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At least 811 records · Page 45Linked to original sources
PubMed2005

Applications of ribosome display to antibody drug discovery.

Ribosome display is a polymerase chain reaction-based in vitro display technology that is well suited to the selection and evolution of high affinity antibodies. Both eukaryotic and prokaryotic translation systems have been applied to ribosome display, and the technology's utility has been demonstrated in the antibody isolation process. In particular, ribosome display lends itself to the evolution of functional characteristics, such as potency, of lead candidate antibodies to provide therapeutic antibodies. Large libraries (10(12)) can be rapidly constructed, antibodies selected, and sequence space extensively explored by targeted mutagenesis techniques or by random mutagenesis throughout the antibody sequence. Using such approaches in ribosome display systems lead antibodies derived from phage display or from immunised animals have been improved > 1000-fold in potency within 6 months. This review will discuss the technology and give an insight into how ribosome display is being applied to the antibody lead discovery and optimisation processes.

Animals↗
PubMed1993

An anatomicosurgical study of the temporal branch of the facial nerve.

The surgical anatomy of the temporal branch of the facial nerve was studied bilaterally in 10 embalmed cadaveric heads. Particular attention was paid to the relationships between the temporal branch, the galeal-fascial layers, and the fat pads of the temporal-zygomatic region. The temporal branch of the facial nerve pierces the parotidomasseteric fascia below the zygomatic arch. This branch travels first in the subcutaneous tissue and then, above the zygomatic arch, in the subgaleal space. The temporal branch divides into an anterior, a middle (frontal), and a posterior ramus soon after it pierces the parotid fascia. The course of the terminal twigs of the temporal branch of the facial nerve in the subgaleal space is extremely variable, with their location being at times posterior to the anterior one-fourth of the temporalis muscle. Occasionally, a twig for the frontalis muscle may run in between the two layers of the superficial temporal fascia. Because of these findings (anteroposterior variability of temporal branch twigs and recurrent intrafascial twig), Yasargil's interfascial dissection may at times fail. A combined frontotemporal scalp/superficial temporal fascia dissection is anatomically suited to preserve the temporal branch of the facial nerve.

Adipose Tissue↗
PubMed2006

Coupled substitution of type A and B carbonate in sodium-bearing apatite.

A suite of Na-bearing type A-B carbonate hydroxyapatites {Ca(10-y)Na(y)[(PO4)(6-y)(CO3)y][(OH)(2-2x)(CO3)x], x approximately = y} has been synthesized at 1200 degrees C and 0.5-1.0 GPa, and investigated by single-crystal X-ray structure and FTIR spectroscopy. Crystal data for the maximum content of carbonate (11.1 wt%) are a = 9.3855(7), c = 6.9142(4) A, space group P6(3)/m, R = 0.023, R(w) = 0.014. Structural accommodation of the substitutions requires local coupling of Na and channel (type A) and phosphate (type B) carbonate ion defects. The type B carbonate ion is located on the sloping faces of the substituted phosphate group, but is inclined at an angle of 53 degrees to the mirror plane. FTIR spectra have minimal nu3 absorption beyond 1500 cm(-1) and dominant nu2 absorption at 873 cm(-1). Synthetic Na-bearing type A-B apatites (with a high content of type A carbonate) are thus similar in both chemical composition and infrared spectra to biological apatites. The latter are reinterpreted as Na-bearing type A-B carbonate apatites with channel carbonate up to 50% of total carbonate.

Apatites↗
PubMed2003

Angiogenic responses of vascular endothelial growth factors in periadventitial tissue.

