bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase I Study of Weekly Topotecan in Combination with Pemetrexed in Patients with Advanced Malignancies
Authors: Burris Howard A. , Infante Jeffrey R. , Jewell Roxanne C. , Spigel David R. , Greco F. Anthony , Thompson Dana S. , Jones Suzanne F.
Published: August 2010

Introduction.

This phase I study evaluated the safety, tolerability, preliminary antitumor activity, and pharmacokinetic interaction of weekly topotecan (days 1 and 8) in combination with pemetrexed (day 1 only) in patients with advanced solid tumors.

Methods.

Patients received topotecan (3.0–4.0 mg/m2 i.v. days 1 and 8) and pemetrexed (375–500 mg/m2 i.v. day 1) over 21-day cycles. Patients were accrued across five different dose levels and were observed for safety, tolerability, and preliminary activity.

Results.

Twenty-six patients received 120 cycles of pemetrexed and topotecan, including five patients who received 8, 8, 10, 12, and 17 cycles without dose reductions, confirming a lack of cumulative myelosuppression. Four patients received topotecan (4.0 mg/m2 i.v.) and pemetrexed (500 mg/m2 i.v.), but experienced two dose-limiting toxicities (febrile neutropenia, grade 4 thrombocytopenia). As a result, the topotecan (3.5 mg/m2 i.v.) and pemetrexed (500 mg/m2 i.v.) group was expanded to 12 patients. The only grade 3 or 4 nonhematologic toxicity was one episode of grade 3 fatigue; no grade 3 or 4 nausea/vomiting/diarrhea, mucositis, or rash was reported. One non-small cell lung cancer (NSCLC) patient (12 months) and one soft tissue sarcoma patient (6 months) achieved a partial response.

Conclusions.

Weekly topotecan plus every-3-week pemetrexed was well tolerated and active. Full doses of topotecan plus pemetrexed caused brief reversible myelosuppression with minimal dose delays/reductions; no grade 3 or 4 nausea/vomiting/diarrhea, mucositis, or rash was reported. All six NSCLC patients at the recommended phase II dose had at least stable disease as a best response, including one partial response lasting 12 months. There was no evidence of an effect of pemetrexed on topotecan pharmacokinetics. Collectively, these data suggest that further phase II exploration of weekly topotecan plus every-3-week pemetrexed for advanced malignancies is indicated.
Therapeutic Cancer Vaccines in Prostate Cancer: The Paradox of Improved Survival Without Changes in Time to Progression
Authors: Madan Ravi A. , Gulley James L. , Fojo Tito , Dahut William L.
Published: August 2010

Therapeutic cancer vaccines represent a new class of agents in the treatment of cancer. Sipuleucel-T is an antigen-presenting cell–based vaccine that recently demonstrated a significant 4.8-month improvement in overall survival in advanced prostate cancer patients and was well tolerated. The findings of that study have been met with skepticism, primarily because the agent did not change initial disease progression and yet led to longer survival. Although the commonly accepted treatment paradigm suggests that treatments should initially decrease tumor volume, perhaps vaccines work differently. Vaccines may induce delayed responses not seen in the first few months of therapy or they may initiate a dynamic immune response that ultimately slows the tumor growth rate, resulting in longer survival. Subsequent therapies may also combine with the induced immune response, resulting in a combination that is more effective than conventional treatments alone. Also, other treatments may alter tumor-associated antigen expression, enhancing the immune response. Future trials are currently planned to investigate these hypotheses; however, the results of the sipuleucel-T vaccine in prostate cancer should not be dismissed. Results with another vaccine in prostate cancer are similar, perhaps suggesting a class effect. In a broader context, clinicians may need to reconsider how they measure success. Several agents have been approved that produce superior disease progression results, but do not affect overall survival. Given the toxicity and costs of cancer therapies, perhaps studies should put more weight on long-term survival endpoints than on short-term endpoints that may be less consequential.
Diabetic Retinopathy and Cognitive Decline in Older People With Type 2 Diabetes
Authors: Ding Jie , Strachan Mark W.J. , Reynolds Rebecca M. , Frier Brian M. , Deary Ian J. , Gerald F. Fowkes R. , Lee Amanda J. , McKnight Janet , Halpin Patricia , Swa Ken , Price Jackie F. ,   on behalf of the Edinburgh Type 2 Diabetes Study (ET2DS) Investigators
Published: August 2010

OBJECTIVE

Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.

RESEARCH DESIGN AND METHODS

In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60–75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.

RESULTS

After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.

CONCLUSIONS

DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.
Black-White Divergence in the Relation of White Blood Cell Count to Metabolic Syndrome in Preadolescents, Adolescents, and Young Adults: The Bogalusa Heart Study
Authors: Chen Wei , Srinivasan Sathanur R. , Xu Jihua , Berenson Gerald S.
Published: August 2010

OBJECTIVE

To examine the association between white blood cell (WBC) count and metabolic syndrome (MetS) by growth periods in black versus white individuals in the general population.

RESEARCH DESIGN AND METHODS

The study cohort consisted of 4,184 black and white preadolescents, adolescents, and adults. In this cohort, 743 adults were followed for 8.1–20.8 years longitudinally.

RESULTS

White versus black subjects had a significantly higher WBC count in all age-groups. WBC count was associated with more MetS components in whites than in blacks. Mean values of WBC increased significantly with increasing number of MetS components with adverse levels in adolescents and adults, with a stronger trend in whites. WBC count was longitudinally associated with MetS in whites only (P < 0.001).

