bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of HIV Tat DNA on regulating the immune response of HIV DNA vaccine in mice
Authors: Liu Ye , Li Fusheng , Qi Zhi , Hao Yanling , Hong Kunxue , Liu Yong , Cong Yulong , Shao Yiming 
Published: September 2013

Abstract

Background
HIV trans-activator protein (Tat) is the crucial factor to control HIV transcription, and is usually considered as an important immunogen for the design of HIV vaccine. Recent studies reported some special bio-activities of Tat protein on immunoregulation. However, to date, few studies have focused on exploring the effects of Tat expression plasmid (pTat) on regulating the immune responses induced by HIV DNA vaccines. In this study, our main objective is to investigate the immunoregulation mediated by pTat in mice.

Methods
Four gene-coding plasmids (pTat, pGag, pEnv and pPol) were constructed, and the gene expression was detected by western blot method. The effects of pTat on regulating the immune responses to antigens Gag, Env, Pol were assessed by enzyme-linked immunospot and enzyme-linked immunosorbent assay. The data was analysed by one-way analysis of variance.

Results
After two immunizations, mice vaccinated with antigen expressing plasmid (pGag, pEnv or pPol) plus pTat exhibited significantly stronger IFN-gamma response than that vaccinated with the corresponding antigen alone. Moreover, mice receiving two injections of antigen plus pTat exhibited the same strong IFN-gamma response as those receiving three injections of antigen alone did. Furthermore, addition of pTat not only induced a more balanced Th1 and Th2 response, but also broadened IgG subclass responses to antigens Gag and Pol.

Conclusion
pTat exhibited the appreciable effects on modulating immune responses to HIV antigens Gag, Env and Pol, providing us interesting clues on how to optimize HIV DNA vaccine.
Diversity of flora used for the cure of equine diseases in selected peri-urban areas of Punjab, Pakistan
Authors: Goraya Khurram , Iqbal Zafar , Sajid Muhammad Sohail , Muhammad Ghulam , Ain Qurat ul , Saleem Muhammad 
Published: September 2013

Abstract

Background
Plants have widely been used and documented for their therapeutic potential in many parts of the world. There are, however, few reports on the use of plants for the treatment of diseases of equines. To this end, participatory epidemiology and rapid rural appraisal techniques were used to document the plants having pharmacotherapeutic significance against different ailments of equines in selected population of Punjab, Pakistan.

Methods
A survey was conducted to interview a total of 450 respondents (150 from each of the districts of Faisalabad, Lahore and Sargodha of Pakistan) to collect information about disease recognition of the equines and their treatment on a well − structured questionnaire. A total of 60 plants belonging to 40 families were documented. An inventory was developed depicting detailed information of plants used in treatment of different conditions of equines.

Results
The top ten species of plants used were: Allium cepa, Zingiber officinale, Vernonia anthelmintica, Capsicum annum, Brassica campestris, Trachyspermum ammi, Anethum graveolens, Picrorhiza kurroa, Azadirachta indica, and Citrullus colocynthis. Seeds were the most frequently used (n = 16/60) parts, followed by leaves (n = 12/60) and fruits (n = 11/60) of plants. Based on the combination of different parts of plants used in different ratios and variation in their dose or mode of preparation led to a large number of recipes/remedies against wounds, lameness, bronchitis, colic, anorexia, dermatitis, weakness, parasitism (internal & external), fever, heat stress, urine retention, swelling, toxemia, and indigestion.

Conclusions
This study generated lot of data on phytomedicinal approach for the treatment of ailments in the equines in some selected areas. It would, therefore, be imperative to expand similar studies in other parts of Pakistan and elsewhere. Moreover, use of the documented plants may be validated employing standard scientific procedures, which may have their application in the drug discovery/development by the pharmaceutical industry.
Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose
Authors: Bernabe Luis Feo , Portela Roberta , Nguyen Sandra , Kisseberth William C , Pennell Michael , Yancey Mark F , London Cheryl A 
Published: September 2013

Abstract

Background
The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy.

Results
Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD.

Conclusions
Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that associated with the label dose of toceranib. This lower dose range of toceranib should be considered for future use in dogs with cancer.
MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm
Authors: Jiang Yugang , Zhang Mingming , He Hua , Chen Jia , Zeng Hua , Li Jia , Duan Ranhui 
Published: September 2013

Abstract

Background
Intracranial aneurysm (IA) is one of the most lethal forms of cerebrovascular diseases characterized by endothelial dysfunction, vascular smooth muscle cell phenotypic modulation, inflammation and consequently loss of vessel cells and extracellular matrix degradation. Besides environmental factors, genetics seem to be a very important factor in the genesis of this disease. Previous mRNA expression studies revealed a large number of differentially expressed genes between IA and control tissue. However, microRNAs (miRNA), small non-coding RNAs which are post-transcriptional regulators of gene expression, have been barely studied. Studying miRNAs could provide a hypothetical mechanism underlying rupture of IA.

