cssi/SciSciGPT-SciSciNet huggingface dataset:
Uncovering the Geometry of Barrierless Reactions Using Lagrangian Descriptors

Transition-state theories describing barrierless chemical reactions, or more general activated problems, are often hampered by the lack of a saddle around which the dividing surface can be constructed. For example, the time-dependent transition-state trajectory uncovering the nonrecrossing dividing surface in thermal reactions in the framework of the Langevin equation has relied on perturbative approaches in the vicinity of the saddle. We recently obtained an alternative approach using Lagrangian descriptors to construct time-dependent and recrossing-free dividing surfaces. This is a nonperturbative approach making no reference to a putative saddle. Here we show how the Lagrangian descriptor can be used to obtain the transition-state geometry of a dissipated and thermalized reaction across barrierless potentials. We illustrate the method in the case of a 1D Brownian motion for both barrierless and step potentials; however, the method is not restricted and can be directly applied to different kinds of potentials and higher dimensional systems.
Myosin and the PAR proteins polarize microfilament-dependent forces that shape and position mitotic spindles in Caenorhabditis elegans

In Caenorhabditis elegans, the partitioning proteins (PARs), microfilaments (MFs), dynein, dynactin, and a nonmuscle myosin II all localize to the cortex of early embryonic cells. Both the PARs and the actomyosin cytoskeleton are required to polarize the anterior-posterior (a-p) body axis in one-cell zygotes, but it remains unknown how MFs influence embryonic polarity. Here we show that MFs are required for the cortical localization of PAR-2 and PAR-3. Furthermore, we show that PAR polarity regulates MF-dependent cortical forces applied to astral microtubules (MTs). These forces, which appear to be mediated by dynein and dynactin, produce changes in the shape and orientation of mitotic spindles. Unlike MFs, dynein, and dynactin, myosin II is not required for the production of these forces. Instead, myosin influences embryonic polarity by limiting PAR-3 to the anterior cortex. This in turn produces asymmetry in the forces applied to MTs at each pole and allows PAR-2 to accumulate in the posterior cortex of a one-cell zygote and maintain asymmetry.
The DØ Luminosity Monitor Operations and Performance

Abstract The D0 Luminosity Monitor (LM) plays a crucial role in D0 physics analyses by providing the normalization for many cross section measurements. The detector consists of two sets of 24 scintillator wedges read out with photomultiplier tubes. The detector is located in the forward regions surrounding the beam pipe, covering a pseudo-rapidity range of 2.7
In vitro assessment of the oncogenic potential of nitroimidazole radiosensitizers.

Abstract Two hypoxic cell radiosensitizers, RSU-1069 and Ro-03-8799 were investigated for their in vitro cytotoxicity and ability to induce oncogenic transformation and sister chromatid exchanges in the C3H 10T 1 2 cell system. Their effects were then compared to those of the clinically used sensitizer misonidazole. Equitoxic doses of Ro-03-8799 and RSU-1069 were approximately 3–fold and 150–fold less than misonidazole, respectively, with both agents exhibiting dose and contact time dependence for cell killing. Both sensitizers appeared no more oncogenic than misonidazole when administered at equitoxic dosages. At doses of equivalent sensitizing efficiencies relative to misonidazole, RSU-1069, but not Ro-03-8799, induced significantly higher transformation incidence. In conjunction with γ-irradiation, both Ro-03-8799 and misonidazole induced an additive transformation response. Preliminary studies also indicate that RSU-1069, at a concentration of 0.03 mM, induced significantly higher sister chromatid exchanges (SCE) per chromosome than either Ro-03-8799 or misonidazole at concentrations 30-fold higher. Although several earlier studies have indicated that RSU-1069 may be more efficient than misonidazole as an hypoxic cell sensitizer, the present findings suggest that it may also carry a higher risk of inducing tumors by itself at clinically relevant concentrations.
Two-Dimensional Radiative Equilibrium

Abstract An exact formulation for the radiative flux and the emissive power is presented for a two-dimensional, finite, planar, absorbing-emitting, gray medium in radiative equilibrium. Exact expressions are obtained for a medium subjected to the following types of boundary conditions: ( A ) cosine varying collimated radiation, ( B ) a strip of collimated radiation, ( C ) cosine varying diffuse radiation, and ( D ) a uniform temperature strip. The solution for the cosine varying collimated radiation model is used to construct the solutions for the other boundary conditions. The two-dimensional equations are reduced to one-dimensional equations by the method of separation of variables.
Determination of urinary prostanoids by capillary gas chromatography/high-resolution mass spectrometry

Abstract A stable isotope-dilution gas-chromatography/high-resolution mass spectrometry method for the determination of prostaglandin E 2 (PGE 2 ) and 6-keto-prostaglandin F 1α (6-keto-PGF 1α ) in urine as their methoxime/t-butyldimethylsilyl ether/t-butyl-dimethylsilyl ester derivatives is described. The derivatives are prepared by a novel derivatization scheme in which the pentafluorobenzyl esters are formed prior to the silylation step in which the t-butyldimethylsilyl esters are formed in an apparent exchange reaction. Recoveries through the entire extraction and derivatization procedure are 70.6% for PGE 2 and 64.4% for 6-keto-PGF 1α . Quantitation at mass resolutions approaching 10 000 eliminated all interferences in the PGE 2 chromatograms while lower resolutions were sufficient for 6-keto-PGF 1α . Limits of detection of 50 pg ml −1 for each prostanoid were obtained. For PGE 2 , a lower limit of detection was obtained at a mass resolution of 10 000 (50 pg ml −1 ) than was obtained at a mass resolution of 1000 (80 pg ml −1 ), illustrating the selectivity of detection.
The evaluation of corporate contributions: A reply

