Miracle-dz/UniFAR-FTUs huggingface dataset:
TRUCKs: the fourth generation of CARs

Introduction: Adoptive cell therapy of malignant diseases takes advantage of the cellular immune system to recognize and destroy cancer cells. This is impressively demonstrated by redirecting T cells with a chimeric antigen receptor (CAR) towards CD19, inducing complete and lasting remission of leukemia in more than two-thirds of patients in early phase trials. Areas covered: We outline how the CAR strategy is highly specific in redirecting T cells towards pre-defined target cells, however, reaches its limits when targeting solid tumors with a tremendous phenotypic heterogeneity. After initial tumor reduction by CAR T cells, antigen-negative cancer cells not recognized by CAR may give rise to tumor relapse. The situation may be overcome by CAR-mediated activation of T cells in the tumor, releasing inducible IL-12 which augments T-cell activation and attracts and activates innate immune cells to eliminate antigen-negative cancer cells in the targeted lesion. Expert opinion: CAR T cells with a transgenic ‘payload’, so-called TRUCK T cells or the ‘fourth-generation’ CAR T cells, are worthwhile to explore to shape the tumor environment by the inducible release of transgenic immune modifiers. Such TRUCK T cells are moreover envisioned to be applied in fields beyond cancer therapy including the therapy of virus infections, auto-immune diseases or metabolic disorders.
Game-Based Incentive Mechanisms for Cooperation in P2P Networks

Peer-to-Peer networks are gaining popularity as architecture for sharing resources. However, these systems easily suffer from a high level of free-riders, whereby some users consume resources without providing any resources. In order to reduce the free-riders and promote the cooperation among peers, we propose an incentive mechanism for cooperation based on game theory. Simulations show that the proposed mechanism can significantly improve the network performance as well as effectively alleviate peers only consuming resources in P2P networks.
Allopregnanolone (THP) Mediates Anesthetic Effects of Progesterone in Rat Brain

Intravenous infusion of the progesterone or that of progesterone 5 alpha-reduced metabolite, 3 alpha-hydroxy-5 alpha-pregnan-20-one (THP), induces the loss of righting reflex in freely moving rats at the doses of 49 +/- 15 mg/kg or 5.6 +/- 2.2 mg/kg, respectively. The recovery time of righting reflex was 71 +/- 12 min and 21 +/- 5 min for progesterone and THP, respectively. The time course of brain concentrations of THP, but not that of progesterone, correlated with the loss and the recovery of righting reflex. The pretreatment of animals with uncompetitive inhibitor of 5 alpha-reductase 17 beta (N,N-diisopropylcarbamoyl)-androst-3-diene-3-carboxylic acid (SKF 105111) significantly reduces the anesthetic activity of progesterone, but not that of THP. Following progesterone infusion brain level of THP in SKF 105111 pretreated rats was 12% that of vehicle-treated control, and the level of progesterone was 160%. No effect of SKF 105111 on brain THP level was detected in animals infused with THP. These results demonstrate that anesthetic effect of progesterone is mediated through its conversion to THP and support the hypothesis that endogenous metabolites of progesterone may be involved in the regulation of behavior in rats.
Analysis of Air-Gap Field Modulation and Magnetic Gearing Effects in Switched Flux Permanent Magnet Machines

In this paper, switched flux permanent magnet (SFPM) machines are analyzed from the perspective of the air-gap field harmonics. It is found that the modulation of the salient rotor to PM and armature reaction fields in SFPM machines is similar to that of the iron pieces to those fields in the magnetic gear and magnetically geared machine. The magnetic gearing effect is analyzed in SFPM machines with different stator/rotor pole combinations, winding configurations, and stator lamination segment types by a simple magnetomotive force-permeance model, and validated by finite-element (FE) analysis. Different from fractional-slot surface-mounted PM machines in which the working air-gap field harmonic generates 95% of the average electromagnetic torque, 95% of the average electromagnetic torque in SFPM machines having ps stator pole pairs and nr rotor poles are contributed by several dominating field harmonics, i.e., rotating ones with |knr ± (2i - 1)ps| pole pair (k = 1, i = 1, 2, 3) and static ones with (2i - 1)ps pole pair (i = 1, 2, 3). The FE predicted average static torques in SFPM machines are validated by measurements on prototype machines.
Understanding the Needs and Concerns of Senior Faculty in Academic Medicine: Building Strategies to Maintain This Critical Resource

