GPU-accelerated Red Blood Cells Simulations with Transport Dissipative Particle Dynamics.

Mesoscopic numerical simulations provide a unique approach for the quantification of the chemical influences on red blood cell functionalities. The transport Dissipative Particles Dynamics (tDPD) method can lead to such effective multiscale simulations due to its ability to simultaneously capture mesoscopic advection, diffusion, and reaction. In this paper, we present a GPU-accelerated red blood cell simulation package based on a tDPD adaptation of our red blood cell model, which can correctly recover the cell membrane viscosity, elasticity, bending stiffness, and cross-membrane chemical transport. The package essentially processes all computational workloads in parallel by GPU, and it incorporates multi-stream scheduling and non-blocking MPI communications to improve inter-node scalability. Our code is validated for accuracy and compared against the CPU counterpart for speed. Strong scaling and weak scaling are also presented to characterizes scalability. We observe a speedup of 10.1 on one GPU over all 16 cores within a single node, and a weak scaling efficiency of 91% across 256 nodes. The program enables quick-turnaround and high-throughput numerical simulations for investigating chemical-driven red blood cell phenomena and disorders.

Chromatin modification mapping in nanochannels.

We report the simultaneous mapping of multiple histone tail modifications on chromatin that has been confined to nanofluidic channels. In these channels, chromatin is elongated, and histone modification can be detected using fluorescently tagged monoclonal antibodies. Using reconstituted chromatin with three distinct histone sources and two histone tail modification probes (H3K4me3 and H3K9ac), we were able to distinguish chromatin from the different sources. Determined ratios of the two modifications were consistent with the bulk composition of histone mixtures. We determined that the major difficulty in transitioning the mapping method to site-specific profiling within single genomic molecules is the interference of naturally aggregating, off-the shelf antibodies with the internal structure of chromatin.

Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release.

In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase in circulating testosterone. The activation of pituitary cells by Kp was inhibited by preadministration of the GNRH receptor antagonist acyline. Altogether, our results demonstrate that peripheral Kp54 activates the gonadotropic axis by stimulating GNRH release and indicate that an appropriate protocol of long-term systemic Kp administration can recrudesce a photo-inhibited reproductive axis.

Differential regulation of kiss1 expression by melatonin and gonadal hormones in male and female Syrian hamsters.

In seasonal breeders, reproduction is synchronized to seasons by day length via the pineal hormone melatonin. Recently, we have demonstrated that Kiss1, a key activator of the reproductive function, is down-regulated in sexually inactive hamsters maintained in inhibitory short days (SDs). In rodents, Kiss1 is expressed in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus (ARC). Because both the duration of the nocturnal peak of melatonin and circulating sex steroid levels vary with photoperiod, the aim of this study was to determine whether melatonin and sex steroids differentially regulate Kiss1 expression in the ARC and the AVPV. Kiss1 expression was examined by in situ hybridization in both male and female hamsters kept in various experimental conditions, and we observed that 1) SD exposure markedly reduced Kiss1 expression in the ARC and AVPV of male and female hamsters as compared to LD animals, 2) sex steroid treatment in SD-adapted male and female hamsters increased the number of Kiss1 neurons in the AVPV but decreased it in the ARC, 3) melatonin administration to LD-adapted hamsters decreased Kiss1 mRNA level in both the AVPV and the ARC in intact animals, whereas in castrated hamsters, melatonin rapidly inhibited Kiss1 expression in the ARC but not in the AVPV, and 4) pinealectomy of male or female SD-adapted hamsters increased the number of Kiss1 neurons in the ARC but not in the AVPV. In conclusion, our data demonstrate that Kiss1 expression in the Syrian hamster hypothalamus is down-regulated in SD via different mechanisms. In the ARC, melatonin inhibits Kiss1 via a direct effect on the hypothalamus, and this effect is probably sex steroid dependent, whereas in the AVPV, the decrease in Kiss1 expression appears to be secondary to the melatonin-driven reduction of sex steroid levels. Taken together, our data support the hypothesis that ARC Kiss1 neurons mediate melatonin effects on the gonadotropic axis of the Syrian hamster.

The bed nucleus of the stria terminalis in the Syrian hamster (Mesocricetus auratus): absence of vasopressin expression in standard and wild-derived hamsters and galanin regulation by seasonal changes in circulating sex steroids.

