cssi/SciSciGPT-SciSciNet huggingface dataset:
Digenic mutations of human OCRL paralogs in Dent's disease type 2 associated with Chiari I malformation.

OCRL1 and its paralog INPP5B encode phosphatidylinositol 5-phosphatases that localize to the primary cilium and have roles in ciliogenesis. Mutations in OCRL1 cause the X-linked Dent disease type 2 (DD2; OMIM# 300555), characterized by low-molecular weight proteinuria, hypercalciuria, and the variable presence of cataracts, glaucoma and intellectual disability without structural brain anomalies. Disease-causing mutations in INPP5B have not been described in humans. Here, we report the case of an 11-year-old boy with short stature and an above-average IQ; severe proteinuria, hypercalciuria and osteopenia resulting in a vertebral compression fracture; and Chiari I malformation with cervico-thoracic syringohydromyelia requiring suboccipital decompression. Sequencing revealed a novel, de novo DD2-causing 462 bp deletion disrupting exon 3 of OCRL1 and a maternally inherited, extremely rare (ExAC allele frequency 8.4×10−6) damaging missense mutation in INPP5B (p.A51V). This mutation substitutes an evolutionarily conserved amino acid in the protein’s critical PH domain. In silico analyses of mutation impact predicted by SIFT, PolyPhen2, MetaSVM and CADD algorithms were all highly deleterious. Together, our findings report a novel association of DD2 with Chiari I malformation and syringohydromyelia, and document the effects of digenic mutation of human OCRL paralogs. These findings lend genetic support to the hypothesis that impaired ciliogenesis may contribute to the development of Chiari I malformation, and implicates OCRL-dependent PIP3 metabolism in this mechanism. DNA sequencing identified mutations in two genes that cause a novel variation of Dent’s disease, a rare congenital kidney disorder. Kristopher T. Kahle and his team at Yale’s Department of Neurosurgery in New Haven, Connecticut, and colleagues from the Mayo Clinic evaluated and treated an 11-year-old boy with kidney problems and central nervous system abnormalities. Clinical diagnosis of type 2 Dent’s disease was molecularly confirmed by identifying a novel mutation in the known disease-causing OCRL1 gene on the X chromosome. The presence of neurological alterations led them to suspect the presence of further genetic alterations. Sequencing the entire protein-coding portion of the boy’s genome revealed a mutation in INPP5B, a gene on chromosome 1 with similar function to OCRL1. This mutational combination could explain the boy’s atypical Dent’s disease and associated central nervous system findings.
Using Pre-Assessment and In-Class Questions to Change Student Understanding of Molecular Movements

Understanding how different types of molecules move through cell membranes is a fundamental part of cell biology. To identify and address student misconceptions surrounding molecular movement through cell membranes, we surveyed student understanding on this topic using pre-class questions, in-class clicker questions, and subsequent exam questions in a large introductory biology course. Common misconceptions identified in student responses to the pre-class assessment questions were used to generate distractors for clicker questions. Two-tier diagnostic clicker questions were used to probe incoming common student misconceptions (first tier) and their reasoning (second tier). Two subsequent lectures with assessment clicker questions were used to help students construct a new framework to understand molecular movement through cell membranes. Comparison of pre-assessment and post-assessment (exam) performance showed dramatic improvement in students' understanding of molecular movement: student answers to exam questions were 74.6% correct with correct reasoning while only 1.3% of the student answers were correct with correct reasoning on the pre-class assessment. Our results show that students' conceptual understanding of molecular movement through cell membranes progressively increases through discussions of a series of clicker questions and suggest that this clicker-based teaching strategy was highly effective in correcting common student misconceptions on this topic.
Human Resource Productivity and Organisational Excellence

With the onset of globalisation, where economics and markets play a dominant role in organisational sustainability, no individual organisation can guarantee success based on its own efforts alone. Over the years, the role of those, running an organisation, has undergone a major change-from dependence to independence and now interdependence. The era of interdependence-where teamwork and group dynamics can make or break the business-becomes a necessity and the accepted way of doing things. But with the entry of educated rational managers, freedom of thought and expression; the managers are encouraged to think independently bringing about a higher degree of initiative and quicker decisionmaking. Although there are flashes of brilliance from star performers, the organisation's collective performance is often disappointing and less spectacular. Participation is vital in the viability and survival of an organisation. Motivated and empowered employees are crucial in achieving and meeting organisational goal. Quality products or services are attained when people in an organisation work in tandem aligning their personal goals to the organisational goals and are ready to take the extra step towards achieving excellence. When employees put their hands, heads- and most importantly their hearts in their respective jobs, they produce even astounding results in quality and quantity, productivity and profitability. Every member of an organisation is a store-house of ideas, an uncut diamond and an untapped reservoir of talent that, when properly harnessed, can bring enormous results. Developing quality consciousness in the interest of the organisation among people is like planting trees. It takes a lot of patience but the fruits are very satisfying at the end. In this context, this paper is an endeavour to have a conceptual and theoretical framework to focus on all such possible areas of human resource productivity, being responsible towards achieving organisational excellence. Basically, in this paper, an attempt is theoretically made to visualise different parameters of employee participation in an organisational functioning and how it leads towards achieving organisational success.
FRB 121102: A repeatedly combed neutron star by a nearby low-luminosity accreting super-massive black hole