Recent discovery of new members of the vascular endothelial growth factor (VEGF) family has generated much interest as to which members may be best suited for therapeutic angiogenesis in various tissues. In this study we evaluated angiogenic responses of the different members of the VEGF family in vivo using adenoviral gene transfer. Adenoviruses (1 x 10(9) plaque-forming units [pfu]) encoding for VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-C(deltaNdeltaC) and VEGF-D(deltaNdeltaC) (deltaNdeltaC are proteolytically cleaved forms) were transferred locally to the periadventitial space of the rabbit carotid arteries using a collar technique that allows efficient local transfection of the periadventitial tissue. Expression of the transfected VEGFs was confirmed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Seven days after the gene transfer maximum neovessel formation was observed in VEGF-A-, VEGF-D-, and VEGF-D(deltaNdeltaC)-transfected arteries. VEGF-C(deltaNdeltaC) also showed angiogenic activity whereas VEGF-B was not effective in inducing angiogenesis. Pericytes were detected around the neovessels, which also frequently showed the presence of intraluminal erythrocytes. Infiltration of inflammatory cells in response to VEGF-D and VEGF-D(deltaNdeltaC) was less prominent than that caused by other VEGFs. In line with the absence of lymphatics in the normal carotid arteries no significant evidence of lymphatic vessel formation was seen in response to any of the studied VEGFs in the periadventitial space. The results help to define possibilities for local angiogenic therapy around blood vessels and support the concept that angiogenic effects may be tissue-specific and depend both on the growth factor ligands and the target tissues. It is concluded that VEGF-A, VEGF-D, and VEGF-D(deltaNdeltaC) are the best candidates for therapeutic angiogenesis when delivered around large arteries.

Adenoviridae↗
PubMed1998

Thoracoscopic microsurgical excision of a thoracic schwannoma. Case report.

A 6-cm-diameter schwannoma located at T-2 was resected completely by using transthoracic microsurgical endoscopy. The partially cystic tumor widened the neural foramen and extended into the apex of the right thoracic cavity but did not extend intradurally. The tumor was accessed by means of three 15-mm incisions made in the intercostal spaces. The operative blood loss was only 200 ml, and there were no complications. The patient was discharged on the 2nd postoperative day and returned to full activity 1 week after surgery. Thoracoscopy provides an excellent alternative to thoracotomy for peripheral thoracic nerve sheath tumors that originate within the neural foramen or more distally along the intercostal nerves within the thorax. An anterior approach is required for intrathoracic tumors but is not suited for intradural tumors. An open posterior or posterolateral approach to the thoracic spine is required for intradural tumors to allow the dura to be closed adequately.

Activities of Daily Living↗
PubMedDate not supplied

Networked incubators. Hothouses of the new economy.

Business incubators such as Hotbank, CMGI, and Idealab! are a booming industry. Offering office space, funding, and basic services to start-ups, these organizations have become the hottest way to nurture and grow fledgling businesses. But are incubators a fleeting phenomenon born of an overheated stock market, or are they an important and lasting way of creating value and wealth in the new economy? The authors argue that one type of incubator, called a networked incubator, represents a fundamentally new and enduring organizational model uniquely suited to growing businesses in the Internet economy. It shares certain features with other incubators--mainly, it fosters a spirit of entrepreneurship and offers economies of scale. But its key distinguishing feature is its ability to give start-ups preferential access to a network of potential partners. Such incubators institutionalize their networking--they have systems in place to encourage networking, helping start-ups, for example, to meet with potential business allies. That doesn't mean incubatees get preferential treatment; it means only that they have built-in access to partnerships that might not have existed without the incubator. Even with this advantage, however, networked incubators can easily follow the road to ruin. To avoid failure, they must create a portfolio of companies and advisers that their incubatees can leverage. That can be done by strategically investing in portfolio firms and by enlisting a large set of business allies. It can also be done by establishing connections and relationships that are anchored more to the incubator than to particular individuals.

Cooperative Behavior↗
PubMed2005

Persistence of invading gypsy moth populations in the United States.

Exotic invasive species are a mounting threat to native biodiversity, and their effects are gaining more public attention as each new species is detected. Equally important are the dynamics of exotic invasives that are previously well established. While the literature reports many examples of the ability of a newly arrived exotic invader to persist prior to detection and population growth, we focused on the persistence dynamics of an established invader, the European gypsy moth (Lymantria dispar) in the United States. The spread of gypsy moth is largely thought to be the result of the growth and coalescence of isolated colonies in a transition zone ahead of the generally infested area. One important question is thus the ability of these isolated colonies to persist when subject to Allee effects and inimical stochastic events. We analyzed the US gypsy moth survey data and identified isolated colonies of gypsy moth using the local indicator of spatial autocorrelation. We then determined region-specific probabilities of colony persistence given the population abundance in the previous year and its relationship to a suite of ecological factors. We observed that colonies in Wisconsin, US, were significantly more likely to persist in the following year than in other geographic regions of the transition zone, and in all regions, the abundance of preferred host tree species and land use category did not appear to influence persistence. We propose that differences in region-specific rates of persistence may be attributed to Allee effects that are differentially expressed in space, and that the inclusion of geographically varying Allee effects into colony-invasion models may provide an improved paradigm for addressing the establishment and spread of gypsy moth and other invasive exotic species.

