cssi/SciSciGPT-SciSciNet huggingface dataset:
Incorporation of Alemtuzumab into Front-Line Therapy of Adult Acute Lymphoblastic Leukemia (ALL) Is Feasible: A Phase I/II Study from the Cancer and Leukemia Group B (CALGB 10102).

Eradication of minimal residual disease (MRD) during the first months of treatment for patients (pts) with ALL is associated with improved disease-free survival (DFS). We hypothesized that Alemtuzumab, a humanized monoclonal antibody directed against CD52, might be an effective, novel agent for eradication of MRD in ALL based on data demonstrating strong CD52 expression in other lymphoid malignancies and in several ALL cell lines, and from case reports of clinical activity in advanced ALL. In CALGB 10102, to define the percentage of CD52+ cases and to demonstrate feasibility, we tested dose escalation of Alemtuzumab in sequential cohorts to a target dose of 30 mg administered sc 3X/week for 4 weeks (12 doses) during post-remission therapy. Pts are eligible to receive Alemtuzumab if lymphoblast CD52 expression at diagnosis is ≥ 10% as determined in a CALGB reference laboratory. The 10102 therapy is composed of monthly treatment modules outlined below: Treatment module sequence is: A,B,C, D, A, B, C followed by maintenance therapy for a total of 2 years. Antimicrobial prophylaxis for cytomegalovirus (CMV) (e.g. acyclovir 800 mg qid) and pneumocystis carinii is mandated. Weekly quantitative monitoring for CMV viremia is performed. 150 pts with untreated ALL have enrolled: Median age is 48 yrs. 124 (83%) pts have precursor-B; 19(13%) have precursor T-ALL and 7 (4%) have biphenotypic or bilineal ALL. Of 139 evaluable pts, 95 (68%) had CD52 ≥ 10%. By immunophenotype, 72% of precursor B and 61% of precursor T pts were eligible to receive Alemtuzumab. Phase I dose escalation was recently completed. Dose limiting toxicity (DLT) for Phase I was defined as the inability to proceed with protocol treatment within 6 weeks of the last dose of Alemtuzumab. Non-heme toxicities have been mild and sc Alemtuzumab administration was well tolerated. Hematologic and infectious toxicities are summarized below: Myelosuppression was transient and use of G-CSF was permitted during Module D. 2 pts were treated for CMV viremia due to rising CMV titers in 2 sequential assays. 6 other pts had transient CMV elevations during or immediately following completion of Alemtuzumab that did not require treatment. 22/24 phase I pts received all 12 doses of Alemtuzumab. There were 2 DLTs reported: 1 pt in cohort 2 due to CMV viremia requiring gancyclovir following completion of Alemtuzumab; and 1 pt in cohort 3 due to ANC
Structural Comparisons of PEI/DNA and PEI/siRNA Complexes Revealed with Molecular Dynamics Simulations

Polyplexes composed of polyethyleneimine (PEI) and DNA or siRNA have attracted great attention for their use in gene therapy. Although many physicochemical characteristics of these polyplexes remain unknown, PEI/DNA complexes have been repeatedly shown to be more stable than their PEI/siRNA counterparts. Here, we examine potential causes for this difference using atomistic molecular dynamics simulations of complexation between linear PEI and DNA or siRNA duplexes containing the same number of bases. The two types of polyplexes are stabilized by similar interactions, as PEI amines primarily interact with nucleic acid phosphate groups but also occasionally interact with groove atoms of both nucleic acids. However, the number of interactions in PEI/DNA complexes is greater than in comparable PEI/siRNA complexes, with interactions between protonated PEI amines and DNA being particularly enhanced. These results indicate that structural differences between DNA and siRNA may play a role in the increased stabilit...
GaN Nanowire MOSFET With Near-Ideal Subthreshold Slope

Wrap-around gate GaN nanowire MOSFETs using Al2O3 as gate oxide have been experimentally demonstrated. The fabricated devices exhibit a minimum subthreshold slope of 60 mV/dec, an average subthreshold slope of 68 mV/dec over three decades of drain current, drain-induced barrier lowering of 27 mV/V, an on-current of $42~\mu \text {A}/\mu \text{m}$ (normalized by nanowire circumference), on/off ratio over $10^{8}$ , an intrinsic transconductance of $27.8~\mu \text {S}/\mu \text{m}$ , for a switching efficiency figure of merit, ${Q}={g}_{m}$ /SS of $0.41~\mu \text{S}/\mu \text{m}$ -dec/mV. These performance metrics make GaN nanowire MOSFETs a promising candidate for emerging low-power applications, such as sensors and RF for the Internet of Things.
Diagnosis makes a difference: Perceptions of older persons with dementia symptoms.

Background/Study Context: Employing the stereotype content model and terror management theory, we examined whether stereotypes and feelings about persons with dementia vary depending on the type of...
Mucinous Histology Signifies Poor Oncologic Outcome in Young Patients With Colorectal Cancer.

BACKGROUND:The incidence of colorectal cancer in the young (under age 40) is increasing, and this population has worse oncologic outcomes. Mucinous histology is a potential prognostic factor in colorectal cancer, but has not been evaluated specifically in young patients.OBJECTIVE:The objective of th
Influenza vaccine failure: failure to protect or failure to understand?

