Non-lead hollow point bullet

DOEpatents

Vaughn, Norman L.; Lowden, Richard A.

2003-04-15

The non-lead hollow point bullet of the instant invention comprises a mixed construction slug further comprising, a monolithic metal insert having a tapered (preferred conical) hollow point tip and a tapered (preferred conical) tail protrusion, and an unsintered powdered metal composite core in tandem alignment with the insert. The core has a hollow tapered (preferred conical) cavity tip portion coupled with the tapered (preferred conical) tail protrusion on the insert. An open tip jacket envelops at least a portion of the insert and the core. The jacket is swaged at the open tip.

Proper assessment of the JFK assassination bullet lead evidence from metallurgical and statistical perspectives.

PubMed

Randich, Erik; Grant, Patrick M

2006-07-01

The bullet evidence in the JFK assassination investigation was reexamined from metallurgical and statistical standpoints. The questioned specimens are comprised of soft lead, possibly from full-metal-jacketed Mannlicher-Carcano (MC), 6.5-mm ammunition. During lead refining, contaminant elements are removed to specified levels for a desired alloy or composition. Microsegregation of trace and minor elements during lead casting and processing can account for the experimental variabilities measured in various evidentiary and comparison samples by laboratory analysts. Thus, elevated concentrations of antimony and copper at crystallographic grain boundaries, the widely varying sizes of grains in MC bullet lead, and the 5-60 mg bullet samples analyzed for assassination intelligence effectively resulted in operational sampling error for the analyses. This deficiency was not considered in the original data interpretation and resulted in an invalid conclusion in favor of the single-bullet theory of the assassination. Alternate statistical calculations, based on the historic analytical data, incorporating weighted averaging and propagation of experimental uncertainties also considerably weaken support for the single-bullet theory. In effect, this assessment of the material composition of the lead specimens from the assassination concludes that the extant evidence is consistent with any number between two and five rounds fired in Dealey Plaza during the shooting.

Proper Assessment of the JFK Assassination Bullet Lead Evidence from Metallurgical and Statistical Perspectives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Randich, E; Grant, P M

2006-08-29

The bullet evidence in the JFK assassination investigation was reexamined from metallurgical and statistical standpoints. The questioned specimens are comprised of soft lead, possibly from full-metal-jacketed Mannlicher-Carcano, 6.5-mm ammunition. During lead refining, contaminant elements are removed to specified levels for a desired alloy or composition. Microsegregation of trace and minor elements during lead casting and processing can account for the experimental variabilities measured in various evidentiary and comparison samples by laboratory analysts. Thus, elevated concentrations of antimony and copper at crystallographic grain boundaries, the widely varying sizes of grains in Mannlicher-Carcano bullet lead, and the 5-60 mg bullet samples analyzedmore » for assassination intelligence effectively resulted in operational sampling error for the analyses. This deficiency was not considered in the original data interpretation and resulted in an invalid conclusion in favor of the single-bullet theory of the assassination. Alternate statistical calculations, based on the historic analytical data, incorporating weighted averaging and propagation of experimental uncertainties also considerably weaken support for the single-bullet theory. In effect, this assessment of the material composition of the lead specimens from the assassination concludes that the extant evidence is consistent with any number between two and five rounds fired in Dealey Plaza during the shooting.« less

Detection of lead nanoparticles in game meat by single particle ICP-MS following use of lead-containing bullets.

PubMed

Kollander, Barbro; Widemo, Fredrik; Ågren, Erik; Larsen, Erik H; Loeschner, Katrin

2017-03-01

This study investigated whether game meat may contain nanoparticles of lead from ammunition. Lead nanoparticles in the range 40 to 750 nm were detected by ICP-MS in single particle mode in game shot with lead-containing bullets. The median diameter of the detected nanoparticles was around 60 nm. The particle mass concentration ranged from 290 to 340 ng/g meat and the particle number concentrations from 27 to 50 million particles/g meat. The size limit of detection strongly depended on the level of dissolved lead and was in the range of 40 to 80 nm. In game meat sampled more than 10 cm away from the wound channel, no lead particles with a diameter larger than 40 nm were detected. In addition to dissolved lead in meat that originated from particulates, the presence of lead nano particles in game meat represents a hitherto unattended source of lead with a largely unknown toxicological impact to humans. Graphical Abstract Detection of lead nanoparticles in game meat by single particle ICP-MS following use of leadcontaining bullets.

Simulation of impact ballistic of Cu-10wt%Sn frangible bullet using smoothed particle hydrodynamics

NASA Astrophysics Data System (ADS)

Hidayat, Mas Irfan P.; Widyastuti, Simaremare, Peniel

2018-04-01

Frangible bullet is designed to disintegrate upon impact against a hard target. Understanding the impact response and performance of frangible bullet is therefore of highly interest. In this paper, simulation of impact ballistic of Cu-IOwt%Sn frangible bullet using smoothed particle hydrodynamics (SPH) method is presented. The frangible bullet is impacted against a hard, cylindrical stainless steel target. Effect of variability of the frangible bullet material properties due to the variation of sintering temperature in its manufacturing process to the bullet frangibility factor (FF) is investigated numerically. In addition, the bullet kinetic energy during impact as well as its ricochet and fragmentation are also examined and simulated. Failure criterion based upon maximum strain is employed in the simulation. It is shown that the SPH simulation can produce good estimation for kinetic energy of bullet after impact, thus giving the FF prediction with respect to the variation of frangible bullet material properties. In comparison to explicit finite element (FE) simulation, in which only material/element deletion is shown, convenience in showing frangible bullet fragmentation is shown using the SPH simulation. As a result, the effect of sintering temperature to the way of the frangible bullet fragmented can be also observed clearly.

Method of making a non-lead hollow point bullet

DOEpatents

Vaughn, Norman L.; Lowden, Richard A.

2003-10-07

The method of making a non-lead hollow point bullet has the steps of a) compressing an unsintered powdered metal composite core into a jacket, b) punching a hollow cavity tip portion into the core, c) seating an insert, the insert having a hollow point tip and a tail protrusion, on top of the core such that the tail protrusion couples with the hollow cavity tip portion, and d) swaging the open tip of the jacket.

Terminal Performance of Lead Free Pistol Bullets in Ballistic Gelatin Using Retarding Force Analysis from High Speed Video

DTIC Science & Technology

2016-04-04

Terminal Performance of Lead-Free Pistol Bullets in Ballistic Gelatin Using Retarding Force Analysis from High Speed Video ELIJAH COURTNEY, AMY...quantified using high speed video . The temporary stretch cavities and permanent wound cavities are also characterized. Two factors tend to re- duce the...Performance of Lead-Free Pistol Bullets in Ballistic Gelatin Using Retarding Force Analysis from High Speed Video cavity. In addition, stretching can also

Terminal ballistics of the 9mm with Action Safety bullet or Blitz-Action-Trauma (BAT) ammunition.

PubMed

Lantz, P E; Stone, R S; Broudy, D; Morgan, T M

1994-05-01

Specialty ammunition creating atypical gunshot wounds of entrance can create confusion and may be misinterpreted by pathologists unfamiliar with the terminal ballistics of these projectiles. The previously unreported wound ballistics caused by the 9mm with Action Safety bullet described in a homicide highlights the atypical entrance wound(s) and wounding capacity of this novel ammunition. Manufactured by Geco division of Dynamit Nobel, the bullet consists of a nonjacketed solid copper alloy bullet body without a conventional lead core. The large deformation well and part of the smaller central channel is filled with a hard plastic core and post that creates a round nose bullet. The internal ballistics and unique design allow the plastic nose cap and post to separate from the copper alloy base while still in the barrel. The radiolucent nose cap leaves the bullet's path but can still penetrate tissue giving the appearance of a separate but smaller entrance wound. The sharp leading edge of the deformation well and relative high velocity of the bullet body creates a punched out entrance wound with minimal marginal abrasion. When the plastic nose cap or fragments of the plastic post impact the subject, test firings may allow an inference to the muzzle-target distance even in the absence of soot deposition or stippling.

Lead poisoning due to bullets lodged in the human body.

PubMed

Gerstner Garcés, Juan Bernardo; Manotas Artuz, Rafael Ignacio

2012-07-01

With the increased violence and use of firearms in Colombia, we may see more cases of lead poisoning in our environment, and must be prepared to diagnose and treat them. Subtle signs and symptoms as unexplained anemia, gastro-intestinal discomfort and abdominal cramps, as well as severe signs such as changes in behavior and neurological status, nephropathy, and unexplained death, may be associated with a history of gunshot wounds and bullets in the human body. We must offer the patient knowledge and management strategies of pathology.

Lead poisoning due to bullets lodged in the human body

PubMed Central

Manotas Artuz, Rafael Ignacio

2012-01-01

With the increased violence and use of firearms in Colombia, we may see more cases of lead poisoning in our environment, and must be prepared to diagnose and treat them. Subtle signs and symptoms as unexplained anemia, gastro-intestinal discomfort and abdominal cramps, as well as severe signs such as changes in behavior and neurological status, nephropathy, and unexplained death, may be associated with a history of gunshot wounds and bullets in the human body. We must offer the patient knowledge and management strategies of pathology. PMID:24893198

A study of ignition by rifle bullets

Treesearch

Mark A. Finney; Trevor B. Maynard; Sara S. McAllister; Ian J. Grob

2013-01-01

Experiments were conducted to examine the potential for rifle bullets to ignite organic matter after impacting a hard surface. The tests were performed using a variety of common cartridges (7.62x51, 7.62x39, 7.62x54R, and 5.56x45) and bullet materials (steel core, lead core, solid copper, steel jacket, and copper jacket). Bullets were fired at a steel plate that...

Bullet trajectory reconstruction - Methods, accuracy and precision.

PubMed

Mattijssen, Erwin J A T; Kerkhoff, Wim

2016-05-01

Based on the spatial relation between a primary and secondary bullet defect or on the shape and dimensions of the primary bullet defect, a bullet's trajectory prior to impact can be estimated for a shooting scene reconstruction. The accuracy and precision of the estimated trajectories will vary depending on variables such as, the applied method of reconstruction, the (true) angle of incidence, the properties of the target material and the properties of the bullet upon impact. This study focused on the accuracy and precision of estimated bullet trajectories when different variants of the probing method, ellipse method, and lead-in method are applied on bullet defects resulting from shots at various angles of incidence on drywall, MDF and sheet metal. The results show that in most situations the best performance (accuracy and precision) is seen when the probing method is applied. Only for the lowest angles of incidence the performance was better when either the ellipse or lead-in method was applied. The data provided in this paper can be used to select the appropriate method(s) for reconstruction and to correct for systematic errors (accuracy) and to provide a value of the precision, by means of a confidence interval of the specific measurement. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Management of migrating intracranial bullets: lessons learned from surviving an AK-47 bullet through the lateral brainstem.

PubMed

Rammo, Richard A; DeFazio, Michael V; Bullock, M Ross

2012-01-01

Survival after a gunshot wound (GSW) to the head is becoming more common, with an accompanying increase in spontaneous migration of these intracranial bullet fragments. This phenomenon is well described in current literature and is a potentially life-threatening delayed complication of GSW to the head. We present the case of a 17-year-old boy who survived a penetrating GSW to the cranium and cerebellum after an accident involving an AK (Automatic Kalashnikov)-47 (7.62 mm). Following initial attempts to remove the bullet and associated hematoma from the cerebellar hemisphere, intraoperative fluoroscopy revealed that the bullet had migrated to lie within the right middle cerebellar peduncle with the development of intraoperative cardiac arrhythmia. The bullet could not be retrieved without risk of damage to the superior and inferior cerebellar arteries. The patient then developed bacterial meningitis, and further imaging revealed the bullet had again migrated under the cerebellar cortex to an accessible location. The infection was treated with aggressive antibiotic therapy and the bullet was removed from the posterior fossa, thus preventing recurrence of infection and further migration. The patient regained full motor, speech, and proprioceptive function within months after injury. The potential for spontaneous migration exists with any penetrating brain injury involving a retained foreign body. When a retained intracranial foreign body is unable to be safely extracted during initial debridement, close clinical evaluation is essential and plain-film or computed tomographic imaging should be considered in order to enhance the early detection of delayed-onset life-threatening deterioration, such as meningitis and occlusion of cerebrospinal fluid drainage, because of spontaneous migration. Copyright © 2012 Elsevier Inc. All rights reserved.

Lead contamination of golden eagles Aquila chrysaetos within the range of the California condor Gymnogyps californianus

USGS Publications Warehouse

Bloom, P.H.; Scott, J.M.; Pattee, O.H.; Smith, M.R.; Meyburg, B-U.; Chancellor, R.D.

1989-01-01

Blood samples were taken from 66 golden eagles from June 1985 to January 1986 and analyzed for their lead content. Thirty-nine percent had blood lead levels greater than 0.2 ppm, indicating exposure to environmental lead. Within the exposed group, 3 had blood levels exceeding 0.6 ppm and one exceeded 1.0 ppm. These data suggest that lead, probably in the form of shot, bullets, or bullet fragments, poses a hazard to scavenging birds within the range of the California condor.

Endoscopic Removal of a Bullet in Rosenmuller Fossa: Case Report

PubMed Central

Burks, Joshua D.; Glenn, Chad A.; Conner, Andrew K.; Bonney, Phillip A.; Sanclement, Jose A.; Sughrue, Michael E.

2016-01-01

Fractures of the anterior skull base may occur in gunshot victims and can result in traumatic cerebrospinal fluid (CSF) leak. Less commonly, CSF leaks occur days or even weeks after the trauma occurred. Here, we present the case of a 21-year-old man with a delayed-onset, traumatic CSF leak secondary to a missile injury that left a bullet fragment in the Rosenmuller fossa. The patient was treated successfully with endoscopic, endonasal extraction of the bullet, and repair with a nasal septal flap. Foreign bodies lodged in Rosenmuller fossa can be successfully treated with endoscopic skull base surgery. PMID:27330924

Experimental duplication of the important physical evidence of the lapel bulge of the jacket worn by Governor Connally when bullet 399 went through him.

PubMed

Lattimer, J K; Laidlaw, A; Heneghan, P; Haubner, E J

1994-05-01

By duplicating the wound to the neck of President Kennedy, which caused bullet 399 to turn sideways, and having it then hit a Connally-type rib cage with shirt and jacket, we reproduced the right-sided bulge of the jacket worn by Connally, with lapel eversion, which is so significant in frame 224. The extensive damage to his shirtfront was from the hail of rib fragments and soft tissue, exactly as described with his own shirt. Our tumbling bullet then went on to fracture a radius and be recovered intact except that it was somewhat flattened and bent and had lead extruded from the rear, as did bullet 399. Fragments of this lead were scraped off on the ragged bone-ends of some of our fractured radiuses, just as with Governor Connally's radius. It is believed that this duplication of the jacket and lapel bulge of Governor Connally, which occurred dependably, when we reproduced the circumstances at Dallas, confirmed this very important detail in this technical demonstration of the findings in the shooting of President Kennedy and Governor Connally. The bulge and the lapel eversion of the jacket worn by Governor Connally, starting in Zapruder frame 224, does indeed establish, beyond any shadow of a doubt, the exact moment when bullet 399 went through him. The right arms of both men were seen to react simultaneously, immediately thereafter. It also permits us to establish that there was plenty of time (three and one-half seconds) between the first two shots (frames 160 to 224) and even more time (five seconds) between the last two shots (frames 224 to 313), for Oswald to reload, reacquire his target (the head of President Kennedy) plus two full seconds to lock onto it. If the bullet does not traverse the neck of President Kennedy, it does not cause Governor Connally's jacket and lapel to bulge. The lapel bulge is a very important bit of actual physical evidence in establishing the fact that one bullet hit both men and that Oswald had plenty of time to hit the President

Cluster bulleticity

NASA Astrophysics Data System (ADS)

Massey, Richard; Kitching, Thomas; Nagai, Daisuke

2011-05-01

The unique properties of dark matter are revealed during collisions between clusters of galaxies, such as the bullet cluster (1E 0657-56) and baby bullet (MACS J0025-12). These systems provide evidence for an additional, invisible mass in the separation between the distributions of their total mass, measured via gravitational lensing, and their ordinary 'baryonic' matter, measured via its X-ray emission. Unfortunately, the information available from these systems is limited by their rarity. Constraints on the properties of dark matter, such as its interaction cross-section, are therefore restricted by uncertainties in the individual systems' impact velocity, impact parameter and orientation with respect to the line of sight. Here we develop a complementary, statistical measurement in which every piece of substructure falling into every massive cluster is treated as a bullet. We define 'bulleticity' as the mean separation between dark matter and ordinary matter, and we measure the signal in hydrodynamical simulations. The phase space of substructure orbits also exhibits symmetries that provide an equivalent control test. Any detection of bulleticity in real data would indicate a difference in the interaction cross-sections of baryonic and dark matter that may rule out hypotheses of non-particulate dark matter that are otherwise able to model individual systems. A subsequent measurement of bulleticity could constrain the dark matter cross-section. Even with conservative estimates, the existing Hubble Space Telescope archive should yield an independent constraint tighter than that from the bullet cluster. This technique is then trivially extendable to and benefits enormously from larger, future surveys.

OBSERVING CASCADES OF SOLAR BULLETS AT HIGH RESOLUTION. II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scullion, E.; Engvold, O.; Lin, Y.

High resolution observations from the Swedish 1-m Solar Telescope revealed bright, discrete, blob-like structures (which we refer to as solar bullets) in the Hα 656.28 nm line core that appear to propagate laterally across the solar atmosphere as clusters in active regions (ARs). These small-scale structures appear to be field aligned and many bullets become triggered simultaneously and traverse collectively as a cluster. Here, we conduct a follow-up study on these rapidly evolving structures with coincident observations from the Solar Dynamics Observatory/Atmospheric Imaging Assembly. With the co-aligned data sets, we reveal (a) an evolving multithermal structure in the bullet clustermore » ranging from chromospheric to at least transition region temperatures, (b) evidence for cascade-like behavior and corresponding bidirectional motions in bullets within the cluster, which indicate that there is a common source of the initial instability leading to bullet formation, and (c) a direct relationship between co-incident bullet velocities observed in Hα and He ii 30.4 nm and an inverse relationship with respect to bullet intensity in these channels. We find evidence supporting that bullets are typically composed of a cooler, higher density core detectable in Hα with a less dense, hotter, and fainter co-moving outer sheath. Bullets unequivocally demonstrate the finely structured nature of the AR corona. We have no clear evidence for bullets being associated with locally heated (or cooled), fast flowing plasma. Fast MHD pulses (such as solitons) could best describe the dynamic properties of bullets whereas the presence of a multithermal structure is new.« less

Extra-Articular Retained Missiles; Is Surveillance of Lead Levels Needed?

PubMed

Nickel, Walter N; Steelman, Theodore J; Sabath, Zena R; Potter, Benjamin K

2018-03-01

Although gunshot wounds are relatively common, lead toxicity associated with extra-articular retained missiles (EARMs) is an uncommon, yet potentially devastating, complication. Although the risk of lead toxicity with intra-articular retained missiles is well known, EARMs are routinely left in situ or only removed in selected circumstances secondary to the relatively rare occurrence of complications. We first describe a patient with systemic lead poisoning associated with retained lead fragments after a gunshot-induced left femoral shaft fracture. We then performed a systematic review of the literature to answer the following questions: (1) In the setting of retained extra-articular bullets and/or bullet fragments, is regular monitoring and/or surveillance of lead levels in the blood routinely indicated? and, if so, (2) what are the selected factors that portend an increased risk for elevations in blood lead levels in the setting of retained extra-articular bullets and/or bullet fragments? The systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines, of the English language literature utilizing Medline (PubMed), EMBASE, Cochrane, and CINAHL on the topic of lead poisoning, retained bullet, and gunshot wound, and then searched for additional references by manually searching of bibliographies of the included references. Studies were included if they provided clinical data on one or both of our study questions; included studies were evaluated using the accepted levels of evidence. Routine monitoring or surveillance of lead levels in blood is recommended in all cases of EARM at the time of hospital admission and again at discharge, followed by monthly intervals until 3 mo post-injury and then again at 1 yr post-injury. The studies identified demonstrated significant risk factors for elevated blood lead levels in the setting of EARM, which included the number of retained missiles and

Lead Toxicity Risks in Gunshot Victims

PubMed Central

de Araújo, Gabriel Costa Serrão; Mourão, Natália Teixeira; Pinheiro, Igor Natário; Xavier, Analúcia Rampazzo; Gameiro, Vinicius Schott

2015-01-01

Background Gunshot wounds require surgeons to decide whether to remove or leave bullet fragments in the body. Surgeons also decide how to follow up with patients who have lead fragments retained in their body. Current literature recommends to remove only intra-articular fragments without the need for a follow-up for patients with the metal retained. Therefore, this study investigates chronic lead toxicity for gunshot wounds. Methods The study was performed in the metropolitan area of Rio de Janeiro/Brazil, between 2013 and 2015. It was a case-control study that included 45 victims of gunshot lesions with metallic fragments retained for more than 6 months. The 45 controls were matched for gender, age, and race. We compared the lead blood levels and frequency of symptoms. Results The control group had average blood lead levels of 2.17 μg/dL (95% Confidence Interval [CI]; 1.71–2.63) and median 2.1 μg/dL. The case group had average values of 9.01 μg/dL (CI; 6.07–11.96) and median values of 6.5 μg/dL with p-values < = 0.001. The case group reported the following more frequently: irritancy, bad mood, headache, memory losses, daylight drowsiness, myalgia, weakness, abdominal pain, joint pain, trembling, tingling limbs. There was statistical significance for the differences of symptoms frequencies and for odds ratio between groups. Conclusions Although the mean lead levels found were lower than the current laboratory references, low levels have been associated with both rising morbidity and mortality. The WHO stated: “There is no known level of lead exposure that is considered safe”. In conclusion, this work showed that bullets retained in the body are not innocuous. There are impacts in the blood lead levels and symptoms related to it, even with few fragments, extra-articular located or existing with low blood lead levels. PMID:26509498

Ground Squirrel Shooting and Potential Lead Exposure in Breeding Avian Scavengers

PubMed Central

Eagles-Smith, Collin A.; Wagner, Mason T.

2016-01-01

Recreational ground squirrel shooting is a popular activity throughout the western United States and serves as a tool for managing ground squirrel populations in agricultural regions. Belding’s ground squirrels (Spermophilus beldingi) are routinely shot in California, Nevada, and Oregon across habitats that overlap with breeding avian scavengers. Ground squirrels shot with lead (Pb)-based bullets may pose a risk to avian scavengers if they consume carcasses containing Pb fragments. To assess the potential risk to breeding avian scavengers we developed a model to estimate the number, mass, and distribution of Pb fragments in shot ground squirrels using radiographic images. Eighty percent of shot carcasses contained detectible Pb fragments with an average of 38.6 mg of Pb fragments. Seven percent of all carcasses contained Pb fragment masses exceeding a lethal dose for a model raptor nestling (e.g. American kestrel Falco sparverius). Bullet type did not influence the number of fragments in shot ground squirrels, but did influence the mass of fragments retained. Belding’s ground squirrels shot with .17 Super Mag and unknown ammunition types contained over 28 and 17 times more mass of Pb fragments than those shot with .22 solid and .22 hollow point bullets, respectively. Ground squirrel body mass was positively correlated with both the number and mass of Pb fragments in carcasses, increasing on average by 76% and 56% respectively across the range of carcass masses. Although the mass of Pb retained in ground squirrel carcasses was small relative to the original bullet mass, avian scavenger nestlings that frequently consume shot ground squirrels may be at risk for Pb-induced effects (e.g., physiology, growth, or survival). Using modeling efforts we found that if nestling golden eagles (Aquila chrysaetos), red-tailed hawks (Buteo jamaicensis), and Swainson’s hawks (B. swainsoni) consumed shot ground squirrels proportionately to the nestling’s mass, energy needs

Ground squirrel shooting and potential lead exposure in breeding avian scavengers

USGS Publications Warehouse

Herring, Garth; Eagles-Smith, Collin A.; Wagner, Mason T.

2016-01-01

Recreational ground squirrel shooting is a popular activity throughout the western United States and serves as a tool for managing ground squirrel populations in agricultural regions. Belding’s ground squirrels (Spermophilus beldingi) are routinely shot in California, Nevada, and Oregon across habitats that overlap with breeding avian scavengers. Ground squirrels shot with lead (Pb)-based bullets may pose a risk to avian scavengers if they consume carcasses containing Pb fragments. To assess the potential risk to breeding avian scavengers we developed a model to estimate the number, mass, and distribution of Pb fragments in shot ground squirrels using radiographic images. Eighty percent of shot carcasses contained detectible Pb fragments with an average of 38.6 mg of Pb fragments. Seven percent of all carcasses contained Pb fragment masses exceeding a lethal dose for a model raptor nestling (e.g. American kestrel Falco sparverius). Bullet type did not influence the number of fragments in shot ground squirrels, but did influence the mass of fragments retained. Belding’s ground squirrels shot with .17 Super Mag and unknown ammunition types contained over 28 and 17 times more mass of Pb fragments than those shot with .22 solid and .22 hollow point bullets, respectively. Ground squirrel body mass was positively correlated with both the number and mass of Pb fragments in carcasses, increasing on average by 76% and 56% respectively across the range of carcass masses. Although the mass of Pb retained in ground squirrel carcasses was small relative to the original bullet mass, avian scavenger nestlings that frequently consume shot ground squirrels may be at risk for Pb-induced effects (e.g., physiology, growth, or survival). Using modeling efforts we found that if nestling golden eagles (Aquila chrysaetos), red-tailed hawks (Buteo jamaicensis), and Swainson’s hawks (B. swainsoni) consumed shot ground squirrels proportionately to the nestling’s mass, energy needs

Muzzle-loading weapons discharging spherical lead bullets: two case studies and experimental simulation using a skin-soap composite model.

PubMed

Große Perdekamp, Markus; Braunwarth, Roland; Kromeier, Jan; Nadjem, Hadi; Pollak, Stefan; Thierauf, Annette

2013-07-01

In current forensic practice, fatal injuries from black powder guns are rare events. In contact and close-range shots, the intensity of GSR deposition (soot, powder particles) is much greater than that in shots with smokeless powder ammunition. The same applies to any burning effects from the combustion gases. Besides, a wad of felt interposed between the propellant and the lead bullet may enter the wound channel. Apart from these findings seen in close-range shots, another characteristic feature results from the mostly spherical shape of the missiles causing maximum tissue damage at the entrance site. Two fatal injuries inflicted with muzzle-loading weapons are reported. In the first case, suicide was committed with a cal. 11.6 mm miniature cannon by firing a contact shot to the back of the neck. In test shots using black powder (1 and 2 g) as propellant, the mean bullet velocity measured 1 m away from the weapon was 87.11 and 146.85 m/s, respectively, corresponding to a kinetic energy of 32.49 and 92.95 J, respectively. Contact test shots to composite models consisting of ballistic soap covered by pig skin at the entrance site were evaluated by CT and revealed cone-like cavitations along the bullet path as known from spherical missiles and penetration depths up to 25 cm. The second case presented deals with a homicidal close-range shot discharged from a muzzle-loading percussion pistol cal. .44. The skin around the entrance site (root of the nose) was densely covered with blackish soot and powder particles, whereas the eyebrows and eyelashes showed singeing of the hairs. The flattened bullet and the wad had got stuck under the scalp of the occipital region. In both cases, there was a disproportionally large zone of tissue destruction in the initial parts of the wound tracks.

The importance of hydration thermodynamics in fragment-to-lead optimization.

PubMed

Ichihara, Osamu; Shimada, Yuzo; Yoshidome, Daisuke

2014-12-01

Using a computational approach to assess changes in solvation thermodynamics upon ligand binding, we investigated the effects of water molecules on the binding energetics of over 20 fragment hits and their corresponding optimized lead compounds. Binding activity and X-ray crystallographic data of published fragment-to-lead optimization studies from various therapeutically relevant targets were studied. The analysis reveals a distinct difference between the thermodynamic profile of water molecules displaced by fragment hits and those displaced by the corresponding optimized lead compounds. Specifically, fragment hits tend to displace water molecules with notably unfavorable excess entropies-configurationally constrained water molecules-relative to those displaced by the newly added moieties of the lead compound during the course of fragment-to-lead optimization. Herein we describe the details of this analysis with the goal of providing practical guidelines for exploiting thermodynamic signatures of binding site water molecules in the context of fragment-to-lead optimization. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Craniomaxillofacial falling bullet injuries and management.

PubMed

Shuker, Sabri T; Sadda, Raid

2010-07-01

The purpose of this study was to bring attention to craniocerebral maxillofacial perforating/penetrating injuries due to AK-47 Kalashnikov falling bullets (FBs); these dangerous injuries to both civilians and soldiers are rare. A review of the literature shows no reports on AK-47 FBs leading to double craniocerebral perforation and settling into the maxillofacial region. The number of victims, the AK-47's availability, the associated morbidity and mortality rates, and the rarity of cases prompted this article. The treatment of injuries to the craniocerebral facial clinical profile due to FBs is challenging, and an understanding of the neurosurgical and maxillofacial management of these low-velocity FB injuries is required. We treated 11 cases due to AK-47 rifle FBs and 1 due to anti-aircraft Dashka 12.7-mm FBs. Craniocerebral facial injuries were treated and lodged bullets removed from different challenging locations in the base of the skull, without increasing morbidity and with avoidance of unnecessary surgical trauma to the affected area by the bullets. The required identification of such injuries can be difficult, and the removal of the lodged bullet to prevent secondary complications and reduce the chance of secondary infection can be graver than in other parts of the body. AK-47 FBs are a major public health concern internationally and require serious attention in terms of protection and management for civilians and soldiers in uniform. Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Combat-related intradural gunshot wound to the thoracic spine: significant improvement and neurologic recovery following bullet removal.

PubMed

Louwes, Thijs M; Ward, William H; Lee, Kendall H; Freedman, Brett A

2015-02-01

The vast majority of combat-related penetrating spinal injuries from gunshot wounds result in severe or complete neurological deficit. Treatment is based on neurological status, the presence of cerebrospinal fluid (CSF) fistulas, and local effects of any retained fragment(s). We present a case of a 46-year-old male who sustained a spinal gunshot injury from a 7.62-mm AK-47 round that became lodged within the subarachnoid space at T9-T10. He immediately suffered complete motor and sensory loss. By 24-48 hours post-injury, he had recovered lower extremity motor function fully but continued to have severe sensory loss (posterior cord syndrome). On post-injury day 2, he was evacuated from the combat theater and underwent a T9 laminectomy, extraction of the bullet, and dural laceration repair. At surgery, the traumatic durotomy was widened and the bullet, which was laying on the dorsal surface of the spinal cord, was removed. The dura was closed in a water-tight fashion and fibrin glue was applied. Postoperatively, the patient made a significant but incomplete neurological recovery. His stocking-pattern numbness and sub-umbilical searing dysthesia improved. The spinal canal was clear of the foreign body and he had no persistent CSF leak. Postoperative magnetic resonance imaging of the spine revealed contusion of the spinal cord at the T9 level. Early removal of an intra-canicular bullet in the setting of an incomplete spinal cord injury can lead to significant neurological recovery following even high-velocity and/or high-caliber gunshot wounds. However, this case does not speak to, and prior experience does not demonstrate, significant neurological benefit in the setting of a complete injury.

Combat-Related Intradural Gunshot Wound to the Thoracic Spine: Significant Improvement and Neurologic Recovery Following Bullet Removal

PubMed Central

Louwes, Thijs M; Ward, William H; Lee, Kendall H

2015-01-01

The vast majority of combat-related penetrating spinal injuries from gunshot wounds result in severe or complete neurological deficit. Treatment is based on neurological status, the presence of cerebrospinal fluid (CSF) fistulas, and local effects of any retained fragment(s). We present a case of a 46-year-old male who sustained a spinal gunshot injury from a 7.62-mm AK-47 round that became lodged within the subarachnoid space at T9-T10. He immediately suffered complete motor and sensory loss. By 24-48 hours post-injury, he had recovered lower extremity motor function fully but continued to have severe sensory loss (posterior cord syndrome). On post-injury day 2, he was evacuated from the combat theater and underwent a T9 laminectomy, extraction of the bullet, and dural laceration repair. At surgery, the traumatic durotomy was widened and the bullet, which was laying on the dorsal surface of the spinal cord, was removed. The dura was closed in a water-tight fashion and fibrin glue was applied. Postoperatively, the patient made a significant but incomplete neurological recovery. His stocking-pattern numbness and sub-umbilical searing dysthesia improved. The spinal canal was clear of the foreign body and he had no persistent CSF leak. Postoperative magnetic resonance imaging of the spine revealed contusion of the spinal cord at the T9 level. Early removal of an intra-canicular bullet in the setting of an incomplete spinal cord injury can lead to significant neurological recovery following even high-velocity and/or high-caliber gunshot wounds. However, this case does not speak to, and prior experience does not demonstrate, significant neurological benefit in the setting of a complete injury. PMID:25705346

[Bullet and shrapnel injuries in the face and neck regions. Current aspects of wound ballistics].

PubMed

Hauer, T; Huschitt, N; Kulla, M; Kneubuehl, B; Willy, C

2011-08-01

A basic understanding of the ballistic behaviour of projectiles or fragments after entering the human body is essential for the head and neck surgeon in the military environment in order to anticipate the diagnostic and therapeutic consequences of this type of injury. Although a large number of factors influence the missile in flight and after penetration of the body, the most important factor is the amount of energy transmitted to the tissue. Long guns (rifles or shotguns) have a much higher muzzle energy compared to handguns, explaining why the remote effects beyond the bullet track play a major role. While most full metal jacket bullets release their energy after 12-20 cm (depending on the calibre), soft point bullets release their energy immediately after entry into the human body. This results in a major difference in extremity wounds, but not so much in injuries with long bullet paths (e.g. diagonal shots). Shrapnel wounds are usually produced with similarly high kinetic energy to those caused by hand- and long guns. However, fragments tend to dissipate the entire amount of energy within the body, which increases the degree of tissue disruption. Of all relevant injuries in the head and neck region, soft tissue injuries make up the largest proportion (60%), while injuries to the face are seen three times more often than injuries to the neck. Concomitant intracranial or spinal injury is seen in 30% of cases. Due to high levels of wound contamination, the infection rate is approximately 15%, often associated with a complicated and/or multiresistant spectrum of germs.

Fragment-based lead discovery: challenges and opportunities

NASA Astrophysics Data System (ADS)

Sun, Chaohong; Petros, Andrew M.; Hajduk, Philip J.

2011-07-01

Fragment-based lead discovery has undergone remarkable changes over the last 15 years. During this time, the pharmaceutical industry has changed dramatically as well, and continued evolution of the industry is assured. These changes present many challenges but also several opportunities for executing fragment-based drug design. This article will explore some of the more significant changes in the industry and how they may affect future discovery efforts related to fragment-based initiatives.

Fragment-to-Lead Medicinal Chemistry Publications in 2015.

PubMed

Johnson, Christopher N; Erlanson, Daniel A; Murray, Christopher W; Rees, David C

2017-01-12

Fragment-based drug discovery (FBDD) is now well-established as a technology for generating new chemical leads and drugs. This Miniperspective provides a tabulated overview of the fragment-to-lead literature published in the year 2015, together with a commentary on trends observed across the FBDD field during this time. It is hoped that this tabulated summary will provide a useful point of reference for both FBDD practitioners and the wider medicinal chemistry community.

The Silver Bullet Syndrome.

ERIC Educational Resources Information Center

Dehne, George C.

1995-01-01

Many colleges address complex problems with a single "silver bullet" strategy. Because value shifts according to the consumer's situation or goal, private colleges should become more aware of their "situational value" and exploit it. This requires an understanding of how students choose colleges. In contrast, popular silver bullets target…

Bullet identification: a case of a fatal hunting accident resolved by comparison of lead shot using instrumental neutron activation analysis.

PubMed

Capannesi, G; Sedda, A F

1992-03-01

Bullet identification by chemical analysis often provides a powerful clue in forensic science. A case is reported in which a hunting accident was resolved by using instrumental neutron activation analysis (INAA) for direct comparison of the trace element content in lead shot. Different preparation batches of lead shot appear to have a high within-group composition homogeneity, and good differentiation is achieved between different batches. Determination of the nickel and antimony content on a bush branch demonstrated that the branch had been perforated by one of the shot pellets, and this helped the detectives in reconstruction of the crime scene.

SRM 2460/2461 Standard Bullets and Casings Project

PubMed Central

Song, J.; Whitenton, E.; Kelley, D.; Clary, R.; Ma, L.; Ballou, S.; Ols, M.

2004-01-01

The National Institute of Standards and Technology Standard Reference Material (SRM) 2460/2461 standard bullets and casings project will provide support to firearms examiners and to the National Integrated Ballistics Information Network (NIBIN) in the United States. The SRM bullet is designed as both a virtual and a physical bullet profile signature standard. The virtual standard is a set of six digitized bullet profile signatures originally traced from six master bullets fired at the Bureau of Alcohol, Tobacco and Firearms (ATF) and the Federal Bureau of Investigation (FBI). By using the virtual signature standard to control the tool path on a numerically controlled diamond turning machine, 40 SRM bullets were produced. A profile signature measurement system was established for the SRM bullets. The profile signature differences are quantified by the maximum of the cross correlation function and by the signature difference between pairs of compared profile signatures measured on different SRM bullets. Initial measurement results showed high reproducibility for both the measurement system and production process of the SRM bullets. A traceability scheme has been proposed to establish the measurement traceability for nationwide bullet signature measurements to NIST, ATF and FBI. Prototype SRM casings have also been developed. PMID:27366632

Ballistics reviews: mechanisms of bullet wound trauma.

PubMed

Maiden, Nicholas

2009-01-01

The location of an entrance wound (bullet placement) and the projectile path are the most important factors in causing significant injury or death following a shooting. The head followed by the torso are the most vulnerable areas, with incapacitation resulting from central nervous system (brain or cord) disruption, or massive organ destruction with hemorrhage. Tissue and organ trauma result from the permanent wound cavity caused by direct destruction by the bullet, and also from radial stretching of surrounding tissues causing a temporary wound cavity. The extent of tissue damage is influenced by the type of bullet, its velocity and mass, as well as the physical characteristics of the tissues. The latter includes resistance to strain, physical dimensions of an organ, and the presence or absence of surrounding anatomical constraints. Bullet shape and construction will also affect tissue damage and bullets which display greater yaw will be associated with increased temporary cavitation. Military bullet designs do not include bullets that will expand or flatten as these cause greater wound trauma and are regulated by convention.

Gluon fragmentation into quarkonium at next-to-leading order

DOE PAGES

Artoisenet, Pierre; Braaten, Eric

2015-04-22

Here, we present the first calculation at next-to-leading order (NLO) in α s of a fragmentation function into quarkonium whose form at leading order is a nontrivial function of z, namely the fragmentation function for a gluon into a spin-singlet S-wave state at leading order in the relative velocity. To calculate the real NLO corrections, we introduce a new subtraction scheme that allows the phase-space integrals to be evaluated in 4 dimensions. We extract all ultraviolet and infrared divergences in the real NLO corrections analytically by calculating the phase-space integrals of the subtraction terms in 4 – 2ϵ dimensions. Wemore » also extract the divergences in the virtual NLO corrections analytically, and detail the cancellation of all divergences after renormalization. The NLO corrections have a dramatic effect on the shape of the fragmentation function, and they significantly increase the fragmentation probability.« less

Wound ballistics 101: the mechanisms of soft tissue wounding by bullets.

PubMed

Stefanopoulos, P K; Pinialidis, D E; Hadjigeorgiou, G F; Filippakis, K N

2017-10-01

The mechanisms of soft tissue injury by bullets are reviewed, in the belief that the current incidence of firearm injuries in many urban areas necessitates an understanding of wound ballistics on the part of trauma surgeons who may not be familiar with the wounding factors involved. Review of the literature, with technical information obtained from appropriate non-medical texts. Despite numerous publications concerning the treatment of gunshot wounds, relatively few papers contain details on the mechanisms of ballistic trauma, with the main body of evidence derived from previous laboratory and animal studies which have only recently been systematically appraised. These studies have shown that in rifle injuries the main wound tract is surrounded by an area of damaged tissue as a result of the temporary cavitation induced once the bullet becomes destabilized or deformed. On the other hand, the more commonly encountered non-deforming handgun bullets cause damage limited to the bullet's path, mainly as a result of localized crush injury. The bullet's construction and ballistic behavior within tissue determine to what extent the previously overestimated velocity factor may influence wound severity. The damage produced from temporary cavitation depends on the tensile properties of the tissues involved, and in high-energy injuries may lead to progressive muscle tissue necrosis. Therefore, the term "high-energy" should be reserved for those injuries with substantial tissue damage extending beyond the visible wound tract.

Protective ability of the standard U.S. Military Personal Armor System, Ground Troops (PASGT) fragmentation vest against common small arms projectiles.

PubMed

Roberts, G K; Bullian, M E

1993-08-01

This study analyzes the ballistic protection provided by the standard U.S. Military Personal Armor System, Ground Troops fragmentation vest against threats from handgun and shotgun projectiles. Damage assessment was conducted using 10% ordnance gelatin, a tissue simulant which has been proven to have a close correlation with living tissue. The standard fragmentation vest was shown to provide protection from commonly encountered handgun bullets and shotgun pellets, but not from shotgun slugs or center-fire rifle bullets.

Fragment-to-Lead Medicinal Chemistry Publications in 2016.

PubMed

Johnson, Christopher N; Erlanson, Daniel A; Jahnke, Wolfgang; Mortenson, Paul N; Rees, David C

2018-03-08

The popularity of fragment-based drug discovery (FBDD) is demonstrated by the number of recent successful fragment-to-lead (F2L) publications. This Miniperspective provides a tabulated summary of the F2L literature published in the year 2016, along with discussion of general trends. It uses the same format as our summary of the 2015 literature and is intended to be a resource for both FBDD practitioners and medicinal chemists in general.

75 FR 70246 - Lead Fishing Sinkers; Disposition of TSCA Section 21 Petition

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... distribution in commerce of (1) lead bullets and shot; and (2) lead fishing sinkers. On August 27, 2010, EPA denied the first request due to a lack of authority to regulate lead in bullets and shot under TSCA. EPA... commerce of (1) lead bullets and shot; and (2) lead fishing gear. With respect to fishing gear, petitioners...

An Elusive Bullet in the Gastrointestinal Tract: A Rare Case of Bullet Embolism in the Gastrointestinal Tract and a Review of Relevant Literature

PubMed Central

Biswas, Saptarshi

2014-01-01

Bullet embolism within the gastrointestinal system is extremely rare. Such bullet injuries are infrequently covered in the general literature, but the surgeon should be aware of the phenomenon. Smaller caliber bullets are more common in civilian gunshot wound (GSW) events. These bullets are able to tumble through the gastrointestinal tract and cause perforation of the intestinal lumen which is small enough to be easily missed. Bullets retained in the abdominal cavity should not be dismissed as fixed and should be carefully monitored to ensure that they do not embolize within the bowel and cause occult lesions during their migration. We present a unique case wherein a bullet caused a minute perforation in the small bowel, before migrating to the distal colon, which resulted in late presentation of sepsis secondary to peritonitis. PMID:24829839

In Vitro Magnetic Resonance Imaging Evaluation of Fragmented, Open-Coil, Percutaneous Peripheral Nerve Stimulation Leads.

PubMed

Shellock, Frank G; Zare, Armaan; Ilfeld, Brian M; Chae, John; Strother, Robert B

2018-04-01

Percutaneous peripheral nerve stimulation (PNS) is an FDA-cleared pain treatment. Occasionally, fragments of the lead (MicroLead, SPR Therapeutics, LLC, Cleveland, OH, USA) may be retained following lead removal. Since the lead is metallic, there are associated magnetic resonance imaging (MRI) risks. Therefore, the objective of this investigation was to evaluate MRI-related issues (i.e., magnetic field interactions, heating, and artifacts) for various lead fragments. Testing was conducted using standardized techniques on lead fragments of different lengths (i.e., 50, 75, and 100% of maximum possible fragment length of 12.7 cm) to determine MRI-related problems. Magnetic field interactions (i.e., translational attraction and torque) and artifacts were tested for the longest lead fragment at 3 Tesla. MRI-related heating was evaluated at 1.5 Tesla/64 MHz and 3 Tesla/128 MHz with each lead fragment placed in a gelled-saline filled phantom. Temperatures were recorded on the lead fragments while using relatively high RF power levels. Artifacts were evaluated using T1-weighted, spin echo, and gradient echo (GRE) pulse sequences. The longest lead fragment produced only minor magnetic field interactions. For the lead fragments evaluated, physiologically inconsequential MRI-related heating occurred at 1.5 Tesla/64 MHz while under certain 3 Tesla/128 MHz conditions, excessive temperature elevations may occur. Artifacts extended approximately 7 mm from the lead fragment on the GRE pulse sequence, suggesting that anatomy located at a position greater than this distance may be visualized on MRI. MRI may be performed safely in patients with retained lead fragments at 1.5 Tesla using the specific conditions of this study (i.e., MR Conditional). Due to possible excessive temperature rises at 3 Tesla, performing MRI at that field strength is currently inadvisable. © 2017 International Neuromodulation Society.

Fragment-Based Phenotypic Lead Discovery: Cell-Based Assay to Target Leishmaniasis.

PubMed

Ayotte, Yann; Bilodeau, François; Descoteaux, Albert; LaPlante, Steven R

2018-05-02

A rapid and practical approach for the discovery of new chemical matter for targeting pathogens and diseases is described. Fragment-based phenotypic lead discovery (FPLD) combines aspects of traditional fragment-based lead discovery (FBLD), which involves the screening of small-molecule fragment libraries to target specific proteins, with phenotypic lead discovery (PLD), which typically involves the screening of drug-like compounds in cell-based assays. To enable FPLD, a diverse library of fragments was first designed, assembled, and curated. This library of soluble, low-molecular-weight compounds was then pooled to expedite screening. Axenic cultures of Leishmania promastigotes were screened, and single hits were then tested for leishmanicidal activity against intracellular amastigote forms in infected murine bone-marrow-derived macrophages without evidence of toxicity toward mammalian cells. These studies demonstrate that FPLD can be a rapid and effective means to discover hits that can serve as leads for further medicinal chemistry purposes or as tool compounds for identifying known or novel targets. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The identification of lead ammunition as a source of lead exposure in First Nations: the use of lead isotope ratios.

PubMed

Tsuji, Leonard J S; Wainman, Bruce C; Martin, Ian D; Sutherland, Celine; Weber, Jean-Philippe; Dumas, Pierre; Nieboer, Evert

2008-04-15

The use of lead shotshell to hunt water birds has been associated with lead-contamination in game meat. However, evidence illustrating that lead shotshell is a source of lead exposure in subsistence hunting groups cannot be deemed definitive. This study seeks to determine whether lead shotshell constitutes a source of lead exposure using lead isotope ratios. We examined stable lead isotope ratios for lichens, lead shotshell and bullets, and blood from residents of Fort Albany and Kashechewan First Nations, and the City of Hamilton, Ontario, Canada. Data were analyzed using ANOVA and regression analyses. ANOVA of isotope ratios for blood revealed significant differences with respect to location, but not sex. Hamilton differed from both Kashechewan and Fort Albany; however, the First Nations did not differ from each other. ANOVA of the isotope ratios for lead ammunition and lichens revealed no significant differences between lichen groups (north and south) and for the lead ammunition sources (pellets and bullets). A plot of (206)Pb/(204)Pb and (206)Pb/(207)Pb values illustrated that lichens and lead ammunition were distinct groupings and only the 95% confidence ellipse of the First Nations group overlapped that of lead ammunition. In addition, partial correlations between blood-lead levels (adjusted for age) and isotope ratios revealed significant (p<0.05) positive correlations for (206)Pb/(204)Pb and (206)Pb/(207)Pb, and a significant negative correlation for (208)Pb/(206)Pb, as predicted if leaded ammunition were the source of lead exposure. In conclusion, lead ammunition was identified as a source of lead exposure for First Nations people; however, the isotope ratios for lead shotshell pellets and bullets were indistinguishable. Thus, lead-contaminated meat from game harvested with lead bullets may also be contributing to the lead body burden.

Lead concentration in meat from lead-killed moose and predicted human exposure using Monte Carlo simulation.

PubMed

Lindboe, M; Henrichsen, E N; Høgåsen, H R; Bernhoft, A

2012-01-01

Lead-based hunting ammunitions are still common in most countries. On impact such ammunition releases fragments which are widely distributed within the carcass. In Norway, wild game is an important meat source for segments of the population and 95% of hunters use lead-based bullets. In this paper, we have investigated the lead content of ground meat from moose (Alces alces) intended for human consumption in Norway, and have predicted human exposure through this source. Fifty-two samples from different batches of ground meat from moose killed with lead-based bullets were randomly collected. The lead content was measured by atomic absorption spectroscopy. The lead intake from exposure to moose meat over time, depending on the frequency of intake and portion size, was predicted using Monte Carlo simulation. In 81% of the batches, lead levels were above the limit of quantification of 0.03 mg kg(-1), ranging up to 110 mg kg(-1). The mean lead concentration was 5.6 mg kg(-1), i.e. 56 times the European Commission limit for lead in meat. For consumers eating a moderate meat serving (2 g kg(-1) bw), a single serving would give a lead intake of 11 µg kg(-1) bw on average, with maximum of 220 µg kg(-1) bw. Using Monte Carlo simulation, the median (and 97.5th percentile) predicted weekly intake of lead from moose meat was 12 µg kg(-1) bw (27 µg kg(-1) bw) for one serving per week and 25 µg kg(-1) bw (45 µg kg(-1) bw) for two servings per week. The results indicate that the intake of meat from big game shot with lead-based bullets imposes a significant contribution to the total human lead exposure. The provisional tolerable weekly intake set by the World Health Organization (WHO) of 25 µg kg(-1) bw is likely to be exceeded in people eating moose meat on a regular basis. The European Food Safety Authority (EFSA) has recently concluded that adverse effects may be present at even lower exposure doses. Hence, even occasional consumption of big game meat with lead levels as

Photonic Switching Devices Using Light Bullets

NASA Technical Reports Server (NTRS)

Goorjian, Peter M. (Inventor)

1997-01-01

The present invention is directed toward a unique ultra-fast, all-optical switching device or switch made with readily available, relatively inexpensive, highly nonlinear photonic glasses. These photonic glasses have a sufficiently negative group velocity dispersion and high nonlinear index of refraction to support stable light bullets. The light bullets counterpropagate through, and interact within the waveguide to selectively change each others' directions of propagation into predetermined channels. In one embodiment, the switch utilizes a rectangularly planar slab waveguide, and further includes two central channels and a plurality of lateral channels for guiding the light bullets into and out of the waveguide. One advantage presented by the present all-optical switching device lies in its practical use of light bullets, thus preventing the degeneration of the pulses due to dispersion and diffraction at the front and back of the pulses. Another feature of the switching device is the relative insensitivity of the collision process to the time difference in which the counter-propagating pulses enter the waveguide. since. contrary to conventional co-propagating spatial solitons, the relative phase of the colliding pulses does not affect the interaction of these pulses. Yet another feature of the present all-optical switching device is the selection of the light pulse parameters which enables the generation of light bullets in highly nonlinear glasses.

Possible influences on bullet trajectory deflection in ballistic gelatine.

PubMed

Riva, Fabiano; Kerkhoff, Wim; Bolck, Annabel; Mattijssen, Erwin J A T

2017-02-01

The influence of the distance to the top and bottom of a gelatine block and to bullet tracks from previously fired shots on a bullet's trajectory, when passing through ballistic gelatine, was studied. No significant difference in deflection was found when trajectories of 9mm Luger bullets, fired at a 3.5cm distance to the top and bottom of a gelatine block and to bullet tracks from previously fired shots, were compared to trajectories of bullets fired 7cm or more away from any of the aforementioned aspects. A surprisingly consistent 6.5° absolute deflection angle was found when these bullets passed through 22.5 to 23.5cm of ballistic gelatine. The projection angle, determined by the direction of the deflection, appeared to be random. The consistent absolute angle, in combination with the random projection angle, resulted in a cone-like deflection pattern. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Ballistic Reconstruction of a Migrating Bullet in the Parapharyngeal Space

PubMed Central

Bächinger, David; Bolliger, Stephan; Huber, Gerhard F.; Laske, Roman D.

2015-01-01

A 21-year-old male suffering from severe throat pain after being hit by a bullet in Syria claimed that he was shot through his eye and that the bullet subsequently descended behind his throat. Even though the first medical report stated that this course is implausible, meticulous workup provided evidence that the bullet might have entered the parapharyngeal space in a more cranial position than the one it was found eight months later. Our case highlights that bullets are able to move within the body, rendering ballistic reconstruction difficult. However, after removal of the bullet the patient's symptoms completely resolved. PMID:26770857

Plasma bullet current measurements in a free-stream helium capillary jet

NASA Astrophysics Data System (ADS)

Oh, Jun-Seok; Walsh, James L.; Bradley, James W.

2012-06-01

A commercial current monitor has been used to measure the current associated with plasma bullets created in both the positive and negative half cycles of the sinusoidal driving voltage sustaining a plasma jet. The maximum values of the positive bullet current are typically ˜750 µA and persist for 10 µs, while the peaks in the negative current of several hundred μA are broad, persisting for about 40 µs. From the time delay of the current peaks with increasing distance from the jet nozzle, an average bullet propagation speed has been measured; the positive and negative bullets travel at 17.5 km s-1 and 3.9 km s-1 respectively. The net space charge associated with the bullet(s) has also been calculated; the positive and negative bullets contain a similar net charge of the order of 10-9 C measured at all monitor positions, with estimated charged particle densities nb of ˜1010-1011 cm-3 in the bullet.