The origin of fast radio bursts (FRBs) remains mysterious. Recently, the only repeating FRB source, FRB 121102, was reported to possess an extremely large and variable rotation measure (RM). The inferred magnetic field strength in the burst environment is comparable to that in the vicinity of the super-massive black hole Sagittarius A* of our Galaxy. Here we show that all the observational properties of FRB 121102 (including the high RM and its evolution, the high linear polarization degree, an invariant polarization angle across each burst and other properties previously known) can be interpreted within the cosmic comb model invoking a regular neutron star whose magnetosphere is sporadically and marginally combed by a variable outflow from a nearby low-luminosity accreting super-massive black hole in the host galaxy. We propose three falsifiable predictions of the model and discuss other FRBs within the context of the cosmic comb model as well as the challenges encountered by other repeating FRB models in light of the new observations.
TEMPORAL CHANGES IN LIVER STIFFNESS AFTER FONTAN OPERATION: RESULTS OF SERIAL MAGNETIC RESONANCE ELASTOGRAPHY

The relationship between temporal progression of magnetic resonance elastography derived liver stiffness (MRE-LS) and progression of Fontan associated liver disease (FALD) is unknown. To assess this relationship, we hypothesized that progression of MRE-LS correlated with progression FALD severity
An analysis of scale and rotation invariance in the bag-of-features method for histopathological image classification

The bag-of-features method has emerged as a useful and flexible tool that can capture medically relevant image characteristics. In this paper, we study the effect of scale and rotation invariance in the bag-offeatures framework for Renal Cell Carcinoma subtype classification. We estimated the performance of different features by linear support vector machine over 10 iterations of 3-fold cross validation. For a very heterogeneous dataset labeled by an expert pathologist, we achieve a classification accuracy of 88% with four subtypes. Our study shows that rotation invariance is more important than scale invariance but combining both properties gives better classification performance.
Abstract TP567: Identification of Il-17/Cxcl5 as a Novel Regulator of Endothelial-Oligodendrocyte Signaling in Ischemic White Matter Disease

Introduction: Cardiovascular risk factors including obesity accelerate the rate of ischemic white matter lesions through unknown mechanisms. Disruption of the normal signaling between endothelial c...
A CASE OF A VERY PROLONGED ANTI-D: CONFUSION SURROUNDING RH IMMUNOGLOBULIN VS. RH ALLOIMMUNIZATION

Objectives To discuss a case where several doses of Rh immunoglobulin (RhIG) were given during a short period with several miscarriages close together. Although RhIG was only given with bleeding in the first trimester of the most recent pregnancy, the patient was subsequently anti-D positive up to and including 28 weeks gestation. This prolonged anti-D result led to uncertainty as to whether the patient had undergone alloimmunization or a lasting effect from the RhIg. Methods A case report with insight from the obstetrician and transfusion specialist involved in this patient's care and a literature review regarding RhIG. Results Declining anti-D levels and a negative anti-D titre at 30 weeks gestation helped in determining that the prolonged elevation of anti-D was indeed a product of RhIG administration. The literature does not report a prior case of RhIG lasting 22 weeks, and this report discusses the possible factors that may lead to prolonged detection of anti-D subsequent to RhIG including lab testing, dosages of RhIG, status of the baby, and amnestic reactions. Conclusions In the literature, RhIG administration generally leads to positive anti-D titres up to 12 weeks post injection. However, the case shows that positive titers can be observed up to 22 weeks post injection. One important differential to consider in a patient with positive antibodies, in addition to isoimmunization, is extended RhIG effect which can be suggested by declining anti-D titre levels.
The Role of rhBMP-2 in Oral and Maxillofacial Reconstruction

One of the challenges we face today is developing reliable methods to adequately induce osteoinductive properties in osteoconductive grafting materials. By incorporating growth factors, the natural regeneration process is enhanced, and comorbidities associated with requiring a harvesting site are eliminated. While there are drawbacks, namely, increased inflammation and swelling, rhBMP-2 with collagen sponges has been shown to result in bone grafting volume and retention comparable to autografts in a variety of defect sizes and locations.
Quality and accessibility of oncology-related clinical trials information: A content analysis of Internet media.

6547 Background: The Internet is a communication tool that may be used to improve awareness of and access to cancer-related clinical trials; however, few data characterize how the Internet may enco...
Acute Effects of Virtual Reality Exercise Biking on College Students' Physical Responses.

