Patellofemoral Dislocation in Pediatric and Adolescent Patients

Background:Patellofemoral instability is common in the pediatric and adolescent population, yet prognosis after the first dislocation has been difficult to determine.Purpose:To describe the demographics of pediatric and adolescent patients with a first-time patellofemoral dislocation and to determine predictors of recurrent instability.Study Design:Case-control study; Level of evidence, 3.Methods:A search of the Mayo Medical Index database between 1998 to 2010 was performed, and 2039 patients were identified. Inclusion criteria were (1) age 18 years or younger, (2) no history of patellofemoral subluxation/dislocation of the affected knee, (3) radiographs within 4 weeks of the initial instability episode, and (4) a dislocated patella requiring reduction or convincing history/findings suggestive of acute patellar dislocation (effusion/hemarthrosis, tenderness along medial parapatellar structures, and apprehension with lateral patellar translation). Radiographs were evaluated for trochlear dysplasia (Dejour ...
Signal and noise in magneto-optical readout

For a magneto‐optical readout system which uses the Kerr effect, the power spectral density of the read signal has been derived. The noise components originating in the photodetection and amplification stages appear as additive terms in the expression for the overall spectral density, enabling us to define a signal to noise ratio for the readout system. Adjustable parameters of the system are then optimized and a multilayer disk structure is introduced which enhances the Kerr effect and, consequently, results in an increased signal to noise ratio.
Financial incentives for smoking abstinence in patients diagnosed with pulmonary disease

Aims: Chronic obstructive pulmonary disease (COPD) is a serious respiratory illness predominantly caused by cigarette smoking. While smoking cessation is identified as the single most effective intervention to slow the rate of disease progression and reduce COPD-related mortality, abstinence rates following smoking cessation among COPD patients are notoriously poor. We have an ongoing pilot study investigating the initial efficacy of an intensive, incentive-based intervention for promoting smoking abstinence in patients with COPD. Methods: Participants must report smoking>10 cigs/day, have a clinical diagnosis of COPD and have chronic airflow obstruction (post-bronchodilator FEV1/FVC<70%). Participants attend the clinic daily for 14 days and provide breath CO and urinary cotinine samples at each visit for monitoring of smoking status. Thus far, sevenparticipants (54yrsold, 29%male, 15cigs/day, 53%FEV1/FVC) have been randomized to one of two experimental groups: Contingent participants (n=4) earn voucher-based incentives ($362.50 max) contingent upon biochemically verified smoking abstinence and Noncontingent participants (n=3) receive vouchers independent of smoking status. Results: While abstinence is generally high for both groups, preliminary analyses show a trend toward greater biochemically verified smoking abstinence among Contingent vs. Noncontingent participants (68% vs. 50% negative samples, respectively; p= .11). By June 2013 wewill have full data from the completed pilot study (n=20), including primary outcomes of biochemically verified smoking abstinence as well as measures of nicotine withdrawal, craving and pulmonary functioning. Conclusions: Overall, this pilot study is positioned to provide thefirst demonstration that smokers diagnosedwithCOPDcan successfully quit smoking and inform efforts to develop an effective, longer-term smoking cessation intervention for this challenging and costly population of smokers. Financial support: Supported in part by T32 DA007242.
Preference of the Mother Affects Selection and Avoidance of Foods by Lambs Differing in Age

