bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of Impact Forces, Hip Angles and Velocities during Simulated Forward Falls Using a Novel Propelled Upper Limb Fall ARrest Impact System (PULARIS)
Authors: Burkhart Timothy A. , Clarke Don , Andrews David M.
Published: January 2012

Previous forward fall simulation methods have provided good kinematic and kinetic data, but are limited in that they have started the falls from a stationary position and have primarily simulated uni-directional motion. Therefore, a novel Propelled Upper Limb fall ARest Impact System (PULARIS) was designed to address these issues during assessments of a variety of fall scenarios. The purpose of this study was to present PULARIS and evaluate its ability to impact the upper extremities of participants with repeatable velocities, hand forces and hip angles in postures and with vertical and horizontal motion consistent with forward fall arrest. PULARIS consists of four steel tubing crossbars in a scissor-like arrangement that ride on metal trolleys within c-channel tracks in the ceiling. Participants are suspended beneath PULARIS by the legs and torso in a prone position and propelled horizontally via a motor and chain drive until they are quick released, and then impact floor-mounted force platforms with both hands. PULARIS velocity, hip angles and velocities and impact hand forces of ten participants (five male, five female) were collected during three fall types (straight-arm, self-selected and bent-arm) and two fall heights (0.05 m and 0.10 m) to assess the reliability of the impact conditions provided by the system. PULARIS and participant hip velocities were found to be quite repeatable (mean ICC = 0.81) with small between trial errors (mean = 0.03 m/s). The ratio of horizontal to vertical hip velocity components (∼0.75) agreed well with previously reported data (0.70-0.80). Peak vertical hand impact forces were also found to be relatively consistent between trials with a mean ICC of 0.73 and mean between trial error of 13.4 N. Up to 83% of the horizontal hand impact forces displayed good to excellent reliability (ICC > 0.6) with small between trial differences. Finally, the ICCs for between trial hip angles were all classified as good to excellent. Overall, PULARIS is a reliable method and is appropriate for studying the response of the distal upper extremity to impact loading during non-stationary, multi-directional movements indicative of a forward fall. This system performed well at different fall heights, and allows for a variety of upper and lower extremity, and hip postures to be tested successfully in different landing scenarios consistent with elderly and sport-related falls.
The Long and Winding Road
Remedy and Reaction
The Peculiar American Struggle over Health Care Reform

by Paul Starr

Yale University Press, New Haven, CT, 2011. 336 pp. $28.50. ISBN 9780300171099.
Authors: Oberlander Jonathan
Published: January 2012

Examining the nature and fate of efforts to reform the healthcare system in the United States, Starr describes how it has become such a politically charged topic there.
The Final Flight of a Sun-Diving Comet
Authors: Lisse Carey M.
Published: January 2012

A suite of space-based observatories has captured the details of a comet as it disintegrates in the solar corona.
Report Notes China's Influence in Emerging Asian Science Zone
Authors: Mervis Jeffrey
Published: January 2012

The 2012 edition of NSF's biennial
Science and Engineering Indicators
report, released this week, shows a sharp rise in intra-Asian collaborations and the growing share of top-cited papers by Chinese authors.
Heads-Up on a Whale's Gulp
Authors: Pennisi Elizabeth
Published: January 2012

Researchers described a new sensory organ in jaws of gulping whales and gave a detailed accounting of whale feeding bouts, showing how the animals unexpectedly twist as they take in water.
Experimental Cancer Therapies Move to the Front Line
Authors: Couzin-Frankel Jennifer
Published: January 2012

It's standard to test drugs in advanced cancer; now, some doctors are using experimental drugs earlier in disease and juggling the challenges that come with doing so.
Notch4
Normalization Reduces Blood Vessel Size in Arteriovenous Malformations
Authors: Murphy Patrick A. , Kim Tyson N. , Lu Gloria , Bollen Andrew W. , Schaffer Chris B. , Wang Rong A.
Published: January 2012

Normalization of Notch expression restores enlarged blood vessels to microvessels through EphB4-mediated reprogramming of arterial endothelial cells.
Arteriovenous Malformations in Five Dimensions
Authors: Kitajewski Jan
Published: January 2012

A tightly controlled Notch4 molecular switch in blood vessel endothelial cells induces regression of arteriovenous malformations in mice.
Feeling SNP-y? Better Analysis Is the Cure
Authors: Cheng Mickie
Published: January 2012

Functional analysis of rare genetic variants in
GCKR
gene sheds light on lipid phenotypes.
Just a Spoonful of Drug Makes Diversity Go Down
Authors: Nyendak Melissa
Published: January 2012

A single dose of clindamycin alters intestinal microbial density in mice and makes them susceptible to
Clostridium difficile
infections.
Your Brain, in HD
Authors: Wang Wei
Published: January 2012

A new electrode “camcorder” records brain activity in high definition for seizure diagnosis and brain-machine interface applications.
Molecular Detection of Campylobacter jejuni as a Cause of Culture-Negative Spondylodiscitis
Authors: Tappe Dennis , Schulze Marco H. , Oesterlein Anett , Abele-Horn Marianne , Baron Stefan , Durchholz Daniel , Langen Heinz-Jakob , Jany Berthold , Schoen Christoph
Published: January 2012