Animals↗
PubMed1989

[20th anniversary of sonographic diagnosis of the pancreas].

During the past 20 years sonographic diagnosis of pancreatic diseases has developed from isolated case reports into a differentiated method. It is particularly suited for prognostic reviewing of acute pancreatitis and for detection of typical complications in acute pancreatitis and pancreatic trauma. Its contribution to the detection of chronic pancreatitis in on-target examination is also highly significant. Carcinomas of the pancreas can be detected with a good degree of sensitivity if their diameter is equal to or exceeds 1.5 cm. Other problems deserving attention are those of differential diagnosis of low-echo space-occupying growths at the pancreas and the differentiation against circumscribed chronic pancreatitis. Sonographically aimed fine needle puncture is a suitable complementary examination. Doubts must be voiced against the value of sonographic diagnosis of the pancreas within the overall framework of so-called mass screenings.

Acute Disease↗
PubMed1989

Human tolerance to 100% oxygen at 9.5 psia during five daily simulated 8-hour EVA exposures.

Extravehicular activity (EVA) currently involves decompression to 4.3 psia. This degree of decompression carries a significant potential for decompression sickness (DCS) which could be alleviated if a pressure of 9.5 psia could be maintained in the pressure suit. Previous studies have not evaluated the potential for oxygen toxicity at 9.5 psia. Twenty-one subjects were exposed to 100% oxygen at 9.5 psia for 5 consecutive days, 8 h.d-1 while performing moderate exercise to simulate a typical work-week in the proposed pressure suit environment. No DCS or venous gas bubbles were detected. Pulmonary function tests, physical exams, blood analyses, arterial oxygen saturation monitoring, and X-rays showed no evidence of oxygen toxicity under these conditions. These results suggest that a 100% oxygen, 9.5 psia pressure suit environment could avoid both DCS and oxygen toxicity during EVAs of comparable duration and physical activity.

Adult↗
PubMed1991

Synthetic immunogens. Part IV: Conformational studies on gastrin conjugates with the human immunoglobulin G1 hinge peptide 225-232/225'-232'.

Hybrids of the double-chain bis-cystinyl fragment 225-232/225'-232' of human immunoglobulin G1 (IgG1) with the human little-gastrin sequence 2-17 were found to induce in animals a strong antigastrin humoral immune response with antibody titers comparable to those raised with conventional gastrin/carrier-protein conjugates. The observed gastrin receptor-like specificity of the polyclonal antibodies led to the assumption that the gastrin component of the hybrids is still capable of folding into its preferred bioactive structure and thus to express a similar conformational epitope in the dynamic process of recognition by the B-cell receptors. CD measurements on these hybrid compounds in aqueous and aqueous organic media confirmed the free conformational space for the antigenic gastrin moiety, which is essentially randomly coiled in aqueous solution but retains its ability to fold into the gastrin-specific ordered structure in aqueous organic media as used to mimic the water-limited environment of peptides while interacting with target cells at receptor level. The absence of reciprocal conformational restriction in such hybrid molecules suggests that a compact, rigid heterodetic cyclic structure as the hinge peptide is well suited for the multiple attachment of antigenic sequences in view of the preparation of fully synthetic immunogens.

Amino Acid Sequence↗
PubMed1997

The nature of spatiotemporal changes in cerebral hemodynamics as manifested in functional magnetic resonance imaging.

The nature of changes in rapidly acquired magnetic resonance images of the brain was studied by using a denoising method and spectral techniques optimally suited to short time series. It was found that the stimulus related changes have a complex spatiotemporal structure even for simple visual stimuli. Apart from a low frequency window, the non-stimulus-related changes were found to correspond in detail to either breathing or heartbeat, although these two sources show different patterns of spatial coherence in the image. At low frequencies, oscillations with frequencies around 0.1 Hz were observed, also with nontrivial space-time structure, which are likely to be vasomotor in origin.

Blood Vessels↗
PubMed1990

A method for the characterization of foldings in protein ribbon models.

