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Objective Critical limb ischemia (CLI) is a progressive form of peripheral artery disease (PAD). Patients with CLI have poor long-term prognosis. The aim of this study was to investigate the value of sarcopenia in terms of 1-year mortality in patients with below-the-knee lesions who underwent endovascular treatment for CLI. Methods A total of 190 patients with critical limb ischemia who underwent endovascular treatment (EVT) for below-the-knee (BTK) lesions were enrolled in this study. Sarcopenia was defined using the psoas muscle index (PMI). PMI was obtained by calculating the average psoas muscle area (APMA) of the left and right psoas muscles at the third lumbar vertebra level and dividing by the square of the height (cm2/m2). The primary endpoint of the study was 1-year mortality and the secondary endpoint was 1-year amputation. Patients were divided into 2 groups according to presence of sarcopenia. Results We detected sarcopenia in 64 patients. The mean age, height, and EF were higher in sarcopenia group. The psoas muscle area, weight, psoas muscle index, body-mass index, albumin level, and GFR were lower in sarcopenia group. The incidence of amputation (11.9% vs 29.7%, p = 0.003) and mortality (15.1% vs 35.9%, p = 0.001) were higher in patients with sarcopenia. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of amputation and mortality. The survival curve for 1-year using the sarcopenia was analyzed using the Kaplan–Meier method, and statistical analysis was performed with the log-rank test. The presence of sarcopenia, glomerular filtration rate level, and low ejection fraction were found to be independent predictors of mortality. Conclusions Sarcopenia was associated with 1-year mortality in patients with CLI undergoing EVT for BTK lesions. Also, patients with sacropenia had higher 1-year amputation rates. Sarcopenia may be a simple method to help patient selection, assessment, and intervention strategy for EVT and may improve patient outcomes.

DNA repair genes may be related with the onset of primary ovarian failure (POF). The study was planned to investigate whether the polymorphisms in the DNA repair genes modulate the risk of POF.This prospective study included 25 women diagnosed with POF and 25 healthy controls. The genotyping and allele of XRCC1 and XPD genes were determined by using Polymerase Chain Reaction and fluorescence melting curve analysis.The genotype and allele distribution of the Arg194Trp and Arg399Lys polymorphism of the XRCC1 gene did not differ statistically between those of the POF and control groups. The frequency of the C (Gln) allele was significantly lower in patients diagnosed with POF when compared to that in healthy controls [48% vs. 76%, p=0.040, OR: 3.43 (CI: 1.03-11.48)]. The Lys/Lys genotype for XPD-Lys751Gln polymorphism in patients diagnosed with POF was more common than in healthy controls (p=0.028, 52% vs. 24%).The genotype distribution and allele frequency of XPD-Lys751Gln, XRCC1-Arg194Trp and XRCC1-Arg399 Gln did not regulate the risk of developing POF. Gln/Gln+Lys/Gln and XPD-Lys751Gln polymorphism may have a possible protective role against the development of POF.

Background Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease and is characterized by self-limiting episodes of fever and polyserositis. The aim of this study was to determine the atopic clinical findings associated with the MEFV gene. Methods A retrospective chart review was conducted of pediatric patients who had received a diagnosis of familial Mediterranean fever between August 2015 and November 2018. Results A total of 454 patients with familial Mediterranean fever were evaluated. The median age of diagnosis was 60 months (min–max: 6–228) and the percentage of patients who were male was 57.5%. A MEFV gene mutation was determined in 310 (68.3%) children. The most frequent genetic mutation was a R202Q heterozygote mutation, which was found in 95 patients (20.9%). When compared with MEFV-negative patients, elevation of serum amyloid A and fibrinogen levels during an episode of FMF was found to occur more frequently in MEFV-positive patients (p = 0.019 and 0.027, respectively). Male gender, cigarette exposure, and a younger diagnosis age were seen more frequently in patients who had episodes with fever (p = 0.039, 0.022, and 0.001, respectively). Chronic cough with sputum and persistent purulent rhinitis were more frequent in the group which did not experience fever episodes (p = 0.003 and 0.002, respectively). Conclusions While being a periodic fever syndrome, familial Mediterranean fever also presents as a multisystemic disease with heterogeneous clinical symptoms. Severe atopic diseases and recurrent respiratory tract infections are characteristic features of this disease.