Ballistics Modeling for Non-Axisymmetric Hypervelocity Smart Bullets

DTIC Science & Technology

2014-06-03

can in principle come from experiments or computational fluid dynamics ( CFD ) calculations. CFD calculations are carried out for a standard bullet...come from experiments or com- putational fluid dynamics ( CFD ) calculations. CFD calculations are carried out for a standard bullet (0.308” 168 grain...11 2. Spin and Pitch Damping 11 3. Magnus Moment 12 IV. CFD Simulations and Ballistic Trajectories 12 A. CFD Modeling of a Standard Bullet 12 B

Novel approach of fragment-based lead discovery applied to renin inhibitors.

PubMed

Tawada, Michiko; Suzuki, Shinkichi; Imaeda, Yasuhiro; Oki, Hideyuki; Snell, Gyorgy; Behnke, Craig A; Kondo, Mitsuyo; Tarui, Naoki; Tanaka, Toshimasa; Kuroita, Takanobu; Tomimoto, Masaki

2016-11-15

A novel approach was conducted for fragment-based lead discovery and applied to renin inhibitors. The biochemical screening of a fragment library against renin provided the hit fragment which showed a characteristic interaction pattern with the target protein. The hit fragment bound only to the S1, S3, and S3 SP (S3 subpocket) sites without any interactions with the catalytic aspartate residues (Asp32 and Asp215 (pepsin numbering)). Prior to making chemical modifications to the hit fragment, we first identified its essential binding sites by utilizing the hit fragment's substructures. Second, we created a new and smaller scaffold, which better occupied the identified essential S3 and S3 SP sites, by utilizing library synthesis with high-throughput chemistry. We then revisited the S1 site and efficiently explored a good building block attaching to the scaffold with library synthesis. In the library syntheses, the binding modes of each pivotal compound were determined and confirmed by X-ray crystallography and the library was strategically designed by structure-based computational approach not only to obtain a more active compound but also to obtain informative Structure Activity Relationship (SAR). As a result, we obtained a lead compound offering synthetic accessibility as well as the improved in vitro ADMET profiles. The fragments and compounds possessing a characteristic interaction pattern provided new structural insights into renin's active site and the potential to create a new generation of renin inhibitors. In addition, we demonstrated our FBDD strategy integrating highly sensitive biochemical assay, X-ray crystallography, and high-throughput synthesis and in silico library design aimed at fragment morphing at the initial stage was effective to elucidate a pocket profile and a promising lead compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rifle bullet penetration into ballistic gelatin.

PubMed

Wen, Yaoke; Xu, Cheng; Jin, Yongxi; Batra, R C

2017-03-01

The penetration of a rifle bullet into a block of ballistic gelatin is experimentally and computationally studied for enhancing our understanding of the damage caused to human soft tissues. The gelatin is modeled as an isotropic and homogeneous elastic-plastic linearly strain-hardening material that obeys a polynomial equation of state. Effects of numerical uncertainties on penetration characteristics are found by repeating simulations with minute variations in the impact speed and the angle of attack. The temporary cavity formed in the gelatin and seen in pictures taken by two high speed cameras is found to compare well with the computed one. The computed time histories of the hydrostatic pressure at points situated 60 mm above the line of impact are found to have "two peaks", one due to the bullet impact and the other due to the bullet tumbling. Contours of the von Mises stress and of the effective plastic strain in the gelatin block imply that a very small region adjacent to the cavity surface is plastically deformed. The angle of attack is found to noticeably affect the penetration depth at the instant of the bullet tumbling through 90°. Copyright © 2016 Elsevier Ltd. All rights reserved.

A prospective observational study assessing the feasibility of measuring blood lead levels in New Zealand hunters eating meat harvested with lead projectiles.

PubMed

Buenz, Eric J; Parry, Gareth J; Bauer, Brent A; Matheny, Lauren M; Breukel, Klaasz

2017-03-01

There is no safe level of lead exposure. Correlations suggest that hunters harvesting wild game with lead bullets may be at risk of lead exposure through eating minute lead particles from shrapnel in their wild game. This feasibility study will determine if it is possible to conduct an interventional controlled, blinded study to evaluate if there is a causal relationship between meat harvested with lead bullets and elevated blood lead levels in those who consume the meat. This is an observational case crossover study and the primary outcome is blood lead levels. Individuals will have blood lead levels measured 2-4 days after eating one serving of meat harvested with lead bullets. At three potential washout periods these same individuals will have a subsequent blood lead level analysis. This observational study will provide the data necessary to determine the washout period and sample size for a prospective interventional study to evaluate if meat harvested with lead bullets raises blood-lead levels in those who consume the meat. This study has been approved by the Health and Disabilities Ethics Committees of New Zealand. NCT02775890.

Photonic Switching Devices Using Light Bullets

NASA Technical Reports Server (NTRS)

Goorjian, Peter M. (Inventor)

1999-01-01

A unique ultra-fast, all-optical switching device or switch is made with readily available, relatively inexpensive, highly nonlinear optical materials. which includes highly nonlinear optical glasses, semiconductor crystals and/or multiple quantum well semiconductor materials. At the specified wavelengths. these optical materials have a sufficiently negative group velocity dispersion and high nonlinear index of refraction to support stable light bullets. The light bullets counter-propagate through, and interact within the waveguide to selectively change each others' directions of propagation into predetermined channels. In one embodiment, the switch utilizes a rectangularly planar slab waveguide. and further includes two central channels and a plurality of lateral channels for guiding the light bullets into and out of the waveguide. An advantage of the present all-optical switching device lies in its practical use of light bullets, thus preventing the degeneration of the pulses due to dispersion and diffraction at the front and back of the pulses. Another advantage of the switching device is the relative insensitivity of the collision process to the time difference in which the counter-propagating pulses enter the waveguide. since. contrary to conventional co-propagating spatial solitons, the relative phase of the colliding pulses does not affect the interaction of these pulses. Yet another feature of the present all-optical switching device is the selection of the light pulse parameters which enables the generation of light bullets in nonlinear optical materials. including highly nonlinear optical glasses and semiconductor materials such as semiconductor crystals and/or multiple quantum well semiconductor materials.

The Math Emporium: Higher Education's Silver Bullet

ERIC Educational Resources Information Center

Twigg, Carol A.

2011-01-01

Throughout the 1990's, many people saw information technology as a silver bullet that could solve many of higher education's problems, among them the need to improve learning outcomes and control the ever-upward trajectory of higher education costs. The term "silver bullet" connotes a direct and effortless solution to a problem.…

Firearms, bullets, and wound ballistics: an imaging primer.

PubMed

Hanna, Tarek N; Shuaib, Waqas; Han, Tatiana; Mehta, Ajeet; Khosa, Faisal

2015-07-01

Based on its intrinsic mass and velocity, a bullet has an upper limit of wounding potential. Actual wound severity is a function of the bullet construction and trajectory, as well as the properties of the tissues traversed. Interpreting physicians must evaluate the bullet trajectory and describe patterns of injury resulting from the effect of energy transfer from the projectile into living tissue. A basic understanding of firearms, projectiles, and wound ballistics can help the interpreting physicians in conceptualizing these injuries and interpreting these cases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hunting of roe deer and wild boar in Germany: Is non-lead ammunition suitable for hunting?

PubMed

Martin, Annett; Gremse, Carl; Selhorst, Thomas; Bandick, Niels; Müller-Graf, Christine; Greiner, Matthias; Lahrssen-Wiederholt, Monika

2017-01-01

Non-lead hunting ammunition is an alternative to bullets that contain lead. The use of lead ammunition can result in severe contamination of game meat, thus posing a health risk to consumers. With any kind of ammunition for hunting, the terminal effectiveness of bullets is an animal welfare issue. Doubts about the effectiveness of non-lead bullets for a humane kill of game animals in hunting have been discussed. The length of the escape distance after the shot has been used previously as an indicator for bullet performance. The object of this study was to determine how the bullet material (lead or non-lead) influences the observed escape distances. 1,234 records of the shooting of roe deer (Capreolus capreolus) and 825 records of the shooting of wild boar (Sus scrofa) were evaluated. As the bullet material cannot be regarded as the sole cause of variability of escape distances, interactions of other potential influencing variables like shot placement, shooting distance, were analyzed using conditional regression trees and two-part hurdle models. The length of the escape distance is not influenced by the use of lead or non-lead ammunition with either roe deer or wild boar. With roe deer, the length of the escape distance is influenced significantly by the shot placement and the type of hunting. Increasing shooting distances increased the length of the escape distance. With wild boar, shot placement and the age of the animals were found to be a significant influencing factor on the length of the escape distance. The length of the escape distance can be used as an indicator for adequate bullet effectiveness for humane killings of game animals in hunting.Non-lead bullets already exist which have an equally reliable killing effect as lead bullets.

Hunting of roe deer and wild boar in Germany: Is non-lead ammunition suitable for hunting?

PubMed Central

Gremse, Carl; Selhorst, Thomas; Bandick, Niels; Müller-Graf, Christine; Greiner, Matthias; Lahrssen-Wiederholt, Monika

2017-01-01

Background Non-lead hunting ammunition is an alternative to bullets that contain lead. The use of lead ammunition can result in severe contamination of game meat, thus posing a health risk to consumers. With any kind of ammunition for hunting, the terminal effectiveness of bullets is an animal welfare issue. Doubts about the effectiveness of non-lead bullets for a humane kill of game animals in hunting have been discussed. The length of the escape distance after the shot has been used previously as an indicator for bullet performance. Objective The object of this study was to determine how the bullet material (lead or non-lead) influences the observed escape distances. Methods 1,234 records of the shooting of roe deer (Capreolus capreolus) and 825 records of the shooting of wild boar (Sus scrofa) were evaluated. As the bullet material cannot be regarded as the sole cause of variability of escape distances, interactions of other potential influencing variables like shot placement, shooting distance, were analyzed using conditional regression trees and two-part hurdle models. Results The length of the escape distance is not influenced by the use of lead or non-lead ammunition with either roe deer or wild boar. With roe deer, the length of the escape distance is influenced significantly by the shot placement and the type of hunting. Increasing shooting distances increased the length of the escape distance. With wild boar, shot placement and the age of the animals were found to be a significant influencing factor on the length of the escape distance. Conclusions The length of the escape distance can be used as an indicator for adequate bullet effectiveness for humane killings of game animals in hunting.Non-lead bullets already exist which have an equally reliable killing effect as lead bullets. PMID:28926620

Rubber bullet injury: case report with autopsy observation and literature review.

PubMed

Kobayashi, Masahiko; Mellen, Paul F

2009-09-01

Rubber bullets are one of the less-lethal (nonlethal) weapons, which are increasingly used to incapacitate dangerous individuals, avoiding use of firearms. An autopsy examination of a man who was shot with improved rubber bullets revealed that the bullet caused pulmonary contusion. The bullet was 30 g in weight and consisted of a sponge foam nose with 40-mm diameter and a plastic body. He was not incapacitated and died of suicidal gunshot wound. The case raised a question as to how severe an injury is necessary to deter a person without causing death. A variety of rubber bullets have been used in the world, and they have occasionally produced severe or lethal injuries. A review of the literature demonstrated that the feature of injuries appeared to be related to the type of missile. It becomes more important for a forensic pathologist to be familiar with rubber bullets and injuries caused by them as the use of less-lethal weapon increases.

Complete endoscopic management of a retained bullet in the bladder.

PubMed

Friedman, Ariella A; Trinh, Quoc-Dien; Kaul, Sanjeev; Bhandari, Akshay

2013-01-01

A 25-year-old male gunshot victim presented at our institution with gross hematuria following Foley catheter insertion. Computed tomography and cystogram did not show a bladder perforation, but were notable for a left ischial fracture and the presence of a bullet within the bladder. After failed attempts at retrieving the bullet with a resectoscope and loop, as well as a cystoscope and stone crusher, a 26 French nephroscope was inserted transurethrally, and the bullet was successfully engaged and removed using a Perc NCircle (Cook Medical, Bloomington, IN) grasper. The extra-peritoneal injury was managed conservatively with catheter drainage. To our knowledge, this represents the first case of successful transurethral management of a retained intravesical bullet. Such an approach may benefit patients with retained intravesical bullets or other challenging intravesical foreign bodies and may be helpful in select circumstances to spare patients from more extensive surgeries.

Optical bullets and "rockets" in nonlinear dissipative systems and their transformations and interactions.

PubMed

Soto-Crespo, J M; Grelu, Philippe; Akhmediev, Nail

2006-05-01

We demonstrate the existence of stable optical light bullets in nonlinear dissipative media for both cases of normal and anomalous chromatic dispersion. The prediction is based on direct numerical simulations of the (3+1)-dimensional complex cubic-quintic Ginzburg-Landau equation. We do not impose conditions of spherical or cylindrical symmetry. Regions of existence of stable bullets are determined in the parameter space. Beyond the domain of parameters where stable bullets are found, unstable bullets can be transformed into "rockets" i.e. bullets elongated in the temporal domain. A few examples of the interaction between two optical bullets are considered using spatial and temporal interaction planes.

Lead isotope ratios for bullets, forensic evaluation in a Bayesian paradigm.

PubMed

Sjåstad, Knut-Endre; Lucy, David; Andersen, Tom

2016-01-01

Forensic science is a discipline concerned with collection, examination and evaluation of physical evidence related to criminal cases. The results from the activities of the forensic scientist may ultimately be presented to the court in such a way that the triers of fact understand the implications of the data. Forensic science has been, and still is, driven by development of new technology, and in the last two decades evaluation of evidence based on logical reasoning and Bayesian statistic has reached some level of general acceptance within the forensic community. Tracing of lead fragments of unknown origin to a given source of ammunition is a task that might be of interest for the Court. Use of data from lead isotope ratios analysis interpreted within a Bayesian framework has shown to be suitable method to guide the Court to draw their conclusion for such task. In this work we have used isotopic composition of lead from small arms projectiles (cal. .22) and developed an approach based on Bayesian statistics and likelihood ratio calculation. The likelihood ratio is a single quantity that provides a measure of the value of evidence that can be used in the deliberation of the court. Copyright © 2015 Elsevier B.V. All rights reserved.

The experimental and numerical investigation of pistol bullet penetrating soft tissue simulant.

PubMed

Wang, Yongjuan; Shi, Xiaoning; Chen, Aijun; Xu, Cheng

2015-04-01

Gelatin, a representative simulant for soft tissue of the human body, was used to study the effects of 9 mm pistol bullet's penetration. The behavior of a bullet penetrating gelatin was quantified by the temporary cavity sizes in ballistic gelatin and the pressure values of bullet's impact. A numerical simulation model of a bullet penetrating the soft tissue simulant gelatin was built using the finite element method (FEM). The model was validated by the comparison between the numerical results and the experimental results. During a bullet penetrating ballistic gelatin, four stages were clearly observed in both the experiment and the numerical simulation: a smooth attenuation stage, a rolling stage, a full penetration stage, and a stage of expansion and contraction. The cavity evolution, equivalent stress field and the strain field in gelatin were analyzed by numerical simulation. Moreover, the effects of the bullet's impact velocities and angles of incidence on the temporary cavity in gelatin, its velocity attenuation, and its rolling angle were investigated, as well as the bullet's resistance and energy variation. The physical process and the interactive mechanism during a pistol bullet penetrating gelatin were comprehensively revealed. This may be significant for research in wound ballistics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Three-dimensional light bullets in a Bragg medium with carbon nanotubes

NASA Astrophysics Data System (ADS)

Zhukov, Alexander V.; Bouffanais, Roland; Belonenko, Mikhail B.; Dvuzhilov, Ilya S.; Nevzorova, Yulia V.

2017-07-01

We present a theoretical study of the propagation of three-dimensional extremely short electromagnetic pulses (a.k.a. light bullets) through a Bragg medium containing an immersed array of carbon nanotubes. We demonstrate the possible stable propagation of such light bullets. In particular, our results suggest these light bullets can carry information about the Bragg medium itself.

Lead Poisoning in Wild Birds

USGS Publications Warehouse

Lahner, Lesanna L.; Franson, J. Christian

2009-01-01

Lead in its various forms has been used for thousands of years, originally in cooking utensils and glazes and more recently in many industrial and commercial applications. However, lead is a potent, potentially deadly toxin that damages many organs in the body and can affect all animals, including humans. By the mid 1990s, lead had been removed from many products in the United States, such as paint and fuel, but it is still commonly used in ammunition for hunting upland game birds, small mammals, and large game animals, as well as in fishing tackle. Wild birds, such as mourning doves, bald eagles, California condors, and loons, can die from the ingestion of one lead shot, bullet fragment, or sinker. According to a recent study on loon mortality, nearly half of adult loons found sick or dead during the breeding season in New England were diagnosed with confirmed or suspected lead poisoning from ingestion of lead fishing weights. Recent regulations in some states have restricted the use of lead ammunition on certain upland game hunting areas, as well as lead fishing tackle in areas frequented by common loons and trumpeter swans. A variety of alternatives to lead are available for use in hunting, shooting sports, and fishing activities.

Infection of Retained Defibrillator Lead Fragment after Heart Transplant

PubMed Central

Durante-Mangoni, Emanuele; Vitrone, Martina; Mattucci, Irene; Caprioli, Vincenzo; Maiello, Ciro

2017-01-01

A 59-year old heart transplant recipient was admitted due to continuous pain in her left axilla. A purulent collection was found at the site of prior defibrillator placement, where a remnant proximal segment of an electric lead was found. Two years before, the patient had had pocket infection treated with revision, but without device extraction. The remnant lead was eventually removed transvenously without complications. This is the first description of infection complicating retention of lead fragments after heart transplant. The role of biofilm and net immune state on the persistence and late recurrence of infection is discussed. PMID:28458812

Fragment-based lead generation: identification of seed fragments by a highly efficient fragment screening technology

NASA Astrophysics Data System (ADS)

Neumann, Lars; Ritscher, Allegra; Müller, Gerhard; Hafenbradl, Doris

2009-08-01

For the detection of the precise and unambiguous binding of fragments to a specific binding site on the target protein, we have developed a novel reporter displacement binding assay technology. The application of this technology for the fragment screening as well as the fragment evolution process with a specific modelling based design strategy is demonstrated for inhibitors of the protein kinase p38alpha. In a fragment screening approach seed fragments were identified which were then used to build compounds from the deep-pocket towards the hinge binding area of the protein kinase p38alpha based on a modelling approach. BIRB796 was used as a blueprint for the alignment of the fragments. The fragment evolution of these deep-pocket binding fragments towards the fully optimized inhibitor BIRB796 included the modulation of the residence time as well as the affinity. The goal of our study was to evaluate the robustness and efficiency of our novel fragment screening technology at high fragment concentrations, compare the screening data with biochemical activity data and to demonstrate the evolution of the hit fragments with fast kinetics, into slow kinetic inhibitors in an in silico approach.

Bullet Impact Safety Study of PBX-9502

NASA Astrophysics Data System (ADS)

Ferranti, Louis

2013-06-01

A new small arms capability for performing bullet impact testing into energetic materials has recently been activated at Lawrence Livermore National Laboratory located in the High Explosives Applications Facility (HEAF). The initial capability includes 0.223, 0.30, and 0.50 testing calibers with the flexibility to add other barrels in the near future. An initial test series has been performed using the 0.50 caliber barrel shooting bullets into targets using the TATB based explosive PBX-9502 and shows an expected non-violent reaction. Future experiments to evaluate the safety of new explosive formulations to bullet impact are planned. A highlight of the new capability along with discussion of the initial experiments to date will be presented including future areas of research. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Use of a Minimally Invasive Retractor System for Retrieval of Intracranial Fragments in Wartime Trauma.

PubMed

Rymarczuk, George N; Davidson, Laurence; Severson, Meryl A; Armonda, Rocco A

2015-10-01

Wartime penetrating brain injury can result in deep-seated parenchymal and intraventicular shrapnel, bullets, and bone. Large fragments pose a risk of secondary injury from migration, infection, and metal toxicity. It has been recommended that aggressive removal of fragments be avoided. The goal of this study is to report our technique of minimally invasive removal of select deep-seated fragments using a tubular retractor system. A retrospective review of our database of service members presenting with penetrating traumatic brain injuries incurred during Operations Iraqi Freedom and Enduring Freedom and treated at the Walter Reed Army Medical Center and the National Naval Medical Center was performed. Six individuals were identified in which the Vycor ViewSite retractor system (Vycor Medical, Boca Raton, Florida, USA) was used to remove a ventricular or deep intraparenchymal fragment. All patients were male and ranged in age from 21 to 29 years. Fragment location included the foramen of Monro; the atrium of the right lateral ventricle; parasagittally within the right occipital lobe; the occipital horn of the right lateral ventricle; the deep white matter of the dominant temporal lobe; and within the posterior right temporal lobe deep to the junction of the transverse and sigmoid dural venous sinuses. Fragments included in-driven bone, shrapnel from improvised explosive devices, and bullets. In all cases the fragment was successfully removed. No patient had worsening of their neurologic condition following surgery. Deep parenchymal and intraventricular fragments can be safely removed using a tubular retractor system. Published by Elsevier Inc.

Impact of the California lead ammunition ban on reducing lead exposure in golden eagles and turkey vultures.

PubMed

Kelly, Terra R; Bloom, Peter H; Torres, Steve G; Hernandez, Yvette Z; Poppenga, Robert H; Boyce, Walter M; Johnson, Christine K

2011-04-06

Predatory and scavenging birds may be exposed to high levels of lead when they ingest shot or bullet fragments embedded in the tissues of animals injured or killed with lead ammunition. Lead poisoning was a contributing factor in the decline of the endangered California condor population in the 1980s, and remains one of the primary factors threatening species recovery. In response to this threat, a ban on the use of lead ammunition for most hunting activities in the range of the condor in California was implemented in 2008. Monitoring of lead exposure in predatory and scavenging birds is essential for assessing the effectiveness of the lead ammunition ban in reducing lead exposure in these species. In this study, we assessed the effectiveness of the regulation in decreasing blood lead concentration in two avian sentinels, golden eagles and turkey vultures, within the condor range in California. We compared blood lead concentration in golden eagles and turkey vultures prior to the lead ammunition ban and one year following implementation of the ban. Lead exposure in both golden eagles and turkey vultures declined significantly post-ban. Our findings provide evidence that hunter compliance with lead ammunition regulations was sufficient to reduce lead exposure in predatory and scavenging birds at our study sites.

Impact of the California Lead Ammunition Ban on Reducing Lead Exposure in Golden Eagles and Turkey Vultures

PubMed Central

Kelly, Terra R.; Bloom, Peter H.; Torres, Steve G.; Hernandez, Yvette Z.; Poppenga, Robert H.; Boyce, Walter M.; Johnson, Christine K.

2011-01-01

Predatory and scavenging birds may be exposed to high levels of lead when they ingest shot or bullet fragments embedded in the tissues of animals injured or killed with lead ammunition. Lead poisoning was a contributing factor in the decline of the endangered California condor population in the 1980s, and remains one of the primary factors threatening species recovery. In response to this threat, a ban on the use of lead ammunition for most hunting activities in the range of the condor in California was implemented in 2008. Monitoring of lead exposure in predatory and scavenging birds is essential for assessing the effectiveness of the lead ammunition ban in reducing lead exposure in these species. In this study, we assessed the effectiveness of the regulation in decreasing blood lead concentration in two avian sentinels, golden eagles and turkey vultures, within the condor range in California. We compared blood lead concentration in golden eagles and turkey vultures prior to the lead ammunition ban and one year following implementation of the ban. Lead exposure in both golden eagles and turkey vultures declined significantly post-ban. Our findings provide evidence that hunter compliance with lead ammunition regulations was sufficient to reduce lead exposure in predatory and scavenging birds at our study sites. PMID:21494329

Ames Lab 101: osgBullet

ScienceCinema

McCorkle, Doug

2017-12-27

Ames Laboratory scientist Doug McCorkle explains osgBullet, a 3-D virtual simulation software, and how it helps engineers design complex products and systems in a realistic, real-time virtual environment.

Current perspectives in fragment-based lead discovery (FBLD)

PubMed Central

Lamoree, Bas; Hubbard, Roderick E.

2017-01-01

It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most ‘conventional’ targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protein–protein interactions. The main application is to identify tractable chemical startpoints that non-covalently modulate the activity of a biological molecule. In this essay, we overview current practice in the methods and discuss how they have had an impact in lead discovery – generating a large number of fragment-derived compounds that are in clinical trials and two medicines treating patients. In addition, we discuss some of the more recent applications of the methods in chemical biology – providing chemical tools to investigate biological molecules, mechanisms and systems. PMID:29118093

Lead intoxication in dogs: risk assessment of feeding dogs trimmings of lead-shot game.

PubMed

Høgåsen, Helga R; Ørnsrud, Robin; Knutsen, Helle K; Bernhoft, Aksel

2016-07-25

Expanding lead-based bullets, commonly used for hunting of big game, produce a scattering of lead particles in the carcass around the wound channel. Trimmings around this channel, which are sometimes fed to dogs, may contain lead particles. The aim of this study was to assess potential health effects of feeding dogs such trimmings. Lead ingestion most commonly causes gastrointestinal and neurological clinical signs, although renal, skeletal, haematological, cardiovascular and biochemical effects have also been reported. Experimental data indicate that a daily dose of around 1 mg lead as lead acetate/kg body weight for ten days may be considered as a Lowest Observed Effect Level in dogs. Acute toxicity documentation from the Centers for Disease Control and Prevention indicates 300 mg/kg body weight as the lowest dose of lead acetate causing death in dogs after oral ingestion. Our assessment suggests that dogs fed trimmings of lead-shot game may be affected by the amounts of lead present, and that even deadly exposure could occasionally occur. The intestinal absorption of lead from bullets was assumed to be 10-80 % of that of lead acetate, reflecting both the variability in particle size and uncertainty about the bioavailability of metallic lead in dogs. Despite data gaps, this study indicates that feeding dogs trimmings of lead-shot game may represent a risk of lead intoxication. More research is needed to assess the exact consequences, if lead-based bullets are still to be used. Meanwhile, we recommend that trimmings close to the wound channel should be made inaccessible to dogs, as well as to other domestic or wild animals.

Failure mechanism of resistance-spot-welded specimens impacted on base material by bullets

NASA Astrophysics Data System (ADS)

Fan, Chunlei; Ma, Bohan; Chen, Danian; Wang, Huanran; Ma, Dongfang

2018-01-01

The tests of bullet impact on the base material (BM) of a simple specimen with a single resistance-spot-welded (RSW) nugget of TRIP800 steel are performed to investigate the response of the RSW specimen to the ballistic debris impact on the RSW specimen. A one-stage gas gun is used to fire the bullets while a laser velocity interferometer system for any reflector (VISAR) is used to measure the velocity histories of the free surfaces of the RSW specimen. The recovered RSW specimens are examined with the three-dimensional super depth digital microscope (SDDM) and the scanning electro microscope (SEM). For the tests of small multiple-bullet impact, it is revealed that the wave train of the VISAR measured results and the detachment of the base material interfaces in the recovered RSW specimens are directly related to the reflection and refraction of the curved stress waves incoming to the interfaces and the free surfaces in the RSW specimens. The detachment of BM interfaces can lead to the impact failure of the RSW joints for the larger multiple-bullet impact at higher velocity, the mechanism of which is different from the case for normal incidence (spalling). For the tests of single large bullet impact, it is brought to light experimentally that the plastic strain concentration at the "notch tip" spurs either the crack near the RSW joint or the split of the nugget. The numerical simulation shows up the process of splitting the nugget: a crack initiates at the "notch tip", propagates across the nugget interface and splits the nugget into two parts. It is indicated that the interaction between the stress waves and many interfaces/free surfaces in the RSW specimen under ballistic impact causes variable local stress triaxialities and stress Lode angles, which affects the deformation and fracture mechanism of the RSW specimen including stretching and shearing failure. It is shown that the impact failure of the RSW joints is a mixture of brittle fracture and ductile

75 FR 58377 - Lead in Ammunition and Fishing Sinkers; Disposition of TSCA Section 21 Petition

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2010-0681; FRL-8847-5] Lead in Ammunition and Fishing..., and distribution in commerce of (1) lead bullets and shot; and (2) lead fishing sinkers. On August 27, 2010, EPA denied the first request due to a lack of authority to regulate lead in bullets and shot...

Enterococcus faecalis causing delayed spondylodiscitis in a case with retained intraspinal bullet.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Reddy, Srikanth; Rajasekaran, Shanmuganathan

2016-12-01

Delayed presentations have been reported following gunshot wounds (GSW) with retained intraspinal bullets due to migration of projectile or lead intoxication. We report on the rare occurrence of delayed pyogenic spondylodiscitis and neurological dysfunction following injury from low velocity GSW to the spine with a retained projectile. A 55-year-old male presented 4 months following GSW to the abdomen which resulted in colonic injury and L5 fracture. The patient was treated initially with ileo-transverse anastomosis, antibiotics, without retrieval of the bullet. He developed low back pain, claudication 4 months following GSW and investigations suggested a pyogenic spondylodiscitis at L5-S1. The patient was treated with surgical debridement of infective focus and stabilisation with definitive fusion being performed after an interval of 14 days. The biopsy of the lesion confirmed findings of spondylodiscitis and the culture isolated Enterococcus faecalis species. The patient was treated with antibiotics as per sensitivity and made an uneventful recovery over 4 weeks. The follow-up radiographs showed satisfactory healing at final follow up of 24 months. GSW with colonic perforation have higher incidence of infective complications however majority to these occur in the early postoperative period. This case report demonstrates the possibility of late onset presentation due to spinal infection occurring following colonic perforation with retained intraspinal bullet.

Enterococcus faecalis causing delayed spondylodiscitis in a case with retained intraspinal bullet

PubMed Central

Aiyer, Siddharth N.; Kanna, Rishi; Reddy, Srikanth; Rajasekaran, Shanmuganathan

2016-01-01

Delayed presentations have been reported following gunshot wounds (GSW) with retained intraspinal bullets due to migration of projectile or lead intoxication. We report on the rare occurrence of delayed pyogenic spondylodiscitis and neurological dysfunction following injury from low velocity GSW to the spine with a retained projectile. A 55-year-old male presented 4 months following GSW to the abdomen which resulted in colonic injury and L5 fracture. The patient was treated initially with ileo-transverse anastomosis, antibiotics, without retrieval of the bullet. He developed low back pain, claudication 4 months following GSW and investigations suggested a pyogenic spondylodiscitis at L5–S1. The patient was treated with surgical debridement of infective focus and stabilisation with definitive fusion being performed after an interval of 14 days. The biopsy of the lesion confirmed findings of spondylodiscitis and the culture isolated Enterococcus faecalis species. The patient was treated with antibiotics as per sensitivity and made an uneventful recovery over 4 weeks. The follow-up radiographs showed satisfactory healing at final follow up of 24 months. GSW with colonic perforation have higher incidence of infective complications however majority to these occur in the early postoperative period. This case report demonstrates the possibility of late onset presentation due to spinal infection occurring following colonic perforation with retained intraspinal bullet. PMID:28097252

Quantitative/Statistical Approach to Bullet-to-Firearm Identification with Consecutively Manufactured Barrels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peter Striupaitis; R.E. Gaensslen

Efforts to use objective image comparison and bullet scanning technologies to distinguish bullets from consecutively manufactured handgun barrels from two manufacturers gave mixed results. The ability of a technology to reliably distinguish between matching and non-matching bullets, where the non-matching bullets were as close in pattern to the matching ones as is probably possible, would provide evidence that the distinctions could be made ''objectively'', and independently of human eyes. That evidence is identical or very close to what seems to be needed to satisfy Daubert standards. It is fair to say that the FTI IBIS image comparison technology correctly distinguishedmore » between all the Springfield barrel bullets, and between most but not all of the HiPoint barrel bullets. In the HiPoint cases that were not distinguished 100% of the time, they would he distinguished correctly at least 83% of the time. These results, although obviously limited to the materials used in the comparisons, provide strong evidence that barrel-to-bullet matching is objectively reliable. The results with SciClops were less compelling. The results do not mean that bullet-to-barrel matching is not objectively reliable--rather, they mean that this version of the particular technology could not quite distinguish between these extremely similar yet different bullets as well as the image comparison technology did. In a number of cases, the numerical results made the correct distinctions, although they were close to one another. It is hard to say from this data that this technology differs in its ability to make distinctions between the manufacturers, because the results are very similar with both. The human examiner results were as expected. We did not expect any misidentifications, and there were not any. It would have been preferable to have a higher return rate, and thus more comparisons in the overall sample. As noted, the ''consecutively manufactured barrel exercise'' has been done

EDITORIAL: Plasma jets and plasma bullets Plasma jets and plasma bullets

NASA Astrophysics Data System (ADS)

Kong, M. G.; Ganguly, B. N.; Hicks, R. F.

2012-06-01

-mentioned early studies has witnessed a considerable and exciting growth in terms of new phenomena observed, new physics and chemistry uncovered, new plasma jet sources conceived, and new applications developed. Examples include the observations of plasma bullets on a nanosecond scale [16], the similarity of plasma bullets to streamers [17], arrays of plasma jets as metamaterials [18], and a rapid increase of applications in biomedicine [19]. However the considerable growth in the research of plasma jets has not been adequately supported, so far, by a sound fundamental underpinning, partly resulting from a somewhat underdevelopment of effective diagnostics and modelling tools. Recognizing the critical importance of basic science for future growth of low-temperature plasma jet technology, this special issue on plasma jets and bullets aims to address some of the most important fundamental questions. Many of the special issue papers continue the established line of investigation to characterize the formation of plasma bullets, using typically ultrafast imaging, electrical detection including electric field and plasma conductivity measurement, and optical emission spectrometry [20]-[26]. These offer strong experimental evidence for the well-known hypothesis that a plasma jet is a form of streamer, and that the ionization wave plays a critical role in their formation. The interaction of two parallel plasma jets [27] and manipulation of plasma jet characteristics [28, 29] are also reported using a similar combination of experimental techniques. Some of the common characteristics of plasma jets are summarized in a review paper in this special issue [30]. A somewhat different line of investigation is employed in a detailed experimental characterization of deterministic chaos in atmospheric plasma jets [31], one of the few non-bullet modes of plasma jets. Although chaos in ionized gases have been observed in other types of discharge plasmas, their applications have not so far been linked

Fragment screening for drug leads by weak affinity chromatography (WAC-MS).

PubMed

Ohlson, Sten; Duong-Thi, Minh-Dao

2018-02-23

Fragment-based drug discovery is an important tool for design of small molecule hit-to-lead compounds against various biological targets. Several approved drugs have been derived from an initial fragment screen and many such candidates are in various stages of clinical trials. Finding fragment hits, that are suitable for optimisation by medicinal chemists, is still a challenge as the binding between the small fragment and its target is weak in the range of mM to µM of K d and irrelevant non-specific interactions are abundant in this area of transient interactions. Fortunately, there are methods that can study weak interactions quite efficiently of which NMR, surface plasmon resonance (SPR) and X-ray crystallography are the most prominent. Now, a new technology based on zonal affinity chromatography, weak affinity chromatography (WAC), has been introduced which has remedied many of the problems with other technologies. By combining WAC with mass spectrometry (WAC-MS), it is a powerful tool to identify binders quantitatively in terms of affinity and kinetics either from fragment libraries or from complex mixtures of biological extracts. As WAC-MS can be multiplexed by analysing mixtures of fragments (20-100 fragments) in one sample, this approach yields high throughput, where a whole library of e.g. >2000 fragments can be analysed quantitatively within a day. WAC-MS is easy to perform, where the robustness and quality of HPLC is fully utilized. This review will highlight the rationale behind the application of WAC-MS for fragment screening in drug discovery. Copyright © 2018 Elsevier Inc. All rights reserved.

A Bullet-Block Experiment That Explains the Chain Fountain

ERIC Educational Resources Information Center

Pantaleone, J.; Smith, R.

2018-01-01

It is common in science for two phenomena to appear to be very different, but in fact follow from the same basic principles. Here we consider such a case, the connection between the chain fountain and a bullet-block collision experiment. When an upward moving bullet strikes a wooden block resting on a horizontal table, the block will rise to a…

Chronic Lead Intoxication From Eating Wild-Harvested Game.

PubMed

Buenz, Eric J; Parry, Gareth J

2018-05-01

The purpose of this article is to determine if conversion from eating wild game harvested with lead-based ammunition to nonlead-based ammunition results in lower blood lead levels. Supersonic injection of toxin-leeching frangible projectiles into food is intuitively bad. As much as 95% of the ~13.7 million hunters in the United States choose shrapnel-inducing lead bullets to kill game; in addition, not harvesting meat is an incarcerable crime. A lead ammunition ban on certain federal lands was recently rescinded and the National Rifle Association refutes any risk from eating lead bullet-harvested game. A patient subsisting solely on lead-shot meat was converted to non-lead ammunition and his blood lead level tracked. Concomitant with his conversion to nonlead ammunition, a controlled experiment was performed using the patient's bullets to determine his daily lead intake from lead-shot meat. While eating lead-shot meat, the patient was consuming 259.3 ± 235.6 µg of lead daily and his blood lead level was 74.7 µg/dL. Conversion to nonlead ammunition was associated with a reduced blood lead level. Unsafe blood lead levels can occur from eating game harvested with lead ammunition. Physicians should warn hunting patients of this potential risk and counsel them about the availability of nonlead ammunition alternatives. Copyright © 2018 Elsevier Inc. All rights reserved.

A Bullet-Block Experiment that Explains the Chain Fountain

NASA Astrophysics Data System (ADS)

Pantaleone, J.; Smith, R.

2018-05-01

It is common in science for two phenomena to appear to be very different, but in fact follow from the same basic principles. Here we consider such a case, the connection between the chain fountain and a bullet-block collision experiment. When an upward moving bullet strikes a wooden block resting on a horizontal table, the block will rise to a higher height when the bullet strikes near the end of the block. This is because the quickly rotating block experiences an additional upward "reaction" force from its contact with the table. Such a reaction force also explains the chain fountain. When a chain falls from a pile in a container to the floor below, the chain rises up above the container. This rise occurs because the quickly rotating links in the container push off of the surface beneath them. We derive a model that accurately describes our measurements in the bullet-block experiment, and then use this same model to calculate an approximate expression for the distance the chain rises above the container. More extensive discussions of the chain fountain are available elsewhere.

Lead poisoning: The invisible disease

USGS Publications Warehouse

Friend, Milton

1989-01-01

Lead poisoning is an intoxication resulting from absorption of hazardous levels of lead into body tissues. Lead pellets from shot shells, when ingested, are the most common source of lead poisoning in migratory birds. Other far less common sources include lead fishing sinkers, mine wastes, paint pigments, bullets, and other lead objects that are swallowed.

Fragmentation functions at next-to-next-to-leading order accuracy

DOE PAGES

Anderle, Daniele P.; Stratmann, Marco; Ringer, Felix

2015-12-01

We present a first analysis of parton-to-pion fragmentation functions at next-to-next-to-leading order accuracy in QCD based on single-inclusive pion production in electron-positron annihilation. Special emphasis is put on the technical details necessary to perform the QCD scale evolution and cross section calculation in Mellin moment space. Lastly, we demonstrate how the description of the data and the theoretical uncertainties are improved when next-to-next-to-leading order QCD corrections are included.

[Morphology of bullet wounds when using police ammunition, type QD-P.E.P].

PubMed

Stein, Kirsten Marion; Wagner, Thomas; Ain, Stephan

2006-01-01

6 years after introduction of the police ammunition QD-P.E.P. (9 mm caliber), 9 bullet wounds are presented from forensic investigations along with the results of experimental shots at pig carcasses. The evaluation reveals the characteristic pattern of such bullet wounds: a skin defect which is almost as large as the caliber and has a sharp-edged border thus looking like it has been punched out; the contusion ring ("abrasion ring") is conspicuously narrow. These findings can be explained by the shape and design of the projectile. In regular police work immediate incapacitation has not always been achieved, depending on the entry location of the bullet. Experimental shots at pig carcasses showed that in the case of shots at extremities, the residual energy of the exiting bullet may be sufficient to generate another penetrating bullet wound.

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets.

PubMed

Wasko, Michael J; Pellegrene, Kendy A; Madura, Jeffry D; Surratt, Christopher K

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for "growing" the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets

PubMed Central

Wasko, Michael J.; Pellegrene, Kendy A.; Madura, Jeffry D.; Surratt, Christopher K.

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for “growing” the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies. PMID:26441817

Generation and control of sound bullets with a nonlinear acoustic lens.

PubMed

Spadoni, Alessandro; Daraio, Chiara

2010-04-20

Acoustic lenses are employed in a variety of applications, from biomedical imaging and surgery to defense systems and damage detection in materials. Focused acoustic signals, for example, enable ultrasonic transducers to image the interior of the human body. Currently however the performance of acoustic devices is limited by their linear operational envelope, which implies relatively inaccurate focusing and low focal power. Here we show a dramatic focusing effect and the generation of compact acoustic pulses (sound bullets) in solid and fluid media, with energies orders of magnitude greater than previously achievable. This focusing is made possible by a tunable, nonlinear acoustic lens, which consists of ordered arrays of granular chains. The amplitude, size, and location of the sound bullets can be controlled by varying the static precompression of the chains. Theory and numerical simulations demonstrate the focusing effect, and photoelasticity experiments corroborate it. Our nonlinear lens permits a qualitatively new way of generating high-energy acoustic pulses, which may improve imaging capabilities through increased accuracy and signal-to-noise ratios and may lead to more effective nonintrusive scalpels, for example, for cancer treatment.

Masked urinary bladder injury with a bullet expulsed spontaneously during voiding.

PubMed

Calışkan, Müjgan; Evren, Ismail; Kabak, Ismail; Atak, Ibrahim; Gökcan, Recai

2011-09-01

We report a case with gunshot to the pelvis. The injury site was the soft tissue between the rectum and urinary bladder. Several days later, the bullet was expulsed spontaneously during voiding. In the literature, only a few case reports have described spontaneous expulsion of an intravesical bullet. A 19-year-old male was wounded on the left hip by gunshot. Radiographic examinations showed a bullet in the pelvis, which was localized in the soft tissue between the rectum and urinary bladder, with no accompanying visceral injury on abdominopelvic computerized tomography. Macroscopic hematuria was noticed after urethral catheterization. Rectosigmoidoscopy and retrograde cystoscopic examinations were both negative. The patient was monitored closely and treated conservatively with no surgical intervention. The urinary catheter was removed on the fifth postoperative day, and the bullet was expulsed spontaneously via the urethra during normal voiding three hours after catheter removal. Thereafter, a retrograde urethrography was performed, which showed no evidence of urinary tract or bladder injury.

Consumption of lead-shot cervid meat and blood lead concentrations in a group of adult Norwegians.

PubMed

Meltzer, H M; Dahl, H; Brantsæter, A L; Birgisdottir, B E; Knutsen, H K; Bernhoft, A; Oftedal, B; Lande, U S; Alexander, J; Haugen, M; Ydersbond, T A

2013-11-01

Several recent investigations have reported high concentrations of lead in samples of minced cervid meat. This paper describes findings from a Norwegian study performed in 2012 among 147 adults with a wide range of cervid game consumption. The main aim was to assess whether high consumption of lead-shot cervid meat is associated with increased concentration of lead in blood. A second aim was to investigate to what extent factors apart from game consumption explain observed variability in blood lead levels. Median (5 and 95 percentile) blood concentration of lead was 16.6 µg/L (7.5 and 39 µg/L). An optimal multivariate linear regression model for log-transformed blood lead indicated that cervid game meat consumption once a month or more was associated with approximately 31% increase in blood lead concentrations. The increase seemed to be mostly associated with consumption of minced cervid meat, particularly purchased minced meat. However, many participants with high and long-lasting game meat intake had low blood lead concentrations. Cervid meat together with number of bullet shots per year, years with game consumption, self-assembly of bullets, wine consumption and smoking jointly accounted for approximately 25% of the variation in blood lead concentrations, while age and sex accounted for 27% of the variance. Blood lead concentrations increased approximately 18% per decade of age, and men had on average 30% higher blood lead concentrations than women. Hunters who assembled their own ammunition had 52% higher blood lead concentrations than persons not making ammunition. In conjunction with minced cervid meat, wine intake was significantly associated with increased blood lead. Our results indicate that hunting practices such as use of lead-based ammunition, self-assembling of lead containing bullets and inclusion of lead-contaminated meat for mincing to a large extent determine the exposure to lead from cervid game consumption. © 2013 Elsevier Inc. All rights

The transition to non-lead rifle ammunition in Denmark: National obligations and policy considerations.

PubMed

Kanstrup, Niels; Thomas, Vernon G; Krone, Oliver; Gremse, Carl

2016-09-01

The issue of Denmark regulating use of lead-free rifle ammunition because of potential risks of lead exposure in wildlife and humans was examined from a scientific and objective policy perspective. The consequences of adopting or rejecting such regulation were identified. Denmark is obliged to examine this topic because of its national policy on lead reduction, its being a Party to the UN Bonn Convention on Migratory Species, and its role in protecting White-tailed Sea Eagles (Haliaeetus albicilla), a species prone to lead poisoning from lead ingestion. Lead-free bullets suited for deer hunting are available at comparable cost to lead bullets, and have been demonstrated to be as effective. National adoption of lead-free bullets would complete the Danish transition to lead-free ammunition use. It would reduce the risk of lead exposure to scavenging wildlife, and humans who might eat lead-contaminated wild game meat. Opposition from hunting organizations would be expected.

[The forensic medical characteristics of the entrance bullet holes created by the shots from pneumatic rifles].

PubMed

Legin, G A; Bondarchuk, A O; Perebetjuk, A N

2015-01-01

The objective of the present study was to compare the injurious action of three types of the bullets for the pneumatic weapons shot from different distances using the Gamo pump air pistol and the BAM B22-1 pneumatic rifle. The following four kinds of the bullets were tested: "the fireball", "Luman cap 0.3", "Luman Field Target 0.68" and "DIABOLO". It was experimentally shown that the injurious action of the bullets fired from the same distance from the pneumatic weapons depends on the type of both the bullet and the weapon, as well as the properties of the target material. Specifically, the action of bullets fired from the piston pneumatic rifle remained stable whereas that of the bullets shot from the gas-balloon air pistol decreased as the gas was exhausted. The studies by the contact-diffusion method have demonstrated that the entrance bullet holes created by the shots from pneumatic weapons are surrounded by dispersed metal particles which makes it possible to estimate the shooting distance. Moreover, the bullets fired from the pneumatic weapons leave the muzzle face imprint on certain target materials.

Ignition potential of rifle bullets

Treesearch

Trevor Maynard; Mark Finney; Sara McAllister; Ian Grob

2013-01-01

In January 2013, the U.S. Department of Agriculture Forest Service's Rocky Mountain Research Station and National Technology and Development Centers performed experiments to evaluate the potential for rifle bullets to ignite organic matter after striking hard surfaces. Outdoor target shooting is often suspected as a wildfire cause, but investigators currently do...

Lead-free hunting rifle ammunition: product availability, price, effectiveness, and role in global wildlife conservation.

PubMed

Thomas, Vernon George

2013-10-01

Proposals to end the use of lead hunting ammunition because of the established risks of lead exposure to wildlife and humans are impeded by concerns about the availability, price, and effectiveness of substitutes. The product availability and retail prices of different calibers of lead-free bullets and center-fire rifle ammunition were assessed for ammunition sold in the USA and Europe. Lead-free bullets are made in 35 calibers and 51 rifle cartridge designations. Thirty-seven companies distribute internationally ammunition made with lead-free bullets. There is no major difference in the retail price of equivalent lead-free and lead-core ammunition for most popular calibers. Lead-free ammunition has set bench-mark standards for accuracy, lethality, and safety. Given the demonstrated wide product availability, comparable prices, and the effectiveness of high-quality lead-free ammunition, it is possible to phase out the use of lead hunting ammunition world-wide, based on progressive policy and enforceable legislation.

Generation and control of sound bullets with a nonlinear acoustic lens

PubMed Central

Spadoni, Alessandro; Daraio, Chiara

2010-01-01

Acoustic lenses are employed in a variety of applications, from biomedical imaging and surgery to defense systems and damage detection in materials. Focused acoustic signals, for example, enable ultrasonic transducers to image the interior of the human body. Currently however the performance of acoustic devices is limited by their linear operational envelope, which implies relatively inaccurate focusing and low focal power. Here we show a dramatic focusing effect and the generation of compact acoustic pulses (sound bullets) in solid and fluid media, with energies orders of magnitude greater than previously achievable. This focusing is made possible by a tunable, nonlinear acoustic lens, which consists of ordered arrays of granular chains. The amplitude, size, and location of the sound bullets can be controlled by varying the static precompression of the chains. Theory and numerical simulations demonstrate the focusing effect, and photoelasticity experiments corroborate it. Our nonlinear lens permits a qualitatively new way of generating high-energy acoustic pulses, which may improve imaging capabilities through increased accuracy and signal-to-noise ratios and may lead to more effective nonintrusive scalpels, for example, for cancer treatment. PMID:20368461

Polarization resolved electric field measurements on plasma bullets in N2 using four-wave mixing

NASA Astrophysics Data System (ADS)

van der Schans, Marc; Boehm, Patrick; Nijdam, Sander; Ijzerman, Wilbert; Czarnetzki, Uwe

2016-09-01

Atmospheric pressure plasma jets generated by kHz AC or pulsed DC voltages typically consist of discrete guided ionization waves called plasma bullets. In this work, the electric field of plasma bullets generated in a pulsed DC jet with N2 as feed gas is investigated using the four-wave mixing method. In this diagnostic two laser beams, where one is Stokes shifted from the other, non-linearly interact with the N2 molecules and the bullet's electric field. As a result of the interaction a coherent anti-Stokes Raman scattered (CARS) beam and an infrared beam are generated from which the electric field can be determined. Compared to emission-based methods, this technique has the advantage of being able to also probe the electric field in regions around the plasma bullet where no photons are emitted. The four-wave mixing method and its analysis have been adapted to work with the non-uniform electric field of plasma bullets. In addition, an ex-situ calibration procedure using an electrode geometry different from the discharge geometry has been developed. An experimentally obtained radial profile of the axial electric field component of a plasma bullet in N2 is presented. The position of this profile is related to the location of the propagating bullet from temporally resolved images.

China's bullet trains facilitate market integration and mitigate the cost of megacity growth.

PubMed

Zheng, Siqi; Kahn, Matthew E

2013-04-02

Megacity growth in the developing world is fueled by a desire to access their large local labor markets. Growing megacities suffer from high levels of traffic congestion and pollution, which degrade local quality of life. Transportation technology that allows individuals to access the megacity without living within its boundaries offers potentially large social benefits, because individuals can enjoy the benefits of urban agglomeration while not paying megacity real estate rents and suffering from the city's social costs. This paper presents evidence supporting the claim that China's bullet trains are playing this role. The bullet train is regarded as one of the most significant technological breakthroughs in passenger transportation developed in the second half of the 20th century. Starting in 2007, China has introduced several new bullet trains that connect megacities such as Beijing, Shanghai, and Guangzhou with nearby cities. Through facilitating market integration, bullet trains will stimulate the development of second- and third-tier cities. By offering households and firms a larger menu of location alternatives, bullet trains help to protect the quality of life of the growing urban population. We document that this transport innovation is associated with rising real estate prices in the nearby secondary cities.

Endoscopic Removal of a Bullet That Migrated to the Third Ventricle Causing Hydrocephalus.

PubMed

Aydoseli, Aydın; Unal, Tugrul Cem; Aras, Yavuz; Sabanci, Pulat Akın; Altunrende, Emre; Izgi, Nail

2017-09-01

Hydrocephalus caused by an intraventricular bullet is a rare event. We report a case of endoscopic removal of an intraventricular bullet. A 66-year-old man was admitted with a gunshot wound to the head after a suicide attempt. The bullet migrated from the frontal parenchyma to the third ventricle day 4 of admission. On day 21 of admission, the patient developed hydrocephalus with obstruction of the cerebral aqueduct. The bullet was accessed through an endoscopic third ventriculostomy and removed using an endoscope. Hydrocephalus may develop in patients with intraventricular foreign objects. When such objects must be removed, the endoscopic approach is a safe, efficient, and minimally invasive procedure. To our knowledge, this is the first case in the literature of foreign object removal from the ventricle via a transcortical endoscopic approach. Copyright © 2017 Elsevier Inc. All rights reserved.

Electric-field sensors for bullet detection systems

NASA Astrophysics Data System (ADS)

Vinci, Stephen; Hull, David; Ghionea, Simon; Ludwig, William; Deligeorges, Socrates; Gudmundsson, Thorkell; Noras, Maciej

2014-06-01

Research and experimental trials have shown that electric-field (E-field) sensors are effective at detecting charged projectiles. E-field sensors can likely complement traditional acoustic sensors, and help provide a more robust and effective solution for bullet detection and tracking. By far, the acoustic sensor is the most prevalent technology in use today for hostile fire defeat systems due to compact size and low cost, yet they come with a number of challenges that include multipath, reverberant environments, false positives and low signal-to-noise. Studies have shown that these systems can benefit from additional sensor modalities such as E-field sensors. However, E-field sensors are a newer technology that is relatively untested beyond basic experimental trials; this technology has not been deployed in any fielded systems. The U.S. Army Research Laboratory (ARL) has conducted live-fire experiments at Aberdeen Proving Grounds (APG) to collect data from E-field sensors. Three types of E-field sensors were included in these experiments: (a) an electric potential gradiometer manufactured by Quasar Federal Systems (QFS), (b) electric charge induction, or "D-dot" sensors designed and built by the Army Research Lab (ARL), and (c) a varactor based E-field sensor prototype designed by University of North Carolina-Charlotte (UNCC). Sensors were placed in strategic locations near the bullet trajectories, and their data were recorded. We analyzed the performance of each E-field sensor type in regard to small-arms bullet detection capability. The most recent experiment in October 2013 allowed demonstration of improved versions of the varactor and D-dot sensor types. Results of new real-time analysis hardware employing detection algorithms were also tested. The algorithms were used to process the raw data streams to determine when bullet detections occurred. Performance among the sensor types and algorithm effectiveness were compared to estimates from acoustics signatures

Targeting active cancer cells with smart bullets.