CONCLUSIONS

The findings on the association between higher WBC count and MetS beginning in childhood, particularly in whites, underscore a potentially mechanistic link between systemic inflammation, MetS, and cardiovascular risk.
The Effect of Iron and Erythropoietin Treatment on the A1C of Patients With Diabetes and Chronic Kidney Disease
Authors: Ng Jen M. , Cooke Michelle , Bhandari Sunil , Atkin Stephen L. , Kilpatrick Eric S.
Published: August 2010

OBJECTIVE

To examine the effect of intravenous iron and erythropoietin-stimulating agents (ESAs) on glycemic control and A1C of patients with diabetes and chronic kidney disease (CKD).

RESEARCH DESIGN AND METHODS

This was a prospective study of patients with type 2 diabetes and CKD stage IIIB or IV undergoing intravenous iron (group A) and/or ESA (group B). Full blood profiles were determined over the study period. Glycemic control was monitored using A1C, seven-point daily glucose three times weekly, and continuous glucose monitoring (CGM).

RESULTS

There were 15 patients in both group A and group B. Mean A1C (95% CI) values fell in both groups (7.40% [6.60–8.19] to 6.96% [6.27–7.25], P < 0.01, with intravenous iron and 7.31% [6.42–8.54] to 6.63% [6.03–7.36], P = 0.013, ESA). There was no change in mean blood glucose in group A (9.55 mmol/l [8.20–10.90] vs. 9.71 mmol/l [8.29–11.13], P = 0.07) and in group B (8.72 mmol/l [7.31–10.12] vs. 8.78 mmol/l [7.47–9.99], P = 0.61) over the study period. Hemoglobin and hematocrit values significantly increased following both treatments. There was no linear relationship found between the change in A1C values and the rise of hemoglobin following either treatment.

CONCLUSIONS

Both iron and ESA cause a significant fall in A1C values without a change to glycemic control in patients with diabetes and CKD. At the present time, regular capillary glucose measurements and the concurrent use of CGM remain the best alternative measurements of glycemic control in this patient group.
Morphological patterns of poly(N-isopropylacrylamide) derivatives synthesized with EGDMA, DEGDMA, and TEGDMA crosslinkers for application as thermosensitive drug carriers
Authors: Musial Witold , Kokol Vanja , Fecko Tivadar , Voncina Bojana
Published: August 2010

A number of poly(N-isopropylacrylamide) (polyNIPAM) microgels were prepared with dimethacrylate cross-linking agents of various lengths, ether and ester groups in the backbone, and pendant vinylidine functionality. These materials were characterized by examining their morphological patterns using optical and scanning electron microscopy. When ethylene glycol dimethacrylate (EGDMA) was used as a cross-linking agent, microspheres of approximately 1 μm in diameter were obtained. Diethylene glycol dimethacrylate (DEGDMA) cross-linking resulted in relatively large spherical structures (1–5 μm) as well as spherical nanostructures (200 nm). Using triethylene glycol dimethacrylate (TEGDMA) resulted in spheres with diameters between 1 μm and 3 μm. The hydrodynamic particle diameter decreased with the increasing chain length of the dimethacrylate cross-linking agents. The turbidity increased with the temperature of transition points occurring at approximately 31–32°C confirming the thermosensitivity of the obtained polymeric structures.
Regeneration of the transected rat sciatic nerve after suturing or adhesion with cyanoacrylate glue
Authors: Roth Jonathan , Shtokman Jonathan , Shamir Merav H. , Nissan Moshe , Shchetinkov Leonid , Trejo Leonor L. , Rochkind Shimon
Published: August 2010

Object

Traditional treatment of transected peripheral nerves has been by suturing the nerve ends to each other. Because this approach is not widely available and is technically demanding, the authors evaluated an easier method for end-to-end anastomosis using cyanoacrylate-based glue.

Methods

The authors used a rat sciatic nerve model. The sciatic nerve was transected in one hind limb in each of 40 rats. In 20 rats, end-to-end anastomosis was performed with suturing, while in the other 20 it was performed using only cyanoacrylate glue. The outcome variables were incapacitance test results; the functional sciatic index; somatosensory evoked potentials; axon counts and sizes at the proximal, anastomotic, and distal levels; local adhesions; and automutilation injuries. Outcomes were measured in a manner blinded to the anastomotic technique.

Results

Only the somatosensory evoked potentials and degree of local adhesions were significantly better in the Suture Group than in the Glue Group. With respect to the remaining outcomes (automutilation injuries, counts of large and medium axons combined, and counts of small axons), either the results were significantly better in the Glue Group or the between-groups difference was not statistically significant. There were no consistent significant correlations between the various outcome measures.

Conclusions

Using cyanoacrylate-based glue for microanastomosis of cut nerves appears to be as effective as microsuturing the nerve ends. Despite more local adhesions in the glued nerves, most functional outcomes were not influenced by the anastomotic technique. Validation of these findings awaits studies of larger groups of animals.
Gamma Knife radiosurgery for larger-volume vestibular schwannomas
Authors: Yang Huai-che , Kano Hideyuki , Awan Nasir Raza , Lunsford L. Dade , Niranjan Ajay , Flickinger John C. , Novotny Josef , Bhatnagar Jagdish P. , Kondziolka Douglas
Published: August 2010

Object

Stereotactic radiosurgery (SRS) is an important management option for patients with small- and medium-sized vestibular schwannomas. To assess the potential role of SRS in larger tumors, the authors reviewed their recent experience.

