Miracle-dz/UniFAR-FTUs huggingface dataset:
AB‐Bind: Antibody binding mutational database for computational affinity predictions

Antibodies (Abs) are a crucial component of the immune system and are often used as diagnostic and therapeutic agents. The need for high‐affinity and high‐specificity antibodies in research and medicine is driving the development of computational tools for accelerating antibody design and discovery. We report a diverse set of antibody binding data with accompanying structures that can be used to evaluate methods for modeling antibody interactions. Our Antibody‐Bind (AB‐Bind) database includes 1101 mutants with experimentally determined changes in binding free energies (ΔΔG) across 32 complexes. Using the AB‐Bind data set, we evaluated the performance of protein scoring potentials in their ability to predict changes in binding free energies upon mutagenesis. Numerical correlations between computed and observed ΔΔG values were low (r = 0.16–0.45), but the potentials exhibited predictive power for classifying variants as improved vs weakened binders. Performance was evaluated using the area under the curve (AUC) for receiver operator characteristic (ROC) curves; the highest AUC values for 527 mutants with |ΔΔG| > 1.0 kcal/mol were 0.81, 0.87, and 0.88 using STATIUM, FoldX, and Discovery Studio scoring potentials, respectively. Some methods could also enrich for variants with improved binding affinity; FoldX and Discovery Studio were able to correctly rank 42% and 30%, respectively, of the 80 most improved binders (those with ΔΔG < −1.0 kcal/mol) in the top 5% of the database. This modest predictive performance has value but demonstrates the continuing need to develop and improve protein energy functions for affinity prediction.
Molecular Biology of Breast Cancer in the Horn of Africa: Case Series—A Pilot Study of Breast Cancer from Eritrea

Background. Recently, gene expression profiling and its surrogate immunohistochemistry (IHC) markers classified breast cancer into four distinct molecular subtypes, which have different prognoses, targeted therapies, and/or clinical outcomes. Objective. To conduct a preliminary study, to correlate the clinical pathological profiles and taxonomy of molecular subtypes of breast cancer in Eritrea, in the Horn of Africa. Design. Review of pathology reports from Jan. 1 to Nov. 30, 2009, provided 22 cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Cytokeratin 5/6). Result. Twenty patients were female and most of them (68%) were under 50 years at presentation. 90% were invasive invasive carcinoma of no special type and were histological grade 3. The molecular subtypes were luminal A (55%), luminal B (5%), HER2 (5%), basal-like (10%), and unclassified (25%). Triple negative carcinoma (basal-like and unclassified combined) was 35%, mostly (71%) in women under 50 years with grade 3 tumours. Conclusion. Breast carcinoma in Eritrean women presents at a younger age and with a high histologic grade. The two predominant molecular subtypes are luminal A and triple negative. Determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Eritrean women with breast cancer.
Beyond basins: φ,ψ preferences of a residue depend heavily on the φ,ψ values of its neighbors

The Ramachandran plot distributions of nonglycine residues from experimentally determined structures are routinely described as grouping into one of six major basins: β, PII, α, αL, ξ and γ'. Recent work describing the most common conformations adopted by pairs of residues in folded proteins [i.e., (φ,ψ)2‐motifs] showed that commonly described major basins are not true single thermodynamic basins, but are composed of distinct subregions that are associated with various conformations of either the preceding or following neighbor residue. Here, as documentation of the extent to which the conformational preferences of a central residue are influenced by the conformations of its two neighbors, we present a set of φ,ψ‐plots that are delimited simultaneously by the φ,ψ‐angles of its neighboring residues on both sides. The level of influence seen here is typically greater than the influence associated with considering the identities of neighboring residues, implying that the use of this heretofore untapped information can improve the accuracy of structure prediction algorithms and low resolution protein structure refinement.
The yeast transcription elongation factor Spt4/5 is a sequence‐specific RNA binding protein