PubMed

Martel, Sylvain

2017-03-01

Paul Ehrlich's 'magic bullet' concept has stimulated research for therapeutic agents with the capability to go straight to their intended targets. The 'magic bullet' concept is still considered the ultimate approach to maximize the therapeutic effects of a given therapeutic agent without affecting nontargeted tissues. But so far, there has never been a therapeutic agent or a delivery system that goes straight to the target in the body, and no approach has provided anything better than just a few percents of the total administered dose reaching the intended target sites. But engineering principles can transform systematically circulating vectors that so far were based primarily on physical characteristics and biochemical principles alone, as smart therapeutic agents with the required propulsion-navigation-homing capabilities to enable them to go straight to their intended targets.

Bullet trajectory predicts the need for damage control: an artificial neural network model.

PubMed

Hirshberg, Asher; Wall, Matthew J; Mattox, Kenneth L

2002-05-01

Effective use of damage control in trauma hinges on an early decision to use it. Bullet trajectory has never been studied as a marker for damage control. We hypothesize that this decision can be predicted by an artificial neural network (ANN) model based on the bullet trajectory and the patient's blood pressure. A multilayer perceptron ANN predictive model was developed from a data set of 312 patients with single abdominal gunshot injuries. Input variables were the bullet path, trajectory patterns, and admission systolic pressure. The output variable was either a damage control laparotomy or intraoperative death. The best performing ANN was implemented on prospectively collected data from 34 patients. The model achieved a correct classification rate of 0.96 and area under the receiver operating characteristic curve of 0.94. External validation showed the model to have a sensitivity of 88% and specificity of 96%. Model implementation on the prospectively collected data had a correct classification rate of 0.91. Sensitivity analysis showed that systolic pressure, bullet path across the midline, and trajectory involving the right upper quadrant were the three most important input variables. Bullet trajectory is an important, hitherto unrecognized, factor that should be incorporated into the decision to use damage control.

Curvilinear trajectory estimation of a supersonic bullet using ballistic shock wave arrivals at asynchronous acoustic sensor nodes.

PubMed

Lo, Kam W

2017-06-01

The trajectory of a supersonic bullet, which is subjected to drag and gravity, is curvilinear and the supersonic flight of the bullet generates a ballistic shock wave (SW). A model for the differential time of arrival (DTOA) of the SW at a pair of acoustic sensors is derived for a given bullet trajectory, which is fully described by seven parameters including the drag coefficient exponent and ballistic constant of the bullet. Assuming that the drag coefficient exponent is 0.5, the DTOA model is used to develop a nonlinear least-squares (NLS) method to estimate the other six trajectory parameters using DTOA of SW measurements from each node (which comprises a small acoustic sensor array) of an asynchronous sensor network. The position of the shooter and the muzzle speed of the bullet are then determined by tracing the estimated bullet trajectory back to topographic or man-made obstructions on a digital map. The effectiveness of the NLS method is verified using simulated data for different types of real bullets, and the error standard deviations in the parameter estimates are close to the Cramer-Rao lower bounds.

Ablation effects in oxygen-lead fragmentation at 2.1 GeV/nucleon

NASA Technical Reports Server (NTRS)

Townsend, L. W.

1984-01-01

The mechanism of particle evaporation was used to examine ablation effects in the fragmentation of 2.1 GeV/nucleon oxygen nuclei by lead targets. Following the initial abrasion process, the excited projectile prefragment is assumed to statistically decay in a manner analogous to that of a compound nucleus. The decay probabilities for the various particle emission channels are calculated by using the EVAP-4 Monte Carlo computer program. The input excitation energy spectrum for the prefragment is estimated from the geometric ""clean cut'' abrasion-ablation model. Isotope production cross sections are calculated and compared with experimental data and with the predictions from the standard geometric abrasion-ablation fragmentation model.

Beyond magic bullets: true innovation in health care.

PubMed

Narayan, Vaibhav A; Mohwinckel, Marco; Pisano, Gary; Yang, Michael; Manji, Husseini K

2013-02-01

The time has come to move beyond product-focused 'magic bullet' therapeutic development strategies towards models that can also incorporate devices, tools and services to provide integrated health-care solutions.

Endovascular Approach for Management of Bullet Embolization to the Heart.

PubMed

Mojtahedi, Alireza; Contractor, Sohail; Kisza, Piotr S

2018-05-01

Bullet embolization to the right heart through the vasculature is seen infrequently in cases presenting with penetrating trauma. Patients with unstable hemodynamic status are managed operatively. For a patient with stable hemodynamic parameters, diagnostic evaluation such as computed tomography angiogram, echocardiogram, or angiography could be performed to select the best treatment option. Endovascular treatment is employed infrequently in these cases but can be a viable option for select patients. We present a case of a bullet embolus to the right ventricle treated successfully with endovascular approach and discuss the technical aspects of this approach.

The Balsa bullet: A high speed, low-cost general aviation aircraft for Aeroworld

NASA Technical Reports Server (NTRS)

Eastland, Kevin; Greenwood, Sean; Kelly, Dan; Leonard, Chuck; Rooff, John; Scherock, Jeff

1994-01-01

The Balsa Bullet is a high speed, low cost six passenger general aviation aircraft. It will cruise at a speed of 55 ft/s with a maximum speed of 75 ft/s for distances in excess of 27000 feet. This range and speed combination provide The Balsa Bullet with the capability to service any two existing airports in Aeroworld in an efficient and timely manner. Overall, three major design drivers have been identified by the design team. The first is to provide a low cost airplane to the Aeroworld market. Maintaining the low cost objective will not simply meet the mission objective, but will also make the Bullet an economically viable option for a wide number of consumers. The Balsa Bullet has a total manufacturing cost of $1000 with a price to the consumer of only $2562. The second major driver is high speed performance. Once again this driver exists not only to meet the mission objective given Long Shot Aeronautics but it provides a desirable feature to the consumer, pride in owning the fastest aircraft in Aeroworld. The third design driver identified is the capability to service any runway in Aeroworld necessitating the ability to takeoff within 28 ft, the length of the shortest runways in Aeroworld. These design drivers provide three great reasons for the general public to purchase a Bullet.

Magnetic Field Interactions of Military and Law Enforcement Bullets at 1.5 and 3 Tesla.

PubMed

Diallo, Idris; Auffret, Mathieu; Attar, Lakdar; Bouvard, Elise; Rousset, Jean; Ben Salem, Douraied

2016-07-01

There are significant numbers of military and law enforcement bullets containing ferromagnetic materials. This study aimed to assess the magnetic field interactions for a representative sample of military and law enforcement ballistic objects at 1.5 and 3 tesla (T) to create a magnetic resonance imaging (MRI) compatibility database. Twenty-nine different bullets underwent MRI evaluation. The deflection angle method and a qualitative torque scale were used. The samples were representative of those commonly used in the North Atlantic Treaty Organization (NATO) military forces (e.g., 5.56 mm NATO), law enforcement agencies (e.g., 9 mm Parabellum), and encountered in war injuries and crime-related trauma (e.g., 7.62 mm Kalashnikov). At all static magnetic field strengths, all non-nickel- and nonsteel-containing bullets exhibited no movement (deflection angle = 0°; torque = 0), whereas eight bullets containing steel core, steel jacket, or nickel jacket exhibited substantial magnetic field interactions over and above what might be regarded as safe in vivo (deflection angle = 90°; torque = 4+). Military and law enforcement non-nickel- or nonsteel-containing bullets appear to be safe for patients in MRI system at 1.5 and 3 T. On the other hand, nickel- and steel-containing bullets exhibit movements that are considered potentially unsafe for patients in an MRI environment. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Hot spot analysis for driving the development of hits into leads in fragment based drug discovery

PubMed Central

Hall, David R.; Ngan, Chi Ho; Zerbe, Brandon S.; Kozakov, Dima; Vajda, Sandor

2011-01-01

Fragment based drug design (FBDD) starts with finding fragment-sized compounds that are highly ligand efficient and can serve as a core moiety for developing high affinity leads. Although the core-bound structure of a protein facilitates the construction of leads, effective design is far from straightforward. We show that protein mapping, a computational method developed to find binding hot spots and implemented as the FTMap server, provides information that complements the fragment screening results and can drive the evolution of core fragments into larger leads with a minimal loss or, in some cases, even a gain in ligand efficiency. The method places small molecular probes, the size of organic solvents, on a dense grid around the protein, and identifies the hot spots as consensus clusters formed by clusters of several probes. The hot spots are ranked based on the number of probe clusters, which predicts the binding propensity of the subsites and hence their importance for drug design. Accordingly, with a single exception the main hot spot identified by FTMap binds the core compound found by fragment screening. The most useful information is provided by the neighboring secondary hot spots, indicating the regions where the core can be extended to increase its affinity. To quantify this information, we calculate the density of probes from mapping, which describes the binding propensity at each point, and show that the change in the correlation between a ligand position and the probe density upon extending or repositioning the core moiety predicts the expected change in ligand efficiency. PMID:22145575

A Bullet Fired in Dry Water: An Investigative Activity to Learn Hydrodynamics Concepts

ERIC Educational Resources Information Center

Leitão, Ulisses Azevedo; dos Anjos Pinheiro da Silva, Antonio; Trindade do Nascimento, Natália Cristina; da Cruz Gervásio, Lilian Mara Benedita

2017-01-01

In this paper we report an investigative activity on hydrodynamics, in the context of an inquiry-based learning project. The aim is to analyse the experiment of a bullet shot underwater. Using "Tracker," a video analysing and modelling software, the displacement of the bullet was measured as function of time, processing a slow motion…

A bullet fired in dry water: an investigative activity to learn hydrodynamics concepts

NASA Astrophysics Data System (ADS)

Azevedo Leitão, Ulisses; dos Anjos Pinheiro da Silva, Antonio; Trindade do Nascimento, Natália Cristina; Mara Benedita da Cruz Gervásio, Lilian

2017-01-01

In this paper we report an investigative activity on hydrodynamics, in the context of an inquiry-based learning project. The aim is to analyse the experiment of a bullet shot underwater. Using Tracker, a video analysing and modelling software, the displacement of the bullet was measured as function of time, processing a slow motion video from YouTube. It was found that the displacement of the bullet is well described in the first 20 ms by the inviscid flow regime, where the Newtonian drag force overcomes the viscous drag. This behaviour is discussed in the context of what Richard Feynman’s famous Lectures on Physics describes as ‘The Flow of Dry Water’.

[The determination of the ballistics of a hunting rifle loaded with a Poleva-3 bullet].

PubMed

Svetlakov, A V; Sotin, A V; Nagornov, M N

2014-01-01

Various approaches are considered to determine the shooting range of a hunting rifle loaded with a Poleva-3 bullet from the specific features of gunshot injuries inflicted by container-type Poleba-3 bullets for hunting rifles.

A Ligand-observed Mass Spectrometry Approach Integrated into the Fragment Based Lead Discovery Pipeline

PubMed Central

Chen, Xin; Qin, Shanshan; Chen, Shuai; Li, Jinlong; Li, Lixin; Wang, Zhongling; Wang, Quan; Lin, Jianping; Yang, Cheng; Shui, Wenqing

2015-01-01

In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially for tough targets. In this study, this approach was integrated into a FBLD program targeting the HCV RNA polymerase NS5B. Our ligand-observed mass spectrometry analysis resulted in the discovery of 10 hits from a 384-member fragment library through two independent screens of complex cocktails and a follow-up validation assay. Moreover, this MS-based approach enabled quantitative measurement of weak binding affinities of fragments which was in general consistent with SPR analysis. Five out of the ten hits were then successfully translated to X-ray structures of fragment-bound complexes to lay a foundation for structure-based inhibitor design. With distinctive strengths in terms of high capacity and speed, minimal method development, easy sample preparation, low material consumption and quantitative capability, this MS-based assay is anticipated to be a valuable addition to the repertoire of current fragment screening techniques. PMID:25666181

Missing Fragments: Detecting Cooperative Binding in Fragment-Based Drug Design

PubMed Central

2012-01-01

The aim of fragment-based drug design (FBDD) is to identify molecular fragments that bind to alternate subsites within a given binding pocket leading to cooperative binding when linked. In this study, the binding of fragments to human phenylethanolamine N-methyltransferase is used to illustrate how (a) current protocols may fail to detect fragments that bind cooperatively, (b) theoretical approaches can be used to validate potential hits, and (c) apparent false positives obtained when screening against cocktails of fragments may in fact indicate promising leads. PMID:24900472

Utilization of the Safe Surgical Dislocation Approach of the Hip to Retrieve a Bullet from the Femoral Head

PubMed Central

Delaney, Ruth; Albright, Maurice; Rebello, Gleeson

2011-01-01

Retained intra-articular missiles from low-velocity handguns can lead to mechanical arthritis, synovitis, and lead toxicity. Various surgical approaches have been described to extract such foreign bodies from the hip joint. We present the case of a 17-year-old male in which the surgical dislocation approach was utilized to retrieve a bullet from the femoral head with a good short-term outcome. This case represents a rare application of the surgical hip dislocation approach for an unusual trauma. PMID:23198205

Blood Back Spatter Caused by a Blunt Bullet Gunshot: Theory and Experiments

NASA Astrophysics Data System (ADS)

Comiskey, Patrick; Yarin, Alexander; Kim, Sungu; Attinger, Daniel

A theoretical model describing the blood back spatter pattern resulting from a blunt bullet gunshot is proposed and compared to experimental data. It is shown that the blunt bullet impact results in blood accelerating towards air opposite of the bullet motion creating a situation for the Rayleigh-Taylor instability which determines droplet sizes and initial velocities. Then, drop trajectories can be predicted accounting for all forces involved: air drag and gravity forces, as well as for the collective effect of drop-drop interaction through air which diminishes the drag force on drops moving in the wake of the others. Experimental data was acquired by shooting a blunt bullet into a porous substrate impregnated with swine blood and the spatter pattern was collected on a vertical surface located between the target and the shooter. The spatter pattern was analyzed for the number of droplets, the area of blood stains, total stain area, and location. Comparisons with the theoretical results reveal satisfactory agreement. The theory also predicts the impact angle at the collection surface, the Weber number corresponding to the drop impact onto the collection surface, and the stain ellipticity. Support of this work by the US National Institute of Justice (award NIJ 2014-DN-BX-K036) is greatly appreciated.

Body models in forensic ballistics: reconstruction of a gunshot injury to the chest by bullet fragmentation after shooting through a finger.

PubMed

Thali, M J; Kneubuehl, B P; Dirnhofer, R; Zollinger, U

2001-11-15

Forensic science uses substitutes to reconstruct injury patterns in order to answer questions regarding the dynamic formation of unusual injuries. Using a case study, an experimental simulation of a finger was designed, for the first time with a combination of hard wood and glycerin soap. With this model as an intermediate target simulation, it was possible not only to demonstrate the "bullet-body (finger) interaction", but also to recreate the wound pattern found in the victim. This case demonstrates that by using ballistic models and body-part substitutes, gunshot cases can be reproduced simply and economically, without coming into conflict with ethical guidelines.

Long Wavelength Electromagnetic Light Bullets Generated by a 10.6 micron CO2 Ultrashort Pulsed Source

DTIC Science & Technology

2016-11-29

AFRL-AFOSR-VA-TR-2016-0365 Long Wavelength Electromagnetic Light Bullets Generated by a 10.6 micron CO2 Ultrashort Pulsed Source Jerome Moloney...SUBTITLE "Long Wavelength Electromagnetic Light Bullets Generated by a 10.6 micron CO2 Ultrashort Pulsed Source 5a. CONTRACT NUMBER FA9550-15-1-0272 5b...afosr.reports.sgizmo.com/s3/> Subject: Final Report to Dr. Arje Nachman Contract/Grant Title: Long Wavelength Electromagnetic Light Bullets Generated by a 10.6

Creating Novel Activated Factor XI Inhibitors through Fragment Based Lead Generation and Structure Aided Drug Design

PubMed Central

Fjellström, Ola; Akkaya, Sibel; Beisel, Hans-Georg; Eriksson, Per-Olof; Erixon, Karl; Gustafsson, David; Jurva, Ulrik; Kang, Daiwu; Karis, David; Knecht, Wolfgang; Nerme, Viveca; Nilsson, Ingemar; Olsson, Thomas; Redzic, Alma; Roth, Robert; Sandmark, Jenny; Tigerström, Anna; Öster, Linda

2015-01-01

Activated factor XI (FXIa) inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1’-S2’ FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1’-S2’ binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC50 of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1’-S2’ binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds. PMID:25629509

[A singular bullet run in a firearm wound in the neck. A case report].

PubMed

Martino, Antonio; De Rienzo, Dino; Evangelista, Marco; La Rocca, Francesco; Maharajan, Gautam; Martino, Giovanni; Sacco, Maria Lucia; Scaglione, Mariano

2009-01-01

The paper deals with the peculiarities of a firearm wound regarding the dynamic of the accident and particularly considering the path followed by the bullet. The patient's firearm wound is described on the basis of the instrumental examinations done. These last give us a precious help to confirm the thesis, already guessed on the clinical examination of an introduction and path followed through the digestive tract, and to show the dynamics and the still positions of the bullet inside the patient's body. The bullet was expelled spontaneously by defecation. After control of no internal damages this firearm wound has been treated simply as a normal tip wound.

Hunting with lead: association between blood lead levels and wild game consumption.

PubMed

Iqbal, Shahed; Blumenthal, Wendy; Kennedy, Chinaro; Yip, Fuyuen Y; Pickard, Stephen; Flanders, W Dana; Loringer, Kelly; Kruger, Kirby; Caldwell, Kathleen L; Jean Brown, Mary

2009-11-01

Wild game hunting is a popular activity in many regions of the United States. Recently, the presence of lead fragments in wild game meat, presumably from the bullets or shot used for hunting, has raised concerns about health risks from meat consumption. This study examined the association between blood lead levels (PbB) and wild game consumption. We recruited 742 participants, aged 2-92 years, from six North Dakota cities. Blood lead samples were collected from 736 persons. Information on socio-demographic background, housing, lead exposure source, and types of wild game consumption (i.e., venison, other game such as moose, birds) was also collected. Generalized estimating equations (GEE) were used to determine the association between PbB and wild game consumption. Most participants reported consuming wild game (80.8%) obtained from hunting (98.8%). The geometric mean PbB were 1.27 and 0.84 microg/dl among persons who did and did not consume wild game, respectively. After adjusting for potential confounders, persons who consumed wild game had 0.30 microg/dl (95% confidence interval: 0.16-0.44 microg/dl) higher PbB than persons who did not. For all game types, recent (<1 month) wild game consumption was associated with higher PbB. PbB was also higher among those who consumed a larger serving size (> or = 2 oz vs. <2 oz); however, this association was significant for 'other game' consumption only. Participants who consumed wild game had higher PbB than those who did not consume wild game. Careful review of butchering practices and monitoring of meat-packing processes may decrease lead exposure from wild game consumption.

Diet-derived microRNAs: unicorn or silver bullet?

PubMed

Witwer, Kenneth W; Zhang, Chen-Yu

2017-01-01

In ancient lore, a bullet cast from silver is the only effective weapon against monsters. The uptake of active diet-derived microRNAs (miRNAs) in consumers may be the silver bullet long sought after in nutrition and oral therapeutics. However, the majority of scientists consider the transfer and regulation of consumer's gene activity by these diet-derived miRNAs to be a fantasy akin to spotting a unicorn. Nevertheless, groups like Dr. Chen-Yu Zhang's lab in Nanjing University have stockpiled breathtaking amounts of data to shoot down these naysayers. Meanwhile, Dr. Ken Witwer at John Hopkins has steadfastly cautioned the field to beware of fallacies caused by contamination, technical artifacts, and confirmation bias. Here, Dr. Witwer and Dr. Zhang share their realities of dietary miRNAs by answering five questions related to this controversial field.

Injuries caused by fragmenting rifle ammunition.

PubMed

Jorgensen, Jorgen Joakim; Naess, Paal Aksel; Gaarder, Christine

2016-09-01

Although penetrating injuries are encountered on a regular basis in high volume trauma centres, most civilian trauma teams will be unfamiliar with the treatment of patients with injuries caused by fragmenting ammunition. The terrorist attacks in Norway on July 22, 2011 included a shooting spree causing 69 deaths and 60 injured. One of the weapons used was a semi-automatic rifle, calibre 5.56mm, with soft tip, short stop ammunition. The aim of the present study was to describe the characteristic injury patterns and lessons learned from the treatment of multiple patients admitted at the regional trauma centre with injuries from this type of ammunition. We undertook an observational study of patients admitted at Oslo University Hospital, Ulleval after the shooting spree at Utoya on July 22, 2011. Data on demographics, injuries, injury severity, surgical procedures and outcome were collected prospectively. Of the 21 patients admitted after the shooting incident, 18 were identified with injuries caused by fragmenting ammunition and included in the study. Median age was 17 years (IQR 16, 19), median ISS 21 (IQR 12, 30) and 12 patients were female. They had been hit by a total of 38 projectiles, of which 32 were fragmenting bullets. Of the seven patients who sustained injuries to the head, neck and face, one patient required a craniotomy and one patient had a non-survivable head injury. Of the 11 patients with torso injuries, six of the eight patients with chest injuries had intra-thoracic injuries that could be treated with chest tubes only. One patient had cardiac tamponade, requiring thoracotomy. Six patients underwent laparotomy, four of them more than one. Of the 10 patients with extremity injuries, two had nerve injuries and six patients had fractures. Five amputations were performed within the first nine days. A total of 101 operations were required within the first four weeks. The majority of these were repeated soft tissue debridements due to progressive necrosis

Damage to apparel layers and underlying tissue due to hand-gun bullets.

PubMed

Carr, Debra; Kieser, Jules; Mabbott, Alexander; Mott, Charlotte; Champion, Stephen; Girvan, Elizabeth

2014-01-01

Ballistic damage to the clothing of victims of gunshot wounds to the chest can provide useful forensic evidence. Anyone shot in the torso will usually be wearing clothing which will be damaged by the penetrating impact event and can reportedly be the source of some of the debris in the wound. Minimal research has previously been reported regarding the effect of bullets on apparel fabrics and underlying tissue. This paper examines the effect of ammunition (9 mm full metal jacket [FMJ] DM11 A1B2, 8.0 g; and soft point flat nose Remington R357M3, 10.2 g) on clothing layers that cover the torso (T-shirt, T-shirt plus hoodie, T-shirt plus denim jacket) and underlying structures represented by porcine thoracic wall (skin, underlying tissue, ribs). Impacts were recorded using a Phantom V12 high speed camera. Ejected bone debris was collected before wound tracts were dissected and measured; any debris found was recovered for further analysis. Size and mass of bony debris was recorded; fibre debris recovered from the wound and impact damage to fabrics were imaged using scanning electron microscopy (SEM). Remington R357M3 ammunition was characteristically associated with stellate fabric damage; individual fibres were less likely to show mushrooming. In contrast, 9 mm FMJ ammunition resulted in punch-out damage to fabric layers, with mushrooming of individual fibres being more common. Entry wound sizes were similar for both types of ammunition and smaller than the diameter of the bullet that caused them. In this work, the Remington R357M3 ammunition resulted in larger exit wounds due to the bullet construction which mushroomed. That fabric coverings did not affect the amount of bony debris produced is interesting, particularly given there was some evidence that apparel layers affected the size of the wound. Recent work has suggested that denim (representative of jeans) can exacerbate wounding caused by high-velocity bullet impacts to the thigh when the bullet does not

The benefit of a tough skin: bullet holes, weathering and the preservation of heritage

NASA Astrophysics Data System (ADS)

Mol, Lisa; Gomez-Heras, M.; Brassey, C.; Green, O.; Blenkinsop, T.

2017-02-01

Projectile damage to building stone is a widespread phenomenon. Sites damaged 100 years ago during the First World War still see daily use, while in a more contemporary setting numerous reports show the damage to buildings in Babylon, Mosul and Palmyra. While research has been carried out on the long-term effects of conflict such as fire damage, little is known about the protracted damage sustained through the impact of bullets, shrapnel and other metal projectiles outside of the field of engineering focused on ceramics and metals. To investigate alterations to mineral structure caused by projectile damage, impacts were created in medium-grained, well-compacted, mesoporous sandstone samples using 0.22 calibre lead bullets shot at a distance of 20 m. Half these samples were treated with a surface consolidant (Wacker OH 100), to mimic natural cementation of the rock surface. These samples were then tested for changes to surface hardness and moisture movement during temperature cycles of 15-65°C. Petrographic thin section analysis was carried out to investigate the micro-scale deformation associated with high-speed impact. The results surprisingly show that stress build-up behind pre-existing cementation of the surface, as found in heritage sites that have been exposed to moisture and temperature fluctuations for longer periods of time, can be alleviated with a bullet impact. However, fracture networks and alteration of the mineral matrices still form a weak point within the structure, even at a relatively low impact calibre. This initial study illustrates the need for geomorphologists, geologists, engineers and heritage specialists to work collectively to gain further insights into the long-term impact of higher calibre armed warfare on heritage deterioration.

A Molecular-line Study of the Interstellar Bullet Engine IRAS05506+2414

NASA Astrophysics Data System (ADS)

Sahai, Raghvendra; Lee, Chin-Fei; Sánchez Contreras, Carmen; Patel, Nimesh; Morris, Mark R.; Claussen, Mark

2017-12-01

We present interferometric and single-dish molecular line observations of the interstellar bullet-outflow source IRAS 05506+2414, whose wide-angle bullet spray is similar to the Orion BN/KL explosive outflow and likely arises from an entirely different mechanism than the classical accretion-disk-driven bipolar flows in young stellar objects. The bullet-outflow source is associated with a large pseudo-disk and three molecular outflows—a high-velocity outflow (HVO), a medium-velocity outflow (MVO), and a slow, extended outflow (SEO). The size (mass) of the pseudo-disk is 10,350 au × 6400 au (0.64-0.17 M ⊙) from a model-fit assuming infall and rotation, we derive a central stellar mass of 8-19 M ⊙. The HVO (MVO) has an angular size ˜5180 (˜3330) au and a projected outflow velocity of ˜140 km s-1 (˜30 km s-1). The SEO size (outflow speed) is ˜0.9 pc (˜6 km s-1). The HVO’s axis is aligned with (orthogonal to) that of the SEO (pseudo-disk). The velocity structure of the MVO is unresolved. The scalar momenta in the HVO and SEO are very similar, suggesting that the SEO has resulted from the HVO interacting with ambient-cloud material. The bullet spray shares a common axis with the pseudo-disk and has an age comparable to that of MVO (few hundred years), suggesting that these three structures are intimately linked. We discuss several models for the outflows in IRAS 05506+2414 (including dynamical decay of a stellar cluster, chance encounter of a runaway star with a dense cloud, and close passage of two protostars), and conclude that second-epoch imaging to derive proper motions of the bullets and nearby stars can help to discriminate between them.

Immunoconjugates: Magic Bullets for Cancer Therapy?

NASA Technical Reports Server (NTRS)

Passeri, Daniel R.; Spiegel, Jack

1993-01-01

Conjugating cytotoxic agents to antibodies allows for site-specific delivery of the agent to tumor cells and should provide increased efficacy and reduced non-specific toxicity. These site-specific cytotoxic agents are known as immunoconjugates or 'magic bullets' and have demonstrated great promise as therapeutic agents for cancer and other diseases. The historical developments and future potential of this new approach to cancer therapy are reviewed.

4. NORTHWEST FRONT, WITH FOUR BULLET GLASS WINDOWS. Edwards ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. NORTHWEST FRONT, WITH FOUR BULLET GLASS WINDOWS. - Edwards Air Force Base, South Base Sled Track, Observation Block House, Station "O" area, east end of Sled Track, Lancaster, Los Angeles County, CA

In silico fragment-based drug discovery: setup and validation of a fragment-to-lead computational protocol using S4MPLE.

PubMed

Hoffer, Laurent; Renaud, Jean-Paul; Horvath, Dragos

2013-04-22

This paper describes the use and validation of S4MPLE in Fragment-Based Drug Design (FBDD)--a strategy to build drug-like ligands starting from small compounds called fragments. S4MPLE is a conformational sampling tool based on a hybrid genetic algorithm that is able to simulate one (conformer enumeration) or more molecules (docking). The goal of the current paper is to show that due to the judicious design of genetic operators, S4MPLE may be used without any specific adaptation as an in silico FBDD tool. Such fragment-to-lead evolution involves either growing of one or linking of several fragment-like binder(s). The native ability to specifically "dock" a substructure that is covalently anchored to its target (here, some prepositioned fragment formally part of the binding site) enables it to act like dedicated de novo builders and differentiates it from most classical docking tools, which may only cope with non-covalent interactions. Besides, S4MPLE may address growing/linking scenarios involving protein site flexibility, and it might also suggest "growth" moves by bridging the ligand to the site via water-mediated interactions if H2O molecules are simply appended to the input files. Therefore, the only development overhead required to build a virtual fragment→ligand growing/linking strategy based on S4MPLE were two chemoinformatics programs meant to provide a minimalistic management of the linker library. The first creates a duplicate-free library by fragmenting a compound database, whereas the second builds new compounds, attaching chemically compatible linkers to the starting fragments. S4MPLE is subsequently used to probe the optimal placement of the linkers within the binding site, with initial restraints on atoms from initial fragments, followed by an optimization of all kept poses after restraint removal. Ranking is mainly based on two criteria: force-field potential energy and RMSD shifts of the original fragment moieties. This strategy was applied to

The rise and fall of a challenger: the Bullet Cluster in Λ cold dark matter simulations

NASA Astrophysics Data System (ADS)

Thompson, Robert; Davé, Romeel; Nagamine, Kentaro

2015-09-01

The Bullet Cluster has provided some of the best evidence for the Λ cold dark matter (ΛCDM) model via direct empirical proof of the existence of collisionless dark matter, while posing a serious challenge owing to the unusually high inferred pairwise velocities of its progenitor clusters. Here, we investigate the probability of finding such a high-velocity pair in large-volume N-body simulations, particularly focusing on differences between halo-finding algorithms. We find that algorithms that do not account for the kinematics of infalling groups yield vastly different statistics and probabilities. When employing the ROCKSTAR halo finder that considers particle velocities, we find numerous Bullet-like pair candidates that closely match not only the high pairwise velocity, but also the mass, mass ratio, separation distance, and collision angle of the initial conditions that have been shown to produce the Bullet Cluster in non-cosmological hydrodynamic simulations. The probability of finding a high pairwise velocity pair among haloes with Mhalo ≥ 1014 M⊙ is 4.6 × 10-4 using ROCKSTAR, while it is ≈34 × lower using a friends-of-friends (FoF)-based approach as in previous studies. This is because the typical spatial extent of Bullet progenitors is such that FoF tends to group them into a single halo despite clearly distinct kinematics. Further requiring an appropriately high average mass among the two progenitors, we find the comoving number density of potential Bullet-like candidates to be of the order of ≈10-10 Mpc-3. Our findings suggest that ΛCDM straightforwardly produces massive, high relative velocity halo pairs analogous to Bullet Cluster progenitors, and hence the Bullet Cluster does not present a challenge to the ΛCDM model.

Janus "nano-bullets" for magnetic targeting liver cancer chemotherapy.

PubMed

Shao, Dan; Li, Jing; Zheng, Xiao; Pan, Yue; Wang, Zheng; Zhang, Ming; Chen, Qi-Xian; Dong, Wen-Fei; Chen, Li

2016-09-01

Tumor-targeted delivery of anti-cancer drugs with controlled drug release function has been recognized as a promising strategy for pursuit of increased chemotherapeutic efficacy and reduced adverse effects. Development of magnetic nanoparticulates as delivery carriers to accommodate cytotoxic drugs for liver cancer treatment has evoked immense interest with respect to their convenience in biomedical application. Herein, we engineered multifunctional Janus nanocomposites, characterized by a head of magnetic Fe3O4 and a body of mesoporous SiO2 containing doxorubicin (DOX) as "nano-bullets" (M-MSNs-DOX). This nanodrug formulation possessed nanosize with controlled aspect-ratio, defined abundance in pore structures, and superior magnetic properties. M-MSN-DOX was determined to induce selective growth inhibition to the cancer cell under magnetic field rather than human normal cells due to its preferable endocytosis by the tumor cells and pH-promoted DOX release in the interior of cancer cells. Ultimately, both subcutaneous and orthotropic liver tumor models in mice have demonstrated that the proposed Janus nano-bullets imposed remarkable suppression of the tumor growth and significantly reduced systematic toxicity. Taken together, this study demonstrates an intriguing targeting strategy for liver cancer treatment based on a novel Janus nano-bullet, aiming for utilization of nanotechnology to obtain safe and efficient treatment of liver cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Release of copper from embedded solid copper bullets into muscle and fat tissues of fallow deer (Dama dama), roe deer (Capreolus capreolus), and wild boar (Sus scrofa) and effect of copper content on oxidative stability of heat-processed meat.

PubMed

Schuhmann-Irschik, I; Sager, M; Paulsen, P; Tichy, A; Bauer, F

2015-10-01

When venison with embedded copper bullets was subjected to different culinary processing procedures, the amount of copper released from the embedded bullet was affected more by the retention period of the bullet in the meat during cool storage, than by the different heating protocols. The presence of copper fragments had no significant effect on levels of thiobarbituric acid reactive substances (TBARS). Conversely, TBARS in lean meat (fallow deer, wild boar, roe deer) were significantly affected by culinary treatment (higher TBARS in boiled and boiled-stored meat than in meat barbecued or boiled in brine). In pork-beef patties doped with up to 28mg/kg Cu, TBARS increased after dry-heating and subsequently storing the meat patties. The amount of copper doping had no effect on TBARS for 0 and 7days of storage, but a significant effect at day 14 (fat oxidation retarded at higher Cu doses). Evidence is presented that wild boar meat may be more sensitive to fat oxidation than pork-beef. Copyright © 2015 Elsevier Ltd. All rights reserved.

The benefit of a tough skin: bullet holes, weathering and the preservation of heritage

PubMed Central

Gomez-Heras, M.; Brassey, C.; Green, O.; Blenkinsop, T.

2017-01-01

Projectile damage to building stone is a widespread phenomenon. Sites damaged 100 years ago during the First World War still see daily use, while in a more contemporary setting numerous reports show the damage to buildings in Babylon, Mosul and Palmyra. While research has been carried out on the long-term effects of conflict such as fire damage, little is known about the protracted damage sustained through the impact of bullets, shrapnel and other metal projectiles outside of the field of engineering focused on ceramics and metals. To investigate alterations to mineral structure caused by projectile damage, impacts were created in medium-grained, well-compacted, mesoporous sandstone samples using 0.22 calibre lead bullets shot at a distance of 20 m. Half these samples were treated with a surface consolidant (Wacker OH 100), to mimic natural cementation of the rock surface. These samples were then tested for changes to surface hardness and moisture movement during temperature cycles of 15–65°C. Petrographic thin section analysis was carried out to investigate the micro-scale deformation associated with high-speed impact. The results surprisingly show that stress build-up behind pre-existing cementation of the surface, as found in heritage sites that have been exposed to moisture and temperature fluctuations for longer periods of time, can be alleviated with a bullet impact. However, fracture networks and alteration of the mineral matrices still form a weak point within the structure, even at a relatively low impact calibre. This initial study illustrates the need for geomorphologists, geologists, engineers and heritage specialists to work collectively to gain further insights into the long-term impact of higher calibre armed warfare on heritage deterioration. PMID:28386411

Self-accelerating Airy-Ince-Gaussian and Airy-Helical-Ince-Gaussian light bullets in free space.

PubMed

Peng, Yulian; Chen, Bo; Peng, Xi; Zhou, Meiling; Zhang, Liping; Li, Dongdong; Deng, Dongmei

2016-08-22

The evolution of the three-dimensional (3D) self-accelerating Airy-Ince-Gaussian (AiIG) and Airy-Helical-Ince-Gaussian (AiHIG) light bullets is investigated by solving the (3+1)D linear spatiotemporal evolution equation of an optical field analytically. As far as we know, the numerical experimental demonstrations of the Ince-Gaussian (IG) and Helical-Ince-Gaussian (HIG) beams in various modes are first developed to study the evolution characteristics of the different 3D spatiotemporal light bullets. A conclusion can be drawn that the different photoelastics, pulse stacked, boundary, elliptical ring and physically separated in-line vortices can be achieved by adjusting the ellipticity, the evolution distance and the mode-number of light bullets.

A Fortunate Story of an Unusual AK-47 Bullet Trajectory: Always Keep a Smartphone in Your Pocket.

PubMed

Thabouillot, Oscar; Perrier, Pierre; Roche, Nicolas-Charles; Agard, David; Barbier, Olivier; Martin, Guillaume; Viant, Eric; Leclere, Jean-Baptiste

2016-06-01

This is a report of a fortunate story of an unusual AK-47 bullet trajectory which took place during the Paris (France) attack of November 13th, 2015. A young man, trying to protect his girlfriend, interfered between her and a shooter. He had been wounded in the posterior compartment of the thigh. The bullet penetrated him and, instead of exiting, rebound against his Smartphone, which was in the front pocket of his pants. Thanks to that, the missile bullet did not injure his girlfriend but ended its trajectory in the fat tissue of his thigh. Thabouillot O , Perrier P , Roche NC , Agard D , Barbier O , Martin G , Viant E , Leclere JB . A fortunate story of an unusual AK-47 bullet trajectory: always keep a Smartphone in your pocket. Prehosp Disaster Med, 2016;31(3):343-345.

Fragment-based virtual screening approach and molecular dynamics simulation studies for identification of BACE1 inhibitor leads.

PubMed

Manoharan, Prabu; Ghoshal, Nanda

2018-05-01

Traditional structure-based virtual screening method to identify drug-like small molecules for BACE1 is so far unsuccessful. Location of BACE1, poor Blood Brain Barrier permeability and P-glycoprotein (Pgp) susceptibility of the inhibitors make it even more difficult. Fragment-based drug design method is suitable for efficient optimization of initial hit molecules for target like BACE1. We have developed a fragment-based virtual screening approach to identify/optimize the fragment molecules as a starting point. This method combines the shape, electrostatic, and pharmacophoric features of known fragment molecules, bound to protein conjugate crystal structure, and aims to identify both chemically and energetically feasible small fragment ligands that bind to BACE1 active site. The two top-ranked fragment hits were subjected for a 53 ns MD simulation. Principle component analysis and free energy landscape analysis reveal that the new ligands show the characteristic features of established BACE1 inhibitors. The potent method employed in this study may serve for the development of potential lead molecules for BACE1-directed Alzheimer's disease therapeutics.

NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds

PubMed Central

Yu, Jun-lan; Chen, Tian-tian; Zhou, Chen; Lian, Fu-lin; Tang, Xu-long; Wen, Yi; Shen, Jing-kang; Xu, Ye-chun; Xiong, Bing; Zhang, Nai-xia

2016-01-01

Aim: Fragment-based lead discovery (FBLD) is a complementary approach in drug research and development. In this study, we established an NMR-based FBLD platform that was used to screen novel scaffolds targeting human bromodomain of BRD4, and investigated the binding interactions between hit compounds and the target protein. Methods: 1D NMR techniques were primarily used to generate the fragment library and to screen compounds. The inhibitory activity of hits on the first bromodomain of BRD4 [BRD4(I)] was examined using fluorescence anisotropy binding assay. 2D NMR and X-ray crystallography were applied to characterize the binding interactions between hit compounds and the target protein. Results: An NMR-based fragment library containing 539 compounds was established, which were clustered into 56 groups (8–10 compounds in each group). Eight hits with new scaffolds were found to inhibit BRD4(I). Four out of the 8 hits (compounds 1, 2, 8 and 9) had IC50 values of 100–260 μmol/L, demonstrating their potential for further BRD4-targeted hit-to-lead optimization. Analysis of the binding interactions revealed that compounds 1 and 2 shared a common quinazolin core structure and bound to BRD4(I) in a non-acetylated lysine mimetic mode. Conclusion: An NMR-based platform for FBLD was established and used in discovery of BRD4-targeted compounds. Four potential hit-to-lead optimization candidates have been found, two of them bound to BRD4(I) in a non-acetylated lysine mimetic mode, being selective BRD4(I) inhibitors. PMID:27238211

In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach

NASA Astrophysics Data System (ADS)

Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.

1992-04-01

A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.

3. NORTH FRONT, BULLET GLASS OBSERVATION WINDOWS FACE SLED TRACK. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. NORTH FRONT, BULLET GLASS OBSERVATION WINDOWS FACE SLED TRACK. - Edwards Air Force Base, South Base Sled Track, Instrumentation & Control Building, South of Sled Track, Station "50" area, Lancaster, Los Angeles County, CA

Inconsistency in 9 mm bullets: correlation of jacket thickness to post-impact geometry measured with non-destructive X-ray computed tomography.

PubMed

Thornby, John; Landheer, Dirk; Williams, Tim; Barnes-Warden, Jane; Fenne, Paul; Norman, Danielle G; Attridge, Alex; Williams, Mark A

2014-01-01

Fundamental to any ballistic armour standard is the reference projectile to be defeated. Typically, for certification purposes, a consistent and symmetrical bullet geometry is assumed, however variations in bullet jacket dimensions can have far reaching consequences. Traditionally, characteristics and internal dimensions have been analysed by physically sectioning bullets--an approach which is of restricted scope and which precludes subsequent ballistic assessment. The use of a non-destructive X-ray computed tomography (CT) method has been demonstrated and validated (Kumar et al., 2011 [15]); the authors now apply this technique to correlate bullet impact response with jacket thickness variations. A set of 20 bullets (9 mm DM11) were selected for comparison and an image-based analysis method was employed to map jacket thickness and determine the centre of gravity of each specimen. Both intra- and inter-bullet variations were investigated, with thickness variations of the order of 200 μm commonly found along the length of all bullets and angular variations of up to 50 μm in some. The bullets were subsequently impacted against a rigid flat plate under controlled conditions (observed on a high-speed video camera) and the resulting deformed projectiles were re-analysed. The results of the experiments demonstrate a marked difference in ballistic performance between bullets from different manufacturers and an asymmetric thinning of the jacket is observed in regions of pre-impact weakness. The conclusions are relevant for future soft armour standards and provide important quantitative data for numerical model correlation and development. The implications of the findings of the work on the reliability and repeatability of the industry standard V50 ballistic test are also discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

6. SOUTH SIDE, DETAIL OF BULLET GLASS WINDOWS AT GROUND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. SOUTH SIDE, DETAIL OF BULLET GLASS WINDOWS AT GROUND LEVEL. - Edwards Air Force Base, South Base Sled Track, Firing Control Blockhouse, South of Sled Track at east end, Lancaster, Los Angeles County, CA

Deep observation of A2163: studying a new bullet cluster

NASA Astrophysics Data System (ADS)

Bourdin, Herve

2011-10-01

Exhibiting a clear spatial separation between the gas and dark matter component of a fastly accreted subcluster, the `bullet cluster', 1E 0657-56, has provided us a unique laboratory to investigate the impact of violent cluster mergers on the Intra-Cluster Medium, galaxies and dark matter properties. In recent analyses of X-ray, optical and weak-lensing data, we show that the massive cluster A2163 also exhibits a crossing gas bullet separated from a galaxy and dark matter over-density, and suggest that both A2163 and 1E 0657-56 share a common merging scenario possibly just differing in the time elapsed after the closest cluster encounters. With this deeper XMM observation of A2163, we propose to refine our knowledge of the dynamics and geometry of the on-going subcluster accretion.

Rogue-wave bullets in a composite (2+1)D nonlinear medium.

PubMed

Chen, Shihua; Soto-Crespo, Jose M; Baronio, Fabio; Grelu, Philippe; Mihalache, Dumitru

2016-07-11

We show that nonlinear wave packets localized in two dimensions with characteristic rogue wave profiles can propagate in a third dimension with significant stability. This unique behavior makes these waves analogous to light bullets, with the additional feature that they propagate on a finite background. Bulletlike rogue-wave singlet and triplet are derived analytically from a composite (2+1)D nonlinear wave equation. The latter can be interpreted as the combination of two integrable (1+1)D models expressed in different dimensions, namely, the Hirota equation and the complex modified Korteweg-de Vries equation. Numerical simulations confirm that the generation of rogue-wave bullets can be observed in the presence of spontaneous modulation instability activated by quantum noise.

Lead and mercury in fall migrant golden eagles from western North America.

PubMed

Langner, Heiko W; Domenech, Robert; Slabe, Vincent A; Sullivan, Sean P

2015-07-01

Lead exposure from ingestion of bullet fragments is a serious environmental hazard to eagles. We determined blood lead levels (BLL) in 178 golden eagles (Aquila chrysaetos) captured during fall migration along a major North American flyway. These eagles spent the breeding season distributed over a large range and are the best currently available representation of free flying golden eagles on the continent. We found 58 % of these eagles containing increased BLL > 0.1 mg/L; 10 % were clinically lead poisoned with BLL > 0.6 mg/L; and 4 % were lethally exposed with BLL > 1.2 mg/L. No statistical difference in BLL existed between golden and bald eagles (Haliaeetus leucocephalus). Golden eagles captured on carrion had higher BLL than those captured using live bait suggesting differences in feeding habits among individuals. Median BLL increased with age class. We propose a conceptual model for the long-term increase in BLL after ingestion of lead particles. The mean blood mercury level in golden eagles was 0.023 mg/L. We evaluate a field test for BLL that is based on anodic stripping voltammetry. This cost-effective and immediate method correlated well with results from inductively coupled plasma-mass spectrometry, although results needed to be corrected for each calibration of the test kit.

The Impact of the Method of Gunshot Injury: War Injuries vs. Stray Bullets vs. Civilian Fighting.

PubMed

Mansor, Salah; Bodalal, Zuhir

2015-04-01

To analyze the impact of the method of Gunshot Injury (GSI) (i.e. war injuries, stray bullets, and civilian fighting) on patient morbidity and mortality. An observational study. Biostatistics Department of Al-Jalaa Hospital in Benghazi, Libya, from January to December 2011. Patients' records were analyzed with the method of gunshot injury as a classifying/comparative parameter. Age, gender, site of injury, receiving department, ICU admission, city of origin, length of stay, morbidity and mortality were determined and compared between the different methods of GSI. During the conflict, 1761 gunshot injuries were treated at the hospital. The method of injury was recorded for 62% (n=1096) of the cases and were classified under war injuries (72.2%, n=791), stray bullets (14.1%, n=155), and civilian fighting (13.7%, n=150). Nearly all the patients being treated for civilian fighting (98%, n=147) were males, (stray bullets, 82.6%, n=128, and war injuries 98.4%, n=778). Women were significantly less involved in a war injury (1.6%, n=13, p < 0.001). Stray bullets affected the younger age groups i.e. ² 19 years (26.5%, n=41) more than either fighting injuries (8%, n=12) or war injuries (11.8%, n=93, p < 0.001). Civilian fighting injuries (83.3%, n=125) mostly involved the 20-39 years age group (p < 0.001). Fighting wounds and stray bullets were more common in an urban (82.7%, n=124) rather than rural setting (p < 0.001); the same was true for stray bullets (76.8%, n = 119). The number of GSI's showed a close relationship with major events in society (i.e. military campaigns, celebration and civilian unrest). Significantly higher mortality rates were observed in civilian fighting injuries (7.7%, n=12, p=0.003) and stray bullets (10%, n=15, p=0.003) compared to general GSI's (5.2%, n=91) and war injuries (4.4%, n=35). Surgeons and general physicians need to be aware that GSI's differ in their salient features and outcome based on the method of injury.

Characterizing the interaction among bullet, body armor, and human and surrogate targets.

PubMed

Shen, Weixin; Niu, Yuqing; Bykanova, Lucy; Laurence, Peter; Link, Norman

2010-12-01

This study used a combined experimental and modeling approach to characterize and quantify the interaction among bullet, body armor, and human surrogate targets during the 10-1000 μs range that is crucial to evaluating the protective effectiveness of body armor against blunt injuries. Ballistic tests incorporating high-speed flash X-ray measurements were performed to acquire the deformations of bullets and body armor samples placed against ballistic clay and gelatin targets with images taken between 10 μs and 1 ms of the initial impact. Finite element models (FEMs) of bullet, armor, and gelatin and clay targets were developed with material parameters selected to best fit model calculations to the test measurements. FEMs of bullet and armor interactions were then assembled with a FEM of a human torso and FEMs of clay and gelatin blocks in the shape of a human torso to examine the effects of target material and geometry on the interaction. Test and simulation results revealed three distinct loading phases during the interaction. In the first phase, the bullet was significantly slowed in about 60 μs as it transferred a major portion of its energy into the body armor. In the second phase, fibers inside the armor were pulled toward the point of impact and kept on absorbing energy until about 100 μs after the initial impact when energy absorption reached its peak. In the third phase, the deformation on the armor's back face continued to grow and energies inside both armor and targets redistributed through wave propagation. The results indicated that armor deformation and energy absorption in the second and third phases were significantly affected by the material properties (density and stiffness) and geometrical characteristics (curvature and gap at the armor-target interface) of the targets. Valid surrogate targets for testing the ballistic resistance of the armor need to account for these factors and produce the same armor deformation and energy absorption as on a

Planar light bullets under conditions of second-harmonic generation.

PubMed

Sazonov, Sergey V; Mamaikin, Mikhail S; Komissarova, Maria V; Zakharova, Irina G

2017-08-01

We study solutions to second-harmonic-generation equations in two-dimensional media with anomalous dispersion. The analytical solution is obtained in an approximate form of the planar spatiotemporal two-component soliton by means of the averaged Lagrangian method. It is shown that a decrease in the amplitudes of both soliton components and an increase in the value of the transverse coordinate are accompanied by an increase in their temporal duration. Within this variational approach, we have managed to find a stability criterion for the light bullet and a period of oscillations of soliton parameters. Then, we use the obtained form as an initial configuration to carry out the direct numerical simulation of soliton dynamics. We demonstrate stable propagation of spatiotemporal solitons undergoing small oscillations predicted analytically for a long distance. The formation of a two-component light bullet is shown when we launch a pulse only at the fundamental frequency. In addition, we investigate the phase and group-velocity mismatch effects on the propagation of pulses.

Simulating direct shear tests with the Bullet physics library: A validation study.

PubMed

Izadi, Ehsan; Bezuijen, Adam

2018-01-01

This study focuses on the possible uses of physics engines, and more specifically the Bullet physics library, to simulate granular systems. Physics engines are employed extensively in the video gaming, animation and movie industries to create physically plausible scenes. They are designed to deliver a fast, stable, and optimal simulation of certain systems such as rigid bodies, soft bodies and fluids. This study focuses exclusively on simulating granular media in the context of rigid body dynamics with the Bullet physics library. The first step was to validate the results of the simulations of direct shear testing on uniform-sized metal beads on the basis of laboratory experiments. The difference in the average angle of mobilized frictions was found to be only 1.0°. In addition, a very close match was found between dilatancy in the laboratory samples and in the simulations. A comprehensive study was then conducted to determine the failure and post-failure mechanism. We conclude with the presentation of a simulation of a direct shear test on real soil which demonstrated that Bullet has all the capabilities needed to be used as software for simulating granular systems.

Virtual fragment preparation for computational fragment-based drug design.

PubMed

Ludington, Jennifer L

2015-01-01

Fragment-based drug design (FBDD) has become an important component of the drug discovery process. The use of fragments can accelerate both the search for a hit molecule and the development of that hit into a lead molecule for clinical testing. In addition to experimental methodologies for FBDD such as NMR and X-ray Crystallography screens, computational techniques are playing an increasingly important role. The success of the computational simulations is due in large part to how the database of virtual fragments is prepared. In order to prepare the fragments appropriately it is necessary to understand how FBDD differs from other approaches and the issues inherent in building up molecules from smaller fragment pieces. The ultimate goal of these calculations is to link two or more simulated fragments into a molecule that has an experimental binding affinity consistent with the additive predicted binding affinities of the virtual fragments. Computationally predicting binding affinities is a complex process, with many opportunities for introducing error. Therefore, care should be taken with the fragment preparation procedure to avoid introducing additional inaccuracies.This chapter is focused on the preparation process used to create a virtual fragment database. Several key issues of fragment preparation which affect the accuracy of binding affinity predictions are discussed. The first issue is the selection of the two-dimensional atomic structure of the virtual fragment. Although the particular usage of the fragment can affect this choice (i.e., whether the fragment will be used for calibration, binding site characterization, hit identification, or lead optimization), general factors such as synthetic accessibility, size, and flexibility are major considerations in selecting the 2D structure. Other aspects of preparing the virtual fragments for simulation are the generation of three-dimensional conformations and the assignment of the associated atomic point charges.

Cell adhesion during bullet motion in capillaries.