Abstract We studied the effects of mother's preference and lamb age on selection of Amelanchier alnifolia and Cercocarpus montanus by lambs. Thirty-six ewes and their lambs were divided into treatment and control groups. Mothers in the treatment group were conditioned to eat A. alnifolia , but avoid C. montanus , by pairing ingestion of C. montanus with lithium chloride (LiCl), a compound that causes gastrointestinal distress. Mothers in the control group were allowed to eat both foods with impunity. After ewes were conditioned, lambs were exposed daily for 5 days with their mothers to either A . alnifolia or C. montanus for 5 min followed by a 5 min exposure to the other food. Half of the lambs in the treatment and control groups were 6 weeks of age during exposure, while the other half were 12 weeks of age. Treatment lambs of both ages ate less C. montanus than control lambs during exposure. Lambs were weaned after exposure and tested 10 days later for preference. Preference indices ( PI ) for C. montanus were calculated as the percentage of total bites contributed by C. montanus . Treatment lambs exposed at 6 weeks of age ate less C. montanus than A. alnifolia compared with control lambs during trials of 5 min day −1 for 7 days ( PI =0.07 vs. 0.44; P C. montanus than A. alnifolia compared with control lambs ( PI =0.26 vs. 0.45; P C. montanus than lambs exposed at 6 weeks of age ( PI =0.26 vs. 0.07; P C. montanus than for A. alnifolia compared with control lambs ( PI =0.10 vs. 0.48; P C. montanus and A. alnifolia ( PI =0.42 vs. 0.42; P >0.05). We conclude that lambs 6 weeks of age were influenced more by their mothers dietary habits than were lambs 12 weeks of age.
Automated tool trajectory planning of industrial robots for painting composite surfaces

Automatic trajectory generation for spray painting is highly desirable for today’s automotive manufacturing. Generating paint gun trajectories for free-form surfaces to satisfy paint thickness requirements is still highly challenging due to the complex geometry of free-form surfaces. In this paper, a CAD-guided paint gun trajectory generation system for free-form surfaces has been developed. The system utilizes the CAD information of a free-form surface and a paint gun model to automatically generate a paint gun trajectory to satisfy the paint thickness requirements. Complex surfaces are divided into patches to satisfy the constraints. A trajectory integration algorithm is developed to integrate the trajectories of the patches. The paint thickness deviation from the required paint thickness is optimized by modifying the paint gun velocity. A paint thickness verification method is also developed to verify the generated trajectories. The results of simulations have shown that the trajectory generation system achieves satisfactory performance. This trajectory generation system can also be applied to generate trajectories for many other CAD-guided robot trajectory planning applications in surface manufacturing.
Peridynamic theory for progressive damage prediction in center-cracked composite laminates

Numerical studies on the failure of composites have mostly employed the finite element method. However, it can be rather challenging to predict failure using this method. The assumption of lamina homogeneity is questionable when predicting failure, though it is suitable for stress analysis. Matrix cracking, fiber breakage, and delamination are inherent to the inhomogeneous nature of the composite, thus the assumption of material homogeneity taints the failure prediction. It is, therefore, essential that the inhomogeneous nature of the composites must be retained in the analysis in order to predict the correct failure modes. Hence, this study considers distinct properties of the fiber and matrix and their volume fractions and fiber orientations while modeling composite laminates. The peridynamic theory is employed to predict the damage in center-cracked laminates with different fiber orientations. The predictions from the peridynamic analysis agree with the experimental observations published in the literature.
Renal cellular transport of exogenous glutathione: heterogeneity at physiological and pharmacological concentrations