Purpose The average age of medical school faculty is increasing, with 30% over age 55 in 2007. In 2012, 56% of Society of Teachers of Family Medicine (STFM) members were at least 50 years old. The authors sought to identify the transition and faculty development needs of this group of senior faculty. Method In 2012 the authors electronically surveyed 1,708 U.S. STFM members who were 50 or older, asking about demographics, highest degree, primary employer, career options considered in the previous year, issues of concern, mentoring needs, retirement plans, and likely activities in retirement. Results The response rate was 45%, with 73% MD/DOs, 62% men, 89% white, and 64% employed by academic institutions. The most frequent issues of concern were balancing personal and work time (67%), maintaining health (66%), and planning for retirement (60%). Nearly a third had considered career advancement, changing employers, or reducing full-time employment. Fifty-one percent were not receiving mentoring of any kind, but 47% reported they would like to have a mentor. Sixty-four percent were planning to retire; in retirement, 75% said they would like to remain active in teaching and 55% in mentoring. Conclusions Senior faculty in family medicine have significant career concerns and mentoring needs as they approach retirement, and these faculty can be valuable resources after retirement. As the age of faculty continues to rise, medical schools and specialty organizations can develop specific programs to meet the needs of these medical educators and better use this expertise in a time of limited resources.
PHENOTYPIC PLASTICITY IN AN INTERTIDAL SNAIL: THE ROLE OF A COMMON CRAB PREDATOR

Prey species may reduce their risk of predation in many ways (for reviews, see Edmunds 1974; Vermeij 1978, 1987). Although avoidance behaviors and chemical defenses can act as deterrents to predation in marine environments, morphological changes have received the greatest emphasis. For example, spines in a marine bryozoan (Harvell 1984), barnacle shape (Lively 1986a), and numerous gastropod shell traits (Vermeij 1978) are known to deter predation. In intertidal environments, predation by invertebrate predators often parallels gradients in wave exposure and is often most important on shores protected from direct wave energy (Menge 1978). Likewise, variation in the shell thickness of intertidal gastropods also tends to parallel gradients in wave exposure and predation intensity. Thick-shelled morphs are typically found on protected shores where crab predators are more abundant, whereas thin-shelled morphs are found on wave-exposed shores (Kitching et al. 1966; Kitching and Lockwood 1974; Reimchen 1982; Palmer 1985a, 1990). Extreme turbulence probably inhibits crab foraging on waveexposed shores (Kitching et al. 1966; Crothers 1968; Menge 1978). Shell thickness of intertidal gastropods varies among intertidal shores, in part because of differential predation by crabs (Kitching et al. 1966; Kitching and Lockwood 1974; Vermeij 1978, 1987; Seeley 1986). Although natural selection by crabs has been suggested to promote the evolution of thicker-shelled snails (Seeley 1986), predator-induced phenotypic plasticity may also influence shell thickness (Appleton and Palmer 1988; Palmer 1990). Predator-induced morphological defenses are a unique example of phenotypic plasticity in which the predator or a cue associated with the predator (often chemical in nature) induces the formation of structures in the prey that deter predation. This phenomenon is common in aquatic rotifer and zooplankton assemblages (for a review, see Dodson 1989). Most examples of predator-induced defenses involve plants (Baldwin and Schultz 1983; Haukioja and Neuvonen 1985; Rhoades 1985) or clonal (e.g., the cladoceran zooplankton examples cited in Dodson 1989) and colonial organisms (Harvell 1984, 1986). Cases of predator-induced defenses in solitary organisms appear to be rare. Curiously, cases involving solitary organisms, with the exception of Bronmark and Miner (1992), have been found in intertidal environments (Lively
SERINC5: not all splice variants work against HIV