PubMed

Takeishi, Naoki; Imai, Yohsuke; Ishida, Shunichi; Omori, Toshihiro; Kamm, Roger D; Ishikawa, Takuji

2016-08-01

A numerical analysis is presented of cell adhesion in capillaries whose diameter is comparable to or smaller than that of the cell. In contrast to a large number of previous efforts on leukocyte and tumor cell rolling, much is still unknown about cell motion in capillaries. The solid and fluid mechanics of a cell in flow was coupled with a slip bond model of ligand-receptor interactions. When the size of a capillary was reduced, the cell always transitioned to "bullet-like" motion, with a consequent decrease in the velocity of the cell. A state diagram was obtained for various values of capillary diameter and receptor density. We found that bullet motion enables firm adhesion of a cell to the capillary wall even for a weak ligand-receptor binding. We also quantified effects of various parameters, including the dissociation rate constant, the spring constant, and the reactive compliance on the characteristics of cell motion. Our results suggest that even under the interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin, which is mainly responsible for leukocyte rolling, a cell is able to show firm adhesion in a small capillary. These findings may help in understanding such phenomena as leukocyte plugging and cancer metastasis. Copyright © 2016 the American Physiological Society.

Filamentation and light bullet formation dynamics in solid-state dielectric media with weak, moderate and strong anomalous group velocity dispersion

NASA Astrophysics Data System (ADS)

Gražulevičiūtė, I.; Garejev, N.; Majus, D.; Jukna, V.; Tamošauskas, G.; Dubietis, A.

2016-02-01

We present a series of measurements, which characterize filamentation dynamics of intense ultrashort laser pulses in the space-time domain, as captured by means of three-dimensional imaging technique in sapphire and fused silica, in the wavelength range of 1.45-2.25 μm, accessing the regimes of weak, moderate and strong anomalous group velocity dispersion (GVD). In the regime of weak anomalous GVD (at 1.45 μm), pulse splitting into two sub-pulses producing a pair of light bullets with spectrally shifted carrier frequencies in both nonlinear media is observed. In contrast, in the regimes of moderate (at 1.8 μm) and strong (at 2.25 μm) anomalous GVD we observe notably different transient dynamics, which however lead to the formation of a single self-compressed quasistationary light bullet with an universal spatiotemporal shape comprised of an extended ring-shaped periphery and a localized intense core that carries the self-compressed pulse.

3. NORTHEAST SIDE, WITH A SINGLE BULLET GLASS WINDOW AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. NORTHEAST SIDE, WITH A SINGLE BULLET GLASS WINDOW AND SOUTHEAST REAR WITH ENTRY DOOR. - Edwards Air Force Base, South Base Sled Track, Observation Block House, Station "O" area, east end of Sled Track, Lancaster, Los Angeles County, CA

Light bullets in transparent dielectrics

NASA Astrophysics Data System (ADS)

Kandidov, Valerii; Chekalin, Sergey; Kompanets, Victor; Dormidonov, Alexander

2017-10-01

The state of research of the light bullets (LB) formation in the process of femtosecond laser pulse filamentation is presented. LB is a near single-cycle wave packet that is formed in the result of the light field self-organization in a nonlinear dispersive medium under matched spatiotemporal radiation self-compression in the regime of anomalous group-velocity dispersion (GVD). The formation of each LB is accompanied by the generation of a discrete portion of supercontinuum (SC) in the anti-Stokes region. LB is a short-lived robust object with parameters determined by fundamental properties of the medium and the laser pulse central wavelength.

Fragment informatics and computational fragment-based drug design: an overview and update.

PubMed

Sheng, Chunquan; Zhang, Wannian

2013-05-01

Fragment-based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment-based cheminformatics tools, high-throughput fragment docking, and fragment-based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research. © 2012 Wiley Periodicals, Inc.

[Fragment-based drug discovery: concept and aim].

PubMed

Tanaka, Daisuke

2010-03-01

Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically <300 Da), have not been employed in conventional high-throughput screening (HTS), the recent significant progress in the biophysical screening methods enables fragment screening at a practical level. The intention of FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to "undruggable targets" (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.

Magma Fragmentation

NASA Astrophysics Data System (ADS)

Gonnermann, Helge M.

2015-05-01

Magma fragmentation is the breakup of a continuous volume of molten rock into discrete pieces, called pyroclasts. Because magma contains bubbles of compressible magmatic volatiles, decompression of low-viscosity magma leads to rapid expansion. The magma is torn into fragments, as it is stretched into hydrodynamically unstable sheets and filaments. If the magma is highly viscous, resistance to bubble growth will instead lead to excess gas pressure and the magma will deform viscoelastically by fracturing like a glassy solid, resulting in the formation of a violently expanding gas-pyroclast mixture. In either case, fragmentation represents the conversion of potential energy into the surface energy of the newly created fragments and the kinetic energy of the expanding gas-pyroclast mixture. If magma comes into contact with external water, the conversion of thermal energy will vaporize water and quench magma at the melt-water interface, thus creating dynamic stresses that cause fragmentation and the release of kinetic energy. Lastly, shear deformation of highly viscous magma may cause brittle fractures and release seismic energy.

Thermophysiological responses caused by ballistic bullet-proof vests.

PubMed

Lehmacher, E J; Jansing, P; Küpper, T

2007-01-01

Little data is available concerning the heat stress experienced by members of staff who wear bullet-proof vests in a warm or hot environment. For this reason, knowledge is limited and, consequently, preventative advice on how to avoid heat sickness or hyperthermia is required. Skin and body temperatures, fluid loss and the heart rate of 30 persons (15 test persons versus 15 control persons) were measured in three situations typical of the test participants' job situations. Environmental data (wind velocity, air humidity, air temperature) were measured during the tests as well. Whereas there was a significant increase in skin temperatures, there was no difference in the core body temperatures of both groups. Maximum core body temperature remained well below 38 degrees C in all subjects. Test persons wearing vests showed a fluid loss of 1.1 l on average (non-vest wearers in the control group 1.0 l). There is no increased risk of heat stroke or hyperthermia for employees wearing bullet-proof vests in comparison with employees who do not wear them. Both groups, however, should be advised to ensure an adequate intake of fluid to maintain a healthy body fluid balance when working in hot environments.

7. BULLET GLASS OBSERVATION WINDOW AT GROUND LEVEL ON WEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. BULLET GLASS OBSERVATION WINDOW AT GROUND LEVEL ON WEST REAR. - Edwards Air Force Base, South Base Sled Track, Firing & Control Blockhouse for 10,000-foot Track, South of Sled Track at midpoint of 20,000-foot track, Lancaster, Los Angeles County, CA

Demonstrating the effect of forensic firearm countermeasures: Bullet characteristics generated due to barrel modifications.

PubMed

O'Keeffe, C; Champion, S; Allsop, D

2015-12-01

Forensic awareness and the declining availability of firearms have resulted in an increase in the use of modified and re-activated firearms in crime. Although some modifications are undertaken to simply acquire a functioning firearm, others are perpetrated as a direct forensic countermeasure to prevent the association between a firearm and a crime. This article describes the effects of these modifications on bullet striation patterns imparted from the barrel to a fired bullet. The key results indicated that the investigated modifications display assessable characteristics. The use of an oversized barrel imparted striations consistent with firing with the absence of typical rifling. Subsequent or consecutively fired bullets possessed striation variations, with the first showing the least evidence of striations. The application of a choke resulted in more obvious bullet elongation compared to a smoothbore barrel. The restriction caused merging of lands and groves of the imparted rifling and obscured their usual definition. Effects of breech adaption were also characterised by observing the buckling and enlargement of the cartridge case. This deformity of the cartridge case was most evident when the barrel pressure increased due to the presence of the choke. From this study it was evident that unique characteristic impressions associated with different modifications most commonly found in criminal investigations can be utilised by a forensic expert and impart significant intelligence to an investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Entrance and exit wounds of high velocity bullet: An autopsy analysis in the event of dispersing the mass rally in Bangkok Thailand, May 2010.

PubMed

Peonim, Vichan; Srisont, Smith; Udnoon, Jitta; Wongwichai, Sompong; Thapon, Arisa; Worasuwannarak, Wisarn

2016-11-01

Fatal mass casualties by high velocity bullets (HVBs) are rare events in peaceful countries. This study presents 27 forensic autopsy cases with 32 shots fired by 5.56×45mm. HVB (M-16 rifle bullets) during the dispersing the mass rally in Bangkok Thailand, May 2010. It was found that twenty-three (71.88%) typical entrance HVB wounds had round sizes less than the bullet diameters. Most entrance wounds had microtears but no collar abrasion since a HVB has a small streamlined spitzer tip and full metal jacket. For exit wounds, there were various sizes and shapes depending on which section of wound ballistics presented when the bullet exited the body. If a bullet exited in the section of temporally cavity formation, there would be a large size exit wound in accordance with the degree of bullet yaw. This is different from civilian bullets whereby the shape looks like a cylindrical round nose and at low velocity that causes entrance wounds with a similar size to the bullet diameter and is usually round or oval shape with collar abrasion. The temporary cavity is not as large as in a HVB so exit wounds are not quite as large and present a ragged border compared to a HVB. We also reported 9 out of 32 shots (28.13%) of atypical entrance wounds that had various characteristics depending on site of injury and destabilization of bullets. These findings may be helpful to forensic pathologists and to give physicians, who need to diagnose HVB wounds, more confidence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dissecting fragment-based lead discovery at the von Hippel-Lindau protein:hypoxia inducible factor 1α protein-protein interface.

PubMed

Van Molle, Inge; Thomann, Andreas; Buckley, Dennis L; So, Ernest C; Lang, Steffen; Crews, Craig M; Ciulli, Alessio

2012-10-26

Fragment screening is widely used to identify attractive starting points for drug design. However, its potential and limitations to assess the tractability of often challenging protein:protein interfaces have been underexplored. Here, we address this question by means of a systematic deconstruction of lead-like inhibitors of the pVHL:HIF-1α interaction into their component fragments. Using biophysical techniques commonly employed for screening, we could only detect binding of fragments that violate the Rule of Three, are more complex than those typically screened against classical druggable targets, and occupy two adjacent binding subsites at the interface rather than just one. Analyses based on ligand and group lipophilicity efficiency of anchored fragments were applied to dissect the individual subsites and probe for binding hot spots. The implications of our findings for targeting protein interfaces by fragment-based approaches are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Confluence or independence of microwave plasma bullets in atmospheric argon plasma jet plumes

NASA Astrophysics Data System (ADS)

Li, Ping; Chen, Zhaoquan; Mu, Haibao; Xu, Guimin; Yao, Congwei; Sun, Anbang; Zhou, Yuming; Zhang, Guanjun

2018-03-01

Plasma bullet is the formation and propagation of a guided ionization wave (streamer), normally generated in atmospheric pressure plasma jet (APPJ). In most cases, only an ionization front produces in a dielectric tube. The present study shows that two or three ionization fronts can be generated in a single quartz tube by using a microwave coaxial resonator. The argon APPJ plumes with a maximum length of 170 mm can be driven by continuous microwaves or microwave pulses. When the input power is higher than 90 W, two or three ionization fronts propagate independently at first; thereafter, they confluence to form a central plasma jet plume. On the other hand, the plasma bullets move independently as the lower input power is applied. For pulsed microwave discharges, the discharge images captured by a fast camera show the ionization process in detail. Another interesting finding is that the strongest lightening plasma jet plumes always appear at the shrinking phase. Both the discharge images and electromagnetic simulations suggest that the confluence or independent propagation of plasma bullets is resonantly excited by the local enhanced electric fields, in terms of wave modes of traveling surface plasmon polaritons.

The weathering and transformation process of lead in China's shooting ranges.

PubMed

Li, Yeling; Zhu, Yongbing; Zhao, Sanping; Liu, Xiaodong

2015-09-01

Corroding steel-core bullets from three shooting ranges in different climate zones of China were collected. Multiple technical methods (EMPA, SEM, XRD, and ICP-OES) were applied to investigate the structure, morphology, and weathering product of this type of bullet in China to analyze the weathering mechanisms in different types of soils. A scanning electron microscope (SEM) was used to view the morphology and microstructure of corrosion layers. On the corroded lead layer surface, unevenness, micro cracks, and spallation were usually present. Around the micro cracks, many types of euhedral and subhedral crystals of the secondary products of lead were formed, most of which were composed of cerussite (PbCO3), while hydrocerussite (Pb3(CO3)2(OH)2) was predominant in the bullet collected from the humid environment. X-ray power diffraction (XRD) results show that the secondary weathering products in the three shooting range soils are clearly different. In the Fangyan shooting range, which has a neutral and semi-arid soil, the lead weathering product was mainly hydrocerussite (Pb3(CO3)2(OH)2), while no substantial amount of crystal phase of lead compound could be found in acidic, damp soils from the Fenghuang shooting range, possibly due to the enhanced dissolution and mobilization of lead compounds at lower pH and higher content of organic matter in the soil. In hot and arid environment of the Baicheng shooting range, cerussite might have undergone thermal decomposition, thus generating shannonite (Pb2O(CO3)). These results indicate that the formation of secondary Pb minerals is largely affected by the climatic zone or the soil properties, which may have implications for range management practices.

Identification of potential glutaminyl cyclase inhibitors from lead-like libraries by in silico and in vitro fragment-based screening.

PubMed

Szaszkó, Mária; Hajdú, István; Flachner, Beáta; Dobi, Krisztina; Magyar, Csaba; Simon, István; Lőrincz, Zsolt; Kapui, Zoltán; Pázmány, Tamás; Cseh, Sándor; Dormán, György

2017-02-01

A glutaminyl cyclase (QC) fragment library was in silico selected by disconnection of the structure of known QC inhibitors and by lead-like 2D virtual screening of the same set. The resulting fragment library (204 compounds) was acquired from commercial suppliers and pre-screened by differential scanning fluorimetry followed by functional in vitro assays. In this way, 10 fragment hits were identified ([Formula: see text]5 % hit rate, best inhibitory activity: 16 [Formula: see text]). The in vitro hits were then docked to the active site of QC, and the best scoring compounds were analyzed for binding interactions. Two fragments bound to different regions in a complementary manner, and thus, linking those fragments offered a rational strategy to generate novel QC inhibitors. Based on the structure of the virtual linked fragment, a 77-membered QC target focused library was selected from vendor databases and docked to the active site of QC. A PubChem search confirmed that the best scoring analogues are novel, potential QC inhibitors.

Automatic identification of bullet signatures based on consecutive matching striae (CMS) criteria.

PubMed

Chu, Wei; Thompson, Robert M; Song, John; Vorburger, Theodore V

2013-09-10

The consecutive matching striae (CMS) numeric criteria for firearm and toolmark identifications have been widely accepted by forensic examiners, although there have been questions concerning its observer subjectivity and limited statistical support. In this paper, based on signal processing and extraction, a model for the automatic and objective counting of CMS is proposed. The position and shape information of the striae on the bullet land is represented by a feature profile, which is used for determining the CMS number automatically. Rapid counting of CMS number provides a basis for ballistics correlations with large databases and further statistical and probability analysis. Experimental results in this report using bullets fired from ten consecutively manufactured barrels support this developed model. Published by Elsevier Ireland Ltd.

Coal-Gen attendees hear there's no magic bullet

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2007-09-15

Those attending COAL-GEN 2007 in August heard that there is no magic bullet for meeting the energy and infrastructure needs facing the USA. The article reports on the conference which addressed topics including development of supercritical circulating fluidized bed coal unit; IGCC projects, the importance of including carbon capture and sequestration, and the need to attract and train personnel to work in the power industry. 3 photos.

Science Fair Projects. LC Science Tracer Bullet. TB 07-6

ERIC Educational Resources Information Center

Howland, Joyce, Comp.

2007-01-01

Selected sources in this bibliography provide guidance to students, parents, and teachers throughout the process of planning, developing, implementing and competing in science fair activities. Sources range in suitability from elementary to high school levels. This guide updates "Library of Congress Science Tracer Bullet" 01-4. More specialized…

Fragment-based drug design.

PubMed

Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H

2011-01-01

Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process.

Formation and dynamics of plasma bullets in a non-thermal plasma jet: influence of the high-voltage parameters on the plume characteristics

NASA Astrophysics Data System (ADS)

Jarrige, Julien; Laroussi, Mounir; Karakas, Erdinc

2010-12-01

Non-thermal plasma jets in open air are composed of ionization waves commonly known as 'plasma bullets' propagating at high velocities. We present in this paper an experimental study of plasma bullets produced in a dielectric barrier discharge linear-field reactor fed with helium and driven by microsecond high-voltage pulses. Two discharges were produced between electrodes for every pulse (at the rising and falling edge), but only one bullet was generated. Fast intensified charge coupled device camera imaging showed that bullet velocity and diameter increase with applied voltage. Spatially resolved optical emission spectroscopy measurements provided evidence of the hollow structure of the jet and its contraction. It was shown that the pulse amplitude significantly enhances electron energy and production of active species. The plasma bullet appeared to behave like a surface discharge in the tube, and like a positive streamer in air. A kinetics mechanism based on electron impact, Penning effect and charge transfer reactions is proposed to explain the propagation of the ionization front and temporal behavior of the radiative species.

Hydrodynamics of back spatter by blunt bullet gunshot with a link to bloodstain pattern analysis

NASA Astrophysics Data System (ADS)

Comiskey, P. M.; Yarin, A. L.; Attinger, D.

2017-07-01

A theoretical model describing the blood spatter pattern resulting from a blunt bullet gunshot is proposed. The predictions are compared to experimental data acquired in the present work. This hydrodynamic problem belongs to the class of the impact hydrodynamics with the pressure impulse generating the blood flow. At the free surface, the latter is directed outwards and accelerated toward the surrounding air. As a result, the Rayleigh-Taylor instability of the flow of blood occurs, which is responsible for the formation of blood drops of different sizes and initial velocities. Thus, the initial diameter, velocity, and acceleration of the atomized blood drops can be determined. Then, the equations of motion are solved, describing drop trajectories in air accounting for gravity, and air drag. Also considered are the drop-drop interactions through air, which diminish air drag on the subsequent drops. Accordingly, deposition of two-phase (blood-drop and air) jets on a vertical cardstock sheet located between the shooter and the target (and perforated by the bullet) is predicted and compared with experimental data. The experimental data were acquired with a porous polyurethane foam sheet target impregnated with swine blood, and the blood drops were collected on a vertical cardstock sheet which was perforated by the blunt bullet. The highly porous target possesses a low hydraulic resistance and therefore resembles a pool of blood shot by a blunt bullet normally to its free surface. The back spatter pattern was predicted numerically and compared to the experimental data for the number of drops, their area, the total stain area, and the final impact angle as functions of radial location from the bullet hole in the cardstock sheet (the collection screen). Comparisons of the predicted results with the experimental data revealed satisfactory agreement. The predictions also allow one to find the impact Weber number on the collection screen, which is necessary to predict stain

Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and Fragmentation During Rosette Formation in Fuchs Endothelial Corneal Dystrophy

PubMed Central

Halilovic, Adna; Schmedt, Thore; Benischke, Anne-Sophie; Hamill, Cecily; Chen, Yuming; Santos, Janine Hertzog

2016-01-01

Abstract Aims: Fuchs endothelial corneal dystrophy (FECD), a leading cause of age-related corneal edema requiring transplantation, is characterized by rosette formation of corneal endothelium with ensuing apoptosis. We sought to determine whether excess of mitochondrial reactive oxygen species leads to chronic accumulation of oxidative DNA damage and mitochondrial dysfunction, instigating cell death. Results: We modeled the pathognomonic rosette formation of postmitotic corneal cells by increasing endogenous cellular oxidative stress with menadione (MN) and performed a temporal analysis of its effect in normal (HCEnC, HCECi) and FECD (FECDi) cells and ex vivo specimens. FECDi and FECD ex vivo specimens exhibited extensive mtDNA and nDNA damage as detected by quantitative PCR. Exposure to MN triggered an increase in mitochondrial superoxide levels and led to mtDNA and nDNA damage, while DNA amplification was restored with NAC pretreatment. Furthermore, MN exposure led to a decrease in ΔΨm and adenosine triphosphate levels in normal cells, while FECDi exhibited mitochondrial dysfunction at baseline. Mitochondrial fragmentation and cytochrome c release were detected in FECD tissue and after MN treatment of HCEnCs. Furthermore, cleavage of caspase-9 and caspase-3 followed MN-induced cytochrome c release in HCEnCs. Innovation: This study provides the first line of evidence that accumulation of oxidative DNA damage leads to rosette formation, loss of functionally intact mitochondria via fragmentation, and subsequent cell death during postmitotic cell degeneration of ocular tissue. Conclusion: MN induced rosette formation, along with mtDNA and nDNA damage, mitochondrial dysfunction, and fragmentation, leading to activation of the intrinsic apoptosis via caspase cleavage and cytochrome c release. Antioxid. Redox Signal. 24, 1072–1083. PMID:26935406

Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and Fragmentation During Rosette Formation in Fuchs Endothelial Corneal Dystrophy.

PubMed

Halilovic, Adna; Schmedt, Thore; Benischke, Anne-Sophie; Hamill, Cecily; Chen, Yuming; Santos, Janine Hertzog; Jurkunas, Ula V

2016-06-20

Fuchs endothelial corneal dystrophy (FECD), a leading cause of age-related corneal edema requiring transplantation, is characterized by rosette formation of corneal endothelium with ensuing apoptosis. We sought to determine whether excess of mitochondrial reactive oxygen species leads to chronic accumulation of oxidative DNA damage and mitochondrial dysfunction, instigating cell death. We modeled the pathognomonic rosette formation of postmitotic corneal cells by increasing endogenous cellular oxidative stress with menadione (MN) and performed a temporal analysis of its effect in normal (HCEnC, HCECi) and FECD (FECDi) cells and ex vivo specimens. FECDi and FECD ex vivo specimens exhibited extensive mtDNA and nDNA damage as detected by quantitative PCR. Exposure to MN triggered an increase in mitochondrial superoxide levels and led to mtDNA and nDNA damage, while DNA amplification was restored with NAC pretreatment. Furthermore, MN exposure led to a decrease in ΔΨm and adenosine triphosphate levels in normal cells, while FECDi exhibited mitochondrial dysfunction at baseline. Mitochondrial fragmentation and cytochrome c release were detected in FECD tissue and after MN treatment of HCEnCs. Furthermore, cleavage of caspase-9 and caspase-3 followed MN-induced cytochrome c release in HCEnCs. This study provides the first line of evidence that accumulation of oxidative DNA damage leads to rosette formation, loss of functionally intact mitochondria via fragmentation, and subsequent cell death during postmitotic cell degeneration of ocular tissue. MN induced rosette formation, along with mtDNA and nDNA damage, mitochondrial dysfunction, and fragmentation, leading to activation of the intrinsic apoptosis via caspase cleavage and cytochrome c release. Antioxid. Redox Signal. 24, 1072-1083.

3D-MSCT imaging of bullet trajectory in 3D crime scene reconstruction: two case reports.

PubMed

Colard, T; Delannoy, Y; Bresson, F; Marechal, C; Raul, J S; Hedouin, V

2013-11-01

Postmortem investigations are increasingly assisted by three-dimensional multi-slice computed tomography (3D-MSCT) and have become more available to forensic pathologists over the past 20years. In cases of ballistic wounds, 3D-MSCT can provide an accurate description of the bullet location, bone fractures and, more interestingly, a clear visual of the intracorporeal trajectory (bullet track). These forensic medical examinations can be combined with tridimensional bullet trajectory reconstructions created by forensic ballistic experts. These case reports present the implementation of tridimensional methods and the results of 3D crime scene reconstruction in two cases. The authors highlight the value of collaborations between police forensic experts and forensic medicine institutes through the incorporation of 3D-MSCT data in a crime scene reconstruction, which is of great interest in forensic science as a clear visual communication tool between experts and the court. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Fragment growing and linking lead to novel nanomolar lactate dehydrogenase inhibitors.

PubMed

Kohlmann, Anna; Zech, Stephan G; Li, Feng; Zhou, Tianjun; Squillace, Rachel M; Commodore, Lois; Greenfield, Matthew T; Lu, Xiaohui; Miller, David P; Huang, Wei-Sheng; Qi, Jiwei; Thomas, R Mathew; Wang, Yihan; Zhang, Sen; Dodd, Rory; Liu, Shuangying; Xu, Rongsong; Xu, Yongjin; Miret, Juan J; Rivera, Victor; Clackson, Tim; Shakespeare, William C; Zhu, Xiaotian; Dalgarno, David C

2013-02-14

Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway. Cancer cells rely heavily on glycolysis instead of oxidative phosphorylation to generate ATP, a phenomenon known as the Warburg effect. The inhibition of LDH-A by small molecules is therefore of interest for potential cancer treatments. We describe the identification and optimization of LDH-A inhibitors by fragment-based drug discovery. We applied ligand based NMR screening to identify low affinity fragments binding to LDH-A. The dissociation constants (K(d)) and enzyme inhibition (IC(50)) of fragment hits were measured by surface plasmon resonance (SPR) and enzyme assays, respectively. The binding modes of selected fragments were investigated by X-ray crystallography. Fragment growing and linking, followed by chemical optimization, resulted in nanomolar LDH-A inhibitors that demonstrated stoichiometric binding to LDH-A. Selected molecules inhibited lactate production in cells, suggesting target-specific inhibition in cancer cell lines.

Atypical gunshot injury to the right side of the face with the bullet lodged in the carotid sheath: a case report.

PubMed

Ongom, Peter A; Kijjambu, Stephen C; Jombwe, Josephat

2014-01-27

Gunshot injuries of the head and neck from the AK-47 rifle (a common assault rifle, submachine gun type) are a significant contributor to morbidity and mortality among civilians in Sub-Saharan Africa. They may cause significant damage to the closely arranged structures in this region, and the bullet's trajectory can be very difficult to determine. We present an unusual case of gunshot injury with an atypical bullet entry wound, profound injury to the face, lodgment in the right carotid sheath, and 'wandering'; a first of its kind in East Africa. A 27-year-old African-Ugandan woman of Nilotic ethnicity was referred to the Accident and Emergency Department of a tertiary hospital in Uganda, having sustained complex injuries due to an inadvertent AK-47 rifle gunshot injury. The gunshot injury was to the right side of her face with a large ragged entry wound and no exit wound. Prior basic wound care and radiological imaging showed a comminuted fracture of her mandible with lodgment of the bullet in her neck, anterior to her sixth and seventh cervical vertebrae. Standard debridement of her wound was done. A computed tomography scan showed an apparent cephalad shift ('wandering') of the bullet, leaving it lying partially anterior to her fifth cervical vertebra as well as within her carotid sheath. Other injuries were to her facial and trigeminal nerves, and her middle ear. The 'wandering' bullet was successfully removed surgically. It had caused no damage to any part of her neck structure. AK-47 rifle bullet injuries may present with uncharacteristically large entry wounds and cause complex structural injuries at the area of impact. The consequent trajectory is difficult to predict making regional examination and radiological investigations essential in management. Bullets may be retained, leaving no exit wound. Securing the airway, controlling hemorrhage and identifying other injuries are the first vital steps. This case illustrates all these interventions and the

Facial fractures caused by less-lethal rubber bullet weapons: case series report and literature review.

PubMed

Amaral, Marcio Bruno Figueiredo; Bueno, Sebastião Cristian; Abdala, Icaro Buchholz; da Silveira, Roger Lanes

2017-09-01

The present study aims to describe three cases of patients inflicted by rubber bullets with severe facial fractures. In addition, a review of English-language literature involving facial fractures by rubber bullets from 1975 to 2016 was performed. This current study demonstrated that the use of the LLRBW is unsafety even when applied by police enforcements exclusively. Management of facial fractures caused by LLRBW is done in a usual manner with closed or open reduction associated with bone mini-plates or reconstruction plates when indicated. Special initial wound care should be done to avoid secondary infection and additional procedures.

Increasing Small Arms Lethality in Afghanistan Taking Back the Infantry Half-Kilometer

DTIC Science & Technology

2009-05-21

John A. Malinowski , and Robert E. Bowen. "Bullet Fragmentation: A Major Cause of Tissue Disruption." JTrauma, 1984: 35-39. 67 Initial muzzle...Fackler, Martin L, M.D., M.A. John S. Surinchak, B.S. John A. Malinowski , and Robert E. Bowen. "Bullet Fragmentation: A Major Cause of Tissue

Suspected lead poisoning in two captive cheetahs (Acinonyx jubatus jubatus) in South Africa, in 2008 and 2013.

PubMed

North, Michelle A; Lane, Emily P; Marnewick, Kelly; Caldwell, Peter; Carlisle, Glen; Hoffman, Louw C

2015-08-13

Whilst lead poisoning in raptors, scavenging birds and waterfowl is well studied and common knowledge, there is surprisingly little literature detailing the risk to mammalian scavengers and captive carnivores fed hunted meat. This case report describes the death of two captive cheetahs (Acinonyx jubatus jubatus) following acute onset of nervous symptoms. Clinical signs included hyper-excitability, seizures, arched back, tail held abnormally high and hyper-salivation. Necropsy findings included bullets or a bullet in their stomachs. Kidney and liver lead levels from one cheetah (15.6 ppm and 17 ppm respectively) were consistent with a diagnosis of lead poisoning; liver from the second cheetah was not available for testing. Both animals were routinely fed hunted antelope or game birds. This is the first report of oral lead poisoning in captive large carnivores, although these are unlikely to be the first cases. Without awareness of the risks of feeding hunted game, lead exposure will continue to be an underdiagnosed reality in the rehabilitation of endangered carnivores.

Path length and spectrum of single-cycle mid-IR light bullets in transparent dielectrics

NASA Astrophysics Data System (ADS)

Chekalin, S. V.; Kompanets, V. O.; Dormidonov, A. E.; Kandidov, V. P.

2018-04-01

Filamentation of femtosecond laser radiation with a wavelength of 800 – 3900 nm and a power slightly exceeding the critical self-focusing power is studied using the spectral method and the method of laser coloration in LiF crystal. It is found that the length of a filament formed in the single-pulse regime increases with increasing excitation wavelength from a few tens of micrometres at 80 nm to hundreds of micrometres at 3900 nm. In the spectral region of anomalous group velocity dispersion, starting from 2600 nm, the initially smooth luminescence profile of the long-lived induced colour centres acquires a periodic structure, demonstrating the formation of a light bullet with a duration of about one cycle of the light field oscillation and a diameter smaller than 10 μm. The path length of such bullets does not exceed 0.5 mm in the single-pulse regime and 2.7 mm in the waveguide regime. A consequence of periodic modulation of the bullet light field in the process of propagation, observed experimentally and confirmed by calculations, is the appearance of sidebands near the excitation wavelength, as well as the appearance of visible spectral components in the supercontinuum radiation, whose angular divergence increases with increasing wavelength.

Firearm suicide committed using an unusual combination of tandem missiles: a bullet, a nail, and a screw.

PubMed

Mihailovic, Zoran; Savic, Slobodan; Atanasijevic, Tatjana

2007-09-01

An interesting case of firearm suicide carried out using an unusual type of handmade weapon and a peculiar combination of tandem missiles is presented. A nail and a screw were placed in the rifle barrel ahead of a bullet, and all 3 were simultaneously discharged. The inflicted injury began with 1 common channel, which later split in 2 separate channels, both directed backwards and upwards; one was caused by the screw, ending in the epistropheal body, and the other, caused by the bullet and the nail, penetrated into the cranial cavity, where it bifurcated in 2 branches, one from the bullet, ending in the cerebellar tissue, and the other from the nail, penetrated through the brain stem. The established site of the entrance suicidal wound, the appearance of the weapon, and the unusual missiles are discussed with regard to the available references dealing with different types of nail injuries to the head.

Bone-patch type secondary projectiles: A report on two shots fired at point-blank range using hollow point bullets.

PubMed

Malbranque, S; Jousset, N; Nedelcu, C; Rougé-Maillart, C

2014-12-01

The number of head wounds due to firearms remains low in France because these cases are primarily linked to suicide (or attempted suicide) and, to a lesser extent, to attacks or hunting accidents [1]. Characterized by the impact of a projectile, which in most cases is made of metal, at high levels of kinetic energy, such acts generally result in severe trans-cerebral lesions with significant levels of morbidity/mortality [2]. Seldom are cases reported in the literature that give a detailed study of intracranial foreign bodies made of bone in such situations [3]. Here we report on the case of two suicides resulting from a transcranial gunshot wounds caused by weapons and ammunition issued by the French police force. Each case helped distinguish a characteristic bone fragment, in the form of a "patch", equivalent in size to the caliber of the bullet. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Blunt trauma with bullet-proof vests. Skin lesions are no reliable predictor of injury severity].

PubMed

Doll, D; Illert, B; Bohrer, S; Richter, C; Woelfl, C

2009-04-01

It is well known that so-called bullet-proof vests offer protection against a wide range of penetrating trauma, but their protection against blunt trauma is less well understood. Fast projectiles may result in hematomas and contusions behind the armour. We report a traffic accident involving a young soldier wearing a ballistic protection vest resulting in a right thoracoabdominal blunt trauma leading to a confined liver compression rupture. As nearly no skin marks were detectable, we point out that every emergency department surgeon should be very suspicious if a patient wore a ballistic vest at the time of the accident--there may be no skin marks despite severe intra-abdominal trauma. Our patient recovered following hypotensive ICU treatment, thrombocyte mobilization, and factor VIIa substitution.

Impacted thoracic foreign bodies after penetrating chest trauma.

PubMed

Sersar, Sameh I; Albohiri, Khalid A; Abdelmohty, Hysam

2016-10-01

Retained foreign bodies in the chest may include shell fragments, bullets, shrapnel, pieces of clothing, bones, and rib fragments. The risks of removal of foreign bodies must be weighed against the complications of leaving them inside the chest. We treated 90 cases of retained intrathoracic foreign bodies in patients admitted to 3 tertiary centers in Saudi Arabia between March 2015 and March 2016. Sixty patients were injured by shrapnel, 26 had one or more bullets, 3 had broken rib fragments, and one had a metal screw. The chest wall was site of impaction in 48 cases, the lungs in 24, pleura in 14, and mediastinum in 4. Removal of the retained foreign body was carried out in 12 patients only: bullets in 9 cases, bone fragments in 2, and a metal screw in one. The predictors for removal were bullets, female sex, and mediastinal position with bilateral chest injury, especially with fracture ribs. Retained intrathoracic foreign bodies due to penetrating chest trauma are treated mainly conservatively unless there is another indication for chest exploration. © The Author(s) 2016.

Fragment-based approaches to TB drugs.

PubMed

Marchetti, Chiara; Chan, Daniel S H; Coyne, Anthony G; Abell, Chris

2018-02-01

Tuberculosis is an infectious disease associated with significant mortality and morbidity worldwide, particularly in developing countries. The rise of antibiotic resistance in Mycobacterium tuberculosis (Mtb) urgently demands the development of new drug leads to tackle resistant strains. Fragment-based methods have recently emerged at the forefront of pharmaceutical development as a means to generate more effective lead structures, via the identification of fragment molecules that form weak but high quality interactions with the target biomolecule and subsequent fragment optimization. This review highlights a number of novel inhibitors of Mtb targets that have been developed through fragment-based approaches in recent years.

Lead particle size and its association with firing conditions and range maintenance: implications for treatment.

PubMed

Dermatas, Dimitris; Chrysochoou, Maria

2007-08-01

Six firing range soils were analyzed, representing different environments, firing conditions, and maintenance practices. The particle size distribution and lead (Pb) concentration in each soil fraction were determined for samples obtained from the backstop berms. The main factors that were found to influence Pb fragment size were the type of soil used to construct the berms and the type of weapon fired. The firing of high velocity weapons, i.e., rifles, onto highly angular soils induced significant fragmentation of the bullets and/or pulverization of the soil itself. This resulted in the accumulation of Pb in the finer soil fractions and the spread of Pb contamination beyond the vicinity of the backstop berm. Conversely, the use of clay as backstop and the use of low velocity pistols proved to be favorable for soil clean-up and range maintenance, since Pb was mainly present as large metallic fragments that can be recovered by a simple screening process. Other factors that played important roles in Pb particle size distribution were soil chemistry, firing distance, and maintenance practices, such as the use of water spray for dust suppression and deflectors prior to impact. Overall, coarse Pb particles provide much easier and more cost-effective maintenance, soil clean-up, and remediation via physical separation. Fine Pb particles release Pb more easily, pose an airborne Pb hazard, and require the application of stabilization/solidification treatment methods. Thus, to ensure sustainable firing range operations by means of cost-effective design, maintenance, and clean-up, especially when high velocity weapons are used, the above mentioned factors should be carefully considered.

High-Speed Bullet Ejections during the AGB to Planetary Nebula Transition: A Study of the Carbon Star V Hydrae

NASA Astrophysics Data System (ADS)

Sahai, Raghvendra

2017-08-01

The carbon star V Hya is experiencing heavy mass loss as it undergoes the transition from an AGB star to a planetary nebula (PN). This is possibly the earliest object known in this brief phase, which is so short that few nearby stars are likely to be caught in the act. Molecular observations reveal that a bipolar nebula has been established even at this early stage. Using STIS, we obtained high spatial-resolution long-slit optical spectra of V Hya spanning 3 epochs spaced apart by a year during each of two periods (2002-2004, 2011-2013). These data reveal high-velocity emission in [SII] lines from compact blobs located both on- and off-source, with the ejection axis executing a flip-flop, both in, and perpendicular to, the sky-plane. We have proposed a detailed model in which V Hya ejects high-speed (200-250 km/s) bullets once every 8.5 yr associated with periastron passage of a binary companion in an eccentric orbit with an 8.5 yr period. We suggest that the jet driver is an accretion disk (produced by gravitational capture of material from the primary) that is warped and precessing. Our model predicts the locations of previously ejected bullets in V Hya and future epochs at which new bullets will emerge. We now propose new STIS observations of these remarkable bullet ejections over two new epochs well separated from previous ones, to robustly test our model. The proposed observations will provide us with an unprecedented opportunity to look on as V Hya's circumstellar envelope is sculpted by these bullets. Our study will help solve the long-standing puzzle of how the spherical mass-loss envelopes of AGB stars evolve into bipolar and multipolar PNe.

Direction, site and the muzzle target distance of bullet in the head and neck at close range as an indication of suicide or homicide.

PubMed

Suwanjutha, T

1988-05-01

Direction, site and muzzle target distance can indicate suicide or homicide. This conclusion can be drawn from autopsies of 57 cases of suicide and 68 cases of homicide by handgun fired at close range to the head and neck together with going to the crimescene in some cases. This study was carried out in Bangkok during the period from January 1983 to January 1986. In order to determine whether it was suicide or homicide, the path of the bullet, the site, the muzzle target distance must be considered. The angle of the bullet would be either elevated (from below upward), horizontal or an angle of depression (from above downward). For suicide, the direction of the bullet should be at an angle of elevation in the majority of cases. The position of the handgun in relation to the head in suicide was most often in tight contact and near contact. For homicide, the direction of the bullet should be horizontal in most cases. The bullet was at close range in the majority of the cases. There are 8 common sites for suicide and homicide and 10 different sites in the case of homicide which are at neck, left cheek, left aural region, lip, left occipital area orbit, chin, left eyebrow, submental and nose.

Non-lead, environmentally safe projectiles and method of making same

DOEpatents

Lowden, Richard A.; McCoig, Thomas M.; Dooley, Joseph B.

1998-01-01

A projectile, such as a bullet, is made by combining two different metals in proportions calculated to achieve a desired density, without using lead. A base constituent, made of a material having density greater than lead, is combined with a binder constituent having less density. The binder constituent is malleable and ductile metallic phase material that forms projectile shapes when subjected to a consolidation force, such as compression. The metal constituents can be selected, rationed, and consolidated to achieve desired frangibility characteristics.

Non-lead, environmentally safe projectiles and method of making same

DOEpatents

Lowden, Richard A.; McCoig, Thomas M.; Dooley, Joseph B.

2000-01-01

A projectile, such as a bullet, is made by combining two different metals in proportions calculated to achieve a desired density, without using lead. A base constituent, made of a material having density greater than lead, is combined with a binder constituent having less density. The binder constituent is malleable and ductile metallic phase material that forms projectile shapes when subjected to a consolidation force, such as compression. The metal constituents can be selected, rationed, and consolidated to achieve desired frangibility characteristics.

Non-lead environmentally safe projectiles and method of making same

DOEpatents

Lowden, Richard A.; McCoig, Thomas M.; Dooley, Joseph B.

1999-01-01

A projectile, such as a bullet, is made by combining two different metals in proportions calculated to achieve a desired density, without using lead. A base constituent, made of a material having density greater than lead, is combined with a binder constituent having less density. The binder constituent is malleable and ductile metallic base material that forms projectile shapes when subjected to a consolidation force, such as compression. The metal constituents can be selected, rationed, and consolidated to achieve desired frangibility characteristics.

Interaction of Interstellar Shocks with Dense Obstacles: Formation of ``Bullets''

NASA Astrophysics Data System (ADS)

Gvaramadze, V. V.

The so-called cumulative effect take place in converging conical shock waves arising behind dense obstacles overtaken by incident interstellar shock. A significant part of energy of converging flow of matter swept-up by a radiative conical shock can be transferred to a dense jet-like ejection (``bullet'') directed along the cone axis. Possible applications of this effect for star-forming regions (e.g., OMC-1) and supernova remnants (e.g., Vela SNR) are discussed.

Lightening Body Armor: Arroyo Support to the Army Response to Section 125 of the National Defense Authorization Act for Fiscal Year 2011

DTIC Science & Technology

2012-01-01

nel from fragmenting munitions, and the addition of SAPI will successfully defend against AK-47 ball ammunition. The ESAPI and XSAPI plates were...d ) Frequency of incidents of firefights 7.62 x 39mm ball Fragmenting munitions Threat X Threat Y Threat E Threat F Threat A Threat C Threat D...the threat in Afghani- stan today is primarily fragmenting munitions, 7.62mm x 39 ball bullets, and 7.62mm x 54R ball bullets. Current body armor

Less-lethal hybrid ammunition wounds: a forensic assessment introducing bullet-skin-bone entity.

PubMed

de Freminville, Humbert; Prat, Nicolas; Rongieras, Frederic; Voiglio, Eric J

2010-09-01

Agencies all around the world now use less-lethal weapons with homogeneous missiles such as bean bag or rubber bullets. Contusions and sometimes significant morbidity have been reported. This study focuses on wounds caused by hybrid ammunition with the pathologists' flap-by-flap procedure. Twenty-four postmortem human subjects were used, and lesions caused on frontal, temporal, sternal, and left tibial regions by a 40-mm hybrid ammunition (33 g weight) were evaluated on various distance range. The 50% risk of fractures occurred at 79.2 m/sec on the forehead, 72.9 m/sec on the temporal, 72.5 m/sec on the sternum, and 76.7 m/sec on the tibia. Skin lesions were not predictors of bone fracture. There was no correlation between soft and bone tissue observed lesions and impact velocity (correlated to distance range). Lesions observed with hybrid ammunition were the result of bullet-skin-bone entity as the interaction of the projectile on skin and bone tissues.

The use of near-infrared photography to image fired bullets and cartridge cases.

PubMed

Stein, Darrell; Yu, Jorn Chi Chung

2013-09-01

An imaging technique that is capable of reducing glare, reflection, and shadows can greatly assist the process of toolmarks comparison. In this work, a camera with near-infrared (near-IR) photographic capabilities was fitted with an IR filter, mounted to a stereomicroscope, and used to capture images of toolmarks on fired bullets and cartridge cases. Fluorescent, white light-emitting diode (LED), and halogen light sources were compared for use with the camera. Test-fired bullets and cartridge cases from different makes and models of firearms were photographed under either near-IR or visible light. With visual comparisons, near-IR images and visible light images were comparable. The use of near-IR photography did not reveal more details and could not effectively eliminate reflections and glare associated with visible light photography. Near-IR photography showed little advantages in manual examination of fired evidence when it was compared with visible light (regular) photography. © 2013 American Academy of Forensic Sciences.

Fragmentation of an elastica

NASA Astrophysics Data System (ADS)

Vandenberghe, Nicolas; Villermaux, Emmanuel

2009-03-01

When a thin rod is submitted to an axial force greater than its critical buckling load it takes the shape of an elastica. As the load further increases, a rod made of a brittle material breaks suddenly. More than two fragments may be formed during this fragmentation. In this work we discuss the sequence of events that lead to the final broken state with two or more fragments. We show that the criterion for breaking is not trivial. In particular, we investigate the effect of the duration of the loading and we show that at a given load the waiting time before breaking is broadly distributed. We discuss the consequences of the time delayed breaking on the distributions of fragment sizes and fragment numbers.

Habitat fragmentation resulting in overgrazing by herbivores.

PubMed

Kondoh, Michio

2003-12-21

Habitat fragmentation sometimes results in outbreaks of herbivorous insect and causes an enormous loss of primary production. It is hypothesized that the driving force behind such herbivore outbreaks is disruption of natural enemy attack that releases herbivores from top-down control. To test this hypothesis I studied how trophic community structure changes along a gradient of habitat fragmentation level using spatially implicit and explicit models of a tri-trophic (plant, herbivore and natural enemy) food chain. While in spatially implicit model number of trophic levels gradually decreases with increasing fragmentation, in spatially explicit model a relatively low level of habitat fragmentation leads to overgrazing by herbivore to result in extinction of the plant population followed by a total system collapse. This provides a theoretical support to the hypothesis that habitat fragmentation can lead to overgrazing by herbivores and suggests a central role of spatial structure in the influence of habitat fragmentation on trophic communities. Further, the spatially explicit model shows (i) that the total system collapse by the overgrazing can occur only if herbivore colonization rate is high; (ii) that with increasing natural enemy colonization rate, the fragmentation level that leads to the system collapse becomes higher, and the frequency of the collapse is lowered.

Non-lead, environmentally safe projectiles and explosives containers

DOEpatents

Lowden, Richard A.; McCoig, Thomas M.; Dooley, Joseph B.; Smith, Cyrus M.

2001-01-16

A solid object having controlled frangibility, such as a bullet or a container for explosives, is made by combining two different metals in proportions calculated to achieve a desired density, without using lead. A wetting material is deposited on the base constituent which is made of a relative dense, hard material. The wetting material enhances the wettability of the base constituent with the binder constituent, which is lighter and softer than the base constituent.

Non-lead environmentally safe projectiles and explosive container

DOEpatents

Lowden, Richard A.; McCoig, Thomas M.; Dooley, Joseph B.; Smith, Cyrus M.

1999-06-15

A solid object having controlled frangibility, such as a bullet or a container for explosives, is made by combining two different metals in proportions calculated to achieve a desired density, without using lead. A wetting material is deposited on the base constituent which is made of a relative dense, hard material. The wetting material enhances the wettability of the base constituent with the binder constituent, which is lighter and softer than the base constituent.

Non-lead, environmentally safe projectiles and method of making same

DOEpatents

Lowden, R.A.; McCoig, T.M.; Dooley, J.B.

1998-06-02

A projectile, such as a bullet, is made by combining two different metals in proportions calculated to achieve a desired density, without using lead. A base constituent, made of a material having density greater than lead, is combined with a binder constituent having less density. The binder constituent is malleable and ductile metallic phase material that forms projectile shapes when subjected to a consolidation force, such as compression. The metal constituents can be selected, rationed, and consolidated to achieve desired frangibility characteristics. 7 figs.

Effective progression of nuclear magnetic resonance-detected fragment hits.

PubMed

Eaton, Hugh L; Wyss, Daniel F

2011-01-01

Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

Undetected penetrating bladder injuries presenting as a spontaneously expulsed bullet during voiding: a rare entity and review of the literature.

PubMed

Kuy, SreyRam; Somberg, Lewis B; Paul, Jasmeet; Brown, Nathaniel; Saving, Allegra; Codner, Panna A

2013-09-01

Patients presenting with a penetrating missile lodged in the pelvis are at risk for having a urinary tract injury. Once in the bladder, the missile can become impacted in the urethra, causing retention that requires extraction. Rarely, the missile can be expulsed spontaneously through the urethra. To describe the world literature regarding undetected penetrating bladder injuries presenting as spontaneously voided bullets and to contribute an additional case to the literature. We present a case report of a 37-year-old man who sustained a gunshot wound to the right buttock, with an undetected urinary system injury and subsequent spontaneous voiding of a bullet. There have been <10 cases reported in the literature of spontaneously expulsed bullets from the urethra, all of which were undetected injuries on initial presentation. Physicians should be aware of the potential for undetected urinary tract injuries in patients with penetrating missiles to the pelvis and understand the appropriate evaluation and management strategies for these injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

Missile pulmonary embolus secondary to abdominal gunshot wound.

PubMed

Mctyre, Emory; McGill, Lee; Miller, Nessa

2012-01-01

Missile pulmonary emboli are rare sequelae of traumatic entry of projectile missiles-generally bullets or bullet fragments-in which access to the systemic venous circulation is established by the missile, making it possible for the missile to migrate to the pulmonary arteries. In the case introduced here, a 24-year-old male presented to the ER with a gunshot wound to the abdomen. In the early course of his care, it was determined that he had suffered a missile pulmonary embolus secondary to a large fragment of a bullet penetrating the IVC. Despite the large perfusion defect created by this missile embolus, the patient recovered uneventfully without embolectomy.

Magnetic nanoparticle-induced hyperthermia with appropriate payloads: Paul Ehrlich's "magic (nano)bullet" for cancer theranostics?

PubMed

Datta, N R; Krishnan, S; Speiser, D E; Neufeld, E; Kuster, N; Bodis, S; Hofmann, H

2016-11-01

Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology. The rapid developments in multifunctional nanoparticles provide ample opportunities to integrate both diagnostic and therapeutic modalities into a single effective cancer "theranostic" vector. Nanoparticles could extravasate passively into the tumour tissues in preference to the adjacent normal tissues by capitalizing on the enhanced permeability and retention effect. Tumour targeting might be further augmented by conjugating tumour-specific peptides and antibodies onto the surface of these nanoparticles or by activation through electromagnetic radiations, laser or ultrasound. Magnetic nanoparticles can induce hyperthermia in the presence of an alternating magnetic field, thereby multifunctionally with tumour-specific payloads empowering tumour specific radiotheranostics (for both imaging and radiotherapy), chemotherapy drug delivery, immunotherapy and gene silencing therapy. Such a (nano)bullet could realise the "magic bullet" conceived by Paul Ehrlich more than a century ago. This article discusses the various aspects of this "magic (nano)bullet" and the challenges that need to be addressed to usher in this new paradigm in modern cancer diagnostics and therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Passive infrared bullet detection and tracking

DOEpatents

Karr, Thomas J.

1997-01-01

An apparatus and method for passively detecting a projectile such as, for example, a bullet using a passive infrared detector. A passive infrared detector is focused onto a region in which a projectile is expected to be located. Successive images of infrared radiation in the region are recorded. Background infrared radiation present in the region is suppressed such that second successive images of infrared radiation generated by the projectile as the projectile passes through the region are produced. A projectile path calculator determines the path and other aspects of the projectile by using the second successive images of infrared radiation generated by the projectile. The present invention, in certain embodiments, also determines the origin of the path of the projectile and takes a photograph of the area surrounding the origin and/or fires at least one projectile at the area surrounding the origin of the path of the projectile.

Passive infrared bullet detection and tracking

DOEpatents

Karr, T.J.

1997-01-21

An apparatus and method for passively detecting a projectile such as, for example, a bullet using a passive infrared detector. A passive infrared detector is focused onto a region in which a projectile is expected to be located. Successive images of infrared radiation in the region are recorded. Background infrared radiation present in the region is suppressed such that second successive images of infrared radiation generated by the projectile as the projectile passes through the region are produced. A projectile path calculator determines the path and other aspects of the projectile by using the second successive images of infrared radiation generated by the projectile. The present invention, in certain embodiments, also determines the origin of the path of the projectile and takes a photograph of the area surrounding the origin and/or fires at least one projectile at the area surrounding the origin of the path of the projectile. 9 figs.

Non-lead environmentally safe projectiles and explosive container

DOEpatents

Lowden, R.A.; McCoig, T.M.; Dooley, J.B.; Smith, C.M.

1999-06-15

A solid object having controlled frangibility, such as a bullet or a container for explosives, is made by combining two different metals in proportions calculated to achieve a desired density, without using lead. A wetting material is deposited on the base constituent which is made of a relative dense, hard material. The wetting material enhances the wettability of the base constituent with the binder constituent, which is lighter and softer than the base constituent. 10 figs.

Assessment of a specifically developed bullet casing gun for the stunning of water buffaloes.

PubMed

Meichtry, Carmen; Glauser, Urs; Glardon, Matthieu; Ross, Steffen G; Lechner, Isabel; Kneubuehl, Beat P; Gascho, Dominic; Spadavecchia, Claudia; von Rotz, Alois; Stojiljkovic, Ana; Stoffel, Michael H

2018-01-01

Water buffaloes and cattle differ considerably with respect to the anatomy of the head. As a result, captive bolt stunners often fail to reliably produce adequate loss of consciousness in water buffaloes and, thus, do not fulfill animal welfare requirements. The goal of the present study was to assess and validate a new stunning device for water buffaloes meeting animal welfare and occupational safety requirements. The newly designed bullet casing gun uses .357Mag/10.2g hollow point bullets and has additional safety features. Its effectiveness and usability were assessed under practical conditions in an abattoir as based on widely accepted criteria. Stunning resulted in deep unconsciousness in 19 out of 20 water buffaloes. One 9-year old male did not immediately collapse. Except for very old bulls, the device presented herewith provides a means to stun water buffaloes of both sexes effectively and reliably while keeping occupational hazards to a minimum. Copyright © 2017 Elsevier Ltd. All rights reserved.

Caffeine citrate - Is it a silver bullet in neonatology?

PubMed

Shrestha, Bikash; Jawa, Gaurav

2017-10-01

Caffeine citrate is one of the most prescribed drug in the present day NICU for apnea. Its efficacy, tolerability, wide therapeutic index and safety margin has made it the drug of choice among the methylxanthines. Its therapeutic uses in apnea of prematurity, mechanical ventilation, bronchopulmonary dysplasia has made it a "silver bullet" in neonatology. However, there are still controversies surrounding this drug. This review is aimed to update the reader about the basic pharmacology, current therapeutic uses, adverse effects, controversies as well as present and future research of caffeine. Copyright © 2017. Published by Elsevier B.V.