In this study, we address the catalytic performance of variously sized Pt nanoparticles (NPs) (from 1.7 to 2.9 nm) supported on magnéli phase titanium oxide (MPTO, Ti4O7) along with commercial solid type carbon (VXC-72R) for oxygen reduction reaction (ORR). Key idea is to utilize a robust and electrically conductive MPTO as a support material so that we employed it to improve the catalytic activity and durability through the strong metal-support interaction (SMSI). Furthermore, we increase the specific surface area of MPTO up to 61.6 m2 g−1 to enhance the SMSI effect between Pt NP and MPTO. After the deposition of a range of Pt NPs on the support materials, we investigate the ORR activity and durability using a rotating disk electrode (RDE) technique in acid media. As a result of accelerated stress test (AST) for 30k cycles, regardless of the Pt particle size, we confirmed that Pt/MPTO samples show a lower electrochemical surface area (ECSA) loss (&lt, 20%) than that of Pt/C (~40%). That is explained by the increased dissolution potential and binding energy of Pt on MPTO against to carbon, which is supported by the density functional theory (DFT) calculations. Based on these results, we found that conductive metal oxides could be an alternative as a support material for the long-term fuel cell operation.

Objective: Patients with coronavirus 2019 (COVID-19), the disease caused by infection with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), frequently have comorbidities and this is thought to be a risk factor for poorer outcomes. The aim of this study was to determine the prevalence and effect of comorbidities on the severity and prognosis of patients hospitalized with a diagnosis of COVID-19.

The effects of commonly used antimicrobial and anticariogenic agents on the adhesion of pit and fissure sealants were investigated in this study.The aim of this study is to evaluate the effects of erbium, chromium: yttrium-scandium-gallium-garnet (Er, Cr:YSGG) laser disinfection, casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) containing paste and sodium hypochlorite application before the placement of a resin-based pit and fissure sealant on the shear bond strength of primary tooth enamel.The shear bond strength test evaluated the bond strength of sealants on the buccal enamel surfaces of primary molar teeth. The study groups were pit and fissure sealant without any preapplication, pre application of disinfection with Er, Cr:YSGG laser, disinfection with Er, Cr:YSGG laser and CPP-ACP containing paste, sodium hypochlorite, sodium hypochlorite and CPP-ACP containing paste and CPP-ACP containing paste. The pit and fissure sealants were placed using 4 mm diameter, 2 mm height cylindrical plastic tubes. Shear force was applied to each sample. The surfaces of the broken samples were detected under stereomicroscope and were grouped as adhesive, cohesive, and mixed. The results of the study were evaluated using the SPSS 16.0 package program for statistical analysis.The groups where sodium hypochlorite and sodium hypochlorite with CPP-ACP were applied showed the lowest bond strength (p0.05). It was observed that most of the failures in these groups were adhesive-type failures. No significant difference was observed between the shear bond strengths of the other groups (p0.05).Er, Cr: YSGG laser and CPP-ACP containing paste are alternative methods for pre-application of fissure sealants.