Well-founded criticisms and additions to published work are generally well regarded by authors interested in seeing their work expanded and improved. Unfortunately, the preceding comments on our paper (L-S) 'The evaluation of corporate contributions' [4] seem to add nothing to the original paper, are often in error, and contain gratuitous and contentious assertions designed not to illuminate the reader interested in corporate charity but rather to obfuscate the central issues of this timely topic. The present paper shows how the comments are in error and reiterates the conclusions reached in our original work. Professors Keim, Meiners, and Fry (KMF) direct eight criticisms at our paper criticisms which are either unfounded, extraneous, or incorrect. More charitably (no pun intended), Professors Bennett and Johnson (B-J) attempt to expand on our regression equations by using a subset of the firms included in our study and adding an additional year and some further variables, which are questionable at best. The paper by B-J is substantive but not particularly illuminating for the reasons outlined below, while the paper by KMF, which we shall examine first, is argumentative and devoid of scholarship. Perhaps the simplest way to begin is to list KMF's criticisms of our paper:
Renal manifestations of hepatitis C virus infection: Extrahepatic complications often are silent-and thus overlooked

PREVIEWInfection with hepatitis C virus (HCV) can lead to chronic active hepatitis, cirrhosis, and liver failure. However, it also is associated with a wide range of extrahepatic features, including renal disease. Membranoproliferative glomerulonephritis (MPGN), with or without cryoglobulinemia, is the most common renal lesion. In this article, Dr Bandi describes the features of renal disease associated with hepatitis C and various therapeutic options.
Real-time control of physically based simulations using gentle forces

Recent advances have brought real-time physically based simulation within reach, but simulations are still difficult to control in real time. We present interactive simulations of passive systems such as deformable solids or fluids that are not only fast, but also directable: they follow given input trajectories while simultaneously reacting to user input and other unexpected disturbances. We achieve such directability using a real-time controller that runs in tandem with a real-time physically based simulation. To avoid stiff and over-controlled systems where the natural dynamics are overpowered, the injection of control forces has to be minimized. This search for gentle forces can be made tractable in real-time by linearizing the system dynamics around the input trajectory, and then using a time-varying linear quadratic regulator to build the controller. We show examples of controlled complex deformable solids and fluids, demonstrating that our approach generates a requested fixed outcome for reasonable user inputs, while simultaneously providing runtime motion variety.
Using liquid cooling for flat panel displays

Active Matrix, Liquid Crystal Displays (AMLCD) are being used extensively in severe environments which require a wide range of optical performance. Conditions vary from high performance military aircraft to rugged use on the ground in both military and commercial vehicle environments. Not only are these displays being exposed to high ambient temperatures, shock and vibration, but also the requirement for readability in direct sunlight imposes conditions where backlight brightness must be greatly increased, imposing added thermal requirements. This paper discusses a fluid immersion, liquid cooling technique that allows great increases in backlight brightness with major improvement in thermal efficiency of the display. Improvements in susceptibility to shock and vibration can also be deduced from the use of this methodology. A prototype has been developed and is described in this paper and results compared to a conventionally cooled unit. A number of other advantages, which result from liquid immersion, are also discussed.
Dopamine and Reward: The Anhedonia Hypothesis 30 years on

The anhedonia hypothesis — that brain dopamine plays a critical role in the subjective pleasure associated with positive rewards — was intended to draw the attention of psychiatrists to the growing evidence that dopamine plays a critical role in the objective reinforcement and incentive motivation associated with food and water, brain stimulation reward, and psychomotor stimulant and opiate reward. The hypothesis called to attention the apparent paradox that neuroleptics, drugs used to treat a condition involving anhedonia (schizophrenia), attenuated in laboratory animals the positive reinforcement that we normally associate with pleasure. The hypothesis held only brief interest for psychiatrists, who pointed out that the animal studies reflected acute actions of neuroleptics whereas the treatment of schizophrenia appears to result from neuroadaptations to chronic neuroleptic administration, and that it is the positive symptoms of schizophrenia that neuroleptics alleviate, rather than the negative symptoms that include anhedonia. Perhaps for these reasons, the hypothesis has had minimal impact in the psychiatric literature. Despite its limited heuristic value for the understanding of schizophrenia, however, the anhedonia hypothesis has had major impact on biological theories of reinforcement, motivation, and addiction. Brain dopamine plays a very important role in reinforcement of response habits, conditioned preferences, and synaptic plasticity in cellular models of learning and memory. The notion that dopamine plays a dominant role in reinforcement is fundamental to the psychomotor stimulant theory of addiction, to most neuroadaptation theories of addiction, and to current theories of conditioned reinforcement and reward prediction. Properly understood, it is also fundamental to recent theories of incentive motivation.
Evaluation of PLGA microspheres as delivery system for antitumor agent-camptothecin.