The battle between viruses and their host is armed by cellular defences, often referred to as restriction factors, on one side, and by the counteracting measures expressed by viral genomes, on the other side. The presence of cell-derived barriers which interfere with virus replication was first revealed for retroviruses in the 70s. Since the description of FV1 (1), a cytoplasmic murine factor inhibiting MLV replication, several blocks that impair replication of viruses on the cell surface, in the cytoplasm, and in the nucleus have later been discovered. The latest addition to the list is SERINC5, a cellular protein which was recently found to block retrovirus delivery into target cells (2,3).
PSYCHIATRIC DISORDERS IN PATIENTS RECEIVING ANTI-TUBERCULOSIS DRUGS

SUMMARY Eleven in-patients of the hospital for Tuberculosis and Chest Diseases, Hyderabad, who presented with psychiatric symptoms resulting in maladjustment were examined and placed in different diagnostic groups. There were five psychotics and six neurotics. Out of the five psychotics, three were manic and two were depressive. Among the six neutrotics, three were depressive and one each of anxiety, obsessive compulsive and phobic neurosis. All the patients improved on withdrawal of anti-tuberculosis drugs and there was no recurrence or symptoms on reintroduction of anti-tuberculosis drugs other than isoniazid. On re-introduction of Isoniazid, symptoms recurred. The psychiatric disorders were most likely due to Isoniazid and they were neither dose nor duration related. However, Isoniazid may be readministered in the less severe forms along with appropriate drugs to control psychiatric side-effects.
Arterial hypertension and aneurysmal dilatation.

Hemodynamic parameters and especially systemic hypertension are considered to be significant factors in the progression of aortic aneurysmal dilatation. We have recently described an original experimental model of aortic aneurysm induced by transparietal infusion of elastase in the rat abdominal aorta. In order to evaluate the effect of hypertension on the aneurysmal remodeling of the arterial wall induced by perfusion of elastase activity, this experimental model was applied to renovascular hypertensive (N = 17), spontaneously hypertensive (N = 18) and normotensive rats (N = 17). The aneurysms were induced by infusion of 15 units of hog pancreatic elastase of a one centimeter isolated aortic segment in anesthetized rats which were sacrificed two weeks later. The aneurysmal length and diameter were measured in vivo using a micrometer in a surgical microscope. The aortas were then fixed in formalin and embedded in paraffin for standard histological study. The animals which died during the experimental period were examined. All rats presented a macroscopic aneurysm two weeks after the infusion of elastase. Histologically, the aneurysmal area was characterized by the disappearance of the normal elastic network and by the presence of a collagenic wall. The dimensions of the aneurysms (transversal diameter and length) were greater in hypertensive than in normotensive animals (F = 11, P less than 0.001) and aneurysmal dimensions were positively correlated with the level of blood pressure (r = 0.56, P less than 0.001). Moreover, the frequency of aortic rupture was greater in renovascular hypertensive (4/17) than in spontaneously hypertensive (1/18) and normotensive (0/17) rats. (ABSTRACT TRUNCATED AT 250 WORDS)
A Modified DDE Index for Use in Epidemiological Studies of Enamel Defects

The aim of this study was to investigate possible modifications to the DDE Index to make it simpler to use and to make the data collected more meaningful and amenable to analyses and interpretation. After the use of the DDE Index in a National Study in Ireland, initial alterations to the Index were tested on a group of children with enamel defects, in Ireland and New Zealand. The DDE Index was then modified to allow for the measurement of demarcated, diffuse, and hypo-plastic defects and their severity. With the Modified Index, the prevalence of defects both on index teeth and all permanent tooth surfaces of 8-and 15-year-old children in fluoridated Cork City and non-fluoridated areas of Cork County and Manchester, U.K., was measured. The prevalence of enamel defects on one or more index teeth of children in the three areas ranged from 30 to 42% in 8-year-olds and from 31 to 38% in 15-year-olds. The percentage of children affected as seen by full-mouth examination was somewhat higher, ranging from 38 to 51 % for 8 year-olds and 58 to 63% for 15-year-olds. The percentage of index teeth affected (7 to 14%) was generally higher than for all teeth (5 to 9%). Demarcated opacities were the most common defect seen. Diffuse opacities were found to be the discriminating factor between the fluoridated and non-fluoridated areas. In all areas, the vast majority of diffuse opacities extended over less than 1/3 of the surface area of the teeth affected. As a result of this study, proposals for a single scoring DDE Index for use in general purpose and screening surveys are made. The modifications to the DDE Index allow for efficient recording of the prevalence and severity of enamel defects.
Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study.