Introduction: I propose that influenza vaccine failure be defined as receipt of a properly stored and administered vaccine with the subsequent development of documented influenza. Several mechanism...
Metro-Goldwyn-Mayer Meets the Atom Bomb

Late in 1945 Metro-Goldwyn-Mayer (MGM), the premier Hollywood motion picture studio, decided to produce a film, on the building of the Atom Bomb. The result, The Beginning or the End, was released in the spring of 1947. To depict living, well-known individuals, MGM had to get their permission, resulting in written and oral interchanges. What follows is based largely on materials in the correspondence of J. Robert Oppenheimer, director of the Los Alamos Laboratory during World War II; Vannevar Bush, head of the Office of Scientific Research and Development (OSRD), which administered the wartime research and development effort including the atom bomb program in its early crucial stages; Leslie R. Groves, a general in the Army Corps of Engineers who headed the Manhattan Project which took over from Bush; and Albert Einstein, whose letter to President Roosevelt in 1939 started the effort (1). The correspondence makes possible a comparison of the original screenplay with various suggested revisions and with the final version as seen by the public. I hope to illuminate the differing viewpoints of the individuals involved in the development of the movie. The process depicted contains clues on issues important for historians and sociologists, as well as those in the mass media. Every genre of exposition — the scientific journal article, the historical monograph, the newspaper article, the novel, the popular motion picture, etc. — imposes a structure and a dynamic on their subject matters.
Spin polarization of photoelectrons in GaAs excited by twisted photons

Interband photoexcitation of electron states with the twisted photons in GaAs, a direct band-gap bulk semiconductor, is considered theoretically. Assuming linearity of the quantum transition amplitudes and applying Wigner-Eckart theorem, we derive a plane-wave expansion of twisted-photon amplitudes. We also obtain relative probabilities for magnetic sublevel population of the photoelectrons in conduction band. The approach for calculating the position-dependent electron polarization, resulting from photoabsorption of twisted light, is described for vertical transitions in the $\mathrm{\ensuremath{\Gamma}}$ point. Theoretical predictions for GaAs show modification of the magnitude and the sign of photoelectron polarization in the region near the photon's phase singularity.
Psychotropic Medication Prescriptions: An Analysis of the Reasons People with Mental Retardation Are Prescribed Psychotropic Medication

A descriptive analysis was undertaken to determine the reasons people with mental retardation are prescribed psychotropic medication. The psychotropic medications and the reasons for which they were prescribed to 71 adults with mental retardation receiving services from a community mental health and mental retardation agency were recorded. There were a total of 145 psychotropic medications prescribed. Of the 145, 85 medications (59%) were prescribed to treat diagnoses or disorders (or both) for which the medications were intended. Twenty-nine of the 145 medications (20%) were prescribed for reasons that did not match the accepted uses of the medications. Results suggest that prescribing practices for people with mental retardation may not always be valid.
Alteration of dietary cysteine affects activities of genes of the transsulfuration and glutathione pathways, and development of skin tissues and feather follicles in chickens

The dietary requirement for cysteine is not determined in poultry since it is not an essential amino acid. The cysteine need is expected to be met through the transsulfuration pathway where homocys...
Dermatology-specific and all-cause 30-day and calendar-year readmissions and costs for dermatologic diseases from 2010 to 2014.

Background Readmissions for skin disease, particularly for the same diagnosis and over time, have not been well studied. Objective To characterize hospital readmissions for skin disease. Methods A cross-sectional observational study examined the Nationwide Readmissions Database from 2010 to 2014, a national sample of hospital discharges in the United States. Results Of the patients in 3,602,599 dermatologic hospitalizations from 2010 to 2014, 9.8% were readmitted for any cause, 3.3% were admitted for the same diagnosis within 30 days, and 7.8% were readmitted for the same diagnosis within the calendar year (CY). The cost of all CY same-cause readmissions was $508 million per year. Mycosis fungoides had the highest 30-day all-cause readmission rate (32%), vascular hamartomas and dermatomyositis had the highest 30-day same-cause readmission rates (21% and 18%, respectively), and dermatomyositis and systemic lupus erythematosus had the highest CY same-cause readmission rates (31% and 24%, respectively). Readmission rates stayed stable from 2010 to 2014. Readmission for the same diagnosis was strongly associated with Medicaid and morbid obesity. Limitations This study is a broad description of hospitalizations for skin disease. Conclusions for individual diseases are not intended. Conclusion The rates and costs of readmissions for skin diseases remained high from 2010 to 2014. This study identifies diseases associated with high risk of hospital readmission, but disease-specific studies are needed. The diseases and risk factors presented should guide additional studies focused on strategies to reduce readmissions in specific skin diseases.
Theory of sampling and sampling practice: edited by Francis F. Pitard, CRC Press, 6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742, 2019, pp. 693 + xxxii, $31.99 (hardback), ISBN: 978-1-13847648-6

The unique feature of this well written comprehensive book is its step-by-step guidance in all thirty-eight chapters under twelve parts. Basic knowledge of calculus, matrix theory and mathematical ...
Characterization of Motor and Non-Motor Behavioral Alterations in the Dj-1 (PARK7) Knockout Rat.