AbstractCamptothecin (CPT) and its analogues are a new class of anticancer agents that have been identified over the past several years. Camptothecin exists in two forms depending on the pH: An active lactone form at pH below 5 and an inactive carboxylate form at basic or physiological neutral pH. Poly(lactide-co-glycolide) (PLGA) microspheres have been considered good delivery vehicles for CPT because of acidic microenvironment formed through PLGA degradation. The objective of this study is to investigate antitumor activity of CPT after it is encapsulated in PLGA microspheres. In this study, PLGA microspheres containing various CPT loadings were prepared and characterized. Cytotoxicity of these microspheres to B16 melanoma cells was then evaluated, and uptake of microspheres by B16 cells was also studied. Analysis of drug stability revealed that CPT is released from the microspheres in its active lactone form over the entire release duration. It was also found that there was no interaction between CPT an...
Energy Dissipation in Non-Hertzian Fretting Contact

A two-dimensional linear elastic contact problem, relevant to fretting fatigue analysis, is formulated and solved numerically. It is assumed that the contact region contains a centrally located stick zone between two regions of micro-slip in which the Amontons-Coulomb law of sliding friction is assumed to apply. The solution yields the contact stress distributions, size and location of the stick zone, relative displacements in the regions of micro-slip and the energy dissipation per cycle of tangential loading. Results for energy dissipation per cycle, and the steady state location of the stick zone versus tangential loading are given for three different values of an interaction parameter. Presented at the 43rd Annual Meeting in Cleveland, Ohio May 9–12, 1988
Relationship between macroscopic and microscopic models of surfactant adsorption dynamics at fluid interfaces.

In a companion preceding paper, we presented an experimental investigation into the adsorption dynamics of a diblock copolymer surfactant to a polymer/polymer interface and found them to be well-described by a microscopic model of diffusion in a potential generated using self-consistent field theory. We compare the predictions of the microscopic approach with a macroscopic (adsorption−diffusion) model and demonstrate the equivalence of the two models when the free-energy well underlying surfactant adsorption is flanked by barriers that are significantly larger than thermal energy (kT). However, when the energy barriers are nonexistent, as is the case for the experimental system of interest, a finite interfacial width must be introduced into the classical model to obtain physically meaningful results (i.e., nonnegative desorption rates). Surprisingly, we find that the predictions of the macroscopic finite interfacial width model with no adjustable parameters are in excellent agreement with experimental dat...
Treatment of neuromyelitis optica/neuromyelitis optica spectrum disorders with methotrexate

To review our experience using methotrexate as a single long-term immunosuppressant (IS) therapy in neuromyelitis optica/neuromyelitis optica spectrum disorders (NMO/NMOSD). We performed a retrospective chart review of all patients with a diagnosis of NMO/NMOSD, supported by a positive NMO-IgG testing, who were treated with methotrexate. A paired sample 2 tailed t test was used to assess the annualized relapse rate during 18 months pre treatment with methotrexate to annualized relapse rate 18 months post treatment with methotrexate. We followed 9 patients meeting criteria for the study for a median of 62 months. All patients were stabilized during attacks with high-dose steroids and/or plasmapheresis. Five patients (55.55%) were started on methotrexate as an initial long-term immunosuppressant strategy. Three patients (33.33%) were initially treated with pulse cyclophosphamide followed by methotrexate as a preplanned step-down strategy. One patient was started on azathioprine prior to methotrexate. No patient had side effects requiring change in methotrexate therapy. Five patients (55.55%) had stabilization of Expanded Disability Status Scale (EDSS) on methotrexate. One patient had a small increase in EDSS due to concomitant illness. Three patients (33.33%) had methotrexate treatment failure evidenced by worsening EDSS and ongoing relapses while on methotrexate, mandating a change in methotrexate therapy. Average annualized relapse rate in the entire group comparing 18 months prior versus 18 months after methotrexate treatment was reduced by an absolute value of 64% (3.11 vs 1.11). A paired t-test showed this reduction was highly significant (p = .009). In our experience, methotrexate is safe and possibly efficacious as a single long-term IS therapy along with low dose corticosteroids that can reasonably be offered to patients with NMO/NMOSD.
Complex dynamics at the interface between wild and domestic viruses of finfish.

Viral traffic occurs readily between wild and domesticated stocks of finfish because aquatic environments have greater connectivity than their terrestrial counterparts and because the global expansion and dynamic nature of intensive aquaculture provide multiple pathways of transmission and unique drivers of virus adaptation. Supported by examples from the literature, we provide reasons why viruses move from wild fish reservoirs to infect domestic fish in aquaculture more readily than ‘domestic’ viruses move across the interface to infect wild stocks. We also hypothesize that ‘wild’ viruses moving across the interface to domestic populations of finfish are more frequently associated with disease outbreaks and host switches compared to domestic viruses that cross the interface to infect wild fish.
Vaginal mullerian cyst presenting as a cystocele

Background Vaginal cysts occur rarely, are usually discovered incidentally on examination, and can cause a variety of symptoms. Case This article discusses a 34-year-old para 2 female with a large anterior vaginal wall cyst that arose at 20 weeks' gestation and was originally diagnosed as a cystocele. The unusual timing of its occurrence and the characteristics of the anterior vaginal wall prompted ancillary testing and reexamination. Conclusion The timing of onset and general characteristics of prolapse as well as defecography and magnetic resonance imaging can be used to aid the gynecologist in diagnosing vaginal cysts instead of the more common condition of vaginal prolapse.
ITO/poly(aniline)/sol-gel glass: An optically transparent, pH-responsive substrate for supported lipid bilayers.