CONTEXT The outcome of patients receiving mechanical ventilation for particular indications has been studied, but the outcome in a large number of unselected, heterogeneous patients has not been reported. OBJECTIVE To determine the survival of patients receiving mechanical ventilation and the relative importance of factors influencing survival. DESIGN, SETTING, AND SUBJECTS Prospective cohort of consecutive adult patients admitted to 361 intensive care units who received mechanical ventilation for more than 12 hours between March 1, 1998, and March 31, 1998. Data were collected on each patient at initiation of mechanical ventilation and daily throughout the course of mechanical ventilation for up to 28 days. MAIN OUTCOME MEASURE All-cause mortality during intensive care unit stay. RESULTS Of the 15 757 patients admitted, a total of 5183 (33%) received mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean (SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall mortality rate in the intensive care unit was 30.7% (1590 patients) for the entire population, 52% (120) in patients who received ventilation because of acute respiratory distress syndrome, and 22% (115) in patients who received ventilation for an exacerbation of chronic obstructive pulmonary disease. Survival of unselected patients receiving mechanical ventilation for more than 12 hours was 69%. The main conditions independently associated with increased mortality were (1) factors present at the start of mechanical ventilation (odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR, 3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway pressure >35 cm H(2)O), and (3) developments occurring over the course of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO(2) to fraction of inspired oxygen <100). CONCLUSION Survival among mechanically ventilated patients depends not only on the factors present at the start of mechanical ventilation, but also on the development of complications and patient management in the intensive care unit.
Improving the Fixation of an Artificial Intervertebral Disc

The fixation of an artificial intervertebral disc has been studied especially with respect to the dimensions, the convexity of the endplates and the size of the fixation elements. From literature and cadaveric vertebrae, the dimensions and shape of the lumbar vertebral endplates were determined and the dimensions of fixation ribs for the artificial intervertebral disc were calculated. To withstand shear forces and prevent dislocation, two sagittal ribs, each 3.5 mm in height and at least 20 mm in length and four transversal ribs, each 1.5 mm in height and with a total length of 60 mm are sufficient. A range of five different sagittal diameters was selected as sufficient for all patients. At least 72.6 % of the endplate of the vertebrae is covered. A convexity with a radius of 140 mm limits the gap to 0.62 mm.
AN UPDATE ON ACUTE KIDNEY INJURY AFTER CARDIAC SURGERY

Abstract Renal dysfunction following cardiac surgery is well recognised and mainly is of ischaemic origin. The spectrum varies from subclinical injury to established renal failure requiring renal replacement therapy. Depending on definitions, acute kidney injury (AKI) may occur in up to 30% of post cardiac surgery patients. A new grading system for renal dysfunction, based on three levels of plasma creatinine and urine output, as well as the use of biomarkers may help the early identification of patients at risk and thereby hopefully improve outcome. Despite therapeutic advances, the morbidity and mortality associated with AKI have not changed markedly in the last decade.
The Sun Fireplane SMP interconnect in the Sun Fire 3800-6800

Worldwide server revenue is dominated by symmetric multiprocessor (SMP) systems. The architecture and implementation of the interconnect that maintains system-wide cache coherency is critical to the performance and scalability of SMP systems. This paper describes the Sun/sup TM/ Fireplane SMP interconnect protocol, and the implementation choices we made for the mid-sized Sun Fire/sup TM/ 3800-6800 servers.
Ecological Specialization in Fossil Mammals Explains Cope’s Rule