The heterodimeric transcription elongation factor Spt4/Spt5 (Spt4/5) tightly associates with RNAPII to regulate both transcriptional elongation and co‐transcriptional pre‐mRNA processing; however, the mechanisms by which Spt4/5 acts are poorly understood. Recent studies of the human and Drosophila Spt4/5 complexes indicate that they can bind nucleic acids in vitro. We demonstrate here that yeast Spt4/5 can bind in a sequence‐specific manner to single stranded RNA containing AAN repeats. Furthermore, we show that the major protein determinants for RNA‐binding are Spt4 together with the NGN domain of Spt5 and that the KOW domains are not required for RNA recognition. These findings attribute a new function to a domain of Spt4/5 that associates directly with RNAPII, making significant steps towards elucidating the mechanism behind transcriptional control by Spt4/5.
Transoral Submandibular Ganglion Neurectomy

Background: The management of sialorrhea can be difficult for both the patient and the clinician. Current management includes behavioral modification, anticholinergics, botulinum injections, and a variety of surgical options, which all have demonstrated some efficacy. As minimally invasive procedures flourish, we explore the feasibility of highly selective transoral submandibular neurectomy (TOSN) for the management of sialorrhea. Methods: Ten human cadaver dissections of the floor of mouth were performed bilaterally, for a total of 20 separate cases. An intraoral technique for highly selective, submandibular ganglion neurectomy is demonstrated. Results: A transoral submandibular ganglion neurectomy was performed in 10 cadavers (20 neurectomies) easily and reliably, without injury to the submandibular duct or the main trunk of the lingual nerve. Conclusion: Transoral submandibular neurectomy is an attractive addition to the armamentarium of surgical options for the treatment of medically intractable sialorrhea. Further study in selected patients would need to be performed to demonstrate clinical feasibility.
Structure of an acetylating aldehyde dehydrogenase from the thermophilic ethanologen Geobacillus thermoglucosidasius

Acetylating aldehyde dehydrogenases (AcAldDH) catalyse the acetylation of Coenzyme‐A (CoA), or in reverse generate acetaldehyde from Acetyl‐CoA using NADH as a co‐factor. This article reports the expression, purification, enzyme assay, and X‐ray crystal structures of an AcAldDH from Geobacillus thermoglucosidasius (GtAcAldDH) to 2. 1Å and in complex with CoA and NAD+ to 4. 0Å. In the structure, the AcAldDH forms a close‐knit dimer, similar to that seen in other Alcohol Dehydrogenase (ADH) structures. In GtAcAldDH, these dimers associate via their N‐termini to form weakly interacting tetramers. This mode of tetrameric association is also seen in an unpublished AcAldDH deposited in the PDB, but is in contrast to all other ADH structures, (including the one other published AcAldDH found in a bacterial microcompartment), in which the dimers bury a large surface area including the C‐termini. This novel mode of association sequesters the active sites and potentially reactive acyl‐enzyme intermediates in the center of the tetramer. In other respects, the structure is very similar to the other AcAldDH, binding the cofactors in a corresponding fashion. This similarity enabled the identification of a shortened substrate cavity in G. thermoglucosidasius AcAldDH, explaining the limitations on the length of substrate accepted by the enzyme.
Access to Moving Image Documents: Background Concepts and Proposals for Surrogates for film and video Works

This study examines the fashioning of a model for a surrogate to facilitate user selection of the most appropriate film or video work for a particular use. Such a surrogate is intended to enable a user to bring to a collection of moving image documents the habits of scrutiny characteristic of the selection and critical use of print linguistic works. Images bear a different relationship to objects and events than do words and the manner in which moving image documents generate meaning differs from the way strings of words communicate. A matrix of a time line and several characteristics of the film or video document is proposed as the primary aspect of the surrogate graphic record. Issues of description and sampling within the abstracting process are raised. The proposed surrogate is seen as a system for achieving an individual, more book‐like use of film and video documents.
Office-Based Balloon Sinus Dilation

