Understanding Hydrogen-Bond Patterns in Proteins using a Novel Statistical Model

Proteins are built from basic structural elements and their systematic characterization is of interest. Searching for recurring patterns in protein contact maps, we found several network motifs, patterns that occur more frequently in experimentally determined protein contact maps than in randomized contact maps with the same properties. Some of these network motifs correspond to sub-structures of alpha helices, including topologies not previously recognized in this context. Other motifs characterize beta-sheets, again some of which appear to be novel. This topological characterization of patterns serves as a tool to characterize proteins, and to reveal a high detailed differences map for comparing protein structures solved by X-ray crystallography, NMR and molecular dynamics (MD) simulations. Both NMR and MD show small but consistent differences from the crystal structures of the same proteins, possibly due to the pair-wise energy functions used. Network motifs analysis can serve as a base for many-body energy statistical energy potential, and suggests a dictionary of basic elements of which protein secondary structure is made

On Certain Large Random Hermitian Jacobi Matrices with Applications to Wireless Communications

In this paper we study the spectrum of certain large random Hermitian Jacobi matrices. These matrices are known to describe certain communication setups. In particular we are interested in an uplink cellular channel which models mobile users experiencing a soft-handoff situation under joint multicell decoding. Considering rather general fading statistics we provide a closed form expression for the per-cell sum-rate of this channel in high-SNR, when an intra-cell TDMA protocol is employed. Since the matrices of interest are tridiagonal, their eigenvectors can be considered as sequences with second order linear recurrence. Therefore, the problem is reduced to the study of the exponential growth of products of two by two matrices. For the case where $K$ users are simultaneously active in each cell, we obtain a series of lower and upper bound on the high-SNR power offset of the per-cell sum-rate, which are considerably tighter than previously known bounds

Innate immune memory: implications for development of pediatric immunomodulatory agents and adjuvanted vaccines

Unique features of immunity early in life include a distinct immune system particularly reliant on innate immunity, with weak T helper (Th)1-polarizing immune responses, and impaired responses to certain vaccines leading to a heightened susceptibility to infection. To these important aspects, we now add an increasingly appreciated concept that the innate immune system displays epigenetic memory of an earlier infection or vaccination, a phenomenon that has been named “trained immunity”. Exposure of neonatal leukocytes in vitro or neonatal animals or humans in vivo to specific innate immune stimuli results in an altered innate immune set point. Given the particular importance of innate immunity early in life, trained immunity to early life infection and/or immunization may play an important role in modulating both acute and chronic diseases

On Information Rates of the Fading Wyner Cellular Model via the Thouless Formula for the Strip

We apply the theory of random Schr\"odinger operators to the analysis of multi-users communication channels similar to the Wyner model, that are characterized by short-range intra-cell broadcasting. With $H$ the channel transfer matrix, $HH^\dagger$ is a narrow-band matrix and in many aspects is similar to a random Schr\"odinger operator. We relate the per-cell sum-rate capacity of the channel to the integrated density of states of a random Schr\"odinger operator; the latter is related to the top Lyapunov exponent of a random sequence of matrices via a version of the Thouless formula. Unlike related results in classical random matrix theory, limiting results do depend on the underlying fading distributions. We also derive several bounds on the limiting per-cell sum-rate capacity, some based on the theory of random Schr\"odinger operators, and some derived from information theoretical considerations. Finally, we get explicit results in the high-SNR regime for some particular cases.Comment: Submitted to IEEE Transactions on Information Theor

Medium to long-term outcome of thoracoscapular arthrodesis with screw fixation for facioscapulohumeral muscular dystrophy

Background: Shoulder girdle muscle weakness is the most constant feature of facioscapulohumeral muscular dystrophy and leads to scapular winging. Mechanical fixation of the scapula to the thoracic wall provides a stable fulcrum on which the deltoid muscle can exert its action on the humerus. The aim of this study was to evaluate the medium to long-term outcome of thoracoscapular arthrodesis with screw fixation (the modified Howard-Copeland technique). Methods: All patients with facioscapulohumeral dystrophy who underwent thoracoscapular arthrodesis with screw fixation and bone-grafting from July 1997 to July 2010 were retrospectively reviewed. Preoperative and postoperative clinical assessment included active shoulder elevation, the Constant score, a patient satisfaction score, and cosmetic satisfaction. Union was determined both clinically and radiographically. Results: Thoracoscapular arthrodesis was performed in thirty-five shoulders in twenty-four patients; eleven patients underwent bilateral procedures. The principal study group consisted of thirty-two shoulders in twenty-one patients with a minimum follow-up of twenty-four months (Mean, eighty-eight months; range, twenty-four to 174 months). The mean Constant score increased from 30 (range, 17 to 41) preoperatively to 61 (range, 30 to 90) postoperatively. The mean satisfaction score increased from 1 (range, 0 to 4) to 8.4 (range, 4 to 10). Early complications consisted of one pneumothorax, one superficial wound infection, and four early failures, two of which were associated with noncompliance with the postoperative regimen. Late complications consisted of one posttraumatic fracture resulting in loosening and one painful nonunion; both were treated successfully with revision. Conclusions: Thoracoscapular arthrodesis with screw fixation prevented scapular winging and improved short-term and long-term shoulder function in patients with facioscapulohumeral dystrophy. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Neonatal Host Defense against Staphylococcal Infections