Methods
A microarray study was carried out to determine difference in microRNAs and mRNA between patients’ IA tissues and controls. Quantitative RT-PCR assay compared the expression level between two groups (14 IA domes vs. 14 controls) were used for validation. Validated miRNAs were analyzed using Ingenuity Pathway Analysis (IPA) to identify the networks and pathways.

Results
18 miRNAs were confirmed by qPCR to be robustly down-regulated in 14 ruptured IA patients including hsa-mir-133b, hsa-mir-133a, hsa-mir-1, hsa-mir-143-3p, hsa-mir-145-3p, hsa-mir-145-5p, hsa-mir-455-5p, hsa-mir-143-5p, hsa-mir-23b-3p etc., of which 11 miRNAs are clusters: hsa-mir-1/has-mir-133a, hsa-mir-143/hsa-mir-145, hsa-mir-23b/hsa-mir-24-1, and hsa-mir-29b-2/hsa-mir-29c. 12 predicted functions were generated using IPA which showed significant associations with migration of phagocytes, proliferation of mononuclear leukocytes, cell movement of mononuclear leukocytes, cell movement of smooth muscle cells etc.

Conclusion
These data support common disease mechanisms that may be under miRNA control and provide exciting directions for further investigations aimed at elucidating the miRNA mechanisms and targets that may yield new therapies for IA.
Understanding the sequential activation of Type III and Type VI Secretion Systems in Salmonella typhimurium using Boolean modeling
Authors: Das Chandrani , Dutta Anirban , Rajasingh Hannah , Mande Sharmila S 
Published: September 2013

Abstract

Background
Three pathogenicity islands, viz. SPI-1 (Salmonella pathogenicity island 1), SPI-2 (Salmonella pathogenicity island 2) and T6SS (Type VI Secretion System), present in the genome of Salmonella typhimurium have been implicated in the virulence of the pathogen. While the regulation of SPI-1 and SPI-2 (both encoding components of the Type III Secretion System - T3SS) are well understood, T6SS regulation is comparatively less studied. Interestingly, inter-connections among the regulatory elements of these three virulence determinants have also been suggested to be essential for successful infection. However, till date, an integrated view of gene regulation involving the regulators of these three secretion systems and their cross-talk is not available.

Results
In the current study, relevant regulatory information available from literature have been integrated into a single Boolean network, which portrays the dynamics of T3SS (SPI-1 and SPI-2) and T6SS mediated virulence. Some additional regulatory interactions involving a two-component system response regulator YfhA have also been predicted and included in the Boolean network. These predictions are aimed at deciphering the effects of osmolarity on T6SS regulation, an aspect that has been suggested in earlier studies, but the mechanism of which was hitherto unknown. Simulation of the regulatory network was able to recreate in silico the experimentally observed sequential activation of SPI-1, SPI-2 and T6SS.

Conclusions
The present study integrates relevant gene regulatory data (from literature and our prediction) into a single network, representing the cross-communication between T3SS (SPI-1 and SPI-2) and T6SS. This holistic view of regulatory interactions is expected to improve the current understanding of pathogenesis of S. typhimurium.
Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors
Authors: Catz Sergio Daniel 
Published: September 2013

ABSTRACTThe Rab27 family of GTPases regulates the efficiency and specificity of exocytosis in hematopoietic cells, including neutrophils, CTLs, NK cells, and mast cells. However, the mechanisms regulated by Rab27 GTPases are cell-specific, as they depend on the differential expression and function of particular effector molecules that are recruited by the GTPases. In addition, Rab27 GTPases participate in multiple steps of the regulation of the secretory process, including priming, tethering, docking, and fusion through sequential interaction with multiple effector molecules. Finally, recent reports suggest that Rab27 GTPases and their effectors regulate vesicular trafficking mechanisms other than exocytosis, including endocytosis and phagocytosis. This review focuses on the latest discoveries on the function of Rab27 GTPases and their effectors Munc13-4 and Slp1 in neutrophil function comparatively to their functions in other leukocytes.
Infection and combat injuries
Authors: Penn-Barwell J. G. , Rowlands T. K. 
Published: September 2013