Described here is fabrication of a pH-sensitive, optically transparent transducer composed of a planar indium-tin oxide (ITO) electrode overcoated with a poly(aniline) (PANI) thin film and a porous sol-gel layer. Adsorption of the PANI film renders the ITO electrode sensitive to pH, whereas the sol-gel spin-coated layer makes the upper surface compatible with fusion of phospholipid vesicles to form a planar supported lipid bilayer (PSLB). The response to changes in the pH of the buffer contacting the sol-gel/PANI/ITO electrode is pseudo-Nernstian with a slope of 52 mV/pH over a pH range of 4–9. Vesicle fusion forms a laterally continuous PSLB on the upper sol-gel surface that is fluid with a lateral lipid diffusion coefficient of 2.2 μm2/s measured by fluorescence recovery after photobleaching. Due to its lateral continuity and lack of defects, the PSLB blocks the pH response of the underlying electrode to changes in the pH of the overlying buffer. This architecture is simpler to fabricate than previously reported ITO electrodes derivatized for PSLB formation and should be useful for optical monitoring of proton transport across supported membranes derivatized with ionophores and ion channels.
The role of TNF in hepatic histopathological manifestations and hepatic CD8+ T cell alloresponses in murine MHC class I disparate GVHD.

Transfer of B6 T cells to major histo- compatibility complex (MHC) class I disparate bm1 B6 F1 mice leads to the development of hepatic graft-versus-host disease (GVHD) charac- terized by an active hepatitis with portal and lobu- lar inflammation as well as bile duct inflammation and venulitis. The present studies determined the role of tumor necrosis factor (TNF) in hepatic GVHD. B6 responder cells were cultured with ir- radiated MHC class I disparate bm1 or syngeneic spleen cells (SpC) in the presence or absence of TNF receptor inhibitor (TNFR-immunoglobulin (Ig)). Recipient bm1 B6 F1 mice were irradiated (600 cGy) and reconstituted with 5 10 6 T cell- depleted B6 bone marrow cells and 1 10 7 B6 SpC. Mice were injected with an adenovirus encod- ing TNFR-Ig (TNF inhibitor-encoding adenovirus (Adv-TNFi)) or -galactosidase (Adv-gal). Sever- ity of liver GVHD was assessed by a composite histopathological score consisting of the sum of scores for venulitis, lobular hepatitis, and bile duct inflammation. Addition of TNFR-Ig reduced cell proliferation in mixed lymphocyte cultures using B6 responder SpC by 71% 12.8% and inter- feron- responses by 78% 18%. GVHD-in- duced "wasting disease" was reduced in Adv-TNFi recipients (4.4%5.2% weight loss (n11)) com- pared with Adv-gal recipients (16.1%7.6% weight loss (n11; P0.0004)) 9 days post-trans- plant. Composite histopathological scores and in- dividual venulitis scores were reduced with the ad- dition of Adv-TNFi. Hepatic CD8 T cells in the recipients of Adv-TNFi were reduced as compared with recipients of Adv-gal. In conclusion, Adv- TNFi reduces MHC class I disparate alloprolifera- tive responses and hepatic GVHD. J. Leukoc. Biol. 78: 1001-1007; 2005.
Acute cholecystitis in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a highly fatal thrombotic microangiopathy. The clinical features characterize it are thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, renal dysfunction, and fever. Secondary TTP has a broad range of etiologies and has been associated with a variety of medical conditions including infections, malignancies, pregnancy, autoimmune disorder, HIV, bone marrow transplant and drugs [1, 2]. We report here a case of TTP associated with acute cholecystitis. A review of the medical literature results in only one other published report of TTP occurring in association with cholecystitis [3].
Action Recognition From Video Using Feature Covariance Matrices

We propose a general framework for fast and accurate recognition of actions in video using empirical covariance matrices of features. A dense set of spatio-temporal feature vectors are computed from video to provide a localized description of the action, and subsequently aggregated in an empirical covariance matrix to compactly represent the action. Two supervised learning methods for action recognition are developed using feature covariance matrices. Common to both methods is the transformation of the classification problem in the closed convex cone of covariance matrices into an equivalent problem in the vector space of symmetric matrices via the matrix logarithm. The first method applies nearest-neighbor classification using a suitable Riemannian metric for covariance matrices. The second method approximates the logarithm of a query covariance matrix by a sparse linear combination of the logarithms of training covariance matrices. The action label is then determined from the sparse coefficients. Both methods achieve state-of-the-art classification performance on several datasets, and are robust to action variability, viewpoint changes, and low object resolution. The proposed framework is conceptually simple and has low storage and computational requirements making it attractive for real-time implementation.
Zileuton restores memory impairments and reverses amyloid and tau pathology in aged Alzheimer's disease mice

