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The goal of this study was to systematically review the management and outcomes of patients who developed pseudoaneurysm (PA) after carotid endarterectomy (postendarterectomy PA [PEPA]).Following the PRISMA guidelines, a systematic literature review was performed using PubMed, Scopus, and Web of Science databases from date of inception to June 2022. Studies were selected based on predetermined inclusion and exclusion criteria. Simultaneously, a retrospective review was conducted of patients who underwent neurosurgical evaluation of suspected PEPA at our institution.Of the 321 articles in the original literature search, 62 were selected. A total of 143 patients (93 men, 27 women; mean age, 70.7 years) diagnosed with PEPA were included. Mean time from carotid endarterectomy to PA diagnosis was 41.8 months. Primary repair data were available for 135 patients, including 19 with primary closures, 112 with patch or graft repairs, and 4 with eversion procedures. Fifty-five patients with PA (39%) presented with infection. Staphylococcal species were the most common causative organism. Of infected PAs, 89.1% were treated with open procedures. Overall complication rates of PAs treated via open, endovascular, and hybrid methods were 31%, 15.4%, and 0%, respectively. Open ligation (42.9%) and aneurysmectomy with grafting (36.4%) resulted in the highest rates of complications.Despite higher complication rates after open repair strategies, use of these techniques remains a viable option in situations requiring removal of infected patches or evacuation of large extravascular collections. Endovascular treatment options are associated with low numbers of complications and can be considered for primary PEPA treatment when infection is not present.

A carotid-cavernous fistula (CCF) is an abnormal communication between arteries and veins within the cavernous sinus and may be classified as either direct or indirect. This bibliometric analysis summarizes the most-cited articles on CCFs and highlights the contributing articles to today's evidence-based practice.In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until June 2022. The keyword "carotid cavernous fistula" was used. Our results were arranged in descending order based on the article's citation count. The 100 most-cited articles were selected for analysis. Parameters such as title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact per Paper, and Hirsch index were collected.The keyword-based search showed that 1832 articles were published between 1963 and 2022 on CCFs. The top 100 articles were published between 1963 and 2018. The top 100 most-cited articles collected a total of 8797 citations with an average of 88 citations per paper. The rate of self-citations accounted for an average of 4.71% of the total number of citations.The bibliometric analysis provides a quantitative overview of how medical topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in CCFs by finding the top 100 most-cited papers.

BACKGROUND The Surpass Streamline flow diverter (SSFD) possesses 4 attributes that may offer an important advantage in the treatment of complex pathologies: (1) utilization of an over-the-wire (OTW) delivery system, (2) greater device length, (3) larger potential diameter, and (4) propensity to open in tortuosity. OBSERVATIONS Case 1 leveraged device diameter to embolize a large, recurrent vertebral artery aneurysm. Angiography at 1 year posttreatment showed complete occlusion with a patent SSFD. Case 2 leveraged device length and opening in tortuosity to manage a symptomatic 20-mm cavernous carotid aneurysm. Magnetic resonance imaging at 2 years demonstrated aneurysm thrombosis and patent stents. Case 3 utilized diameter, length, and the OTW delivery system to treat a giant intracranial aneurysm previously treated with surgical ligation and a high-flow bypass procedure. Angiography at 5 months postprocedure demonstrated the return of laminar flow, as the vein graft had healed around the stent construct. Case 4 used diameter, length, and the OTW system to treat a giant, symptomatic, dolichoectatic vertebrobasilar aneurysm. Twelve-month follow-up imaging revealed a patent stent construct with no change to the aneurysm size. LESSONS Increased awareness of the unique attributes of the SSFD may allow a larger number of cases to be treated with the proven mechanism of flow diversion.