Methods

Between 1994 and 2008, 65 patients with vestibular schwannomas between 3 and 4 cm in one extracanalicular maximum diameter (median tumor volume 9 ml) underwent Gamma Knife surgery. Seventeen patients (26%) had previously undergone resection.

Results

The median follow-up duration was 36 months (range 1–146 months). At the first planned imaging follow-up at 6 months, 5 tumors (8%) were slightly expanded, 53 (82%) were stable in size, and 7 (11%) were smaller. Two patients (3%) underwent resection within 6 months due to progressive symptoms. Two years later, with 63 tumors overall after the 2 post-SRS resections, 16 tumors (25%) had a volume reduction of more than 50%, 22 (35%) tumors had a volume reduction of 10–50%, 18 (29%) were stable in volume (volume change < 10%), and 7 (11%) had larger volumes (5 of the 7 patients underwent resection and 1 of the 7 underwent repeat SRS). Eighteen (82%) of 22 patients with serviceable hearing before SRS still had serviceable hearing after SRS more than 2 years later. Three patients (5%) developed symptomatic hydrocephalus and underwent placement of a ventriculoperitoneal shunt. In 4 patients (6%) trigeminal sensory dysfunction developed, and in 1 patient (2%) mild facial weakness (House-Brackmann Grade II) developed after SRS. In univariate analysis, patients who had a previous resection (p = 0.010), those with a tumor volume exceeding 10 ml (p = 0.05), and those with Koos Grade 4 tumors (p = 0.02) had less likelihood of tumor control after SRS.

Conclusions

Although microsurgical resection remains the primary management choice in patients with low comorbidities, most vestibular schwannomas with a maximum diameter less than 4 cm and without significant mass effect can be managed satisfactorily with Gamma Knife radiosurgery.
Understanding the Extent and Sources of Variation in Gut Microbiota Studies; a Prerequisite for Establishing Associations with Disease
Authors: Mai Volker , Ukhanova Maria , Baer David J.
Published: August 2010

Humans harbor distinct commensal microbiota at various anatomic sites. There has been renewed interest in the contributions of microbiota activities to human health and disease. The microbiota of the gut is the most complex of all anatomic sites in terms of total numbers of bacteria that interact closely with the mucosal immune system and contribute various functions to host physiology. Especially in the proximal large intestine a diverse microbiota ferments complex substrates such as dietary fiber and host mucins, but also metabolizes bile acids and phytoestrogens that reach the large intestine. It is now well established that microbiota composition differs between but over time also within individuals. However, a thorough understanding of the sources of variations in microbiota composition, which is an important requirement for large population based microbiota studies is lacking. Microbiota composition varies depending on what kind of sample is collected, most commonly stool samples, stool swabs or superficial rectal or intestinal biopsies, and the time of collection. Microbiota dynamics are affected by life style factors including diet and exercise that determine what nutrients reach the proximal colon and how fast these nutrients pass through (transit time). Here we review sample collection issues in gut microbiota studies and recent findings about dynamics in microbiota composition. We recommend standardizing human microbiota analysis methods to facilitate comparison and pooling between studies. Finally, we outline a need for prospective microbiota studies in large human cohorts.
Enhanced Oil Recovery: An Update Review
Authors: Alvarado Vladimir , Manrique Eduardo
Published: August 2010

With the decline in oil discoveries during the last decades it is believed that EOR technologies will play a key role to meet the energy demand in years to come. This paper presents a comprehensive review of EOR status and opportunities to increase final recovery factors in reservoirs ranging from extra heavy oil to gas condensate. Specifically, the paper discusses EOR status and opportunities organized by reservoir lithology (sandstone and carbonates formations and turbiditic reservoirs to a lesser extent) and offshore and onshore fields. Risk and rewards of EOR methods including growing trends in recent years such as CO2 injection, high pressure air injection (HPAI) and chemical flooding are addressed including a brief overview of CO2-EOR project economics.
Sudden Oak Death-Induced Tanoak Mortality in Coast Redwood Forests: Current and Predicted Impacts to Stand Structure
Authors: Ramage Benjamin S. , O’Hara Kevin L.
Published: August 2010

Tanoak (Notholithocarpus densiflorus syn. Lithocarpus densiflorus) is one of the most widespread and abundant associates of coast redwood (Sequoia sempervirens), but little is known about the structural relationships between these two species. Knowledge of such relationships is essential for a thorough understanding of the impacts of sudden oak death (caused by the exotic pathogen Phytophthora ramorum), which is currently decimating tanoak populations throughout the redwood range. In this study, we utilized a stratified plot design and a stand reconstruction technique to assess structural impacts, at present and in the future, of this emerging disease. We found that residual trees in diseased plots were more aggregated than trees in unaffected plots, and we predicted that the loss of tanoak will lead to the following short-term changes: greater average diameter, height, height-to-live-crown, and crown length, as well as an increase in average nearest neighbor differences for diameter, height, and crown length. In addition, plots lacking tanoak (living or dead)—as compared to plots with tanoak—exhibited greater average diameter and increased nearest neighbor differences with regard to diameter, height, and crown length. We also conducted a preliminary exploration of how sudden oak death-induced structural changes compare with typical old-growth characteristics, and how this disease may affect the structure of old-growth forests.
Can Global Visual Features Improve Tag Recommendation for Image Annotation?
Authors: Lux Mathias , Pitman Arthur , Marques Oge
Published: August 2010