The ribbon model of chain macromolecules is a useful tool for analyzing some of the large-scale shape features of these complex systems. Up to now, the ribbon model has been used mostly to produce graphical displays, which are usually analyzed by visual inspection. In this work we suggest a computational method for characterizing automatically, in a concise and algebraic fashion, some of the important shape features of these ribbon models. The procedure is based on a graph-theoretical and knot-theoretical characterization of three well-defined projections of a space curve associated with the ribbon. The labeled graphs can be characterized by the handedness of the crossovers in the ribbon that are the vertices of the graph. The method can be used to provide a fully algebraic representation of the changes occurring when a molecule, such as a protein, undergoes conformational rearrangements (folding), as well as to provide a shape comparison for a pair of related molecular ribbons. This algebraic representation is well suited for easy storage, retrieval, and computer manipulation of the information on the ribbon's shape. Illustrative examples of the method are provided.

Computer Graphics↗
PubMed2003

Computational assignment of protein backbone NMR peaks by efficient bounding and filtering.

NMR resonance assignment is one of the key steps in solving an NMR protein structure. The assignment process links resonance peaks to individual residues of the target protein sequence, providing the prerequisite for establishing intra- and inter-residue spatial relationships between atoms. The assignment process is tedious and time-consuming, which could take many weeks. Though there exist a number of computer programs to assist the assignment process, many NMR labs are still doing the assignments manually to ensure quality. This paper presents a new computational method based on the combination of a suite of algorithms for automating the assignment process, particularly the process of backbone resonance peak assignment. We formulate the assignment problem as a constrained weighted bipartite matching problem. While the problem, in the most general situation, is NP-hard, we present an efficient solution based on a branch-and-bound algorithm with effective bounding techniques using two recently introduced approximation algorithms. We also devise a greedy filtering algorithm for reducing the search space. Our experimental results on 70 instances of (pseudo) real NMR data derived from 14 proteins demonstrate that the new solution runs much faster than a recently introduced (exhaustive) two-layer algorithm and recovers more correct peak assignments than the two-layer algorithm. Our result demonstrates that integrating different algorithms can achieve a good tradeoff between backbone assignment accuracy and computation time.

Algorithms↗
PubMed1994

Crystallization and preliminary X-ray analysis of phenol hydroxylase from Trichosporon cutaneum.

Recombinant phenol hydroxylase from the soil yeast Trichosporon cutaneum has been crystallized with PEG 4000 as precipitant. The crystals are monoclinic, space group P2(1) with cell dimensions a = 101.8 A, b = 153.0 A, c = 116.0 A and beta = 114.8 degrees. The crystal asymmetric unit most likely contains two dimers of phenol hydroxylase corresponding to a packing density in the crystals of 2.54 A 3/Da. The self-rotation function is consistent with the packing of two dimers in the asymmetric unit. The observed diffraction pattern extends beyond 2.8 A resolution and the crystals are well suited for structural analysis by X-ray diffraction methods.

Crystallization↗
PubMed2006

[Morel-Lavallée lesion. A grave soft tissue injury].

The Morel-Lavallée lesion is a rare condition that was first described by the French physician Maurice Morel-Lavallée in 1853. The lesion is caused by forces of pressure and shear stress at the borders of subcutaneous tissue to the muscle fascia or bone as they are seen in run-over accidents. It leads to a shear of skin and subcutaneous tissue from the neighboring fascia followed by the development of a blood-filled hollow space at predestined regions of the body. If therapy is insufficient, large areas of necrosis can form, which will negatively influence operative measures. We report about three patients with the diagnosis of a Morel-Lavallée lesion. The history and the impressive clinical findings are demonstrated as well as the differential operative therapy performed, partially with osteosynthesis of accompanying bone injuries. According to the recommendations of the literature known to us, an adjusted therapeutic regime suited to the particular findings was carried out and in all three cases uncomplicated healing can be reported. Our results are in line with the existing recommendations, which are to relieve the soft tissue hematoma in time and sufficiently, and secondly to carry out débridements initially as well as planned second-look operations.

Accidental Falls↗
PubMed2004

Rotations in a vertebrate setting: evaluation of the symmetry group of the disynaptic canal-neck projection.