The enzyme 5-lipoxygenase (5LO) is upregulated in Alzheimer's disease (AD), and its pharmacologic blockade with zileuton slows down the development of the AD-like phenotype in young AD mice. However, its efficacy after the AD pathology is established is unknown. To this end, starting at 12 months of age triple transgenic mice (3xTg) received zileuton, a selective 5LO inhibitor, or placebo for 3 months, and then the effect of this treatment on behavior, amyloid, and tau pathology assessed. Although mice on placebo showed worsening of their memory, treated mice performed even better than at baseline. Compared with placebo, treated mice had significantly less Aβ deposits and tau phosphorylation secondary to reduced γ-secretase and CDK-5 activation, respectively. Our data provide novel insights into the disease-modifying action of pharmacologically inhibiting 5LO as a viable AD therapeutic approach. They represent the successful completion of preclinical studies for the development of this class of drug as clinically applicable therapy for the disease.
Formative Evaluation of a Framework for High Quality, Evidence-Based Services in School Mental Health

The purpose of this study was to test a three component framework for enhancing quality in school mental health (SMH), focusing on quality assessment and improvement (QAI), family engagement/empowerment, and modular evidence-based practice (EBP) implementation in three established SMH programs. The study involved a 2-year, multisite (Delaware, Maryland, Texas) formative evaluation with clinicians randomly assigned to participate in either the QAI (target) intervention or a Wellness Plus Information (WPI, comparison) intervention. As hypothesized, clinicians who participated in the QAI condition demonstrated significantly greater implementation of quality indicators and greater implementation of EBP as compared to clinicians in the WPI condition. However, contrary to original hypotheses, findings did not reveal differences between the conditions in knowledge or attitudes toward EBP, clinician self-efficacy, or student psychosocial outcomes. Implications for future research on quality improvement in SMH are discussed, with an emphasis on the need to examine the impact of increased implementation and resource support to SMH clinicians.
Cyclin-dependent kinases regulate the antiproliferative function of Smads

Transforming growth factor-beta (TGF-beta) potently inhibits cell cycle progression at the G1 phase. Smad3 has a key function in mediating the TGF-beta growth-inhibitory response. Here we show that Smad3 is a major physiological substrate of the G1 cyclin-dependent kinases CDK4 and CDK2. Except for the retinoblastoma protein family, Smad3 is the only CDK4 substrate demonstrated so far. We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity, leading to higher expression of the CDK inhibitor p15. Mutation of the CDK phosphorylation sites of Smad3 also increases its ability to downregulate the expression of c-myc. Using Smad3(-/-) mouse embryonic fibroblasts and other epithelial cell lines, we further show that Smad3 inhibits cell cycle progression from G1 to S phase and that mutation of the CDK phosphorylation sites in Smad3 increases this ability. Taken together, these findings indicate that CDK phosphorylation of Smad3 inhibits its transcriptional activity and antiproliferative function. Because cancer cells often contain high levels of CDK activity, diminishing Smad3 activity by CDK phosphorylation may contribute to tumorigenesis and TGF-beta resistance in cancers.
Concomitant Waldenstrom macroglobulinemia and IgA plasmablastic myeloma in a patient with untreated IgM paraproteinemia: sequential development of biclonal B-cell neoplasms over a 10-year period in a single individual

Waldenstrom macroglobulinemia and plasma cell myeloma are both mature B-cell neoplasms primarily involving bone marrow and frequently demonstrating paraproteinemia. Plasma cell myeloma has been described in association with other indolent B-cell lymphomas, particularly chronic lymphocytic leukemia, but concomitant Waldenstrom macroglobulinemia and plasma cell myeloma has not been previously described. We report the first case of sequential development of Waldenstrom macroglobulinemia and plasma cell myeloma over a 10-year period in a 73-year-old man with untreated IgM paraproteinemia. The bone marrow biopsy demonstrated dual populations of lymphoid cells: small mature lymphocytes and immature plasma cells. Although both Waldenstrom macroglobulinemia and plasma cell myeloma were restricted to κ light chain, plasma cell myeloma expressed IgA, whereas the plasmacytic component in Waldenstrom macroglobulinemia produced IgM. The biclonal nature of these 2 B-cell neoplasms was further supported by immunofixation electrophoresis and cytogenetic studies. Although the clinical outcome of plasma cell myeloma when concomitant with other indolent B-cell neoplasms is unfavorable, our patient seemed to respond to high-dose bortezomib plus lenalidomide.
Genetic evaluation and counseling in head and neck syndromes.