Parkinson’s disease is a neurodegenerative disorder that encompasses a constellation of motor and non-motor symptoms. The etiology of the disease is still poorly understood because of complex interactions between environmental and genetic risk factors. Using animal models to assess these risk factors may lead to a better understanding of disease manifestation. In this study, we assessed the Dj-1 knockout (KO) genetic rat model in a battery of motor and non-motor behaviors. We tested the Dj-1 KO rat, as well as age-matched wild-type (WT) control rats, in several sensorimotor tests at 2, 4, 7, and 13 months of age. The Dj-1-deficient rats were found to rear and groom less, and to have a shorter stride length than their WT counterparts, but to take more forelimb and hindlimb steps. In non-motor behavioral tasks, performed at several different ages, we evaluated the following: olfactory function, anxiety-like behavior, short-term memory, anhedonia, and stress coping behavior. Non-motor testing was conducted as early as 4.5 months and as late as 17 months of age. We found that Dj-1 KO animals displayed deficits in short-term spatial memory as early as 4.5 months of age during place preference testing, as well as impaired coping strategies in the forced swim test, which are consistent with a parkinsonian-like phenotype. In some instances, effects of chronic stress were evaluated in the Dj-1-deficient rats, as an initial test of an environmental challenge combined with a genetic disposition for PD. Although some of the results were mixed with differential effects across several of the behaviors, the combination of the changes we observed indicates that the Dj-1 KO rat may be a promising model for the assessment of the prodromal stage of Parkinson’s disease, but further evaluation is necessary.
Mantle Cell Lymphoma: First-line Therapy in Patients Not Eligible for Stem Cell Transplantation

Mantle cell lymphoma is a distinct subtype of non-Hodgkin’s lymphoma, which has historically been associated with a poor prognosis. It is now recognized as a heterogeneous disease with variable biologic and clinical behavior. Treatment paradigms have evolved along two lines. Younger, fit mantle cell lymphoma (MCL) patients are generally treated with intensive strategies and older less fit patients with non-intensive strategies. Most of the published literature has focused on intensive strategies, which appear to result in more durable remissions, but with an unclear impact on overall survival. The literature is more sparse for the roughly 50 % of patients who are not candidates for intensive strategies, and no “standard” approach has been established for this patient population. However, clues are emerging. Randomized clinical trials have (a) established that bendamustine-rituximab (BR) is more efficacious and less toxic than rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); (b) established that bortezomib should replace vincristine if using an R-CHOP backbone; and (c) established that maintenance rituximab (MR) is beneficial after an R-CHOP induction. In our opinion, it is reasonable to extrapolate the data supporting MR after R-CHOP and apply MR after a BR induction. In our practice, we recommend BR followed by MR for 2 years to MCL patients not eligible for intensive therapy. An ongoing US intergroup trial is testing the addition of bortezomib to the BR backbone and the addition of lenalidomide to MR. This trial may establish a standard of care in the older MCL population. In addition, exciting options for relapsed MCL have emerged in the last few years, with the introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and the development of the lenalidomide-rituximab combination. In this article, we will discuss the current available options for these older MCL patients and the evidence supporting those options.
Advancing Divide-and-Conquer Phylogeny Estimation

One of the Grand Challenges in Science is the construction of the Tree of Life, an evolutionary tree containing several million species, spanning all life on earth. However, the construction of the Tree of Life is enormously computationally challenging, as all the current most accurate methods are either heuristics for NP-hard optimization problems or Bayesian MCMC methods that sample from tree space. One of the most promising approaches for improving scalability and accuracy for phylogeny estimation uses divide-and-conquer: a set of species is divided into overlapping subsets, trees are constructed on the subsets, and then merged together using a "supertree method". Here, we present Exact-RFS-2, the first polynomial-time algorithm to find an optimal supertree of two trees, using the Robinson-Foulds Supertree (RFS) criterion (a major approach in supertree estimation that is related to maximum likelihood supertrees), and we prove that finding the RFS of three input trees is NP-hard. We also present GreedyRFS (a greedy heuristic that operates by repeatedly using Exact-RFS-2 on pairs of trees, until all the trees are merged into a single supertree). We evaluate Exact-RFS-2 and GreedyRFS, and show that they have better accuracy than the current leading heuristic for RFS. Exact-RFS-2 and GreedyRFS are available in open source form on Github at https://github.com/yuxilin51/GreedyRFS.
The interdependence of renal epithelial and endothelial metabolism and cell state

In this issue of Science Signaling, Lovisa et al. demonstrate the contribution of endothelial-to-mesenchymal transition (EndMT) to kidney fibrosis development. Their studies reveal the interdependence of endothelial and epithelial metabolism in health and disease.
Inland Water Body Mapping Using CYGNSS Coherence Detection