Purpose: Current evidence regarding the use of commercially available immersive virtual reality (VR) headsets and compatible VR exercise apparatus in the promotion of individuals' physical activity (PA) is lacking. This exploratory study investigated the acute effects of a VirZoom VR exercise bike (vBike) on college students' physical responses compared to an exergaming bike (eBike) and a traditional stationary exercise bike (tBike). Method: Forty-eight college students (34 females, Xage = 23.58 ± 3.39; XBMI = 23.81 ± 3.57) completed three separate 20-minute cycling sessions on the vBike, eBike, and tBike in a counterbalanced order. Outcomes included rating of perceived exertion (RPE), assessed at 4-minute intervals throughout each cycling session, and overall PA, operationalized as pedal revolution counts (PRC) during each session. Results: Linear models indicated significant group differences between exercise modalities for RPE (F (2,138) = 14.76-27.30, all p < .001, η2 = 0.17-0.27) and PRC (F (2,138) = 74.862, p < .001, η2 = 0.48). Pairwise comparisons revealed that RPE was reported significantly higher at each time point (i.e., 4th minute, 8th minute, 12th minute, 16th minute, and 20th minute) during the tBike session vs. the vBike and eBike sessions (p < .001) and that participants had higher PRC during the vBike session vs. the eBike and tBike sessions (p < .001). Conclusion: A commercially available VR exercise bike would trigger greater overall PA as compared to exergaming and traditional cycling while being perceived less intense. Future intervention studies conducted in real-world settings to determine cause and effect relationship are warranted.
Preservation and Maintenance of Eubacteria

Publisher Summary This chapter focuses on the preservation and maintenance of eubacteria. Bacteria are morphologically, physiologically, biochemically, and genetically diverse groups of organisms. The morphologically simple forms of these organisms separate into three general categories—namely, cocci, rods, and spirals. However, subgroupings exist within each category. Physiologically, bacteria exhibit the widest range of possibilities. They exist as mesophiles, thermophiles, or psychrophiles; some fastidiously require narrow temperature ranges for growth, whereas others tolerate wide ranges. Bacteria can be saprophytic, pathogenic, parasitic, or symbiotic. Some of these characteristics play important roles in the preservation and maintenance of the organisms. One of the oldest and most traditional methods for preserving bacterial cultures is continuous subculturing. Organisms have to be grown on optimum media; some species require transfer after days or weeks, whereas others need to be transferred after several months or years. Lyophilization obviates many of the disadvantages associated with the subculturing procedure. One of the most significant advantages of this procedure is reduction of variability because of the infrequency of producing new cultures, and the length of survival time.
Implementing the Use of a Brief Cognitive Assessment on Individuals Diagnosed With Schizophrenia in an Acute Psychiatric Facility

Cognitive impairments are prevalent in schizophrenia. The use of a brief cognitive assessment allows for early detection and improves functional outcomes. The purpose of this quality improvement study was to implement the Montreal Cognitive Assessment (MoCA) into the nursing admission assessment for patients who are diagnosed with schizophrenia or related disorders. Nurses administered the MoCA in 67.3% of eligible patients. The high acuity and uncooperative states were the major barriers to screening. The majority of nurses reported confidence in their ability to perform the screening and believed that the results triggered clinical actions to address psychosocial or cognitive deficits.
Multiorgan dysfunction related to chronic ketamine abuse

Ketamine abuse is being increasingly reported worldwide. The drug can produce a dissociative state and hallucinations, making ketamine a favorite recreational agent among drug addicts. Chronic ketamine abuse can damage many organs, including the brain, heart, liver, gastrointestinal tract, and genitourinary system. We report a patient with chronic ketamine abuse who presented with severe cachexia, upper gastrointestinal involvement, hepatobiliary dysfunction, and acute kidney injury.
NEW DETAILS OF THE ULTRASTRUCTURE OF THE OUTER SEGMENTS AND CILIARY CONNECTIVES OF THE RODS OF HUMAN AND MACAQUE RETINAS.

Critical examination of the fine structure of the outer segments of human rods shows that the membranes of at least some and probably most of the flattened saccules filling the outer segment are neither connected with the cell membrane nor with that of other saccules. The saccules typically possess a scalloped edge. The nine pairs of filaments in the ciliary connective become nine singlets in the base of the outer segment and lose their precise orientation before terminating somewhere in the length of the outer segment. The centriolar base in the inner segment possesses nine triplets of filaments and irregular numbers of club-like, fibrous satellites. Rarely tubules insert in the satellite bodies and these may connect to the cell membrane.
Toward Automatic Hint Generation for Logic Proof Tutoring Using Historical Student Data

We have proposed a novel application of Markov decision processes (MDPs), a reinforcement learning technique, to automatically generate hints for an intelligent tutor that learns. We demonstrate the feasibility of this approach by extracting MDPs from four semesters of student solutions in a logic proof tutor, and calculating the probability that we will be able to generate hints at any point in a given problem. Our results indicate that extracted MDPs and our proposed hint-generating functions will be able to provide hints over 80% of the time. Our results also indicate that we can provide valuable tradeoffs between hint specificity and the amount of data used to create an MDP.
A capillary tube pregnancy test.