Introduction Intracranial pseudoaneurysms (IPA) are rare and potentially life‐altering lesions. Although IPAs represent less than 1% of all intracranial aneurysms, they account for more than 19% of pediatric intracranial aneurysms. The goal of this study was to systematically review the management and outcomes of pediatric patients who developed pseudoaneurysms following head trauma. Methods Following PRISMA guidelines, a systematic literature review was performed using PubMed, EMBASE, OVID Medline and Web of Science databases from date of database inception to May 2022. Studies were selected based on predetermined inclusion and exclusion criteria. Simultaneously, a retrospective analysis was conducted on pediatric patients who underwent endovascular evaluation and treatment for intracranial pseudoaneurysms originating from head trauma at a single institution. Results A total of 221 articles were identified in our review, 51 studies met inclusion criteria. A total of 80 patients were treated for 81 intracranial traumatic pseudoaneurysms, including 5 cases from our institution, with 46 males, 28 females, and a mean age of 9.90 years (range 0.04 ‐18 years). 71 total pseudoaneurysms were the result of external trauma while 10 resulted from iatrogenic trauma. Vessels of the anterior circulation were injured in 75.3% (61/81) of cases. Posterior circulation was involved in 24.7% (20/81) of cases. The internal carotid artery was the most impacted vessel at 45.7% (37/81). The next most common territory injured was the anterior cerebral artery and its distal branches, including the pericallosal and callosomarginal arteries, at 17.3% (14/81). The basilar artery was the third most affected artery, representing 12.3% (10/81) of cases. Hemorrhage was present in 41 patients (51.3%). Subarachnoid hemorrhage was present in 33.8% (27/80), while intracerebral hemorrhage and interventricular hemorrhage (IVH) were present 22.5% and 18.8% of cases, respectively. A total of 92 procedures were performed, with only 8 patients requiring more than 1 procedure for treatment. Only 1 patient required more than 2 procedures. Aneurysm embolization, parent vessel occlusion, parent vessel reconstruction, and aneurysm trapping were performed in 31.5%, 22.8%, 43.5%, and 2.2% of cases, respectively. The intraoperative complication rate was 3.26%, all were ischemic in nature. Two of these ischemic complications resulted focal neurological deficits from parent vessel occlusion. Aneurysm recurrence was encountered in 7 cases, with 6 of these resulting from coil embolization. In patients treated with parent vessel reconstruction, 1 aneurysm ruptured post‐treatment and 2 patients experienced in‐stent thrombosis. Overall, 83.8% of patients had a good neurological outcome and 77.8% of aneurysms were completed occluded on follow‐up imaging. Conclusions The development of pseudoaneurysms in the pediatric population are an important consideration in cases of traumatic head injuries or iatrogenic vessel trauma. These lesions grow rapidly and can carry a high risk of morbidity and mortality if left untreated. Our findings suggest that endovascular treatment of traumatic pseudoaneurysms in the pediatric populations is safe and effective, with high rates of aneurysm occlusion and good neurological outcome. Overall, complications rates are low. Aneurysm embolization can carry an increased risk of aneurysm recurrence.

Introduction We present a patient with a giant vertebrobasilar system aneurysm. This case provides an in‐depth analysis of the pathologic mechanism resulting in catastrophic distal hemorrhage following stent deployment due to the shared effects of normal perfusion pressure breakthrough (NPPB) and the Windkessel phenomenon. The Windkessel phenomenon and NPPB occur before and after treatment of various vascular malformations, respectively. These phenomena are hypothesized to contribute to the loss of cerebrovascular autoregulation. High flow lesions and giant aneurysms reduce blood flow in downstream vessels, causing chronic distal vasodilation to protect against ischemia. Sudden restoration of normal pulsatile flow, following treatment, compromises the integrity of distal vessels leading to potential catastrophic intracerebral hemorrhage. Methods A retrospective review of the patient’s medical record was performed. Results A 60‐year‐old female initially presenting with pulsatile neck mass was found to have dolichoectasia of the right cervical internal carotid artery and two large, irregular, vertebrobasilar aneurysms. Managed conservatively for 10 years before developing gait ataxia, new imaging revealed growth of the now giant, more distal aneurysm. Flow diversion with partial coiling of the aneurysms was pursued. Following deployment, DynaCT demonstrated catastrophic thalamic and midbrain hemorrhage with intraventricular extension. A review of intra‐aneurysmal pressure measurements, angiography, MRI, and neuromonitoring data strongly suggests rupture of multiple deep perforators following the conversion to laminar flow when the flow diverting chain was finalized. This suggests giant aneurysms chronically depress the distal pulse pressure by acting as a Windkessel reservoir. Flow diversion bypasses the reservoir increasing pulse pressure distal to the aneurysm, exceeding autoregulatory capacity, leading to hemorrhage. Conclusions This is the first case in the literature to describe NPPB and the Windkessel phenomenon in the attempt to treat giant aneurysms with flow diversion. Flow diversion bypasses the reservoir, suddenly changing turbulent flow to laminar flow. The resultant dramatic rise in pulse pressure distal to the aneurysm can exceed the autoregulatory mechanisms of small distal vessels such as perforating branches. While demonstrating a poor outcome, awareness of these mechanisms and meticulous intra‐operative blood pressure management may reduce or prevent complications. Further modeling of flow dynamics both before and following treatment of these aneurysms may lead to altered guidelines in the temporality of treatment due to potential catastrophic sequelae.