This work demonstrates the creation of dynamic inland water body masks at spatial resolutions ranging from 1 to 3 km through the use of a recently developed coherence detector for the delay-Doppler maps produced by the cyclone global navigation satellite system (CYGNSS) constellation. The use of the coherence of the observed measurements reduces many of the uncertainties associated with previous signal-to-noise ratio-based water body detection approaches for CYGNSS. Using data from January 2018 to February 2020 and producing maps representing time intervals ranging from 3 months to 2 years, the water body masks created are found to be associated with a probability of detection that exceeds 80% as compared to the Pekel water mask developed from Landsat observations. The analysis presented in this work highlights the potential of using spaceborne Global Navigation Satellite Systems Reflectometry (GNSS-R) systems for dynamic inland water body mapping.
Balancing Stability and Stiffness Through the Optimization of Parallel Compliance: Using Coupled Tendon Routing

Having a wide range of achievable stiffness is essential for a robotic manipulator to robustly and safely interact with unknown environments. However, the achievable controller stiffness is fundamentally bounded by the system's passive stiffness, which introduces problems for compliant robots with series elasticity. Since strong passive stiffness is undesirable in uncertain environments, in this article, we introduce coupled tendon routing (CTR) along with nonlinear parallel compliance (NPC) to effectively shift this boundary with minimal change to the overall stiffness. We present a novel method for optimization and physical implementation to systematically determine the NPC, meet stability goals, and further reduce the overall stiffness through CTR. Experiments are carried out with two tendon-driven two degrees of freedom (2 DoF) planar fingers to demonstrate and validate the effectiveness of the proposed method.
CuNA: Cumulant-based Network Analysis of genotype-phenotype associations in Parkinson’s Disease

Abstract Parkinson’s Disease (PD) is a progressive neurodegenerative movement disorder characterized by loss of striatal dopaminergic neurons. Progression of PD is usually captured by a host of clinical features represented in different rating scales. PD diagnosis is associated with a broad spectrum of non-motor symptoms such as depression, sleep disorder as well as motor symptoms such as movement impairment, etc. The variability within the clinical phenotype of PD makes detection of the genes associated with early onset PD a difficult task. To address this issue, we developed CuNA, a cumulant-based network analysis algorithm that creates a network from higher-order relationships between eQTLs and phenotypes as captured by cumulants. We also designed a multi-omics simulator, CuNAsim to test CuNA’s qualitative accuracy. CuNA accurately detects communities of clinical phenotypes and finds genes associated with them. When applied on PD data, we find previously unreported genes INPP5J, SAMD1 and OR4K13 associated with symptoms of PD affecting the kidney, muscles and olfaction. CuNA provides a framework to integrate and analyze RNA-seq, genotype and clinical phenotype data from complex diseases for more targeted diagnostic and therapeutic solutions in personalized medicine. CuNA and CuNAsim binaries are available upon request.
Delay in adjuvant chemotherapy administration for patients with FIGO stage I epithelial ovarian carcinoma is associated with worse survival

Objectives: Administration of adjuvant chemotherapy within 42 days from surgery is one of the quality measures for ovarian cancer per SGO. The aim of the present study was to evaluate the impact of chemotherapy delay on the survival of patients with FIGO stage I epithelial ovarian carcinoma (EOC). Methods: The National Cancer Database (NCDB) was accessed and patients diagnosed between 2004-2015 with pathological stage I EOC without a history of another tumor who received multi-agent chemotherapy with known surgery-chemotherapy interval and had at least one month of follow-up were identified. Overall survival (OS) was compared between patients who received multi-agent chemotherapy 1-6 weeks and 6-12 weeks from staging surgery with the log-rank test following generation of Kaplan-Meier curves. A Cox multivariate model was constructed to control for confounders. Results: A total of 8549 patients who met the inclusion criteria and received adjuvant chemotherapy at a median 35 days from surgery were identified; 67.7% received adjuvant chemotherapy 1-6 weeks from staging surgery while 32.3% experienced a delay. Patients who experienced a delay were more likely to be older than 65 years (21.8% vs 18%, p 10 days) (6.2% vs 2.3%, p Conclusions: For patients with early stage EOC administration of adjuvant chemotherapy within 6 weeks from surgery was associated with better survival.
Artificial Intelligence in Age-Related Macular Degeneration (AMD)

Age-related macular degeneration (AMD) is the leading cause of legal blindness in developed countries. Based on clinical features, the disease can be classified into early, intermediate, and late stages. In some patients, AMD advances to the late vision-threatening stage slowly; in others, the disease progresses faster and may quickly lead to a loss of vision in one or both eyes. There is, therefore, a critical need to detect AMD severity accurately. As deep learning has become a rapidly expanding field in imaging-based analysis of AMD, we provide a short overview of recent advances in deep learning applied to AMD severity classification. Our aims are to: (1) give a brief introduction to AMD; (2) indicate how deep learning has been applied to fundus photographs for AMD detection and classification; (3) highlight the potential utility of deep learning methodologies to assist and enhance clinical decision-making in patients with AMD; and (4) provide a starting point for researchers who are interested in this field by providing useful resources such as code and data.
Mutation analysis of the cellulose-binding domain of the Clostridium cellulovorans cellulose-binding protein A.