Although COVID-19 has a milder course in pediatric patients than in adults, it can have a severe and fatal course in children with an underlying disease (UD).In this study, we aimed to evaluate the demographic, clinical, laboratory, and radiological characteristics, treatment methods, and prognosis of pediatric patients diagnosed with COVID-19.The files of patients aged 0-18 years diagnosed with COVID-19 were retrospectively evaluated. Clinically and radiologically suspicious cases were accepted as confirmed cases if SARS-CoV-2 PCR positivity was found in nasopharyngeal swab samples. The severity of the disease was defined as asymptomatic, mild, moderate, and severe according to clinical, laboratory, and radiological features.A total of 322 pediatric patients, 51.2% male and 48.8% female, were included in the study. The median age of the patients was 12.08 years (1 month-18 years). Of the 322 patients, 81 (25.1%) were asymptomatic. Disease severity was as follows: 218 were (67.7%) mild, 14 were (4.3%) moderate, and 9 (2.7%) were severe. 35.7% of the patients were hospitalized. Six percent were admitted to the intensive care unit, and three (0.93%) patients died. The mortality rate in patients with the UD was 3.3%.In our study, we determined that the disease had a more severe course in patients with initial procalcitonin, D-dimer, troponin increase, and thrombocytopenia. Although COVID-19 has a mild course in children, this is unfortunately not true for children with an UD.

Objective: to examine any correlations between tumor maximum standard uptake values (SUVmax) in positron emission tomography-computed tomography (PET-CT) and homogeneous/heterogeneous tumor FDG uptake in PET-CT, and the diagnostic success of the procedure in thoracic ultrasonography (US)-guided transthoracic fine needle aspiration biopsy (TFNAB). Methods: the files of patients who underwent thoracic US-guided TFNAB between 2013 and 2018 were examined. Patients who underwent thoracic US-guided TFNAB and were diagnosed as having primary lung cancer were considered as the US-TFNAB diagnostic group. Patients whose disease was diagnosed as primary lung cancer using a different diagnostic method (e.g. CT-guided biopsies, fiberoptic bronchoscopy) due to a lack of diagnosis despite undergoing thoracic US-guided TFNAB were allocated to the US-TFNAB non-diagnostic group. The clinical and radiologic characteristics and PET-CT parameters of the two groups were compared. Results: a total of 104 patients were included in the study; 79 (76%) patients whose disease was diagnosed using US-guided TFNAB, and 25 (24%) patients whose primary lung cancer could not be diagnosed with US-guided TFNAB. The mean SUVmax value of the US-TFNAB diagnostic group was 19.5 ± 10.1, whereas it was 15.1 ± 8.9 in the US-TFNAB non-diagnostic group (p = 0.016). Whether a lesion showed homogeneous or heterogeneous FDG uptake did not effect diagnostic success (p = 0.289). SUVmax value was the only effective independent factor in the diagnostic success of the procedure (p = 0.035). Conclusions: high SUVmax values in PET-CT in lung cancers may increase the diagnostic success of US guided-TFNAB procedures., NA

In this study, immiscible blends of 75 wt% polylactide (PLA) with 25 wt% of poly[(butylene adipate)-co-ter-ephthalate] (PBAT) were prepared through an injection-molding (IM) process as well as a twin-screw extruder (TSE) followed by IM. An amorphous and a semi-crystalline PLA were also used as the matrix to investigate the matrix crystallization effect on morphology and properties development of the blends. Blend of PLA with 25 wt% of poly[(butylene succinate)-co-adipate] (PBSA) was also prepared through IM to compare its mechanical properties with those of PLA-PBAT blends. Eventually, the tensile and flexural properties of the prepared blends were explored and their dependency on the evolution of the blend morphology was investigated. The tensile results showed that when IM is used as the sole processing technique, the ductility and toughness were significantly improved only when the semi-crystalline PLA was used as the matrix. Preprocessing through TSE also resulted in enhancement of the PLA blends’ strain at break. According to the flexural experimental results, the morphology variation effect on the PLA blends’ flexural properties was not as determinative as it appeared in PLA blends’ tensile properties.