Properties and kinetics of GSH transport into proximal tubular (PT) and distal tubular (DT) cells from rat kidney were determined to validate further the hypothesis that cellular differences in handling of GSH contribute to the greater susceptibility of DT cells to oxidant injury. PT and DT cells were incubated with a broad range of GSH concentrations, encompassing physiologically relevant (0.001 to 0.1 mM) to pharmacological (0.25 to 5 mM) levels of GSH. GSH uptake in PT cells was rapid, exhibiting an overshoot with a maximum at 1-min incubation. GSH uptake in DT cells reached maximal intracellular levels at 2- to 5-min incubations. GSH uptake in PT cells was resolved into two kinetically distinct processes, with Km values of 41.7 and 540 microM and Vmax values of 183 and 4885 pmol/min per 10(6) cells. In contrast, GSH uptake in DT cells was best described by one process, with Km and Vmax values of 1480 microM and 2094 pmol/min per 10(6) cells, respectively. Rates of GSH synthesis from 1 mM precursor amino acids were approximately 3-fold faster in PT cells, but rates of cysteine accumulation were 3.5-fold faster in DT cells. Accumulation of intracellular GSH in PT cells was 8-fold faster after incubation with 1 mM GSH than after incubation with 1 mM precursor amino acids. At both a physiological (10 microM) and a pharmacological (5 mM) GSH concentration, uptake exhibited marked Na+ and energy dependence, sensitivity to substrates for the organic anion and dicarboxylate carriers, and sensitivity to various gamma-glutamyl amino acids in PT cells only. Na+-dependent GSH uptake in PT cells was accounted for completely by activity of the organic anion and dicarboxylate carriers. These results indicate that DT cells possess limited capacity to transport GSH and suggest that exogenous GSH may not be effective in protecting other segments of the nephron besides the PT region from oxidants or other agents that alter GSH status.
High-speed, label-free second harmonic generation holographic microscopy of biological specimens

We apply holography to second harmonic generation (SHG) microscopy to obtain three-dimensional images of biological specimens without the use of external labeling. Nonlinear scanning microscopy techniques like SHG, has proven to be a powerful technique for imaging biological samples such as collagen, myosin, and muscle fibrils, but it lacks in acquisition speed for video rate 3D imaging. In nonlinear holography however, full 3D images can be numerically reconstructed from one hologram, the recorded intensity interference pattern between the endogenous SHG and coherent reference fields. The femtosecond Yb:KGW laser oscillator used in these experiments appears in biologically compatible window at a center wavelength near 1 μm. The limited absorption helps prevent damage to our samples, even for prolonged exposures. Holograms were recorded with exposure times as short as 1 ms using a fast mechanical shutter. Extrapolating the trend measured above this limit, we anticipate a 10 dB SNR at 40 μs integration time. Such high 3D image frame rates would yield a great deal of information of chemical waves, neurological networks, and other biological systems.
Stabilization of neurofilament transcripts during postnatal development

Neurofilament (NF) mRNAs in primary sensory neurons are long-lived transcripts that undergo transcription-dependent destabilization when placed in primary culture [32]. Destabilization of NF transcripts implies that the transcripts are stabilized in high-expressing neurons and that stabilization may coordinate and increase levels of NF expression. The present study examines the stabilities of the three NF subunit mRNAs in postnatal cultures of dorsal root ganglia (DRG) to determine whether increased stability of NF mRNAs could be responsible for the coordinate postnatal upregulation of the three NF subunits [29]. The studies show that the light (NF-L), mid-sized (NF-M) and heavy (NF-H) NF mRNAs are lost at 8 and 16 h in primary cultures from postnatal day 2 (P2) rats, but much less so in cultures from postnatal day 16 (P16) and day 30 (P30) rats. Losses of each NF mRNAs in P2 cultures occurs simultaneously in the presence or absence of actinomycin. The findings support the view that stabilization of NF transcripts contribute to the high and coordinate level NF expression and that components of the stabilizing process are acquired during postnatal development.
Faith In The Model And Resistance To Research

Under the current model, acts of child sexual abuse (CSA) should traumatize and/or sexualize a child, producing signs and symptoms of these conditions that can be detected reliably by experts in the CSA field. A review of the last 20 years of research on CSA does not support the view that the majority of children known to have been sexually abused exhibit signs or symptoms of trauma. Neither do the majority of abused children reliably exhibit sexualized behavior. There is no sign or symptom that characterizes the majority of abused children. A significant percentage of children known to have been abused appears to be asymptomatic. For expert evaluation to be useful to victims and expert testimony to be useful to the legal system, experts conducting evaluations must incorporate knowledge of the absence of differential probabilities of indicators for abuse/no abuse into their professional opinions.
Improved diagnostic procedures in attenuated mucopolysaccharidosis