Aneurysms located on the middle cerebral artery (MCA) range from 22% to 31.5% in prevalence of all aneurysms in anterior cerebral circulation. This bibliometric analysis summarizes the most-cited articles on MCA aneurysms and highlights the landmark publications that contributed to today's evidence-based practice.In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until August 2022. The keyword "(middle cerebral artery OR MCA) AND aneurysm" was used. Our results were arranged in descending order based on the article's citation count. The 100 most-cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact Per Paper (SNIP), and Hirsch index were collected.The keyword-based search showed that 1206 articles were published up to August 2022 on MCA Aneurysms. The top 100 articles were published between 1940 and 2019. The top 100 most cited articles collected a total of 6232 citations with an average of 62.3 citations per paper. The rate of self-citations accounted for an average of 5.75% of the total number of citations.The bibliometric analysis provides a quantitative overview of how medical literature and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in research regarding MCA aneurysms by finding the top 100 most cited papers.

Cerebral cavernous malformations (CCM), or cavernomas, are low-flow sinusoidal vascular anomalies of the central nervous system comprised of capillary networks filled with blood in various stages of thrombosis. This bibliometric analysis summarizes the most-cited articles on CCM and highlights the contributing articles to today's evidence-based practice.In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until June 2022. The keyword "cerebral cavernous malformations" OR "cerebral cavernous hemangioma" OR "cerebral cavernous angioma" OR "cerebral cavernoma." was used. Our results were arranged in descending order based on the article's citation count. The 100 most-cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact Per Paper (SNIP), and Hirsch index were collected.The keyword-based search showed that 806 articles were published between 1974 and 2022 on CCMs. The top 100 articles were published between 1980 and 2018. The top 100 most cited articles collected a total of 12,928 citations with an average of 129.3 citations per paper. The rate of self-citations accounted for an average of 2.79% of the total number of citations.The bibliometric analysis provides a quantitative overview of how medical topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in CCMs by analyzing the top 100 most cited papers.

BACKGROUND The artery of Davidoff and Schechter (ADS) is an uncommonly encountered meningeal branch originating from the posterior cerebral artery typically identified in the setting of pathology, often dural arteriovenous fistulas (DAVFs). Here, the authors describe the first reported case of an ADS aneurysm, discovered in the setting of subarachnoid hemorrhage (SAH) and complicating a high-grade DAVF. OBSERVATIONS A 57-year-old female presented after experiencing the worst headache of her life. Noncontrast computed tomography scanning of the head demonstrated SAH. Angiography revealed a high-grade DAVF centered around the anterior straight sinus, consistent with the Galenic subtype of tentorial DAVF. Predominant arterial supply was from the bilateral middle meningeal and occipital arteries. Vertebral artery imaging revealed a 12-mm irregular aneurysm. The prospect that the target artery represented the noneloquent ADS was confirmed by Wada testing. Given the fusiform nature of the aneurysm, treatment required concomitant coil embolization of the aneurysm and parent artery sacrifice. A week later, the DAVF was treated with liquid embolic. The patient tolerated treatment without neurological compromise. LESSONS The authors describe the first reported case of an ADS aneurysm discovered in the setting of SAH complicating a high-grade DAVF and the lessons learned during our experience managing this unique pathology.

Objectives: Congenital vascular lesions commonly present in the head and neck, and most are managed conservatively. Location and rapid growth, however, may necessitate surgical intervention. Endoscopic endonasal surgery (EES) in the pediatric population has emerged as a viable option in treating sinonasal and skull base lesions. Utilizing these techniques in newborns carries unique challenges. The objective of this report is to describe the successful use of direct intralesional embolization followed by endoscopic endonasal resection of a venous malformation in a postnatal patient. Methods: We reviewed the case reported and reviewed the pertinent literature. Results: A 6-week-old infant was found to have a large right-sided sinonasal lesion confirmed as a venous malformation. Rapid growth, impending orbital compromise, and potential long-term craniofacial abnormalities demanded the need for urgent surgical intervention. Risk of bleeding was mitigated with direct intralesional embolization. Immediately afterward, the patient underwent endoscopic endonasal resection of the lesion. EES in the very young presents multiple challenges both anatomically and behaviorally. A multidisciplinary approach lead to a successful outcome. Conclusion: We report a case of a 6-week-old infant, the youngest reported patient to the authors’ knowledge, who successfully underwent direct intralesional embolization followed by endoscopic endonasal resection of a sinonasal vascular malformation. This report highlights the challenges of this technique in the very young and demonstrates it as a viable treatment strategy for sinonasal vascular anomalies in this population.