Organizational structures intrinsic to nervous systems can be more precisely analyzed and compared with other logical structures once they are expressed in mathematical languages. A standard mathematical language for expressing organizational structure is that of groups. Groups are especially well suited to organizational structures involving multiple symmetries such as spatial structures. The vestibular system is widely believed to mediate many neural functions involving spatial structure. The vestibular nuclei receive direct projections from the vestibular endorgans, the semicircular canals and the otolith organs. The near-orthogonal directions of the semicircular canals are embedded in the bone. However, those canal directions are external to the nervous system. This study addresses the way the three-dimensional space of rotations is also embedded in the group structure of neural connectivity. Although we know a great deal about physical rotation, it is not clear that nervous systems organize rotations in the same way as physicists do. It would make sense for nervous systems to organize rotations in such a way as to provide physiologically relevant information about performing or compensating for rotations. The vestibular nuclei, which might be expected to display an organization that binds rotations into a rotation space, do not give a clear organization. This may be because of the multiplicity of spatial functions performed by the vestibular nuclei; rather than one spatial organization, the vestibular nuclei are likely to accommodate multiple, related spatial organizations. This study evaluates one particular data set from the literature that specifies the organization of the disynaptic canal-neck projection; other projections and neuronal populations may have other intrinsic organizations. The data are evaluated directly for their symmetry group. In the symmetry group, the vertebrate requirement that physiology have a right and left is found to be satisfied in two ways: (i) by a hexagonal symmetry arising from the right-left doubling of front and back, (ii) along with separate organizations on the two sides that may be required to operate independently to some extent. The eight observed muscle innervation patterns from the data are the complete set of possible combinations of inhibitory/excitatory polarities from three canal pairs. These eight innervation patterns are organized as the vertices of a cube. The two types of side muscles provide the vertical direction. As the head rotates in physical space, the cube rotates in sensorimotor space. Like the canal-neck projection, otolith projections and proprioceptive afferents contact both the vestibular nuclei and neck motoneurons. They may have a similar organization, perhaps with extensions of the same pattern. Otherwise, like a checkerboard superimposed over a paisley, they will form an overlapping organization with the disynaptic canal-neck projection. Further research is required to determine whether the sensorimotor spatial structure of the canal-neck projection is widespread in nervous systems or whether there are several complete structures that are fragmented and reintegrated.

Animals↗
PubMed2005

Reproductive experience differentially affects spatial reference and working memory performance in the mother.

The transition to motherhood results in a number of hormonal, neurological, and behavioral changes necessary to ensure offspring survival. Once motherhood is established, further neurological and behavioral changes may result with additional parity and mothering. Recent research has shown that motherhood enhances both hippocampal-dependent learning and memory and oxytocin-induced long-term potentiation, suggesting that the hippocampus is affected by mothering. In turn, degree of maternal behavior, either high or low, has been shown to affect spatial learning and memory performance in adult offspring. The present experiment aimed to investigate the effect of reproductive experience (nulli-, primi-, and multiparity and mothering) and degree of maternal behavior on hippocampus-dependent learning and memory in the mother. Results show that regardless of error type, primiparous rats make fewer errors compared to nulliparous rats, while multiparous rats show a trend towards making fewer errors compared to nulliparous rats. In addition, mothers who spend less time licking and nursing offspring had fewer reference memory errors. Perhaps the enhanced learning and memory in the inexperienced, new mother allows her to effectively acquire the suite of maternal behaviors necessary to ensure offspring survival and achieve reproductive success with subsequent reproductive experience.

Animals↗
PubMed2026

A benchmarking study of feature screening approaches across type 1 diabetes omics studies classification settings.

In recent years, high dimensional omics analyses have become more commonplace for investigating complex biological systems. Typically, these studies attempt to identify key biomolecules associated with a particular biological process. Often, machine learning (ML) is used to identify these biomolecules, typically by learning which biomolecules are highly predictive of a treatment, biological outcome, or phenotype. A major challenge of applying ML to high throughput omics is overcoming noise when sample size is limited and unbalanced with respect to tens of thousands of biomolecules measured. Thus, feature selection (the process of reducing the number of predictors) is both a critical and common step in the ML analysis pipeline. While much attention has been given to embedding and wrapping techniques for feature selection in the omics space, filter-based methods for model-free feature selection have appealing theoretical properties. This manuscript evaluates sure screening, a class of filter-based feature selection methods which provide analytical guarantees for true feature set retention. Here, we cover existing feature screening methods based on the sure screening principal, available software, methods to improve feature screening, and contextualize feature screening in the larger discussion of feature selection for omics data analysis. Additionally, a suite of model-free sure screening approaches is applied and compared for several omics biomedical applications in a ML classification context. We identified BcorSIS as the most effective and computationally efficient screening method across various omics datasets, consistently outperforming others like CSIS and DCSIS in runtime.

Humans↗