Cellulose-binding protein A (CbpA) has been previously shown to mediate the interaction between crystalline cellulose substrates and the cellulase enzyme complex of Clostridium cellulovorans. CbpA contains a family III cellulose-binding domain (CBD) which, when expressed independently, binds specifically to crystalline cellulose. A series of N- and C-terminal deletions and a series of small internal deletions of the CBD were created to determine whether the entire region previously described as a CBD is required for the cellulose-binding function. The N- and C-terminal deletions reduced binding affinity by 10- to 100-fold. Small internal deletions of the CBD resulted in substantial reduction of CBD function. Some, but not all, point mutations throughout the sequence had significant disruptive effects on the binding ability of the CBD. Thus, mutations in any region of the CBD had effects on the binding of the fragment to cellulose. The results indicate that the entire 163-amino-acid region of the CBD is required for maximal binding to crystalline cellulose. Images
Carriacou String Band Serenade

Reviewed Medium: book Authors: Rebecca S. Miller Year: 2008 Pages: 312 Publisher: Wesleyan University Press ISBN: 978-0-8195-6858-8 (hard cover). Prices: $49.95 USD(hard cover).
Mayday: distributed filtering for internet services

Mayday is an architecture that combines overlay networks with lightweight packet filtering to defend against denial of service attacks. The overlay nodes perform client authentication and protocol verification, and then relay the requests to a protected server. The server is protected from outside attack by simple packet filtering rules that can be efficiently deployed even in backbone routers. Mayday generalizes earlier work on Secure Overlay Services. Mayday improves upon this prior work by separating the overlay routing and the filtering, and providing a more powerful set of choices for each. Through this generalization, Mayday supports several different schemes that provide different balances of security and performance, continuum, and supports mechanisms that achieve better security or better performance than earlier systems. To evaluate both Mayday and previous work, we also present several practical attacks, two of them novel, that are effective against filtering-based systems.
Ractopamine treatment biases in the prediction of pork carcass composition.

Carcass and live measurements of 45 barrows were used to evaluate the magnitude of ractopamine (RAC) treatment prediction biases for measures of carcass composition. Barrows (body weight = 69.6 kg) were allotted by weight to three dietary treatments and fed to an average body weight of 114 kg. Treatments were: 1) 16% crude protein, 0.82% lysine control diet (CON); 2) control diet + 20 ppm RAC (RAC16); 3) a phase feeding sequence with 20 ppm RAC (RAC-P) consisting of 18% crude protein (1.08%. lysine) during wk 1 and 4, 20% crude protein (1.22% lysine) during wk 2 and 3, 16% crude protein (0.94% lysine) during wk 6, and 16% crude protein (0.82% lysine) during wk 6. The four lean cuts from the right side of the carcasses (n = 15/treatment) were dissected into lean and fat tissue. The other cut soft tissue was collected from the jowl, ribs, and belly. Proximate analyses were completed on these three tissue pools and a sample of fat tissue from the other cut soft tissue. Prediction equations were developed for each of five measures of carcass composition: fat-free lean, lipid-free soft tissue, dissected lean in the four lean cuts, total carcass fat tissue, and soft-tissue lipid mass. Ractopamine treatment biases were found for equations in which midline backfat, ribbed carcass, and live ultrasonic measures were used as single technology sets of measurements. Prediction equations from live or carcass measurements underpredicted the lean mass of the RAC-P pigs and underpredicted the lean mass of the CON pigs. Only 20 to 50% of the true difference in fat-free lean mass or lipid-free soft-tissue mass between the control pigs and pigs fed RAC was predicted from equations including standard carcass measurements. The soft-tissue lipid and total carcass fat mass of RAC-P pigs was overpredicted from the carcass and live ultrasound measurements. Prediction equations including standard carcass measurements with dissected ham lean alone or with dissected loin lean reduced the residual standard deviation and magnitude of biases for the three measures of carcass lean mass. Prediction equations including the percentage of lipid of the other cut soft tissue improved residual standard deviation and reduced the magnitude of biases for total carcass fat mass and soft-tissue lipid. Prediction equations for easily obtained carcass or live ultrasound measures will only partially predict the true effect of RAC to increase carcass leanness. Accurate prediction of the carcass composition of RAC-fed pigs requires some partial dissection, chemical analysis, or alternative technologies.
Postprandial colonic transit and motor activity in chronic constipation

The aim of this study was to correlate colonic motility and transit in patients with constipation and symptoms of the irritable bowel syndrome. Studies were performed in 16 patients with constipation and compared with the results in 12 healthy subjects. Intraluminal pressure was measured with perfused catheter ports in the transverse colon, splenic flexure, and descending and sigmoid colon. Movement of the luminal contents was measured by following the movement of Technetium-99m-DTPA that was instilled as a bolus in the splenic flexure. In both healthy subjects and patients with constipation there was no movement of the intraluminal tracer and no increase in intraluminal pressure during fasting. After eating a meal, healthy subjects and one group of the constipated patients had an increase in the radioactive marker in the transverse colon (p less than 0.03) and in the sigmoid colon (p less than 0.03). The movement of the intraluminal contents was associated with a positive pressure gradient between the descending colon and the transverse and sigmoid colon. There was no retrograde movement of the intraluminal contents and no postprandial increase in intraluminal pressure in the second group of patients with constipation. In healthy subjects, propagating contractions, which were associated with the rapid movement of intraluminal contents, began 60 min after eating. There were no propagating contractions in patients with constipation. These studies suggest that (a) the movement of intraluminal contents in healthy and constipated patients is determined by the postprandial pressure gradients within the colon, and (b) the propagating contraction is necessary for a normal bowel habit.
Assessing risks in two projects: a strategic opportunity and a necessary evil