OBJECTIVE Head and neck arteriovenous malformations (AVMs) are complex lesions that represent a subset of vascular anomalies (VAs). The authors present an analysis of their institutional experience managing these lesions as a multidisciplinary team. METHODS A retrospective chart review was performed of head and neck AVM patients treated at the authors’ institution from 2012 to 2022. Recorded data included patient demographic characteristics, details of clinical presentation, Schöbinger clinical scale and Yakes AVM classification results, and details of all endovascular and surgical treatments. The primary outcome of the study was clinical response to treatment. Angiographic occlusion and complication rates were reported. Chi-square tests were used for comparative statistics. RESULTS Sixteen patients (9 female, 56%) with AVMs of the head and neck presented from age 3 to 77 years. The Schöbinger stage was stage II in 56% of patients (n = 9) and stage III in 44% of patients (n = 7). The Yakes AVM classification was nidus type (2a, 2b, or 4) in 7 patients (43%) and fistula type (1, 3a, or 3b) in 9 patients (57%). The majority of patients (n = 11, 69.0%) were managed with embolization as the only treatment modality, with an average of 1.5 embolizations/patient (range 1–3). Surgical resection was employed in 5 patients (4 in combination with embolization). Symptom resolution and symptom control were achieved in 69% and 31% of patients, respectively, in the entire cohort. A radiographic cure was demonstrated in 50% of patients. There were no statistical differences in clinical outcomes or radiographic cure rates between patients treated with different modalities. CONCLUSIONS Head and neck AVMs can be treated successfully with a primarily endovascular management strategy by a multidisciplinary team with the goal of symptomatic control.

Once mainly known as a menu item in American and Canadian Thanksgiving dinners, cranberries have branched out to become a major commercial crop in the United States. Cranberries, along with blueberries and concord grapes, are the only native fruits grown commercially in the United States. Wisconsin leads the United States in cranberry production. The growth of this industry has led to a net economic gain to the community and region. This paper initiates the discussion of the cranberry industry to the State of Wisconsin’s economy; adding it as a topic in the field of economic development. This paper uses "input output analysis" in an effort to estimate the economic value of this crop.

Transformation Induced Plasticity (TRIP) steels have not yet been successfully joined by any welding technique. It is desirable to search for a suitable welding technique that opens up for full usability of TRIP steels. In this study, the potential of joining TRIP steel with Friction Stir Spot Welding (FSSW) is investigated. The aim of the study is to investigate whether acceptable welds can be produced, and additionally, to obtain an understanding of the microstructural changes during welding. The microstructure was investigated with a combination of microscopical techniques with the aim of identifying the transformations occurring during welding. Reflected light microscopy, scanning electron microscopy, and electron backscatter diffraction were among the methods applied for detailed investigations. The microstructure adjacent to the welds can generally be subdivided in two thermo-mechanically affected zones (TMAZ), and two heat-affected zones (HAZ). The dual behavior of the microstructure in the zones is related to the two transition temperatures in steel: A1 and A3. In parts of the TMAZ the microstructure contains ultra fine-grained ferrite. This finding parallels the observation in thermo-mechanically processed steels, where severe deformation at elevated temperatures is used to produce ultra fine-grained microstructures. Several possible transformation mechanisms could in principle explain the development of ultra fine-grained ferrite, e.g. dynamic recrystallization, strain-induced ferrite transformation and dynamic recovery.

Friction stir spot welding has been shown to be a viable method of joining ultra high strength steel, both in terms of joint strength and process cycle time. However, the cost of tooling must be reasonable in order for this method to be adopted as an industrial process. Recently a new tool alloy has been developed, using a blend of polycrystalline cubic boron nitride (PCBN) and tungsten rhenium (W–Re) in order to improve the toughness of the tool. Wear testing results are presented for two of these alloys: one with a composition of 60% PCBN and 40% W–Re, and one with 70% PCBN and 30% W–Re. The sheet material used for all wear testing was 1·4 mm DP 980. Lap shear testing was used to show the relationship between tool wear and joint strength. The Q70 tool provided the best combination of wear resistance and joint strength.