Recent advances in the fields of digital photography, networking and computing, have made it easier than ever for users to store and share photographs. However without sufficient metadata, e.g., in the form of tags, photos are difficult to find and organize. In this paper, we describe a system that recommends tags for image annotation. We postulate that the use of low-level global visual features can improve the quality of the tag recommendation process when compared to a baseline statistical method based on tag co-occurrence. We present results from experiments conducted using photos and metadata sourced from the Flickr photo website that suggest that the use of visual features improves the mean average precision (MAP) of the system and increases the system's ability to suggest different tags, therefore justifying the associated increase in complexity.
C60 Intercalated Graphite as Nanolubricants
Authors: Miura Kouji , Ishikawa Makoto
Published: August 2010

We synthesized the novel nanocomposite consisting of alternately stacked single graphene sheets and a C60 monolayer by using the graphite intercalation technique in which alkylamine molecules help intercalate large C60 molecules into the graphite. It is found that the intercalated C60 molecules can rotate in between single graphene sheets by using 13C NMR measurements. The grease with the nanocomposite materials provides a much better lubricating performance than that with other additives that have been well-known up to now. This result exhibits that a C60 monolayer intercalated between graphenes plays an important role in lubricating behavior.
Cytotoxic Tirucallane Triterpenoids from Melia azedarach Fruits
Authors: Ntalli Nikoletta G. , Cottiglia Filippo , Bueno Carlos A. , Alché Laura E. , Leonti Marco , Vargiu Simona , Bifulco Ersilia , Menkissoglu-Spiroudi Urania , Caboni Pierluigi
Published: August 2010

The phytochemical investigation of the dichloromethane-soluble part of the methanol extract obtained from the fruits of Melia azedarach afforded one new tirucallane-type triterpene, 3-α-tigloylmelianol (1) and three known tirucallanes, melianone (2), 21-β-acetoxy-melianone (3), and methyl kulonate (4). The structure of the isolated compounds was mainly determined by 1D and 2D NMR experiments as well as HPLC-Q-TOF mass spectrometry. The cytotoxicity of the isolated compounds toward the human lung adenocarcinoma epithelial cell line A549 was determined, while no activity was observed against the phytonematode Meloidogyne incognita.
Discovery and Development of Anti-HBV Agents and Their Resistance
Authors: Kim Kyun-Hwan , Kim Nam Doo , Seong Baik-Lin
Published: August 2010

Hepatitis B virus (HBV) infection is a prime cause of liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma. The current drugs clinically available are nucleot(s)ide analogues that inhibit viral reverse transcriptase activity. Most drugs of this class are reported to have viral resistance with breakthrough. Recent advances in methods for in silico virtual screening of chemical libraries, together with a better understanding of the resistance mechanisms of existing drugs have expedited the discovery and development of novel anti-viral drugs. This review summarizes the current status of knowledge about and viral resistance of HBV drugs, approaches for the development of novel drugs as well as new viral and host targets for future drugs.
Modular Synthesis of Polyphenolic Benzofurans, and Application in the Total Synthesis of Malibatol A and Shoreaphenol
Authors: Chen David Y.-K. , Kang Qiang , Wu T. Robert
Published: August 2010

A modular strategy for the synthesis of hexacyclic dimeric resveratrol polyphenolic benzofurans is reported. The developed synthetic technology was applied to the total synthesis of malibatol A, shoreaphenol, and other biologically relevant poly-phenols.
An Efficient Procedure Based on a MW-Assisted Horner–Wadsworth-Emmons Reaction for the Synthesis of (Z)-3,3-Trisubstituted-a,b-unsaturated Esters
Authors: Rossi Daniela , Baraglia Anna Carnevale , Serra Massimo , Azzolina Ornella , Collina Simona
Published: August 2010

A microwave-assisted HWE olefination process of readily accessible aryl-alkyl ketones has been developed to provide a rapid access to (Z)-3,3-trisubstituted-α,β-unsaturated methyl esters, key building blocks for the synthesis of biologically active compounds.
Using RFID to Enhance Security in Off-Site Data Storage
Authors: Lopez-Carmona Miguel A. , Marsa-Maestre Ivan , De la Hoz Enrique , Velasco Juan R.
Published: August 2010

Off-site data storage is one of the most widely used strategies in enterprises of all sizes to improve business continuity. In medium-to-large size enterprises, the off-site data storage processes are usually outsourced to specialized providers. However, outsourcing the storage of critical business information assets raises serious security considerations, some of which are usually either disregarded or incorrectly addressed by service providers. This article reviews these security considerations and presents a radio frequency identification (RFID)-based, off-site, data storage management system specifically designed to address security issues. The system relies on a set of security mechanisms or controls that are arranged in security layers or tiers to balance security requirements with usability and costs. The system has been successfully implemented, deployed and put into production. In addition, an experimental comparison with classical bar-code-based systems is provided, demonstrating the system’s benefits in terms of efficiency and failure prevention.
Identifying and Tracking Pedestrians Based on Sensor Fusion and Motion Stability Predictions
Authors: Musleh Basam , García Fernando , Otamendi Javier , Armingol José Mª , De la Escalera Arturo
Published: August 2010