Spondylodiscitis caused by
Campylobacter
species is a rare disease which is most often caused by
Campylobacter fetus
. We report a case of culture-negative spondylodiscitis and a psoas abscess due to
Campylobacter jejuni
in a 68-year-old woman, as revealed by 16S rRNA gene and
Campylobacter
-specific PCRs from biopsied tissue.
West Nile Virus Infections Suppress Early Viral RNA Synthesis and Avoid Inducing the Cell Stress Granule Response
Authors: Courtney S. C. , Scherbik S. V. , Stockman B. M. , Brinton M. A.
Published: January 2012

West Nile virus (WNV) recently became endemic in the United States and is a significant cause of human morbidity and mortality. Natural WNV strain infections do not induce stress granules (SGs), while W956IC (a lineage 2/1 chimeric WNV infectious clone) virus infections produce high levels of early viral RNA and efficiently induce SGs through protein kinase R (PKR) activation. Additional WNV chimeric viruses made by replacing one or more W956IC genes with the lineage 1 Eg101 equivalent in the W956IC backbone were analyzed. The Eg-NS4b+5, Eg-NS1+3+4a, and Eg-NS1+4b+5 chimeras produced low levels of viral RNA at early times of infection and inefficiently induced SGs, suggesting the possibility that interactions between viral nonstructural proteins and/or between viral nonstructural proteins and cell proteins are involved in suppressing early viral RNA synthesis and membrane remodeling during natural WNV strain infections. Detection of exposed viral double-stranded RNA (dsRNA) in W956IC-infected cells suggested that the enhanced early viral RNA synthesis surpassed the available virus-induced membrane protection and allowed viral dsRNA to activate PKR.
Mutation of the F-Protein Cleavage Site of Avian Paramyxovirus Type 7 Results in Furin Cleavage, Fusion Promotion, and Increased Replication
In Vitro
but Not Increased Replication, Tissue Tropism, or Virulence in Chickens
Authors: Xiao Sa , Khattar Sunil K. , Subbiah Madhuri , Collins Peter L. , Samal Siba K.
Published: January 2012

We constructed a reverse genetics system for avian paramyxovirus serotype 7 (APMV-7) to investigate the role of the fusion F glycoprotein in tissue tropism and virulence. The AMPV-7 F protein has a single basic residue arginine (R) at position −1 in the F cleavage site sequence and also is unusual in having alanine at position +2 (LPSS
R
↓FA) (underlining indicates the basic amino acids at the F protein cleavage site, and the arrow indicates the site of cleavage.). APMV-7 does not form syncytia or plaques in cell culture, but its replication
in vitro
does not depend on, and is not increased by, added protease. Two mutants were successfully recovered in which the cleavage site was modified to mimic sites that are found in virulent Newcastle disease virus isolates and to contain 4 or 5 basic residues as well as isoleucine in the +2 position: (
RR
Q
KR
↓FI) or (
RRKKR
↓FI), named Fcs-4B or Fcs-5B, respectively. In cell culture, one of the mutants, Fcs-5B, formed protease-independent syncytia and grew to 10-fold-higher titers compared to the parent and Fcs-4B viruses. This indicated the importance of the single additional basic residue (K) at position −3. Syncytium formation and virus yield of the Fcs-5B virus was impaired by the furin inhibitor decanoyl-RVKR-CMK, whereas parental APMV-7 was not affected. APMV-7 is avirulent in chickens and is limited in tropism to the upper respiratory tract of 1-day-old and 2-week-old chickens, and these characteristics were unchanged for the two mutant viruses. Thus, the acquisition of furin cleavability by APMV-7 resulted in syncytium formation and increased virus yield
in vitro
but did not alter virus yield, tropism, or virulence in chickens.
Arterivirus Minor Envelope Proteins Are a Major Determinant of Viral Tropism in Cell Culture
Authors: Tian Debin , Wei Zuzhang , Zevenhoven-Dobbe Jessika C. , Liu Runxia , Tong Guangzhi , Snijder Eric J. , Yuan Shishan
Published: January 2012

Arteriviruses are enveloped positive-strand RNA viruses for which the attachment proteins and cellular receptors have remained largely controversial. Arterivirus particles contain at least eight envelope proteins, an unusually large number among RNA viruses. These appear to segregate into three groups: major structural components (major glycoprotein GP5 and membrane protein [M]), minor glycoproteins (GP2a, GP3, and GP4), and small hydrophobic proteins (E and the recently discovered ORF5a protein). Biochemical studies previously suggested that the GP5-M heterodimer of porcine reproductive and respiratory syndrome virus (PRRSV) interacts with porcine sialoadhesin (pSn) in porcine alveolar macrophages (PAM). However, another study proposed that minor protein GP4, along with GP2a, interacts with CD163, another reported cellular receptor for PRRSV. In this study, we provide genetic evidence that the minor envelope proteins are the major determinant of arterivirus entry into cultured cells. A PRRSV infectious cDNA clone was equipped with open reading frames (ORFs) encoding minor envelope and E proteins of equine arteritis virus (EAV), the only known arterivirus displaying a broad tropism in cultured cells. Although PRRSV and EAV are only distantly related and utilize diversified transcription-regulating sequences (TRSs), a viable chimeric progeny virus was rescued. Strikingly, this chimeric virus (vAPRRS-EAV2ab34) acquired the broad
in vitro
cell tropism of EAV, demonstrating that the minor envelope proteins play a critical role as viral attachment proteins. We believe that chimeric arteriviruses of this kind will be a powerful tool for further dissection of the arterivirus replicative cycle, including virus entry, subgenomic RNA synthesis, and virion assembly.
Protruding Domain of Capsid Protein Is Necessary and Sufficient To Determine Murine Norovirus Replication and Pathogenesis
In Vivo
Authors: Strong David W. , Thackray Larissa B. , Smith Tom J. , Virgin Herbert W.
Published: January 2012