Preterm infants are especially susceptible to late-onset sepsis that is often due to Gram-positive bacterial infections resulting in substantial morbidity and mortality. Herein, we will describe neonatal innate immunity to Staphylococcus spp. comparing differences between preterm and full-term newborns with adults. Newborn innate immunity is distinct demonstrating diminished skin integrity, impaired Th1-polarizing responses, low complement levels, and diminished expression of plasma antimicrobial proteins and peptides, especially in preterm newborns. Characterization of distinct aspects of the neonatal immune response is defining novel approaches to enhance host defense to prevent and/or treat staphylococcal infection in this vulnerable population

Reverse total shoulder replacement for patients with "weight-bearing" shoulders.

Reverse total shoulder arthroplasty (rTSA) has gained popularity in recent years and is indicated for a wide variety of shoulder pathologies. However, use of rTSA in patients with "weight-bearing" shoulders that support wheelchair use or crutches has higher risk. The aim of this study was to assess the results of rTSA in such patients. Between 2005 and 2014, 24 patients (30 shoulders) with weight-bearing shoulders were treated with rTSA at our unit. Patients had cuff arthropathy (n=21), rheumatoid arthritis (n=3), osteoarthritis (n=1), acute fracture (n=3), or fracture sequela (n=2). Postoperatively, patients were advised not to push themselves up and out of their wheelchair for 6 weeks. The study surgeries were performed in 2016, and 21 patients (27 shoulders) who were available for a mean follow-up of 5.6 years (range, 2-10 years). The mean age on surgery day was 78 years (range, 54-90 years). Constant-Murley score improved from 9.4 (range, 2-26) preoperatively to 59.8 (range, 29-80) at the final follow-up (P=0.001). Pain improved from 2/15 (range, 0-8) to 13.8/15 (range, 9-15) (P=0.001). Patient satisfaction (Subjective Shoulder Value) improved from 0.6/10 to 8.7/10 (P=0.001) at final follow-up. Significant improvement in mean range of motion from 46° to 130° of elevation, 13° to 35° of external rotation, and 29° to 78° internal rotation was recorded (P=0.001). Final mean Activities of Daily Living External and Internal Rotation was 32.4/36 (range, 16-36). There were three patients with Sirveaux-Nerot grade-1 (10%) glenoid notching and three with grade 2 (10%). rTSA can be used for treatment of patients with weight-bearing shoulders. Such patients reported pain free movement, resumed daily activities, and high satisfaction rates

Antimicrobial peptide LL-37 and recombinant human mannose-binding lectin express distinct age- and pathogen-specific antimicrobial activity in human newborn cord blood in vitro

Background: There is a need to prevent and treat infection in newborns. One approach is administration of antimicrobial proteins and peptides (APPs) such as LL-37, a membrane-active cathelicidin antimicrobial peptide, and mannose-binding lectin (MBL), a pattern-recognition protein that binds to microbial surface polysaccharides resulting in opsonization and complement activation. Low plasma/serum levels of LL-37 and of MBL have been correlated with infection and exogenous administration of these agents may enhance host defense. Methods: The antimicrobial activity of LL-37 (15 µg/ml) or rMBL (0.5, 2 and 10 µg/ml) was tested in hirudin-anticoagulated preterm and term human cord blood (N = 12-14) against Staphylococcus aureus (SA) USA 300 (2x10 4 CFU/ml), Staphylococcus epidermis (SE) 1457 (2x10 4 CFU/ml) and Candida albicans (CA) SC5314 (1x10 4 CFU/ml). After incubation (1, 45, or 180 min), CFUs were enumerated by plating blood onto agar plates. Supernatants were collected for measurement of MBL via ELISA. Results: Preterm cord blood demonstrated impaired endogenous killing capacity against SA and SE compared to term blood. Addition of LL-37 strongly enhanced antimicrobial/antifungal activity vs SA, SE and CA in term blood and SE and CA in preterm blood. By contrast, rMBL showed modest fungistatic activity vs CA in a sub-analysis of term newborns with high basal MBL levels. Baseline MBL levels varied within preterm and term cohorts with no correlation to gestational age. In summary, exogenous LL-37 demonstrated significant antimicrobial activity against SA, SE and CA in term and SE and CA in preterm human blood tested in vitro. rMBL demonstrated modest antifungal activity in term cord blood of individuals with high baseline MBL levels. Conclusions: To the extent that our in vitro results predict the effects of APPs in vivo, development of APPs for prevention and treatment of infection should take into account host age as well as the target pathogen