Objective: Balloon sinus dilation (BSD) instruments afford the opportunity for office-based sinus procedures in properly selected patients with chronic rhinosinusitis (CRS). This study evaluated patient-reported outcomes 1 year after office-based BSD. Methods: Adult patients with medically refractory CRS were prospectively enrolled into a multicenter, single-arm study and treated with office-based BSD under local anesthesia. Follow-up on 203 patients was conducted at 2, 8, and 24 weeks postsurgery using validated outcome measures for quality of life (SNOT-20) and computed tomography imaging (Lund-Mackay score). After 24 weeks, patients were re-enrolled for 1-year follow-up to evaluate changes in SNOT-20 scores and revisions. Results: All patients who re-enrolled (n = 122) completed the study, with an average follow-up of 1.4 years. Neither preoperative SNOT-20 nor Lund-Mackay CT scores were predictive of re-enrollment and return for follow-up. Compared to baseline, improvements in SNOT-20 scores remained statistically significant (P < .001) and clinically meaningful (mean decrease ≥ 0.8). In patients followed to 1.4 years, 9 of 122 (7.4%) had revision surgery. Conclusion: Following office-based BSD, significant improvements in quality of life observed at 24 weeks were maintained 1 year postsurgery. These extended results provide further evidence of office-based BSD as an effective, minimally invasive procedure for appropriately selected patients with CRS.
Enhanced red upconversion emission, magnetoluminescent behavior, and bioimaging application of NaSc0.75Er0.02Yb0.18Gd0.05F4@AuNPs nanoparticles.

The present study reports significant enhancement in the red upconversion emission of Er(3+) in NaSc0.8Er0. 02Yb0.18F4 upconversion nanoparticles (UCNPs), via a two step process, (i) codoping of Gd(3+) ion at Sc(3+) site and (ii) attaching gold nanoparticles (AuNPs) at the surface of these codoped nanostructures, and further probes the use of these Gd:UCNPs@AuNPs for bioimaging application. The Gd(3+) codoping tailors the particle size (reduces) of UCNPs and bring out Er(3+)-Yb(3+) ion pair in close proximity, which promotes the cross relaxation mechanism and boosts the population in red emitting level (4)F9/2. Further, attachment of AuNPs on the surface of UCNPs gives 2-fold advantages, that is, reduction in green band (through resonance energy transfer with efficiency 31.54%) and enhancement in red band (through plasmonic effect). It gives red to green (R/G) ratio nearly 20:1 (almost single band red UC), which is quite promising for imaging application. In addition to this, codoping of Gd(3+) enhances the magnetic moment appreciably and the obtained magnetic moment for NaSc0.75Er0. 02Yb0.18Gd0. 05F4 UCNPs (∼1.7 emu/g) is close to the reported values for bioseparation in case of NPs. This shows the potential of the material for multimodal (optical and magnetic both) imaging application. These magnetoluminescence particles were found safe up to 1 mg/mL dose as assessed by cytotoxicity measurement in human cervical cancer (HeLa) and lung cancer (A549) cells. Ultrafine nanoparticles, transparent, and stable colloidal solution and the unique red UC emission endow these NPs as optical probe for imaging applications.
Optimum sequence multisets for synchronous code-division multiple-access channels

It is shown that the sum capacity of the symbol-synchronous code-division multiple-access channel with equal average-input-energy constraints is maximized precisely by those spreading sequence multisets that meet Welch's lower bound on total squared correlation. It is further shown that the symmetric capacity of the channel determined by these same sequence multisets is equal to the sum capacity. >
Universal coding for the Slepian-Wolf data compression system and the strong converse theorem

Universal coding for the Slepian-Wolf (1973) data compression system is considered. We shall demonstrate based on a simple observation that the error exponent given by Csiszar and Korner (1980) for the universal coding system can strictly be sharpened in general for a region of relatively higher rates. This kind of observation can be carried over also to the case of lower rates outside the Slepian-Wolf region, which establishes the strong converse along with the optimal exponent. >
A mechanistic study of helicases with magnetic traps

Helicases are a broad family of enzymes that separate nucleic acid double strand structures (DNA/DNA, DNA/RNA, or RNA/RNA) and thus are essential to DNA replication and the maintenance of nucleic acid integrity. We review the picture that has emerged from single molecule studies of the mechanisms of DNA and RNA helicases and their interactions with other proteins. Many features have been uncovered by these studies that were obscured by bulk studies, such as DNA strands switching, mechanical (rather than biochemical) coupling between helicases and polymerases, helicase‐induced re‐hybridization and stalled fork rescue.
Efficient fuzzy c-means clustering for image data