Human noroviruses (HuNoVs) are the major cause of epidemic, nonbacterial gastroenteritis worldwide. Due to the lack of a tractable model system and the inability to grow HuNoVs in cell culture, factors required for the norovirus (NoV) life cycle and pathogenesis in the host remain largely unknown. The discovery of murine norovirus (MNV) and the development of reverse-genetics systems for this virus provide an opportunity to study these aspects of NoV infection
in vitro
and
in vivo
. Previous studies identified a single amino acid at residue 296 in the protruding (P) domain of the capsid protein that is responsible for determining the virulence of the MNV clone MNV1.CW1 in 12956/SvEv background STAT1-deficient (STAT1
−/−
) mice. In this report, we identified and characterized another determinant of lethality in the P domain that is necessary and sufficient to determine the replication and pathogenesis of the MNV clones MNV1.CW3 and CR6.STL1 in C57BL/6 background STAT1
−/−
mice. Furthermore, we describe how the role of residue 296 in MNV virulence differs between STAT1
−/−
mouse strains. We also describe potential interactions between subdomains of the P domain, as well as between other virus elements, which facilitate recovery of MNV using a reverse-genetics system.
Early stage of nucleic acid electrochemistry. Detection of DNA damage in X-ray-irradiated rats
Authors: Paleček Emil
Published: January 2012

First papers on electroactivity of DNA and RNA were published more then 50 years ago. For about 8 years oscillographic polarography at controlled a.c. (OP, proposed by J. Heyrovský already in 1941) was the method of choice for DNA analysis. Since approximately 1954 Robert Kalvoda developed OP for wide application in various fields. It is shown that already before 1960 it was possible to detect damage to DNA in X-ray-irradiated rats by means of OP. DNA samples from irradiated animals produced significantly larger OP anodic guanine signal indicating changes in the DNA structure. At present, radiation-induced strand breaks and damage to bases in DNA can be electrochemically detected at high sensitivity.
Quality standards and samples in genetic testing
Authors: Ravine David , Suthers Graeme
Published: January 2012

The most critical performance indicator for medical laboratories is the delivery of accurate test results. In any laboratory, there is always the possibility that random or systematic errors may occur and place human health and welfare at risk. Laboratory quality assurance programmes continue to drive improvements in analytical accuracy. The most rigorously scrutinised data on laboratory errors, which come from transfusion medicine, reveal that the incidence of analytical errors has fallen to levels where most of the residual risk is now found in preanalytical links in the chain from patient to result, particularly activities associated with ordering of tests and sample collection. This insight is important for genetic testing because, like pretransfusion testing of patients with unknown blood groups, a substantial proportion of genotyping results cannot be immediately verified. An increasing number of clinical decisions, associated personal and social choices, and legal outcomes are now influenced by genetic test results in the absence of other confirmatory data. An incorrect test result may lead to unnecessary and irreversible interventions, which may in themselves have associated risks for the patient, inaccurate risk assessment regarding the disease, missed opportunities for disease prevention or even wrongful conviction in a court of law. Unfortunately, there is limited information available about the risk of preanalytical errors associated with, and few published guidelines regarding, sample collection for genetic testing. The growing number and range of important decisions made on the basis of genetic findings warrant a reappraisal of current standards to minimise risks in genetic testing.
Delineation of the infrequent mosaicism ofKRASmutational status in metastatic colorectal adenocarcinomas
Authors: Bossard Céline , Küry Sébastien , Jamet Philippe , Senellart Hélène , Airaud Fabrice , Ramée Jean-François , Bézieau Stéphane , Matysiak-Budnik Tamara , Laboisse Christian L , Mosnier Jean-François
Published: January 2012

This study addresses the extent of the heterogeneity ofKRASstatus, present in a minority of metastatic colorectal carcinomas (mCRCs), on the basis of a thorough analysis of surgical resection specimens. Eighteen patients with mCRC were included.KRASmutations (exon 2, codons 12 and 13) were determined using PCR and subsequent direct sequencing. This analysis included primary tumours (n=21), synchronous (n=10) and metachronous (n=18) matched metastases, and pelvic recurrence (n=1). Heterogeneity ofKRASstatus consisted inKRASmutated in (i) the primary tumour but not in its synchronous metastasis, (ii) the metastasis but not in the primary tumour, (iii) the pelvic recurrence but not in the primary tumour, (iiii) some metastases and not in others from the same patient. Finally, theKRASstatus varied among different areas of the same metastatic focus. This study defines the concept ofKRASmosaicism that affects a minority of mCRCs.
The effect of Higgs boson radiation from TeV black holes on the hadronic cross section at the LHC
Authors: Sepehri A. , Zomorrodian M.E. , Moradi Marjaneh A. , Eslami P. , Shoorvazi S.
Published: January 2012