General physicians and rheumatologists play a key role in suspecting a diagnosis of mucopolysaccharidosis for a range of multi-organ presenting symptoms in adults. Prompt diagnosis and treatment maximizes outcomes for these rare and extremely debilitating diseases. Earlier diagnosis may help to prevent irreversible disease.
Opening Government

Open government initiatives in the U.S. government focus on three main aspects: transparency, participation, and collaboration. Especially the collaboration mandate is relatively unexplored in the literature. In practice, government organizations recognize the need to include external problem solvers into their internal innovation creation processes. This is partly derived from a sense of urgency to improve the efficiency and quality of government service delivery. Another formal driver is the America Competes Act that instructs agencies to search for opportunities to meaningfully promote excellence in technology, education, and science. Government agencies are responding to these requirements by using open innovation OI approaches to invite citizens to crowdsource and peer produce solutions to public management problems. These distributed innovation processes occur at all levels of the U.S. government and it is important to understand what design elements are used to create innovative public management ideas. This article systematically reviews existing government crowdsourcing and peer production initiatives and shows that after agencies have defined their public management problem, they go through four different phases of the OI process: 1 idea generation through crowdsourcing, 2 incubation of submitted ideas with peer voting and collaborative improvements of favorite solutions, 3 validation with a proof of concept of implementation possibilities, and 4 reveal of the selected solution and the internal implementation of the winning idea. Participation and engagement are incentivized both with monetary and nonmonetary rewards, which lead to tangible solutions as well as intangible innovation outcomes, such as increased public awareness.
Demographics and outcome of unintentional insulin overdoses managed by three poison centers.

AbstractInsulin dosing errors are one of the most dangerous medication issues due to the risk of profound hypoglycemia. The incidence of insulin dosing errors is increasing and there is no standard of care for management location. Objective. To determine the types of insulin, follow-up time, number of phone calls, incidence of hypoglycemia, and case outcomes for unintentional insulin overdoses managed by Poison Centers (PCs). Methods. Observational case series: records of patients with unintentional injected insulin errors from three PCs over a 22-month period were manually reviewed for insulin type, management site, time of exposure, insulin dose, number of calls, presence of hypoglycemia, and case outcome. Results. There were 642 cases: 97.5% occurred in the home and the majority of patients (77.3%) were managed on site with only 17.4% resulting in Emergency Department treatment. Clinical or numerical (blood sugar < 60 mg/dL) hypoglycemia occurred 15.9% (n = 102) of the time in all cases, with 6.9% (n =...
Peptide bond isosteres: ester or (E)-alkene in the backbone of the collagen triple helix.

Collagen is the most abundant protein in animals. Interstrand N−H···OC hydrogen bonds between backbone amide groups form a ladder in the middle of the collagen triple helix. Isosteric replacement of the hydrogen-bond-donating amide with an ester or (E)-alkene markedly decreases the conformational stability of the triple helix. Thus, this recurring hydrogen bond is critical to the structural integrity of collagen. In this context, an ester isostere confers more stability than does an (E)-alkene.
Evolution of Antigenic Variation

processes that shape genetic variability and evolutionary change.The causes of variability and change provide the basis for understanding why simple vaccines work well against some viruses, whereas complex vaccine strategies achieve only limited success against other viruses. The battle between host and parasite often comes down to the rates at which attacker and defender molecules bind or evade each other. The biochemical details of binding and recognition set the rules of engagement that shape the pace, scale, and pattern of diversity and the nature of evolutionary change [45]. The first section of this chapter lists the different ways in which parasites can gain by varying their antigenic molecules. The parasites may, for example, extend their time of infection within a particular host by changing their antigenic molecules to evade the specific recognition built up by the host immune system. Or the parasites may vary to attack hosts that had been exposed previously and had built up specific recognition against prior antigenic molecules. The second section focuses on the nature of binding and recognition between host and parasite molecules. I summarize the different ways in which parasites generate new variants in order to escape molecular recognition. The third section builds up the individual molecular interactions into the dynamics of a single infection within a host. The parasites spread in the host, triggering immune attack against dominant antigens.The battle within the host develops through changes in population numbers – the numbers of parasites with particular antigens and the numbers of immune cells that specifically bind to particular antigens. The fourth and fifth sections discuss how the successes and failures of different parasite antigens within each host determine the rise and fall of parasite variants over space and time. The distribution of parasite variants sets the immune memory profiles of different hosts, which in turn
A facile synthesis of radioiodinated (Z)-vinyl iodides via vinylboronates.