We investigated cytological changes in oral mucosa smears from patients treated with cryotherapy to determine whether cryotherapy prevented mucositis caused by 5-fluorouracil (5-FU) therapy. Patients with gastrointestinal malignancies were divided into four groups; control patients before 5-FU therapy, patients after 5-FU therapy without cryotherapy, patients with cryotherapy before 5-FU therapy and patients with cryotherapy after 5-FU therapy. Oral mucosa samples from all patients were assessed at the beginning and on day 14 of chemotherapy. We used exfoliative cytology to evaluate cellular changes in the oral mucosa that were caused by 5-FU. Smears from each patient were stained using the Papanicolaou method and analyzed using stereology. Smears were taken from each group before and after 5-FU infusion. We found that nuclear volume was decreased significantly in cells of the 5-FU therapy after cryotherapy patients compared to the 5-FU therapy before cryotherapy patients. We also found significantly decreased cytoplasmic volumes in the 5-FU therapy after cryotherapy patients compared to the 5-FU therapy before cryotherapy patients. The results of cytomorphometric estimations revealed that cryotherapy may be used to prevent damage to oral tissue and may decrease the frequency and duration of oral mucositis caused by 5-FU.

The concentrations of constituent elements were determined in soil samples collected from different parts of the Maritza Basin, Edirne, Turkey. Neutron activation analysis, an extremely accurate technique, and the comparator method (using a standard) were applied for the first time in this region. After preparing the soil samples for neutron activation analysis, they were activated with thermal neutrons in a nuclear reactor, TRIGA-MARK II, at Istanbul Technical University. The activated samples were analyzed using a high-efficiency high-purity germanium detector, and gamma spectrometry was employed to determine the elemental concentration in the samples. Eight elements (chromium, manganese, cobalt, zinc, arsenic, molybdenum, cadmium, and barium) were qualitatively and quantitatively identified in 36 samples. The concentrations of some elements in the soil samples were high compared with values reported in the literature.

Background A recent randomized-withdrawal, active- and placebo-controlled, double-blind phase 3 study showed that tapentadol prolonged release (PR) was effective and well tolerated for managing moderate to severe, chronic malignant tumour-related pain in patients who were opioid naive or dissatisfied with current treatment (Pain Physician, 2014, 17, 329–343). This post hoc, subgroup analysis evaluated the efficacy and tolerability of tapentadol PR in patients who previously received and were dissatisfied with tramadol for any reason and who had a pain intensity ≥5 (11-point numerical rating scale) before converting directly to tapentadol PR. Methods In the original study, eligible patients had been randomized (2:1) and titrated to their optimal dose of tapentadol PR (100–250 mg bid) or morphine sulphate-controlled release (40–100 mg bid) over 2 weeks. The present report focuses on results during the titration period for a subgroup of patients randomized to tapentadol PR after having been on tramadol treatment prior to randomization in the study (n = 129). Results for this subgroup are compared with results for all 338 patients who received tapentadol PR during titration (overall tapentadol PR group). Results Responder rates (responders: completed titration, mean pain intensity

Magnéli phase titanium oxides (MPTOs), possess high electrical conductivity and chemical stability, are promising support materials for the development of novel electrocatalyst in polymer electrolyte fuel cells (PEFCs). Despite MPTO's extremely low specific surface area (1 m2/g or less), high Pt loading (40 wt%) and excellent Pt particle-size distribution were obtained by the modified borohydride method. The reasons were discussed and compared with polyol method. Membrane electrode assembly (MEA) performance of those Pt/MPTO catalysts were found to be 169.7 and 366.2 mA/cm2 at 0.7 V for H2/air and H2/O2, respectively. The accelerated stress tests (ASTs) showed superior durability of the Pt/MPTO catalyst as a cathode electrode. After 10,000 cycles of high-voltage cycling test from 0.9 V and 1.3 V RHE, no significant performance degradation of the Pt/MPTO electrode was observed comparing with Pt/C. Thus, MPTOs can be considered as a good substitute of carbon supports in fuel cells.

A fluorescence-based electro-optical high-throughput method and setup for testing the oxygen reduction reaction (ORR) activity and electrochemical stability of 60 materials in parallel is described. We present thus a quantitative method for activity measurements for ORR-catalysts by optical fluorescence data acquisition. The fluorescence behavior of fluorescein, phloxine B, and umbelliferone as indicators is presented. The effect of oxygen concentration, saturation, and supply on electrochemical response is presented. Corrections for internal resistance differences and intensity differences are described. The final method allowed position independent determination of activities on the working-electrode library, containing up to 60 different electrocatalysts. A total of 378 selected mixed oxides have been studied. Cu/Ni/Mn and Co/Ni/Mn oxides proved electrochemically most active and comparable to a Pt-containing reference catalyst.