Cope’s rule is the trend toward increasing body size in a lineage over geological time. The rule has been explained either as passive diffusion away from a small initial body size or as an active trend upheld by the ecological and evolutionary advantages that large body size confers. An explicit and phylogenetically informed analysis of body size evolution in Cenozoic mammals shows that body size increases significantly in most inclusive clades. This increase occurs through temporal substitution of incumbent species by larger-sized close relatives within the clades. These late-appearing species have smaller spatial and temporal ranges and are rarer than the incumbents they replace, traits that are typical of ecological specialists. Cope’s rule, accordingly, appears to derive mainly from increasing ecological specialization and clade-level niche expansion rather than from active selection for larger size. However, overlain on a net trend toward average size increase, significant pulses in origination of large-sized species are concentrated in periods of global cooling. These pulses plausibly record direct selection for larger body size according to Bergmann’s rule, which thus appears to be independent of but concomitant with Cope’s.
Comparison of stator DC-excited vernier reluctance machines with synchronous reluctance machines

Stator DC-excited vernier reluctance machines (DC-VRMs) are vernier reluctance machines equiped with additional DC field winding in stator to generate the exciting field, a rotating field similar to synchronous reluctance machines (SynRMs). This paper compares the electromagnetic performance of two non-PM reluctacne machines including DC-VRMs and SynRMs. First, the basic operation principle of DC-VRMs and SynRMs are briefly reviewed. Then, four machine models, two DC-VRMs and two SynRMs are designed and optimized for comparison. For a fair comparison, the phase current, current density, slot fill factor and dimensions including the stator outer diameter, air gap and stack length are designed the same. The electromagnetic performance including flux density, torque quality, overload capacity, power factor and losses are compared in detail.
Sympathetic alpha(2)-adrenoceptors prevent cardiac hypertrophy and fibrosis in mice at baseline but not after chronic pressure overload.

AIMS alpha(2)-Adrenoceptors modulate cardiovascular function by vasoconstriction or dilatation, by central inhibition of sympathetic activity, or by feedback inhibition of norepinephrine release from sympathetic neurons. Despite detailed knowledge about subtype-specific functions of alpha(2)-receptors, the relative contributions of sympathetic vs. non-sympathetic receptors involved in these cardiovascular effects have not been identified. The aim of this study was to define the physiological and pharmacological role of alpha(2A)-adrenoceptors in adrenergic vs. non-adrenergic cells at baseline and during sympathetic stress. METHODS AND RESULTS Transgenic mice expressing alpha(2A)-adrenoceptors under control of the dopamine beta-hydroxylase (Dbh) promoter were generated and crossed with mice carrying a constitutive deletion in the alpha(2A)- and alpha(2C)-adrenoceptor genes. alpha(2AC)-deficient mice showed increased norepinephrine plasma levels, cardiac hypertrophy, and fibrosis at baseline. Expression of the Dbh-alpha(2A) transgene in sympathetic neurons prevented these effects. In contrast, Dbh-alpha(2A) receptors mediated only a minor part of the bradycardic and hypotensive effects of the alpha(2)-agonist medetomidine. After chronic pressure overload as induced by transverse aortic constriction in mice, the Dbh-alpha(2A) transgene did not reduce norepinephrine spillover, cardiac dysfunction, hypertrophy, or fibrosis. In isolated wild-type atria, alpha(2)-agonist-induced inhibition of [3H]norepinephrine release was significantly desensitized after pressure overload. In primary sympathetic neurons from Dbh-alpha(2A) transgenic mice, norepinephrine and medetomidine induced endocytosis of alpha(2A)-adrenoceptors into neurite processes. CONCLUSION alpha(2A)-Adrenoceptors expressed in adrenergic cells are essential feedback inhibitors of sympathetic norepinephrine release to prevent cardiac hypertrophy and fibrosis at baseline. However, these receptors are desensitized by chronic pressure overload which in turn may contribute to the pathogenesis of this condition.