Abstract A direct radioiodination of ( Z )-vinylboronic acid esters to the corresponding vinyl iodides using Na 123 I and chloramine-T is described. The boronates were prepared from vinyl iodides via palladium coupling reactions.
Piconewton Level Loading and Sub-Cellular Deformation of Bone Cells Using a Novel Stokesian Fluid Stimulus Probe (SFSP)

A new quantifiable in vitro force probe, the Stokesian Fluid Stimulus Probe (SFSP), is developed to hydrodynamically stimulate local regions of the osteocyte whereby neither antibody decoration nor probe membrane perturbation is necessary. Osteocytes are imbedded in hard mineralized matrix where single-cell, in vivo experimentation is extremely challenging. Whole bone tissue loading induces cyclic fluid flow throughout the bone porosity to hydrodynamically load osteocytic networks within the lacunar-canalicular-system (LCS). A theoretical model has been developed to describe the fluid flow through the dynamic and structurally complex microenvironment surrounding the osteocytic network within the LCS. The model predicts tensile forces of 1–10pN to occur at discrete attachment sites connecting the osteocyte cell process to canalicular wall projections during physiological loading1. Our new force probe’s design and implementation has successfully 1) reproduced in vivo level forces at subcellular precision to assess cellular polarity in vitro and 2) demonstrated that cellular signaling is initiated at integrin attachment sites along the cell process.Copyright © 2011 by ASME
Color-Based Motion Processing Is Stronger in Infants Than in Adults:

One hallmark of vision in adults is the dichotomy between color and motion processing. Specifically, areas of the brain that encode an object's direction of motion are thought to receive little information about object color. We investigated the development of this dichotomy by conducting psychophysical experiments with human subjects (2-, 3-, and 4-month-olds and adults), using a novel red-green stimulus that isolates color-based input to motion processing. When performance on this red-green motion stimulus was quantified with respect to performance on a luminance (yellow-black) standard, we found stronger color-based motion processing in infants than in adults. These results suggest that color input to motion areas is greater early in life, and that motion areas then specialize to the adultlike state by reweighting or selectively pruning their inputs over the course of development.
Magnetic properties of 3d transition metals and nitrogen functionalized armchair graphene nanoribbon

First-principles density functional theory (DFT) calculations were performed to study the stability and magnetic properties of TM–CxNy (TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu and Zn; x/y = 0, 1 and 2 and x + y = 2) edge defects in armchair graphene nanoribbon (9-AGNR). The results showed that the edge functionalization of 9-AGNR by TM–N2 defects is energetically more favorable compared to the edge functionalization by TM–C2 and TM–CN defects. Furthermore, we found that edge TM–CxNy defects in 9-AGNR support high and localized magnetic moments. The magnetic moment of TMs in TM–CxNy edge defects increases with an increase in the number of unpaired electrons in the 3d orbitals, and the calculated magnetic moment is largest for an edge Mn–N2 defect. The analysis of magnetization of TMs reveals that the magnetic moment mainly comes from the electrons in the 3d orbitals and the contribution of 4s electrons to the total magnetic moment is very small. Our calculations also show that the magnetic moment of TMs in edge TM–N2 defects in AGNR is independent of edge TM–N2 defect concentrations and AGNR width in the present study. The interedge magnetic coupling between the edge TM–N2 defects is explored by investigating the competing ferromagnetic and antiferromagnetic spin structures. We found that the interedge magnetic coupling depends on the type of TMs in edge TM–N2 defects and TM–N2 edge defect concentrations.
Anti-HIV Host Factor SAMHD1 Regulates Viral Sensitivity to Nucleoside Reverse Transcriptase Inhibitors via Modulation of Cellular Deoxyribonucleoside Triphosphate (dNTP) Levels