The role of the dysmorphologist in caring for patients with craniofacial anomalies focuses on accurate diagnosis and counseling. Traditionally, the clinical geneticist has assumed responsibility for providing information to the patient and family on the causation of birth defects, prognosis, and recurrence risks. Accurate diagnosis permits counseling. The dysmorphologist, like other physicians, is trained to associate abnormal findings in multiple organ systems in identifying syndromes. For the dysmorphologist, however, patterns of malformation, not pathophysiology, provide the clues to diagnosis. At least 2% of liveborn infants have a major anomaly, and one third of these major anomalies involve the face and head. Although, with rare exception, birth defects undoubtedly have a genetic component, the cause of most birth defects (60%) remains unidentified. Approximately 7.5% can be attributed to single gene mutations (autosomal dominant, autosomal recessive, and X-linked). Chromosomal aberrations are responsible for another 6%. At least 20% are multifactorial, induced by the exposure of a genetically susceptible fetus to deleterious, largely unidentified environmental effects. Some other birth defects can be attributed to maternal effects such as diabetes, but these, too, may not manifest unless the fetus is susceptible. 1 Despite tremendous advances in recent years in the fields of molecular and developmental biology, the understanding of dysmorphogenesis is still incomplete. Discoveries of the types and classes of molecules involved in normal development, most identified through studies in lower organisms and transgenic mice, have provided the framework for constructing the important pathways in human embryogenesis. Gratitude is owed to the patients and their families who, by participating in linkage studies for the purpose of positional cloning of disease genes, have permitted the identification of important developmental genes in humans. This article reviews recent developments that have contributed to the understanding of the genetics of abnormal craniofacial development and the applicability of this knowledge to patient care. The speed of the bench to bedside transition in DNA diagnostics could leave such an article outdated before it is published. Fortunately, public agencies and academic medical centers have assumed some of the responsibility for providing the clinician with current databases through the World Wide Web.
Prehospital intravenous fluid administration is associated with higher mortality in trauma patients: a National Trauma Data Bank analysis.

Objective: Prehospital intravenous (IV) fluid administration is common in trauma patients, although little evidence supports this practice. We hypothesized that trauma patients who received prehospital IV fluids have higher mortality than trauma patients who did not receive IV fluids in the prehospital setting. Methods: We performed a retrospective cohort study of patients from the National Trauma Data Bank. Multiple logistic regression was used with mortality as the primary outcome measure. We compared patients with versus without prehospital IV fluid administration, using patient demographics, mechanism, physiologic and anatomic injury severity, and other prehospital procedures as covariates. Subset analysis was performed based on mechanism (blunt/penetrating), hypotension, immediate surgery, severe head injury, and injury severity score. Results:Atotalof776,734patientswerestudied.Approximatelyhalf(49.3%) received prehospital IV. Overall mortality was 4.6%. Unadjusted mortality was significantly higher in patients receiving prehospital IV fluids (4.8% vs. 4.5%, P < 0.001). Multivariable analysis demonstrated that patients receiving IV fluids were significantly more likely to die (odds ratio [OR] 1.11, 95% confidenceinterval[CI]1.05‐1.17).Theassociationwasidentifiedinnearlyall subsets of trauma patients. It is especially marked in patients with penetrating mechanism (OR 1.25, 95% CI 1.08‐1.45), hypotension (OR 1.44, 95% CI 1.29‐1.59), severe head injury (OR 1.34, 95% CI 1.17‐1.54), and patients undergoing immediate surgery (OR 1.35, 95% CI 1.22‐1.50). Conclusions: The harm associated with prehospital IV fluid administration is significant for victims of trauma. The routine use of prehospital IV fluid administration for all trauma patients should be discouraged. (Ann Surg 2011;00:00‐00)
Pyrolysis-molecular weight chromatography: A new on-line system for analysis of polymers. II. Thermal decomposition of polyolefins: Polyethylene, polypropylene, polyisobutylene

The thermal decomposition of low-density polyethylene, isotactic polypropylene, and polyisobutylene has been studied in helium at a heating rate of 20°C/min using an experimental system which consists of a programmable pyrolyzer, a thermal conductivity cell, and a mass chromatograph. For low-density polyethylene, the formation of a homologous series of volatile products corresponding to alkanes and alkanes is interpreted in terms of an intramolecular radical transfer process in the primary macroradicals to the 5th, 9th, 13th, and 17th carbon atoms of the chain. For isotactic polypropylene, the formation of a homologous series of volatile products corresponding to monomer, dimers, trimers, and higher oligomers is explained also in terms of intramolecular radical transfer processes. Transfers to the 5th, 9th, and 13th carbon atoms in the secondary macroradicals (indexing from the secondary carbon atom at the chain end) and transfers to the 6th, 10th, and 12th carbon atoms in the primary macroradicals are shown to account for the major products of pyrolysis. For polyisobutylene, in addition to the depolymerization process which accounts for the extensive formation of monomer, intramolecular radical transfer processes in the primary and tertiary macroradicals (the processes proceeding predominantly in the primary macroradicals) are shown to account for the formation of the dimers, trimers, and higher oligomers that occur in the volatile products of decomposition.
Transdermal extraction of interstitial fluid by low-frequency ultrasound quantified with 3H2O as a tracer molecule.