High surface area Magnèli Phase Titanium Oxides (MPTOs), synthesized by high temperature reduction and mechanical milling of TiO2 as a catalyst support material for a polymer electrolyte fuel cells (PEFCs). Pt as an active metal distributed on the prepared supports by impregnation-reduction method. The catalyst structure and composition of the Pt/HS_MPTO were determined by X-ray diffractometer (XRD), Field Emission Transmission Electron Spectroscopy (FE-TEM) and Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP). The catalytic activity for the oxygen reduction reaction (ORR) and stability against high potential were examined and compared with commercial Pt/C catalyst. The durability of Pt/HS_MPTO catalysts was examined by potential holding at 1.3 V for 24 h. Pt/HS_MPTO catalyst showed nearly no changes in the half-wave potentials representing much higher durability compared to the commercial Pt/C catalysts.

Supportless Pt catalysts have several advantages over conventional carbon-supported Pt catalysts in that they are not susceptible to carbon corrosion. However, the need for high Pt loadings in membrane electrode assemblies (MEAs) to achieve state-of-the-art fuel cell performance has limited their application in proton exchange membrane fuel cells. Herein, we report a new approach to the design of a supportless Pt catalyst in terms of catalyst layer architecture, which is crucial for fuel cell performance as it affects water management and oxygen transport in the catalyst layers. Large Pt hollow spheres (PtHSs) 100 nm in size were designed and prepared using a carbon template method. Despite their large size, the unique structure of the PtHSs, which are composed of a thin-layered shell of Pt nanoparticles (ca. 7 nm thick), exhibited a high surface area comparable to that of commercial Pt black (PtB). The PtHS structure also exhibited twice the durability of PtB after 2000 potential cycles (0-1.3 V, 50 mV/s). A MEA fabricated with PtHSs showed significant improvement in fuel cell performance compared to PtB-based MEAs at high current densities (800 mA/cm

A case-control study was performed to determine the effects of HIV-1-specific cellular immune responses on the odds of acquiring a second HIV-1 infection (superinfection). Changes in the frequency of cytokine-producing or cytolytic CD8+ or CD4+ T cells were not associated with significant alterations in the odds of superinfection, suggesting that HIV-1 specific cellular immune responses at the level induced by chronic infection do not appear to significantly contribute to protection from HIV-1 superinfection.

The human immunodeficiency virus type 1 (HIV-1) variants that are transmitted to newly infected individuals are the primary targets of interventions, such as vaccines and microbicides, aimed at preventing new infections. Newly acquired subtype A, B, and C variants have been the focus of neutralization studies, although many of these viruses, particularly of subtypes A and B, represent viruses circulating more than a decade ago. In order to better represent the global diversity of transmitted HIV-1 variants, an additional 31 sexually transmitted Kenyan HIV-1 env genes, representing several recent infections with subtype A, as well as subtypes A/D, C, and D, were cloned, and their neutralization profiles were characterized. Most env variants were resistant to neutralization by the monoclonal antibodies (MAbs) b12, 4E10, 2F5, and 2G12, suggesting that targeting the epitopes of these MAbs may not be effective against variants that are spreading in areas of endemicity. However, significant cross-subtype neutralization by plasma was observed, indicating that there may be other epitopes, not yet defined by the limited available MAbs, which could be recognized more broadly.