This study examines how student practice of scientific argumentation using socioscientific bioethics issues affects both teacher expectations of students’ general performance and student confidence in their own work. When teachers use bioethical issues in the classroom students can gain not only biology content knowledge but also important decision-making skills. Learning bioethics through scientific argumentation gives students opportunities to express their ideas, formulate educated opinions and value others’ viewpoints. Research has shown that science teachers’ expectations of student success and knowledge directly influence student achievement and confidence levels. Our study analyzes pre-course and post-course surveys completed by students enrolled in a university level bioethics course (n = 111) and by faculty in the College of Biology and Agriculture faculty (n = 34) based on their perceptions of student confidence. Additionally, student data were collected from classroom observations and interviews. Data analysis showed a disconnect between faculty and students perceptions of confidence for both knowledge and the use of science argumentation. Student reports of their confidence levels regarding various bioethical issues were higher than faculty reports. A further disconnect showed up between students’ preferred learning styles and the general faculty’s common teaching methods; students learned more by practicing scientific argumentation than listening to traditional lectures. Students who completed a bioethics course that included practice in scientific argumentation, significantly increased their confidence levels. This study suggests that professors’ expectations and teaching styles influence student confidence levels in both knowledge and scientific argumentation.

In response to increasing public awareness and negative long-term health effects of concussions, the National Football League implemented the “Crown-of-the-Helmet Rule” (CHR). The CHR imposes penalties on players who initiate contact using the top of the helmet. This paper examines the intended effect of this policy and its potential for unintended consequences. We find evidence supporting the intended effect of the policy- a reduction in weekly concussion reports among defensive players by as much as 32% (34% for all head and neck injuries), but also evidence of an increase in weekly lower extremity injury reports for offensive players by as much as 34%.

The genomes of three strains of Listeria monocytogenes that have been associated with food-borne illness in the USA were subjected to whole genome comparative analysis. A total of 51, 97 and 69 strain-specific genes were identified in L.monocytogenes strains F2365 (serotype 4b, cheese isolate), F6854 (serotype 1/2a, frankfurter isolate) and H7858 (serotype 4b, meat isolate), respectively. Eighty-three genes were restricted to serotype 1/2a and 51 to serotype 4b strains. These strain- and serotype-specific genes probably contribute to observed differences in pathogenicity, and the ability of the organisms to survive and grow in their respective environmental niches. The serotype 1/2a-specific genes include an operon that encodes the rhamnose biosynthetic pathway that is associated with teichoic acid biosynthesis, as well as operons for five glycosyl transferases and an adenine-specific DNA methyltransferase. A total of 8603 and 105 050 high quality single nucleotide polymorphisms (SNPs) were found on the draft genome sequences of strain H7858 and strain F6854, respectively, when compared with strain F2365. Whole genome comparative analyses revealed that the L.monocytogenes genomes are essentially syntenic, with the majority of genomic differences consisting of phage insertions, transposable elements and SNPs.

Desulfovibrio vulgaris Hildenborough is a model organism for studying the energy metabolism of sulfate-reducing bacteria (SRB) and for understanding the economic impacts of SRB, including biocorrosion of metal infrastructure and bioremediation of toxic metal ions. The 3,570,858 base pair (bp) genome sequence reveals a network of novel c-type cytochromes, connecting multiple periplasmic hydrogenases and formate dehydrogenases, as a key feature of its energy metabolism. The relative arrangement of genes encoding enzymes for energy transduction, together with inferred cellular location of the enzymes, provides a basis for proposing an expansion to the 'hydrogen-cycling' model for increasing energy efficiency in this bacterium. Plasmid-encoded functions include modification of cell surface components, nitrogen fixation and a type-III protein secretion system. This genome sequence represents a substantial step toward the elucidation of pathways for reduction (and bioremediation) of pollutants such as uranium and chromium and offers a new starting point for defining this organism's complex anaerobic respiration.