In curved space–time near TeV black holes many gluons and quarks produced by the Unruh effect interact with each other and create Higgs bosons. We study the Unruh effect and show that, for gluons and quarks, the internal stationary state of a Schwarzschild black hole can be represented by a maximally entangled two-mode squeezed state of outgoing and infalling Hawking radiation. We consider different channels for Higgs boson production near event horizons of mini black holes at the Large Hadron Collider (LHC) and obtain the cross section in each channel. We observe that the cross section of a Higgs boson produced via gluon fusion near a single black hole is much larger for smaller black hole masses. This is because the temperature of the black hole becomes larger as the mass becomes smaller and the thermal radiation of the gluons is enhanced. At lower mass, MBH < 4 TeV, the black hole will not be able to emit Higgs, but will still be able to produce a quark; for MBH < 3 TeV the black hole can only emit massless gluons. We show that as the black hole mass at the LHC increases (4 TeV < MBH < 8 TeV) most of the Higgs boson production is due to the Unruh effect near the event horizon of the black hole. Comparing these Higgs boson cross sections with Higgs boson cross sections in perturbative quantum chromodynamics, we find that micro black holes can be a source of Higgs production at the LHC. Finally, we calculate the effects of Higgs boson radiation due to mini black holes on the hadronic cross section at the LHC. We observe that as the order of perturbation theory increases this effect becomes systematically more significant because at higher orders there exist more channels for Higgs production and, in our calculations, Higgs decay into massive quark–antiquark pairs. At smaller masses, MBH < 2 TeV, the hadronic cross section at leading order is large while the cross sections at next-to-leading order and at next-to-next-to-leading order are rising at MBH ∼ 2 and 3 TeV, respectively, and exhibit a turn-over at moderate values of black hole mass.
Photon–photon scattering: a tutorial
Authors: Liang Yi , Czarnecki Andrzej
Published: January 2012

Long-established results for low-energy photon–photon scattering, γγ → γγ, have recently been questioned. We analyze that claim and demonstrate that it is inconsistent with experience. We demonstrate that the mistake originates from an erroneous manipulation of divergent integrals and discuss the connection with another recent claim about the Higgs decay into two photons. We show a simple way of correctly computing low-energy γγ scattering.
Hydrodynamics behaviour of a fluid flow in micro-venturi
Authors: Maqableh A.M. , Ammourah S.A. , Khadrawi A.F. , Al-Nimr M.A. , Benim A.C.
Published: January 2012

Hydrodynamic behaviour of a fluid flow in micro-venturi is investigated numerically taking into account the effect of the Knudsen number (Kn), diameter ratio (β), and Reynolds number (Re). It is found that the velocity jump in the throat of the venturi increases with increasing Re. The axial velocity takes its maximum values at the narrowest section, and these values increase with decreasing Kn. Also, it is found that the dimensionless pressure distribution and the net pressure loss increase as Kn decreases while pressure attains its maximum values at the entrance section. On the other hand, it is observed that increasing Kn and decreasing β cause the discharge coefficient to decrease.
COSMOLOGICAL PERTURBATIONS AND THE RUNNING COSMOLOGICAL CONSTANT MODEL
Authors: VELASQUEZ-TORIBIO ALAN M.
Published: January 2012

We study the matter density fluctuations in the running cosmological constant (RCC) model using linear perturbations in the longitudinal gauge. Using this observable, we calculate the growth rate of structures and the matter power spectrum, and compare these results to SDSS data and the available data for linear growth rate. The distribution of collapsed structures may also constrain models of dark energy. It is shown that the RCC model enhances departures from the ΛCDM model for both cluster number and cumulative cluster number predicted. In general, increasing the characteristic parameter ν leads to significant growth of the cluster number. We found that the theory of perturbations provides a useful tool to distinguish between the new model RCC and the standard cosmological model ΛCDM.
FUTURE TRENDS IN PRODUCT/PROCESS INNOVATION
Authors: SORLI MIKEL , STOKIC DRAGAN
Published: January 2012

The approaches to support innovation in industry, including ICT tools, have experienced tremendous changes in last decades and are likely to be a subject of further evolution. Many research trends could be observed that are likely to provide new innovation approaches and effective means to support such new innovation processes. This paper provides an overview of some of the key trends in product/process innovation in industry. The emphasis is on new approaches for innovation that are already emerging and will find their wide application in industry. Special emphasis is made upon ICT as a key facilitator of the innovation process in future.
Cytokine elevation and transaminitis after laparoscopic donor nephrectomy
Authors: Yap Steven , Park Sang Won , Egan Brian , Lee H. Thomas
Published: January 2012

Acute kidney injury frequently occurs in the critically ill and often progresses into multiorgan dysfunction syndrome, resulting in high mortality. We previously showed that nephrectomized mice had increased interleukin (IL)-6 and tumor necrosis factor (TNF)-α that directly contributed to systemic inflammation and hepatic injury. In this study, we examined whether patients undergoing laparoscopic donor nephrectomy have increased postoperative cytokine levels with injury to the liver and whether the remaining kidney sustains injury. Serial serum and urine samples were collected from 32 patients undergoing laparoscopic donor nephrectomy and 17 patients undergoing nonrenal laparoscopic surgery. Serum IL-6, IL-18, TNF-α and monocyte chemotactic protein-1 (MCP-1) (markers of systemic inflammation) and urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), MCP-1, and IL-18 (markers of acute kidney injury) were quantified by enzyme-linked immunosorbent assay. We also analyzed serum creatinine, aspartate transaminase (AST), and alanine transaminase to assess liver injury. Patients who underwent donor nephrectomy not only demonstrated increased serum creatinine but also had significant increases in serum IL-6, MCP-1, and AST. Serum TNF-α also trended upward in donor nephrectomy patients. Finally, the donor nephrectomy group showed increased urinary NGAL but not KIM-1 at 24 h. Taken together, our findings of increased serum IL-6, MCP-1, and AST after donor nephrectomy suggest that an acute reduction of kidney function induces systemic inflammation and may have distant effects on the liver. Further studies are needed to correlate increased urinary NGAL after donor nephrectomy both as a potential marker for renal tubular stress and/or hypertrophy in the contralateral kidney.
Cocaine sensitization inhibits the hyperpolarization-activated cation current Ih and reduces cell size in dopamine neurons of the ventral tegmental area
Authors: Arencibia-Albite Francisco , Vázquez Rafael , Velásquez-Martinez María C. , Jiménez-Rivera Carlos A.
Published: January 2012