Blast and ballistic weapons used on the battlefield cause devastating injuries rarely seen outside armed conflict. These extremely high-energy injuries predominantly affect the limbs and are usually heavily contaminated with soil, foliage, clothing and even tissue from other casualties. Once life-threatening haemorrhage has been addressed, the military surgeon’s priority is to control infection. Combining historical knowledge from previous conflicts with more recent experience has resulted in a systematic approach to these injuries. Urgent debridement of necrotic and severely contaminated tissue, irrigation and local and systemic antibiotics are the basis of management. These principles have resulted in successful healing of previously unsurvivable wounds. Healthy tissue must be retained for future reconstruction, vulnerable but viable tissue protected to allow survival and avascular tissue removed with all contamination. While recent technological and scientific advances have offered some advantages, they must be judged in the context of a hard-won historical knowledge of these wounds. This approach is applicable to comparable civilian injury patterns. One of the few potential benefits of war is the associated improvement in our understanding of treating the severely injured; for this positive effect to be realised these experiences must be shared.
Near-infrared spectroscopy and chemometrics for rapid profiling of plant secondary metabolites
Authors: Mokgalaka Ntebogeng S. , Lepule Sello P. , Regnier Thierry , Combrinck Sandra 
Published: September 2013

Abstract
In this study, near-infrared (NIR) spectroscopy, in combination with chemometrics, was used as a rapid tool for determining if exposure to contamination from mine tailings influences the matrices of the specimens, compared to those from natural populations. Principal component analysis (PCA) plots were made from the chemometric models obtained to establish if season of harvest, geographical origin, and level of soil contamination play a determining role in the chemical profiles of the individual specimens harvested from mine sites or natural populations. The random distribution on PCA score plots corroborated the intraspecies variation of Lippia scaberrima previously observed by gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) essential oil profiles. Clustering according to the season and origin of the individual plants confirmed that the geographic location and the season of harvest influence the chemical profiles of L. scaberrima. The NIR data could not be correlated with the level of soil contamination to which the specimens were exposed. The PCA scores and loadings plots obtained from NIR data of Searsia pendulina suggest that the species is tolerant to pollution from mine tailings. Although separation was obtained in a three-component PCA model between specimens sampled during different seasons, some clustering was observed by specimens from the same geographical origin.
Benign adrenal adenomas secreting excess mineralocorticoids and glucocorticoids
Authors: Yoon Vivienne , Heyliger Aliya , Maekawa Takashi , Sasano Hironobu , Carrick Kelley , Woodruff Stacey , Rabaglia Jennifer , Auchus Richard J , Ghayee Hans K 
Published: September 2013

Summary
Objective: To recognize that benign adrenal adenomas can co-secrete excess aldosterone and cortisol, which can change clinical management.
Methods: We reviewed the clinical and histological features of an adrenal tumor co-secreting aldosterone and cortisol in a patient. Biochemical testing as well as postoperative immunohistochemistry was carried out on tissue samples for assessing enzymes involved in steroidogenesis.
Results: A patient presented with hypertension, hypokalemia, and symptoms related to hypercortisolism. The case demonstrated suppressed renin concentrations with an elevated aldosterone:renin ratio, abnormal dexamethasone suppression test results, and elevated midnight salivary cortisol concentrations. The patient had a right adrenal nodule with autonomous cortisol production and interval growth. Right adrenalectomy was carried out. Postoperatively, the patient tolerated the surgery, but he was placed on a short course of steroid replacement given a subnormal postoperative serum cortisol concentration. Long-term follow-up of the patient showed that his blood pressure and glucose levels had improved. Histopathology slides showed positive staining for 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, and 21 hydroxylase.
Conclusion: In addition to the clinical manifestations and laboratory values, the presence of these enzymes in this type of tumor provides support that the tumor in this patient was able to produce mineralocorticoids and glucocorticoids. The recognition of patients with a tumor that is co-secreting aldosterone and cortisol can affect decisions to treat with glucocorticoids perioperatively to avoid adrenal crisis.

Learning points

Recognition of the presence of adrenal adenomas co-secreting mineralocorticoids and glucocorticoids.