The lack of trustworthy sensors makes development of Advanced Driver Assistance System (ADAS) applications a tough task. It is necessary to develop intelligent systems by combining reliable sensors and real-time algorithms to send the proper, accurate messages to the drivers. In this article, an application to detect and predict the movement of pedestrians in order to prevent an imminent collision has been developed and tested under real conditions. The proposed application, first, accurately measures the position of obstacles using a two-sensor hybrid fusion approach: a stereo camera vision system and a laser scanner. Second, it correctly identifies pedestrians using intelligent algorithms based on polylines and pattern recognition related to leg positions (laser subsystem) and dense disparity maps and u-v disparity (vision subsystem). Third, it uses statistical validation gates and confidence regions to track the pedestrian within the detection zones of the sensors and predict their position in the upcoming frames. The intelligent sensor application has been experimentally tested with success while tracking pedestrians that cross and move in zigzag fashion in front of a vehicle.
Locating Sensors for Detecting Source-to-Target Patterns of Special Nuclear Material Smuggling: A Spatial Information Theoretic Approach
Authors: Przybyla Jay , Taylor Jeffrey , Zhou Xuesong
Published: August 2010

In this paper, a spatial information-theoretic model is proposed to locate sensors for detecting source-to-target patterns of special nuclear material (SNM) smuggling. In order to ship the nuclear materials from a source location with SNM production to a target city, the smugglers must employ global and domestic logistics systems. This paper focuses on locating a limited set of fixed and mobile radiation sensors in a transportation network, with the intent to maximize the expected information gain and minimize the estimation error for the subsequent nuclear material detection stage. A Kalman filtering-based framework is adapted to assist the decision-maker in quantifying the network-wide information gain and SNM flow estimation accuracy.
SLT-VEGF Reduces Lung Metastases, Decreases Tumor Recurrence, and Improves Survival in an Orthotopic Melanoma Model
Authors: Ackerman Rachel , Backer Joseph M. , Backer Marina , Skariah Sini , Hamby Carl V.
Published: August 2010

SLT-VEGF is a recombinant cytotoxin comprised of Shiga-like toxin (SLT) subunit A fused to human vascular endothelial growth factor (VEGF). It is highly cytotoxic to tumor endothelial cells overexpressing VEGF receptor-2 (VEGFR-2/KDR/Flk1) and inhibits the growth of primary tumors in subcutaneous models of breast and prostate cancer and inhibits metastatic dissemination in orthotopic models of pancreatic cancer. We examined the efficacy of SLT-VEGF in limiting tumor growth and metastasis in an orthotopic melanoma model, using NCR athymic nude mice inoculated with highly metastatic Line IV Cl 1 cultured human melanoma cells. Twice weekly injections of SLT-VEGF were started when tumors became palpable at one week after intradermal injection of 1 × 106 cells/mouse. Despite selective depletion of VEGFR-2 overexpressing endothelial cells from the tumor vasculature, SLT-VEGF treatment did not affect tumor growth. However, after primary tumors were removed, continued SLT-VEGF treatment led to fewer tumor recurrences (p = 0.007), reduced the incidence of lung metastasis (p = 0.038), and improved survival (p = 0.002). These results suggest that SLT-VEGF is effective at the very early stages of tumor development, when selective killing of VEGFR-2 overexpressing endothelial cells can still prevent further progression. We hypothesize that SLT-VEGF could be a promising adjuvant therapy to inhibit or prevent outgrowth of metastatic foci after excision of aggressive primary melanoma lesions.
Development of Treatment Concepts for the Use of Botulinum Toxin A in Children with Cerebral Palsy
Authors: Placzek Richard , Siebold Dagmar , Funk Julia  F.
Published: August 2010

The treatment of children with cerebral palsy with Botulinum toxin A injections is well established, safe and effective. However, a standardized injection strategy is still missing and the used dosage has escalated over the years. In the recent past, the recommended dosages in Europe were, however, reduced due to a better understanding of the relationship between dosage, severe side effects and the kind of anesthesia used. To combine safety and efficacy, the trend tends to a lower dosage, but combined with a more specific selection of injected muscles. The treatment of these key-muscles takes into account the best support for motor development to attain each individual motor milestone.
Increasing the Efficacy of Oncolytic Adenovirus Vectors
Authors: Toth Karoly , Wold William S. M.
Published: August 2010

Oncolytic adenovirus (Ad) vectors present a new modality to treat cancer. These vectors attack tumors via replicating in and killing cancer cells. Upon completion of the vector replication cycle, the infected tumor cell lyses and releases progeny virions that are capable of infecting neighboring tumor cells. Repeated cycles of vector replication and cell lysis can destroy the tumor. Numerous Ad vectors have been generated and tested, some of them reaching human clinical trials. In 2005, the first oncolytic Ad was approved for the treatment of head-and-neck cancer by the Chinese FDA. Oncolytic Ads have been proven to be safe, with no serious adverse effects reported even when high doses of the vector were injected intravenously. The vectors demonstrated modest anti-tumor effect when applied as a single agent; their efficacy improved when they were combined with another modality. The efficacy of oncolytic Ads can be improved using various approaches, including vector design, delivery techniques, and ancillary treatment, which will be discussed in this review.
Glucose-Based Peritoneal dialysis solution suppresses adiponectin synthesis through oxidative stress in an experimental model of peritoneal dialysis
Authors: Huh Joo Young , Seo Eun-Young , Lee Hi Bahl , Ha Hunjoo
Published: August 2010

Objective

Accumulation of visceral fat is one of the major risk factors for the development of cardiovascular disease in peritoneal dialysis (PD) patients. Adiponectin, an adipokine commonly regarded as a negative indicator of metabolic disease, is reported to be downregulated in its gene level in end-stage renal disease patients. Since excessive fat deposit is involved in increased reactive oxygen species (ROS), PD solution (PDS) may contribute to ROS production, resulting in dysregulation of adiponectin. In this study, we tested our hypothesis that oxidative stress induced by PDS may play a role in the regulation of adiponectin.