Abstract The experience with a new, simple, and sensitive capillary tube pregnancy test requiring no refrigeration is described. The results of this test and other tests are compared against histologic results. The ½ unit capillary test, defined as having a sensitivity of 0.5 I.U. of HCG per milliliter, had a higher percentage of agreement with histopathologic results (99.65 per cent) than all other tests studied. The false-positive rate was 0.07 per cent and the false-negative rate was 0.28 per cent. In this series of 1,486 tests, 21 cases of pregnancy, identified by a ½ unit test, were missed by one or two unit tests. The earliest detection of pregnancy by the ½ unit capillary test confirmed by histology was 3 weeks from the last menstrual period (four cases).
Tissue‐specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor‐α knock‐out mice

Angiotensin-converting enzyme (ACE) and ACE2 and the AT1 and AT2 receptors are pivotal points of regulation in the renin-angiotensin system. ACE and ACE2 are key enzymes in the formation and degradation of angiotensin II (Ang II) and angiotensin-(1-7)(Ang-(1-7)). Ang II acts at either the AT1 or the AT2 receptor to mediate opposing actions of vasoconstriction or vasodilatation respectively. While it is known that oestrogen acts to downregulate ACE and the AT(1) receptor, its regulation of ACE2 and the AT2 receptor and the involvement of a specific oestrogen receptor subtype are unknown. To investigate the role of oestrogen receptor-alpha (ERalpha) in the regulation by oestrogen of ACE/ACE2 and AT1/AT2 mRNAs in lung and kidney, ovariectomized female mice lacking apolipoprotein E (ee) with the ERalpha (AAee) or without the ERalpha (alphaalphaee) were treated with 17beta-oestradiol (6 microg day(-1)) or placebo for 3 months. ACE, ACE2, AT1 receptor and AT2 receptor mRNAs were measured using reverse transcriptase, real-time polymerase chain reaction. In the kidney, 17beta-oestradiol showed 1.7-fold downregulation of ACE mRNA in AAee mice, with 2.1-fold upregulation of ACE mRNA in alphaalphaee mice. 17beta-Oestradiol showed 1.5- and 1.8-fold downregulation of ACE2 and AT1 receptor mRNA in AAee mice; this regulation was lost in alphaalphaee mice. 17beta-Oestradiol showed marked (81-fold) upregulation of the AT(2) receptor mRNA in AAee mice. In the lung, 17beta-oestradiol treatment had no effect on AT1 receptor mRNA in AAee mice, but resulted in a 1.5-fold decreased regulation of AT1 mRNA in alphaalphaee mice. There was no significant interaction of oestrogen with ERalpha in the lung for ACE, ACE2 and AT2 receptor genes. These studies reveal tissue-specific regulation by 17beta-oestradiol of ACE/ACE2 and AT1/AT2 receptor genes, with the ERalpha receptor being primarily responsible for the regulation of kidney ACE2, AT1 receptor and AT2 receptor genes.
In the Spirit of Selden Bacon: The Sociology Of Drinking and Drug Problems.

In 1943, the sociologist Selden Bacon proposed studying drinking behavior from a “sociologic” perspective. Since then, a problem-oriented approach – a sociology of problem drinking and problem drug use, not a sociology of drinking and drug use behavior – has dominated the literature on alcohol and other drugs. However, a review of the literature reveals a sociology of drinking and drug problems in the spirit of the research that Bacon proposed. This article suggests that the sociology of drinking and drug problems can be regarded as a multidisciplinary field of study and usefully divided among three primary perspectives: (1) a sociocultural perspective that considers social change, modern society, and cultural influence; (2) a socio-environmental perspective that explores social learning, social setting, and alienation; and (3) an ideological perspective that examines cultural, institutional, and professional ideologies. The sociology of drinking and drug problems exposes the considerable influence of “sociologic” factors on problem drinking and problem drug use across scientific disciplines and, in particular, that problem drinking and problem drug use, from a multidisciplinary standpoint, are not caused exclusively by biologic traits. However, the sociology of drinking and drug problems is limited by the problem-oriented approach. More research needs to analyze the normal use of alcohol and other drugs to better understand the connection between substance use and social life.
The Duty to Take Rescue Precautions

There is much philosophical literature on the duty to rescue. Individuals who encounter and could save, at relatively little cost to themselves, a person at risk of losing life or limb are morally obligated to do so. Yet little has been said about the other side of the issue. There are cases in which the need for rescue could have been reasonably avoided by the rescuee. We argue for a duty to take rescue precautions, providing an account of the circumstances in which it arises. This novel duty has important implications for public policy. We apply it to the situation of some of the uninsured in the United States. Given the US clinician's duty to provide emergency care to all people regardless of ability to pay, some of the uninsured have a moral duty to purchase health insurance. We defend the duty against objections, including the possibility that a right to rescue can be waived, thus undermining a duty to take rescue precautions, that the duty of many professionals is voluntarily incurred, and that a distinction between actively assumed and passively assumed risks matters morally.
Abstract 171: T Cell Mediated Immune Responses Regulate Cardiac Remodeling and Survival in Pressure Overload Induced Heart Failure