Newly identified anti-HIV host factor, SAMHD1, restricts replication of lentiviruses such as HIV-1, HIV-2, and simian immunodeficiency virus in macrophages by enzymatically hydrolyzing and depleting cellular dNTPs, which are the substrates of viral DNA polymerases. HIV-2 and some simian immunodeficiency viruses express viral protein X (VPX), which counteracts SAMHD1 and elevates cellular dNTPs, enhancing viral replication in macrophages. Because nucleoside reverse transcriptase inhibitors (NRTIs), the most commonly used anti-HIV drugs, compete against cellular dNTPs for incorporation into proviral DNA, we tested whether SAMHD1 directly affects the efficacy of NRTIs in inhibiting HIV-1. We found that reduction of SAMHD1 levels with the use of virus-like particles expressing Vpx- and SAMHD1-specific shRNA subsequently elevates cellular dNTPs and significantly decreases HIV-1 sensitivity to various NRTIs in macrophages. However, virus-like particles +Vpx treatment of activated CD4+ T cells only minimally reduced NRTI efficacy. Furthermore, with the use of HPLC, we could not detect SAMHD1-mediated hydrolysis of NRTI-triphosphates, verifying that the reduced sensitivity of HIV-1 to NRTIs upon SAMHD1 degradation is most likely caused by the elevation in cellular dNTPs. Background: SAMHD1 is an enzyme that maintains low dNTP concentrations in macrophages. Results: Depletion of SAMHD1 decreases HIV-1 sensitivity to nucleoside reverse transcriptase inhibitors (NRTIs) in macrophages, but does not significantly alter sensitivity in T cells. Conclusion: SAMHD1 expression levels in macrophages directly impact the efficacy of NRTIs by modulating cellular dNTP concentrations. Significance: SAMHD1 controls HIV-1 sensitivity to NRTIs.
The relation between Eulerian time and space spectra

Simultaneous observations of space correlations and time correlations verify that Taylor's hypothesis x = Ut is valid for intervals up to at least 90 m, and for relative intensities of turbulence at least up to 0·26. It is also shown that, when the stratification is stable, the longitudinal scale of turbulence tends to be much larger along the flow than across it. In an unstable layer, the scale is of the same order of magnitude in all directions.
Spermine Binding to Parkinson's Protein α-Synuclein and Its Disease-Related A30P and A53T Mutants

Aggregation of α-synuclein (α-syn), a protein implicated in Parkinson’s disease (PD), is believed to progress through formation of a partially folded intermediate. Using nanoelectrospray ionization (nano-ESI) mass spectrometry combined with ion mobility measurements we found evidence for a highly compact partially folded family of structures for α-syn and its disease-related A53T mutant with net charges of −6, −7, and −8. For the other early onset PD mutant, A30P, this highly compact population was only evident when the protein had a net charge of −6. When bound to spermine near physiologic pH, all three proteins underwent a charge reduction from the favored solution charge state of −10 to a net charge of −6. This charge reduction is accompanied by a dramatic size reduction of about a factor of 2 (cross section of 2600 A2 (−10 charge state) down to 1430 A2 (−6 charge state)). We conclude that spermine increases the aggregation rate of α-syn by inducing a collapsed conformation, which then proceeds to form...
Repair of the truncal valve and associated interrupted arch in neonates with truncus arteriosus.