Methods

Commercial PDS containing 3.86% glucose (20 - 30 mL) was administered to SD rats for 12 weeks with and without N-acetylcysteine (NAC; 10 mmol/L). ELISA was used to quantify adiponectin in plasma and spent dialysate. For in vitro studies, fully differentiated 3T3-L1 adipocytes and adipocytes isolated from abdominal fat were treated with a high glucose solution, PDS, and H2O2. Adiponectin levels in the conditioned media were measured by ELISA and immunoblot assays. The mRNA levels of adiponectin in mature adipocytes were examined using real-time RT-PCR.

Results

The levels of adiponectin in plasma and spent dialysate were significantly downregulated by PDS and this effect was suppressed by NAC. In 3T3-L1 adipocytes, adiponectin secretion was inhibited by 50 mmol/L glucose, PDS diluted 2-fold, and H2O2 (200 μmol/L). In addition, H2O2 downregulated expression of adiponectin mRNA and secretion of adiponectin oligomer complexes.

Conclusions

Our data suggest that ROS induced by conventional glucose-based PDS may contribute to pathophysiological changes in abdominal fat and down regulate adiponectin secreted from adipocytes during long-term PD.
Police politique, magistrats, terreur
Authors: Rittersporn Gábor T.
Published: August 2010

Résumé La politique pénale qui a précédé la Terreur de 1937 et de 1938 ne permet pas de conclure que cette dernière avait été planifiée de longue date. Durant quatre années les dirigeants ont encouragé le Parquet à contrôler les pratiques de la police politique dans des domaines aussi cruciaux qu’arrestations ou jugements. La pratique pénale reflétait les incertitudes du régime face à ses ennemis présumés. Le remarquable formalisme juridique alors dominant n’exclua pas la persécution de contre-révolutionnaires imaginaires et de gens jugés socialement dangereux sans qu’ils soient pour autant accusés d’avoir commis des crimes. À la veille même de la Grande Terreur les autorités insistèrent pour que ceux-ci soient poursuivis dans un cadre légalement défini. Ce formalisme fut balayé un temps par la terreur, devenue incontrôlable. Mais il fut rétabli en 1939, malgré l’opposition de la police secrète. Le nombre des affaires politiques et des éléments socialement dangereux baissa, les travailleurs indisciplinés devant la cible prioritaire de la répression.
Les fonctionnaires régionaux du NKVD face aux purges de 1937-1938
Authors: Leibovitch Oleg
Published: August 2010

Résumé Cet article propose l’une des premières études détaillées du milieu des fonctionnaires du NKVD dans une région précise (celle de Perm, dans l’Oural) avant et pendant la Grande Terreur de 1937-1938. Il analyse la place du NKVD dans la nomenklatura régionale, les rapports entre le NKVD et le parti au niveau local, le « quotidien » de l’activité, devenue quelque peu routinière, des fonctionnaires du NKVD. Puis survient la « grande secousse » du printemps 1937, au cours de laquelle la plupart des dirigeants régionaux du parti sont arrêtés sous prétexte de « comploter » contre Staline. À partir de ce moment-là, le NKVD est profondément remanié : nouveaux cadres, nouvelles méthodes, nouvelle hiérarchie. On ne peut pas comprendre l’implication du NKVD dans les « opérations secrètes de masse » sans tenir compte des changements profonds et des purges qui affectent, au même moment, le NKVD lui-même.
Spermiogenesis particularities of a sperm storage species: Helicolenus dactylopterus (Teleostei: Scorpaenidae)
Authors: Vila Silvia , Sàbat Maria , Muñoz Marta , Casadevall Margarida
Published: August 2010

A study of the spermiogenesis and spermatozoa of Helicolenus dactylopterus was conducted. Females of this species have the capacity to store sperm within their ovaries, and male gametes have a considerable cytoplasmic mass surrounding their heads to survive the long period of intraovarian sperm storage. Our observations show that early spermatids are round-shaped cells and have a spherical nucleus with diffuse chromatin. The nuclear volume decreases as a result of progressive chromatin condensation during spermiogenesis, causing the nucleus to take on a U-shape. Flagellar insertion is not central to the nucleus but consistently occurs at an oblique angle towards one side of it. The flagellum is inserted into the nuclear fossa, without subsequent nuclear rotation. In mature spermatozoa, the flagellum is adjacent to the nucleus. A comparison of the spermatozoa in the testicular lobules and those in the intraovarian storage structures suggests that the increase in volume of the cytoplasmic mass may occur in the posterior region of the testis, in the testicular duct. Spermatozoa enter the ovary in groups that reach the ovarian lumen and are surrounded by the ovarian epithelium for storage in sperm storage crypts.
Spatial distribution of benthic macrofauna in subtidal sediments of the Ría de Aldán (Galicia, northwest Spain)
Authors: Lourido Antía , Moreira Juan , Troncoso Jesús S.
Published: August 2010