Minimum cause--maximum effect: the travelogue of a bullet.

PubMed

Hartert, Marc; Dahm, Manfred; Neufang, Achim; Vahl, Christian-Friedrich

2010-11-01

This case report involves a 57-year-old male, accidentally shot in the chest with a small bore firearm. The bullet entered the left hemithorax, disrupting the left internal mammarian artery. It then penetrated the anterior wall of the right ventricle causing a pericardial tamponade. After leaving the base of the right heart it perforated the diaphragm, the liver, the spleen and the pancreas. Finally, it penetrated the abdominal aorta 3 cm proximally to the coeliac trunk and reached its final position paravertebrally. This case report illustrates that the management of even minimum gunshot wounds requires a maximum variety of surgical skills.

Fragment library design: using cheminformatics and expert chemists to fill gaps in existing fragment libraries.

PubMed

Kutchukian, Peter S; So, Sung-Sau; Fischer, Christian; Waller, Chris L

2015-01-01

Fragment based screening (FBS) has emerged as a mainstream lead discovery strategy in academia, biotechnology start-ups, and large pharma. As a prerequisite of FBS, a structurally diverse library of fragments is desirable in order to identify chemical matter that will interact with the range of diverse target classes that are prosecuted in contemporary screening campaigns. In addition, it is also desirable to offer synthetically amenable starting points to increase the probability of a successful fragment evolution through medicinal chemistry. Herein we describe a method to identify biologically relevant chemical substructures that are missing from an existing fragment library (chemical gaps), and organize these chemical gaps hierarchically so that medicinal chemists can efficiently navigate the prioritized chemical space and subsequently select purchasable fragments for inclusion in an enhanced fragment library.

Intraorbital foreign body: A rifle bullet removed 20 years after the accident.

PubMed

Clarós, P; Fokouo, J V F; Clarós, A

2017-02-01

Trauma of the orbit and eyeball is common, but intraorbital bullet is a relatively rare event. The authors report the management of a patient with chorioretinitis sclopetaria secondary to a gunshot wound twenty years previously. The clinical, diagnostic and therapeutic aspects of this unusual case of intraorbital foreign body are discussed. Copyright © 2016. Published by Elsevier Masson SAS.

Fragment-assisted hit investigation involving integrated HTS and fragment screening: Application to the identification of phosphodiesterase 10A (PDE10A) inhibitors.

PubMed

Varnes, Jeffrey G; Geschwindner, Stefan; Holmquist, Christopher R; Forst, Janet; Wang, Xia; Dekker, Niek; Scott, Clay W; Tian, Gaochao; Wood, Michael W; Albert, Jeffrey S

2016-01-01

Fragment-based drug design (FBDD) relies on direct elaboration of fragment hits and typically requires high resolution structural information to guide optimization. In fragment-assisted drug discovery (FADD), fragments provide information to guide selection and design but do not serve as starting points for elaboration. We describe FADD and high-throughput screening (HTS) campaign strategies conducted in parallel against PDE10A where fragment hit co-crystallography was not available. The fragment screen led to prioritized fragment hits (IC50's ∼500μM), which were used to generate a hypothetical core scaffold. Application of this scaffold as a filter to HTS output afforded a 4μM hit, which, after preparation of a small number of analogs, was elaborated into a 16nM lead. This approach highlights the strength of FADD, as fragment methods were applied despite the absence of co-crystallographical information to efficiently identify a lead compound for further optimization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Advances in fragment-based drug discovery platforms.

PubMed

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

Dosing of adult pigeons with as little as one #9 lead pellet caused severe δ-ALAD depression, suggesting potential adverse effects in wild populations.

PubMed

Holladay, Jeremy P; Nisanian, Mandy; Williams, Susan; Tuckfield, R Cary; Kerr, Richard; Jarrett, Timothy; Tannenbaum, Lawrence; Holladay, Steven D; Sharma, Ajay; Gogal, Robert M

2012-11-01

Avian wildlife species commonly ingest lead (Pb) spent shot or bullet fragments as grit or mistakenly as food. In previous studies in our laboratory and others, the toxicity varied based on the diet as well as type and quantity of Pb ingested. In the current study, domestic pigeons were gavaged with 1, 2, or 3 Pb pellets and then followed with weekly radiographs and blood physiologic endpoints for 28 days. Pellet retention decreased by roughly 50 % per week as pellets were either absorbed or excreted, except for week 4 where pellet number no longer was diminished. Size of retained pellets visually decreased over retention time. Birds dosed with a single #9 pellet showed mean blood Pb levels over 80 times higher than those of the controls, verifying Pb pellet absorption from the gut. A single Pb pellet also reduced plasma δ-aminolevulinic acid dehydratase (δ-ALAD) activity by over 80 % compared to controls, suggesting the potential for population injury in Pb pellet-exposed pigeons.

Introduction to fragment-based drug discovery.

PubMed

Erlanson, Daniel A

2012-01-01

Fragment-based drug discovery (FBDD) has emerged in the past decade as a powerful tool for discovering drug leads. The approach first identifies starting points: very small molecules (fragments) that are about half the size of typical drugs. These fragments are then expanded or linked together to generate drug leads. Although the origins of the technique date back some 30 years, it was only in the mid-1990s that experimental techniques became sufficiently sensitive and rapid for the concept to be become practical. Since that time, the field has exploded: FBDD has played a role in discovery of at least 18 drugs that have entered the clinic, and practitioners of FBDD can be found throughout the world in both academia and industry. Literally dozens of reviews have been published on various aspects of FBDD or on the field as a whole, as have three books (Jahnke and Erlanson, Fragment-based approaches in drug discovery, 2006; Zartler and Shapiro, Fragment-based drug discovery: a practical approach, 2008; Kuo, Fragment based drug design: tools, practical approaches, and examples, 2011). However, this chapter will assume that the reader is approaching the field with little prior knowledge. It will introduce some of the key concepts, set the stage for the chapters to follow, and demonstrate how X-ray crystallography plays a central role in fragment identification and advancement.

Rapid experimental SAD phasing and hot-spot identification with halogenated fragments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bauman, Joseph D.; Harrison, Jerry Joe E. K.; Arnold, Eddy

2016-01-01

Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a `magic bullet' that is capable of binding at many of the ligand `hot spots' found in HIV-1 reverse transcriptase (RT). The binding locations can be in pockets that are `hidden' in the unliganded crystal form, allowing rapid identification of these sites forin silicoscreening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structuresmore » of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K) by single-wavelength anomalous dispersion (SAD) from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals.« less

Halogen-Enriched Fragment Libraries as Leads for Drug Rescue of Mutant p53

PubMed Central

2012-01-01

The destabilizing p53 cancer mutation Y220C creates a druggable surface crevice. We developed a strategy exploiting halogen bonding for lead discovery to stabilize the mutant with small molecules. We designed halogen-enriched fragment libraries (HEFLibs) as starting points to complement classical approaches. From screening of HEFLibs and subsequent structure-guided design, we developed substituted 2-(aminomethyl)-4-ethynyl-6-iodophenols as p53-Y220C stabilizers. Crystal structures of their complexes highlight two key features: (i) a central scaffold with a robust binding mode anchored by halogen bonding of an iodine with a main-chain carbonyl and (ii) an acetylene linker, enabling the targeting of an additional subsite in the crevice. The best binders showed induction of apoptosis in a human cancer cell line with homozygous Y220C mutation. Our structural and biophysical data suggest a more widespread applicability of HEFLibs in drug discovery. PMID:22439615

Lead in the environment

USGS Publications Warehouse

Pattee, Oliver H.; Pain, Deborah J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

2003-01-01

. and the .reduction of lead in gasoline has resulted in lower tissue lead concentrations in humans and wildlife from many, particularly urban, locations. However, it has been suggested that increasing use of organic lead compounds as catalysts for the production of plastics and as wood preservatives and biocides could adversely affect wildlife. The most significant source of direct wildlife mortality from lead is spent gunshot and fishing sinkers. Elevated mortality from shot ingestion in avian species resulted in the introduction of nontoxic (steel) shot zones along certain flyways in the United States in the mid-1970s and a total ban on the use of lead for waterfowl and coot hunting nationwide by 1992. Several other countries are now following suit and have either banned or are in the process of restricting the use of lead shot for waterfowl hunting. In the United States it has been estimated that since the 1986 hunting season. when the use of nontoxic shot became widespread. over 6 million ducks have not been lost to lead poisoning. Raptors, especially eagles, have also apparently benefited. although lead poisoning from ingestion of bullet fragments remains a problem for the critically threatened California condor. Quantifying reductions in lead mortality rates would be difficult since eagle populations throughout North America are rapidly recovering from other anthropogenic perturbations, especially organochlorine pesticides.

Study the fragment size distribution in dynamic fragmentation of laser shock loding tin

NASA Astrophysics Data System (ADS)

He, Weihua; Xin, Jianting; Chu, Genbai; Shui, Min; Xi, Tao; Zhao, Yongqiang; Gu, Yuqiu

2017-06-01

Characterizing the distribution of fragment size produced from dynamic fragmentation process is very important for fundamental science like predicting material dymanic response performance and for a variety of engineering applications. However, only a few data about fragment mass or size have been obtained due to its great challenge in its dynamic measurement. This paper would focus on investigating the fragment size distribution from the dynamic fragmentation of laser shock-loaded metal. Material ejection of tin sample with wedge shape groove in the free surface is collected with soft recovery technique. Via fine post-shot analysis techniques including X-ray micro-tomography and the improved watershed method, it is found that fragments can be well detected. To characterize their size distributions, a random geometric statistics method based on Poisson mixtures was derived for dynamic heterogeneous fragmentation problem, which leads to a linear combinational exponential distribution. Finally we examined the size distribution of laser shock-loaded tin with the derived model, and provided comparisons with other state-of-art models. The resulting comparisons prove that our proposed model can provide more reasonable fitting result for laser shock-loaded metal.

Fragmentation contributions to J / ψ photoproduction at HERA

DOE PAGES

Bodwin, Geoffrey T.; Chung, Hee Sok; Kim, U-Rae; ...

2015-10-28

Here, we compute leading-power fragmentation corrections to J/ψ photoproduction at DESY HERA, making use of the nonrelativistic QCD factorization approach. Our calculations include parton production cross sections through order α 3 s, fragmentation functions though order α 2 s, and leading logarithms of the transverse momentum divided by the charm-quark mass to all orders in α s. We find that the leading-power fragmentation corrections, beyond those that are included through next-to-leading order in α s, are small relative to the fixed-order contributions through next-to-leading order in α s. Consequently, an important discrepancy remains between the experimental measurements of the J/ψmore » photoproduction cross section and predictions that make use of nonrelativistic-QCD long-distance matrix elements that are extracted from the J/ψ hadroproduction cross-section and polarization data.« less

Forensic value of gunpowder tattooing in identification of multiple entrance wounds from one bullet.

PubMed

Tokdemir, Mehmet; Kafadar, Huseyin; Turkoglu, Abdurrahim; Bork, Turgay

2007-05-01

Multiple entrance gunshot wounds can give useful information in forensic evaluation of deaths from homicide and suicide. Although the presence of multiple entrance gunshot wounds does not absolutely exclude the possibility of suicide, they are important to the forensic investigators and pathologists in cases of assault, attempted homicide and suicide as they provide important clues for determination of number of shots fired and direction of firing. We present a case of 16 years of young woman who was shot to death by her husband. External examination revealed an entrance wound with semi-lunar shot residue at the dorsal side of her left hand at 5th metacarpus, and exit wound on the hypothenar muscle. There was also a second wound entrance located on her left zygoma. Direction of the bullet was downward traveling from left-to-right. Initially it was thought that there were two close shots, but when her left hand was placed over the malar area her face, it was determined that the gunshot powder tattoos were completing the nature of a single shot from a close distance. Crime scene investigation revealed only one cartridge casing. The autopsy and radiography findings showed that the bullet was entered from dorsal site of the left hand exiting from the palm and re-entering from the zygomatic region, hit the base of the skull, and remained in the soft tissue of the right mandible after passing the soft palate. The bullet was caused an incomplete laceration of the right internal arteria carotid and she died of internal and external bleeding. Detailed investigation of gunshot residues can provide important information for clarification of close distance gunshot wounding. We present this case due to its interesting nature, and to highlight the importance of detailed investigation of the gun powder residues in cases with multiple entry wounds.

Targeting the latest hallmark of cancer: another attempt at 'magic bullet' drugs targeting cancers' metabolic phenotype.

PubMed

Cuperlovic-Culf, M; Culf, A S; Touaibia, M; Lefort, N

2012-10-01

The metabolism of tumors is remarkably different from the metabolism of corresponding normal cells and tissues. Metabolic alterations are initiated by oncogenes and are required for malignant transformation, allowing cancer cells to resist some cell death signals while producing energy and fulfilling their biosynthetic needs with limiting resources. The distinct metabolic phenotype of cancers provides an interesting avenue for treatment, potentially with minimal side effects. As many cancers show similar metabolic characteristics, drugs targeting the cancer metabolic phenotype are, perhaps optimistically, expected to be 'magic bullet' treatments. Over the last few years there have been a number of potential drugs developed to specifically target cancer metabolism. Several of these drugs are currently in clinical and preclinical trials. This review outlines examples of drugs developed for different targets of significance to cancer metabolism, with a focus on small molecule leads, chemical biology and clinical results for these drugs.

Fragment-based drug discovery using rational design.

PubMed

Jhoti, H

2007-01-01

Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

Fragment Screening of Soluble Epoxide Hydrolase for Lead Generation-Structure-Based Hit Evaluation and Chemistry Exploration.

PubMed

Xue, Yafeng; Olsson, Thomas; Johansson, Carina A; Öster, Linda; Beisel, Hans-Georg; Rohman, Mattias; Karis, David; Bäckström, Stefan

2016-03-04

Soluble epoxide hydrolase (sEH) is involved in the regulation of many biological processes by metabolizing the key bioactive lipid mediator, epoxyeicosatrienoic acids. For the development of sEH inhibitors with improved physicochemical properties, we performed both a fragment screening and a high-throughput screening aiming at an integrated hit evaluation and lead generation. Followed by a joint dose-response analysis to confirm the hits, the identified actives were then effectively triaged by a structure-based hit-classification approach to three prioritized series. Two distinct scaffolds were identified as tractable starting points for potential lead chemistry work. The oxoindoline series bind at the right-hand side of the active-site pocket with hydrogen bonds to the protein. The 2-phenylbenzimidazole-4-sulfonamide series bind at the central channel with significant induced fit, which has not been previously reported. On the basis of the encouraging initial results, we envision that a new lead series with improved properties could be generated if a vector is found that could merge the cyclohexyl functionality of the oxoindoline series with the trifluoromethyl moiety of the 2-phenylbenzimidazole-4-sulfonamide series. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Passive Reactive Berm (PRBerm) to Provide Low Maintenance Lead Containment at Active Small Arms Firing Ranges

DTIC Science & Technology

2011-10-01

CO3 )2, hydrocerrusite]. Overall lead solubility in a natural system is fundamentally determined by the concentrations of the anions in solution (e.g...with a potential seed crystal for heterogeneous nucleation of lead-pyromorphites (Wright et al. 2004). Depending on the presence of certain metals in...comparison will be $ per running foot of PRBerm as compared to $ per running foot of earthen berm and purchase and installation of a single steel bullet trap

NuSTAR observations of the bullet cluster: constraints on inverse Compton emission

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wik, Daniel R.; Hornstrup, A.; Molendi, S.

2014-08-13

Here, the search for diffuse non-thermal inverse Compton (IC) emission from galaxy clusters at hard X-ray energies has been undertaken with many instruments, with most detections being either of low significance or controversial. Because all prior telescopes sensitive at E > 10 keV do not focus light and have degree-scale fields of view, their backgrounds are both high and difficult to characterize. The associated uncertainties result in lower sensitivity to IC emission and a greater chance of false detection. In this work, we present 266 ks NuSTAR observations of the Bullet cluster, which is detected in the energy range 3-30more » keV. NuSTAR's unprecedented hard X-ray focusing capability largely eliminates confusion between diffuse IC and point sources; however, at the highest energies, the background still dominates and must be well understood. To this end, we have developed a complete background model constructed of physically inspired components constrained by extragalactic survey field observations, the specific parameters of which are derived locally from data in non-source regions of target observations. Applying the background model to the Bullet cluster data, we find that the spectrum is well—but not perfectly—described as an isothermal plasma with kT = 14.2 ± 0.2 keV. To slightly improve the fit, a second temperature component is added, which appears to account for lower temperature emission from the cool core, pushing the primary component to kT ~ 15.3 keV. We see no convincing need to invoke an IC component to describe the spectrum of the Bullet cluster, and instead argue that it is dominated at all energies by emission from purely thermal gas. The conservatively derived 90% upper limit on the IC flux of 1.1 × 10 –12 erg s –1 cm –2 (50-100 keV), implying a lower limit on B ≳ 0.2 μG, is barely consistent with detected fluxes previously reported. In addition to discussing the possible origin of this discrepancy, we remark on the

Two bullets to the head and an early winter: fate permits Kutuzov to defeat Napoleon at Moscow.

PubMed

Kushchayev, Sergiy V; Belykh, Evgenii; Fishchenko, Yakiv; Salei, Aliaksei; Teytelboym, Oleg M; Shabaturov, Leonid; Cruse, Mark; Preul, Mark C

2015-07-01

General Mikhail Kutuzov (circa 1745-1813) brilliantly repelled Napoleon's invasion of Russia. Honored as a national hero and a savior of Russia, Kutuzov has a unique medical story. He was shot in the head twice while fighting the Turks (1774 and 1788) and survived the serious injuries seemingly against all odds. The first bullet "ran through the head from one temple to the other behind both eyes." The second bullet entered the cheek, destroyed upper teeth, traveled through the head, and exited the occiput. Massot, a French surgeon with the Russian army, wrote after treating Kutuzov's seemingly two mortal wounds: "It must be believed that fate appoints Kutuzov to something great, because he was still alive after two injuries, a death sentence by all the rules of medical science." Aided by Massot's expert surgical technique, Kutuzov lived to become intimately engaged in events that altered world history. His health did, however, suffer significant effects due to the bullet wounds. In 1812, as Napoleon's Grande Armée approached, Kutuzov realized he could not confront Napoleon and he strategically retreated from Moscow, submitting the French to the harsh winter and Russian cavalry. Napoleon's devastated army retreated to Paris, and Kutuzov became the personification of Russian spirit and character. Kutuzov's survival of two nearly mortal head wounds created the legends, additional mystery, and drama surrounding him, not the least astonishing of which was the skilled neurosurgical care that probably saved his life.

Fixation Strength of Polyetheretherketone Sheath-and-Bullet Device for Soft Tissue Repair in the Foot and Ankle.

PubMed

Christensen, Jay; Fischer, Brian; Nute, Michael; Rizza, Robert

Tendon transfers are often performed in the foot and ankle. Recently, interference screws have been a popular choice owing to their ease of use and fixation strength. Considering the benefits, one disadvantage of such devices is laceration of the soft tissues by the implant threads during placement that potentially weaken the structural integrity of the grafts. A shape memory polyetheretherketone bullet-in-sheath tenodesis device uses circumferential compression, eliminating potential damage from thread rotation and maintaining the soft tissue orientation of the graft. The aim of this study was to determine the pullout strength and failure mode for this device in both a synthetic bone analogue and porcine bone models. Thirteen mature bovine extensor tendons were secured into ten 4.0 × 4.0 × 4.0-cm cubes of 15-pound per cubic foot solid rigid polyurethane foam bone analogue models or 3 porcine femoral condyles using the 5 × 20-mm polyetheretherketone soft tissue anchor. The bullet-in-sheath device demonstrated a mean pullout of 280.84 N in the bone analog models and 419.47 N in the porcine bone models. (p = .001). The bullet-in-sheath design preserved the integrity of the tendon graft, and none of the implants dislodged from their original position. Copyright © 2017 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Fatal wounds sustained from "falling bullets": maintaining a high index of suspicion in a forensic setting.

PubMed

Rapkiewicz, Amy V; Shuman, Mark J; Hutchins, Kenneth D

2014-01-01

Celebratory gunfire injuries from "falling bullets" occur when guns are fired into the air during celebrations without realizing that this can cause serious injuries or even fatalities. Fatal celebratory gunfire injury is an uncommonly reported event in the continental United States. Our electronic database was queried for homicides occurring within days of July 4th and December 31st over a 14-year period. We describe two cases of fatal gunfire injury due to celebratory gunfire occurring during New Year's Eve in Southern Florida. The relevant literature is reviewed. These case reports illustrate that fatal gunfire injuries sustained from "falling bullets" may pose as an unexpected mimic to sudden natural deaths especially in patients with prior medical history. A high index of suspicion to recognize such injury is required particularly during holidays. 2013 American Academy of Forensic Sciences Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.

Effective field theory approach to heavy quark fragmentation

DOE PAGES

Fickinger, Michael; Fleming, Sean; Kim, Chul; ...

2016-11-17

Using an approach based on Soft Collinear Effective Theory (SCET) and Heavy Quark Effective Theory (HQET) we determine the b-quark fragmentation function from electron-positron annihilation data at the Z-boson peak at next-to-next-to leading order with next-to-next-to leading log resummation of DGLAP logarithms, and next-to-next-to-next-to leading log resummation of endpoint logarithms. This analysis improves, by one order, the previous extraction of the b-quark fragmentation function. We find that while the addition of the next order in the calculation does not much shift the extracted form of the fragmentation function, it does reduce theoretical errors indicating that the expansion is converging. Usingmore » an approach based on effective field theory allows us to systematically control theoretical errors. Furthermore, while the fits of theory to data are generally good, the fits seem to be hinting that higher order correction from HQET may be needed to explain the b-quark fragmentation function at smaller values of momentum fraction.« less

Assessment of Methods for Estimating Risk to Birds from ...

EPA Pesticide Factsheets

The U.S. EPA Ecological Risk Assessment Support Center (ERASC) announced the release of the final report entitled, Assessment of Methods for Estimating Risk to Birds from Ingestion of Contaminated Grit Particles. This report evaluates approaches for estimating the probability of ingestion by birds of contaminated particles such as pesticide granules or lead particles (i.e. shot or bullet fragments). In addition, it presents an approach for using this information to estimate the risk of mortality to birds from ingestion of lead particles. Response to ERASC Request #16

Fragment Screening and HIV Therapeutics

PubMed Central

Bauman, Joseph D.; Patel, Disha; Arnold, Eddy

2013-01-01

Fragment screening has proven to be a powerful alternative to traditional methods for drug discovery. Biophysical methods, such as X-ray crystallography, NMR spectroscopy, and surface plasmon resonance, are used to screen a diverse library of small molecule compounds. Although compounds identified via this approach have relatively weak affinity, they provide a good platform for lead development and are highly efficient binders with respect to their size. Fragment screening has been utilized for a wide-range of targets, including HIV-1 proteins. Here, we review the fragment screening studies targeting HIV-1 proteins using X-ray crystallography or surface plasmon resonance. These studies have successfully detected binding of novel fragments to either previously established or new sites on HIV-1 protease and reverse transcriptase. In addition, fragment screening against HIV-1 reverse transcriptase has been used as a tool to better understand the complex nature of ligand binding to a flexible target. PMID:21972022

Transverse momenta of fragments of relativistic sulfur and lead nuclei after their interaction with track-emulsion nuclei at energies of 200 and 160 GeV per nucleon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lepekhin, F. G., E-mail: lepfed@yandex.ru; Tkach, L. N.

2011-05-15

Transverse-momentum distributions of doubly charged fragments of sulfur and lead nuclei having energies of 200 and 160 GeV per nucleon and interacting with nuclei in a track emulsion were investigated. No trace of compression or heating of nuclear matter in the interaction of these nuclei with track-emulsion nuclei was revealed experimentally. Transverse momenta of fragments of relativistic nuclei were found to obey a normal distribution that corresponds to a degenerate momentum distribution of nucleons in the ground state of a nucleus before its interaction with a track-emulsion nucleus. There is no piece of evidence that fragments of relativistic nuclei originatemore » from some excited state of an intermediate nucleus. This picture of the fragmentation of relativistic nuclei complies with the naive parton model proposed by Feynman and Gribov. In summary, the fragmentation of relativistic nuclei at energies of 160 and 200 GeV per nucleon is cold and fast.« less

Experiences in fragment-based drug discovery.

PubMed

Murray, Christopher W; Verdonk, Marcel L; Rees, David C

2012-05-01

Fragment-based drug discovery (FBDD) has become established in both industry and academia as an alternative approach to high-throughput screening for the generation of chemical leads for drug targets. In FBDD, specialised detection methods are used to identify small chemical compounds (fragments) that bind to the drug target, and structural biology is usually employed to establish their binding mode and to facilitate their optimisation. In this article, we present three recent and successful case histories in FBDD. We then re-examine the key concepts and challenges of FBDD with particular emphasis on recent literature and our own experience from a substantial number of FBDD applications. Our opinion is that careful application of FBDD is living up to its promise of delivering high quality leads with good physical properties and that in future many drug molecules will be derived from fragment-based approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lead exposure at firing ranges-a review.

PubMed

Laidlaw, Mark A S; Filippelli, Gabriel; Mielke, Howard; Gulson, Brian; Ball, Andrew S

2017-04-04

Lead (Pb) is a toxic substance with well-known, multiple, long-term, adverse health outcomes. Shooting guns at firing ranges is an occupational necessity for security personnel, police officers, members of the military, and increasingly a recreational activity by the public. In the United States alone, an estimated 16,000-18,000 firing ranges exist. Discharge of Pb dust and gases is a consequence of shooting guns. The objectives of this study are to review the literature on blood lead levels (BLLs) and potential adverse health effects associated with the shooting population. The search terms "blood lead", "lead poisoning", "lead exposure", "marksmen", "firearms", "shooting", "guns", "rifles" and "firing ranges" were used in the search engines Google Scholar, PubMed and Science Direct to identify studies that described BLLs in association with firearm use and health effects associated with shooting activities. Thirty-six articles were reviewed that included BLLs from shooters at firing ranges. In 31 studies BLLs > 10 μg/dL were reported in some shooters, 18 studies reported BLLs > 20 μg/dL, 17 studies > 30 μg/d, and 15 studies BLLs > 40 μg/dL. The literature indicates that BLLs in shooters are associated with Pb aerosol discharge from guns and air Pb at firing ranges, number of bullets discharged, and the caliber of weapon fired. Shooting at firing ranges results in the discharge of Pb dust, elevated BLLs, and exposures that are associated with a variety of adverse health outcomes. Women and children are among recreational shooters at special risk and they do not receive the same health protections as occupational users of firing ranges. Nearly all BLL measurements compiled in the reviewed studies exceed the current reference level of 5 μg/dL recommended by the U.S. Centers for Disease Control and Prevention/National Institute of Occupational Safety and Health (CDC/NIOSH). Thus firing ranges, regardless of type and user classification

Spatial scale, means and gradients of hydrographic variables define pelagic seascapes of bluefin and bullet tuna spawning distribution.

PubMed

Alvarez-Berastegui, Diego; Ciannelli, Lorenzo; Aparicio-Gonzalez, Alberto; Reglero, Patricia; Hidalgo, Manuel; López-Jurado, Jose Luis; Tintoré, Joaquín; Alemany, Francisco

2014-01-01

Seascape ecology is an emerging discipline focused on understanding how features of the marine habitat influence the spatial distribution of marine species. However, there is still a gap in the development of concepts and techniques for its application in the marine pelagic realm, where there are no clear boundaries delimitating habitats. Here we demonstrate that pelagic seascape metrics defined as a combination of hydrographic variables and their spatial gradients calculated at an appropriate spatial scale, improve our ability to model pelagic fish distribution. We apply the analysis to study the spawning locations of two tuna species: Atlantic bluefin and bullet tuna. These two species represent a gradient in life history strategies. Bluefin tuna has a large body size and is a long-distant migrant, while bullet tuna has a small body size and lives year-round in coastal waters within the Mediterranean Sea. The results show that the models performance incorporating the proposed seascape metrics increases significantly when compared with models that do not consider these metrics. This improvement is more important for Atlantic bluefin, whose spawning ecology is dependent on the local oceanographic scenario, than it is for bullet tuna, which is less influenced by the hydrographic conditions. Our study advances our understanding of how species perceive their habitat and confirms that the spatial scale at which the seascape metrics provide information is related to the spawning ecology and life history strategy of each species.

The persistent problem of lead poisoning in birds from ammunition and fishing tackle

USGS Publications Warehouse

Haig, Susan M.; D'Elia, Jesse; Eagles-Smith, Collin A.; Fair, Jeanne M.; Gervais, Jennifer; Herring, Garth; Rivers, James W.; Schulz, John H.

2014-01-01

Lead (Pb) is a metabolic poison that can negatively influence biological processes, leading to illness and mortality across a large spectrum of North American avifauna (>120 species) and other organisms. Pb poisoning can result from numerous sources, including ingestion of bullet fragments and shot pellets left in animal carcasses, spent ammunition left in the field, lost fishing tackle, Pb-based paints, large-scale mining, and Pb smelting activities. Although Pb shot has been banned for waterfowl hunting in the United States (since 1991) and Canada (since 1999), Pb exposure remains a problem for many avian species. Despite a large body of scientific literature on exposure to Pb and its toxicological effects on birds, controversy still exists regarding its impacts at a population level. We explore these issues and highlight areas in need of investigation: (1) variation in sensitivity to Pb exposure among bird species; (2) spatial extent and sources of Pb contamination in habitats in relation to bird exposure in those same locations; and (3) interactions between avian Pb exposure and other landscape-level stressors that synergistically affect bird demography. We explore multiple paths taken to reduce Pb exposure in birds that (1) recognize common ground among a range of affected interests; (2) have been applied at local to national scales; and (3) engage governmental agencies, interest groups, and professional societies to communicate the impacts of Pb ammunition and fishing tackle, and to describe approaches for reducing their availability to birds. As they have in previous times, users of fish and wildlife will play a key role in resolving the Pb poisoning issue.

To drink or grasp? How bullet ants ( Paraponera clavata) differentiate between sugars and proteins in liquids

NASA Astrophysics Data System (ADS)

Jandt, Jennifer; Larson, Hannah K.; Tellez, Peter; McGlynn, Terrence P.

2013-12-01

Flexibility in behavior can increase the likelihood that a forager may respond optimally in a fluctuating environment. Nevertheless, physiological or neuronal constraints may result in suboptimal responses to stimuli. We observed foraging workers of the giant tropical ant (also referred to as the "bullet ant"), Paraponera clavata, as they reacted to liquid solutions with varying concentrations of sugar and protein. We show that when protein/sucrose concentration is high, many bullet ants will often try to grasp at the droplet, rather than gather it by drinking. Because P. clavata actively hunt for prey, fixed action patterns and rapid responses to protein may be adaptively important, regardless of the medium in which it is presented. We conclude that, in P. clavata, food-handling decisions are made in response to the nutrient content of the food rather than the texture of the food. Further, we suggest that colonies that maintain a mixture of individuals with consistent fixed or flexible behavioral responses to food-handling decisions may be better adapted to fluctuating environmental conditions, and we propose future studies that could address this.

Dual Fragment Impact of PBX Charges

NASA Astrophysics Data System (ADS)

Haskins, Peter; Briggs, Richard; Leeming, David; White, Nathan; Cheese, Philip; DE&S MoD UK Team; Ordnance Test Solutions Ltd Team

2017-06-01

Fragment impact can pose a significant hazard to many systems containing explosives or propellants. Testing for this threat is most commonly carried out using a single fragment. However, it can be argued that an initial fragment strike (or strikes) could sensitise the energetic material to subsequent impacts, which may then lead to a more violent reaction than would have been predicted based upon single fragment studies. To explore this potential hazard we have developed the capability to launch 2 fragments from the same gun at a range of velocities, and achieve impacts on an acceptor charge with good control over the spatial and temporal separation of the strikes. In this paper we will describe in detail the experimental techniques we have used, both to achieve the dual fragment launch and observe the acceptor charge response. In addition, we will describe the results obtained against PBX filled explosive targets; discuss the mechanisms controlling the target response and their significance for vulnerability assessment. Results of these tests have clearly indicated the potential for detonation upon the second strike, at velocities well below those needed for shock initiation by a single fragment.

Driven fragmentation of granular gases.

PubMed

Cruz Hidalgo, Raúl; Pagonabarraga, Ignacio

2008-06-01

The dynamics of homogeneously heated granular gases which fragment due to particle collisions is analyzed. We introduce a kinetic model which accounts for correlations induced at the grain collisions and analyze both the kinetics and relevant distribution functions these systems develop. The work combines analytical and numerical studies based on direct simulation Monte Carlo calculations. A broad family of fragmentation probabilities is considered, and its implications for the system kinetics are discussed. We show that generically these driven materials evolve asymptotically into a dynamical scaling regime. If the fragmentation probability tends to a constant, the grain number diverges at a finite time, leading to a shattering singularity. If the fragmentation probability vanishes, then the number of grains grows monotonously as a power law. We consider different homogeneous thermostats and show that the kinetics of these systems depends weakly on both the grain inelasticity and driving. We observe that fragmentation plays a relevant role in the shape of the velocity distribution of the particles. When the fragmentation is driven by local stochastic events, the long velocity tail is essentially exponential independently of the heating frequency and the breaking rule. However, for a Lowe-Andersen thermostat, numerical evidence strongly supports the conjecture that the scaled velocity distribution follows a generalized exponential behavior f(c) approximately exp(-cn) , with n approximately 1.2 , regarding less the fragmentation mechanisms.

Is estimated bullet trajectory a reliable predictor of severe injury? Case report of a thoraco-abdominal gunshot with a protracted trajectory managed nonoperatively.

PubMed

Khan, Muhammad Sohaib; Khan, Bilal Masood; Naz, Sumbul; Pirzada, Muhammad Taqi

2013-02-15

Operative management of all gunshot's traumas carries a high rate of unwarranted interventions that are known to cause serious complications. Selective nonoperative management is thus being increasingly practiced which has reduced these avoidable interventions. Physical examination and computed tomography scans are most sensitive in assessing need of laparotomy. Assessment of internal injuries on the basis of an estimated bullet trajectory is often practiced but has seldom been studied. We report a case of conservative management of a thoraco abdominal gun shot patient where an estimated bullet trajectory was indicative of serious injuries. To the best of our knowledge this is the first report of a thoraco abdominal gunshot that, despite of a protracted trajectory, had no sequelae and was thus managed nonoperatively. A 30 year old male patient having height of 180 cm and weight of 70 kg (Body Mass Index 21.6) presented with complaint of a penetrating injury at left side of upper torso. The patient had no symptoms or obvious bleeding and was vitally stable. On examination a 1 cm × 1 cm entry wound at the left 3rd intercostal space in the mid clavicular line was identified. The chest and abdomen were otherwise unremarkable on examination. The chest radiograph displayed clear lung fields. The abdominal radiographs displayed a bullet in the upper left quadrant of the abdomen lateral to the spine. The bullets estimated trajectory from 3rd intercostal space and its lodgment in the abdomen lateral to the spine indicated severe visceral injury. The computed tomography scan showed that the bullet was lodged postero-medially to the left kidney. All thoracic, intra peritoneal and retroperitoneal visceral structures were identified to be normal. The patient remained clinically and vitally stable, hence was managed nonoperatively being discharged after 48 h of observation. From this case we conclude that decision for managing gun shot patients should be based on objective

Is estimated bullet trajectory a reliable predictor of severe injury? Case report of a thoraco-abdominal gunshot with a protracted trajectory managed nonoperatively

PubMed Central

2013-01-01

Background Operative management of all gunshot’s traumas carries a high rate of unwarranted interventions that are known to cause serious complications. Selective nonoperative management is thus being increasingly practiced which has reduced these avoidable interventions. Physical examination and computed tomography scans are most sensitive in assessing need of laparotomy. Assessment of internal injuries on the basis of an estimated bullet trajectory is often practiced but has seldom been studied. We report a case of conservative management of a thoraco abdominal gun shot patient where an estimated bullet trajectory was indicative of serious injuries. To the best of our knowledge this is the first report of a thoraco abdominal gunshot that, despite of a protracted trajectory, had no sequelae and was thus managed nonoperatively. Case presentation A 30 year old male patient having height of 180 cm and weight of 70 kg (Body Mass Index 21.6) presented with complaint of a penetrating injury at left side of upper torso. The patient had no symptoms or obvious bleeding and was vitally stable. On examination a 1 cm × 1 cm entry wound at the left 3rd intercostal space in the mid clavicular line was identified. The chest and abdomen were otherwise unremarkable on examination. The chest radiograph displayed clear lung fields. The abdominal radiographs displayed a bullet in the upper left quadrant of the abdomen lateral to the spine. The bullets estimated trajectory from 3rd intercostal space and its lodgment in the abdomen lateral to the spine indicated severe visceral injury. The computed tomography scan showed that the bullet was lodged postero-medially to the left kidney. All thoracic, intra peritoneal and retroperitoneal visceral structures were identified to be normal. The patient remained clinically and vitally stable, hence was managed nonoperatively being discharged after 48 h of observation. Conclusion From this case we conclude that decision for managing gun

Comparison of Gunshot Entrance Morphologies Caused by .40-Caliber Smith & Wesson, .380-Caliber, and 9-mm Luger Bullets: A Finite Element Analysis Study

PubMed Central

Matoso, Rodrigo Ivo; Freire, Alexandre Rodrigues; Santos, Leonardo Soriano de Mello; Daruge Junior, Eduardo; Rossi, Ana Claudia; Prado, Felippe Bevilacqua

2014-01-01

Firearms can cause fatal wounds, which can be identified by traces on or around the body. However, there are cases where neither the bullet nor gun is found at the crime scene. Ballistic research involving finite element models can reproduce computational biomechanical conditions, without compromising bioethics, as they involve no direct tests on animals or humans. This study aims to compare the morphologies of gunshot entrance holes caused by.40-caliber Smith & Wesson (S&W), .380-caliber, and 9×19-mm Luger bullets. A fully metal-jacketed.40 S&W projectile, a fully metal-jacketed.380 projectile, and a fully metal-jacketed 9×19-mm Luger projectile were computationally fired at the glabellar region of the finite element model from a distance of 10 cm, at perpendicular incidence. The results show different morphologies in the entrance holes produced by the three bullets, using the same skull at the same shot distance. The results and traits of the entrance holes are discussed. Finite element models allow feasible computational ballistic research, which may be useful to forensic experts when comparing and analyzing data related to gunshot wounds in the forehead. PMID:25343337

Lead identification for the K-Ras protein: virtual screening and combinatorial fragment-based approaches

PubMed Central

Pathan, Akbar Ali Khan; Panthi, Bhavana; Khan, Zahid; Koppula, Purushotham Reddy; Alanazi, Mohammed Saud; Sachchidanand; Parine, Narasimha Reddy; Chourasia, Mukesh

2016-01-01

Objective Kirsten rat sarcoma (K-Ras) protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results Interestingly, the designed compounds exhibit a binding preference for the “off” state over “on” state conformation of K-Ras protein. Moreover, the designed compounds’ interactions are similar to guanosine diphosphate and, thus, could presumably act as a potential lead for K-Ras. The predicted drug-likeness properties of these compounds suggest that these compounds follow the Lipinski’s rule of five and have tolerable absorption, distribution, metabolism, excretion and toxicity values. Conclusion Thus, through the current study, we propose targeting only “off” state conformations as a promising strategy for the design of reversible inhibitors to pharmacologically inhibit distinct conformations of K-Ras protein. PMID:27217775

Pseudotumor cerebri (toxic effect of the "magic bullet").

PubMed

Alemayehu, W

1995-10-01

A 10 year-old female patient presented to the outpatient unit of the ophthalmology department of Menelik II Hospital with complaints of inward deviation of the left eye, of three weeks' duration. The patient was on a mega dose of vitamin A 200,000 I.U. (the "magic bullet") daily for two months prior to the onset of the present illness. Physical examination revealed left sixth nerve palsy and bilateral papilloedema in an alert and oriented patient without localizing neurologic findings. The cerebrospinal fluid pressure ( > 250 mm water) was increased and skull X-ray findings were suggestive of increased intracranial pressure (IIP). This case meets the modified Dandy criteria except that a highly likely cause, hypervitaminosis A, is associated. Therefore, a diagnosis of Idiopathic Intracranial Hypertension (IIH) or Pseudotumor Cerebri was made. This disorder and its management is discussed and literature reviewed. The serious and potentially blinding toxic effect of Vitamin A, if consumed in excessive amounts, is emphasized.

Lead generation and examples opinion regarding how to follow up hits.

PubMed

Orita, Masaya; Ohno, Kazuki; Warizaya, Masaichi; Amano, Yasushi; Niimi, Tatsuya

2011-01-01

In fragment-based drug discovery (FBDD), not only identifying the starting fragment hit to be developed but also generating a drug lead from that starting fragment hit is important. Converting fragment hits to leads is generally similar to a high-throughput screening (HTS) hits-to-leads approach in that properties associated with activity for a target protein, such as selectivity against other targets and absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox), and physicochemical properties should be taken into account. However, enhancing the potency of the fragment hit is a key requirement in FBDD, unlike HTS, because initial fragment hits are generally weak. This enhancement is presently achieved by adding additional chemical groups which bind to additional parts of the target protein or by joining or combining two or more hit fragments; however, strategies for effecting greater improvements in effective activity are needed. X-ray analysis is a key technology attractive for converting fragments to drug leads. This method makes it clear whether a fragment hit can act as an anchor and provides insight regarding introduction of functional groups to improve fragment activity. Data on follow-up chemical synthesis of fragment hits has allowed for the differentiation of four different strategies: fragment optimization, fragment linking, fragment self-assembly, and fragment evolution. Here, we discuss our opinion regarding how to follow up on fragment hits, with a focus on the importance of fragment hits as an anchor moiety to so-called hot spots in the target protein using crystallographic data. Copyright © 2011 Elsevier Inc. All rights reserved.

Sub-fragmentation of structural-reactive-material casings under explosion

NASA Astrophysics Data System (ADS)

Zhang, Fan

2015-06-01

The sub-fragmentation of structural reactive material (SRM) thick-casings is to generate fine fragments during casing fragmentation under explosive loading for their efficient energy release to enhance air blast. This has been investigated using a cylindrical casing made from either rich Al-MoO3 or Al-W-based granular composites. The former composite was to study the concept of reactive hot spots where the reaction of reactive particles, which were distributed into base SRM in a fuel-rich equivalence ratio, created heat and gas products during SRM fragmentation. The expansion of these distributed hot spots initiated local fractures of the casing, leading to fine fragments. The Al-W-based composite investigated the concept of impedance mismatch, where shock dynamics at the interfaces of different impedance ingredients resulted in non-uniform, high local temperatures and stresses and late in times the dissimilar inertia resulted in different accelerations, leading to material separation and fine fragments. The casings were manufactured through both hot iso-static pressing and cold gas dynamic spray deposition. Explosion experiments were conducted in a 3 m diameter, 23 m3 cylindrical chamber for these cased charges in a casing-to-explosive mass ratio of 1.75. The results demonstrated the presence of fine fragments and more efficient fragment combustion, compared with previous results, and indicated the effectiveness of both concepts. This work was jointly funded by Defence R&D Canada and the Advanced Energetics Program of DTRA (Dr. William H. Wilson).

Effect of type and transfer of conventional weapons on civilian injuries: retrospective analysis of prospective data from Red Cross hospitals

PubMed Central

Coupland, Robin M; Samnegaard, Hans O

1999-01-01

Objective To examine the link between different weapons used in modern wars and their potential to injury civilians. Design Retrospective analysis of prospectively collected data about hospital admissions. Setting Hospitals of the International Committee of the Red Cross. Subjects 18 877 people wounded by bullets, fragmentation munitions, or mines. Of these, 2012 had been admitted to the hospital in Kabul within six hours of injury. Main outcome measures Age and sex of wounded people according to cause of injury and whether they were civilians (women and girls, boys under 16 years old, or men of 50 or more). Results 18.7% of those injured by bullets, 34.1% of those injured by fragments, and 30.8% of those injured by mines were civilians. Of those admitted to the Red Cross hospital in Kabul within six hours of injury, 39.1% of those injured by bullets, 60.6% of those injured by fragments, and 55.0% of those injured by mines were civilians. Conclusions The proportion of civilians injured differs between weapon systems. The higher proportion injured by fragments and mines is explicable in terms of the military efficiency of weapons, the distance between user and victim, and the effect that the kind of weapon has on the psychology of the user. Key messagesDuring war, mines and fragmenting munitions (mortars, bombs, and shells) are more likely than bullets to injure civiliansCivilians in a city under siege are particularly at risk of being injured by weapons whose users are not able to see the victimThe inherent nature of weapons may be a factor in determining whether civilians are killed or injuredThere is a need for greater respect for the Fourth Geneva Convention and for greater controls on weapons being transferred to untrained and undisciplined forces PMID:10445921

Integration of fragment screening and library design.

PubMed

Siegal, Gregg; Ab, Eiso; Schultz, Jan

2007-12-01

With more than 10 years of practical experience and theoretical analysis, fragment-based drug discovery (FBDD) has entered the mainstream of the pharmaceutical and biotech industries. An array of biophysical techniques has been used to detect the weak interaction between a fragment and the target. Each technique presents its own requirements regarding the fragment collection and the target; therefore, in order to optimize the potential of FBDD, the nature of the target should be a driving factor for simultaneous development of both the library and the screening technology. A roadmap is now available to guide fragment-to-lead evolution when structural information is available. The next challenge is to apply FBDD to targets for which high-resolution structural information is not available.

Forest-climate interactions in fragmented tropical landscapes.

PubMed

Laurance, William F

2004-03-29

In the tropics, habitat fragmentation alters forest-climate interactions in diverse ways. On a local scale (less than 1 km), elevated desiccation and wind disturbance near fragment margins lead to sharply increased tree mortality, thus altering canopy-gap dynamics, plant community composition, biomass dynamics and carbon storage. Fragmented forests are also highly vulnerable to edge-related fires, especially in regions with periodic droughts or strong dry seasons. At landscape to regional scales (10-1000 km), habitat fragmentation may have complex effects on forest-climate interactions, with important consequences for atmospheric circulation, water cycling and precipitation. Positive feedbacks among deforestation, regional climate change and fire could pose a serious threat for some tropical forests, but the details of such interactions are poorly understood.

The Evolution of Grain Size Distribution in Explosive Rock Fragmentation - Sequential Fragmentation Theory Revisited

NASA Astrophysics Data System (ADS)

Scheu, B.; Fowler, A. C.

2015-12-01

Fragmentation is a ubiquitous phenomenon in many natural and engineering systems. It is the process by which an initially competent medium, solid or liquid, is broken up into a population of constituents. Examples occur in collisions and impacts of asteroids/meteorites, explosion driven fragmentation of munitions on a battlefield, as well as of magma in a volcanic conduit causing explosive volcanic eruptions and break-up of liquid drops. Besides the mechanism of fragmentation the resulting frequency-size distribution of the generated constituents is of central interest. Initially their distributions were fitted empirically using lognormal, Rosin-Rammler and Weibull distributions (e.g. Brown & Wohletz 1995). The sequential fragmentation theory (Brown 1989, Wohletz at al. 1989, Wohletz & Brown 1995) and the application of fractal theory to fragmentation products (Turcotte 1986, Perfect 1997, Perugini & Kueppers 2012) attempt to overcome this shortcoming by providing a more physical basis for the applied distribution. Both rely on an at least partially scale-invariant and thus self-similar random fragmentation process. Here we provide a stochastic model for the evolution of grain size distribution during the explosion process. Our model is based on laboratory experiments in which volcanic rock samples explode naturally when rapidly depressurized from initial pressures of several MPa to ambient conditions. The physics governing this fragmentation process has been successfully modelled and the observed fragmentation pattern could be numerically reproduced (Fowler et al. 2010). The fragmentation of these natural rocks leads to grain size distributions which vary depending on the experimental starting conditions. Our model provides a theoretical description of these different grain size distributions. Our model combines a sequential model of the type outlined by Turcotte (1986), but generalized to cater for the explosive process appropriate here, in particular by

Lead toxicity as an etiology for abdominal pain in the emergency department.

PubMed

Moriarity, Risa S; Harris, James T; Cox, Robert D

2014-02-01

Abdominal pain is an uncommon presentation of lead toxicity in the emergency department (ED). However, making the diagnosis is important in avoiding unnecessary testing and the long-term sequelae of lead toxicity. To illustrate possible presentations of abdominal pain secondary to lead toxicity and highlight the importance of taking a thorough patient history. We report 2 patients who presented to the ED with abdominal pain and underwent extensive evaluations that did not reveal an etiology. At follow-up visits, their occupational histories revealed possible lead exposures from working for a bullet-recycling company. Tests revealed that each patient had extremely high lead levels and they were both treated for lead toxicity. Their abdominal pain resolved as their lead levels decreased. These cases demonstrate a rare but significant cause of abdominal pain in the ED. Although history-taking in the ED is necessarily brief, these cases underscore the importance of obtaining an occupational history. Copyright © 2014 Elsevier Inc. All rights reserved.

Atmospheric-pressure plasma jets: Effect of gas flow, active species, and snake-like bullet propagation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, S.; Wang, Z.; Huang, Q.

2013-02-15

Cold atmospheric-pressure plasma jets have recently attracted enormous interest owing to numerous applications in plasma biology, health care, medicine, and nanotechnology. A dedicated study of the interaction between the upstream and downstream plasma plumes revealed that the active species (electrons, ions, excited OH, metastable Ar, and nitrogen-related species) generated by the upstream plasma plume enhance the propagation of the downstream plasma plume. At gas flows exceeding 2 l/min, the downstream plasma plume is longer than the upstream plasma plume. Detailed plasma diagnostics and discharge species analysis suggest that this effect is due to the electrons and ions that are generatedmore » by the upstream plasma and flow into the downstream plume. This in turn leads to the relatively higher electron density in the downstream plasma. Moreover, high-speed photography reveals a highly unusual behavior of the plasma bullets, which propagate in snake-like motions, very differently from the previous reports. This behavior is related to the hydrodynamic instability of the gas flow, which results in non-uniform distributions of long-lifetime active species in the discharge tube and of surface charges on the inner surface of the tube.« less

Quantifying Friction Effects of Molybdenum Disulfide, Tungsten Disulfide, Hexagonal Boron Nitride, and Lubalox as Bullet Coating

DTIC Science & Technology

2012-07-30

is not cost effective for most applications . 15. SUBJECT TERMS armor penetration, brass, copper, full metal jacket, steel penetrator 16... applications . Introduction High barrel friction reduces the muzzle velocity of bullets that is important in maintaining long range trajectories...be effective in a variety of high-temperature and high-pressure applications .[2-4] However, the problem of reducing the force required to push a

Habitat fragmentation leads to reduced pollinator visitation, fruit production and recruitment in urban mangrove forests.

PubMed

Hermansen, Tyge D; Minchinton, Todd E; Ayre, David J

2017-10-01

Mangrove forests worldwide undergo anthropogenic fragmentation that may threaten their existence, and yet there have been few tests of the effects of fragmentation on demographic processes critical for mangrove regeneration. Predicting the effects of habitat fragmentation on mangroves is problematic as pollinators may move more freely across water than terrestrial habitat, and propagules can be widely dispersed by water. Here, within each of two estuaries, we compared pollinator diversity and activity, reproductive effort and output, and rates of recruitment for sets of three large (>1500 trees), medium (300-500) and small (<50) stands. As predicted, most measures of reproductive activity and success were inversely related to stand size with large stands typically producing significantly more and larger fruit, and significantly more seedlings. Most strikingly, we found the effect of fragmentation on the abundance of pollinators (honeybees), the production and quality of fruit and the survival rate of seedlings to be similar, showing significant reduction of recruitment in small stands. This study provides the first rigorous evidence that recruitment of mangroves, like for many terrestrial plants, is negatively impacted by habitat fragmentation. From a management perspective, we argue that in the short term our data imply the importance of conserving the largest possible stands. However, additional work is needed to determine (1) the proportion of recruits within small stands that originate within large stands, (2) how seedling performance varies with fruit size and genotype, and (3) how seedling size and performance vary with the abundance and diversity of pollen.

Accurate Binding Free Energy Predictions in Fragment Optimization.

PubMed

Steinbrecher, Thomas B; Dahlgren, Markus; Cappel, Daniel; Lin, Teng; Wang, Lingle; Krilov, Goran; Abel, Robert; Friesner, Richard; Sherman, Woody

2015-11-23

Predicting protein-ligand binding free energies is a central aim of computational structure-based drug design (SBDD)--improved accuracy in binding free energy predictions could significantly reduce costs and accelerate project timelines in lead discovery and optimization. The recent development and validation of advanced free energy calculation methods represents a major step toward this goal. Accurately predicting the relative binding free energy changes of modifications to ligands is especially valuable in the field of fragment-based drug design, since fragment screens tend to deliver initial hits of low binding affinity that require multiple rounds of synthesis to gain the requisite potency for a project. In this study, we show that a free energy perturbation protocol, FEP+, which was previously validated on drug-like lead compounds, is suitable for the calculation of relative binding strengths of fragment-sized compounds as well. We study several pharmaceutically relevant targets with a total of more than 90 fragments and find that the FEP+ methodology, which uses explicit solvent molecular dynamics and physics-based scoring with no parameters adjusted, can accurately predict relative fragment binding affinities. The calculations afford R(2)-values on average greater than 0.5 compared to experimental data and RMS errors of ca. 1.1 kcal/mol overall, demonstrating significant improvements over the docking and MM-GBSA methods tested in this work and indicating that FEP+ has the requisite predictive power to impact fragment-based affinity optimization projects.