Abstract Objective: Truncal valve regurgitation and interrupted aortic arch have frequently been identified as risk factors in the repair of truncus arteriosus. We wished to examine these factors in the current era including the impact of truncal valve repair. Methods: Between January 1992 and August 1998, 50 patients underwent surgical repair of truncus arteriosus. Their ages ranged from 2 days to 6 months (median, 2 weeks). Nine patients had associated interrupted aortic arch. Of the 14 patients (28%) in whom truncal valve regurgitation was diagnosed preoperatively, 5 had mild regurgitation, 5 had moderate regurgitation, and 4 had severe regurgitation. Five underwent truncal valve repair and 1 underwent homograft replacement of the truncal valve with coronary reimplantation. Results: The actuarial survival was 96% at 30 days, 1 year, and 3 years. There were no deaths in patients with associated interrupted aortic arch. The 2 deaths in the series occurred in patients with truncal valve regurgitation, neither of whom underwent repair. Postoperative transthoracic echocardiography in patients who underwent valve repair showed minimal residual valvular regurgitation. None of the patients has required reoperation because of truncal valve problems or aortic arch stenosis at a median follow-up of 23 months (range, 1-60 months). Conduit replacement has been done in 17 patients (34%) after a mean duration of 2 years. The freedom from reoperation for those who had an aortic homograft was 4 years and for those who had a pulmonary homograft was 3 years. Conclusion: Despite the magnitude of the operation, excellent results can be achieved in complex forms of truncus arteriosus. In the current era interrupted aortic arch is no longer a risk factor for repair of truncus. Aggressive application of truncal valvuloplasty methods should neutralize the traditional risk factor of truncal valve regurgitation. (J Thorac Cardiovasc Surg 2000;119:508-14)
HIV-1 Nef Assembles a Src Family Kinase-ZAP-70/Syk-PI3K Cascade to Downregulate Cell-Surface MHC-I

HIV-1 Nef, which is required for the efficient onset of AIDS, enhances viral replication and infectivity by exerting multiple effects on infected cells. Nef downregulates cell-surface MHC-I molecules by an uncharacterized PI3K pathway requiring the actions of two Nef motifs-EEEE(65) and PXXP(75). We report that the Nef EEEE(65) targeting motif enables Nef PXXP(75) to bind and activate a trans-Golgi network-localized Src family tyrosine kinase (SFK). The Nef/SFK complex then recruits and phosphorylates the tyrosine kinase ZAP-70, which binds class I PI3K to trigger MHC-I downregulation in primary CD4+ T cells. In promonocytic cells, Nef/SFK recruits the ZAP-70 homolog Syk to downregulate MHC-I, implicating this PI3K pathway in multiple HIV-1 reservoirs. Isoform-specific PI3K inhibitors repress MHC-I downregulation, identifying them as potential therapeutic agents to combat HIV-1. The discovery of this Nef-SFK-ZAP-70/Syk-PI3K signaling pathway explains the hierarchal role of the Nef motifs in effecting immunoevasion.
Comparison of mutation frequencies obtained using transgenes and specific-locus mutation systems in male mouse germ cells.

A directed effort to assay and quantify genetic risks from human exposure to mutagenic chemicals is urgently needed; otherwise genetic toxicology may well lose its credibility. Genetic biomonitoring provides us with an indication of mutagenic effectiveness in human somatic cells. The populations and chemicals selected for such studies form a useful data base for genetic risk assessment studies. Extrapolation to what can be expected in germ cells of exposed individuals should be possible by using good dosimetry (adducts) and a parallelogram approach. The principle is that genetic damage which is not measurable in human germ cells can be estimated by determining the effects on lymphocytes (or other somatic cells) from humans and mice and in germ cells of mice. Worldwide, opportunities for the costly mouse germ-cell studies are limited. This poses serious problems in genetic risk assessment studies. The paper by Malling and Burkhart which follows below makes a first contribution to such an approach. I hope that it may lead to a constructive discussion which should be helpful to clarify some points which cannot yet be solved with the available data.