The aim of the present study was to evaluate epicardial fat thickness (EFT) in patients with chronic obstructive pulmonary disease (COPD) having right ventricular systolic dysfunction (RVSD).This study was comprised of 98 patients with COPD and 40 healthy controls. All the study participants underwent 2-dimensional, pulsed and tissue-doppler transthoracic echocardiographic examination for the measurements of EFT and parameters of right and left ventricular functions. Patients with COPD were divided into mild and severe RVSD groups according to right ventricular fractional area changes (RVFACs).Age, gender, prevalence of diabetes mellitus, hypertension, body-mass-index (BMI) and dyslipidemia were similar between COPD patients and controls, as were between mild, and severe RVSD groups. Prevalence of smoking were higher in COPD patients than in controls. Right ventricular end-diastolic diameter, myocardial performance index and peak pulmonary systolic pressure were found to be higher in COPD patients, while tricuspid annular plane systolic, excursion, isovolumic accelerating time, EFT and EFT/BMI were found to be lower in COPD patients. COPD patients with severe RVSD had thinner EFT and lower EFT/BMI values than those with mild RVSD (4.10 ± 0.77 vs 5.48 ± 1.28 mm, p0.001, respectively).The present study shows that the EFT decreases in patients with COPD and it is also associated with the degree of RVSD. Therefore, evaluating EFT in patient with COPD may provide information about the severity of the disease.

High hydrostatic pressure kinetics (D, z and k values) of aerobic bacteria (AB) and Listeria monocytogenes inactivation were determined in brain heart infusion broth (BHIB) and foods. The D and k values of L. monocytogenes ranged from 12.1 to 1.14 min and from 0.1907 to 2.0202 min−1, respectively in BHIB at a pressure range 200–700 MPa. D values were about 3.04 and 2.43 min for AB and L. monocytogenes, respectively, in milk at 600 MPa, 2.13 and 1.52 min, respectively, in peach juice, and 1.24 and 0.87 min, respectively, in orange juice. The k values for L. monocytogenes in orange juice (ranged from 0.8024 to 2.6471 min−1) were greater than BHIB (ranged from 0.1907 to 2.0202 min−1), peach juice (ranged from 0.3733 to 1.5151 min−1) and milk (ranged from 0.2096 to 0.0.9477 min−1) at same pressure. The z values of L. monocytogenes were 578, 480, 506 and 576 for L. monocytogenes in milk, BHIB, peach juice and orange juice, respectively. There were significant (p

Summary Listeria monocytogenes was subjected to ultra high hydrostatic pressure (UHHP) treatments from 200 to 700 MPa at 25 °C in broth, raw milk, peach juice and orange juice. Survivor curves showed that cell death increased as pressure increased. After 10 min pressure treatment at 400 MPa reductions of about 2.09 and 2.76 log CFU mL−1 in aerobic bacteria and L. monocytogenes, respectively, were produced in raw milk, this increased to 5.09 and 6.47 log CFU mL−1, respectively, at 600 MPa. Death of bacteria at UHHP treatment was greater in orange juice than peach juice, and in peach juice than milk. Listeria monocytogenes was more sensitive to increased pressure than increased pressurization time. Injury of L. monocytogenes occurred from 0 to 100%. Factors effecting the rate of microbial inactivation are: pressure, age of cell, composition of medium, and pressurization time. UHHP inactivation can be used to extend shelf life and increase food quality during storage, and may also contribute to inactivation of L. monocytogenes.

Inactivation of Escherichia coli by high hydrostatic pressure (UHHP) was determined in broth, milk and orange and peach juices inoculated with the bacteria. HHP ranged from 200 to 700 MPa at 25 C and different treatment times. No cell growth occurred in broth after 60, 25, 15, 10 and 7 min at 300, 400, 500, 600 and 700 MPa, respectively. Reduction of aerobic bacteria in milk and peach juice were 3.08 and 6.07 log units after 15 min at 400 MPa, respectively, while all bacterial cells were inactivated in orange juice. Sterilisation of raw milk contaminated with E. coli occurred at 600 MPa for 30 min, while peach and orange juices needed 12 and 10 min, respectively. The injury of cells in broth at 300 MPa ranged from 8.8 to 100% depending on magnitude of pressure and treated time. In general, inactivation of aerobic bacteria and E. coli was enhanced significantly (P

We performed a case-control study of women at risk of HIV-1 superinfection to understand the relationship between immune activation and HIV-1 acquisition. An increase in the frequency of HIV-1 target cells, but not in other markers of T cell activation, was associated with a 1.7-fold increase in the odds of superinfection. This suggests that HIV-1 acquisition risk is influenced more by the frequency of target cells than by the generalized level of immune activation.