We have applied “whole-genome shotgun sequencing” to microbial populations collected en masse on tangential flow and impact filters from seawater samples collected from the Sargasso Sea near Bermuda. A total of 1.045 billion base pairs of nonredundant sequence was generated, annotated, and analyzed to elucidate the gene content, diversity, and relative abundance of the organisms within these environmental samples. These data are estimated to derive from at least 1800 genomic species based on sequence relatedness, including 148 previously unknown bacterial phylotypes. We have identified over 1.2 million previously unknown genes represented in these samples, including more than 782 new rhodopsin-like photoreceptors. Variation in species present and stoichiometry suggests substantial oceanic microbial diversity. Microorganisms are responsible for most of the biogeochemical cycles that shape the environment of Earth and its oceans. Yet, these organisms are the least well understood on Earth, as the ability to study and understand the metabolic potential of microorganisms has been hampered by the inability to generate pure cultures. Recent studies have begun to explore environ

Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis.

The genome of Chlamydophila caviae (formerly Chlamydia psittaci, GPIC isolate) (1 173 390 nt with a plasmid of 7966 nt) was determined, representing the fourth species with a complete genome sequence from the Chlamydiaceae family of obligate intracellular bacterial pathogens. Of 1009 annotated genes, 798 were conserved in all three other completed Chlamydiaceae genomes. The C.caviae genome contains 68 genes that lack orthologs in any other completed chlamydial genomes, including tryptophan and thiamine biosynthesis determinants and a ribose-phosphate pyrophosphokinase, the product of the prsA gene. Notable amongst these was a novel member of the virulence-associated invasin/intimin family (IIF) of Gram-negative bacteria. Intriguingly, two authentic frameshift mutations in the ORF indicate that this gene is not functional. Many of the unique genes are found in the replication termination region (RTR or plasticity zone), an area of frequent symmetrical inversion events around the replication terminus shown to be a hotspot for genome variation in previous genome sequencing studies. In C.caviae, the RTR includes several loci of particular interest including a large toxin gene and evidence of ancestral insertion(s) of a bacteriophage. This toxin gene, not present in Chlamydia pneumoniae, is a member of the YopT effector family of type III-secreted cysteine proteases. One gene cluster (guaBA-add) in the RTR is much more similar to orthologs in Chlamydia muridarum than those in the phylogenetically closest species C.pneumoniae, suggesting the possibility of horizontal transfer of genes between the rodent-associated Chlamydiae. With most genes observed in the other chlamydial genomes represented, C.caviae provides a good model for the Chlamydiaceae and a point of comparison against the human atherosclerosis-associated C.pneumoniae. This crucial addition to the set of completed Chlamydiaceae genome sequences is enabling dissection of the roles played by niche-specific genes in these important bacterial pathogens.

Shewanella oneidensis is an important model organism for bioremediation studies because of its diverse respiratory capabilities, conferred in part by multicomponent, branched electron transport systems. Here we report the sequencing of the S. oneidensis genome, which consists of a 4,969,803-base pair circular chromosome with 4,758 predicted protein-encoding open reading frames (CDS) and a 161,613-base pair plasmid with 173 CDSs. We identified the first Shewanella lambda-like phage, providing a potential tool for further genome engineering. Genome analysis revealed 39 c-type cytochromes, including 32 previously unidentified in S. oneidensis, and a novel periplasmic [Fe] hydrogenase, which are integral members of the electron transport system. This genome sequence represents a critical step in the elucidation of the pathways for reduction (and bioremediation) of pollutants such as uranium (U) and chromium (Cr), and offers a starting point for defining this organism's complex electron transport systems and metal ion-reducing capabilities.

The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome.

The complete genome of the green-sulfur eubacterium Chlorobium tepidum TLS was determined to be a single circular chromosome of 2,154,946 bp. This represents the first genome sequence from the phylum Chlorobia , whose members perform anoxygenic photosynthesis by the reductive tricarboxylic acid cycle. Genome comparisons have identified genes in C. tepidum that are highly conserved among photosynthetic species. Many of these have no assigned function and may play novel roles in photosynthesis or photobiology. Phylogenomic analysis reveals likely duplications of genes involved in biosynthetic pathways for photosynthesis and the metabolism of sulfur and nitrogen as well as strong similarities between metabolic processes in C. tepidum and many Archaeal species.