The clustering process can be quite slow when there is a large data set to be clustered. We investigate four efficient fuzzy c-means clustering methods qFCMs, based on the quad-tree application to multispectral image feature compression and/or an aggregation process to reduce the number of exemplars for image analysis. An image is first partitioned into multiresolution blocks with variable size to extract the representative ones by homogeneity criteria. The blocks can be represented by a mean or fuzzy number to represent the image information. The first algorithm qFCMb is performed by applying only the representative blocks to a weighted FCM, which can speed up the clustering. To further improve the clustering efficiency, the reduction is done by aggregating similar examples and using a weighted exemplar in the clustering process (qFCMba). Based on the same processes used in qFCMb and qFCMba, nonhomogeneous regions including pixel information can also be supplemented to refine the clustering results, which are termed qFCMp and qFCMpa, respectively. Because of the merit of higher efficiency with the aggregation process, we recommend qFCMba and qFCMpa. A set of 14 images is used for experiments, comparison, and discussion. Performances are reported by the mean reduction rate, speedup, mean correspondence rate, and root mean square error. Results show that the mean reduction rate of both qFCMba and qFCMpa can be as high as 98% reduction in sample size. Average speedups of as much as 40 to 150 times (100 to 200 times) a traditional implementation FCM are obtained using qFCMpa (qFCMba), while producing partitions that are equivalent to those produced by FCM. On the measure of root mean square error, qFCMba is the better choice, as indicated in the experiment of clustering a noisy image.
Foundations of Image Science

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Structures and kinetics for plant nucleoside triphosphate diphosphohydrolases support a domain motion catalytic mechanism

Extracellular nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes that hydrolyze extracellular nucleotides to the respective monophosphate nucleotides. In the past 20 years, NTPDases belonging to mammalian, parasitic and prokaryotic domains of life have been discovered, cloned and characterized. We reveal the first structures of NTPDases from the legume plant species Trifolium repens (7WC) and Vigna unguiculata subsp. cylindrica (DbLNP). Four crystal structures of 7WC and DbLNP were determined at resolutions between 1.9 and 2.6 Å. For 7WC, structures were determined for an ‐apo form (1.89 Å) and with the product AMP (2.15 Å) and adenine and phosphate (1.76 Å) bound. For DbLNP, a structure was solved with phosphate and manganese bound (2.60 Å). Thorough kinetic data and analysis is presented. The structure of 7WC and DbLNP reveals that these NTPDases can adopt two conformations depending on the molecule and co‐factor bound in the active site. A central hinge region creates a “butterfly‐like” motion of the domains that reduces the width of the inter‐domain active site cleft upon molecule binding. This phenomenon has been previously described in Rattus norvegicus and Legionella pneumophila NTPDaseI and Toxoplasma gondii NTPDaseIII suggesting a common catalytic mechanism across the domains of life.
Insights into PG‐binding, conformational change, and dimerization of the OmpA C‐terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi

Salmonella enterica serovar Typhimurium can induce both humoral and cell‐mediated responses when establishing itself in the host. These responses are primarily stimulated against the lipopolysaccharide and major outer membrane (OM) proteins. OmpA is one of these major OM proteins. It comprises a N‐terminal eight‐stranded β‐barrel transmembrane domain and a C‐terminal domain (OmpACTD). The OmpACTD and its homologs are believed to bind to peptidoglycan (PG) within the periplasm, maintaining bacterial osmotic homeostasis and modulating the permeability and integrity of the OM. Here we present the first crystal structures of the OmpACTD from two pathogens: S. typhimurium (STOmpACTD) in open and closed forms and causative agent of Lyme Disease Borrelia burgdorferi (BbOmpACTD), in closed form. In the open form of STOmpACTD, an aspartate residue from a long β2‐α3 loop points into the binding pocket, suggesting that an anion group such as a carboxylate group from PG is favored at the binding site. In the closed form of STOmpACTD and in the structure of BbOmpACTD, a sulfate group from the crystallization buffer is tightly bound at the binding site. The differences between the closed and open forms of STOmpACTD, suggest a large conformational change that includes an extension of α3 helix by ordering a part of β2‐α3 loop. We propose that the sulfate anion observed in these structures mimics the carboxylate group of PG when bound to STOmpACTD suggesting PG‐anchoring mechanism. In addition, the binding of PG or a ligand mimic may enhance dimerization of STOmpACTD, or possibly that of full length STOmpA.
Model-based 3-D segmentation of multiple sclerosis lesions in dual-echo MRI data