Abstract The transdermal extraction of interstitial fluid by low‐frequency ultrasound offers a potential minimally invasive method of obtaining a fluid sample for at‐home blood glucose monitoring. Here we show that the application of low‐frequency ultrasound (20 kHz) enhances the transdermal transport of interstitial fluid across hairless rat skin. Using 3 H 2 O as a tracer injected intravenously, a measurable amount of water (>1 μL) was extracted without producing any histologic evidence of injury, even after repeated exposures. Piezoelectric transducers were imbedded in the extraction chamber and used to correlate ultrasound spectral properties to the amount of fluid extracted. Results indicate that the highest amount of water extracted occurs when the acoustic coupling media on the surface of the skin is cavitating, resulting in mild ablation of the stratum corneum and a reduction in its resistance to water mass transfer. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1170–1179, 2000
Unique patterns of CpG island methylation in inflammatory bowel disease‐associated colorectal cancers

Background: CpG island (CGI) hypermethylation at discrete loci is a prevalent cancer-promoting abnormality in sporadic colorectal carcinomas (S-CRCs). We investigated genome-wide CGI methylation in inflammatory bowel disease (IBD)-associated CRCs (IBD-CRCs). Methods: Methylation microarray analyses were conducted on seven IBD-CRCs, 17 S-CRCs, and eight normal control colonic tissues from patients without CRC or IBD. CGI methylator phenotype (CIMP), a surrogate marker for widespread cancer-specific CGI hypermethylation, was examined in 30 IBD-CRCs and 43 S-CRCs. Results: The genome-wide CGI methylation pattern of IBD-CRCs was CIMP status-dependent. Based on methylation array data profiling of all autosomal loci, CIMP+ IBD-CRCs grouped together with S-CRCs, while CIMP− IBD-CRCs grouped together with control tissues. CIMP− IBD-CRCs demonstrated less methylation than did age-matched CIMP− S-CRCs at autosomal CGIs (z-score −0.17 vs. 0.09, P = 3 × 10−3) and CRC-associated hypermethylation target CGIs (z-score −0.43 vs. 0.68, P = 1 × 10−4). Age-associated hypermethylation target CGIs were significantly overrepresented in CGIs that were hypermethylated in S-CRCs (P = 1 × 10−192), but not in CGIs that were hypermethylated in IBD-CRCs (P = 0.11). In contrast, KRAS mutation prevalence was similar between IBD-CRCs and S-CRCs. Notably, CIMP+ prevalence was significantly higher in older than in younger IBD-CRC cases (50.0 vs. 4.2, P = 0.02), but not in S-CRC cases (9.7 vs. 16.7, P = 0.92). Conclusions: Cancer-specific CGI hypermethylation and age-associated CGI hypermethylation are diminished in IBD-CRCs relative to S-CRCs, while the KRAS mutation rate is comparable between these cancers. CGI hypermethylation appears to play only a minor role in IBD-associated carcinogenesis. We speculate that aging, rather than inflammation per se, promotes CIMP+ CRCs in IBD patients. (Inflamm Bowel Dis 2011;)
Standard model of color vision: problems and an alternative

The standard model of early color processing postulates an achromatic magno LGN non- opponent pathway summing the outputs of the L and M cones; a red-green parvo LGN opponent cell system differencing L and M cones; and a yellow-blue or tritan parvo LGN opponent cell system differencing S from the (L + M) cones. A number of psychophysical and perceptual findings, however, do not agree with this standard model, and we have suggested an alternative. Our model diverges from that above in three fundamental ways: (1) L-M and M-L cells do not constitute the `red-green' system, but serve as the principal inputs to both the red-green and yellow-blue systems; (2) S-LM and LM-S opponent cells do not constitute the yellow-blue system, but rather combine at a third stage with the LM opponent cells in different ways to produce both the red-green and the yellow-blue systems, serving a modulatory role to break the one effective LGN response axis into separate red-green and yellow-blue perceptual color axes at some cortical site; (3) in addition to chromatic information, the parvo opponent cells (as well as the magno cells) carry intensity information, the chromatic and intensity components being separated at the third stage.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Computer-Aided Wheel Profile Design for Railway Vehicles

Wheel-rail geometry parameters strongly affect the dynamic performance of rail vehicles through their influence on the interaction forces between the wheel and rail. This paper presents an approach that uses nonlinear programming and optimization methods to systematically design wheel profiles that satisfy dynamic performance and wear constraints for conventional rail vehicles. Theoretical studies conducted to this point indicate this approach to be feasible.
Structured interview for partial seizures: Clinical phenomenology and diagnosis

We administered a modified version of the Psychosensory-Psychomotor Phenomena Interview (PPPI) to 128 patients with complex partial seizures (CPS), 20 patients with generalized seizures, and 58 controls (30 normals, 28 back pain) to study the symptoms of partial seizures. The PPPI is a structured interview used by a physician to survey a spectrum of potential seizure symptoms. Use of the PPPI led to the following changes in diagnosis: 10 patients with generalized tonic-clonic seizures were found to have onset with simple partial seizures, 18 patients with complex partial seizures were found for the first time to have auras, and 4 patients with simple partial seizures were also found to have CPS. Overall, auras precede some CPS in 89% of patients. The PPPI led to recognition of more than twice the number of ictal symptoms than standard history and review of previous reports. Differences in symptom frequency (ictal and interictal) between the two seizure groups and between each seizure group and controls were studied. Although several significant associations were found, because of multiple statistical comparisons, results must be interpreted with caution. The PPPI is a valuable tool for examining paroxysmal symptoms in seizure patients, although time constraints limit its use in routine clinical practice.
The effect of local controlled release of sodium fluoride on the stimulation of bone growth