A shot through the window.

PubMed

Burnett, B R

2001-03-01

At issue in this case was whether an unusual window defect seen in two of the crime scene photographs was due to a bullet and if so, if that same bullet fatally wounded the victim. The window appeared to have been cracked prior to the apparent shot through it. A .22 bullet recovered from autopsy, when examined only by light microscopy, failed to show associated glass fragments. A previously cracked test window was shot a number of times with .22 caliber bullets near the cracks in an effort to simulate the window defect seen in the crime scene photographs. Several of the defects produced by the test window shots appeared similar to the crime scene window defect. The .22 bullet taken from the victim and several of the test bullets (collected by a cotton box) were examined by scanning electron microscopy/energy dispersive X-ray spectroscopy. The test bullets showed glass particles on and embedded in their surfaces. Particles of similar size and composition were found embedded in the surface of the bullet from the victim. The bullet likely struck the window prior to hitting the victim. It was apparent by the morphology of some of the mushroomed test .22 bullets that they hit the window crack. These bullets showed that the glass on one side of a crack often fails before the other side during the strike. Aggregations of powdered glass on many of the mushroomed surfaces of the .22 bullets suggest that as the bullet mushrooms during impact on the window surface, the glass in contact with the bullet powderizes and coats the mushroomed surface of the bullet with a layer of fine glass particles.

Lead poisoning following ingestion of pieces of lead roofing plates: pica-like behavior in an adult.

PubMed

Sabouraud, Sabine; Testud, François; Descotes, Jacques; Benevent, Monique; Soglu, Gilbert

2008-03-01

A 37-year-old man was admitted to hospital after complaining of abdominal pain for the past two weeks. On admission the abdominal radiograph showed multiple radio-opaque flecks dispersed throughout the gastrointestinal tract. Blood testing showed hemoglobin level 8.7 g/dL and a blood lead level of 112.4 microg/dL. The family interview revealed that the patient had pica-like behavior since childhood. He was a site foreman and had been ingesting pieces of roofing plates for a few weeks. The patient was treated with laxatives and CaNa(2)EDTA therapy was initiated. The blood lead level then dropped to 69.9 microg/dL. The patient received two subsequent courses of oral succimer and the blood lead level decreased to 59 microg/dL 21 days after the first course. The follow-up abdominal X-ray 20 days after the first examination was normal. Four months later, an outpatient follow-up visit showed a blood lead level within normal limits (14.5 microg/dL) and a psychiatric follow-up was initiated. Lead poisoning following the ingestion of lead-containing foreign bodies is particularly rare in adults, while it is sometimes observed in children. Pica behavior is a well-identified risk factor of lead intoxication in children but is quite exceptional in adults, where it is usually considered to be a psychiatric condition. Other unusual sources of lead poisoning include the ingestion of lead bullets, ceramic lead glaze or glazed earthenware, lead-contaminated candies, ethnic or herbal remedies.

A Death Involving a Fired and Deflected Bullet: A Case Report from Lyon University Institute of Forensic Science, France.

PubMed

Maujean, Géraldine; Guinet, Tiphaine; Malicier, Daniel

2016-01-01

In case of gunshot deaths, atypical wounds can make the distinction between entrance and exit wounds harder. They may be due either to anatomical reasons or to diverse cogent ballistic arguments. The reported case pertains to a fatal hunting accident involving an expanded conical point bullet against the neck with both atypical entrance and exit wounds. Ballistic analyses including test firings allowed a better understanding of the external and internal findings. Upon premature impact with an intermediary target, the bullet experienced expansion in the formation of sharp brass petals responsible for a star-shaped entry wound. The trajectory of the deformed high energy projectile through the victim's body was then deviated by the cervical column, causing it to be tangential to the skin when exiting the body. The description of such atypical cases may benefit other experts and may assist in their investigation into similar cases. © 2015 American Academy of Forensic Sciences.

75 FR 36107 - Notice of Intent to Repatriate Cultural Items: U.S. Department of Defense, Army Corps of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

..., 5 cores, 2 digging stick handles, 2 flake perforators, 2 hafted drills, 1 piece of incised bone, 7 pestles, 2 projectile points, and 1 fragment of worked bone. The 32 lots of objects are 4 lots of animal... worked bone fragment, 1 bottle fragment, 13 bullet cartridges, 3 copper pendants, 6 cores, 1 digging...

A systematic review on ricochet gunshot injuries.

PubMed

Yong, Yuw-Er

2017-05-01

Ricocheted bullets may still retain sufficient kinetic energy to cause gunshot injuries. Accordingly, this paper reviews the literature surrounding gunshot injuries caused by ricocheted bullets. In doing so, it discusses the characteristics of ricochet entrance wounds and wound tracks, noting several important considerations for assessment of a possible ricochet incident. The shapes of ricochet entrance wounds vary, ranging from round holes to elliptical, large and irregular shapes. Pseudo-stippling or pseudo-gunpowder tattooing, pseudo-soot blackening and tumbling abrasions seen on the skin surrounding the bullet hole are particularly associated with ricochet incidents. Ricocheted bullets have a reduced capability for tissue penetration. Most of the resulting wound tracks are short, of large diameter and irregular-all artefacts of the instability of a bullet that has ricocheted. A ricocheted hollow-point bullet, in particular, may overpenetrate the tissue when the bullet nose is deformed or fails to enter the body in a nose-forward orientation. Similarly, internal ricochet may occur when a bullet strikes hard tissue. Postmortem computed tomographic imaging is useful for localising a bullet and its fragments in the body and characterising the wound track. Ricochet cannot be ruled out in normal-appearing entrance wounds unless that finding is supported by other evidence, including the geometrical constraints of the shooting scene and the absence of ricochet marks and a ricocheted bullet. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-psychotropic analgesic drugs from the endocannabinoid system: "magic bullet" or "multiple-target" strategies?

PubMed

Starowicz, Katarzyna; Di Marzo, Vincenzo

2013-09-15

The exploitation of preparations of Cannabis sativa to combat pain seems to date back to time immemorial, although their psychotropic effects, which are at the bases of their recreational use and limit their therapeutic use, are at least as ancient. Indeed, it has always been different to tease apart the unwanted central effects from the therapeutic benefits of Δ⁹-tetrahydrocannabinol (THC), the main psychotropic component of cannabis. The discovery of the cannabinoid receptors and of their endogenous ligands, the endocannabinoids, which, unlike THC, play a pro-homeostatic function in a tissue- and time-selective manner, offered the opportunity to develop new analgesics from synthetic inhibitors of endocannabinoid inactivation. The advantages of this approach over direct activation of cannabinoid receptors as a therapeutic strategy against neuropathic and inflammatory pain are discussed here along with its potential complications. These latter have been such that clinical success has been achieved so far more rapidly with naturally occurring THC or endocannabinoid structural analogues acting at a plethora of cannabinoid-related and -unrelated molecular targets, than with selective inhibitors of endocannabinoid enzymatic hydrolysis, thus leading to revisit the potential usefulness of "multi-target" versus "magic bullet" compounds as new analgesics. © 2013 Elsevier B.V. All rights reserved.

[Understanding mitochondrial genome fragmentation in parasitic lice (Insecta: Phthiraptera)].

PubMed

Dong, Wen-Ge; Guo, Xian-Guo; Jin, Dao-Chao; Xue, Shi-Peng; Qin, Feng; Simon, Song; Stephen, C Barker; Renfu, Shao

2013-07-01

Lice are obligate ectoparasites of mammals and birds. Extensive fragmentation of mitochondrial genomes has been found in some louse species in the families Pediculidae, Pthiridae, Philopteridae and Trichodectidae. For example, the mt genomes of human body louse (Pediculus humanus), head louse (Pediculus capitis), and public louse (Pthirus pubis) have 20, 20 and 14 mini-chromosomes, respectively. These mini-chromosomes might be the results of deletion and recombination of mt genes. The factors and mechanisms of mitochondrial genome fragmentation are currently unknown. The fragmentation might be the results of evolutionary selection or random genetic drift or it is probably related to the lack of mtSSB (mitochondrial single-strand DNA binding protein). Understanding the fragmentation of mitochondrial genomes is of significance for understanding the origin and evolution of mitochondria. This paper reviews the recent advances in the studies of mito-chondrial genome fragmentation in lice, including the phenomena of mitochondrial genome fragmentation, characteristics of fragmented mitochondrial genomes, and some factors and mechanisms possibly leading to the mitochondrial genome fragmentation of lice. Perspectives for future studies on fragmented mt genomes are also discussed.

Design Principles for Fragment Libraries: Maximizing the Value of Learnings from Pharma Fragment-Based Drug Discovery (FBDD) Programs for Use in Academia.

PubMed

Keserű, György M; Erlanson, Daniel A; Ferenczy, György G; Hann, Michael M; Murray, Christopher W; Pickett, Stephen D

2016-09-22

Fragment-based drug discovery (FBDD) is well suited for discovering both drug leads and chemical probes of protein function; it can cover broad swaths of chemical space and allows the use of creative chemistry. FBDD is widely implemented for lead discovery in industry but is sometimes used less systematically in academia. Design principles and implementation approaches for fragment libraries are continually evolving, and the lack of up-to-date guidance may prevent more effective application of FBDD in academia. This Perspective explores many of the theoretical, practical, and strategic considerations that occur within FBDD programs, including the optimal size, complexity, physicochemical profile, and shape profile of fragments in FBDD libraries, as well as compound storage, evaluation, and screening technologies. This compilation of industry experience in FBDD will hopefully be useful for those pursuing FBDD in academia.

Experimental modelling of fragmentation applied to volcanic explosions

NASA Astrophysics Data System (ADS)

Haug, Øystein Thordén; Galland, Olivier; Gisler, Galen R.

2013-12-01

Explosions during volcanic eruptions cause fragmentation of magma and host rock, resulting in fragments with sizes ranging from boulders to fine ash. The products can be described by fragment size distributions (FSD), which commonly follow power laws with exponent D. The processes that lead to power-law distributions and the physical parameters that control D remain unknown. We developed a quantitative experimental procedure to study the physics of the fragmentation process through time. The apparatus consists of a Hele-Shaw cell containing a layer of cohesive silica flour that is fragmented by a rapid injection of pressurized air. The evolving fragmentation of the flour is monitored with a high-speed camera, and the images are analysed to obtain the evolution of the number of fragments (N), their average size (A), and the FSD. Using the results from our image-analysis procedure, we find transient empirical laws for N, A and the exponent D of the power-law FSD as functions of the initial air pressure. We show that our experimental procedure is a promising tool for unravelling the complex physics of fragmentation during phreatomagmatic and phreatic eruptions.

Characteristic fragment size distributions in dynamic fragmentation

NASA Astrophysics Data System (ADS)

Zhou, Fenghua; Molinari, Jean-François; Ramesh, K. T.

2006-06-01

The one-dimensional fragmentation of a dynamically expanding ring (Mott's problem) is studied numerically to obtain the fragment signatures under different strain rates. An empirical formula is proposed to calculate an average fragment size. Rayleigh distribution is found to describe the statistical properties of the fragment populations.

NMR screening in fragment-based drug design: a practical guide.

PubMed

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (<300-350 Da) and lower initial potency but higher ligand efficiency when compared to those from high-throughput screening. NMR spectroscopy has been widely used for FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.

PubMed

Han, Byeonggu; Ahn, Hee-Chul

2016-01-01

During the past decade fragment-based drug discovery (FBDD) has rapidly evolved and several drugs or drug candidates developed by FBDD approach are clinically in use or in clinical trials. For example, vemurafenib, a V600E mutated BRAF inhibitor, was developed by utilizing FBDD approach and approved by FDA in 2011. In FBDD, screening of fragments is the starting step for identification of hits and lead generation. Fragment screening usually relies on biophysical techniques by which the protein-bound small molecules can be detected. NMR spectroscopy has been extensively used to study the molecular interaction between the protein and the ligand, and has many advantages in fragment screening over other biophysical techniques. This chapter describes the practical aspects of fragment screening by saturation transfer difference NMR.

The rise of fragment-based drug discovery.

PubMed

Murray, Christopher W; Rees, David C

2009-06-01

The search for new drugs is plagued by high attrition rates at all stages in research and development. Chemists have an opportunity to tackle this problem because attrition can be traced back, in part, to the quality of the chemical leads. Fragment-based drug discovery (FBDD) is a new approach, increasingly used in the pharmaceutical industry, for reducing attrition and providing leads for previously intractable biological targets. FBDD identifies low-molecular-weight ligands (∼150 Da) that bind to biologically important macromolecules. The three-dimensional experimental binding mode of these fragments is determined using X-ray crystallography or NMR spectroscopy, and is used to facilitate their optimization into potent molecules with drug-like properties. Compared with high-throughput-screening, the fragment approach requires fewer compounds to be screened, and, despite the lower initial potency of the screening hits, offers more efficient and fruitful optimization campaigns. Here, we review the rise of FBDD, including its application to discovering clinical candidates against targets for which other chemistry approaches have struggled.

Visualization of sneeze ejecta: steps of fluid fragmentation leading to respiratory droplets

NASA Astrophysics Data System (ADS)

Scharfman, B. E.; Techet, A. H.; Bush, J. W. M.; Bourouiba, L.

2016-02-01

Coughs and sneezes feature turbulent, multiphase flows that may contain pathogen-bearing droplets of mucosalivary fluid. As such, they can contribute to the spread of numerous infectious diseases, including influenza and SARS. The range of contamination of the droplets is largely determined by their size. However, major uncertainties on the drop size distributions persist. Here, we report direct observation of the physical mechanisms of droplet formation at the exit of the mouth during sneezing. Specifically, we use high-speed imaging to directly examine the fluid fragmentation at the exit of the mouths of healthy subjects. We reveal for the first time that the breakup of the fluid into droplets continues to occur outside of the respiratory tract during violent exhalations. We show that such breakup involves a complex cascade of events from sheets, to bag bursts, to ligaments, which finally break into droplets. Finally, we reveal that the viscoelasticity of the mucosalivary fluid plays an important role in delaying fragmentation by causing the merger of the droplet precursors that form along stretched filaments; thereby affecting the final drop size distribution farther downstream.

The multiple roles of computational chemistry in fragment-based drug design

NASA Astrophysics Data System (ADS)

Law, Richard; Barker, Oliver; Barker, John J.; Hesterkamp, Thomas; Godemann, Robert; Andersen, Ole; Fryatt, Tara; Courtney, Steve; Hallett, Dave; Whittaker, Mark

2009-08-01

Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry.

PubMed

Mondal, Milon; Radeva, Nedyalka; Fanlo-Virgós, Hugo; Otto, Sijbren; Klebe, Gerhard; Hirsch, Anna K H

2016-08-01

Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

A model of posttraumatic epilepsy after penetrating brain injuries: effect of lesion size and metal fragments.

PubMed

Kendirli, M Tansel; Rose, Dominique T; Bertram, Edward H

2014-12-01

Penetrating brain injury (PBI) has the highest risk for inducing posttraumatic epilepsy, and those PBIs with retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-electroencephalography (EEG). A separate set of animals was examined for possible acute seizures in the week following the injury. Twenty-two of the 23 animals with copper wire developed chronic epilepsy, compared to three of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute postinjury seizures. Lesion size may contribute to epilepsy development in lesion-only animals. Copper may be an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Identifying Interactions that Determine Fragment Binding at Protein Hotspots.

PubMed

Radoux, Chris J; Olsson, Tjelvar S G; Pitt, Will R; Groom, Colin R; Blundell, Tom L

2016-05-12

Locating a ligand-binding site is an important first step in structure-guided drug discovery, but current methods do little to suggest which interactions within a pocket are the most important for binding. Here we illustrate a method that samples atomic hotspots with simple molecular probes to produce fragment hotspot maps. These maps specifically highlight fragment-binding sites and their corresponding pharmacophores. For ligand-bound structures, they provide an intuitive visual guide within the binding site, directing medicinal chemists where to grow the molecule and alerting them to suboptimal interactions within the original hit. The fragment hotspot map calculation is validated using experimental binding positions of 21 fragments and subsequent lead molecules. The ligands are found in high scoring areas of the fragment hotspot maps, with fragment atoms having a median percentage rank of 97%. Protein kinase B and pantothenate synthetase are examined in detail. In each case, the fragment hotspot maps are able to rationalize a Free-Wilson analysis of SAR data from a fragment-based drug design project.

Direct connection between the different QCD orders for parton distribution and fragmentation functions

NASA Astrophysics Data System (ADS)

Shevchenko, O. Yu.

2013-06-01

The formulas directly connecting parton distribution functions and fragmentation functions at the next-to-leading-order QCD with the same quantities at the leading order are derived. These formulas are universal, i.e., have the same form for all kinds of parton distribution functions and fragmentation functions, differing only in the respective splitting functions entering there.

Gunshot injuries due to celebratory gun shootings.

PubMed

Ozdemir, Mevci; Unlü, Ağahan

2009-01-01

Traditional shooting with guns often occurs and leads to unwanted gunshot injuries in areas where celebrations are held. Such injuries have been classified as celebratory gun shooting injury in the international disease classification system. An 8-year-old female patient presented with respiratory arrest. The heartbeats normalized upon cardiopulmonary resuscitation. On physical examination, the only pathological finding was a skin defect measuring 1 x 1 cm on the midline and located 2 cm in front of the coronal suture. Cranial CT revealed a bone defect of 0.5 cm in the area 2 cm in front of the coronal suture on the midline, tetraventricular and extensive subarachnoid hemorrhage and parenchymal hematoma in the frontal area. It was initially thought to be a gunshot injury; however, on cranial CT, no bullet fragments or bullet exit hole was observed. A cervicothoracal direct graph was obtained and an image that might have been compatible with a bullet core was detected at Th 2-3 vertebra level. Although gunshot injuries are generally well- known, this may not be a very familiar topic for neurosurgeons. The primary aim of this report is to emphasize that a bullet round randomly fired into the air ascends in reverse direction to gravity and after reaching a zero point, it returns to the ground at a high velocity that facilitates its penetration into the skull according to a principal physics law.

Radio-emitting component kinematics in SS433

NASA Astrophysics Data System (ADS)

Stirling, A. M.; Jowett, F. H.; Spencer, R. E.; Paragi, Z.; Ogley, R. N.; Cawthorne, T. V.

2002-12-01

SS433 is a galactic X-ray binary source, variable across most wavelengths of observation. On arcsecond-scales the radio emission is composed of a bright core and the famous bipolar `corkscrew' radio jets. A series of MERLIN observations at 5 GHz were taken in 1991 December and 1992 January. The emission from the radio jet was categorized by replacing discrete features with Gaussian flux-density profiles. These fitted components were used to derive proper motions, ejection position-angles and ejection dates for evolving features in the jets. The observed component position-angles and ejection dates were compared to those predicted by the kinematic model of epoch 1989. The position-angle of the precession cone was refined to . A discrepancy was discovered in the observed precessional phase which was leading that of the kinematic model by 7-10 d. This observed discrepancy was in agreement with a transient deviation in precessional phase as measured by the redshifts of optical bullets at a similar time. Analysis of the proper motions of all the fitted components leads to a distance measurement of 4.61 +/- 0.35 pc. A pair of symmetrically ejected knots with a velocity much lower than 0.26c were also discovered. Their ejection time overlapped with a period of unusual Doppler shift residuals and fragmentation of optical bullets. These events may represent the first evidence for an interaction between radio components and optical bullets.

Searching for substructures in fragment spaces.

PubMed

Ehrlich, Hans-Christian; Volkamer, Andrea; Rarey, Matthias

2012-12-21

A common task in drug development is the selection of compounds fulfilling specific structural features from a large data pool. While several methods that iteratively search through such data sets exist, their application is limited compared to the infinite character of molecular space. The introduction of the concept of fragment spaces (FSs), which are composed of molecular fragments and their connection rules, made the representation of large combinatorial data sets feasible. At the same time, search algorithms face the problem of structural features spanning over multiple fragments. Due to the combinatorial nature of FSs, an enumeration of all products is impossible. In order to overcome these time and storage issues, we present a method that is able to find substructures in FSs without explicit product enumeration. This is accomplished by splitting substructures into subsubstructures and mapping them onto fragments with respect to fragment connectivity rules. The method has been evaluated on three different drug discovery scenarios considering the exploration of a molecule class, the elaboration of decoration patterns for a molecular core, and the exhaustive query for peptides in FSs. FSs can be searched in seconds, and found products contain novel compounds not present in the PubChem database which may serve as hints for new lead structures.

Biographical Sources in the Sciences--Life, Earth and Physical Sciences (1989-2006). LC Science Tracer Bullet. TB 06-4

ERIC Educational Resources Information Center

Freitag, Ruth, Comp.; Bradley, Michelle Cadoree, Comp.

2006-01-01

This guide offers a systematic approach to the wide variety of published biographical information on men and women of science in the life, earth and physical sciences, primarily from 1989 to 2006, and complements Library of Congress Science Tracer Bullet "TB88-3" ("Biographical Sources in the Sciences," compiled 1988 [ED306074]) and "TB06-7"…

Self-action of Bessel wave packets in a system of coupled light guides and formation of light bullets

NASA Astrophysics Data System (ADS)

Balakin, A. A.; Mironov, V. A.; Skobelev, S. A.

2017-01-01

The self-action of two-dimensional and three-dimensional Bessel wave packets in a system of coupled light guides is considered using the discrete nonlinear Schrödinger equation. The features of the self-action of such wave fields are related to their initial strong spatial inhomogeneity. The numerical simulation shows that for the field amplitude exceeding a critical value, the development of an instability typical of a medium with the cubic nonlinearity is observed. Various regimes are studied: the self-channeling of a wave beam in one light guide at powers not strongly exceeding a critical value, the formation of the "kaleidoscopic" picture of a wave packet during the propagation of higher-power radiation along a stratified medium, the formation of light bullets during competition between self-focusing and modulation instabilities in the case of three-dimensional wave packets, etc. In the problem of laser pulse shortening, the situation is considered when the wave-field stratification in the transverse direction dominates. This process is accompanied by the self-compression of laser pulses in well enough separated light guides. The efficiency of conversion of the initial Bessel field distribution to two flying parallel light bullets is about 50%.

A Model of Post-Traumatic Epilepsy After Penetrating Brain Injuries: Effect of Lesion Size and Metal Fragments

PubMed Central

Kendirli, M. Tansel; Rose, Dominique T.; Bertram, Edward H.

2014-01-01

Objective Penetrating brain injury (PBI) has the highest risk for inducing post-traumatic epilepsy and retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Methods Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-EEG. A separate set of animals was examined for possible acute seizures in the week following the injury. Results 22 of the 23 animals with copper wire developed chronic epilepsy compared to 3 of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Conclusions Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute post-injury seizures. Lesion size may contribute to epilepsy development in lesion only animals. Copper maybe an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. PMID:25470332

The ways and means of fragment-based drug design.

PubMed

Doak, Bradley C; Norton, Raymond S; Scanlon, Martin J

2016-11-01

Fragment-based drug design (FBDD) has emerged as a mainstream approach for the rapid and efficient identification of building blocks that can be used to develop high-affinity ligands against protein targets. One of the strengths of FBDD is the relative ease and low cost of the primary screen to identify fragments that bind. However, the fragments that emerge from primary screens often have low affinities, with K D values in the high μM to mM range, and a significant challenge for FBDD is to develop the initial fragments into more potent ligands. Successful fragment elaboration often requires co-structures of the fragments bound to their target proteins, as well as a range of biophysical and biochemical assays to track potency and efficacy. These challenges have led to the development of specific chemical strategies for the elaboration of weakly-binding fragments into more potent "hits" and lead compounds. In this article we review different approaches that have been employed to meet these challenges and describe some of the strategies that have resulted in several fragment-derived compounds entering clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

A BRIGHT SUBMILLIMETER SOURCE IN THE BULLET CLUSTER (1E0657-56) FIELD DETECTED WITH BLAST

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rex, Marie; Devlin, Mark J.; Dicker, Simon R.

2009-09-20

We present the 250, 350, and 500 {mu}m detection of bright submillimeter emission in the direction of the Bullet Cluster measured by the Balloon-borne Large-Aperture Submillimeter Telescope (BLAST). The 500 {mu}m centroid is coincident with an AzTEC 1.1 mm point-source detection at a position close to the peak lensing magnification produced by the cluster. However, the 250 {mu}m and 350 {mu}m centroids are elongated and shifted toward the south with a differential shift between bands that cannot be explained by pointing uncertainties. We therefore conclude that the BLAST detection is likely contaminated by emission from foreground galaxies associated with themore » Bullet Cluster. The submillimeter redshift estimate based on 250-1100 {mu}m photometry at the position of the AzTEC source is z{sub phot} = 2.9{sup +0.6}{sub -0.3}, consistent with the infrared color redshift estimation of the most likely Infrared Array Camera counterpart. These flux densities indicate an apparent far-infrared (FIR) luminosity of L{sub FIR} = 2 x 10{sup 13} L {sub sun}. When the amplification due to the gravitational lensing of the cluster is removed, the intrinsic FIR luminosity of the source is found to be L{sub FIR} <= 10{sup 12} L{sub sun}, consistent with typical luminous infrared galaxies.« less

Embedded fragments from U.S. military personnel--chemical analysis and potential health implications.

PubMed

Centeno, José A; Rogers, Duane A; van der Voet, Gijsbert B; Fornero, Elisa; Zhang, Lingsu; Mullick, Florabel G; Chapman, Gail D; Olabisi, Ayodele O; Wagner, Dean J; Stojadinovic, Alexander; Potter, Benjamin K

2014-01-23

The majority of modern war wounds are characterized by high-energy blast injuries containing a wide range of retained foreign materials of a metallic or composite nature. Health effects of retained fragments range from local or systemic toxicities to foreign body reactions or malignancies, and dependent on the chemical composition and corrosiveness of the fragments in vivo. Information obtained by chemical analysis of excised fragments can be used to guide clinical decisions regarding the need for fragment removal, to develop therapeutic interventions, and to better anticipate future medical problems from retained fragment related injuries. In response to this need, a new U.S Department of Defense (DoD) directive has been issued requiring characterization of all removed fragments to provide a database of fragment types occurring in combat injuries. The objective of this study is to determine the chemical composition of retained embedded fragments removed from injured military personnel, and to relate results to histological findings in tissue adjacent to fragment material. We describe an approach for the chemical analysis and characterization of retained fragments and adjacent tissues, and include case examples describing fragments containing depleted uranium (DU), tungsten (W), lead (Pb), and non-metal foreign bodies composed of natural and composite materials. Fragments obtained from four patients with penetrating blast wounds to the limbs were studied employing a wide range of chemical and microscopy techniques. Available adjacent tissues from three of the cases were histologically, microscopically, and chemically examined. The physical and compositional properties of the removed foreign material surfaces were examined with energy dispersive x-ray fluorescence spectrometry (EDXRF), scanning electron microscopy (SEM), laser ablation inductively-coupled plasma mass-spectrometry (LA-ICP-MS), and confocal laser Raman microspectroscopy (CLRM). Quantitative chemical

Embedded Fragments from U.S. Military Personnel—Chemical Analysis and Potential Health Implications

PubMed Central

Centeno, José A.; Rogers, Duane A.; van der Voet, Gijsbert B.; Fornero, Elisa; Zhang, Lingsu; Mullick, Florabel G.; Chapman, Gail D.; Olabisi, Ayodele O.; Wagner, Dean J.; Stojadinovic, Alexander; Potter, Benjamin K.

2014-01-01

Background: The majority of modern war wounds are characterized by high-energy blast injuries containing a wide range of retained foreign materials of a metallic or composite nature. Health effects of retained fragments range from local or systemic toxicities to foreign body reactions or malignancies, and dependent on the chemical composition and corrosiveness of the fragments in vivo. Information obtained by chemical analysis of excised fragments can be used to guide clinical decisions regarding the need for fragment removal, to develop therapeutic interventions, and to better anticipate future medical problems from retained fragment related injuries. In response to this need, a new U.S Department of Defense (DoD) directive has been issued requiring characterization of all removed fragments to provide a database of fragment types occurring in combat injuries. Objectives: The objective of this study is to determine the chemical composition of retained embedded fragments removed from injured military personnel, and to relate results to histological findings in tissue adjacent to fragment material. Methods: We describe an approach for the chemical analysis and characterization of retained fragments and adjacent tissues, and include case examples describing fragments containing depleted uranium (DU), tungsten (W), lead (Pb), and non-metal foreign bodies composed of natural and composite materials. Fragments obtained from four patients with penetrating blast wounds to the limbs were studied employing a wide range of chemical and microscopy techniques. Available adjacent tissues from three of the cases were histologically, microscopically, and chemically examined. The physical and compositional properties of the removed foreign material surfaces were examined with energy dispersive x-ray fluorescence spectrometry (EDXRF), scanning electron microscopy (SEM), laser ablation inductively-coupled plasma mass-spectrometry (LA-ICP-MS), and confocal laser Raman

Advancement of magma fragmentation by inhomogeneous bubble distribution.

PubMed

Kameda, M; Ichihara, M; Maruyama, S; Kurokawa, N; Aoki, Y; Okumura, S; Uesugi, K

2017-12-01

Decompression times reported in previous studies suggest that thoroughly brittle fragmentation is unlikely in actual explosive volcanic eruptions. What occurs in practice is brittle-like fragmentation, which is defined as the solid-like fracture of a material whose bulk rheological properties are close to those of a fluid. Through laboratory experiments and numerical simulation, the link between the inhomogeneous structure of bubbles and the development of cracks that may lead to brittle-like fragmentation was clearly demonstrated here. A rapid decompression test was conducted to simulate the fragmentation of a specimen whose pore morphology was revealed by X-ray microtomography. The dynamic response during decompression was observed by high-speed photography. Large variation was observed in the responses of the specimens even among specimens with equal bulk rheological properties. The stress fields of the specimens under decompression computed by finite element analysis shows that the presence of satellite bubbles beneath a large bubble induced the stress concentration. On the basis of the obtained results, a new mechanism for brittle-like fragmentation is proposed. In the proposed scenario, the second nucleation of bubbles near the fragmentation surface is an essential process for the advancement of fragmentation in an upward magma flow in a volcanic conduit.

Impact fragmentation of a brittle metal compact

NASA Astrophysics Data System (ADS)

Tang, Megan; Hooper, Joseph P.

2018-05-01

The fragmentation behavior of a metal powder compact which is ductile in compression but brittle in tension is studied via impact experiments and analytical models. Consolidated metal compacts were prepared via cold-isostatic pressing of <10 μm zinc powder at 380 MPa followed by moderate annealing at 365 °C. The resulting zinc material is ductile and strain-hardening in high-rate uniaxial compression like a traditional metal, but is elastic-brittle in tension with a fracture toughness comparable to a ceramic. Cylindrical samples were launched up to 800 m/s in a gas gun into thin aluminum perforation targets, subjecting the projectile to a complex multiaxial and time-dependent stress state that leads to catastrophic fracture. A soft-catch mechanism using low-density artificial snow was developed to recover the impact debris, and collected fragments were analyzed to determine their size distribution down to 30 μm. Though brittle fracture occurs along original particle boundaries, no power-law fragmentation behavior was observed as is seen in other low-toughness materials. An analytical theory is developed to predict the characteristic fragment size accounting for both the sharp onset of fragmentation and the effect of increasing impact velocity.

Design and synthesis of dihydroisoquinolones for fragment-based drug discovery (FBDD).

PubMed

Palmer, Nick; Peakman, Torren M; Norton, David; Rees, David C

2016-02-07

This study describes general synthesis aspects of fragments for FBDD, as illustrated by the dihydroisoquinolones 1-3. Previous Rh(III) methodology is extended to incorporate amines, heteroatoms (N and S), and substituents (halogen, ester) as potential binding groups and/or synthetic growth points for fragment-to-lead elaboration.

Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β.

PubMed

Wang, Yikai; Wach, Jean-Yves; Sheehan, Patrick; Zhong, Cheng; Zhan, Chenyang; Harris, Richard; Almo, Steven C; Bishop, Joshua; Haggarty, Stephen J; Ramek, Alexander; Berry, Kayla N; O'Herin, Conor; Koehler, Angela N; Hung, Alvin W; Young, Damian W

2016-09-08

Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure-activity relationship, and finally lead to the synthesis of a more potent compound.

Evaluation of spinal missile injuries with respect to bullet trajectory, surgical indications and timing of surgical intervention: a new guideline.

PubMed

Duz, Bulent; Cansever, Tufan; Secer, Halil Ibrahim; Kahraman, Serdar; Daneyemez, Mehmet Kadri; Gonul, Engin

2008-09-15

Analysis of the patients with spinal missile injury (SMI). Choosing the optimum treatment for SMI with respect to bullet trajectory, evaluation of surgical indications, and timing of surgical intervention. A few guidelines were reported for the management of SMI. But there is still no consensus about the indication and timing of the surgery. The relationship between the surgery and bullet trajectory was not reported previously. One hundred twenty-nine patients with spinal missile injury were admitted to our department from 1994 to 2006 and 122 of them could be functionally monitored. Functional recovery and complications in surgical and conservative treatment groups were evaluated. Surgical indications were discussed. The injuries were classified with respect to the bullet's trajectory. Seventy-four patients were treated surgically, of whom 60 (81%) had incomplete injuries. All 17 patients whose vertebral column was injured with side-to-side trajectory were operated on because of instability. In the surgical group, 33 (56.9%) showed improvement, 20 (34.5%) showed no change, and 5 (8.6%) worsened. The best results were obtained by the patients who received operations because of rapid neurologic decline, compression, and instability in the spinal canal (P < 0.0001). Twenty-three (31%) complications and associated injuries were seen in the surgically treated patients and 18 (34.6%) were seen in the conservatively treated patients. Anteroposterior and oblique trajectories [Gulhane Military Medical Academy (GATA)-SMI I and GATA-SMI II] of SMI must be recognized as highly infective in the lumbar region. A side-to-side trajectory (GATA-SMI III) missile causing spinal cord injury is unstable and needs further stabilization. The spinal cord is not injured by the GATA-SMI IV trajectory, and thus, the best approach in this case is conservative. The best results from neurosurgical interventions may be achieved after rapid neurologic deteriorations because of spinal compression

Characterization of Hypervelocity Metal Fragments for Explosive Initiation

NASA Astrophysics Data System (ADS)

Yeager, John; Bowden, Patrick; Guildenbecher, Daniel; Olles, Joseph

2017-06-01

The off-normal detonation behavior of two plastic-bonded explosive (PBX) formulations was studied using explosively-driven aluminum fragments moving at hypersonic velocity. Witness plate materials, including copper and polycarbonate, were used to characterize the distribution of particles, finding that the aluminum did not fragment homogeneously but rather with larger particles in a ring surrounding finer particles. Digital holography experiments were conducted to measure three-dimensional shape and size of the fastest-moving fragments, which ranged between 100 and 700 microns and traveled between 2 and 3.5 km/s. Crucially, these experiments showed variability in the fragmentation in terms of the number of fragments at the leading edge of the fragment field, indicating that both single and multiple shock impacts could be imparted to the target material. Lower density PBX 9407 (RDX-based) was initiable at up to 4.5 inches, while higher density PBX 9501 (HMX-based) was only initiable at up to 0.25 inches. This type of data is critical for safety experiments and hydrocode simulations to quantify shock-to-detonation transition mechanisms and the associated risk-margins for these materials.

Searching Fragment Spaces with feature trees.

PubMed

Lessel, Uta; Wellenzohn, Bernd; Lilienthal, Markus; Claussen, Holger

2009-02-01

Virtual combinatorial chemistry easily produces billions of compounds, for which conventional virtual screening cannot be performed even with the fastest methods available. An efficient solution for such a scenario is the generation of Fragment Spaces, which encode huge numbers of virtual compounds by their fragments/reagents and rules of how to combine them. Similarity-based searches can be performed in such spaces without ever fully enumerating all virtual products. Here we describe the generation of a huge Fragment Space encoding about 5 * 10(11) compounds based on established in-house synthesis protocols for combinatorial libraries, i.e., we encode practically evaluated combinatorial chemistry protocols in a machine readable form, rendering them accessible to in silico search methods. We show how such searches in this Fragment Space can be integrated as a first step in an overall workflow. It reduces the extremely huge number of virtual products by several orders of magnitude so that the resulting list of molecules becomes more manageable for further more elaborated and time-consuming analysis steps. Results of a case study are presented and discussed, which lead to some general conclusions for an efficient expansion of the chemical space to be screened in pharmaceutical companies.

Causes and consequences of habitat fragmentation in river networks.

PubMed

Fuller, Matthew R; Doyle, Martin W; Strayer, David L

2015-10-01

Increases in river fragmentation globally threaten freshwater biodiversity. Rivers are fragmented by many agents, both natural and anthropogenic. We review the distribution and frequency of these major agents, along with their effects on connectivity and habitat quality. Most fragmentation research has focused on terrestrial habitats, but theories and generalizations developed in terrestrial habitats do not always apply well to river networks. For example, terrestrial habitats are usually conceptualized as two-dimensional, whereas rivers often are conceptualized as one-dimensional or dendritic. In addition, river flow often leads to highly asymmetric effects of barriers on habitat and permeability. New approaches tailored to river networks can be applied to describe the network-wide effects of multiple barriers on both connectivity and habitat quality. The net effects of anthropogenic fragmentation on freshwater biodiversity are likely underestimated, because of time lags in effects and the difficulty of generating a single, simple signal of fragmentation that applies to all aquatic species. We conclude by presenting a decision tree for managing freshwater fragmentation, as well as some research horizons for evaluating fragmented riverscapes. © 2015 New York Academy of Sciences.

ACFIS: a web server for fragment-based drug discovery

PubMed Central

Hao, Ge-Fei; Jiang, Wen; Ye, Yuan-Nong; Wu, Feng-Xu; Zhu, Xiao-Lei; Guo, Feng-Biao; Yang, Guang-Fu

2016-01-01

In order to foster innovation and improve the effectiveness of drug discovery, there is a considerable interest in exploring unknown ‘chemical space’ to identify new bioactive compounds with novel and diverse scaffolds. Hence, fragment-based drug discovery (FBDD) was developed rapidly due to its advanced expansive search for ‘chemical space’, which can lead to a higher hit rate and ligand efficiency (LE). However, computational screening of fragments is always hampered by the promiscuous binding model. In this study, we developed a new web server Auto Core Fragment in silico Screening (ACFIS). It includes three computational modules, PARA_GEN, CORE_GEN and CAND_GEN. ACFIS can generate core fragment structure from the active molecule using fragment deconstruction analysis and perform in silico screening by growing fragments to the junction of core fragment structure. An integrated energy calculation rapidly identifies which fragments fit the binding site of a protein. We constructed a simple interface to enable users to view top-ranking molecules in 2D and the binding mode in 3D for further experimental exploration. This makes the ACFIS a highly valuable tool for drug discovery. The ACFIS web server is free and open to all users at http://chemyang.ccnu.edu.cn/ccb/server/ACFIS/. PMID:27150808

Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β

PubMed Central

2016-01-01

Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure–activity relationship, and finally lead to the synthesis of a more potent compound. PMID:27660690

Fragment-based approaches to the discovery of kinase inhibitors.

PubMed

Mortenson, Paul N; Berdini, Valerio; O'Reilly, Marc

2014-01-01

Protein kinases are one of the most important families of drug targets, and aberrant kinase activity has been linked to a large number of disease areas. Although eminently targetable using small molecules, kinases present a number of challenges as drug targets, not least obtaining selectivity across such a large and relatively closely related target family. Fragment-based drug discovery involves screening simple, low-molecular weight compounds to generate initial hits against a target. These hits are then optimized to more potent compounds via medicinal chemistry, usually facilitated by structural biology. Here, we will present a number of recent examples of fragment-based approaches to the discovery of kinase inhibitors, detailing the construction of fragment-screening libraries, the identification and validation of fragment hits, and their optimization into potent and selective lead compounds. The advantages of fragment-based methodologies will be discussed, along with some of the challenges associated with using this route. Finally, we will present a number of key lessons derived both from our own experience running fragment screens against kinases and from a large number of published studies.

Double Parton Fragmentation Function and its Evolution in Quarkonium Production

NASA Astrophysics Data System (ADS)

Kang, Zhong-Bo

2014-01-01

We summarize the results of a recent study on a new perturbative QCD factorization formalism for the production of heavy quarkonia of large transverse momentum pT at collider energies. Such a new factorization formalism includes both the leading power (LP) and next-to-leading power (NLP) contributions to the cross section in the mQ2/p_T^2 expansion for heavy quark mass mQ. For the NLP contribution, the so-called double parton fragmentation functions are involved, whose evolution equations have been derived. We estimate fragmentation functions in the non-relativistic QCD formalism, and found that their contribution reproduce the bulk of the large enhancement found in explicit NLO calculations in the color singlet model. Heavy quarkonia produced from NLP channels prefer longitudinal polarization, in contrast to the single parton fragmentation function. This might shed some light on the heavy quarkonium polarization puzzle.

Signature of the Fragmentation of a Color Flux Tube

DOE PAGES

Wong, Cheuk-Yin

2015-10-07

The production of quark-antiquark pairs along a color flux tube precedes the fragmentation of the tube. Because of the local conservation of momentum and charge, the production of amore » $q$-$$\\bar q$$ pair will lead to correlations of adjacently produced mesons (mostly pions). Adjacently produced pions however can be signalled by the their rapidity difference $$\\Delta y$$ falling within the window of $$|\\Delta y | < 1/(dN_\\pi/dy)$$, on account of the space-time-rapidity ordering of produced pions in a flux tube fragmentation. Therefore, the local conservation of momentum will lead to a suppression of azimuthal two-pion correlation $$dN/(d\\Delta \\phi\\, d\\Delta y)$$ on the near side at $$(\\Delta \\phi, \\Delta y) \\sim 0$$, but an enhanced azimuthal correlation on the back-to-back, away side at $$(\\Delta \\phi$$$\\sim$$$ \\pi,\\Delta y$$$\\sim$$0). Similarly, in a flux tube fragmentation, the local conservation of charge will forbid the production of like charge pions within $$|\\Delta y | < 1/(dN_\\pi/dy)$$, but there is no such prohibition for $$|\\Delta y| >1/(dN_\\pi/dy)$$. These properties may be used as the signature for the fragmentation of a color flux tube.« less

An endogenously produced fragment of cardiac myosin-binding protein C is pathogenic and can lead to heart failure.

PubMed

Razzaque, Md Abdur; Gupta, Manish; Osinska, Hanna; Gulick, James; Blaxall, Burns C; Robbins, Jeffrey

2013-08-16

A stable 40-kDa fragment is produced from cardiac myosin-binding protein C when the heart is stressed using a stimulus, such as ischemia-reperfusion injury. Elevated levels of the fragment can be detected in the diseased mouse and human heart, but its ability to interfere with normal cardiac function in the intact animal is unexplored. To understand the potential pathogenicity of the 40-kDa fragment in vivo and to investigate the molecular pathways that could be targeted for potential therapeutic intervention. We generated cardiac myocyte-specific transgenic mice using a Tet-Off inducible system to permit controlled expression of the 40-kDa fragment in cardiomyocytes. When expression of the 40-kDa protein is induced by crossing the responder animals with tetracycline transactivator mice under conditions in which substantial quantities approximating those observed in diseased hearts are reached, the double-transgenic mice subsequently experience development of sarcomere dysgenesis and altered cardiac geometry, and the heart fails between 12 and 17 weeks of age. The induced double-transgenic mice had development of cardiac hypertrophy with myofibrillar disarray and fibrosis, in addition to activation of pathogenic MEK-ERK pathways. Inhibition of MEK-ERK signaling was achieved by injection of the mitogen-activated protein kinase (MAPK)/ERK inhibitor U0126. The drug effectively improved cardiac function, normalized heart size, and increased probability of survival. These results suggest that the 40-kDa cardiac myosin-binding protein C fragment, which is produced at elevated levels during human cardiac disease, is a pathogenic fragment that is sufficient to cause hypertrophic cardiomyopathy and heart failure.

Fragment Screening of Human Kynurenine Aminotransferase-II.

PubMed

Jayawickrama, Gayan S; Nematollahi, Alireza; Sun, Guanchen; Church, W Bret

2018-03-01

Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT family, of which it is the primary homologue responsible for KYNA production in the mammalian brain. KAT-II is targeted for inhibition as KYNA is implicated in diseases such as schizophrenia, where it is found in elevated concentrations. Previously, many different approaches have been taken to develop KAT-II inhibitors, and herein fragment-based drug design (FBDD) approaches have been exploited to provide further lead compounds that can be designed into novel inhibitors. Surface plasmon resonance (SPR) was used to screen a fragment library containing 1000 compounds, of which 41 hits were identified. These hits were further evaluated with SPR, and 18 were selected for inhibition studies. From these hits, two fragments, F6037-0164 and F0037-7280, were pursued and determined to have an IC 50 of 524.5 (± 25.6) μM and 115.2 (± 4.5) μM, respectively. This strategy shows the viability of using FBDD in gleaning knowledge about KAT-II inhibition and generating leads for the production of KAT-II inhibitors.

Characterization of hypervelocity metal fragments for explosive initiation

NASA Astrophysics Data System (ADS)

Yeager, John D.; Bowden, Patrick R.; Guildenbecher, Daniel R.; Olles, Joseph D.

2017-07-01

The fragment impact response of two plastic-bonded explosive (PBX) formulations was studied using explosively driven aluminum fragments. A generic aluminum-capped detonator generated sub-mm aluminum particles moving at hypersonic velocities. The ability of these fragments to initiate reaction or otherwise damage two PBX materials was assessed using go/no-go experiments at standoff distances of up to 160 mm. Lower density PBX 9407 (RDX-based) was initiable at up to 115 mm, while higher density PBX 9501 (HMX-based) was only initiable at up to 6 mm. Several techniques were used to characterize the size, distribution, and velocity of the particles. Witness plate materials, including copper and polycarbonate, and backlit high speed video were used to characterize the distribution of particles, finding that the aluminum cap did not fragment homogeneously but rather with larger particles in a ring surrounding finer particles. Finally, precise digital holography experiments were conducted to measure the three-dimensional shape and size of the fastest-moving fragments, which ranged between 100 and 700 μm and traveled between 2.2 and 3.2 km/s. Crucially, these experiments showed variability in the fragmentation in terms of the number of fragments at the leading edge of the fragment field, indicating that both single and multiple shock impacts could be imparted to the target material. These types of data are critical for safety experiments and hydrocode simulations to quantify shock-to-detonation transition mechanisms and the associated risk-margins for these materials.

Forest Fragmentation

Treesearch

Kurt H. Riitters

2007-01-01

What Is Forest Fragmentation,and Why Is It Important? Forest fragmentation refers to a loss of forest and the division of the remaining forest into smaller blocks. Fragmentation is of concern primarily because of its impact on the conservation of biological diversity. Forest fragmentation can affect the amount and quality of habitat for many wildlife species (Fahrig...

Self-action of Bessel wave packets in a system of coupled light guides and formation of light bullets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balakin, A. A., E-mail: balakin.alexey@yandex.ru; Mironov, V. A.; Skobelev, S. A., E-mail: sk.sa1981@gmail.com

The self-action of two-dimensional and three-dimensional Bessel wave packets in a system of coupled light guides is considered using the discrete nonlinear Schrödinger equation. The features of the self-action of such wave fields are related to their initial strong spatial inhomogeneity. The numerical simulation shows that for the field amplitude exceeding a critical value, the development of an instability typical of a medium with the cubic nonlinearity is observed. Various regimes are studied: the self-channeling of a wave beam in one light guide at powers not strongly exceeding a critical value, the formation of the “kaleidoscopic” picture of a wavemore » packet during the propagation of higher-power radiation along a stratified medium, the formation of light bullets during competition between self-focusing and modulation instabilities in the case of three-dimensional wave packets, etc. In the problem of laser pulse shortening, the situation is considered when the wave-field stratification in the transverse direction dominates. This process is accompanied by the self-compression of laser pulses in well enough separated light guides. The efficiency of conversion of the initial Bessel field distribution to two flying parallel light bullets is about 50%.« less

Penetration and perforation of skin by bullets and missiles. A review of the literature.

PubMed

DiMaio, V J

1981-06-01

A review of the literature on perforation of skin by bullets and missiles indicates that there is a range of velocity below which a missile cannot perforate the skin. Velocities of between 38.1 and 61.6 meters/second (125 and 202 ft./second) will produce at least minimal damage to the surface of the skin, though without perforation. In order for a missile to perforate the skin and enter the underlying subcutaneous tissue and muscle, a minimum velocity in the order of 70 meters/second (230 ft./second) is necessary with an energy/area of presentation of approximately 2.1 m-kg/cm2.

A bright, dust-obscured, millimetre-selected galaxy beyond the Bullet Cluster (1E0657-56)

NASA Astrophysics Data System (ADS)

Wilson, G. W.; Hughes, D. H.; Aretxaga, I.; Ezawa, H.; Austermann, J. E.; Doyle, S.; Ferrusca, D.; Hernández-Curiel, I.; Kawabe, R.; Kitayama, T.; Kohno, K.; Kuboi, A.; Matsuo, H.; Mauskopf, P. D.; Murakoshi, Y.; Montaña, A.; Natarajan, P.; Oshima, T.; Ota, N.; Perera, T. A.; Rand, J.; Scott, K. S.; Tanaka, K.; Tsuboi, M.; Williams, C. C.; Yamaguchi, N.; Yun, M. S.

2008-11-01

Deep 1.1mm continuum observations of 1E0657-56 (the `Bullet Cluster') taken with the millimeter-wavelength camera AzTEC on the 10-m Atacama Submillimeter Telescope Experiment (ASTE), have revealed an extremely bright (S1.1mm = 15.9mJy) unresolved source. This source, MMJ065837-5557.0, lies close to a maximum in the density of underlying mass distribution, towards the larger of the two interacting clusters as traced by the weak-lensing analysis of Clowe et al. Using optical-infrared (IR) colours, we argue that MMJ065837-5557.0 lies at a redshift of z = 2.7 +/- 0.2. A lensing-derived mass model for the Bullet Cluster shows a critical line (caustic) of magnification within a few arcsec of the AzTEC source, sufficient to amplify the intrinsic millimetre-wavelength flux of the AzTEC galaxy by a factor of >>20. After subtraction of the foreground cluster emission at 1.1mm due to the Sunyaev-Zel'dovich effect, and correcting for the magnification, the rest-frame far-IR luminosity of MMJ065837-5557.0 is <=1012Lsolar, characteristic of a luminous infrared galaxy (LIRG). We explore various scenarios to explain the colours, morphologies and positional offsets between the potential optical and IR counterparts, and their relationship with MMJ065837-5557.0. Until higher resolution and more sensitive (sub)millimetre observations are available, the detection of background galaxies close to the caustics of massive lensing clusters offers the only opportunity to study this intrinsically faint millimetre-galaxy population.

Fragment-Based Drug Discovery Using NMR Spectroscopy

PubMed Central

Harner, Mary J.; Frank, Andreas O.; Fesik, Stephen W.

2013-01-01

Nuclear magnetic resonance (NMR) spectroscopy has evolved into a powerful tool for fragment-based drug discovery over the last two decades. While NMR has been traditionally used to elucidate the three-dimensional structures and dynamics of biomacromolecules and their interactions, it can also be a very valuable tool for the reliable identification of small molecules that bind to proteins and for hit-to-lead optimization. Here, we describe the use of NMR spectroscopy as a method for fragment-based drug discovery and how to most effectively utilize this approach for discovering novel therapeutics based on our experience. PMID:23686385

Oligo-branched peptides for tumor targeting: from magic bullets to magic forks.

PubMed

Falciani, Chiara; Pini, Alessandro; Bracci, Luisa

2009-02-01

Selective targeting of tumor cells is the final goal of research and drug discovery for cancer diagnosis, imaging and therapy. After the invention of hybridoma technology, the concept of magic bullet was introduced into the field of oncology, referring to selective killing of tumor cells, by specific antibodies. More recently, small molecules and peptides have also been proposed as selective targeting agents. We analyze the state of the art of tumor-selective agents that are presently available and tested in clinical settings. A novel approach based on 'armed' oligo-branched peptides as tumor targeting agents, is discussed and compared with existing tumor-selective therapies mediated by antibodies, small molecules or monomeric peptides. Oligo-branched peptides could be novel drugs that combine the advantages of antibodies and small molecules.

Binding-Site Assessment by Virtual Fragment Screening

PubMed Central

Huang, Niu; Jacobson, Matthew P.

2010-01-01

The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules) would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock ∼11000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors. PMID:20404926

Evolutions in fragment-based drug design: the deconstruction–reconstruction approach

PubMed Central

Chen, Haijun; Zhou, Xiaobin; Wang, Ailan; Zheng, Yunquan; Gao, Yu; Zhou, Jia

2014-01-01

Recent advances in the understanding of molecular recognition and protein–ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction–reconstruction strategy by utilizing privileged fragments of reported ligands. PMID:25263697

The drone ambulance [A-UAS]: golden bullet or just a blank?

PubMed

Van de Voorde, P; Gautama, S; Momont, A; Ionescu, C M; De Paepe, P; Fraeyman, N

2017-07-01

Defibrillation within the first minutes after sudden cardiac arrest can save many quality-adjusted life years. Yet, despite enormous investments, 'healthcare' is still unable to provide this for the majority of patients. Emergency Medical Services often have a too long mean response time and many issues surround Public Access Defibrillation programs. In this article we argument that AED-equipped drones could be the 'magic bullet'. They are easily deployed and fast, and have a relatively low operational cost. As such they could rapidly bring an AED next to the victim, irrespective of most geographical circumstances, give visual feedback and situational awareness to the EMS dispatcher and thus assist a bystander to provide better CPR. Although there are many real-life barriers to actual deployment, we argument these might all get solved once we have solved the described technological issues. Copyright © 2017 Elsevier B.V. All rights reserved.