Background: Clinical data support that inflammation and the improper regulation of the immune response are intimately associated with Heart Failure (HF), however, the type of immune response involved and whether it regulates cardiac remodeling remains largely unexplored. We hypothesize that T cell mediated immune responses and their recruitment into the heart influence cardiac remodeling and contribute to the pathogenesis of pressure overload induced HF. Methods and Results: Using quantitative flow cytometry we found that T cells infiltrated the heart as Wild-type mice (WT) developed systolic dysfunction and LV hypertrophy in response to transverse aortic constriction (TAC) (p<0.01 TAC vs Sham). Real time imaging demonstrated that T cells from TAC mice adhered to activated heart endothelial cells in higher numbers than T cells from Sham mice under physiological flow conditions in vitro (P<0.05) indicating a systemic T cell activation to pressure overload induced by TAC. Similarly, circulating T cells from...
Discriminating Between Individuals with and without Musculoskeletal Disorders of the Upper Extremity by Means of Items Related to Computer Keyboard Use

Introduction Identifying postures and behaviors during keyboard use that can discriminate between individuals with and without musculoskeletal disorders of the upper extremity (MSD-UE) is important for developing intervention strategies. This study explores the ability of models built from items of the Keyboard-Personal Computer Style instrument (K-PeCS) to discriminate between subjects who have MSD-UE and those who do not. Methods Forty-two subjects, 21 with diagnosed MSD-UE (cases) and 21 without MSD-UE (controls), were videotaped while using their keyboards at their onsite computer workstations. These video clips were rated using the K-PeCS. The K-PeCS items were used to generate models to discriminate between cases and controls using Classification and Regression Tree (CART) methods. Results Two CART models were generated; one that could accurately discriminate between cases and controls when the cases had any diagnosis of MSD-UE (69% accuracy) and one that could accurately discriminate between cases and controls when the cases had neck-related MSD-UE (93% accuracy). Both models had the same single item, “neck flexion angle greater than 20°”. In both models, subjects who did not have a neck flexion angle of greater than 20° were accurately identified as controls. Conclusions The K-PeCS item “neck flexion greater than 20°” can discriminate between subjects with and without MSD-UE. Further research with a larger sample is needed to develop models that have greater accuracy.
Some structural features of the retinal Müllerian cells in the juxta-optic nerve region

Abstract Mullerian cells in the human retina near the optic nerve have been studied with light and electron microscopy. The Mullerian cell processes which are located vitreally to the ganglion cell layer were gathered together in groups, reaching the vitreous surface where their processes spread out to form footplates. In cross-section, each group was seen to consist of several processes, slightly separated from each other. Their cytoplasm contained well-developed, smooth-surfaced endoplasmic reticulum, abundant glycogen particles, mitochondria, and fibrous material. The basal lamina on the vitreal surface of the retina was about 0·4 μm thick. Externally, the pigment epithelial cells were turned slightly vitreally, making contact with the end of the outer nuclear layer. Atrophic photoreceptors, without outer segments, were present in a zone about 50 μm wide surrounding the nerve. The Mullerian cell nuclei in this region were always located in the inner nuclear layer which terminated anterior (vitreally and peripherally) to the outer nuclear layer. Their processes, extending toward the external limiting membrane, were seen near the outer margin of the retina and only a few cell organelles were found in this region.
Approach to learning of medical students in a Caribbean medical school

Introduction : Students’ perception of the learning environment, the curriculum and assessment may influence their approach to learning. Student approach to learning has not been previously studied at Xavier University School of Medicine, Aruba. Hence the present study was carried out. Objective : Obtain information about respondents’ conceptions of learning, approaches to studying and preferences for different types of courses and teaching Method : The Approaches and study skills inventory (ASSIST) was administered to first to fourth semester undergraduate medical (MD) students during the last week of September 2013. Different personal characteristics were noted. The median scores for conceptions of learning, approaches to studying and types of teaching among different subgroups of respondents were compared using appropriate non-parametric tests (p<0.05). Result : Seventy-one of the 86 students (82.5%) participated. Respondents predominantly used deep and strategic approaches to studying and there was a slight preference for a transmitting information type of teaching. Students aged between 20 to 25 years used more deep approach to learning and preferred a supporting understanding teaching approach. First and third semester students used more surface apathetic learning approaches and showed greater syllabus boundedness. Canadian students showed greater deep approach to learning. Conclusion : Deep and strategic learning approaches were mainly used. The influence of the integrated curriculum on learning approaches can be investigated through longitudinal studies. Studies among clinical students and in other medical schools are required.
Matter and energy flows in biological and ecological systems

Basic concepts are presented for a new theory to represent the dynamics of matter and energy flows in biological and ecological systems. It is a mechanistic theory based on the transport, storage and transformation of matter and the energy required to cause these processes. The descriptions of system structure and component objects are discussed, and state variables are identified from energetic considerations. Procedures for the development of conceptual and mathematical models are outlined. First generation conceptual models are presented for an autotroph in its environment and for carbon flow in a general ecosystem.
Regulatory role of the engagement of MHC class II on the activation and proliferation of human T cells. ♦ 56