This paper describes the development and use of a brain tissue probability model for the segmentation of multiple sclerosis lesions in magnetic resonance (MR) images of the human brain. Based on MR data obtained from a group of healthy volunteers, the model was constructed to provide prior probabilities of grey matter, white matter, ventricular cerebrospinal fluid (CSF), and external CSF distribution per unit voxel in a standardized 3- dimensional `brain space. ' In comparison to purely data-driven segmentation, the use of the model to guide the segmentation of multiple sclerosis lesions reduced the volume of false positive lesions by 50%.
The solution structure of the Mg2+ form of soybean calmodulin isoform 4 reveals unique features of plant calmodulins in resting cells

Soybean calmodulin isoform 4 (sCaM4) is a plant calcium‐binding protein, regulating cellular responses to the second messenger Ca2+. We have found that the metal ion free (apo‐) form of sCaM4 possesses a half unfolded structure, with the N‐terminal domain unfolded and the C‐terminal domain folded. This result was unexpected as the apo‐forms of both soybean calmodulin isoform 1 (sCaM1) and mammalian CaM (mCaM) are fully folded. Because of the fact that free Mg2+ ions are always present at high concentrations in cells (0.5–2 mM), we suggest that Mg2+ should be bound to sCaM4 in nonactivated cells. CD studies revealed that in the presence of Mg2+ the initially unfolded N‐terminal domain of sCaM4 folds into an α‐helix‐rich structure, similar to the Ca2+ form. We have used the NMR backbone residual dipolar coupling restraints 1DNH, 1DCαHα, and 1DC′Cα to determine the solution structure of the N‐terminal domain of Mg2+‐sCaM4 (Mg2+‐sCaM4‐NT). Compared with the known structure of Ca2+‐sCaM4, the structure of the Mg2+‐sCaM4‐NT does not fully open the hydrophobic pocket, which was further confirmed by the use of the fluorescent probe ANS. Tryptophan fluorescence experiments were used to study the interactions between Mg2+‐sCaM4 and CaM‐binding peptides derived from smooth muscle myosin light chain kinase and plant glutamate decarboxylase. These results suggest that Mg2+‐sCaM4 does not bind to Ca2+‐CaM target peptides and therefore is functionally similar to apo‐mCaM. The Mg2+‐ and apo‐structures of the sCaM4‐NT provide unique insights into the structure and function of some plant calmodulins in resting cells.
Amyloidogenesis of Tau protein

The role of microtubule‐associated protein Tau in neurodegeneration has been extensively investigated since the discovery of Tau amyloid aggregates in the brains of patients with Alzheimer's disease (AD). The process of formation of amyloid fibrils is known as amyloidogenesis and attracts much attention as a potential target in the prevention and treatment of neurodegenerative conditions linked to protein aggregation. Cerebral deposition of amyloid aggregates of Tau is observed not only in AD but also in numerous other tauopathies and prion diseases. Amyloidogenesis of intrinsically unstructured monomers of Tau can be triggered by mutations in the Tau gene, post‐translational modifications, or interactions with polyanionic molecules and aggregation‐prone proteins/peptides. The self‐assembly of amyloid fibrils of Tau shares a number of characteristic features with amyloidogenesis of other proteins involved in neurodegenerative diseases. For example, in vitro experiments have demonstrated that the nucleation phase, which is the rate‐limiting stage of Tau amyloidogenesis, is shortened in the presence of fragmented preformed Tau fibrils acting as aggregation templates (“seeds”). Accordingly, Tau aggregates released by tauopathy‐affected neurons can spread the neurodegenerative process in the brain through a prion‐like mechanism, originally described for the pathogenic form of prion protein. Moreover, Tau has been shown to form amyloid strains—structurally diverse self‐propagating aggregates of potentially various pathological effects, resembling in this respect prion strains. Here, we review the current literature on Tau aggregation and discuss mechanisms of propagation of Tau amyloid in the light of the prion‐like paradigm.