In the summer of 1997, 27 subtidal stations were quantitatively sampled in the Ría de Aldán. A total of 81770 individuals were collected, comprising 496 species. The distribution and composition of benthic assemblages was correlated to the sedimentary characteristics which, in turn, depend on the hydrodynamic features; those patterns are reflected in a sedimentary gradient present along the ria, which is characterized by an increasing grain size from the inner margins towards the mouth. Several faunal assemblages were determined through multivariate analyses and their composition is compared with that of several communities or facies previously described from similar sediments. The Venus fasciata community was present in clean coarse sediments of the outer ria, the Venus gallina and Tellina fabula-Tellina tenuis communities in the fine-sand bottoms at the centre and margins of the ria, a transition assemblage between the Venus fasciata and the Venus gallina communities in the medium-sand sediments, and a mix of species from the Syndosmya alba and the Amphiura communities in shallower and muddy sediments in the inner areas. In general, subtidal sediments of the Ría de Aldán showed a high benthic diversity which is related to the great sedimentary heterogeneity and the lack of significant anthropogenic alterations.
Trazando el mapa del pasado postmoderno
Authors: Hodder Ian
Published: August 2010

Este artículo empieza describiendo los pasos que deben darse para desarrollar un método de excavación reflexivo en Çatalhöyük. Entre estos 12 pasos, destacamos cuatro temas: relacionalidad (contextualidad) del significado, reflexión (crítica), interactividad y multivocalidad. La idea que subyace en todos ellos es la necesidad de introducir un pensamiento no dicotómico en arqueología. Esta necesidad se basa principalmente en el sistema global moderno (o posmoderno) en el que, cada vez más, trabajan los arqueólogos. Está clara la necesidad de fluidez y ruptura de fronteras en un mundo postcolonial inmerso en los sistemas de información.
Elefantes e intervención humana en los yacimientos del Pleistoceno Inferior y Medio de África y Europa
Authors: Martos Romero Juan Antonio
Published: August 2010

En el presente artículo se revisan yacimientos africanos y europeos donde se ha planteado la existencia de una intervención humana sobre elefantes. Se establece una diferencia entre sitios con un sólo individuo (tipo 1) o un número alto de elefantes (tipo 2). Con independencia del carácter de la intervención humana, cuando ésta es evidente, tales diferencias responden a unos procesos de formación distintos con problemáticas singulares que condicionan finalmente la capacidad informativa del yacimiento.
Las industrias líticas de la Gruta Nova de Columbeira (Bombarral, Portugal) en el contexto del Musteriense Final de la Península Ibérica
Authors: Raposo Luís , Cardoso João Luís
Published: August 2010

La Gruta Nova de Columbeira, descubierta en 1962, constituye uno de los más importantes sitios del Paleolítico Medio en Portugal. La industria lítica, que aquí se caracteriza por primera vez, puede describirse genéricamente como un Musteriense de denticulados rico en raederas, de talla y facies levallois, sin signo alguno que la aproxime a patrones asimilables al Paleolítico Superior.
Dos dataciones C14 de los dos niveles de ocupación humana de la base de la secuencia (28900 ± 900 y 26400 ± 750 BP) confieren un interés especial a esta localidad, que se incluye en el conjunto de casi dos decenas de sitios ibéricos (sur de España y Portugal) en que fué comprobada la subsistencia del Musteriense y de los neandertales hasta incluso después de 30000 BP. Se plantea una argumentación paleobiogeográfíca para explicar este fenómeno, en el cuadro de la evolución histórica documentada en las tres penínsulas meridionales (ibérica, itálica y balcánica) del continente europeo.
Las publicaciones periódicas de Historia Antigua, Prehistoria y Arqueología: difusión internacional
Authors: García Marín Ángeles , Román Román Adelaida
Published: August 2010

Actualmente la evaluación de las revistas científicas se apoya fundamentalmente en la presencia o ausencia de éstas en los índices de Citas. El trabajo que ahora se presenta propone un sistema alternativo de evaluación basado en múltiples indicadores de calidad complementarios que se aplican experimentalmente a las revistas de Arqueología, Prehistoria e Historia Antigua. Se estudia de manera especial la difusión internacional de las revistas a través de las Bases de Datos internacionales más importantes así como en algunos catálogos colectivos de publicaciones periódicas.
Las cuevas de Levante (Benalup, Cadiz): un yacimiento al aire libre del Paleolítico Superior en Andalucía suroccidental
Authors: Ripoll López Sergio , Mas Cornélla Martí , Jordá Pardo Jesús F.
Published: August 2010

En este artículo damos a conocer los resultados de la excavación arqueológica realizada en el yacimiento al aire libre situado delante de las Cuevas de Levante (Cádiz, España) durante 1991, así como la interpretación geoarqueológica del mismo. La industria lítica recuperada nos permite encuadrar esta estación en el Solutrense.
Aproximación al estudio de las transformaciones históricas en las sociedades del VI al III milenio a.C. en el Sureste peninsular
Authors: Román Díaz M. de la Paz , Martínez Padilla Catalina
Published: August 2010