We have employed specific monoclonal antibodies to engage the major histocompatibility complex (MHC) class II on the T cell surface, and assayed for several intracellular events to study the role of MHC class II in human activated T cells. We have characterized in the engaged T cells the phosphorylation of cellular proteins, of the enzymes phosphotyrosine kinases(PTK) and phospholipase C (PLC), the Ca++ mobilization, and the antigen-specific proliferation. The engagement of surface MHC class II was associated with an overall increase in cellular protein tyrosine phosphorylation. There was an increase in the tyrosine phosphorylated p56lck and p59fyn, but not ZAP-70. The tyrosine phosphorylation of PLC-γ1, which co-immunoprecipitated with surface MHC class II in an apparent complex with the adaptor protein Grb-2, was significantly augmented after the engagement of MHC class II. The engagement of MHC class II, either with or without cross-linking ligation by anti-species antibody, increased the intracellular Ca++ mobilization at a comparable level to anti-CD3 treatment. In contrast, such engagement of MHC class II on T cells partially inhibited antigen-specific proliferation. These data suggest that surface MHC class II involves both the PTK and PLC pathways, probably via a complex comprising MHC class II, the enzymes, and the adaptor protein Grb-2. We conclude that the engagement of surface MHC class II, which leads to T cell activation but partially inhibits its proliferation, could play a role in the regulation of immunological responses.
Household Smoking Restrictions Relate to Time to First Cigarette Smoked in the Morning

Introduction: The time a smoker waits until the first cigarette of the morning is often used as a measure of dependence with the rationale that more dependent smokers will smoke sooner upon waking than will less dependent smokers after going several hours without a cigarette overnight. Aims: We sought to examine the relationship between time-to-first-cigarette (TTFC) and household smoking restrictions in two independent samples. Methods: Two samples of smokers, one treatment-seeking community sample ( N = 433) and one non-treatment seeking sample of smokers with serious mental illness (i.e., Schizophrenia, Schizoaffective Disorder, or Bipolar I Disorder) ( N = 94), provided information on cigarette dependence with the Fagerstrom Test for Nicotine Dependence (FTND) and on household smoking restrictions. Results: Half (50%) of smokers with serious mental illness and 36.7% of smokers from the general population reported that there were no limitations to smoking in their home. Household smoking restrictions were significantly and positively related to TTFC in both samples. Conclusions: These data indicate that greater attention to TTFC may be warranted. The TTFC item is intended to measure dependence based on the premise that greater dependence should be associated with shorter TTFC. If TTFC is related to a household smoking ban, however, this item may not be assessing dependence as intended in some cases.
The synthesis of 3β,11β,17,21-tetrahydroxy-Δ-pregnene-20-one and its 11-keto analog

3β,11β,17,21-Tetrahydroxy-Δ5-pregnene-20-one and its 11-keto analog have been synthesized from hydrocortisone-BMD. Sodium bismuthate oxidation of the unsaturated tetrolone yielded 3β,11β-dihydroxy-5,6α-oxidoandrostane-17-one as well as the expected 3β,11β-dihydroxy-Δ5-androstene-17-one. The 5α,6α-oxide was identical with the major product from the monoperphthalic acid oxidation of 3β,11β-dihydroxy-Δ5-androstene-17-one.
Structure and projections of white matter neurons in the postnatal rat visual cortex.

Transient contributions of subplate neurons to the initial development of the cortex are well-characterized, yet little data are available on a subpopulation of subplate neurons that persist in the white matter (WM) of the cerebral cortex across development. To characterize the WM neurons, differential interference contrast and Nomarski optics were used to visualize individual cells in the WM in slices of rat visual cortex at postnatal ages 9–23. Soma-dendritic morphology and local axonal projection patterns, including probable synaptic innervation sites of their axons, were identified by intracellular filling with biocytin during electrophysiologic recordings. Dendritic branches of all WM neurons, tripartitioned here into upper, middle, and deep divisions, extend throughout the WM and frequently into the overlying cortex. Axonal arborizations from most WM neurons, including apparent boutons, project into adjacent WM with many also innervating overlying cortical layers, whereas some project into the stratum oriens/alveus of the hippocampal formation. Processes of a subset of WM neurons appear to be confined to the WM itself. By using antimicrotubule associated protein (MAP2) immunostaining to quantify the density of WM neurons in rat visual cortex, we find that their overall numbers decrease to approximately 30% of initial levels during postnatal development. During this same developmental period, an increasing percentage of WM neurons contain the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), as evaluated by immunostaining. Thus, WM neurons that survive the initial perinatal period of cell death are positioned under the laminae of the maturing cortex to potentially modulate the integration of visual signals through either conventional synaptic or nonconventional (diffusible NO signaling) mechanisms. J. Comp. Neurol. 434:233–252, 2001. © 2001 Wiley-Liss, Inc.
Investigating the electro-thermal origin of breakdown in low-K/Cu dielectrics under short duration over stressed pulsed regime