This study was performed to test the feasibility of using a biodegradable delivery system for the local controlled release of sodium fluoride as a mechanism for the stimulation of local bone growth. Sodium fluoride grains were mixed with poly-DL-lactic acid (PLA), and the mixture was then dissolved in acetone. After driving off the solvent, sheets of this material were rolled into rods 3.2 mm in diameter and 28.6 mm long. These were inserted into the intramedullary canals of the right femora of adult New Zealand White rabbits. A sham implant, made the same way but containing no fluoride, was inserted into the contralateral left leg. The effects of three different concentrations of sodium fluoride, 0.125 g NaF/g PLA, 0.250 g NaF/g PLA, and 0.500 g NaF/g PLA, were determined after a 4-week implantation period. In a second set of experiments, the concentration was fixed at 0.500 g NaF/g PLA with implantation durations of 4, 8, and 16 weeks. Expressed in terms of property ratios (experimental/control), bending strengths of the femora were significantly raised in most groups with the notable exception of Group 3 (0.500 g NaF/g PLA, 4 weeks). Cross-sectional area ratios in the distal femora were increased in all groups compared to right/left values for a normal unoperated group (p less than 0.05), with the highest ratio being 1.50 (SD = 0.44) for Group 4 (0.500 g NaF/g PLA, 8 weeks). Only Group 4 animals showed significant (p less than 0.05) increases in midshaft area ratio and none had responses proximally. Growth rates, measured by sequential fluorochrome labeling of bone followed the area ratio data and were only significant for the distal femora.
Experimental Observables Near a Nematic Quantum Critical Point in the Pnictide and Cuprate Superconductors

The newly discovered high temperature superconductor SmFeAs(O1-xFx) shows a clear nematic transition where the square lattice of Fe ions has a rectangular distortion. Similar nematic ordering has also been observed in the cuprate superconductors. We provide a detailed theory of experimental observables near such a nematic transition: we calculate the scaling of specific heat, local density of states (LDOS) and NMR relaxation rate 1/T_1T.
SHORE ICE PILE-UP AND RIDE-UP: FIELD OBSERVATIONS, MODELS, THEORETICAL ANALYSES

Abstract A review of the literature on shore ice pile-up and ride-up in arctic and subarctic waters is presented, along with an account of recent observations made by the authors. Cross-sectional profiles of these features are presented from which models and theoretical analyses were made. The expressions derived give the force required to overcome gravitational potential and friction occurring during ice-piling and ride-up. It was estimated that the distributed force required during ice-piling or ride-up was of the order of 10 to 350 kPa (about 1.5 to 50 psi). Field observations revealed that shore ice pile-up or ride-up appears to occur within a period of less than 30 minutes, at any time of year but most often in the spring and fall. Pile-up seldom occurs more than 10 m inland from the sea but ride-up frequently extends 50 m or more inland, regardless of ice thickness. While steeply sloping shores do not favor ice ride-up, sea ice has mounted the steep, 9-m-high bluff at Barrow, Alaska, destroying structures and taking lives.
Effects of Salt Deposition and Temperature on Polarization Resistance of Steel and the Galvanic Current of Steel-Aluminum Couples During Exposure to Cyclic Humidity

Abstract Use of aluminum alloys for automotive applications is growing steadily. However, galvanic corrosion is a major concern with those alloys. Because of the predominate use of steels in the au...
Water transport across polystyrenesulfonate/alumina composite membranes

Abstract We have investigated the water-transport properties of composite membranes prepared by coating a thin film of a sulfonated polystyrene across the surface of a microporous alumina support membrane. Such composite membranes are designated PSS/Al2O3 composites in this paper. The transport data were obtained by exposing the PSS face of the PSS/Al2O3 composite to a vapor phase of known water partial pressure. Water was sorbed by the PSS and transported across the composite membrane to a stream of dry argon. The concentration of water in the permeate stream (as a result of transport of water across the membrane) was measured using a dew-point measuring device. A mathematical model (used in a previous investigation of water transport in the sulfonated perfluorocarbon polymer Nafion®) was used to analyze the transport data for the PSS/Al2O3 composite membranes. These investigations showed that the solubility of water in the PSS film increased with water vapor pressure in the feed stream. The permeability coefficient for water in the PSS film also increased with water vapor pressure in the feed stream. In contrast, diffusion coefficients for water decreased with vapor pressure in the feed stream, and hence with water content of the PSS film. The effect of sulfonation level and of the nature of the counterion on the magnitude of the water diffusion coefficient was also investigated.
Shuttle solid rocket motor nozzle alternate ablative evaluation

A series of subscale tests are shown to suggest that a lower-cost ablative material than the rayon-based carbon ablative currently used in the Space Shuttle Solid Rocket Motor (SRM) may be used as a substitute. Six such ablatives with outstanding performance characteristics, using spun PAN and continuous pitch and PAN fibers instead of the present, continuous rayon, were identified in the course of tests with HTPB/AL/AP solid propellant grains with a burn time of 12 sec. The test nozzle features an initial throat diameter of 2.2 in. and a 6.1 expansion ratio. In addition to nozzle structural feature drawings, extensive test data tables and propellant formulation and properties tables are provided.