The bed nucleus of the stria terminalis (BNST) is a nucleus of the forebrain highly sensitive to sex steroids and containing vasopressin neurons implicated in several social- and reproduction-related behaviours such as scent-marking, aggression, pair bonding and parental behaviour. Sexually dimorphic vasopressin expression in BNST neurons has been reported in almost all rodents, with the notable exception of the Syrian hamster. In this species, vasopressin expression is completely absent in the BNST. Because almost all Syrian hamsters used in research are derived from a very small breeding stock captured in 1930, we compared commercially available Syrian hamsters with a recently captured, wild-derived breeding stock. We checked for vasopressin expression using in situ hybridization and immunohistochemistry. Vasopressin expression in BNST neurons was completely absent in both breeding stocks, confirming the absence of BNST vasopressin expression in Mesocricetus auratus and ruling out a breeding artefact. Because vasopressin expression in BNST neurons appears to be strictly dependent on circulating sex steroids, the absence of vasopressin expression in Syrian hamster BNST neurons might be due to an insensitivity of these neurons to sex steroids. BNST vasopressin neurons also express galanin. Although galanin expression in the BNST is not sexually dimorphic in the Syrian hamster, it appears to be regulated by sex steroids. In the Djungarian hamster, photoperiodically driven seasonal variations of circulating sex steroids result in a seasonal rhythm of galanin expression in BNST neurons. We analysed the sex steroid dependence of galanin expression in the Syrian hamster. Castration and short photoperiod-induced sexual quiescence both resulted in downregulation of galanin mRNA in cell bodies (BNST) and immunoreactivity in the fibres (lateral septum). Testosterone supplementation of short photoperiod-adapted animals was able to restore galanin expression. Thus Syrian hamster BNST neurons respond to circulating sex steroids and their seasonal variations as observed in other rodent species.

Outcome after fixation of unstable posterior pelvic ring injuries.

Between June 1989 and May 1995, the authors surgically treated 64 patients with unstable posterior pelvic in juries. Fracture types included Tile Type C1 (75%), C2 (8%), and C3 (17%). There were 19 sacroiliac dislocations, 12 sacral fractures, 4 transiliac fractures, and 29 sacroiliac fracture dislocations. Average patient age was 32 years and Injury Severity Score was 27 points. Posterior fixation was accomplished by percutaneous iliosacral screw insertion in 53 patients (83%). Only pure transiliac fractures were treated without iliosacral screws. There were no iatrogenic nerve palsies. During the study, there was increased reliance on internal fixation of the anterior pelvic ring that aided in anatomic alignment of the pelvis for posterior fixation and resulted in decreased chronic pubic tenderness. The use of external fixation for definitive treatment was abandoned. Patients were observed for an average of 36 months (range, 5-74 months). Fifty-two patients were available for recent complete followup. Fifty-one patients (98%) healed their pelvic disruptions; there was 1 sacral nonunion. A 40-point pelvic outcome grading scale was developed based on physical examination, pain, radiographic analysis, and activity/work status. Scores obtained by this scale correlated closely with the Short Form-36 Health Survey scores. Patient functional outcome after posterior pelvic fracture was not associated with Injury Severity Score or fracture location.

A sequential protocol for management of severe open tibial fractures.

Fifty consecutive open fractures of the tibia, including 22 Grade IIIB and 4 Grade IIIC, were treated using a protocol of debridement, immediate wound coverage, and intramedullary nailing. Fasciocutaneous flaps were used extensively to cover areas of exposed bone. The severity of the soft tissue injury dictated the timing of definitive fixation. Fracture location determined implant selection and nailing technique. Patients were observed for an average of 21 months. Ninety-eight percent of the fractures united < 6 months postoperatively. There was 1 infection (2%), 2 malunions (4%), and 1 case of partial flap necrosis. Locking screws broke in 1 patient (2%); the fracture united with < 5 mm of shortening. Immediate postdebridement wound coverage, and intramedullary nailing after reconstruction of the soft tissue envelope facilitate fracture healing in these complex open injuries. Intramedullary nailing can be performed safely to include all grades of open tibial fractures from the proximal to distal metaphysis.

Intramedullary nail and lag-screw fixation of proximal femur fractures. Operative technique and preliminary results.

Fifty patients with intertrochanteric and subtrochanteric fractures of the femur were treated with closed reduction and internal fixation with Vector intramedullary nail (Biomet Inc, Warsaw, Indiana) and lag-screw fixation. Sixty-five percent of intertrochanteric fractures were unstable, with subtrochanteric extension in 12 cases. Lag-screw fixation preceded closed, unreamed nailing. Weight bearing, as tolerated, was initiated on the first post-operative day in all patients. Overall mortality and complications were lower than those reported in comparable series of intertrochanteric fractures treated with internal fixation. One nail breakage occurred. No cases of lag-screw cutout, nonunion, or femoral shaft fracture were documented. The Vector nail has recently been introduced as an alternative form of fixation for complex proximal femur fractures. In the present study, consistently good results were obtained, despite the stability or location of the fracture. We especially recommend using the Vector nail for managing complex, unstable intertrochanteric and subtrochanteric fractures.