We have determined that Borrelia burgdorferi strain B31 MI carries 21 extrachromosomal DNA elements, the largest number known for any bacterium. Among these are 12 linear and nine circular plasmids, whose sequences total 610 694 bp. We report here the nucleotide sequence of three linear and seven circular plasmids (comprising 290 546 bp) in this infectious isolate. This completes the genome sequencing project for this organism; its genome size is 1 521 419 bp (plus about 2000 bp of undetermined telomeric sequences). Analysis of the sequence implies that there has been extensive and sometimes rather recent DNA rearrangement among a number of the linear plasmids. Many of these events appear to have been mediated by recombinational processes that formed duplications. These many regions of similarity are reflected in the fact that most plasmid genes are members of one of the genome's 161 paralogous gene families; 107 of these gene families, which vary in size from two to 41 members, contain at least one plasmid gene. These rearrangements appear to have contributed to a surprisingly large number of apparently non-functional pseudogenes, a very unusual feature for a prokaryotic genome. The presence of these damaged genes suggests that some of the plasmids may be in a period of rapid evolution. The sequence predicts 535 plasmid genes ≥300 bp in length that may be intact and 167 apparently mutationally damaged and/or unexpressed genes (pseudogenes). The large majority, over 90%, of genes on these plasmids have no convincing similarity to genes outside Borrelia, suggesting that they perform specialized functions.

A new system for aligning whole genome sequences is described. Using an efficient data structure called a suffix tree, the system is able to rapidly align sequences containing millions of nucleotides. Its use is demonstrated on two strains of Mycoplasma tuberculosis, on two less similar species of Mycoplasma bacteria and on two syntenic sequences from human chromosome 12 and mouse chromosome 6. In each case it found an alignment of the input sequences, using between 30 s and 2 min of computation time. From the system output, information on single nucleotide changes, translocations and homologous genes can easily be extracted. Use of the algorithm should facilitate analysis of syntenic chromosomal regions, strain-to-strain comparisons, evolutionary comparisons and genomic duplications.

The genome of the bacterium Borrelia burgdorferi B31, the aetiologic agent of Lyme disease, contains a linear chromosome of 910,725 base pairs and at least 17 linear and circular plasmids with a combined size of more than 533,000 base pairs. The chromosome contains 853 genes encoding a basic set of proteins for DNA replication, transcription, translation, solute transport and energy metabolism, but, like Mycoplasma genitalium, it contains no genes for cellular biosynthetic reactions. Because B. burgdorferi and M. genitalium are distantly related eubacteria, we suggest that their limited metabolic capacities reflect convergent evolution by gene loss from more metabolically competent progenitors. Of 430 genes on 11 plasmids, most have no known biological function; 39% of plasmid genes are paralogues that form 47 gene families. The biological significance of the multiple plasmid-encoded genes is not clear, although they may be involved in antigenic variation or immune evasion.

Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.

Friction stir spot welding has been shown to be a viable method of joining ultra high strength steel (UHSS), both in terms of joint strength and process cycle time. However, the cost of tooling must be reasonable in order for this method to be adopted as an industrial process. Several tooling materials have been evaluated in prior studies, including silicon nitride and polycrystalline cubic boron nitride (PCBN). Recently a new tool alloy has been developed, where a blend of PCBN and tungsten rhenium (W-Re) was used in order to improve the toughness of the tool. Wear testing results are presented for two of these alloys: one with a composition of 60% PCBN and 40% W-Re (designated as Q60), and one with 70% PCBN and 30% W-Re (designated at Q70). The sheet material used for all wear testing was DP 980. Tool profiles were measured periodically during the testing process in order to show the progression of wear as a function of the number of spots produced. Lap shear testing was done each time a tool profile was taken in order to show the relationship between tool wear and joint strength. For the welding parameters chosen for this study the Q70more » tool provided the best combination of wear resistance and joint strength.« less

Friction stir welding (FSW) is a relatively new joining technology invented by The Welding Institute in 1991. The general use has been for welding soft, low melting materials such as aluminum. Advances in tool technology has allowed for the implementation of FSW into steel, stainless steel and nickel base alloys. The benefits of FSW include low heat input, elimination of solidification defects, the ability to join difficult and historically unweldable materials all while improving the mechanical properties over conventional welding processes. The oil and gas industry utilizes many specialized materials for performance and corrosion resistance. This paper will present and report progress on the different material properties and applications of FSW within the oil and gas industry.

Logic is the lifeblood of American law. In case after case, prosecutors, defense counsel, civil attorneys, and judges call upon the rules of logic to structure their arguments. Law professors, for their part, demand that students defend their comments with coherent, identifiable logic. By now we are all familiar with the great line spoken by Professor Kingsfield in The Paper Chase: “You come in here with a head full of mush and you leave thinking like a lawyer.” What is thinking like a lawyer? It means employing logic to construct arguments.

The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae , the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for ≈80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi , and Leishmania major , three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that—along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions—have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.