The progressive augmentation of motor activity that results from repeated cocaine administration is termed behavioral sensitization. This phenomenon is thought to be a critical component in compulsive drug taking and relapse. Still, the cellular mechanisms that underlie sensitization remain elusive. Cocaine abuse, nonetheless, is known to evoke neuroplastic adaptations in dopamine (DA) neurotransmission originating from the midbrain's ventral tegmental area (VTA). Here, we report that concomitant with the development of locomotor sensitization to cocaine the hyperpolarization-activated cation current ( Ih) amplitude is depressed by ∼40% in VTA DA cells. Such effect did not result from a negative shift in Ih voltage dependence. Nonstationary fluctuation analysis indicates that this inhibition was caused by an ∼45% reduction in the number of h-channels with no change in their unitary properties. The cocaine-induced Ih depression was accompanied by a reduction in cell capacitance of similar magnitude (∼33%), leaving h-current density unaltered. Two implications follow from these data. First, Ih inhibition may contribute to cocaine addiction by increasing bursting probability in DA cells and this effect could be intensified by the decrease in cell capacitance. Second, the cocaine-induced diminution of DA cell capacitance may also lead to reward tolerance promoting drug-seeking behaviors.
Exploring TB-Related Knowledge, Attitude, Behaviour, and Practice among Migrant Workers in Tajikistan
Authors: Gilpin Christopher , de Colombani Pierpaolo , Hasanova Sayohat , Sirodjiddinova Umrinisso
Published: January 2012

A knowledge, attitude, behaviour, and practice survey was conducted among labour migrants in Tajikistan to elucidate key factors influencing access to tuberculosis diagnosis and care both in their labour destination country and at home. 509 labour migrants were interviewed in Khaton and Rasht Valley regions in Tajikistan using a standardised questionnaire. In addition, in-depth interviews were conducted among ten tuberculosis patients who had recently worked abroad. The study showed that migrants have increased vulnerability to tuberculosis due to the working and living conditions in the destination country and that access to health services is limited due to their legal status or the high cost of health services abroad. The average knowledge of migrants regarding tuberculosis is low and misconceptions are frequent. In Tajikistan, although tuberculosis drugs are usually provided free of charge, tuberculosis diagnosis and ancillary treatment are charged, thus creating a significant financial burden for patients and their families. Improving the access of labour migrants to affordable early diagnosis and treatment in both host countries and Tajikistan is a priority.
PTLD Burkitt Lymphoma in a Patient with Remote Lymphomatoid Granulomatosis
Authors: Stravodimou A. , Cairoli A. , Rausch T. , Du Pasquier R. , Michel P.
Published: January 2012

Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of solid organ transplantation. The majority of PTLD is of B-cell origin, and 90% are associated with the Epstein-Barr virus (EBV). Lymphomatoid granulomatosis (LG) is a rare, EBV-associated systemic angiodestructive lymphoproliferative disorder, which has rarely been described in patients with renal transplantation. We report the case of a patient with renal transplantation for SLE, who presented, 9 months after renal transplantation, an EBV-associated LG limited to the intracranial structures that recovered completely after adjustment of her immunosuppressive treatment. Nine years later, she developed a second PTLD disorder with central nervous system initial manifestation. Workup revealed an EBV-positive PTLD Burkitt lymphoma, widely disseminated in most organs. In summary, the reported patient presented two lymphoproliferative disorders (LG and Burkitt's lymphoma), both with initial neurological manifestation, at 9 years interval. With careful reduction of the immunosuppression after the first manifestation and with the use of chemotherapy combined with radiotherapy after the second manifestation, our patient showed complete disappearance of neurologic symptoms and she is clinically well with good kidney function. No recurrence has been observed by radiological imaging until now.
A Variable Neighborhood Search Algorithm for the Leather Nesting Problem
Authors: Alves Cláudio , Brás Pedro , Valério de Carvalho José M. , Pinto Telmo
Published: January 2012

The leather nesting problem is a cutting and packing optimization problem that consists in finding the best layout for a set of irregular pieces within a natural leather hide with an irregular surface and contour. In this paper, we address a real application of this problem related to the production of car seats in the automotive industry. The high quality requirements imposed on these products combined with the heterogeneity of the leather hides make the problem very complex to solve in practice. Very few results are reported in the literature for the leather nesting problem. Furthermore, the majority of the approaches impose some additional constraints to the layouts related to the particular application that is considered. In this paper, we describe a variable neighborhood search algorithm for the general leather nesting problem. To evaluate the performance of our approaches, we conducted an extensive set of computational experiments on real instances. The results of these experiments are reported at the end of the paper.
Delayed Recognition of Disorders of Sex Development (DSD): A Missed Opportunity for Early Diagnosis of Malignant Germ Cell Tumors
Authors: Hersmus Remko , Stoop Hans , White Stefan J. , Drop Stenvert L. S. , Oosterhuis J. Wolter , Incrocci Luca , Wolffenbuttel Katja P. , Looijenga Leendert H. J.
Published: January 2012