McFarlan's IT Project Risk Assessment Framework (Applegate, et al., 1996), identifies three main areas of IT project risk: project size, project structure, and technology familiarity. According to this framework, if two IT projects are of similar size, a project which is designed primarily around emerging technologies will entail significantly higher risks than a project which is designed primarily around traditional technologies. This paper analyzes two comparably sized IT projects. One, a telemedicine initiative at Fletcher-Allen Health Care in Vermont, is designed primarily around emerging technologies. The other, the year 2000 compliance program at the New York Metropolitan Transportation Authority (MTA), is focused primarily on fixing and testing existing systems on traditional platforms. Our assessment identified two additional salient criteria which, when applied to the two projects revealed higher risks at the MTA. These criteria are time constraints (i.e., the immovable deadline of the year 2000) and system interdependence (i.e., the need for applications to share data with other applications, both within the MTA and with numerous external parties). When these two factors are taken into account, it becomes evident that Year 2000 initiatives represent far higher project risks than the emerging technology projects that are considered to be on the "bleeding edge."
Measuring Growth With Vertical Scales

A vertical score scale is needed to measure growth across multiple tests in terms of absolute changes in magnitude. Since the warrant for subsequent growth interpretations depends upon the assumption that the scale has interval properties, the validation of a vertical scale would seem to require methods for distinguishing interval scales from ordinal scales. In taking up this issue, two different perspectives on educational measurement are contrasted: a metaphorical perspective and a classical perspective. Although the metaphorical perspective is more predominant, at present it provides no objective methods whereby the properties of a vertical scale can be validated. In contrast, when taking a classical perspective, the axioms of additive conjoint measurement can be used to test the hypothesis that the latent variable underlying a vertical scale is quantitative (supporting ratio or interval properties) rather than merely qualitative (supporting ordinal or nominal properties). The application of such an approach is illustrated with both a hypothetical example and by drawing upon recent research that has been conducted on the Lexile scale for reading comprehension. Intuitively, the concept of growth does not seem terribly complicated. When I was a child I used to visit my grandmother in Austria once a year during the summer. Upon seeing me, she would invariably exclaim “Look how much you have grown!” And so we would. She would march me over to the designated spot in her hallway and I would stand straight while she marked my height against the wall. Then we would compare the most recent mark to the mark that had been left the summer before using a ruler. At that point my grandmother’s qualitative observation could be quantified with respect to the number of centimeters I had grown over a one year time span. This little ritual captures what most people have in mind when they speak of “measuring growth.” It begins with a qualitative assessment over at least two points
Genetic Predisposition to Elevated Serum Thyrotropin Is Associated with Exceptional Longevity

Context: Exceptional longevity is associated with raised serum TSH. Objective: The aim of this study was to examine whether offspring of people with exceptional longevity have elevated serum TSH and whether specific single nucleotide polymorphisms (SNPs) in the TSH-B gene and TSH receptor (TSHR) gene are associated with this phenotype. Design/Setting/Patients: We measured serum TSH and free T4 in Ashkenazi Jewish centenarians (n = 232; median age, 97 yr), their offspring (n = 366; median age, 69 yr), and age-matched controls without familial longevity (n = 163; median age, 70 yr). We determined TSH heritability, its distribution, and association with SNPs in the TSH-B and TSHR genes. Results: Offspring had higher median serum TSH [1.68 mIU/liter (97.5% confidence interval, 0.65 to 4.79 mIU/liter)], compared to controls [1.50 mIU/liter (97.5% confidence interval, 0.63 to 3.93 mIU/liter); P = 0.02], with estimated heritability of 0.33 (P = 0.004). Allele frequency of two SNPs in the promoter/enhancer region of TSHR gene, associated with increased serum TSH, was higher in centenarians and their offspring compared to controls (rs10149689 G allele frequency, 0.57 and 0.53 vs. 0.48; P = 0.001 and P = 0.08; odds ratio, 1.56 and 1.22, respectively; and rs12050077 A allele frequency, 0.57 and 0.53 vs. 0.46; P = 0.0001 and P = 0.01; odds ratio, 1.68 and 1.32, respectively). Linkage disequilibrium between the two SNPs was high (r2 = 0.95), suggesting interaction between them. Furthermore, GA haplotype frequency was significantly higher among centenarians and offspring compared to controls (0.57 and 0.53 vs. 0.46; P = 0.0001 and P = 0.01, respectively). Conclusions: A heritable phenotype characterized by raised serum TSH is associated with human longevity. Carriers of rs12050077 and rs10149689 SNPs in the TSHR have higher serum TSH, possibly contributing to decreased thyroid function and longevity.
Jahn-Teller distortion, ferromagnetic coupling, and electron delocalization in a high-spin Fe–Fe bonded dimer