The trypanosomatid protozoa Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are related human pathogens that cause markedly distinct diseases. Using information from genome sequencing projects currently underway, we have compared the sequences of large chromosomal fragments from each species. Despite high levels of divergence at the sequence level, these three species exhibit a striking conservation of gene order, suggesting that selection has maintained gene order among the trypanosomatids over hundreds of millions of years of evolution. The few sites of genome rearrangement between these species are marked by the presence of retrotransposon-like elements, suggesting that retrotransposons may have played an important role in shaping trypanosomatid genome organization. A degenerate retroelement was identified in L. major by examining the regions near breakage points of the synteny. This is the first such element found in L. major suggesting that retroelements were found in the common ancestor of all three species.

Pseudomonas putida is a metabolically versatile saprophytic soil bacterium that has been certified as a biosafety host for the cloning of foreign genes. The bacterium also has considerable potential for biotechnological applications. Sequence analysis of the 6.18 Mb genome of strain KT2440 reveals diverse transport and metabolic systems. Although there is a high level of genome conservation with the pathogenic Pseudomonad Pseudomonas aeruginosa (85% of the predicted coding regions are shared), key virulence factors including exotoxin A and type III secretion systems are absent. Analysis of the genome gives insight into the non-pathogenic nature of P. putida and points to potential new applications in agriculture, biocatalysis, bioremediation and bioplastic production.

Virulence and immunity are poorly understood inMycobacterium tuberculosis.We sequenced the complete genome of theM. tuberculosisclinical strain CDC1551 and performed a whole-genome comparison with the laboratory strain H37Rv in order to identify polymorphic sequences with potential relevance to disease pathogenesis, immunity, and evolution. We found large-sequence and single-nucleotide polymorphisms in numerous genes. Polymorphic loci included a phospholipase C, a membrane lipoprotein, members of an adenylate cyclase gene family, and members of the PE/PPE gene family, some of which have been implicated in virulence or the host immune response. Several gene families, including the PE/PPE gene family, also had significantly higher synonymous and nonsynonymous substitution frequencies compared to the genome as a whole. We tested a large sample ofM. tuberculosisclinical isolates for a subset of the large-sequence and single-nucleotide polymorphisms and found widespread genetic variability at many of these loci. We performed phylogenetic and epidemiological analysis to investigate the evolutionary relationships among isolates and the origins of specific polymorphic loci. A number of these polymorphisms appear to have occurred multiple times as independent events, suggesting that these changes may be under selective pressure. Together, these results demonstrate that polymorphisms amongM. tuberculosisstrains are more extensive than initially anticipated, and genetic variation may have an important role in disease pathogenesis and immunity.

Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease.

The 2,160,837–base pair genome sequence of an isolate of Streptococcus pneumoniae , a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low–guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.

The human genome was analyzed for evidence that genes had been laterally transferred into the genome from prokaryotic organisms. Protein sequence comparisons of the proteomes of human, fruit fly, nematode worm, yeast, mustard weed, eukaryotic parasites, and all completed prokaryote genomes were performed, and all genes shared between human and each of the other groups of organisms were collected. About 40 genes were found to be exclusively shared by humans and bacteria and are candidate examples of horizontal transfer from bacteria to vertebrates. Gene loss combined with sample size effects and evolutionary rate variation provide an alternative, more biologically plausible explanation.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284,156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.

The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi , the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes.

Archaeoglobus fulgidus is the first sulphur-metabolizing organism to have its genome sequence determined. Its genome of 2,178,400 base pairs contains 2,436 open reading frames (ORFs). The information processing systems and the biosynthetic pathways for essential components (nucleotides, amino acids and cofactors) have extensive correlation with their counterparts in the archaeon Methanococcus jannaschii. The genomes of these two Archaea indicate dramatic differences in the way these organisms sense their environment, perform regulatory and transport functions, and gain energy. In contrast to M. jannaschii, A. fulgidus has fewer restriction-modification systems, and none of its genes appears to contain inteins. A quarter (651 ORFs) of the A. fulgidus genome encodes functionally uncharacterized yet conserved proteins, two-thirds of which are shared with M. jannaschii (428 ORFs). Another quarter of the genome encodes new proteins indicating substantial archaeal gene diversity.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.

Here we determine the complete genomic sequence of the Gram negative, γ-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the γ-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host ‘addiction’ genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen. Supplementary information The online version of this article (doi:10.1038/35020000) contains supplementary material, which is available to authorized users.