We present a detailed study of low-K/Cu structures under short duration pulse regime and establish a microscopic understanding of breakdown behavior under high current stressing. Random and anomalous behavior of the breakdown characteristics observed under very fast pulsing conditions are explained through electro-thermal instability. A model based on extensive experimental study has been developed to show switching behavior of a conducting path (short failure) due to meltdown of copper. The dumping of critical energy can lead to permanent damage and leads to an open failure. Established breakdown model has been critically linked to the material behavior and extrapolated to understand the TDDB behavior of the low K dielectric.
New clique and independent set algorithms for circle graphs

Abstract Given the interval model of an n -vertex, e -edge circle graph G , it is shown how to find a clique of G of maximum size l (respectively, maximum weight) in O (n log n + min [e,nl log ( 2n l )]) (respectively, O( n log n + min[ n 2 , e log log n ])) time. The best previous algorithms required, respectively, ⊝(n 2 ) and O( n 2 + e log log n ) time. An O( n log n + dn ) time and space algorithm that finds an independent set of maximum weight for the interval model of G is also presented. Here d is the maximum number of intervals crossing any position of the line in the interval model of G . The best previous solution for this problem took time O ( n 3 ).
Cocaine, Appetitive Memory and Neural Connectivity

This review examines existing cognitive experimental and brain imaging research related to cocaine addiction. In section 1, previous studies that have examined cognitive processes, such as implicit and explicit memory processes in cocaine users are reported. Next, in section 2, brain imaging studies are reported that have used chronic users of cocaine as study participants. In section 3, several conclusions are drawn. They are: (a) in cognitive experimental literature, no study has examined both implicit and explicit memory processes involving cocaine related visual information in the same cocaine user, (b) neural mechanisms underlying implicit and explicit memory processes for cocaine-related visual cues have not been directly investigated in cocaine users in the imaging literature, and (c) none of the previous imaging studies has examined connectivity between the memory system and craving system in the brain of chronic users of cocaine. Finally, future directions in the field of cocaine addiction are suggested.
Liver disease in children with pizz α1-antitrypsin deficiency

We present our experience with 18 pediatric patients with alpha 1-antitrypsin deficiency of the PiZZ phenotype. Fifteen patients (83%) presented with neonatal cholestatic jaundice at a mean age of 2 +/- 0.6 months (+/- S.D.). The male:female ratio was 15:3, indicating a male predominance. All metabolic, infectious and obstructive causes of jaundice were ruled out by appropriate tests in the patients with neonatal cholestasis. Liver biopsy in 14 patients with neonatal cholestasis showed a histological picture of cholestasis in all biopsies; neonatal giant cell hepatitis appeared in seven, increased fibrosis in appeared five and established liver cirrhosis appeared in two biopsies. Patients were followed for a mean of 3.7 +/- 2.4 years (+/- S.D.). Of the 15 patients with neonatal cholestasis, 3 under went liver transplantation because of decompensated liver cirrhosis at 3, 3 1/2 and 7 years. Two patients died at 4 months and 3 years from complications of liver cirrhosis. Of the remaining 10 patients, 3 had histological evidence of liver cirrhosis, and the remaining 7 patients continue to have enlarged liver and spleen with abnormal liver function tests. Of the three patients without history of neonatal cholestasis, only one had enlarged liver and spleen, and the remaining two are healthy with normal liver function tests. Our experience indicates serious liver disease is highly likely to develop in patients with PiZZ alpha 1-antitrypsin deficiency who present with neonatal cholestatic jaundice. Our experience differs from more recent reports on such patients.
A general program for the calculation of the kappa coefficient

The kappa coefficient (x) was developed by Cohen (1960) for the purpose of assessing chance-eorrected interrater agreement on nominal data. In its simplest form, )( is defined as follows: )( = (Po-Pc)/(1-pc), where Po is the observed proportion of agreement and P« is the chance or expected proportion of agreement. Over the past three decades, )( has been extended to allow assessment among K > 2 raters (e.g., Conger, 1980; Uebersax, 1982), to allow missing observations (e.g., Conger, 1980; Fleiss, 1971; Uebersax, 1982), to allow nonmutually exclusive response categories (i.e., subjects can be classified into more than one category; e.g., Fleiss, Spitzer, Endicott, & Cohen, 1972; Kraemer, 1980), and to allow for partial disagreement (Cohen, 1968). The sampling distribution of )( has also been identified, allowing variance estimates to be calculated and significance tests to be conducted (Fleiss, Cohen, & Everitt, 1969). Not surprisingly, several computer programs have been offered as efficient means of providing one or more of these )( features (e.g., Bloor, 1983; Burns & Cavallaro, 1982; Chan, 1987; Powers, 1985; Watkins & Larimer, 1980). The present program provides a more comprehensive package by including features found in these earlier programs, while including additional features as well. The program provides for the calculation of )( and weighted )( for any number of raters (subject to the memory constraints of the machine being used). When the number of raters is greater than 2, all pairwise x are also provided. Missing data in the matrix of observations are handled in the calculation of multiple-rater )( by using Uebersax's (1982) generalized approach. This approach is based on the calculation of weighted averages of pairwise estimates for observed agreement (Po) and chance agreement (Pc), each weighted by the number of subjects each pair of judges has in common. For weighted x, the user. suppli~s a weight matrix that indicates the degree of partial credit to be given for different types of disagreement. The careful construction of the weight matrix also allows the calculation of )( when subjects can be classified into more than one category. This arises, for example, in the case of medical or psychiatric diagnosis where more than one condition may be present in the same subject. Relative ordering of these multiple diagnoses is also allowed. Thus, when the order of primary and secondary diagnoses is critical (A-B * B-A), different orders must be considered separate categories with a weight assigned to reflect their partial disagreement.
Safety and efficacy of addition of VEGFR and EGFR-family oral small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: a systematic review and meta-analysis of randomized controlled trials