Fragmentation functions beyond fixed order accuracy

NASA Astrophysics Data System (ADS)

Anderle, Daniele P.; Kaufmann, Tom; Stratmann, Marco; Ringer, Felix

2017-03-01

We give a detailed account of the phenomenology of all-order resummations of logarithmically enhanced contributions at small momentum fraction of the observed hadron in semi-inclusive electron-positron annihilation and the timelike scale evolution of parton-to-hadron fragmentation functions. The formalism to perform resummations in Mellin moment space is briefly reviewed, and all relevant expressions up to next-to-next-to-leading logarithmic order are derived, including their explicit dependence on the factorization and renormalization scales. We discuss the details pertinent to a proper numerical implementation of the resummed results comprising an iterative solution to the timelike evolution equations, the matching to known fixed-order expressions, and the choice of the contour in the Mellin inverse transformation. First extractions of parton-to-pion fragmentation functions from semi-inclusive annihilation data are performed at different logarithmic orders of the resummations in order to estimate their phenomenological relevance. To this end, we compare our results to corresponding fits up to fixed, next-to-next-to-leading order accuracy and study the residual dependence on the factorization scale in each case.

ACFIS: a web server for fragment-based drug discovery.

PubMed

Hao, Ge-Fei; Jiang, Wen; Ye, Yuan-Nong; Wu, Feng-Xu; Zhu, Xiao-Lei; Guo, Feng-Biao; Yang, Guang-Fu

2016-07-08

In order to foster innovation and improve the effectiveness of drug discovery, there is a considerable interest in exploring unknown 'chemical space' to identify new bioactive compounds with novel and diverse scaffolds. Hence, fragment-based drug discovery (FBDD) was developed rapidly due to its advanced expansive search for 'chemical space', which can lead to a higher hit rate and ligand efficiency (LE). However, computational screening of fragments is always hampered by the promiscuous binding model. In this study, we developed a new web server Auto Core Fragment in silico Screening (ACFIS). It includes three computational modules, PARA_GEN, CORE_GEN and CAND_GEN. ACFIS can generate core fragment structure from the active molecule using fragment deconstruction analysis and perform in silico screening by growing fragments to the junction of core fragment structure. An integrated energy calculation rapidly identifies which fragments fit the binding site of a protein. We constructed a simple interface to enable users to view top-ranking molecules in 2D and the binding mode in 3D for further experimental exploration. This makes the ACFIS a highly valuable tool for drug discovery. The ACFIS web server is free and open to all users at http://chemyang.ccnu.edu.cn/ccb/server/ACFIS/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

[The possibilities for the expert diagnostics of the influence of the glance of a bullet on the character of the injuries inflicted by shooting a hunting weapon].

PubMed

Makarov, I Yu; Galkina, A M; Kinle, A F; Fetisov, V A

The objective of the present work was to study and analyze the available data concerning the influence of the glance of a bullet on the character of the injuries inflicted by shooting certain types of hunting weapons. This review gives evidence of the possibility of the objective diagnostics of the injuries inflicted by gunshots using the rifle-bore weapons. However, we have failed to find information about the diagnostic criteria for the evaluation of the wounds inflicted by the bullets shot from smooth-bore hunting rifles after their glance from various surfaces in the available special literature publications. Such situation creates the prerequisites for the erroneous conclusions from the results of forensic medical expertise of the after-penetration blunt wounds.

Characterization of hypervelocity metal fragments for explosive initiation

DOE PAGES

Yeager, John D.; Bowden, Patrick R.; Guildenbecher, Daniel R.; ...

2017-07-17

The fragment impact response of two plastic-bonded explosive (PBX) formulations was studied using explosively driven aluminum fragments. A generic aluminum-capped detonator generated sub-mm aluminum particles moving at hypersonic velocities. The ability of these fragments to initiate reaction or otherwise damage two PBX materials was assessed using go/no-go experiments at standoff distances of up to 160 mm. Lower density PBX 9407 (RDX-based) was initiable at up to 115 mm, while higher density PBX 9501 (HMX-based) was only initiable at up to 6 mm. Several techniques were used to characterize the size, distribution, and velocity of the particles. Witness plate materials, includingmore » copper and polycarbonate, and backlit high speed video were used to characterize the distribution of particles, finding that the aluminum cap did not fragment homogeneously but rather with larger particles in a ring surrounding finer particles. Finally, precise digital holography experiments were conducted to measure the three-dimensional shape and size of the fastest-moving fragments, which ranged between 100 and 700 μm and traveled between 2.2 and 3.2 km/s. Crucially, these experiments showed variability in the fragmentation in terms of the number of fragments at the leading edge of the fragment field, indicating that both single and multiple shock impacts could be imparted to the target material. As a result, these types of data are critical for safety experiments and hydrocode simulations to quantify shock-to-detonation transition mechanisms and the associated risk-margins for these materials.« less

Fragment-Based Identification of Influenza Endonuclease Inhibitors

PubMed Central

2016-01-01

The influenza virus is responsible for millions of cases of severe illness annually. Yearly variance in the effectiveness of vaccination, coupled with emerging drug resistance, necessitates the development of new drugs to treat influenza infections. One attractive target is the RNA-dependent RNA polymerase PA subunit. Herein we report the development of inhibitors of influenza PA endonuclease derived from lead compounds identified from a metal-binding pharmacophore (MBP) library screen. Pyromeconic acid and derivatives thereof were found to be potent inhibitors of endonuclease. Guided by modeling and previously reported structural data, several sublibraries of molecules were elaborated from the MBP hits. Structure–activity relationships were established, and more potent molecules were designed and synthesized using fragment growth and fragment merging strategies. This approach ultimately resulted in the development of a lead compound with an IC50 value of 14 nM, which displayed an EC50 value of 2.1 μM against H1N1 influenza virus in MDCK cells. PMID:27291165

Lead Exposure in the Special Operations Shooter How to Prevent Cognitive Decline and Permanent Disability.

PubMed

Brandon, Jonathan W; Solarczyk, Justin K; Durrani, Timur S

Lead toxicity is an important environmental disease and its effects on the human body can be devastating. Unique exposures to Special Operations Forces personnel may include use of firing ranges, use of automotive fuels, production of ammunition, and bodily retention of bullets. Toxicity may degrade physical and psychological fitness, and cause long-term negative health outcomes. Specific effects on fine motor movements, reaction times, and global function could negatively affect shooting skills and decision-making. Biologic monitoring and chelation treatment are poor solutions for protecting this population. Through primary prevention, Special Operations Forces personnel can be protected, in any environment, from the devastating effects of lead exposure. This article offers tools to physicians, environmental service officers, and Special Operations Medics for primary prevention of lead poisoning in the conventional and the austere or forward deployed environments. 2018.

Dark matter line emission constraints from NuSTAR observations of the bullet cluster

DOE PAGES

Riemer-Sørensen, S.; Wik, D.; Madejski, G.; ...

2015-08-27

Some dark matter candidates, e.g., sterile neutrinos, provide observable signatures in the form of mono-energetic line emission. Here, we present the first search for dark matter line emission in themore » $$3-80\\;\\mathrm{keV}$$ range in a pointed observation of the Bullet Cluster with NuSTAR. We do not detect any significant line emission and instead we derive upper limits (95% CL) on the flux, and interpret these constraints in the context of sterile neutrinos and more generic dark matter candidates. NuSTAR does not have the sensitivity to constrain the recently claimed line detection at $$3.5\\;\\mathrm{keV}$$, but improves on the constraints for energies of $$10-25\\;\\mathrm{keV}$$.« less

Formation of supermassive black holes through fragmentation of torodial supermassive stars.

PubMed

Zink, Burkhard; Stergioulas, Nikolaos; Hawke, Ian; Ott, Christian D; Schnetter, Erik; Müller, Ewald

2006-04-28

We investigate new paths to supermassive black hole formation by considering the general relativistic evolution of a differentially rotating polytrope with a toroidal shape. We find that this polytrope is unstable to nonaxisymmetric modes, which leads to a fragmentation into self-gravitating, collapsing components. In the case of one such fragment, we apply a simplified adaptive mesh refinement technique to follow the evolution to the formation of an apparent horizon centered on the fragment. This is the first study of the onset of nonaxisymmetric dynamical instabilities of supermassive stars in full general relativity.

First determination of D* -meson fragmentation functions and their uncertainties at next-to-next-to-leading order

NASA Astrophysics Data System (ADS)

Soleymaninia, Maryam; Khanpour, Hamzeh; Nejad, S. Mohammad Moosavi

2018-04-01

We present, for the first time, a set of next-to-next-to-leading order (NNLO) fragmentation functions (FFs) describing the production of charmed-meson D* from partons. Exploiting the universality and scaling violations of FFs, we extract the NLO and NNLO FFs through a global fit to all relevant data sets from single-inclusive e+e- annihilation. The uncertainties for the resulting FFs as well as the corresponding observables are estimated using the Hessian approach. We evaluate the quality of the SKM18 FFs determined in this analysis by comparing with the recent results in literature and show how they describe the available data for single-inclusive D*±-meson production in electron-positron annihilation. As a practical application, we apply the extracted FFs to make our theoretical predictions for the scaled-energy distributions of D*±-mesons inclusively produced in top quark decays. We explore the implications of SKM18 for LHC phenomenology and show that our findings of this study can be introduced as a channel to indirect search for top-quark properties.

Identifying protein domains by global analysis of soluble fragment data.

PubMed

Bulloch, Esther M M; Kingston, Richard L

2014-11-15

The production and analysis of individual structural domains is a common strategy for studying large or complex proteins, which may be experimentally intractable in their full-length form. However, identifying domain boundaries is challenging if there is little structural information concerning the protein target. One experimental procedure for mapping domains is to screen a library of random protein fragments for solubility, since truncation of a domain will typically expose hydrophobic groups, leading to poor fragment solubility. We have coupled fragment solubility screening with global data analysis to develop an effective method for identifying structural domains within a protein. A gene fragment library is generated using mechanical shearing, or by uracil doping of the gene and a uracil-specific enzymatic digest. A split green fluorescent protein (GFP) assay is used to screen the corresponding protein fragments for solubility when expressed in Escherichia coli. The soluble fragment data are then analyzed using two complementary approaches. Fragmentation "hotspots" indicate possible interdomain regions. Clustering algorithms are used to group related fragments, and concomitantly predict domain location. The effectiveness of this Domain Seeking procedure is demonstrated by application to the well-characterized human protein p85α. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantitative experimental modelling of fragmentation during explosive volcanism

NASA Astrophysics Data System (ADS)

Thordén Haug, Ø.; Galland, O.; Gisler, G.

2012-04-01

Phreatomagmatic eruptions results from the violent interaction between magma and an external source of water, such as ground water or a lake. This interaction causes fragmentation of the magma and/or the host rock, resulting in coarse-grained (lapilli) to very fine-grained (ash) material. The products of phreatomagmatic explosions are classically described by their fragment size distribution, which commonly follows power laws of exponent D. Such descriptive approach, however, considers the final products only and do not provide information on the dynamics of fragmentation. The aim of this contribution is thus to address the following fundamental questions. What are the physics that govern fragmentation processes? How fragmentation occurs through time? What are the mechanisms that produce power law fragment size distributions? And what are the scaling laws that control the exponent D? To address these questions, we performed a quantitative experimental study. The setup consists of a Hele-Shaw cell filled with a layer of cohesive silica flour, at the base of which a pulse of pressurized air is injected, leading to fragmentation of the layer of flour. The fragmentation process is monitored through time using a high-speed camera. By varying systematically the air pressure (P) and the thickness of the flour layer (h) we observed two morphologies of fragmentation: "lift off" where the silica flour above the injection inlet is ejected upwards, and "channeling" where the air pierces through the layer along sub-vertical conduit. By building a phase diagram, we show that the morphology is controlled by P/dgh, where d is the density of the flour and g is the gravitational acceleration. To quantify the fragmentation process, we developed a Matlab image analysis program, which calculates the number and sizes of the fragments, and so the fragment size distribution, during the experiments. The fragment size distributions are in general described by power law distributions of

Environmental contaminants in California condors

USGS Publications Warehouse

Wiemeyer, Stanley N.; Scott, J.M.; Anderson, M.P.; Bloom, P.H.; Stafford, C.J.

1988-01-01

Five wild Califorinia condors (Gymnogyps californianus) that died in 1980-86 were necropsied and tissues were analyzed for environmental contaminants. Three died of lead (Pb) poisoning, 1 presumably of cyanide (CN) poisoning, and 1 nestling of handling shock. Organochlorine concentrations were low in 4 condors that were analyzed for these contaminants. Blood samples from 14 wild and 14 captive condors were analyzed primarily for Pb. Five of 14 wild condors sampled had elevated (> 0.70 ppm) concentrations of Pb in blood whereas Pb concentrations in all captive condors were low. Lead levels in individual birds often fluctuated over time. Lead exposure, especially poisoning, was a major factor affecting the wild California condor population during 1982-86. The probable source of Pb was bullet fragments in carrion on which condors were feeding.

Optimization of a binding fragment targeting the "enlarged methionine pocket" leads to potent Trypanosoma brucei methionyl-tRNA synthetase inhibitors.

PubMed

Huang, Wenlin; Zhang, Zhongsheng; Ranade, Ranae M; Gillespie, J Robert; Barros-Álvarez, Ximena; Creason, Sharon A; Shibata, Sayaka; Verlinde, Christophe L M J; Hol, Wim G J; Buckner, Frederick S; Fan, Erkang

2017-06-15

Potent inhibitors of Trypanosoma brucei methionyl-tRNA synthetase were previously designed using a structure-guided approach. Compounds 1 and 2 were the most active compounds in the cyclic and linear linker series, respectively. To further improve cellular potency, SAR investigation of a binding fragment targeting the "enlarged methionine pocket" (EMP) was performed. The optimization led to the identification of a 6,8-dichloro-tetrahydroquinoline ring as a favorable fragment to bind the EMP. Replacement of 3,5-dichloro-benzyl group (the EMP binding fragment) of inhibitor 2 using this tetrahydroquinoline fragment resulted in compound 13, that exhibited an EC 50 of 4nM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Agricultural matrices affect ground ant assemblage composition inside forest fragments

PubMed Central

Dos Santos, Iracenir Andrade; Ramos, Flavio Nunes; Majer, Jonathan David; Vilela, Evaldo Ferreira

2018-01-01

The establishment of agricultural matrices generally involves deforestation, which leads to fragmentation of the remaining forest. This fragmentation can affect forest dynamics both positively and negatively. Since most animal species are affected, certain groups can be used to measure the impact of such fragmentation. This study aimed to measure the impacts of agricultural crops (matrices) on ant communities of adjacent lower montane Atlantic rainforest fragments. We sampled nine forest fragments at locations surrounded by different agricultural matrices, namely: coffee (3 replicates); sugarcane (3); and pasture (3). At each site we installed pitfall traps along a 500 m transect from the interior of the matrix to the interior of the fragment (20 pitfall traps ~25 m apart). Each transect was partitioned into four categories: interior of the matrix; edge of the matrix; edge of the fragment; and interior of the fragment. For each sample site, we measured ant species richness and ant community composition within each transect category. Ant richness and composition differed between fragments and matrices. Each sample location had a specific composition of ants, probably because of the influence of the nature and management of the agricultural matrices. Species composition in the coffee matrix had the highest similarity to its corresponding fragment. The variability in species composition within forest fragments surrounded by pasture was greatest when compared with forest fragments surrounded by sugarcane or, to a lesser extent, coffee. Functional guild composition differed between locations, but the most representative guild was ‘generalist’ both in the agricultural matrices and forest fragments. Our results are important for understanding how agricultural matrices act on ant communities, and also, how these isolated forest fragments could act as an island of biodiversity in an ‘ocean of crops’. PMID:29791493

Agricultural matrices affect ground ant assemblage composition inside forest fragments.

PubMed

Assis, Diego Santana; Dos Santos, Iracenir Andrade; Ramos, Flavio Nunes; Barrios-Rojas, Katty Elena; Majer, Jonathan David; Vilela, Evaldo Ferreira

2018-01-01

The establishment of agricultural matrices generally involves deforestation, which leads to fragmentation of the remaining forest. This fragmentation can affect forest dynamics both positively and negatively. Since most animal species are affected, certain groups can be used to measure the impact of such fragmentation. This study aimed to measure the impacts of agricultural crops (matrices) on ant communities of adjacent lower montane Atlantic rainforest fragments. We sampled nine forest fragments at locations surrounded by different agricultural matrices, namely: coffee (3 replicates); sugarcane (3); and pasture (3). At each site we installed pitfall traps along a 500 m transect from the interior of the matrix to the interior of the fragment (20 pitfall traps ~25 m apart). Each transect was partitioned into four categories: interior of the matrix; edge of the matrix; edge of the fragment; and interior of the fragment. For each sample site, we measured ant species richness and ant community composition within each transect category. Ant richness and composition differed between fragments and matrices. Each sample location had a specific composition of ants, probably because of the influence of the nature and management of the agricultural matrices. Species composition in the coffee matrix had the highest similarity to its corresponding fragment. The variability in species composition within forest fragments surrounded by pasture was greatest when compared with forest fragments surrounded by sugarcane or, to a lesser extent, coffee. Functional guild composition differed between locations, but the most representative guild was 'generalist' both in the agricultural matrices and forest fragments. Our results are important for understanding how agricultural matrices act on ant communities, and also, how these isolated forest fragments could act as an island of biodiversity in an 'ocean of crops'.

Assessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery.

PubMed

Coutard, Bruno; Decroly, Etienne; Li, Changqing; Sharff, Andrew; Lescar, Julien; Bricogne, Gérard; Barral, Karine

2014-06-01

Seasonal and pandemic flaviviruses continue to be leading global health concerns. With the view to help drug discovery against Dengue virus (DENV), a fragment-based experimental approach was applied to identify small molecule ligands targeting two main components of the flavivirus replication complex: the NS3 helicase (Hel) and the NS5 mRNA methyltransferase (MTase) domains. A library of 500 drug-like fragments was first screened by thermal-shift assay (TSA) leading to the identification of 36 and 32 fragment hits binding Hel and MTase from DENV, respectively. In a second stage, we set up a fragment-based X-ray crystallographic screening (FBS-X) in order to provide both validated fragment hits and structural binding information. No fragment hit was confirmed for DENV Hel. In contrast, a total of seven fragments were identified as DENV MTase binders and structures of MTase-fragment hit complexes were solved at resolution at least 2.0Å or better. All fragment hits identified contain either a five- or six-membered aromatic ring or both, and three novel binding sites were located on the MTase. To further characterize the fragment hits identified by TSA and FBS-X, we performed enzymatic assays to assess their inhibition effect on the N7- and 2'-O-MTase enzymatic activities: five of these fragment hits inhibit at least one of the two activities with IC50 ranging from 180μM to 9mM. This work validates the FBS-X strategy for identifying new anti-flaviviral hits targeting MTase, while Hel might not be an amenable target for fragment-based drug discovery (FBDD). This approach proved to be a fast and efficient screening method for FBDD target validation and discovery of starting hits for the development of higher affinity molecules that bind to novel allosteric sites. Copyright © 2014 Elsevier B.V. All rights reserved.

[Spinal cord injury due to penetrating missiles].

PubMed

Ohry, Avi

2003-10-01

Gunshot wound of the spine is a major cause of spinal cord injury among US civilian population, members of the military armed conflict personnel, or civilians injured in terrorists attacks. The bullet fragments cause damage to the spinal cord even without penetrating the spinal canal. Concussive effects, heat, fractures or vascular injury may cause the neurological damage. Unfortunately, bullet or shrapnel removal or laminectomy do not change the prognosis. In this article we review the historical background, the Israeli experience, ballistic-forensic considerations, complications, treatment and prognosis.

An unusual fragmentation of oxetane-embedded tetracyclic ketal systems.

PubMed

Rao, G Hari Mangeswara; Khan, Faiz Ahmed

2013-11-01

An unusual route for the synthesis of functionalized cyclobutane derivatives starting from functionalized norbornane derivatives is reported. Base-induced fragmentation of an oxetanol-type moiety embedded in a tetracyclic norbornyl ketal leads to a cyclobutane-fused derivative as the major or exclusive product. The fragmentation reaction for bridgehead-bromine-substituted derivatives was much faster than for the corresponding chlorine-substituted substrates. The functionalized cyclobutane product was formed exclusively in high yield in the former case, while the latter furnished a minor uncyclized side product in varying yields.

Measurement Techniques for Hypervelocity Impact Test Fragments

NASA Technical Reports Server (NTRS)

Hill, Nicole E.

2008-01-01

The ability to classify the size and shape of individual orbital debris fragments provides a better understanding of the orbital debris environment as a whole. The characterization of breakup fragmentation debris has gradually evolved from a simplistic, spherical assumption towards that of describing debris in terms of size, material, and shape parameters. One of the goals of the NASA Orbital Debris Program Office is to develop high-accuracy techniques to measure these parameters and apply them to orbital debris observations. Measurement of the physical characteristics of debris resulting from groundbased, hypervelocity impact testing provides insight into the shapes and sizes of debris produced from potential impacts in orbit. Current techniques for measuring these ground-test fragments require determination of dimensions based upon visual judgment. This leads to reduced accuracy and provides little or no repeatability for the measurements. With the common goal of mitigating these error sources, allaying any misunderstandings, and moving forward in fragment shape determination, the NASA Orbital Debris Program Office recently began using a computerized measurement system. The goal of using these new techniques is to improve knowledge of the relation between commonly used dimensions and overall shape. The immediate objective is to scan a single fragment, measure its size and shape properties, and import the fragment into a program that renders a 3D model that adequately demonstrates how the object could appear in orbit. This information would then be used to aid optical methods in orbital debris shape determination. This paper provides a description of the measurement techniques used in this initiative and shows results of this work. The tradeoffs of the computerized methods are discussed, as well as the means of repeatability in the measurements of these fragments. This paper serves as a general description of methods for the measurement and shape analysis of

Modified stochastic fragmentation of an interval as an ageing process

NASA Astrophysics Data System (ADS)

Fortin, Jean-Yves

2018-02-01

We study a stochastic model based on modified fragmentation of a finite interval. The mechanism consists of cutting the interval at a random location and substituting a unique fragment on the right of the cut to regenerate and preserve the interval length. This leads to a set of segments of random sizes, with the accumulation of small fragments near the origin. This model is an example of record dynamics, with the presence of ‘quakes’ and slow dynamics. The fragment size distribution is a universal inverse power law with logarithmic corrections. The exact distribution for the fragment number as function of time is simply related to the unsigned Stirling numbers of the first kind. Two-time correlation functions are defined, and computed exactly. They satisfy scaling relations, and exhibit aging phenomena. In particular, the probability that the same number of fragments is found at two different times t>s is asymptotically equal to [4πlog(s)]-1/2 when s\\gg 1 and the ratio t/s is fixed, in agreement with the numerical simulations. The same process with a reset impedes the aging phenomenon-beyond a typical time scale defined by the reset parameter.

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.

PubMed

Huschmann, Franziska U; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S; Mueller, Uwe

2016-05-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity.

Structures of endothiapepsin–fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library

PubMed Central

Huschmann, Franziska U.; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S.; Mueller, Uwe

2016-01-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein–ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin–fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity. PMID:27139825

Resilient networks of ant-plant mutualists in Amazonian forest fragments.

PubMed

Passmore, Heather A; Bruna, Emilio M; Heredia, Sylvia M; Vasconcelos, Heraldo L

2012-01-01

The organization of networks of interacting species, such as plants and animals engaged in mutualisms, strongly influences the ecology and evolution of partner communities. Habitat fragmentation is a globally pervasive form of spatial heterogeneity that could profoundly impact the structure of mutualist networks. This is particularly true for biodiversity-rich tropical ecosystems, where the majority of plant species depend on mutualisms with animals and it is thought that changes in the structure of mutualist networks could lead to cascades of extinctions. We evaluated effects of fragmentation on mutualistic networks by calculating metrics of network structure for ant-plant networks in continuous Amazonian forests with those in forest fragments. We hypothesized that networks in fragments would have fewer species and higher connectance, but equal nestedness and resilience compared to forest networks. Only one of the nine metrics we compared differed between continuous forest and forest fragments, indicating that networks were resistant to the biotic and abiotic changes that accompany fragmentation. This is partially the result of the loss of only specialist species with one connection that were lost in forest fragments. We found that the networks of ant-plant mutualists in twenty-five year old fragments are similar to those in continuous forest, suggesting these interactions are resistant to the detrimental changes associated with habitat fragmentation, at least in landscapes that are a mosaic of fragments, regenerating forests, and pastures. However, ant-plant mutualistic networks may have several properties that may promote their persistence in fragmented landscapes. Proactive identification of key mutualist partners may be necessary to focus conservation efforts on the interactions that insure the integrity of network structure and the ecosystems services networks provide.

Transforming fragments into candidates: small becomes big in medicinal chemistry.

PubMed

de Kloe, Gerdien E; Bailey, David; Leurs, Rob; de Esch, Iwan J P

2009-07-01

Fragment-based drug discovery (FBDD) represents a logical and efficient approach to lead discovery and optimisation. It can draw on structural, biophysical and biochemical data, incorporating a wide range of inputs, from precise mode-of-binding information on specific fragments to wider ranging pharmacophoric screening surveys using traditional HTS approaches. It is truly an enabling technology for the imaginative medicinal chemist. In this review, we analyse a representative set of 23 published FBDD studies that describe how low molecular weight fragments are being identified and efficiently transformed into higher molecular weight drug candidates. FBDD is now becoming warmly endorsed by industry as well as academia and the focus on small interacting molecules is making a big scientific impact.

[Computed tomography in gunshot trauma. I. Ballistics elements and the mechanisms of the lesions].

PubMed

Scialpi, M; Magli, T; Boccuzzi, F; Scapati, C

1995-04-01

The knowledge of wound ballistics and of wounding mechanisms is mandatory for the radiologist to interpret the CT findings of gunshot wounds. The severity of a bullet wound depends on the characteristics of the tissue it goes through, i.e., tissue elasticity, density, thickness of the wounded body part, the type of tissue, its specific gravity, internal cohesiveness and anatomical relationships, as well as on missile characteristics, i.e., mass, shape, fragmentation and deformation. Bullet velocity is certainly a major factor in wounding, but it is only one factor. Two major wounding mechanisms exist the crushing of the bullet-struck tissue (forming the permanent cavity) and radial stretching (forming a temporary cavity). Bullet "yaw" is defined as the angle between the long axis of the bullet and its flight path. The yaw is directly proportional to tissue crushing and stretching: the wider the yaw, the most severe tissue crushing and stretching and, therefore, the more severe tissue damage. The basic knowledge of these concepts is of the utmost importance to understand the CT findings of gunshot wounds and can help physicians study and treat gunshot wounds.

Selectable fragmentation warhead

DOEpatents

Bryan, Courtney S.; Paisley, Dennis L.; Montoya, Nelson I.; Stahl, David B.

1993-01-01

A selectable fragmentation warhead capable of producing a predetermined number of fragments from a metal plate, and accelerating the fragments toward a target. A first explosive located adjacent to the plate is detonated at selected number of points by laser-driven slapper detonators. In one embodiment, a smoother-disk and a second explosive, located adjacent to the first explosive, serve to increase acceleration of the fragments toward a target. The ability to produce a selected number of fragments allows for effective destruction of a chosen target.

Towards a population synthesis model of self-gravitating disc fragmentation and tidal downsizing II: the effect of fragment-fragment interactions

NASA Astrophysics Data System (ADS)

Forgan, D. H.; Hall, C.; Meru, F.; Rice, W. K. M.

2018-03-01

It is likely that most protostellar systems undergo a brief phase where the protostellar disc is self-gravitating. If these discs are prone to fragmentation, then they are able to rapidly form objects that are initially of several Jupiter masses and larger. The fate of these disc fragments (and the fate of planetary bodies formed afterwards via core accretion) depends sensitively not only on the fragment's interaction with the disc, but also with its neighbouring fragments. We return to and revise our population synthesis model of self-gravitating disc fragmentation and tidal downsizing. Amongst other improvements, the model now directly incorporates fragment-fragment interactions while the disc is still present. We find that fragment-fragment scattering dominates the orbital evolution, even when we enforce rapid migration and inefficient gap formation. Compared to our previous model, we see a small increase in the number of terrestrial-type objects being formed, although their survival under tidal evolution is at best unclear. We also see evidence for disrupted fragments with evolved grain populations - this is circumstantial evidence for the formation of planetesimal belts, a phenomenon not seen in runs where fragment-fragment interactions are ignored. In spite of intense dynamical evolution, our population is dominated by massive giant planets and brown dwarfs at large semimajor axis, which direct imaging surveys should, but only rarely, detect. Finally, disc fragmentation is shown to be an efficient manufacturer of free-floating planetary mass objects, and the typical multiplicity of systems formed via gravitational instability will be low.

Fast and Efficient Fragment-Based Lead Generation by Fully Automated Processing and Analysis of Ligand-Observed NMR Binding Data.

PubMed

Peng, Chen; Frommlet, Alexandra; Perez, Manuel; Cobas, Carlos; Blechschmidt, Anke; Dominguez, Santiago; Lingel, Andreas

2016-04-14

NMR binding assays are routinely applied in hit finding and validation during early stages of drug discovery, particularly for fragment-based lead generation. To this end, compound libraries are screened by ligand-observed NMR experiments such as STD, T1ρ, and CPMG to identify molecules interacting with a target. The analysis of a high number of complex spectra is performed largely manually and therefore represents a limiting step in hit generation campaigns. Here we report a novel integrated computational procedure that processes and analyzes ligand-observed proton and fluorine NMR binding data in a fully automated fashion. A performance evaluation comparing automated and manual analysis results on (19)F- and (1)H-detected data sets shows that the program delivers robust, high-confidence hit lists in a fraction of the time needed for manual analysis and greatly facilitates visual inspection of the associated NMR spectra. These features enable considerably higher throughput, the assessment of larger libraries, and shorter turn-around times.

Biological and societal dimensions of lead poisoning in birds in the USA

USGS Publications Warehouse

Friend, Milton; Franson, J. Christian; Anderson, William L.

2008-01-01

The ingestion of spent lead shot was known to cause mortality in wild waterfowl in the US a century before the implementation of nontoxic shot regulations began in 1972. The biological foundation for this transition was strongly supported by both field observations and structured scientific investigations. Despite the overwhelming evidence, various societal factors forestalled the full transition to nontoxic shot for waterfowl hunting until 1991. Now, nearly 20 years later, these same factors weigh heavily in current debates about nontoxic shot requirements for hunting other game birds, requiring nontoxic bullets for big game hunting in California Condor range and for restricting the use of small lead sinkers and jig heads for sport-fishing. As with waterfowl, a strong science-based foundation is requisite for further transitions to nontoxic ammunition and fishing weights. Our experiences have taught us that the societal aspects of this transition are as important as the biological components and must be adequately addressed before alternatives to toxic lead ammunition, fishing weights, and other materials will be accepted as an investment in wildlife conservation.

Fragment virtual screening based on Bayesian categorization for discovering novel VEGFR-2 scaffolds.

PubMed

Zhang, Yanmin; Jiao, Yu; Xiong, Xiao; Liu, Haichun; Ran, Ting; Xu, Jinxing; Lu, Shuai; Xu, Anyang; Pan, Jing; Qiao, Xin; Shi, Zhihao; Lu, Tao; Chen, Yadong

2015-11-01

The discovery of novel scaffolds against a specific target has long been one of the most significant but challengeable goals in discovering lead compounds. A scaffold that binds in important regions of the active pocket is more favorable as a starting point because scaffolds generally possess greater optimization possibilities. However, due to the lack of sufficient chemical space diversity of the databases and the ineffectiveness of the screening methods, it still remains a great challenge to discover novel active scaffolds. Since the strengths and weaknesses of both fragment-based drug design and traditional virtual screening (VS), we proposed a fragment VS concept based on Bayesian categorization for the discovery of novel scaffolds. This work investigated the proposal through an application on VEGFR-2 target. Firstly, scaffold and structural diversity of chemical space for 10 compound databases were explicitly evaluated. Simultaneously, a robust Bayesian classification model was constructed for screening not only compound databases but also their corresponding fragment databases. Although analysis of the scaffold diversity demonstrated a very unevenly distribution of scaffolds over molecules, results showed that our Bayesian model behaved better in screening fragments than molecules. Through a literature retrospective research, several generated fragments with relatively high Bayesian scores indeed exhibit VEGFR-2 biological activity, which strongly proved the effectiveness of fragment VS based on Bayesian categorization models. This investigation of Bayesian-based fragment VS can further emphasize the necessity for enrichment of compound databases employed in lead discovery by amplifying the diversity of databases with novel structures.

Fragment screening of cyclin G-associated kinase by weak affinity chromatography.

PubMed

Meiby, Elinor; Knapp, Stefan; Elkins, Jonathan M; Ohlson, Sten

2012-11-01

Fragment-based drug discovery (FBDD) has become a new strategy for drug discovery where lead compounds are evolved from small molecules. These fragments form low affinity interactions (dissociation constant (K(D)) = mM - μM) with protein targets, which require fragment screening methods of sufficient sensitivity. Weak affinity chromatography (WAC) is a promising new technology for fragment screening based on selective retention of fragments by a drug target. Kinases are a major pharmaceutical target, and FBDD has been successfully applied to several of these targets. In this work, we have demonstrated the potential to use WAC in combination with mass spectrometry (MS) detection for fragment screening of a kinase target-cyclin G-associated kinase (GAK). One hundred seventy fragments were selected for WAC screening by virtual screening of a commercial fragment library against the ATP-binding site of five different proteins. GAK protein was immobilized on a capillary HPLC column, and compound binding was characterized by frontal affinity chromatography. Compounds were screened in sets of 13 or 14, in combination with MS detection for enhanced throughput. Seventy-eight fragments (46 %) with K(D) < 200 μM were detected, including a few highly efficient GAK binders (K(D) of 2 μM; ligand efficiency = 0.51). Of special interest is that chiral screening by WAC may be possible, as two stereoisomeric fragments, which both contained one chiral center, demonstrated twin peaks. This ability, in combination with the robustness, sensitivity, and simplicity of WAC makes it a new method for fragment screening of considerable potential.

Occupational lead poisoning in Ohio: surveillance using workers' compensation data.

PubMed

Seligman, P J; Halperin, W E; Mullan, R J; Frazier, T M

1986-11-01

To determine the utility of workers' compensation (WC) data in a system for the surveillance of occupational lead poisoning, we reviewed workers' compensation claims for lead poisoning in Ohio. For the period 1979 through 1983, 92 (81 per cent) of the 114 claims attributed to lead met our case definition of lead poisoning. The likelihood that a company had a case of lead poisoning was strongly correlated with the number of claims against the company. Thirty companies accounted for the 92 cases; two companies accounted for 49 per cent of these. Inspection by the Occupational Safety and Health Administration (OSHA) occurred at 14 of these companies, all of which were cited for violations of the OSHA lead standard. Comparison of the Standard Industrial Classification (SIC) codes for the 14 companies inspected by OSHA with the 15 companies not inspected by OSHA revealed that OSHA inspected battery manufacturers, non-ferrous foundries, secondary smelters, and primary lead smelters, but not bridge painters, manufacturers of electronic components, mechanical power transmission equipment, pumps, and paints, nor a sheriff's office where firing range slugs were remelted to make new bullets. Neither the number of cases of lead poisoning at a company nor the size of a company was related to the likelihood of being inspected by OSHA. Claims for WC appear to be a useful adjunct to an occupational lead poisoning surveillance system; their usefulness should be compared to that of other systems such as laboratory reports of elevated blood lead levels in adults.

Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities.

PubMed

Huang, Boshi; Kang, Dongwei; Zhan, Peng; Liu, Xinyong

2015-12-01

The search for additional drugs to treat HIV infection is a continuing effort due to the emergence and spread of HIV strains resistant to nearly all current drugs. The recent literature reveals that fragment-based drug design/discovery (FBDD) has become an effective alternative to conventional high-throughput screening strategies for drug discovery. In this critical review, the authors describe the state of the art in FBDD strategies for the discovery of anti-HIV drug-like compounds. The article focuses on fragment screening techniques, direct fragment-based design and early hit-to-lead progress. Rapid progress in biophysical detection and in silico techniques has greatly aided the application of FBDD to discover candidate agents directed at a variety of anti-HIV targets. Growing evidence suggests that structural insights on key proteins in the HIV life cycle can be applied in the early phase of drug discovery campaigns, providing valuable information on the binding modes and efficiently prompting fragment hit-to-lead progression. The combination of structural insights with improved methodologies for FBDD, including the privileged fragment-based reconstruction approach, fragment hybridization based on crystallographic overlays, fragment growth exploiting dynamic combinatorial chemistry, and high-speed fragment assembly via diversity-oriented synthesis followed by in situ screening, offers the possibility of more efficient and rapid discovery of novel drugs for HIV-1 prevention or treatment. Though the use of FBDD in anti-HIV drug discovery is still in its infancy, it is anticipated that anti-HIV agents developed via fragment-based strategies will be introduced into the clinic in the future.

Light bullets in coupled nonlinear Schrödinger equations with variable coefficients and a trapping potential.

PubMed

Xu, Si-Liu; Zhao, Guo-Peng; Belić, Milivoj R; He, Jun-Rong; Xue, Li

2017-04-17

We analyze three-dimensional (3D) vector solitary waves in a system of coupled nonlinear Schrödinger equations with spatially modulated diffraction and nonlinearity, under action of a composite self-consistent trapping potential. Exact vector solitary waves, or light bullets (LBs), are found using the self-similarity method. The stability of vortex 3D LB pairs is examined by direct numerical simulations; the results show that only low-order vortex soliton pairs with the mode parameter values n ≤ 1, l ≤ 1 and m = 0 can be supported by the spatially modulated interaction in the composite trap. Higher-order LBs are found unstable over prolonged distances.

The Myth of Fragmentation: Assessing Political Information Online

ERIC Educational Resources Information Center

Wichowski, Alexis M.

2010-01-01

Internet technology has provided people with unprecedented abilities to filter the information they encounter, leading many scholars to fear that people will be exposed to less diversity of perspectives and fragment into homogeneous interest groups. Exposure to a wide range of topics and perspectives about political information in particular is…

Feedback between intracellular flow, signaling and active stresses in Physarum plasmodial fragments

NASA Astrophysics Data System (ADS)

Zhang, Shun; Guy, Robert; Del Alamo, Juan Carlos

2016-11-01

Physarum polycephalum is a multinucleated slime mold whose endoplasm flows periodically driven by the contraction of its ectoplasm, a dense shell of F-actin cross-linked by myosin molecular motors and attached to the cell membrane. Ectoplasm contractions are regulated by calcium ions whose propagation is in turn governed by the flow. We study experimentally how this feedback leads to auto-oscillation by simultaneously measuring endoplasmic flow speed and rheological properties, the traction stresses between the ectoplasm and its substratum and the distribution of endoplasmic free calcium ions. We find that physarum fragments smaller than 100 microns remain round and stay in place. However, larger fragments break symmetry leading to sustained forward locomotion, in process that is reminiscent of an interfacial instability that seems to settle around two different limit cycles (traveling waves and standing waves). By using different adhesive coatings in the substratum we investigate the role of substratum friction in the emergence of coherent endoplasmic flow patterns and overall physarum fragment locomotion.

Atypical sources of childhood lead poisoning in the United States: a systematic review from 1966-2006.

PubMed

Gorospe, Emmanuel C; Gerstenberger, Shawn L

2008-09-01

Lead poisoning from atypical sources, which excludes the well-established lead-based paint ingestions and exposure in occupational settings, are increasingly reported in medical literature. Our objective is to increase awareness on atypical sources of lead exposure and to formulate recommendations for their detection based on actual reported cases. We systematically retrieved and reviewed reports on pediatric lead poisoning in the U.S. from atypical sources by searching Medline, Embase, CINAHL, Academic Search Premier, AltHealth, websites of state lead poisoning prevention programs, and the U.S. Consumer Product Safety Commission database for reports published from January 1966 to December 2006. We retrieved 28 published reports that met our inclusion criteria. Of these reports, 20 are case reports and 8 case series, documenting a total of 82 incidents of lead poisoning in children from atypical sources. There are varied sources of atypical lead exposure among U.S. children. The sources were grouped in the following categories based on their utility: fashion accessories, folk remedies, imported condiments & candies, pellets & bullets, and lastly, recreational & domestic items. Based on these findings, we have formulated a questionnaire that may assist in the identification of atypical lead sources in the home.

Corridors restore animal-mediated pollination in fragmented tropical forest landscapes

PubMed Central

Kormann, Urs; Scherber, Christoph; Tscharntke, Teja; Klein, Nadja; Larbig, Manuel; Valente, Jonathon J.; Hadley, Adam S.; Betts, Matthew G.

2016-01-01

Tropical biodiversity and associated ecosystem functions have become heavily eroded through habitat loss. Animal-mediated pollination is required in more than 94% of higher tropical plant species and 75% of the world's leading food crops, but it remains unclear if corridors avert deforestation-driven pollination breakdown in fragmented tropical landscapes. Here, we used manipulative resource experiments and field observations to show that corridors functionally connect neotropical forest fragments for forest-associated hummingbirds and increase pollen transfer. Further, corridors boosted forest-associated pollinator availability in fragments by 14.3 times compared with unconnected equivalents, increasing overall pollination success. Plants in patches without corridors showed pollination rates equal to bagged control flowers, indicating pollination failure in isolated fragments. This indicates, for the first time, that corridors benefit tropical forest ecosystems beyond boosting local species richness, by functionally connecting mutualistic network partners. We conclude that small-scale adjustments to landscape configuration safeguard native pollinators and associated pollination services in tropical forest landscapes. PMID:26817765

Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design.

PubMed

Benmansour, Fatiha; Trist, Iuni; Coutard, Bruno; Decroly, Etienne; Querat, Gilles; Brancale, Andrea; Barral, Karine

2017-01-05

With the aim to help drug discovery against dengue virus (DENV), a fragment-based drug design approach was applied to identify ligands targeting a main component of DENV replication complex: the NS5 AdoMet-dependent mRNA methyltransferase (MTase) domain, playing an essential role in the RNA capping process. Herein, we describe the identification of new inhibitors developed using fragment-based, structure-guided linking and optimization techniques. Thermal-shift assay followed by a fragment-based X-ray crystallographic screening lead to the identification of three fragment hits binding DENV MTase. We considered linking two of them, which bind to proximal sites of the AdoMet binding pocket, in order to improve their potency. X-ray crystallographic structures and computational docking were used to guide the fragment linking, ultimately leading to novel series of non-nucleoside inhibitors of flavivirus MTase, respectively N-phenyl-[(phenylcarbamoyl)amino]benzene-1-sulfonamide and phenyl [(phenylcarbamoyl)amino]benzene-1-sulfonate derivatives, that show a 10-100-fold stronger inhibition of 2'-O-MTase activity compared to the initial fragments. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

49 CFR Appendix A to Part 223 - Certification of Glazing Materials

Code of Federal Regulations, 2010 CFR

2010-10-01

...-ups, test measuring devices, and test procedures were performed by qualified personnel using... following tests: (i) Ballistic Impact in which a standard 22 caliber long rifle lead bullet of 40 grains in... Impact in which a standard 22 caliber long rifle lead bullet of 40 grains in weight impacts at a minimum...

Long-term landscape change and bird abundance in Amazonian rainforest fragments.

PubMed

Stouffer, Philip C; Bierregaard, Richard O; Strong, Cheryl; Lovejoy, Thomas E

2006-08-01

The rainforests of the Amazon basin are being cut by humans at a rate >20,000 km2/year leading to smaller and more isolated patches of forest, with remaining fragments often in the range of 1-100 ha. We analyzed samples of understory birds collected over 20 years from a standardized mist-netting program in 1- to 100-ha rainforest fragments in a dynamic Amazonian landscape near Manaus, Brazil. Across bird guilds, the condition of second growth immediately surrounding fragments was often as important as fragment size or local forest cover in explaining variation in abundance. Some fragments surrounded by 100 m of open pasture showed reductions in insectivorous bird abundance of over 95%, even in landscapes dominated by continuous forest and old second growth. These extreme reductions may be typical throughout Amazonia in small (< or =10 ha), isolated fragments of rainforest. Abundance for some guilds returned to preisolation levels in 10- and 100-ha fragments connected to continuous forest by 20-year-old second growth. Our results show that the consequences of Amazonian forest loss cannot be accurately described without explicit consideration of vegetation dynamics in matrix habitat. Any dichotomous classification of the landscape into 'forest" and "nonforest" misses essential information about the matrix.

Collapse and Fragmentation of Molecular Cloud Cores. VII. Magnetic Fields and Multiple Protostar Formation

NASA Astrophysics Data System (ADS)

Boss, Alan P.

2002-04-01

Recent observations of star-forming regions suggest that binary and multiple young stars are the rule rather than the exception and implicate fragmentation as the likely mechanism for their formation. Most numerical hydrodynamic calculations of fragmentation have neglected the possibly deleterious effects of magnetic fields, despite ample evidence for the importance of magnetic support of precollapse clouds. We present here the first numerical hydrodynamic survey of the collapse and fragmentation of initially magnetically supported clouds that takes into account several magnetic field effects in an approximate manner. The models are calculated with a three-dimensional, finite differences code that solves the equations of hydrodynamics, gravitation, and radiative transfer in the Eddington and diffusion approximations. Magnetic field effects are included through two simple approximations: magnetic pressure is added to the gas pressure, and magnetic tension is approximated by gravity dilution once collapse is well underway. Ambipolar diffusion of the magnetic field leading to cloud collapse is treated approximately as well. Models are calculated for a variety of initial cloud density profiles, shapes, and rotation rates. We find that in spite of the inclusion of magnetic field effects, dense cloud cores are capable of fragmenting into binary and multiple protostar systems. Initially prolate clouds tend to fragment into binary protostars, while initially oblate clouds tend to fragment into multiple protostar systems containing a small number (of the order of 4) of fragments. The latter are likely to be subject to rapid orbital evolution, with close encounters possibly leading to the ejection of fragments. Contrary to expectation, magnetic tension effects appear to enhance fragmentation, allowing lower mass fragments to form than would otherwise be possible, because magnetic tension helps to prevent a central density singularity from forming and producing a dominant

Universality of fragment shapes.

PubMed

Domokos, Gábor; Kun, Ferenc; Sipos, András Árpád; Szabó, Tímea

2015-03-16

The shape of fragments generated by the breakup of solids is central to a wide variety of problems ranging from the geomorphic evolution of boulders to the accumulation of space debris orbiting Earth. Although the statistics of the mass of fragments has been found to show a universal scaling behavior, the comprehensive characterization of fragment shapes still remained a fundamental challenge. We performed a thorough experimental study of the problem fragmenting various types of materials by slowly proceeding weathering and by rapid breakup due to explosion and hammering. We demonstrate that the shape of fragments obeys an astonishing universality having the same generic evolution with the fragment size irrespective of materials details and loading conditions. There exists a cutoff size below which fragments have an isotropic shape, however, as the size increases an exponential convergence is obtained to a unique elongated form. We show that a discrete stochastic model of fragmentation reproduces both the size and shape of fragments tuning only a single parameter which strengthens the general validity of the scaling laws. The dependence of the probability of the crack plan orientation on the linear extension of fragments proved to be essential for the shape selection mechanism.

Using hadron-in-jet data in a global analysis of D* fragmentation functions

NASA Astrophysics Data System (ADS)

Anderle, Daniele P.; Kaufmann, Tom; Stratmann, Marco; Ringer, Felix; Vitev, Ivan

2017-08-01

We present a novel global QCD analysis of charged D*-meson fragmentation functions at next-to-leading order accuracy. This is achieved by making use of the available data for single-inclusive D*-meson production in electron-positron annihilation, hadron-hadron collisions, and, for the first time, in-jet fragmentation in proton-proton scattering. It is shown how to include all relevant processes efficiently and without approximations within the Mellin moment technique, specifically for the in-jet fragmentation cross section. The presented technical framework is generic and can be straightforwardly applied to future analyses of fragmentation functions for other hadron species, as soon as more in-jet fragmentation data become available. We choose to work within the zero mass variable flavor number scheme which is applicable for sufficiently high energies and transverse momenta. The obtained optimum set of parton-to-D* fragmentation functions is accompanied by Hessian uncertainty sets which allow one to propagate hadronization uncertainties to other processes of interest.

Enzyme-linked immunosorbent assay detection and bioactivity of Cry1Ab protein fragments.

PubMed

Albright, Vurtice C; Hellmich, Richard L; Coats, Joel R

2016-12-01

The continuing use of transgenic crops has led to an increased interest in the fate of insecticidal crystalline (Cry) proteins in the environment. Enzyme-linked immunosorbent assays (ELISAs) have emerged as the preferred detection method for Cry proteins in environmental matrices. Concerns exist that ELISAs are capable of detecting fragments of Cry proteins, which may lead to an overestimation of the concentration of these proteins in the environment. Five model systems were used to generate fragments of the Cry1Ab protein, which were then analyzed by ELISAs and bioassays. Fragments from 4 of the model systems were not detectable by ELISA and did not retain bioactivity. Fragments from the proteinase K model system were detectable by ELISA and retained bioactivity. In most cases, ELISAs appear to provide an accurate estimation of the amount of Cry proteins in the environment, as detectable fragments retained bioactivity and nondetectable fragments did not retain bioactivity. Environ Toxicol Chem 2016;35:3101-3112. © 2016 SETAC. © 2016 SETAC.

One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists.

PubMed

Schiebel, Johannes; Radeva, Nedyalka; Köster, Helene; Metz, Alexander; Krotzky, Timo; Kuhnert, Maren; Diederich, Wibke E; Heine, Andreas; Neumann, Lars; Atmanene, Cedric; Roecklin, Dominique; Vivat-Hannah, Valérie; Renaud, Jean-Paul; Meinecke, Robert; Schlinck, Nina; Sitte, Astrid; Popp, Franziska; Zeeb, Markus; Klebe, Gerhard

2015-09-01

Fragment-based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit-to-lead-to-drug optimization, the screening process should distinguish reliably between binders and non-binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease-relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361-entry library by using a reporter-displacement assay, saturation-transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Large ejecta fragments from asteroids. [Abstract only

NASA Technical Reports Server (NTRS)

Asphaug, E.

1994-01-01

The asteroid 4 Vesta, with its unique basaltic crust, remains a key mystery of planetary evolution. A localized olivine feature suggests excavation of subcrustal material in a crater or impact basin comparable in size to the planetary radius (R(sub vesta) is approximately = 280 km). Furthermore, a 'clan' of small asteroids associated with Vesta (by spectral and orbital similarities) may be ejecta from this impact 151 and direct parents of the basaltic achondrites. To escape, these smaller (about 4-7 km) asteroids had to be ejected at speeds greater than the escape velocity, v(sub esc) is approximately = 350 m/s. This evidence that large fragments were ejected at high speed from Vesta has not been reconciled with the present understanding of impact physics. Analytical spallation models predict that an impactor capable of ejecting these 'chips off Vesta' would be almost the size of Vesta! Such an impact would lead to the catastrophic disruption of both bodies. A simpler analysis is outlined, based on comparison with cratering on Mars, and it is shown that Vesta could survive an impact capable of ejecting kilometer-scale fragments at sufficient speed. To what extent does Vesta survive the formation of such a large crater? This is best addressed using a hydrocode such as SALE 2D with centroidal gravity to predict velocities subsequent to impact. The fragmentation outcome and velocity subsequent to the impact described to demonstrate that Vesta survives without large-scale disassembly or overturning of the crust. Vesta and its clan represent a valuable dataset for testing fragmentation hydrocodes such as SALE 2D and SPH 3D at planetary scales. Resolution required to directly model spallation 'chips' on a body 100 times as large is now marginally possible on modern workstations. These boundaries are important in near-surface ejection processes and in large-scale disruption leading to asteroid families and stripped cores.

Mapping sea ice leads with a coupled numeric/symbolic system

NASA Technical Reports Server (NTRS)

Key, J.; Schweiger, A. J.; Maslanik, J. A.

1990-01-01

A method is presented which facilitates the detection and delineation of leads with single-channel Landsat data by coupling numeric and symbolic procedures. The procedure consists of three steps: (1) using the dynamic threshold method, an image is mapped to a lead/no lead binary image; (2) the likelihood of fragments to be real leads is examined with a set of numeric rules; and (3) pairs of objects are examined geometrically and merged where possible. The processing ends when all fragments are merged and statistical characteristics are determined, and a map of valid lead objects are left which summarizes useful physical in the lead complexes. Direct implementation of domain knowledge and rapid prototyping are two benefits of the rule-based system. The approach is found to be more successfully applied to mid- and high-level processing, and the system can retrieve statistics about sea-ice leads as well as detect the leads.

Fragmentation of organic ions bearing fixed multiple charges observed in MALDI MS.