Disorders of sex development (DSD) are defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical. DSD patients with gonadal dysgenesis or hypovirilization, containing part of the Y chromosome (GBY), have an increased risk for malignant type II germ cell tumors (GCTs: seminomas and nonseminomas). DSD may be diagnosed in newborns (e.g., ambiguous genitalia), or later in life, even at or after puberty. Here we describe three independent male patients with a GCT; two were retrospectively recognized as DSD, based on the histological identification of both carcinomain situand gonadoblastoma in a single gonad as the cancer precursor. Hypospadias and cryptorchidism in their history are consistent with this conclusion. The power of recognition of these parameters is demonstrated by the third patient, in which the precursor lesion was diagnosed before progression to invasiveness. Early recognition based on these clinical parameters could have prevented development of (metastatic) cancer, to be treated by systemic therapy. All three patients showed a normal male 46,XY karyotype, without obvious genetic rearrangements by high-resolution whole-genome copy number analysis. These cases demonstrate overlap between DSD and the so-called testicular dysgenesis syndrome (TDS), of significant relevance for identification of individuals at increased risk for development of a malignant GCT.
Intracranial Metastatic Neuroblastoma Treated with Gamma Knife Stereotactic Radiosurgery: Report of Two Novel Cases
Authors: Rowland Nathan C. , Andrews Jennifer , Patel Daxa , LaBorde David V. , Nowlan Adam , George Bradley , Mazewski Claire , Reisner Andrew , Katzenstein Howard M.
Published: January 2012

Intracranial metastasis of neuroblastoma (IMN) is associated with poor survival. No curative therapy for the treatment of IMN currently exists. Unfractionated radiotherapy may be beneficial in the treatment of IMN given the known radiosensitivity of neuroblastoma as well as its proclivity to metastasize as discrete lesions. We present two patients with IMN treated with Gamma Knife stereotactic radiosurgery (SRS). Single-fraction radiotherapy yielded temporary reduction of tumor burden and stability of disease in both patients. SRS may be a useful palliative tool in the treatment of IMN and expands the overall treatment options for this disease.
Effect of Silicon, Titanium, and Zirconium Ion Implantation on NiTi Biocompatibility
Authors: Meisner L. L. , Lotkov A. I. , Matveeva V. A. , Artemieva L. V. , Meisner S. N. , Matveev A. L.
Published: January 2012

The objective of the work was to study the effect of high-dose ion implantation (HDII) of NiTi surface layers with Si Ti, or Zr, on the NiTi biocompatibility. The biocompatibility was judged from the intensity and peculiarities of proliferation of mesenchymal stem cells (MSCs) on the NiTi specimen surfaces treated by special mechanical, electrochemical, and HDII methods and differing in chemical composition, morphology, and roughness. It is shown that the ion-implanted NiTi specimens are nontoxic to rat MSCs. When cultivated with the test materials or on their surfaces, the MSCs retain the viability, adhesion, morphology, and capability for proliferationin vitro, as evidenced by cell counting in a Goryaev chamber, MTT test, flow cytometry, and light and fluorescence microscopy. The unimplanted NiTi specimens fail to stimulate MSC proliferation, and this allows the assumption of bioinertness of their surface layers. Conversely, the ion-implanted NiTi specimens reveal properties favorable for MSC proliferation on their surface.
Bayesian Analysis of a Lipid-Based Physiologically Based Toxicokinetic Model for a Mixture of PCBs in Rats
Authors: Sasso Alan F. , Georgopoulos Panos G. , Isukapalli Sastry S. , Krishnan Kannan
Published: January 2012

A lipid-based physiologically based toxicokinetic (PBTK) model has been developed for a mixture of six polychlorinated biphenyls (PCBs) in rats. The aim of this study was to apply population Bayesian analysis to a lipid PBTK model, while incorporating an internal exposure-response model linking enzyme induction and metabolic rate. Lipid-based physiologically based toxicokinetic models are a subset of PBTK models that can simulate concentrations of highly lipophilic compounds in tissue lipids, without the need for partition coefficients. A hierarchical treatment of population metabolic parameters and a CYP450 induction model were incorporated into the lipid-based PBTK framework, and Markov-Chain Monte Carlo was applied toin vivodata. A mass balance of CYP1A and CYP2B in the liver was necessary to model PCB metabolism at high doses. The linked PBTK/induction model remained on a lipid basis and was capable of modeling PCB concentrations in multiple tissues for all dose levels and dose profiles.
Metformin Reduces Endogenous Reactive Oxygen Species and Associated DNA Damage
Authors: Algire Carolyn , Moiseeva Olga , Deschênes-Simard Xavier , Amrein Lilian , Petruccelli Luca , Birman Elena , Viollet Benoit , Ferbeyre Gerardo , Pollak Michael N.
Published: January 2012