Abstract Background The approach of combining cytotoxic chemotherapy with oral small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a variety of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. Patients and methods PubMed and the ASCO databases were searched up to March 2013. We included randomized trials in which the FDA approved vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor-family (EGFR)-targeted TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR) were calculated. Results A total of 16,011 patients from 43 trials were included. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32–2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58–2.06), and any severe AE (RR, 1.25; 95% CI, 1.16–1.36). The addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76–0.89), but not OS (HR, 0.99; 95% CI, 0.95–1.03). Conclusions It is important for physicians to weigh the risk of toxicity versus the modest PFS benefit associated with chemotherapy plus TKI in patients with solid cancers.
Numerical Solution of Partial Differential Equations in Science and Engineering

The book by Lapidus and Pinder is a very comprehensive, even exhaustive, survey of the subject. The dust jacket accurately labels the book as a reference/text. In the first three chapters a brief introduction is given to the terminology of partial differential equations followed by a very good description of the basic concepts of finite difference and finite element techniques. The final three chapters deal individually with parabolic, elliptic, and hyperbolic equations. The book is unique in that it covers equally finite difference and finite element methods. Smaller coverage is given to collocation and boundary element methods.
Procreating V-detectors for nonself recognition: an application to anomaly detection in power systems

The artificial immune system approach for self-nonself discrimination and its application to anomaly detection problems in engineering is showing great promise. A seminal contribution in this area is the V-detectors algorithm that can very effectively cover the nonself region of the feature space with a set of detectors. The detector set can be used to detect anomalous inputs. In this paper, a multistage approach to create an effective set of V-detectors is considered. The first stage of the algorithm generates an initial set of V-detectors. In subsequent stage, new detectors are grown from existing ones, by means of a mechanism called procreation. Procreating detectors can more effectively fill hard-to-reach interstices in the nonself region, resulting in better coverage. The effectiveness of the algorithm is first illustrated by applying it to a well-known fractal, the Koch curve. The algorithm is then applied to the problem of detecting anomalous behavior in power distribution systems, and can be of much use for maintenance-related decision-making in electrical utility companies.
Area-Based Social Characteristics of Workplace Homicide Risk

Purpose Community-level factors associated with workplace homicide have not been explored in detail. The aim of our study is to describe socioeconomic (SES) and crime characteristics associated with areas at high-risk for worker homicide. Methods Using GIS methods, North Carolina workplaces were spatially linked to SES data from the census and crime data from law enforcement agencies. Census block groups (n=4076) comprised the unit of analysis and were categorized as being at high (≥ 75 th percentile) or low risk for workplace homicide according to the proportion of workplaces in each block group classified as high-risk for worker homicide (based on pervious research). Separate models were constructed to examine social factors (social organization disruptions and SES advantage) and agency-level crime (index, property and violent) rates, respectively. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results From multivariate models where crime was the primary exposure, violent crime rates > 75 th percentile was associated with block groups at high-risk for workplace homicide (OR=1.48; 95%CI=1.05–2.09). In models examining social organization disruption measures: residential mobility (OR=1.86, 95%CI=1.27–2.72), population density (OR=1.28, 95%CI=1.04–1.58), and low percentages (≤ 25 th percentile) of Black, non-Hispanic (OR=1.36, 95%CI=1.13–1.64) and foreign born (OR=1.40, 95%CI=1.18–1.68) residents were positively associated with high-risk block groups. Level of SES advantage was inversely associated with block groups containing a high proportion of high-risk workplaces (OR=0.57, 95%CI=0.42–0.78). Conclusion Areas with a high violent crime rate, social organization disruption and low SES advantage contain a higher proportion of high-risk workplaces. Elucidating social influences on violence complements current understanding of workplace homicide.
Measuring Referrals: The Use of Paraprofessionals at the Reference Desk

This study documents the number and types of referrals to librarians by a paraprofessional staff member at an academic reference desk. Results indicate that over two semesters, only 7.4% of the reference desk transactions required referral to a librarian. From the results of this and other studies, the authors explore the expanded use of trained paraprofessionals at the reference desk.