En este estudio se expone la necesidad de sustituir el punto de vista tradicional sobre el Neolítico en el Sureste de la Península Ibérica, por una aproximación social e histórica. Tras un breve repaso crítico de los contenidos atribuidos al Neolítico y sus aplicaciones y, consecuentemente, de la periodización clásica, optamos por el análisis de los procesos. Para ello, consideramos como un primer paso dos aspectos relevantes: la sedentarización y el almacenamiento. A partir de sus indicadores arqueológicos hemos distinguido varios grupos de yacimientos que se corresponderían con diferentes formas de vida, siendo todo ello la expresión de transformaciones en las relaciones sociales.
Producción e intercambio durante el Calcolítico en Portugal: el caso de las industrias líticas de talla bifacial
Authors: Forenbaher Stašo
Published: August 2010

Este estudio se centra en la organización económica de las industrias líticas de talla bifacial del Neolítico Final/ Calcolítico en Portugal. Se ha defendido a menudo que las jerarquías sociales aparecieron por primera vez en el occidente de la Península Ibérica durante este periodo (ca. 3500-2500 AC). Los objetivos específicos de la investigación son: determinar el repertorio de la producción en los talleres líticos, examinar la posibilidad de una especialización artesanal (prestando particular atención a la estandarización artefactual), e investigar la distribución geográfica de los artefactos para detectar las evidencias de centralización.
Los análisis muestran que la organización de la economía difiere de forma notable entre las distintas clases de artefactos. La producción de los instrumentos conectados con la subsistencia era descentralizada. Los útiles circulaban a través de redes locales de intercambio, aunque algunos pudieran integrarse en el intercambio a larga distancia. Los artefactos conectados con el prestigio se intercambiaron a larga distancia y, aparentemente, fueron producidos por especialistas. El nivel de especialización y su importancia para la economía siguieron siendo modestos. No hay evidencia de una integración socio-política a gran escala.
Las comunidades campesinas en la cultura castreña
Authors: Fernández-Posse M. Dolores , Sánchez-Palencia F. Javier
Published: August 2010

Se analiza la posibilidad de que la estructura social y económica de las comunidades castreñas prerromanas corresponda al concepto de una sociedad campesina. Para ello se utiliza el registro arqueológico de los castros de la Zona Arqueológica de Las Médulas, en el suroeste de la provincia de León, examinado en tres niveles de análisis: las unidades de ocupación de esos poblados como núcleos básicos de producción y consumo agrícolas, la aptitud de los castros para ser considerados comunidades aldeanas autosuficientes y la especificidad de sus formas de vida, racionalidad y economía como constructoras de un paisaje campesino. Asimismo se discuten cuestiones como la propiedad de la tierra y el grado y tipo de jerarquización de tales comunidades.
El necesario contrapunto lo pone la presencia romana en la zona, que genera un proceso rápido de disolución de esa estructura social indígena. Los intereses mineros provocan un fuerte cambio económico y social, visible en particular en las estrategias de poblamiento y explotación del territorio, en definitiva en la construcción de un nuevo paisaje que puede considerarse minero frente al precedente campesino.
Algunas consideraciones acerca de la espada de Guadalajara. ¿Un excepcional depósito desarticulado del Bronce Medio de la Meseta?
Authors: Brandherm Dirk
Published: August 2010

En la bibliografía reciente, la tan conocida espada de Guadalajara, conservada hoy en el Museo Arqueológico Nacional, por la mayoría de los autores no sólo es tratada como pieza única sino también como hallazgo descontextualizado. No obstante, las primeras referencias publicadas sobre esta pieza, mientras todavía formaba parte de la colección Rodríguez Bauzá, parecen indicar que posiblemente en su origen pertenecía a un depósito que también incorporaba otras dos hojas de espada. Una de aquellas hojas probablemente se puede asociar a la chapa de oro suelta que hoy día se conserva junto con la espada restaurada ya en los años treinta. Durante la nueva restauración de este arma a fines de los años ochenta se hicieron visibles las huellas de dos enmangues distintos, demostrando así que el estado presente, con su suntuosa decoración de oro, corresponde a una modificación secundaria. Aunque en el caso de estas armas y sus enmangues cubiertos de oro se pudiera pensar en una influencia micénica, seguramente en el de los segundos por razones tecnológicas parece más probable un origen en la misma Meseta que en el Sureste, donde, en la cultura de El Argar, más bien se estaría preparado para contar con la intrusión dé elementos egeos.
El desarrollo de tecnologías para la gestión del Patrimonio Arqueológico: hacia un modelo de Evaluación de Impacto Arqueológico
Authors: Barreiro Martínez David , Villoch Vázquez Victoria , Criado Boado Felipe
Published: August 2010

Este texto plantea la necesidad de establecer procedimientos y convenciones de práctica arqueológica para resolver los problemas y demandas en la gestión actual del Patrimonio Arqueológico. En concreto se presenta el programa CAPA (criterios y convenciones en Arqueología del Paisaje y Patrimonio Arqueológico) en vía de realización por nuestro Grupo de Investigación. El objetivo de este programa es contribuir al desarrollo de sistemas y metodologías de gestión y evaluación del Patrimonio Arqueológico y llegar a componer un Manual de Usos Internos que nuestro grupo aplicaría en los diferentes proyectos de investigación y de asistencia técnica. Como ejemplo de estos desarrollos, se considera la Evaluación de Impacto Arqueológico y se propone un esquema metodológico para la realización de este nuevo tipo de práctica arqueológica, que forma parte importante de la Evaluación de Impacto Ambiental.