Pharmacoepidemiologic studies provide evidence that use of metformin, a drug commonly prescribed for type II diabetes, is associated with a substantial reduction in cancer risk. Experimental models show that metformin inhibits the growth of certain neoplasms by cell autonomous mechanisms such as activation of AMP kinase with secondary inhibition of protein synthesis or by an indirect mechanism involving reduction in gluconeogenesis leading to a decline in insulin levels and reduced proliferation of insulin-responsive cancers. Here, we show that metformin attenuates paraquat-induced elevations in reactive oxygen species (ROS), and related DNA damage and mutations, but has no effect on similar changes induced by H202, indicating a reduction in endogenous ROS production. Importantly, metformin also inhibited Ras-induced ROS production and DNA damage. Our results reveal previously unrecognized inhibitory effects of metformin on ROS production and somatic cell mutation, providing a novel mechanism for the reduction in cancer risk reported to be associated with exposure to this drug. Cancer Prev Res; 5(4); 536–43. ©2012 AACR.
Transcranial Ultrasound from Diagnosis to Early Stroke Treatment – Part 2: Prehospital Neurosonography in Patients with Acute Stroke – The Regensburg Stroke Mobile Project
Authors: Schlachetzki Felix , Herzberg Moriz , Hölscher Thilo , Ertl Michael , Zimmermann Markus , Ittner Karl Peter , Pels Hendrik , Bogdahn Ulrich , Boy Sandra
Published: January 2012

Background and Purpose: The primary aim of this study was to investigate the diagnostic accuracy and time frames for neurological and transcranial color-coded sonography (TCCS) assessments in a prehospital ‘911’ emergency stroke situation by using portable duplex ultrasound devices to visualize the bilateral middle cerebral arteries (MCAs). Methods: This study was conducted between May 2010 and January 2011. Patients who had sustained strokes in the city of Regensburg and the surrounding area in Bavaria, Germany, were enrolled in the study. After a ‘911 stroke code’ call had been dispatched, stroke neurologists with expertise in ultrasonography rendezvoused with the paramedic team at the site of the emergency. After a brief neurological assessment had been completed, the patients underwent TCCS with optional administration of an ultrasound contrast agent in cases of insufficient temporal bone windows or if the agent had acute therapeutic relevance. The ultrasound studies were performed at the site of the emergency or in the ambulance during patient transport to the admitting hospital. Relevant timelines, such as the time from the stroke alarm to patient arrival at the hospital and the duration of the TCCS, were documented, and positive and negative predictive values for the diagnosis of major MCA occlusion were assessed. Results: A total of 113 patients were enrolled in the study. MCA occlusion was diagnosed in 10 patients. In 9 of these 10 patients, MCA occlusion could be visualized using contrast-enhanced or non-contrast-enhanced TCCS during patient transport and was later confirmed using computed tomography or magnetic resonance angiography. One MCA occlusion was missed by TCCS and 1 atypical hemorrhage was misdiagnosed. Overall, the sensitivity of a ‘field diagnosis’ of MCA occlusion was 90% [95% confidence interval (CI) 55.5–99.75%] and the specificity was 98% (95% CI 92.89–99.97%). The positive predictive value was 90% (95% CI 55.5–99.75%) and the negative predictive value was 98% (95% CI 92.89–99.97%). The mean time (standard deviation) from ambulance dispatch to arrival at the patient was 12.3 min (7.09); the mean time for the TCCS examination was 5.6 min (2.2); and the overall mean transport time to the hospital was 53 min (18). Conclusion: Prehospital diagnosis of MCA occlusion in stroke patients is feasible using portable duplex ultrasonography with or without administration of a microbubble contrast agent. Prehospital neurological as well as transcranial vascular assessments during patient transport can be performed by a trained neurologist with high sensitivity and specificity, perhaps opening an additional therapeutic window for sonothrombolysis or neuroprotective strategies.
Recent Studies of the Human Chromosome 9p21 Locus, Which Is Associated With Atherosclerosis in Human Populations
Authors: Holdt Lesca M. , Teupser Daniel
Published: January 2012

The chromosome 9p21 (Chr9p21) locus was discovered in 2007 by independent genome-wide association studies for coronary artery disease. Since then, the locus has been replicated numerous times and can be considered the most robust genetic marker of coronary artery disease today. Subsequent work has shown associations of Chr9p21 with a number of additional cardiovascular disease traits, such as carotid artery plaque, stroke, aneurysms, peripheral artery disease, heart failure, and cardiovascular mortality, suggesting a more general role in vascular pathology. Importantly, Chr9p21 lacks associations with common cardiovascular risk factors, such as lipids and hypertension, indicating that the locus exerts its effect through a completely novel mechanism. One of the challenges is that the core haplotype block at Chr9p21 resides in a region of the genome devoid of protein-coding genes. Recent progress has been made by functional studies focusing on differential expression of
antisense noncoding RNA in the INK4
locus (
ANRIL
), which is transcribed from the Chr9p21 locus, as well as neighboring protein-coding genes at the
INK4
/
ARF
locus. The emerging concept suggests that
ANRIL
might constitute a regulator of epigenetic modification and thus modulate cardiovascular risk. Here, we review the current clinical, mechanistic, and diagnostic implications of the Chr9p21 locus in cardiovascular disease.
Proteomics Analysis of Cardiac Extracellular Matrix Remodeling in a Porcine Model of Ischemia/Reperfusion Injury
Authors: Barallobre-Barreiro Javier , Didangelos Athanasios , Schoendube Friedrich A. , Drozdov Ignat , Yin Xiaoke , Fernández-Caggiano Mariana , Willeit Peter , Puntmann Valentina O. , Aldama-López Guillermo , Shah Ajay M. , Doménech Nieves , Mayr Manuel
Published: January 2012

Background—

After myocardial ischemia, extracellular matrix (ECM) deposition occurs at the site of the focal injury and at the border region.