Consideration for perioperative and postoperative glucocorticoid use in the treatment of co-secreting adrenal adenomas.
Offshore Polymer/LPS Injectivity Test with Focus on Operational Feasibility and Near Wellbore Response in a Heidrun Injector
Authors: Selle Olav M. , Fischer Herbert , Standnes Dag C. , Auflem Inge H. , Lambertsen Anne Marie , Svela Per Einar , Mebratu Amare , Gundersen Elisabeth B. , Melien Ingrid 
Published: September 2013

Abstract
Increased oil recovery technologies are very important for the large Heidrun field located in the Norwegian Sea. Very harsh climate and stringent environmental regulations render enhanced oil recovery (EOR) projects challenging. One EOR method evaluated for the field is polymer/LPS (Linked Polymer Solution) with the objective to improve the reservoir sweep. An offshore polymer and LPS injectivity test was performed with the objectives to determine the logistical and operational feasibility of handling polymers and to observe the near wellbore response during polymer and LPS injection.
Prior to the offshore test, laboratory work was performed to qualify a polymer and a LPS system. A yard test was conducted to test necessary instrumentation and mixing/pumping equipment in preparation for the offshore test. The operation was performed by mixing a 5000 ppm polyacrylamide mother solution onshore, which was then shipped and stored offshore in completion tanks on the platform. The polymer mother solution was then injected downstream the choke on the injection well at a final polymer concentration of 300 ppm and 600 ppm, respectively. The test was done with a stepwise rate increase to switch from matrix to fracture injection. Aluminum citrate (AlCit) cross-linker was added at 300:10 and 600:20 polymer-to-cross-linker ratio.
A comprehensive sampling and analysis program was performed both onshore and offshore to secure high-quality polymer solution throughout the logistical chain. High-pressure sampling equipment was constructed to sample polymerized injection water at the wellhead. Furthermore, high-quality injection data was obtained through installation of a bottomhole memory gauge into the injector prior to the test.
The main results from the offshore test proved the feasibility of storing, mixing, transport and injection of polymer solutions without contamination or unwanted shear degradation of the polymer. Good mixing was obtained by feeding the polymer mother solution into the injection stream. Polymer sampling at the wellhead showed good polymer quality based on viscosity and filter ratio results. Well injectivity improved under polymer/LPS injection compared to water injection due to the opening of existing fractures at lower injection rates.
Steerable Drilling Liner Used to Increase Recovery on the Grane Field at the Norwegian Continental Shelf
Authors: Eidem Morten , Grindhaug Gaute , Paulus Marius , Kanzler Christian , Skarsbø Eirik , Schwartze Sascha , Spreckelmeyer Niko , Carl C. Clemmensen 
Published: September 2013

Abstract
Steerable Drilling Liner (SDL) was originally designed to remove downtime related to drilling in unstable formations and/or into depleted formations as it allows the well to be lined/cased off simultaneously as it is drilled. The SDL system consists of a standard drill pipe as the inner-string, inside a conventional liner. The system uses a conventional rotary steerable Bottom Hole Assembly and has been designed to drill complex 3D well trajectories, up to 2000 m long, with the same directional and logging capabilities as conventional drilling. Two sizes are developed: 7" for 8 ½" hole and 9 5/8" for 12 ¼" hole. Using SDL gives several benefits to the drilling process, including:
Reduced openhole time; the liner is always on bottom. Reduced pressure fluctuations; tripping of BHA/innerstring is always in cased hole. Reduced mechanical impact on the formation; stable centralised liner with no lateral movement against formations when drilling.
All the above will contribute greatly in the goal of preventing formation collapse prior to drilling a section to planned total depth (TD).
Based on a request from the Grane field in the Norwegian Continental Shelf (NCS), additional ways of using the SDL technology has now been introduced as an 7" SDL system was drilled fully into open hole and left as an open hole clad (with both the liner top and bottom in a reservoir sand) to prevent unstable intermediate formations to collapse and subsequently prevent drilling the 8 ½" reservoir section to planned TD.
Unstable shale protruding into the reservoir at Grane causes regular adjustment to the wellpath. As the formation instability develops over time, getting the liner/completion through a shale interval has been proven difficult and often results in sidetracks due to wellbore collapse and/or pack-offs. The solution has been to place the well path above the shale intrusions to avoid the stability problems. This drilling practice limits the total reservoir drainage since the gravity based drainage only allows the reservoir above the drilled wellpath to be produced. Using 7" Steerable Drilling Liner (SDL) on a well on the Grane platform allowed drilling through the shale section and seal it off immediately before problems started to develop. This enabled optimisation of the well placement for improved access to reserves that otherwise would be inaccessible due to shale intrusions.
The entire operation was carried out withd great success. SDL not only removed drilling related issues but also contributed to, based on the more optimally placed wellpath, increased reserves. At TD, the liner was released from the inner-string without any issues and left as a horizontal protection through the shale with both ends of the liner in the reservoir sand.