Shot peening was used for improving the fatigue properties of Fe–2Cu–0·5C PM steel. The steel is generally used for production of high performance sintered parts such as small connecting rods for cooling system compressors. To distinguish the effects of each alloying element, Fe, Fe–2Cu, and Fe–0·5C were also investigated. Optimum shot peening intensities are: 25A for pure iron and Fe–2Cu, 30A for Fe–0·5C, and 35A for Fe–2Cu–0·5C. For these intensities, improvements of the fatigue strengths of the materials investigated are as follows: 31% for pure iron, 48% for Fe–0·5C, 46% for Fe–2Cu, and 38% for Fe–2Cu– 0·5C. From the experimental results it could be concluded that both of the alloying additions, carbon and copper, are contributing to the fatigue strength improvements by shot peening.

Natural killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood major lymphocyte population. Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 37 parameters, including 28 NK cell receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 unrelated donors of defined human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6000 to 30,000 phenotypic populations within an individual and >100,000 phenotypes in the donor panel. Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally influenced. Therefore, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors while using adaptable expression patterns of activating and costimulatory receptors to respond to pathogens and tumors. These findings further suggest the possibility that discrete NK cell subpopulations could be harnessed for immunotherapeutic strategies in the settings of infection, reproduction, and transplantation.

Superinfection by a second human immunodeficiency virus type 1 (HIV-1) strain indicates that gaps in protective immunity occur during natural infection. To define the role of HIV-1-specific neutralizing antibodies (NAbs) in this setting, we examined NAb responses in 6 women who became superinfected between ∼1 to 5 years following initial infection compared to 18 women with similar risk factors who did not. Although superinfected individuals had less NAb breadth than matched controls at ∼1 year postinfection, no significant differences in the breadth or potency of NAb responses were observed just prior to the second infection. In fact, four of the six subjects had relatively broad and potent NAb responses prior to infection by the second strain. To more specifically examine the specificity of the NAbs against the superinfecting virus, these variants were cloned from five of the six individuals. The superinfecting variants did not appear to be inherently neutralization resistant, as measured against a pool of plasma from unrelated HIV-infected individuals. Moreover, the superinfected individuals were able to mount autologous NAb responses to these variants following reinfection. In addition, most superinfected individuals had NAbs that could neutralize their second viral strains prior to their reinfection, suggesting that the level of NAbs elicited during natural infection was not sufficient to block infection. These data indicate that preventing infection by vaccination will likely require broader and more potent NAb responses than those found in HIV-1-infected individuals.

The main contribution of this work is the generalisation of the medial axis transform (MAT) and the medial axis inverse transform MAIT) on complete Riemannian manifolds. It is known that almost every solid can be reconstructed from its medial axis and the corresponding radius function. In the past this reconstruction scheme has only been implemented in Euclidean spaces. We will use the concepts of Fermi coordinates that represent a natural generalisation of normal coordinates. However, this concept only works out properly if some substantial conditions for the radius function are established. Several approaches for the computation of the medial axis have been implemented so far but almost all of them lack good numerical results. Usually numerical errors occur because the approaches operate on a discretised model of the corresponding objects. In this work we will assume that both the 3D Riemannian space and the modelled object can be represented by smooth mappings and coordinate charts respectively. Therefore, we can introduce the so called medial equations that will allow us to compute medial surface patches using the implicit function theorem. Finally we will give examples for the MAT and the MAIT and show to what extent the inverse transform is applicable in the context of computer aided geometric design. The geodesic medial modeller is one of those applications.