Methods and Results—

We have applied a novel proteomic method for the analysis of ECM in cardiovascular tissues to a porcine model of ischemia/reperfusion injury. ECM proteins were sequentially extracted and identified by liquid chromatography tandem mass spectrometry. For the first time, ECM proteins such as cartilage intermediate layer protein 1, matrilin-4, extracellular adipocyte enhancer binding protein 1, collagen α-1(XIV), and several members of the small leucine-rich proteoglycan family, including asporin and prolargin, were shown to contribute to cardiac remodeling. A comparison in 2 distinct cardiac regions (the focal injury in the left ventricle and the border region close to the occluded coronary artery) revealed a discordant regulation of protein and mRNA levels; although gene expression for selected ECM proteins was similar in both regions, the corresponding protein levels were much higher in the focal lesion. Further analysis based on >100 ECM proteins delineated a signature of early- and late-stage cardiac remodeling with transforming growth factor-β1 signaling at the center of the interaction network. Finally, novel cardiac ECM proteins identified by proteomics were validated in human left ventricular tissue acquired from ischemic cardiomyopathy patients at cardiac transplantation.

Conclusion—

Our findings reveal a biosignature of early- and late-stage ECM remodeling after myocardial ischemia/reperfusion injury, which may have clinical utility as a prognostic marker and modifiable target for drug discovery.
A Warm-Bin–Cold-Bulk Hybrid Cloud Microphysical Model*
Authors: Onishi Ryo , Takahashi Keiko
Published: January 2012

This study describes a newly developed bin–bulk hybrid cloud microphysical model named MSSG-Bin, which has been implemented in the Multi-Scale Simulator for the Geoenvironment (MSSG). In the hybrid approach, a spectral bin scheme is used for liquid droplets, while a bulk scheme is used for solid particles. That is, the expensive but more reliable spectral bin scheme treats the relatively well-understood physics of the liquid phase, and the computationally efficient but less robust bulk scheme is used to treat the poorly understood physics of the ice phase. In the bulk part, the prognostic variables are the mixing ratios of cloud ice, snow, and graupel and the number density of cloud ice particles. The bulk component is consistent with MSSG-Bulk, which is a conventional bulk model implemented in MSSG. One-dimensional kinetic simulations and three-dimensional cloud simulations have confirmed the reliability of MSSG-Bin for warm clouds, free from the approximations made in bulk parameterizations, and its applicability to cold clouds, without the significant additional costs required for a bin treatment of the ice phase. Compared with MSSG-Bulk, MSSG-Bin with 33 bins requires 8.3 times more floating-point operations for a one-dimensional shallow convection case, and 4.9 times more for a three-dimensional shallow convection case. Present results have shown the feasibility of using this model for a 25-m-resolution simulation of shallow cumulus on a 512 × 512 × 200 grid.
Short-Range (0–12 h) PQPFs from Time-Lagged Multimodel Ensembles Using LAPS
Authors: Chang Hui-Ling , Yuan Huiling , Lin Pay-Liam
Published: January 2012

This study pioneers the development of short-range (0–12 h) probabilistic quantitative precipitation forecasts (PQPFs) in Taiwan and aims to produce the PQPFs from time-lagged multimodel ensembles using the Local Analysis and Prediction System (LAPS). By doing so, the critical uncertainties in prediction processes can be captured and conveyed to the users. Since LAPS adopts diabatic data assimilation, it is utilized to mitigate the “spinup” problem and produce more accurate precipitation forecasts during the early prediction stage (0–6 h).

The LAPS ensemble prediction system (EPS) has a good spread–skill relationship and good discriminating ability. Therefore, though it is obviously wet biased, the forecast biases can be corrected to improve the skill of PQPFs through a linear regression (LR) calibration procedure. Sensitivity experiments for two important factors affecting calibration results are also conducted: the experiments on different training samples and the experiments on the accuracy of observation data. The first point reveals that the calibration results vary with training samples. Based on the statistical viewpoint, there should be enough samples for an effective calibration. Nevertheless, adopting more training samples does not necessarily produce better calibration results. It is essential to adopt training samples with similar forecast biases as validation samples to achieve better calibration results. The second factor indicates that as a result of the inconsistency of observation data accuracy in the sea and land areas, only separate calibration for these two areas can ensure better calibration results of the PQPFs.
A Climatology of Hurricane Eye Formation
Authors: Vigh Jonathan L. , Knaff John A. , Schubert Wayne H.
Published: January 2012

This paper presents a climatology of the initial eye formations of a broad set of Atlantic tropical cyclones (TCs) during 1989–2008. A new dataset of structure and intensity parameters is synthesized from the vortex data messages transmitted by routine aircraft reconnaissance. Using these data together with satellite imagery and other established datasets, the times when each TC achieved various stages of eye development are tabulated to form the basis of the climatology. About 60% of Atlantic TCs form eyes. Most often, aircraft observe the eye structure before it appears in IR satellite imagery. Eyes tend to form in high potential intensity environments characterized by high sea surface temperatures and low-to-moderate environmental vertical wind shear. A notable discovery is that most (67%) TCs that form eyes tend to do so within 48 h of the cyclone’s reaching tropical storm strength. This suggests the existence of an opportune time window during which a TC can readily form an eye. From the lengths of time taken to reach various stages of eye development, the characteristic time scale for eye formation is estimated to be about 36 h.