Abstract Fe2(N,N’-diphenylformamidinate)4, 1, first synthesized in 1994, is one of very few non-organometallic compounds with Fe–Fe distances, (2.46 A) suggestive of an Fe–Fe bond. The electronic structure of 1 has been unclear because of its distorted D2 geometry, as well as its reported S = 4 ground state. Computational investigations using DFT methods have shown that the D2 geometry is the result of a Jahn-Teller distortion away from D4 symmetry, in which the ground state would be orbitally degenerate. Broken symmetry methods have shown that ferromagnetic coupling between the two high-spin Fe(II) ions in 1 is a consequence of spin delocalization caused by a three-electron σ bond and a weaker three-electron δ bond between the Fe atoms. The relationship between ferromagnetic coupling and an Fe–Fe bond is established from results using hybrid functionals having variable amounts of Hartree-Fock exchange, which is found, surprisingly, to mitigate Fe–Fe bonding.
Cytogenetic analyses of somatic chromosomes in a transplantable monomyelocytic leukemia in BALB/c mice.

Abstract In vivo cytogenetic analyses have been performed using G-, C-, and nucleolar organizing region (NOR)-banding techniques, and sister chromatid exchanges (SCE) on a transplantable monomyelocytic leukemia (MML) initially induced in female BALB/c mice by the Rauscher leukemia virus (RLV). Centromeric associations have been found to be greatly increased in MML transplanted mice. Transplantability of the disease has been demonstrated at the cytogenetic level by the presence of female cells in males transplanted with MML cells. G-banding analysis has shown the existence of a marker deleted chromosome 18 in all tissues examined (bone marrow, spleen, and peripheral blood) restricted to female transplanted cells. The NOR-banding analysis has shown a slight increase in the number of Ag-NOR sites per metaphase in MML transplanted mice compared with controls and the existence of an extra chromosome having NOR in MML transplanted mice. No differences were found in C banding between controls and MML transplanted mice. In MML transplanted males, female transformed cells showed a significant reduction in SCE frequency compared with host male cells or controls.
Monte carlo comparison of estimation methods for additive two-way tables

Abstract We considered the problem of estimating effects in the following linear model for data arranged in a two-way table: Response = Common effect + Row effect + Column effect + Residual. This work was occasioned by a project to analyse Federal Aviation Administration (FAA) data on daily temporal deviations from flight plans for commercial US flights, with rows and columns representing origin and destination airports, respectively. We conducted a large Monte Carlo study comparing the accuracy of three methods of estimation: classical least squares, median polish and least absolute deviations (LAD). The experiments included a wide spectrum of tables of different sizes and shapes, with different levels of non-linearity, noise variance, and percentages of empty cells and outliers. We based our comparison on the accuracy of the estimates and on computational speed. We identified factors that significantly affect accuracy and speed, and compared the methods based on their sensitivity to these factors. We co...
Fast calculation of images for high numerical aperture lithography

Many hitherto small effects will become numerically significant in lithography at 70nm and below. The simple assumptions of scalar imaging and uniformly-polarized sources will no longer be tenable. Contrast losses in the resist (e.g. by diffusion) will become appreciable. In addition, the elements of 157nm lenses will be intrinsically polarizing due to spatial dispersion in CaF2, and in general lenses will exhibit residual polarization aberrations. We show here that these effects can be accounted for in a fast "sum-of-coherent-systems" (SOCS) algorithm that is suitable for model-based optical proximity correction (MBOPC). First, we cast the classic equations of vector image formation in a new form that explicitly distinguishes scalar and vector field terms. Lens birefringence is then added to the model; in doing so we take into account the classic phenomenon of double refraction, wherein a given ray splits into two rays each time it passes through an element. In principle, each incident ray then gives rise to an extended family of rays in the exit pupil. However, we show that this coherent set of rays can be merged into a single plane-wave component of the image, allowing a Jones matrix pupil to be defined. Once the vector imaging equations are modified to accommodate customized polarization distributions in the source as well as matrix pupils in the lens, we show that tractable SOCS kernels can be obtained under a generalization of the thin-mask approximation. Such models can be extended to include non-optical effects like resist blur, along with empirical modeling terms. We also discuss computational efficiencies that can be achieved when calculating SOCS kernels, for example by iteratively refining kernels calculated from a reduced basis, and by exploiting system symmetry (radial, dipole, or quadrupole).
Synthesis and determination of the absolute stereochemistry of the enantiomers of adrafinil and modafinil

Abstract Both enantiomers of modafinil, adrafinil, modafinic acid and ethyl modafinate were prepared from the diastereomers formed by reacting racemic β-sulfinyl carboxylic acid with (4R)-phenyl-thiazolidinethione. The absolute stereochemistry of the sulfoxide group was confirmed via X-ray analysis of one of the thiazolidinethione diastereomers.
Speech intelligibility as a function of the number of channels of stimulation for signal processors using sine-wave and noise-band outputs