PubMed

Lou, Xianwen; Li, Bao; de Waal, Bas F M; Schill, Jurgen; Baker, Matthew B; Bovee, Ralf A A; van Dongen, Joost L J; Milroy, Lech-Gustav; Meijer, E W

2018-01-01

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) was used to analyze a series of synthetic organic ions bearing fixed multiple charges. Despite the multiple intrinsic charges, only singly charged ions were recorded in each case. In addition to the pseudo-molecular ions formed by counterion adduction, deprotonation and electron capture, a number of fragment ions were also observed. Charge splitting by fragmentation was found to be a viable route for charge reduction leading to the formation of the observed singly charged fragment ions. Unlike multivalent metal ions, organic ions can rearrange and/or fragment during charge reduction. This fragmentation process will evidently complicate the interpretation of the MALDI MS spectrum. Because MALDI MS is usually considered as a soft ionization technique, the fragment ion peaks can easily be erroneously interpreted as impurities. Therefore, the awareness and understanding of the underlying MALDI-induced fragmentation pathways is essential for a proper interpretation of the corresponding mass spectra. Due to the fragment ions generated during charge reduction, special care should be taken in the MALDI MS analysis of multiply charged ions. In this work, the possible mechanisms by which the organic ions bearing fixed multiple charges fragment are investigated. With an improved understanding of the fragmentation mechanisms, MALDI TOF MS should still be a useful technique for the characterization of organic ions with fixed multiple charges. Copyright © 2017 John Wiley & Sons, Ltd.

Passive Reactive Berm (PRBerm) to Provide Low Maintenance Lead Containment at Active Small Arms Firing Ranges

DTIC Science & Technology

2012-01-01

body, dissolved Pb forms precipitates of Pb hydroxide [Pb(OH)2], Pb carbonate [PbCO3, cerrusite], or basic Pb carbonate [Pb3(OH)2 ( CO3 )2...along with a potential seed crystal for heterogeneous nucleation of Pb-pyromorphites (Wright et al., 2004). Depending on the presence of certain... single steel bullet trap. The sand or dirt berm is the oldest and most basic type of bullet trap. It uses the mass of the berm itself to stop and

Universality of fragment shapes

PubMed Central

Domokos, Gábor; Kun, Ferenc; Sipos, András Árpád; Szabó, Tímea

2015-01-01

The shape of fragments generated by the breakup of solids is central to a wide variety of problems ranging from the geomorphic evolution of boulders to the accumulation of space debris orbiting Earth. Although the statistics of the mass of fragments has been found to show a universal scaling behavior, the comprehensive characterization of fragment shapes still remained a fundamental challenge. We performed a thorough experimental study of the problem fragmenting various types of materials by slowly proceeding weathering and by rapid breakup due to explosion and hammering. We demonstrate that the shape of fragments obeys an astonishing universality having the same generic evolution with the fragment size irrespective of materials details and loading conditions. There exists a cutoff size below which fragments have an isotropic shape, however, as the size increases an exponential convergence is obtained to a unique elongated form. We show that a discrete stochastic model of fragmentation reproduces both the size and shape of fragments tuning only a single parameter which strengthens the general validity of the scaling laws. The dependence of the probability of the crack plan orientation on the linear extension of fragments proved to be essential for the shape selection mechanism. PMID:25772300

Detecting fragmentation extinction thresholds for forest understory plant species in peninsular Spain.

PubMed

Rueda, Marta; Moreno Saiz, Juan Carlos; Morales-Castilla, Ignacio; Albuquerque, Fabio S; Ferrero, Mila; Rodríguez, Miguel Á

2015-01-01

primary importance for the persistence of understory plants, to neglect the impact of fragmentation for some species can lead them to local extinction.

Lead intoxication and knee osteoarthritis after a gunshot: long-term follow-up case report.

PubMed

Gameiro, Vinicius Schott; de Araújo, Gabriel Costa Serrão; Bruno, Felipe Motta Moreira

2013-06-24

This case is of a man who suffered gunshots and developed saturnism. Projectiles were removed from the abdomen, but one was left in the knee for 14 years. The patient presented with weight loss, headaches, loss of sight, tiredness, cramps, painful joints and trembling. We identified ataxic movements such as intense trembling of the limbs and anaemia. The abdominal pain caused eight internments in different hospitals, and the patient always received the diagnosis of intestinal subocclusion. We removed the bullet and did a wide synovectomy. The patient did not receive a clinical treatment with chelates. The symptoms of lead poisoning ceased, but he developed knee osteoarthritis, during the 7 years of follow-up.

Tube pumices as strain markers of the ductile-brittle transition during magma fragmentation

NASA Astrophysics Data System (ADS)

Martí, J.; Soriano, C.; Dingwell, D. B.

1999-12-01

Magma fragmentation-the process by which relatively slow-moving magma transforms into a violent gas flow carrying fragments of magma-is the defining feature of explosive volcanism. Yet of all the processes involved in explosively erupting systems, fragmentation is possibly the least understood. Several theoretical and laboratory studies on magma degassing and fragmentation have produced a general picture of the sequence of events leading to the fragmentation of silicic magma. But there remains a debate over whether magma fragmentation is a consequence of the textural evolution of magma to a foamed state where disintegration of walls separating bubbles becomes inevitable due to a foam-collapse criterion, or whether magma is fragmented purely by stresses that exceed its tensile strength. Here we show that tube pumice-where extreme bubble elongation is observed-is a well-preserved magmatic `strain marker' of the stress state immediately before and during fragmentation. Structural elements in the pumice record the evolution of the magma's mechanical response from viscous behaviour (foaming and foam elongation) through the plastic or viscoelastic stage, and finally to brittle behaviour. These observations directly support the hypothesis that fragmentation occurs when magma undergoes a ductile-brittle transition and stresses exceed the magma's tensile strength.

Fragment size distribution statistics in dynamic fragmentation of laser shock-loaded tin

NASA Astrophysics Data System (ADS)

He, Weihua; Xin, Jianting; Zhao, Yongqiang; Chu, Genbai; Xi, Tao; Shui, Min; Lu, Feng; Gu, Yuqiu

2017-06-01

This work investigates the geometric statistics method to characterize the size distribution of tin fragments produced in the laser shock-loaded dynamic fragmentation process. In the shock experiments, the ejection of the tin sample with etched V-shape groove in the free surface are collected by the soft recovery technique. Subsequently, the produced fragments are automatically detected with the fine post-shot analysis techniques including the X-ray micro-tomography and the improved watershed method. To characterize the size distributions of the fragments, a theoretical random geometric statistics model based on Poisson mixtures is derived for dynamic heterogeneous fragmentation problem, which reveals linear combinational exponential distribution. The experimental data related to fragment size distributions of the laser shock-loaded tin sample are examined with the proposed theoretical model, and its fitting performance is compared with that of other state-of-the-art fragment size distribution models. The comparison results prove that our proposed model can provide far more reasonable fitting result for the laser shock-loaded tin.

Effects of habitat fragmentation on a stream-dwelling species, the flattened musk turtle Sternotherus depressus

USGS Publications Warehouse

Dodd, C.K.

1990-01-01

The flattened musk turtle Sternotherus depressus has disappeared from more than half of its former range because of habitat modifications to stream and river channels in the Warrior River Basin, Alabama. Only 6·9% of its probable historic range contains relatively healthy populations, and most populations are fragmented by extensive areas of unsuitable habitat. Turtles in the best remaining habitats continue to be vulnerable to disease and human-related disturbance, collecting and habitat modification. These factors lead to population declines and abnormal population structure. Habitat fragmentation, especially in small populations, increases vulnerability to human-caused catastrophes and demographic accidents, and could lead to eventual extinction. The threats facing fragmented populations of this turtle probably parallel those affecting many other stream-dwelling species throughout the southeastern United States.

Emergence of energy dependence in the fragmentation of heterogeneous materials

NASA Astrophysics Data System (ADS)

Pál, Gergő; Varga, Imre; Kun, Ferenc

2014-12-01

The most important characteristics of the fragmentation of heterogeneous solids is that the mass (size) distribution of pieces is described by a power law functional form. The exponent of the distribution displays a high degree of universality depending mainly on the dimensionality and on the brittle-ductile mechanical response of the system. Recently, experiments and computer simulations have reported an energy dependence of the exponent increasing with the imparted energy. These novel findings question the phase transition picture of fragmentation phenomena, and have also practical importance for industrial applications. Based on large scale computer simulations here we uncover a robust mechanism which leads to the emergence of energy dependence in fragmentation processes resolving controversial issues on the problem: studying the impact induced breakup of platelike objects with varying thickness in three dimensions we show that energy dependence occurs when a lower dimensional fragmenting object is embedded into a higher dimensional space. The reason is an underlying transition between two distinct fragmentation mechanisms controlled by the impact velocity at low plate thicknesses, while it is hindered for three-dimensional bulk systems. The mass distributions of the subsets of fragments dominated by the two cracking mechanisms proved to have an astonishing robustness at all plate thicknesses, which implies that the nonuniversality of the complete mass distribution is the consequence of blending the contributions of universal partial processes.

In Situ X-Ray Observations of Dendritic Fragmentation During Directional Solidification of a Sn-Bi Alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gibbs, John W.; Tourret, Damien; Gibbs, Paul J.

2015-09-25

Dendrite fragmentation is an important phenomenon in microstructural development during solidification. For instance, it plays a key role in initiating the columnar-to-equiaxed transition (CET). Here, we use x-ray radiography to study dendrite fragmentation rate in a Sn-39.5 wt.% Bi alloy during directional solidification. Experiments were performed in which solidification was parallel and anti-parallel to gravity, leading to significantly different fragmentation rates. We quantify the distribution of fragmentation rate as a function of distance from the solidification front, time in the mushy zone, and volume fraction of solid. While the observed fragmentation rate can be high, there is no evidence ofmore » a CET, illustrating that it requires more than just fragmentation to occur.« less

In Situ X-Ray Observations of Dendritic Fragmentation During Directional Solidification of a Sn-Bi Alloy

DOE PAGES

Gibbs, John W.; Tourret, Damien; Gibbs, Paul J.; ...

2015-09-25

Dendrite fragmentation is an important phenomenon in microstructural development during solidification. For instance, it plays a key role in initiating the columnar-to-equiaxed transition (CET). In this paper, we use x-ray radiography to study dendrite fragmentation rate in a Sn-39.5 wt.% Bi alloy during directional solidification. Experiments were performed in which solidification was parallel and anti-parallel to gravity, leading to significantly different fragmentation rates. We quantify the distribution of fragmentation rate as a function of distance from the solidification front, time in the mushy zone, and volume fraction of solid. Finally, while the observed fragmentation rate can be high, there ismore » no evidence of a CET, illustrating that it requires more than just fragmentation to occur.« less

Extraction of quark transversity distribution and Collins fragmentation functions with QCD evolution

NASA Astrophysics Data System (ADS)

Kang, Zhong-Bo; Prokudin, Alexei; Sun, Peng; Yuan, Feng

2016-01-01

We study the transverse-momentum-dependent (TMD) evolution of the Collins azimuthal asymmetries in e+e- annihilations and semi-inclusive hadron production in deep inelastic scattering processes. All the relevant coefficients are calculated up to the next-to-leading-logarithmic-order accuracy. By applying the TMD evolution at the approximate next-to-leading-logarithmic order in the Collins-Soper-Sterman formalism, we extract transversity distributions for u and d quarks and Collins fragmentation functions from current experimental data by a global analysis of the Collins asymmetries in back-to-back dihadron productions in e+e- annihilations measured by BELLE and BABAR collaborations and semi-inclusive hadron production in deep inelastic scattering data from HERMES, COMPASS, and JLab HALL A experiments. The impact of the evolution effects and the relevant theoretical uncertainties are discussed. We further discuss the TMD interpretation for our results and illustrate the unpolarized quark distribution, transversity distribution, unpolarized quark fragmentation, and Collins fragmentation functions depending on the transverse momentum and the hard momentum scale. We make detailed predictions for future experiments and discuss their impact.

Fragmentation of relativistic nuclei in peripheral interactions in nuclear track emulsion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Artemenkov, D. A., E-mail: artemenkov@lhe.jinr.ru; Bradnova, V.; Chernyavsky, M. M.

2008-09-15

The technique of nuclear track emulsions is used to explore the fragmentation of light relativistic nuclei down to the most peripheral interactions: nuclear 'white' stars. A complete pattern of the relativistic dissociation of a 8B nucleus with target fragment accompaniment is presented. Relativistic dissociation {sup 9}Be {yields} 2{alpha} is explored using significant statistics, and a relative contribution of {sup 8}Be decays from 0+ and 2+ states is established. Target fragment accompaniments are shown for relativistic fragmentation {sup 14}N {yields} 3He +H and {sup 22}Ne {yields} 5He. The leading role of the electromagnetic dissociation on heavy nuclei with respect to breakupsmore » on target protons is demonstrated in all these cases. It is possible to conclude that the peripheral dissociation of relativistic nuclei in nuclear track emulsion is a unique tool to study many-body systems composed of the lightest nuclei and nucleons in the energy scale relevant for nuclear astrophysics.« less

[Detection of UGT1A1*28 Polymorphism Using Fragment Analysis].

PubMed

Huang, Ying; Su, Jian; Huang, Xiaosui; Lu, Danxia; Xie, Zhi; Yang, Suqing; Guo, Weibang; Lv, Zhiyi; Wu, Hongsui; Zhang, Xuchao

2017-12-20

Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism. A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method. Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype. Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It's simple, time-saving, and easy-to-carry.

Genetic effects of chronic habitat fragmentation in a wind-pollinated tree

PubMed Central

Jump, Alistair S.; Peñuelas, Josep

2006-01-01

Habitat fragmentation poses a serious threat to plants through genetic changes associated with increased isolation and reduced population size. However, the longevity of trees, combined with effective seed or pollen dispersal, can enhance their resistance to these effects. The European beech (Fagus sylvatica) dominates forest over large regions of Europe. We demonstrate that habitat fragmentation in this species has led to genetic bottlenecks and the disruption of the species' breeding system, leading to significantly elevated levels of inbreeding, population divergence, and reduced genetic diversity within populations. These results show that, in contrast with the findings of previous studies, forest fragmentation has a negative genetic impact, even in this widespread, wind-pollinated tree. The identification of significant effects of forest fragmentation in beech demonstrates that trees are not at reduced risk from environmental change. This should be accounted for in the management of remaining natural and seminatural forest throughout the world. PMID:16698935

Jet axes and universal transverse-momentum-dependent fragmentation

NASA Astrophysics Data System (ADS)

Neill, Duff; Scimemi, Ignazio; Waalewijn, Wouter J.

2017-04-01

We study the transverse momentum spectrum of hadrons in jets. By measuring the transverse momentum with respect to a judiciously chosen axis, we find that this observable is insensitive to (the recoil of) soft radiation. Furthermore, for small transverse momenta we show that the effects of the jet boundary factorize, leading to a new transverse-momentum-dependent (TMD) fragmentation function. In contrast to the usual TMD fragmentation functions, it does not involve rapidity divergences and is universal in the sense that it is independent of the type of process and number of jets. These results directly apply to sub-jets instead of hadrons. We discuss potential applications, which include studying nuclear modification effects in heavy-ion collisions and identifying boosted heavy resonances.

Ion-polycyclic aromatic hydrocarbon collisions: kinetic energy releases for specific fragmentation channels

NASA Astrophysics Data System (ADS)

Reitsma, G.; Zettergren, H.; Boschman, L.; Bodewits, E.; Hoekstra, R.; Schlathölter, T.

2013-12-01

We report on 30 keV He2 + collisions with naphthalene (C10H8) molecules, which leads to very extensive fragmentation. To unravel such complex fragmentation patterns, we designed and constructed an experimental setup, which allows for the determination of the full momentum vector by measuring charged collision products in coincidence in a recoil ion momentum spectrometer type of detection scheme. The determination of fragment kinetic energies is found to be considerably more accurate than for the case of mere coincidence time-of-flight spectrometers. In fission reactions involving two cationic fragments, typically kinetic energy releases of 2-3 eV are observed. The results are interpreted by means of density functional theory calculations of the reverse barriers. It is concluded that naphthalene fragmentation by collisions with keV ions clearly is much more violent than the corresponding photofragmentation with energetic photons. The ion-induced naphthalene fragmentation provides a feedstock of various small hydrocarbonic species of different charge states and kinetic energy, which could influence several molecule formation processes in the cold interstellar medium and facilitates growth of small hydrocarbon species on pre-existing polycyclic aromatic hydrocarbons.

BARNARD 59: NO EVIDENCE FOR FURTHER FRAGMENTATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roman-Zuniga, C. G.; Frau, P.; Girart, J. M.

2012-03-10

The dense molecular clump at the center of the Barnard 59 (B59) complex is the only region in the Pipe Nebula that has formed a small, stellar cluster. The previous analysis of a high-resolution near-IR dust extinction map revealed that the nuclear region in B59 is a massive, mostly quiescent clump of 18.9 M{sub Sun }. The clump shows a monolithic profile, possibly indicating that the clump is on the way to collapse, with no evident fragmentation that could lead to another group of star systems. In this paper, we present new analysis that compares the dust extinction map withmore » a new dust emission radio-continuum map of higher spatial resolution. We confirm that the clump does not show any significant evidence for prestellar fragmentation at scales smaller than those probed previously.« less

Video camera system for locating bullet holes in targets at a ballistics tunnel

NASA Technical Reports Server (NTRS)

Burner, A. W.; Rummler, D. R.; Goad, W. K.

1990-01-01

A system consisting of a single charge coupled device (CCD) video camera, computer controlled video digitizer, and software to automate the measurement was developed to measure the location of bullet holes in targets at the International Shooters Development Fund (ISDF)/NASA Ballistics Tunnel. The camera/digitizer system is a crucial component of a highly instrumented indoor 50 meter rifle range which is being constructed to support development of wind resistant, ultra match ammunition. The system was designed to take data rapidly (10 sec between shoots) and automatically with little operator intervention. The system description, measurement concept, and procedure are presented along with laboratory tests of repeatability and bias error. The long term (1 hour) repeatability of the system was found to be 4 microns (one standard deviation) at the target and the bias error was found to be less than 50 microns. An analysis of potential errors and a technique for calibration of the system are presented.

Characterizing forest fragments in boreal, temperate, and tropical ecosystems

Treesearch

Arjan J. H. Meddens; Andrew T. Hudak; Jeffrey S. Evans; William A. Gould; Grizelle Gonzalez

2008-01-01

An increased ability to analyze landscapes in a spatial manner through the use of remote sensing leads to improved capabilities for quantifying human-induced forest fragmentation. Developments of spatially explicit methods in landscape analyses are emerging. In this paper, the image delineation software program eCognition and the spatial pattern analysis program...

Negative Ion CID Fragmentation of O-linked Oligosaccharide Aldoses—Charge Induced and Charge Remote Fragmentation

NASA Astrophysics Data System (ADS)

Doohan, Roisin A.; Hayes, Catherine A.; Harhen, Brendan; Karlsson, Niclas Göran

2011-06-01

Collision induced dissociation (CID) fragmentation was compared between reducing and reduced sulfated, sialylated, and neutral O-linked oligosaccharides. It was found that fragmentation of the [M - H]- ions of aldoses with acidic residues gave unique Z-fragmentation of the reducing end GalNAc containing the acidic C-6 branch, where the entire C-3 branch was lost. This fragmentation pathway, which is not seen in the alditols, showed that the process involved charge remote fragmentation catalyzed by a reducing end acidic anomeric proton. With structures containing sialic acid on both the C-3 and C-6 branch, the [M - H]- ions were dominated by the loss of sialic acid. This fragmentation pathway was also pronounced in the [M - 2H]2- ions revealing both the C-6 Z-fragment plus its complementary C-3 C-fragment in addition to glycosidic and cross ring fragmentation. This generation of the Z/C-fragment pairs from GalNAc showed that the charges were not participating in their generation. Fragmentation of neutral aldoses showed pronounced Z-fragmentation believed to be generated by proton migration from the C-6 branch to the negatively charged GalNAc residue followed by charge remote fragmentation similar to the acidic oligosaccharides. In addition, A-type fragments generated by charge induced fragmentation of neutral oligosaccharides were observed when the charge migrated from C-1 of the GalNAc to the GlcNAc residue followed by rearrangement to accommodate the 0,2A-fragmentation. LC-MS also showed that O-linked aldoses existed as interchangeable α/β pyranose anomers, in addition to a third isomer (25% of the total free aldose) believed to be the furanose form.

Coherent control of alkali cluster fragmentation dynamics

NASA Astrophysics Data System (ADS)

Lindinger, Albrecht; Lupulescu, Cosmin; Bartelt, Andreas; Vajda, Štefan; Wöste, Ludger

2003-06-01

Metal clusters exhibit extraordinary chemical and catalytic properties, which sensitively depend upon their size. This behavior makes them interesting candidates for the real-time analysis of ultrafast photo-induced processes—ultimately leading to coherent control scenarii. We have performed transient multi-photon ionization experiments on small alkali clusters of different size in order to probe their wave packet dynamics, structural reorientations, charge transfers and dissociative events in different vibrationally excited electronic states including their ground state. The observed processes were highly dependent on the irradiated pulse parameters, like its phase, amplitude and duration; an emphasis to employ a feedback control system for generating the optimum pulse shapes. Their spectral and temporal behavior reflects interesting properties about the investigated system and the irradiated photochemical process. We present first the vibrational dynamics of bound, dissociated, and pre-dissociated electronically excited states of alkali dimers and trimers. The scheme for observing the wave packet dynamics in the electronic ground state using stimulated Raman-pumping is shown. Since the employed pulse parameters significantly influence the efficiency of the irradiated dynamic pathways photo-induced fragmentation experiments on bifurcating reaction channels were carried out. In these experiments different branching ionization and fragmentation pathways of electronically excited Na 2K were investigated. By employing an evolutionary algorithm for optimizing the phase and amplitude of the applied laser field, the yield of the resulting parent or fragment ions could significantly be influenced and interesting features could be concluded from the obtained optimum pulse shapes revealing the characteristic molecular oscillation period. Moreover, the influence on the optimal pulse shape due to fragmentation from larger clusters into NaK is obtained. The substructure of

Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns.

PubMed

Luise, Nicola; Wyatt, Paul

2018-05-07

Synthesising polar semi-saturated bicyclic heterocycles can lead to better starting points for fragment-based drug discovery (FBDD) programs. This communication highlights the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fragmentation under the Scaling Symmetry and Turbulent Cascade with Intermittency

NASA Technical Reports Server (NTRS)

Gorokhovski, M.

2003-01-01

Fragmentation plays an important role in a variety of physical, chemical, and geological processes. Examples include atomization in sprays, crushing of rocks, explosion and impact of solids, polymer degradation, etc. Although each individual action of fragmentation is a complex process, the number of these elementary actions is large. It is natural to abstract a simple 'effective' scenario of fragmentation and to represent its essential features. One of the models is the fragmentation under the scaling symmetry: each breakup action reduces the typical length of fragments, r (right arrow) alpha r, by an independent random multiplier alpha (0 < alpha < 1), which is governed by the fragmentation intensity spectrum q(alpha), integral(sup 1)(sub 0) q(alpha)d alpha = 1. This scenario has been proposed by Kolmogorov (1941), when he considered the breakup of solid carbon particle. Describing the breakup as a random discrete process, Kolmogorov stated that at latest times, such a process leads to the log-normal distribution. In Gorokhovski & Saveliev, the fragmentation under the scaling symmetry has been reviewed as a continuous evolution process with new features established. The objective of this paper is twofold. First, the paper synthesizes and completes theoretical part of Gorokhovski & Saveliev. Second, the paper shows a new application of the fragmentation theory under the scale invariance. This application concerns the turbulent cascade with intermittency. We formulate here a model describing the evolution of the velocity increment distribution along the progressively decreasing length scale. The model shows that when the turbulent length scale gets smaller, the velocity increment distribution has central growing peak and develops stretched tails. The intermittency in turbulence is manifested in the same way: large fluctuations of velocity provoke highest strain in narrow (dissipative) regions of flow.

Evolution of Particle Size Distributions in Fragmentation Over Time

NASA Astrophysics Data System (ADS)

Charalambous, C. A.; Pike, W. T.

2013-12-01

We present a new model of fragmentation based on a probabilistic calculation of the repeated fracture of a particle population. The resulting continuous solution, which is in closed form, gives the evolution of fragmentation products from an initial block, through a scale-invariant power-law relationship to a final comminuted powder. Models for the fragmentation of particles have been developed separately in mainly two different disciplines: the continuous integro-differential equations of batch mineral grinding (Reid, 1965) and the fractal analysis of geophysics (Turcotte, 1986) based on a discrete model with a single probability of fracture. The first gives a time-dependent development of the particle-size distribution, but has resisted a closed-form solution, while the latter leads to the scale-invariant power laws, but with no time dependence. Bird (2009) recently introduced a bridge between these two approaches with a step-wise iterative calculation of the fragmentation products. The development of the particle-size distribution occurs with discrete steps: during each fragmentation event, the particles will repeatedly fracture probabilistically, cascading down the length scales to a final size distribution reached after all particles have failed to further fragment. We have identified this process as the equivalent to a sequence of trials for each particle with a fixed probability of fragmentation. Although the resulting distribution is discrete, it can be reformulated as a continuous distribution in maturity over time and particle size. In our model, Turcotte's power-law distribution emerges at a unique maturation index that defines a regime boundary. Up to this index, the fragmentation is in an erosional regime with the initial particle size setting the scaling. Fragmentation beyond this index is in a regime of comminution with rebreakage of the particles down to the size limit of fracture. The maturation index can increment continuously, for example under

Numerical Simulations of Light Bullets, Using The Full Vector, Time Dependent, Nonlinear Maxwell Equations

NASA Technical Reports Server (NTRS)

Goorjian, Peter M.; Silberberg, Yaron; Kwak, Dochan (Technical Monitor)

1994-01-01

This paper will present results in computational nonlinear optics. An algorithm will be described that solves the full vector nonlinear Maxwell's equations exactly without the approximations that are currently made. Present methods solve a reduced scalar wave equation, namely the nonlinear Schrodinger equation, and neglect the optical carrier. Also, results will be shown of calculations of 2-D electromagnetic nonlinear waves computed by directly integrating in time the nonlinear vector Maxwell's equations. The results will include simulations of 'light bullet' like pulses. Here diffraction and dispersion will be counteracted by nonlinear effects. The time integration efficiently implements linear and nonlinear convolutions for the electric polarization, and can take into account such quantum effects as Kerr and Raman interactions. The present approach is robust and should permit modeling 2-D and 3-D optical soliton propagation, scattering, and switching directly from the full-vector Maxwell's equations.

Removal of 10-nm contaminant particles from Si wafers using CO2 bullet particles.

PubMed

Kim, Inho; Hwang, Kwangseok; Lee, Jinwon

2012-04-11

Removal of nanometer-sized contaminant particles (CPs) from substrates is essential in successful fabrication of nanoscale devices. The particle beam technique that uses nanometer-sized bullet particles (BPs) moving at supersonic velocity was improved by operating it at room temperature to achieve higher velocity and size uniformity of BPs and was successfully used to remove CPs as small as 10 nm. CO2 BPs were generated by gas-phase nucleation and growth in a supersonic nozzle; appropriate size and velocity of the BPs were obtained by optimizing the nozzle contours and CO2/He mixture fraction. Cleaning efficiency greater than 95% was attained. BP velocity was the most important parameter affecting removal of CPs in the 10-nm size range. Compared to cryogenic Ar or N2 particles, CO2 BPs were more uniform in size and had higher velocity and, therefore, cleaned CPs more effectively.

Numerical Simulations of Light Bullets, Using The Full Vector, Time Dependent, Nonlinear Maxwell Equations

NASA Technical Reports Server (NTRS)

Goorjian, Peter M.; Silberberg, Yaron; Kwak, Dochan (Technical Monitor)

1995-01-01

This paper will present results in computational nonlinear optics. An algorithm will be described that solves the full vector nonlinear Maxwell's equations exactly without the approximations that we currently made. Present methods solve a reduced scalar wave equation, namely the nonlinear Schrodinger equation, and neglect the optical carrier. Also, results will be shown of calculations of 2-D electromagnetic nonlinear waves computed by directly integrating in time the nonlinear vector Maxwell's equations. The results will include simulations of 'light bullet' like pulses. Here diffraction and dispersion will be counteracted by nonlinear effects. The time integration efficiently implements linear and nonlinear convolutions for the electric polarization, and can take into account such quantum effects as Karr and Raman interactions. The present approach is robust and should permit modeling 2-D and 3-D optical soliton propagation, scattering, and switching directly from the full-vector Maxwell's equations.

An Alternative Representation of a Simulated Human Body

DTIC Science & Technology

2013-11-01

Casualty Assessment ( ORCA )3 uses this model to determine injury from insults to the body from fragments and bullets. An alternative representation was...Based Casualty Assessment: ORCA Analyst’s Manual; U.S. Army Research Laboratory: Aberdeen Proving Ground, MD, August 2005; draft. 4 U.S. Army Natick

Hypervelocity Impact Test Fragment Modeling: Modifications to the Fragment Rotation Analysis and Lightcurve Code

NASA Technical Reports Server (NTRS)

Gouge, Michael F.

2011-01-01

Hypervelocity impact tests on test satellites are performed by members of the orbital debris scientific community in order to understand and typify the on-orbit collision breakup process. By analysis of these test satellite fragments, the fragment size and mass distributions are derived and incorporated into various orbital debris models. These same fragments are currently being put to new use using emerging technologies. Digital models of these fragments are created using a laser scanner. A group of computer programs referred to as the Fragment Rotation Analysis and Lightcurve code uses these digital representations in a multitude of ways that describe, measure, and model on-orbit fragments and fragment behavior. The Dynamic Rotation subroutine generates all of the possible reflected intensities from a scanned fragment as if it were observed to rotate dynamically while in orbit about the Earth. This calls an additional subroutine that graphically displays the intensities and the resulting frequency of those intensities as a range of solar phase angles in a Probability Density Function plot. This document reports the additions and modifications to the subset of the Fragment Rotation Analysis and Lightcurve concerned with the Dynamic Rotation and Probability Density Function plotting subroutines.

Effects of chemical composition and test conditions on the dynamic tensile response of Zr-based metallic glasses

NASA Astrophysics Data System (ADS)

Wang, F.; Laws, K.; Martinez, D.; Trujillo, C. P.; Brown, A. D.; Cerreta, E. K.; Hazell, P. J.; Ferry, M.; Quadir, M. Z.; Jiang, J.; Escobedo, J. P.

2017-01-01

The effects of impact velocity and temperature on the dynamic mechanical behavior of two bulk metallic (BMG) alloys with slightly different elemental compositions (Zr55Cu30Ni5Al30 and Zr46Cu38Ag8Al38) have been investigated. Bullet-shaped samples were accelerated by a gas gun to speeds in the 400˜600m/s range and tested at both room temperature and 250°C. The samples impacted steel extrusion dies which subjected the bullets to high strains at relatively high strain-rates. The extruded fragments were subsequently soft recovered by using low density foams and examined by means of optical/scanning electron microscopy and differential scanning calorimetry. It was found that shear banding was the dictating mechanism responsible for the fracture of all BMGs. At room temperature, the Zr55Cu30Ni5Al30 alloy exhibited a higher resistance to fragmentation than the Zr46Cu38Ag8Al38 alloy. At 250°C, significant melting was observed in the recovered fragments of both alloys, which indicates that the BMG glassy structure undergoes a melting process and deformation likely occurs homogeneously.

The coordination between mechanical and chemical subsystems initiates locomotion of Physarum plasmodial fragments

NASA Astrophysics Data System (ADS)

Zhang, Shun; Guy, Robert; Del Alamo, Juan Carlos

2017-11-01

Physarum polycephalum is a multinucleated slime mold whose endoplasm flows periodically driven by the contraction of its ectoplasm, a dense shell of F-actin cross-linked by myosin molecular motors and attached to the cell membrane. We find that physarum fragments smaller than 100 microns remain round and stay in place. However, larger fragments break symmetry leading to sustained forward locomotion, in process that is reminiscent of an interfacial instability that seems to settle around two different limit cycles (traveling waves and standing waves). We use both theory and experiments to study how coordination emerges between the different mechanical and chemical subsystems of the fragment to initiate locomotion. The role of many involved factors, such as fragment size, substratum adhesiveness, rheological properties, actin polymerization and traction stresses are investigated, and we find they agree well with our predictive model.

Fragment capture device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Payne, Lloyd R.; Cole, David L.

2010-03-30

A fragment capture device for use in explosive containment. The device comprises an assembly of at least two rows of bars positioned to eliminate line-of-sight trajectories between the generation point of fragments and a surrounding containment vessel or asset. The device comprises an array of at least two rows of bars, wherein each row is staggered with respect to the adjacent row, and wherein a lateral dimension of each bar and a relative position of each bar in combination provides blockage of a straight-line passage of a solid fragment through the adjacent rows of bars, wherein a generation point ofmore » the solid fragment is located within a cavity at least partially enclosed by the array of bars.« less

Fragment capture device

DOEpatents

Payne, Lloyd R.; Cole, David L.

2010-03-30

A fragment capture device for use in explosive containment. The device comprises an assembly of at least two rows of bars positioned to eliminate line-of-sight trajectories between the generation point of fragments and a surrounding containment vessel or asset. The device comprises an array of at least two rows of bars, wherein each row is staggered with respect to the adjacent row, and wherein a lateral dimension of each bar and a relative position of each bar in combination provides blockage of a straight-line passage of a solid fragment through the adjacent rows of bars, wherein a generation point of the solid fragment is located within a cavity at least partially enclosed by the array of bars.

Grain fragmentation in ultrasonic-assisted TIG weld of pure aluminum.

PubMed

Chen, Qihao; Lin, Sanbao; Yang, Chunli; Fan, Chenglei; Ge, Hongliang

2017-11-01

Under the action of acoustic waves during an ultrasonic-assisted tungsten inert gas (TIG) welding process, a grain of a TIG weld of aluminum alloy is refined by nucleation and grain fragmentation. Herein, effects of ultrasound on grain fragmentation in the TIG weld of aluminum alloy are investigated via systematic welding experiments of pure aluminum. First, experiments involving continuous and fixed-position welding are performed, which demonstrate that ultrasound can break the grain of the TIG weld of pure aluminum. The microstructural characteristics of an ultrasonic-assisted TIG weld fabricated by fixed-position welding are analyzed. The microstructure is found to transform from plane crystal, columnar crystal, and uniform equiaxed crystal into plane crystal, deformed columnar crystal, and nonuniform equiaxed crystal after application of ultrasound. Second, factors influencing ultrasonic grain fragmentation are investigated. The ultrasonic amplitude and welding current are found to have a considerable effect on grain fragmentation. The degree of fragmentation first increases and then decreases with an increase in ultrasonic amplitude, and it increases with an increase in welding current. Measurement results of the vibration of the weld pool show that the degree of grain fragmentation is related to the intensity of acoustic nonlinearity in the weld pool. The greater the intensity of acoustic nonlinearity, the greater is the degree of grain fragmentation. Finally, the mechanism of ultrasonic grain fragmentation in the TIG weld of pure aluminum is discussed. A finite element simulation is used to simulate the acoustic pressure and flow in the weld pool. The acoustic pressure in the weld pool exceeds the cavitation threshold, and cavitation bubbles are generated. The flow velocity in the weld pool does not change noticeably after application of ultrasound. It is concluded that the high-pressure conditions induced during the occurrence of cavitation, lead to grain

A fragment-based approach leading to the discovery of a novel binding site and the selective CK2 inhibitor CAM4066.

PubMed

De Fusco, Claudia; Brear, Paul; Iegre, Jessica; Georgiou, Kathy Hadje; Sore, Hannah F; Hyvönen, Marko; Spring, David R

2017-07-01

Recently we reported the discovery of a potent and selective CK2α inhibitor CAM4066. This compound inhibits CK2 activity by exploiting a pocket located outside the ATP binding site (αD pocket). Here we describe in detail the journey that led to the discovery of CAM4066 using the challenging fragment linking strategy. Specifically, we aimed to develop inhibitors by linking a high-affinity fragment anchored in the αD site to a weakly binding warhead fragment occupying the ATP site. Moreover, we describe the remarkable impact that molecular modelling had on the development of this novel chemical tool. The work described herein shows potential for the development of a novel class of CK2 inhibitors. Copyright © 2017. Published by Elsevier Ltd.

Non-ideal magnetohydrodynamic simulations of the two-stage fragmentation model for cluster formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, Nicole D.; Basu, Shantanu, E-mail: N.Bailey@leeds.ac.uk, E-mail: basu@uwo.ca

2014-01-01

We model molecular cloud fragmentation with thin-disk, non-ideal magnetohydrodynamic simulations that include ambipolar diffusion and partial ionization that transitions from primarily ultraviolet-dominated to cosmic-ray-dominated regimes. These simulations are used to determine the conditions required for star clusters to form through a two-stage fragmentation scenario. Recent linear analyses have shown that the fragmentation length scales and timescales can undergo a dramatic drop across the column density boundary that separates the ultraviolet- and cosmic-ray-dominated ionization regimes. As found in earlier studies, the absence of an ionization drop and regular perturbations leads to a single-stage fragmentation on pc scales in transcritical clouds, somore » that the nonlinear evolution yields the same fragment sizes as predicted by linear theory. However, we find that a combination of initial transcritical mass-to-flux ratio, evolution through a column density regime in which the ionization drop takes place, and regular small perturbations to the mass-to-flux ratio is sufficient to cause a second stage of fragmentation during the nonlinear evolution. Cores of size ∼0.1 pc are formed within an initial fragment of ∼pc size. Regular perturbations to the mass-to-flux ratio also accelerate the onset of runaway collapse.« less

Natural-product-derived fragments for fragment-based ligand discovery

NASA Astrophysics Data System (ADS)

Over, Björn; Wetzel, Stefan; Grütter, Christian; Nakai, Yasushi; Renner, Steffen; Rauh, Daniel; Waldmann, Herbert

2013-01-01

Fragment-based ligand and drug discovery predominantly employs sp2-rich compounds covering well-explored regions of chemical space. Despite the ease with which such fragments can be coupled, this focus on flat compounds is widely cited as contributing to the attrition rate of the drug discovery process. In contrast, biologically validated natural products are rich in stereogenic centres and populate areas of chemical space not occupied by average synthetic molecules. Here, we have analysed more than 180,000 natural product structures to arrive at 2,000 clusters of natural-product-derived fragments with high structural diversity, which resemble natural scaffolds and are rich in sp3-configured centres. The structures of the cluster centres differ from previously explored fragment libraries, but for nearly half of the clusters representative members are commercially available. We validate their usefulness for the discovery of novel ligand and inhibitor types by means of protein X-ray crystallography and the identification of novel stabilizers of inactive conformations of p38α MAP kinase and of inhibitors of several phosphatases.

Optical model calculations of 14.6A GeV silicon fragmentation cross sections

NASA Technical Reports Server (NTRS)

Townsend, Lawrence W.; Khan, Ferdous; Tripathi, Ram K.

1993-01-01

An optical potential abrasion-ablation collision model is used to calculate hadronic dissociation cross sections for a 14.6 A GeV(exp 28) Si beam fragmenting in aluminum, tin, and lead targets. The frictional-spectator-interaction (FSI) contributions are computed with two different formalisms for the energy-dependent mean free path. These estimates are compared with experimental data and with estimates obtained from semi-empirical fragmentation models commonly used in galactic cosmic ray transport studies.

Telomere Restriction Fragment (TRF) Analysis.

PubMed

Mender, Ilgen; Shay, Jerry W

2015-11-20

While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al. , 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al. , 1990; Ouellette et al. , 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

Facile green fabrication of nanostructure ZnO plates, bullets, flower, prismatic tip, closed pine cone: Their antibacterial, antioxidant, photoluminescent and photocatalytic properties.

PubMed

Madan, H R; Sharma, S C; Udayabhanu; Suresh, D; Vidya, Y S; Nagabhushana, H; Rajanaik, H; Anantharaju, K S; Prashantha, S C; Sadananda Maiya, P

2016-01-05

Green synthesis of multifunctional Zinc oxide nanoparticles (NPs) with a variety of morphologies were achieved by low temperature solution combustion route employing neem (Azadirachta indica) extract as fuel. The nanoparticles were characterized by PXRD, FTIR, XPS, Raman and UV-Visible spectroscopic studies. The Morphologies were studied by SEM and TEM analysis. The NPs were subjected for photoluminescence, photocatalytic, antibacterial and antioxidant activity studies. PXRD pattern confirmed the hexagonal wurtzite structure of the product. SEM images indicated the transformation of mushroom like hexagonal disks to bullets, buds, cones, bundles and closed pine cone structured NPs with increase in the concentration of neem extract in reaction mixture. The NPs exhibited prominent green emission due to the presence of intrinsic defect centers. The as-formed bullet shaped ZnO with 4ml of neem extract was found to decolorize Methylene blue (MB) under Sunlight and UV light irradiation. The antibacterial studies indicated that ZnO NPs of concentration 500, 750 and 1000μg resulted in significant antibacterial activity on Klebsiella aerogenes and Staphylococcus aureus but not against Escherichia coli and Pseudomonas aeruginosa in agar well diffusion method. Further, ZnO NPs exhibited significant antioxidant activity against scavenging DPPH free radicals. The current investigation demonstrated green engineering method for the synthesis of multifunctional ZnO NPs with interesting morphologies using neem extract. Copyright © 2015 Elsevier B.V. All rights reserved.

Agarose gel electrophoresis for the separation of DNA fragments.

PubMed

Lee, Pei Yun; Costumbrado, John; Hsu, Chih-Yuan; Kim, Yong Hoon

2012-04-20

Agarose gel electrophoresis is the most effective way of separating DNA fragments of varying sizes ranging from 100 bp to 25 kb(1). Agarose is isolated from the seaweed genera Gelidium and Gracilaria, and consists of repeated agarobiose (L- and D-galactose) subunits(2). During gelation, agarose polymers associate non-covalently and form a network of bundles whose pore sizes determine a gel's molecular sieving properties. The use of agarose gel electrophoresis revolutionized the separation of DNA. Prior to the adoption of agarose gels, DNA was primarily separated using sucrose density gradient centrifugation, which only provided an approximation of size. To separate DNA using agarose gel electrophoresis, the DNA is loaded into pre-cast wells in the gel and a current applied. The phosphate backbone of the DNA (and RNA) molecule is negatively charged, therefore when placed in an electric field, DNA fragments will migrate to the positively charged anode. Because DNA has a uniform mass/charge ratio, DNA molecules are separated by size within an agarose gel in a pattern such that the distance traveled is inversely proportional to the log of its molecular weight(3). The leading model for DNA movement through an agarose gel is "biased reptation", whereby the leading edge moves forward and pulls the rest of the molecule along(4). The rate of migration of a DNA molecule through a gel is determined by the following: 1) size of DNA molecule; 2) agarose concentration; 3) DNA conformation(5); 4) voltage applied, 5) presence of ethidium bromide, 6) type of agarose and 7) electrophoresis buffer. After separation, the DNA molecules can be visualized under uv light after staining with an appropriate dye. By following this protocol, students should be able to: Understand the mechanism by which DNA fragments are separated within a gel matrix Understand how conformation of the DNA molecule will determine its mobility through a gel matrix Identify an agarose solution of appropriate

Bioisostere Identification by Determining the Amino Acid Binding Preferences of Common Chemical Fragments.

PubMed

Sato, Tomohiro; Hashimoto, Noriaki; Honma, Teruki

2017-12-26

To assist in the structural optimization of hit/lead compounds during drug discovery, various computational approaches to identify potentially useful bioisosteric conversions have been reported. Here, the preference of chemical fragments to hydrogen bonds with specific amino acid residues was used to identify potential bioisosteric conversions. We first compiled a data set of chemical fragments frequently occurring in complex structures contained in the Protein Data Bank. We then used a computational approach to determine the amino acids to which these chemical fragments most frequently hydrogen bonded. The results of the frequency analysis were used to hierarchically cluster chemical fragments according to their amino acid preferences. The Euclid distance between amino acid preferences of chemical fragments for hydrogen bonding was then compared to MMP information in the ChEMBL database. To demonstrate the applicability of the approach for compound optimization, the similarity of amino acid preferences was used to identify known bioisosteric conversions of the epidermal growth factor receptor inhibitor gefitinib. The amino acid preference distance successfully detected bioisosteric fragments corresponding to the morpholine ring in gefitinib with a higher ROC score compared to those based on topological similarity of substituents and frequency of MMP in the ChEMBL database.

Characterizing DebriSat Fragments: So Many Fragments, So Much Data, and So Little Time

NASA Technical Reports Server (NTRS)

Shiotani, B.; Rivero, M.; Carrasquilla, M.; Allen, S.; Fitz-Coy, N.; Liou, J.-C.; Huynh, T.; Sorge, M.; Cowardin, H.; Opiela, J.;

Posterior epidural disc fragment masquerading as spinal tumor: Review of the literature.

PubMed

Park, Taejune; Lee, Ho Jun; Kim, Jae Seong; Nam, Kiyeun

2018-03-09

posterior epidural lumbar disc fragment could be masqueraded as spinal tumor, if rim enhancement is observed in MRI scans with sudden symptoms of radiculopathy or cauda equina syndrome, it should be taken into consideration. Early diagnosis can lead to early surgery, which can reduce complications.

Ingested bone fragment in the bowel: Two cases and a review of the literature.

PubMed

Emir, Seyfi; Ozkan, Zeynep; Altınsoy, Hasan Baki; Yazar, Fatih Mehmet; Sözen, Selim; Bali, Ilhan

2013-10-16

Generally, ingested foreign bodies are excreted from the digestive tract without any complications or morbidity. In adults, ingestion of foreign bodies frequently occurs in alcoholics and elderly individuals with dentures. The most commonly ingested foreign bodies are food stuffs or their parts, such as fish bones or fragments of bone and phytobezoars. Sharp foreign bodies like fish and chicken bones can lead to intestinal perforation and peritonitis. We report herein two cases, one of bowel perforation and another of anal impaction, both caused by ingested bone fragments. Complications due to ingested bone fragments are not common and preoperative diagnosis remains a challenge and therefore it must be considered in susceptible cases.

Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.

PubMed

Kutchukian, Peter S; Wassermann, Anne Mai; Lindvall, Mika K; Wright, S Kirk; Ottl, Johannes; Jacob, Jaison; Scheufler, Clemens; Marzinzik, Andreas; Brooijmans, Natasja; Glick, Meir

2015-06-01

A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits. © 2014 Society for Laboratory Automation and Screening.

Large Spin-Wave Bullet in a Ferrimagnetic Insulator Driven by the Spin Hall Effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jungfleisch, M. B.; Zhang, W.; Sklenar, J.

2016-02-01

Due to its transverse nature, spin Hall effects (SHE) provide the possibility to excite and detect spin currents and magnetization dynamics even in magnetic insulators. Magnetic insulators are outstanding materials for the investigation of nonlinear phenomena and for novel low power spintronics applications because of their extremely low Gilbert damping. Here, we report on the direct imaging of electrically driven spin-torque ferromagnetic resonance (ST-FMR) in the ferrimagnetic insulator Y 3Fe 5O 12 based on the excitation and detection by SHEs. The driven spin dynamics in Y 3Fe 5O 12 is directly imaged by spatially-resolved microfocused Brillouin light scattering (BLS) spectroscopy.more » Previously, ST-FMR experiments assumed a uniform precession across the sample, which is not valid in our measurements. A strong spin-wave localization in the center of the sample is observed indicating the formation of a nonlinear, self-localized spin-wave `bullet'.« less

From Protein Structure to Small-Molecules: Recent Advances and Applications to Fragment-Based Drug Discovery.

PubMed

Ferreira, Leonardo G; Andricopulo, Adriano D

2017-01-01

Fragment-based drug discovery (FBDD) is a broadly used strategy in structure-guided ligand design, whereby low-molecular weight hits move from lead-like to drug-like compounds. Over the past 15 years, an increasingly important role of the integration of these strategies into industrial and academic research platforms has been successfully established, allowing outstanding contributions to drug discovery. One important factor for the current prominence of FBDD is the better coverage of the chemical space provided by fragment-like libraries. The development of the field relies on two features: (i) the growing number of structurally characterized drug targets and (ii) the enormous chemical diversity available for experimental and virtual screenings. Indeed, fragment-based campaigns have contributed to address major challenges in lead optimization, such as the appropriate physicochemical profile of clinical candidates. This perspective paper outlines the usefulness and applications of FBDD approaches in medicinal chemistry and drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Incorporation of fragmentation into a volume average solidification model

NASA Astrophysics Data System (ADS)

Zheng, Y.; Wu, M.; Kharicha, A.; Ludwig, A.

2018-01-01

In this study, a volume average solidification model was extended to consider fragmentation as a source of equiaxed crystals during mixed columnar-equiaxed solidification. The formulation suggested for fragmentation is based on two hypotheses: the solute-driven remelting is the dominant mechanism; and the transport of solute-enriched melt through an interdendritic flow in the columnar growth direction is favorable for solute-driven remelting and is the necessary condition for fragment transportation. Furthermore, a test case with Sn-10 wt%Pb melt solidifying vertically downward in a 2D domain (50 × 60 mm2) was calculated to demonstrate the model’s features. Solidification started from the top boundary, and a columnar structure developed initially with its tip growing downward. Furthermore, thermo-solutal convection led to fragmentation in the mushy zone near the columnar tip front. The fragments transported out of the columnar region continued to grow and sink, and finally settled down and piled up in the bottom domain. The growing columnar structure from the top and pile-up of equiaxed crystals from the bottom finally led to a mixed columnar-equiaxed structure, in turn leading to a columnar-to-equiaxed transition (CET). A special macrosegregation pattern was also predicted, in which negative segregation occurred in both columnar and equiaxed regions and a relatively strong positive segregation occurred in the middle domain near the CET line. A parameter study was performed to verify the model capability, and the uncertainty of the model assumption and parameter was discussed.

Fatal contact shot to the chest caused by the gas jet from a muzzle-loading pistol discharging only black powder and no bullet: case study and experimental simulation of the wounding effect.

PubMed

Große Perdekamp, Markus; Glardon, Matthieu; Kneubuehl, Beat P; Bielefeld, Lena; Nadjem, Hadi; Pollak, Stefan; Pircher, Rebecca

2015-01-01

In modern medico-legal literature, only a small number of publications deal with fatal injuries from black powder guns. Most of them focus on the morphological features such as intense soot soiling, blast tattooing and burn effects in close-range shots or describe the wound ballistics of spherical lead bullets. Another kind of "unusual" and potentially lethal weapons are handguns destined for firing only blank cartridges such as starter and alarm pistols. The dangerousness of these guns is restricted to very close and contact range shots and results from the gas jet produced by the deflagration of the propellant. The present paper reports on a suicide committed with a muzzle-loading percussion pistol cal. 45. An unusually large stellate entrance wound was located in the precordial region, accompanied by an imprint mark from the ramrod and a faint greenish discoloration (apparently due to the formation of sulfhemoglobin). Autopsy revealed an oversized powder cavity, multiple fractures of the anterior thoracic wall as well as ruptures of the heart, the aorta, the left hepatic lobe and the diaphragm. In total, the zone of mechanical destruction had a diameter of approx. 15 cm. As there was no exit wound and no bullet lodged in the body, the injury was caused exclusively by the inrushing combustion gases of the propellant (black powder) comparable with the gas jet of a blank cartridge gun. In contact shots to ballistic gelatine using the suicide's pistol loaded with black powder but no projectile, the formation of a nearly spherical cavity could be demonstrated by means of a high-speed camera. The extent of the temporary cavity after firing with 5 g of black powder roughly corresponded to the zone of destruction found in the suicide's body.

D meson production asymmetry, unfavored fragmentation, and consequences for prompt atmospheric neutrino production

NASA Astrophysics Data System (ADS)

Maciuła, Rafał; Szczurek, Antoni

2018-04-01

We consider unfavored light quark/antiquark to D meson fragmentation. We discuss nonperturbative effects for small transverse momenta. The asymmetry for D+ and D- production measured by the LHCb collaboration provides natural constraints on the parton (quark/antiquark) fragmentation functions. We find that already a fraction of q /q ¯→D fragmentation probability is sufficient to account for the measured asymmetry. We make predictions for similar asymmetry for neutral D mesons. Large D -meson production asymmetries are found for large xF which is related to dominance of light quark/antiquark q /q ¯→D fragmentation over the standard c →D fragmentation. As a consequence, prompt atmospheric neutrino flux at high neutrino energies can be much larger than for the conventional c →D fragmentation. The latter can constitute a sizeable background for the cosmic neutrinos claimed to be observed recently by the IceCube Observatory. Large rapidity-dependent D+/D- and D0/D¯0 asymmetries are predicted for low (√{s }=20 - 100 GeV ) energies. The q /q ¯→D fragmentation leads to enhanced production of D mesons at low energies. At √{s }=20 GeV the enhancement factor with respect to the conventional contribution is larger than a factor of five. In the considered picture the large-xF D mesons are produced dominantly via fragmentation of light quarks/antiquarks. Predictions for fixed target p + 4He collisions relevant for a fixed target LHCb experiment are presented.

Preserving lung after traumatic transection of left lower lobe bronchus from bullet injury.

PubMed

Hanif, Muhammad Shoaib; Mishwani, A H; Oparka, J; Buchan, K

2015-06-01

A 22-year-old soldier was shot in the left chest by a bullet from close range. He was found to have a left haemothorax and remained shocked despite aggressive resuscitation. Due to difficult terrain and night time movement restrictions, there were limitations to the transfer of patient. So he was attended at a peripheral hospital. At emergency thoracotomy, three segmental arteries to left upper lobe were ligated and haemostasis was secured. The level of transection of left lower lobe bronchus was identified to be below the origin of the apical segmental bronchus. The lower lobe bronchus was successfully re-attached and followed up with a daily bronchoscopic clearance of distal airway. The patient made a full recovery. Anastomosis of left lower lobe bronchus after traumatic transection is a viable option for preserving an amputated lobe, in trauma settings, provided haemostatic control has been adequately achieved. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

No magic bullets: a systematic review of 102 trials of interventions to improve professional practice.