Vowels, consonants, and sentences were processed through software emulations of cochlear-implant signal processors with 2-9 output channels. The signals were then presented, as either the sum of sine waves at the center of the channels or as the sum of noise bands the width of the channels, to normal-hearing listeners for identification. The results indicate, as previous investigations have suggested, that high levels of speech understanding can be obtained using signal processors with a small number of channels. The number of channels needed for high levels of performance varied with the nature of the test material. For the most difficult material--vowels produced by men, women, and girls--no statistically significant differences in performance were observed when the number of channels was increased beyond 8. For the least difficult material--sentences--no statistically significant differences in performance were observed when the number of channels was increased beyond 5. The nature of the output signal, noise bands or sine waves, made only a small difference in performance. The mechanism mediating the high levels of speech recognition achieved with only few channels of stimulation may be the same one that mediates the recognition of signals produced by speakers with a high fundamental frequency, i.e., the levels of adjacent channels are used to determine the frequency of the input signal. The results of an experiment in which frequency information was altered but temporal information was not altered indicates that vowel recognition is based on information in the frequency domain even when the number of channels of stimulation is small.
Using Lagrangian particle saltation observations for bedload sediment transport modelling

A Lagrangian model for the saltation of sand in water is proposed. Simulated saltation trajectories neglecting particle rotation and turbulence effects compare fairly well with experimental observations. The model for particle motion is coupled with a stochastic model for particle collision with the bed, such that a number of realizations of the saltation process can be simulated numerically. Model predictions of mean values and standard deviations of saltation height, length and streamwise particle velocity agree fairly well with experimental observations. Model predictions of the dynamic friction coefficient are also in good agreement with experimental observations, but they underestimate the value of 0·63 proposed by Bagnold for this coefficient. The saltation model is applied to the estimation of bedload transport rates of sand using a Bagnoldean formulation. Modelled values of the bedload transport rates overestimate those predicted by commonly used bedload formulae, which appears to be a consequence of problems in the definition of the dynamic friction coefficient. These results seem to indicate a few problems with the Bagnoldean formulation, particularly regarding the continuum assumption for the bedload layer, which would be valid only for very high particle concentrations and small particle diameters, and also regarding the evaluation of the shear stress exerted on the bed by the saltating particles. © 1998 John Wiley & Sons, Ltd.
Bayesian area–age–period–cohort model with carcinogenesis age effects in estimating cancer mortality

Abstract Objective : Area–age–period–cohort (AAPC) model has been widely used in studying the spatial and temporal pattern of disease incidence and mortality rates. However, lack of biological plausibility and ease of interpretability on temporal components especially for age effects are generally the weakness of AAPC models. We develop a Bayesian AAPC model where carcinogenesis age effect is incorporated to explain age effects from the underlying disease process. An autoregressive prior structure and an arbitrary linear constraint are used to solve the nonidentifiability issues. Methods : Two multistage carcinogenesis models are employed to derive the hazard functions to substitute the age effects in the AAPC models. The Iowa county-wide lung cancer mortality data are used for the model fitting and Deviance Information Criteria (DIC) is used for model comparison. Results : Our study shows that conventional AAPC model (DIC=19,231.30), AAPC model with Armitage–Doll age effect (DIC=19,233.00) and with two-stage clonal expansion (TSCE) age effect (DIC=19,234.70) achieved the similar DIC values which indicated consistent model fitting among three models. The spatial pattern shows that the high spatial effects are clustered in the south of Iowa and also in largely populated areas. The lung cancer mortality rate is continuously declining by birth cohorts while increasing by the calendar period until 2000–2004. The age effects show an increasing pattern over time which can be easily explained by Armitage–Doll carcinogenesis model since we assume a log-linear relationship between age and hazard function. Conclusions : Our finding suggests that the proposed Bayesian AAPC model can be used to replace the conventional AAPC model without affecting model performance while providing a more biological sound approach from the underlining disease process.
Calibration method choice by comparison of model basis functions to the theoretical instrumental response function

Abstract Sorting through the large array of calibration methods available for first and second order calibration is often a daunting task for initiates into the field of chemometrics. Justifying the selected method as the most appropriate one is even more difficult. Presented here is a justification for calibration method selection based on matching the model employed in the calibration method with the instrumental response function. This is applied to the disparate types of nonlinearities found in both first and second order calibration. Matching the calibration method to the instrumental response function is employed to parse the decision making process for choosing between branches in the first order parsimony tree. The different types of nonlinearities present in second order data and their implications on calibration model selection are discussed.
Pursuit, herding and evasion: A three-agent model of caribou predation

Motivated by problems of pursuit and evasion in coordinated multi-agent systems, we present a model of pursuit, herding and evasion for three agents: a single pursuer, e.g. a bear, chooses a target point along the line connecting two evaders, and the two evaders, e.g. a mother caribou and her calf, each choose a strategy that trades off evasion and herding. The model is based on feedback control of constant speed steered particles on the plane. Dynamics over a reduced set of shape variables are defined. Parallel-motion shape equilibria are studied, with stability analysis and analytic solutions provided for special cases in the parameter space. Simulation results are also presented that suggest existence of optimal strategies for the bear and the caribou in a game theoretic sense.